CA2264193C - A tonometer system for measuring intraocular pressure by applanation and/or indentation - Google Patents

Abstract

A tonometer system for measuring intraocular pressure by accurately providing a predetermined amount of applanation of the cornea, and detecting the amount of force required to achieve the predetermined amount of applanation. The system is also capable of measuring intraocular pressure by identing the cornea using a predetermined force applied using an indenting element, and detecting the distance the indenting element (16) moves into the cornea when the predetermined force is applied, the distance being inversely proportional to intraocular pressure. Also provided is a method of using a tonometer system to measure hydrodynamic characteristics of the eye, especially outflow facility.
The tonometer system includes a contact device for placement in contact with the cornea and an actuation apparatus (6) for actuating the contact device so that a portion thereof projects inwardly against the cornea to provide a predetermined amount of applanation. The system further includes a detecting arrangement (8) for detecting when the predetermined amount of applanation has been achieved, and a calculation unit responsive to the detecting arrangement (8) for determining intraocular pressure based on the amount of force the contact device must apply against the cornea in order to achieve the predetermined amount of applanation. An indentation distance detection arrangement is also provided for use when intraocular pressure is to be deteced by indentation. In carrying out the method, the system is used to detect intraocular pressure between successive steps of forcing intraocular fluid out from the eye.

Description

15CA 02264193 1999-02-26WO 98/09564 PCT/US97/15489A TONOMETER SYSTEM FOR MEASURING INTRAOCULAR PRESSURE BYAPPLANATION AND/OR INDENTATIONBACKGROUND OF THE INVENTIONThe present invention relates to a tonometer system for measuring intraocular pressureby accurately providing a predetermined amount of applanation to the cornea and detectingthe amount of force required to achieve the predetermined amount of applanation. The systemis also capable of measuring intraocular pressure by indenting the cornea using a predeterminedforce applied using an indenting element and detecting the distance the indenting elementmoves into the cornea when the predetermined force is applied, the distance being inverselyproportional to intraocular pressure. The present invention also relates to a method of usingthe tonometer system to measure hydrodynamic characteristics of the eye, especially outflowfacility.The tonometer system of the present invention may also be used to measurehemodynamics of the eye, especially ocular blood flow and pressure in the eye's blood vessels.Additionally, the tonometer system of the present invention may be used to increase andmeasure the eye pressure and evaluate, at the same time, the ocular effects of the increasedpressure.Glaucoma is a leading cause of blindness worldwide and, although it is more commonin adults over age 35, it can occur at any age. Glaucoma primarily arises when intraocularpressure increases to values which the eye cannot withstand.The fluid responsible for pressure in the eye is the aqueous humor. It is a transparentfluid produced by the eye in the ciliary body and collected and drained by a series of channels(trabecular meshwork, Schlemm's canal and venous system). The basic disorder in mostglaucoma patients is caused by an obstruction or interference that restricts the flow of aqueoushumor out of the eye. Such an obstruction or interference prevents the aqueous humor fromleaving the eye at a normal rate. This pathologic condition occurs long before there is aconsequent rise in intraocular pressure. This increased resistance to outflow of aqueous humoris the major cause of increased intraocular pressure in glaucoma-stricken patients.Increased pressure within the eye causes progressive damage to the optic nerve. Asoptic nerve damage occurs, characteristic defects in the visual field develop, which can lead tol015CA 02264193 1999-02-26W0 98l09564 PCT/US97/154892blindness if the disease remains undetected and untreated. Because of the insidious nature ofglaucoma and the gradual and painless loss of vision associated therewith, glaucoma does notproduce symptoms that would motivate an individual to seek help until relatively late in itscourse when irreversible damage has already occurred. As a result, millions of glaucomavictims are unaware that they have the disease and face eventual blindness. Glaucoma can bedetected and evaluated by measuring the eye's fluid pressure using a tonometer and/or bymeasuring the eye fluid outflow facility. Currently, the most frequently used way of measuringfacility of outflow is by doing indentation tonography. According to this technique, the capacityfor flow is determined by placing a tonometer upon the eye. The weight of the instrumentforces aqueous humor through the filtration system, and the rate at which the pressure in theeye declines with time is related to the ease with which the fluid leaves the eye.Individuals at risk for glaucoma and individuals who will develop glaucoma generallyhave a decreased outflow facility. Thus, the measurement of the outflow facility providesinformation which can help to identify individuals who may develop glaucoma, andconsequently will allow early evaluation and institution of therapy before any significantdamage occurs.The measurement of outflow facility is helpfiil in making therapeutic decisions and inevaluating changes that may occur with time, aging, surgery, or the use of medications to alterintraocular pressure. The determination of outflow facility is also an important research toolfor the investigation of matters such as drug effects, the mechanism of action of varioustreatment modalities, assessment of the adequacy of antiglaucoma therapy, detection of widediurnal swings in pressure and to study the pathophysiology of glaucoma.There are several methods and devices available for measuring intraocular pressure,outflow facility, and/or various other glaucoma-related characteristics of the eye. Thefollowing patents disclose various examples of such conventional devices and methods:PATENT NO. PATENTEE5,375,595 Sinha et al.5,295,495 Maddess5,251,627 Morris10152030CA 02264193 1999-02-26WO 98/09564 PCT/US97/154893PATENT NO. PATENTEE5,217,015 Kaye et al.5,183,044 Nishio et al.5,179,953 Kursar5,148,807 Hsu5,109,852 Kaye et al.5,165,409 Coan5,076,274 Matsumoto5,005,577 Frenkel4,951,671 Coan4,947,849 Takahashi et al.4,944,303 Katsuragi4,922,913 Waters, Jr. et al.4,860,755 Erath4,771,792 Seale4,628,938 Lee4,305,399 Beale3,724,263 Rose et al.3,585,849 Grolman3,545,260 Lichtenstein et al.Still other examples of conventional devices and/or methods are disclosed in Morey,Contact Lens Tonometer, RCA Technical Notes, No. 602, December 1964; Russell &Bergmanson, Multiple Applications of the NCT: An Assessment of the Instrument's Effect onIOP, Ophthal. Physiol. Opt., Vol. 9, April 1989, pp. 212-214; Moses & Grodzki, ThePneumatonograph: A Laboratory Study, Arch, Ophthalmol., Vol. 97, March 1979, pp. 547-552; and C. C. Collins, Miniature Passive Pressure Transensor for Implanting in the Eye, IEEETransactions on Bio-medical Engineering, April 1967, pp. 74-83.In general, eye pressure is measured by depressing or flattening the surface of the eye,and then estimating the amount of force necessary to produce the given flattening ordepression. Conventional tonometry techniques using the principle of applanation may providel0152025CA 02264193 1999-02-26W0 93/09564 PCT/US97/154894accurate measurements of intraocular pressure, but are subject to many errors in the way theyare currently being performed. In addition, the present devices either require professionalassistance for their use or are too complicated, expensive or inaccurate for individuals to useat home. As a result, individuals must visit an eye care professional in order to check their eyepressure. The frequent self-checking of intraocular pressure is usefial not only for monitoringtherapy and self-checking for patients with glaucoma, but also for the early detection of risesin pressure in individuals without glaucoma and for whom the elevated pressure was notdetected during their ofiice visit.Pathogens that cause severe eye infection and visual impairment such as herpes andadenovirus as well as the virus that causes AIDS can be found on the surface of the eye and inthe tear film. These microorganisms can be transmitted from one patient to another throughthe tonometer tip or probe. Probe covers have been designed in order to prevent transmissionof diseases but are not widely used because they are not practical and provide less accuratemeasurements. Tonometers which prevent the transmission of diseases, such as the "air-puff"type of tonometer also have been designed, but they are expensive and provide less accuratemeasurements. Any conventional direct contact tonometers can potentially transmit a varietyof systemic and ocular diseases.The two main techniques for the measurement of intraocular pressure require a forcethat flattens or a force that indents the eye, called "applanation" and "indentation" tonometryrespectively.Applanation tonometry is based on the Irnbert-Fick principle. This principle states thatfor an ideal dry, thin walled sphere, the pressure inside the sphere equals the force necessaryto flatten its surface divided by the area of flattening. P=F/A (where P = pressure, F = force,A = area). In applanation tonometry, the cornea is flattened, and by measuring the applanatingforce and knowing the area flattened, the intraocular pressure is determined.By contrast, according to indentation tonometry (Schiotz), a known weight (or force)is applied against the cornea and the intraocular pressure is estimated by measuring the lineardisplacement which results during deformation or indentation of the cornea. The lineardisplacement caused by the force is indicative of intraocular pressure. In particular, forstandard forces and standard dimensions of the indenting device, there are known tables whichcorrelate the linear displacement and intraocular pressure.2025CA 02264193 1999-02-26WO 98/09564 PCTIUS97/154895Conventional measurement techniques using applanation and indentation are subject tomany errors. The most frequently used technique in the clinical setting is contact applanationusing Goldman tonometers. The main sources of errors associated with this method includethe addition of extraneous pressure on the cornea by the examiner, squeezing of the eyelids orexcessive widening of the lid fissure by the patient due to the discomfort caused by thetonometer probe resting upon the eye, and inadequate or excessive amount of dye (fluorescein).In addition, the conventional techniques depend upon operator skill and require that theoperator subjectively determine alignment, angle and amount of depression. Thus, variabilityand inconsistency associated with less valid measurements are problems encountered using theconventional methods and devices.Another conventional technique involves air-puff tonometers wherein a pufi‘ ofcompressed air of a known volume and pressure is applied against the surface of the eye, whilesensors detect the time necessary to achieve a predetermined amount of deformation in theeye's surface caused by application of the air puff. Such a device is described, for example, inU.S. Pat. No. 3,545,260 to Lichtenstein et al. Although the non-contact (air-puff) tonometerdoes not use dye and does not present problems such as extraneous pressure on the eye by theexaminer or the transmission of diseases, there are other problems associated therewith. Suchdevices, for example, are expensive, require a supply of compressed gas, are consideredcumbersome to operate, are difiicult to maintain in proper alignment and depend on the skilland technique of the operator. In addition, the individual tested generally complains of painassociated with the air discharged toward the eye, and due to that discomfort many individualsare hesitant to undergo further measurement with this type of device. The primary advantageof the non-contact tonometer is its ability to measure pressure without transmitting diseases,but they are not accepted in general as providing accurate measurements and are primarilyusefiil for large-scale glaucoma screening programs.Tonometers which use gases, such as the pneumotonometer, have several disadvantagesand limitations. Such device are also subject to the operator errors as with Goldman'stonometry. In addition, this device uses freon gas, which is not considered environmentallysafe. Another problem with this device is that the gas is flammable and as with any otheraerosol-type can, the can may explode if it gets too hot. The gas may also leak and issusceptible to changes in cold weather, thereby producing less accurate measurements.l525CA 02264193 1999-02-26WO 98/09564 PCT/US97/154896Transmission of diseases is also a problem with this type of device if probe covers are notutilized.In conventional indentation tonometry (Schiotz) , the main source of errors are relatedto the application of a relatively heavy tonometer (total weight at least 16.5 g) to the eye andthe differences in the distensibility of the coats of the eye. Experience has shown that a heavyweight causes discomfort and raises the intraocular pressure. Moreover the test depends upona cumbersome technique in which the examiner needs to gently place the tonometer onto thecornea without pressing the tonometer against the globe. The accuracy of conventionalindentation may also be reduced by inadequate cleaning of the instrument as will be describedlater. The danger of transmitting infectious diseases, as with any contact tonometer, is alsopresent with conventional indentation.A variety of methods using a contact lens have been devised, however, such systemssuffer from a number of restrictions and virtually none of these devices is being widely utilizedor is accepted in the clinical setting due to their limitations and inaccurate readings. Moreover,such devices typically include instrumented contact lenses and/or cumbersome and complexcontact lenses.Several instruments in the prior art employ a contact lens placed in contact with thesclera (the white part of the eye). Such systems suffer from many disadvantages anddrawbacks. The possibility of infection and inflammation is increased due to the presence ofa foreign body in direct contact with a vascularized part of the eye. As a consequence, aninflammatory ‘reaction around the device may occur, possibly impacting the accuracy of anymeasurement. In addition, the level of discomfort is high due to a long period of contact witha highly sensitive area of the eye. Furthermore, the device could slide and therefore lose properalignment, and again, preventing accurate measurements to be taken. Moreover, the sclera isa thick and almost non-distensible coat of the eye which may fi.1rther impair the ability toacquire accurate readings. Most of these devices utilize expensive sensors and complicatedelectric circuitry imbedded in the lens which are expensive, difficult to manufacture andsometimes cumbersome.Other methods for sensing pressure using a contact lens on the cornea have beendescribed. Some of the methods in this prior art also employ expensive and complicatedelectronic circuitry and/or transducers imbedded in the contact lens. In addition, some devices1015202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/154897use piezoelectric material in the lens and the metalization of components of the lens overlyingthe optical axis decreases the visual acuity of patients using that type of device. Moreover,accuracy is decreased since the piezoelectric material is atfected by small changes intemperature and the velocity with which the force is applied. There are also contact lenstonometers which utilize fluid in a chamber to cause the deformation of the cornea; however,such devices lack means for alignment and are less accurate, since the flexible elastic materialis unstable and may bulge forward. In addition, the fluid therein has a tendency to accumulatein the lower portion of the chamber, thus failing to produce a stable flat surface which isnecessary for an accurate measurement.Another embodiment uses a coil wound about the inner surface of the contact lens anda magnet subjected to an externally created magnetic field. A membrane with a conductivecoating is compressed against a contact completing a short circuit. The magnetic field forcesthe magnet against the eye and the force necessary to separate the magnet from the contact isconsidered proportional to the pressure. This device suffers from many limitations anddrawbacks. For example, there is a lack of accuracy since the magnet will indent the corneaand when the magnet is pushed against the eye, the sclera and the coats of the eye distort easilyto accommodate the displaced intraocular contents. This occurs because this method does notaccount for the ocular rigidity, which is related to the fact that the sclera of one person's eyeis more easily stretched than the sclera of another. An eye with a low ocular rigidity will bemeasured and read as having a lower intraocular pressure than the actual eye's pressure.Conversely, an eye with a high ocular rigidity distends less easily than the average eye, resultingin a reading which is higher than the actual intraocular pressure. In addition, this design utilizescurrent in the lens which, in turn, is in direct contact with the body. Such contact isundesirable. Unnecessary cost and complexity of the design with circuits imbedded in the lensand a lack of an alignment system are also major drawbacks with this design.Another disclosed contact lens arrangement utilizes a resonant circuit formed from asingle coil and a single capacitor and a magnet which is movable relative to the resonant circuit.A further design from the same disclosure involves a transducer comprised of a pressuresensitive transistor and complex circuits in the lens which ‘constitute the operating circuit forthe transistor. All three of the disclosed embodiments are considered impractical and evenunsafe for placement on a person's eye. Moreover, these contact lens tonometers arel015202530CA 02264193 1999-02-26WO 98109564 PCT/US97Il54898unnecessarily expensive, complex, cumbersome to use and may potentially damage the eye.In addition none of these devices permits measurement of the applanated area, and thus aregenerally not very practical.The prior art also fails to provide a sufficiently accurate technique or apparatus formeasuring outflow facility. Conventional techniques and devices for measuring outflow facilityare limited in practice and are more likely to produce erroneous results because both are subjectto operator, patient and instrument errors.With regard to operator errors, the conventional test for outflow facility requires a longperiod of time during which there can be no tilting of the tonometer. The operator thereforemust position and keep the weight on the cornea without moving the weight and withoutpressing the globe.With regard to patient errors, if during the test the patient blinks, squeezes, moves,holds his breath, or does not maintain fixation, the test results will not be accurate. Sinceconventional tonography takes about four minutes to complete and generally requiresplacement of a relatively heavy tonometer against the eye, the chances of patients becominganxious and therefore reacting to the mechanical weight placed on their eyes is increased.With regard to instrument errors, after each use, the tonometer plunger and foot plateshould be rinsed with water followed by alcohol and then wiped dry with lint-free material. Ifany foreign material drys within the foot plate, it can detrimentally affect movement of theplunger and can produce an incorrect reading.The conventional techniques therefore are very difficult to perform and demand trainedand specialized personnel. The pneumotonograph, besides having the problems associated withthe pneumotonometer itself, was considered "totally unsuited to tonography." (Report by theCommittee on Standardization of Tonometers of the American Academy of Ophthalmology;Archives Ophthalmol. , 97:547-552, 1979) . Another type of tonometer (Non Contact "AirPuff" Tonometer-US. Patent No. 3,545,260) was also considered unsuitable for tonography.(Ophthalmic & Physiological Optics, 9(2):2l2-214, 1989). Presently there are no trulyacceptable means for self-measurement of intraocular pressure and outflow facility.SUMMARY OF THE INVENTIONIn contrast to the various prior art devices, the apparatus of the present invention offers1530CA 02264193 1999-02-26WO 98/09564 PCT/US97/ 154899an entirely new approach for the measurement of intraocular pressure and eye hydrodynamics.The apparatus offers a simple, accurate, low-cost and safe means of detecting and measuringthe earliest of abnonnal changes taking place in glaucoma, and provides a method for thediagnosis of early forms of glaucoma before any irreversible damage occurs. The apparatus ofthis invention provides a fast, safe, virtually automatic, direct—reading, comfortable and accuratemeasurement utilizing an easy-to—use, gentle, dependable and low-cost device, which is suitablefor home use.Besides providing a novel method for a single measurement and self-measurement ofintraocular pressure, the apparatus of the invention can also be used to measure outflow facilityand ocular rigidity. In order to determine ocular rigidity it is necessary to measure intraocularpressure under two different conditions, either with different weights on the tonometer or withthe indentation tonometer and an applanation tonometer. Moreover, the device can performapplanation tonography which is unaffected by ocular rigidity because the amount ofdeformation of the cornea is so very small that very little is displaced with very little change inpressure. Large variations in ocular rigidity, therefore, have little effect on applanationmeasurements.According to the present invention, a system is provided for measuring intraocularpressure by applanation. The system includes a contact device for placement in contact withthe cornea and an actuation apparatus for actuating the contact device so that a portion thereofprojects inwardly against the cornea to provide a predetermined amount of applanation. Thecontact device’ is easily sterilized for multiple use, or alternatively, can be made inexpensivelyso as to render the contact device disposable. The present invention, therefore, avoids thedanger present in many conventional devices of transmitting a variety of systemic and oculardiseases.The system further includes at detecting arrangement for detecting when thepredetermined amount of applanation of the cornea has been achieved and a calculation unitresponsive to the detecting arrangement for determining intraocular pressure based on theamount of force the contact device must apply against the cornea in order to achieve thepredetermined amount of applanation.The contact device preferably includes a substantially rigid annular member, a flexiblemembrane and a movable central piece. The substantially rigid annular member includes anl0l52530CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548910inner concave surface shaped to match an outer surface of the cornea and having a hole definedtherein. The subsannular member preferably has a maximum thickness at the hole and aprogressively decreasing thickness toward a periphery of the substantially rigid annularmember.The flexible membrane is preferably secured to the inner concave surface of thesubstantially rigid annular member. The flexible membrane is coextensive with at least the holein the annular member and includes at least one transparent area. Preferably, the transparentarea spans the entire flexible membrane, and the flexible membrane is coextensive with theentire inner concave surface of the rigid annular member.The movable central piece is slidably disposed within the hole and includes asubstantially flat inner side secured to the flexible membrane. A substantially cylindrical wallis defined circumferentially around the hole by virtue of the increased thickness of the rigidannular member at the periphery of the hole. The movable central piece is preferably slidablydisposed against this wall in a piston-like manner and has a thickness which matches the heightof the cylindrical wall. In use, the substantially flat inner side flattens a portion of the corneaupon actuation of the movable central piece by the actuation apparatus.Preferably, the actuation apparatus actuates the movable central piece to cause slidingof the movable central piece in the piston-like manner toward the cornea. In doing so, themovable central piece and a central portion of the flexible membrane are caused to projectinwardly against the cornea. A portion of the cornea is thereby flattened. Actuation continuesuntil a predetermined amount of applanation is achieved.Preferably, the movable central piece includes a magnetically responsive elementarranged so as to slide along with the movable central piece in response to a magnetic field, andthe actuation apparatus includes a mechanism for applying a magnetic field thereto. Themechanism for applying the magnetic field preferably includes a coil and circuitry for producingan electrical current through the coil in a progressively increasing manner. By progressivelyincreasing the current, the magnetic field is progressively increased. The magnetic repulsionbetween the actuation apparatus and the movable central piece therefore increasesprogressively, and this, in turn, causes a progressively greater force to be applied against thecornea until the predetermined amount of applanation is achieved.Using known principles of physics, it is understood that the electrical current passingl015202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/15489llthrough the coil will be proportional to the amount of force applied by the movable centralpiece against the cornea via the flexible membrane. Since the amount of force required toachieve the predetermined amount of applanation is proportional to intraocular pressure, theamount of current required to achieve the predetermined amount of applanation will also beproportional to the intraocular pressure.The calculation unit therefore preferably includes a memory for storing a current valueindicative of the amount of current passing through the coil when the predetermined amountof applanation is achieved and also includes a conversion unit for converting the current valueinto an indication of intraocular pressure.The magnetically responsive element is circumferentially surrounded by a transparentperipheral portion. The transparent peripheral portion is aligned with the transparent area andpermits light to pass through the contact device to the cornea and also permits light to reflectfrom the cornea back out of the contact device through the transparent peripheral portion.The magnetically responsive element preferably comprises an annular magnet havinga central sight hole through which a patient is able to see while the contact device is located onthe patient's cornea. The central sight hole is aligned with the transparent area of the flexiblemembrane.A display is preferably provided for numerically displaying the intraocular pressuredetected by the system. Alternatively, the display can be arranged so as to give indications ofwhether the intraocular pressure is within certain ranges.Preferably, since different patients may have different sensitivities or reactions to thesame intraocular pressure, the ranges are calibrated for each patient by an attending physician.This way, patients who are more susceptible to consequences from increased intraocularpressure may be alerted to seek medical attention at a pressure less than the pressure at whichother less-susceptible patients are alerted to take the same action.The detecting arrangement preferably comprises an optical applanation detectionsystem. In addition, a sighting arrangement is preferably provided for indicating when theactuation apparatus and the detecting arrangement are properly aligned with the contact device.Preferably, the sighting arrangement includes the central sight hole in the movable central piecethrough which a patient is able to see while the device is located on the patient's cornea. Thecentral sight hole is aligned with the transparent area, and the patient preferably achieves a20CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548912generally proper alignment by directing his vision through the central sight hole toward a targetmark in the actuation apparatus.The system also preferably includes an optical distance measuring mechanism forindicating whether the contact device is spaced at a proper axial distance from the actuationapparatus and the detecting arrangement. The optical distance measurement mechanism ispreferably used in conjunction with the sighting arrangement and preferably provides a visualindication of what corrective action should be taken whenever an improper distance is detected.The system also preferably includes an optical alignment mechanism for indicatingwhether the contact device is properly aligned with the actuation apparatus and the detectingarrangement. The optical alignment mechanism preferably provides a visual indication of whatcorrective action should be taken whenever a misalignment is detected, and is preferably usedin conjunction with the sighting arrangement, so that the optical alignment mechanism merelyprovides indications of minor alignment corrections while the sighting arrangement providesan indication of major alignment corrections.In order to compensate for deviations in corneal thickness, the system of the presentinvention may also include an arrangement for multiplying the detected intraocular pressure bya coefficient (or gain) which is equal to one for corneas of normal thickness, less than one forunusually thick corneas, and a gain greater than one for unusually thin corneas.Similar compensations can be made for corneal curvature, eye size, ocular rigidity, andthe like. For levels of corneal curvature which are higher than normal, the coefficient wouldbe less than one. The same coefiicient would be greater than one for levels of cornealcurvature which are flatter than normal.In the case of eye size compensation, larger than normal eyes would require acoefficient which is less than one, while smaller than normal eyes require a coefiicient whichis greater than one.For patients with "stiffer" than normal ocular rigidities, the coefficient is less than one,but for patients with softer ocular rigidities, the coefficient is greater than one.The coefiicient (or gain) may be manually selected for each patient, or alternatively, thegain may be selected automatically by connecting the apparatus of the present invention to aknown pachymetry apparatus when compensating for corneal thickness, a known keratometerwhen compensating for corneal curvature, and/or a known biometer when compensating forl0l5CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548913eye size.The contact device and associated system of the present invention may also be used todetect intraocular pressure by indentation. When indentation techniques are used in measuringintraocular pressure, a predetermined force is applied against the cornea using an indentationdevice. Because of the force, the indentation device travels in toward the cornea, indenting thecornea as it travels. The distance traveled by the indentation device into the cornea in responseto the predetermined force is known to be inversely proportional to intraocular pressure.Accordingly, there are various known tables which, for certain standard sizes of indentationdevices and standard forces, correlate the distance traveled and intraocular pressure.Preferably, the movable central piece of the contact device also fiinctions as theindentation device In addition, the circuit is switched to operate in an indentation mode.When switched to the indentation mode, the current producing circuit supplies a predeterminedamount of current through the coil. The predetermined amount of current corresponds to theamount of current needed to produce one of the aforementioned standard forces.In particular, the predetermined amount of current creates a magnetic field in theactuation apparatus. This magnetic field, in turn, causes the movable central piece to pushinwardly against the cornea via the flexible membrane. Once the predetermined amount ofcurrent has been applied and a standard force presses against the cornea, it is necessary todetermine how far the movable central piece moved into the cornea.Accordingly, when measurement of intraocular pressure by indentation is desired, thesystem of the present invention further includes a distance detection arrangement for detectinga distance traveled by the movable central piece, and a computation portion in the calculationunit for determining intraocular pressure based on the distance traveled by the movable centralpiece in applying the predetermined amount of force.Preferably, the computation portion is responsive to the current producing circuitry sothat, once the predetermined amount of force is applied, an output voltage from the distancedetection arrangement is received by the computation portion. The computation portion then,based on the displacement associated with the particular output voltage, determines intraocularpressure.In addition, the present invention includes alternative embodiments, as will be describedhereinafter, for performing indentation-related measurements of the eye. Clearly, therefore, the15CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548914present invention is not limited to the aforementioned exemplary indentation device.The aforementioned indentation device of the present invention may also be utilized tonon—invasively measure hydrodynamics of an eye including outflow facility. The method of thepresent invention preferably comprises several steps including the following:According to a first step, an indentation device is placed in contact with the cornea.Preferably, the indentation device comprises the contact device of the present invention.Next, at least one movable portion of the indentation device is moved in toward thecornea using a first predetermined amount of force to achieve indentation of the cornea. Anintraocular pressure is then determined based on a first distance traveled toward the cornea bythe movable portion of the indentation device during application of the first predeterminedamount of force. Preferably, the intraocular pressure is determined using the aforementionedsystem for determining intraocular pressure by indentation.Next, the movable portion of the indentation device is rapidly reciprocated in towardthe cornea and away from the cornea at a first predetermined frequency and using a secondpredetermined amount of force during movement toward the cornea to thereby forceintraocular fluid out from the eye. The second predetermined amount of force is preferablyequal to or more than the_first predetermined amount of force. It is understood, however, thatthe second predetermined amount of force may be less than the first predetermined amount offorce.The movable portion is then moved in toward the cornea using a third predeterminedamount of force to again achieve indentation of the cornea. A second intraocular pressure isthen determined based on a second distance traveled toward the cornea by the movable portionof the indentation device during application of the third predetermined amount of force. Sinceintraocular pressure decreases as a result of forcing intraocular fluid out of the eye during therapid reciprocation of the movable portion, it is generally understood that, unless the eye is sodefective that no fluid flows out therefrom, the second intraocular pressure will be less than thefirst intraocular pressure. This reduction in intraocular pressure is indicative of outflow facility.Next, the movable portion of the indentation device is again rapidly reciprocated intoward the cornea and away from the cornea, but at a second predetermined frequency andusing a fourth predetermined amount of force during movement toward the cornea. The fourthpredetermined amount of force is preferably equal to or greater than the second predeterminedl0l5202530CA 02264193 1999-02-26WO 98/09564 PCTIU S97/ 1548915amount of force; however, it is understood that the fourth predetermined amount of force maybe less than the second predetennined amount of force. Additional intraocular fluid is therebyforced out from the eye.The movable portion is subsequently moved in toward the cornea using a fifihpredetermined amount of force to again achieve indentation of the cornea. Thereafter, a thirdintraocular pressure is determined based on a third distance traveled toward the cornea by themovable portion of the indentation device during application of the fifih predetermined amountof force.The differences are then preferably calculated between the first, second, and thirddistances, which differences are indicative of the volume of intraocular fluid which lefi the eyeand therefore are also indicative of the outflow facility. It is understood that the differencebetween the first and last distances may be used, and in this regard, it is not necessary to usethe differences between all three distances. In fact, the difference between any two of thedistances will suffice.Although the relationship between the outflow facility and the detected differencesvaries when the various parameters of the method and the dimensions of the indentation devicechange, the relationship for given parameters and dimensions can be easily determined byknown experimental techniques and/or using known Friedenwald Tables.Preferably, the method further comprises the steps of plotting the differences betweenthe first, second, and third distance to a create a graph of the differences and comparing theresulting graph of differences to that of a normal eye to determine if any irregularities inoutflow facility are present.The above and other objects and advantages will become more readily apparent whenreference is made to the following description taken in conjunction with the accompanyingdrawings.BRIEF DESCRIPTION OF THE DRAWINGSFigure l is a schematic block diagram illustrating a system for measuring intraocularpressure in accordance with a preferred embodiment of the present invention.Figures 2A~2D schematically illustrate a preferred embodiment of a contact devicel015202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548916according the present invention.Figure 3 schematically illustrates a view seen by a patient when utilizing the systemillustrated in Figure 1.Figures 4 and 5 schematically depict multi-filter optical elements in accordance with apreferred embodiment of the present invention.Figures SA-5F illustrate a preferred embodiment of an applicator for gently applyingthe contact device to the cornea in accordance with the present invention. Figure 6 illustratesan exemplary circuit for carrying out several aspects of the embodiment illustrated in Figure1.Figures 7A and 7B are block diagrams illustrating an arrangement capablecompensating for deviations in corneal thickness according to the present invention.Figures 8A and 8B schematically illustrate a contact device utilizing barcodetechnology in accordance with a preferred embodiment of the present invention.Figures 9A and 9B schematically illustrate a contact device utilizing color detectiontechnology in accordance with a preferred embodiment of the present invention.Figure 10 illustrates an alternative contact device in accordance with yet anotherpreferred embodiment of the present invention.Figures 11A and l lB schematically illustrate an indentation distance detectionarrangement in accordance with a preferred embodiment of the present invention.Figure 12 is a cross-sectional view of an alternative contact device in accordance withanother preferred embodiment of the present invention.Figures 13A-15 are cross-sectional views of alternative contact devices in accordancewith other embodiments of the present invention.Figure 16 schematically illustrates an alternative embodiment of the system formeasuring intraocular pressure by applanation, according to the present invention.Figure 16A is a graph depicting force (F) as a fimction of the distance (X) separatinga movable central piece from the pole of a magnetic actuation apparatus in accordance with thepresent invention.Figure 17 schematically illustrates an alternative optical alignment system in accordancewith the present invention.Figures 18 and 19 schematically illustrate arrangements for guiding the patient during2530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548917alignment of his/her eye in the apparatus of the present invention.Figures 20A and 20B schematically illustrate an alternative embodiment for measuringintraocular pressure by indentation.Figures 21 and 22 schematically illustrate embodiments of the present invention whichfacilitate placement of the contact device on the sclera of the eye.Figure 23 is a plan view of an alternative contact device which may be used to measureepiscleral venous pressure in accordance with the present invention.Figure 24 is a cross-sectional view of the alternative contact device which may be usedto measure episcleral venous pressure in accordance with the present invention.Figure 25 schematically illustrates an alternative embodiment of the present invention,which includes a contact device with a pressure transducer mounted therein.Figure 25A is a cross-sectional view of the alternative embodiment illustrated in Figure25.Figure 26 is a cross-sectional view illustrating the pressure transducer of Figure 25.Figure 27 schematically illustrates the alternative embodiment of Figure 25 whenlocated in a patient's eye.Figure 28 illustrates an alternative embodiment wherein two pressure transducers areutilized.Figure 29 illustrates an alternative embodiment utilizing a centrally disposed pressuretransducer.Figure '30 illustrates a preferred mounting of the alternative embodiment to eye glassframes.Figure 31 is a block diagram of a preferred circuit defined by the alternativeembodiment illustrated in Figure 25.DESCRIPTION OF THE PREFERRED EMBODIMENTSAPPLANATIONA preferred embodiment of the present invention will now be described with referenceto the drawings. According to the preferred embodiment illustrated in Figure 1, a system isprovided for measuring intraocular pressure by applanation. The system includes a contactdevice 2 for placement in contact with the cornea 4, and an actuation apparatus 6 for actuating101520'25CA 02264193 1999-02-26WO 98/09564 PCTIU S97/ 1548918the contact device 2 so that a portion thereof projects inwardly against the cornea 4 to providea predetermined amount of applanation. The system further includes a detecting arrangement8 for detecting when the predetermined amount of applanation of the cornea 4 has beenachieved and a calculation unit 10 responsive to the detecting arrangement 8 for determiningintraocular pressure based on the amount of force the contact device 2 must apply against thecornea 4 in order to achieve the predetermined amount of applanation.The contact device 2 illustrated in Figure 1 has an exaggerated thickness to more clearlydistinguish it from the cornea 4. Figures 2A-2D more accurately illustrate a preferredembodiment of the contact device 2 which includes a substantially rigid annular member 12, aflexible membrane 14 and a movable central piece 16. The substantially rigid annular member12 includes an inner concave surface 18 shaped to match an outer surface of the cornea 4 andhaving a hole 20 defined therein. The substantially rigid annular member 12 has a maximumthickness (preferably approximately 1 millimeter) at the hole 20 and a progressively decreasingthickness toward a periphery 21 of the substantially rigid annular member 12. The diameterof the rigid annular member is approximately 11 millimeters and the diameter of the hole 20 isapproximately 5.1 millimeters according to a preferred embodiment. Preferably, thesubstantially rigid annular member 12 is made of transparent polymethylmethacrylate; however,it is understood that many other materials, such as glass and appropriately rigid plastics andpolymers, may be used to make the annular member 12. Preferably, the materials are chosenso as not to interfere with light directed at the cornea or reflected back therefrom.The flexible membrane 14 is preferably secured to the inner concave surface 18 of thesubstantially rigid annular member 12 to provide comfort for the wearer by preventingscratches or abrasions to the corneal epithelial layer. The flexible membrane 14 is coextensivewith at least the hole 20 in the annular member 12 and includes at least one transparent area22. Preferably, the transparent area 22 spans the entire flexible membrane 14, and the flexiblemembrane 14 is coextensive with the entire inner concave surface 18 of the rigid annularmember 12. According to a preferred arrangement, only the periphery of the flexible membrane14 and the periphery of the rigid annular member 12 are secured to one another. This tendsto minimize any resistance the flexible membrane might exert against displacement of themovable central piece 16 toward the cornea 4.According to an alternative arrangement, the flexible membrane 14 is coextensive withI5202530CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548919the rigid armular member and is heat-sealed thereto over its entire extent except for a circularregion within approximately one millimeter of the hole 20.Although the flexible membrane 14 preferably consists of a soft and thin polymer, suchas transparent silicone elastic, transparent silicon rubber (used in conventional contact lens),transparent flexible acrylic (used in conventional intraocular lenses), transparent hydrogel, orthe like, it is well understood that other materials may be used in manufacturing the flexiblemembrane 14.The movable central piece 16 is slidably disposed within the hole 20 and includes asubstantially flat inner side 24 secured to the flexible membrane 14. The engagement of theinner side 24 to the flexible membrane 14 is preferably provided by glue or thermo-contacttechniques. It is understood, however, that various other techniques may be used in order tosecurely engage the inner side 24 to the flexible membrane 14. Preferably, the movable centralpiece 16 has a diameter of approximately 5.0 millimeters and a thickness of approximately 1millimeter.A substantially cylindrical wall 42 is defined circumferentially around the hole 20 byvirtue of the increased thickness of the rigid annular member 12 at the periphery of the hole 20The movable central piece 16 is slidably disposed against this wall 42 in a piston-like mannerand preferably has a thickness which matches the height of the cylindrical wall 42. In use, thesubstantially flat inner side 24 flattens a portion of the cornea 4 upon actuation of the movablecentral piece 16 by the actuation apparatus 6.The overall dimensions of the substantially rigid annular member 12, the flexiblemembrane 14 and the movable central piece 16 are determined by balancing several factors,including the desired range of forces applied to the cornea 4 during applanation, the discomforttolerances of the patients, the minimum desired area of applanation, and the requisite stabilityof the contact device 2 on the cornea 4. In addition, the dimensions of the movable centralpiece 16 are preferably selected so that relative rotation between the movable central piece 16and the substantially rigid annular member 12 is precluded, without hampering theaforementioned piston-like sliding.The materials used to manufacture the contact device 2 are preferably selected so as tominimize any interference with light incident upon the cornea 4 or reflected thereby.Preferably, the actuation apparatus 6 illustrated in Figure 1 actuates the movable central10152025CA 02264193 1999-02-26W0 98/09564 PCTIUS97/1548920piece 16 to cause sliding of the movable central piece 16 in the piston-like manner toward thecornea 4. In doing so, the movable central piece 16 and a central portion of the flexiblemembrane 14 are caused to project inwardly against the cornea 4. This is shown in Figures 2Cand 2D. A portion of the cornea 4 is thereby flattened. Actuation continues until apredetermined amount of applanation is achieved.Preferably, the movable central piece l6 includes a magnetically responsive element 26arranged so as to slide along with the movable central piece 16 in response to a magnetic field,and the actuation apparatus 6 includes a mechanism 28 for applying a magnetic field thereto.Although it is understood that the mechanism 28 for applying the magnetic field may includea selectively positioned bar magnet, according to a preferred embodiment, the mechanism 28for applying the magnetic field includes a coil 30 of long wire wound in a closely packed helixand circuitry 32 for producing an electrical current through the coil 30 in a progressivelyincreasing manner. By progressively increasing the current, the magnetic field is progressivelyincreased. The magnetic repulsion between the actuation apparatus 6 and the movable centralpiece 16 therefore increases progressively, and this, in turn, causes a progressively greater forceto be applied against the cornea 4 until the predetermined amount of applanation is achieved.Using known principles of physics, it is understood that the electrical current passingthrough the coil 30 will be proportional to the amount of force applied by the movable centralpiece 16 against the cornea 4 via the flexible membrane 14. Since the amount of force requiredto achieve the predetermined amount of applanation is proportional to intraocular pressure, theamount of current required to achieve the predetermined amount of applanation will also beproportional to the intraocular pressure. Thus, a conversion factor for converting a value ofcurrent to a value of intraocular pressure can easily be determined experimentally upondimensions of the system, the magnetic responsiveness of the magnetically responsive element26, number of coil windings, and the like.Besides using experimentation techniques, the conversion factor may also be determinedusing known techniques for calibrating a tonometer. Such known techniques are based on aknown relationship which exists between the inward displacement of an indentation device andthe volume changes and pressure in the indented eye. Examples of such techniques are setforth in Shiotz, Communications: Tonometry, The Brit. J. of Ophthalmology, June 1920, p.249-266; Fnedenwald, Tonometer Calibration, Trans. Amer. Acad. of O. & 0., Jan-Feb 1957,1015CA 02264193 1999-02-26W0 98/09554 PCT/US97/1548921pp. 108-126; and Moses, Theory and Calibration of the Schiotz Tonometer VII: ExperimentalResults of Tonometric Measurements: Scale Reading Versus Indentation Volume, InvestigativeOphthalmology, September 1971, Vol. 10, No. 9, pp. 716 - 723 .In light of the relationship between current and intraocular pressure, the calculation unit10 includes a memory 33 for storing a current value indicative of the amount of current passingthrough the coil 30 when the predetermined amount of applanation is achieved. The calculationunit 10 also includes a conversion unit 34 for converting the current value into an indicationof intraocular pressure.Preferably, the calculation unit 10 is responsive to the detecting arrangement 8 so thatwhen the predetermined amount of applanation is achieved, the current value (correspondingto the amount of current flowing through the coil 30) is immediately stored in the memory 33.At the same time, the calculation unit 10 produces an output signal directing the currentproducing circuitry 32 to terminate the flow of current. This, in turn, terminates the forceagainst the cornea 4. In an alternative embodiment, the current producing circuitry 32 couldbe made directly responsive to the detecting arrangement 8 (i.e., not through the calculationunit 10) so as to automatically terminate the flow of current through the coil 30 upon achievingthe predetermined amount of applanation. ’The current producing circuitry 32 may constitute any appropriately arranged circuitfor achieving the progressively increasing current. However, a preferred current producingcircuit 32 includes a switch and a DC power supply, the combination of which is capable ofproducing a step fimction. The preferred current producing circuitry 32 further comprises anintegrating amplifier which integrates the step function to produce the progressively increasingcurrent.The magnetically responsive element 26 is circumferentially surrounded by a transparentperipheral portion 36. The transparent peripheral portion 36 is aligned with the transparentarea 22 and permits light to pass through the contact device 2 to the cornea 4 and also permitslight to reflect from the cornea 4 back out of the contact device 2 through the transparent onperipheral portion 36. Although the transparent peripheral portion 36 may consist entirely ofan air gap, for reasons of accuracy and to provide smoother sliding of the movable central piece16 through the rigid annular member 12, it is preferred that a transparent solid materialconstitute the transparent peripheral portion 36. Exemplary transparent solid materials include102025CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548922polymethyl methacrylate, glass, hard acrylic, plastic polymers, and the like.The magnetically responsive element 26 preferably comprises an annular magnet havinga central sight hole 38 through which a patient is able to see while the contact device 2 islocated on the patient's cornea 4. The central sight hole 3 8 is aligned with the transparent area22 of the flexible membrane 14 and is preferably at least 1-2 millimeters in diameter.Although the preferred embodiment includes an annular magnet as the magneticallyresponsive element 26, it is understood that various other magnetically responsive elements 26may be used, including various ferromagnetic materials and/or suspensions of magneticallyresponsive particles in liquid. The magnetically responsive element 26 may also consist of aplurality of small bar magnets arranged in a circle, to thereby define an opening equivalent tothe illustrated central sight hole 38. A transparent magnet may also be used.A display 40 is preferably provided for numerically displaying the intraocular pressuredetected by the system. The display 40 preferably comprises a liquid crystal display (LCD) orlight emitting diode (LED) display connected and responsive to the conversion unit 34 of thecalculation unit 10.Alternatively, the display 40 can be arranged so as to give indications of whether theintraocular pressure is within certain ranges. In this regard, the display 40 may include a greenLED 40A, a yellow LED 40B, and a red LED 40C. When the pressure is within apredetermined high range, the red LED 40C is illuminated to indicate that medical attention isneeded. When the intraocular pressure is within a normal range, the green LED 40A isilluminated. The yellow LED 40B is illuminated when the pressure is between the normal rangeand the high range to indicate that the pressure is somewhat elevated and that, although medicalattention is not currently needed, careful and frequent monitoring is recommended.Preferably, since different patients may have different sensitivities or reactions to thesame intraocular pressure, the ranges corresponding to each LED 4OA,40B,40C are calibratedfor each patient by an attending physician. This way, patients who are more susceptible toconsequences from increased intraocular pressure may be alerted to seek medical attention ata pressure less than the pressure at which other less-susceptible patients are alerted to take thesame action. The range calibrations may be made using any known calibration device 40Dincluding variable gain amplifiers or voltage divider networks with variable resistances.The detecting arrangement 8 preferably comprises an optical detection system includingl525CA 02264193 1999-02-26W0 98/09564 PCT/US97/1548923two primary beam emitters 44,46; two light sensors 48,50; and two converging lenses 52,54.Any of a plurality of commercially available beam emitters may be used as emitters 44,46,including low—power laser beam emitting devices and infra-red (IR) beam emitting devices.Preferably, the device 2 and the primary beam emitters 44,46 are arranged with respect to oneanother so that each of the primary beam emitters 44,46 emits a primary beam of light towardthe cornea through the transparent area 22 of the device and so that the primary beam of lightis reflected back through the device 2 by the cornea 4 to thereby produce reflected beams 60,62of light with a direction of propagation dependent upon the amount of applanation ofthecornea. The two light sensors 48,50 and two converging lenses 52,54 are preferably arrangedso as to be aligned with the reflected beams 60,62 of light only when the predetermined amountof applanation of the cornea 4 has been achieved. Preferably, the primary beams 56,58 passthrough the substantially transparent peripheral portion 36.Although Figure 1 shows the reflected beams 60,62 of light diverging away from oneanother and well away from the two converging lenses 52,54 and light sensors 48,50, it isunderstood that as the cornea 4 becomes applanated the reflected beams 60,62 will approachthe two light sensors 48,50 and the two converging lenses 52,54. When the predeterminedamount of applanation is achieved, the reflected beams 60,62 will be directly aligned with theconverging lenses 52,54 and the sensors 48,50. The sensors 48,50 are therefore able to detectwhen the predetermined amount of applanation is achieved by merely detecting the presenceof the reflected beams 60,62. Preferably, the predetermined amount of applanation is deemedto exist whenall of the sensors 48,50 receive a respective one of the reflected beams 60,62.Although the illustrated arrangement is generally effective using two primary beamemitters 44,46 and two light sensors 48,50, better accuracy can be achieved in patients withastigmatisms by providing four beam emitters and four light sensors arranged orthogonally withrespect to one another about the longitudinal axis of the actuation apparatus 6. As in the casewith two beam emitters 44,46 and light sensors 48,50, the predetermined amount ofapplanation is preferably deemed to exist when all of the sensors receive a respective one of thereflected beams.A sighting arrangement is preferably provided for indicating when the actuationapparatus 6 and the detecting arrangement 8 are properly aligned with the device 2. Preferably,the sighting arrangement includes the central sight hole 38 in the movable central piece 161015'25CA 02264193 1999-02-26WO 98/09564 PCT /US97l 1548924through which a patient is able to see while the device 2 is located on the patient's cornea 4.The central sight hole 38 is aligned with the transparent area 22. In addition, the actuationapparatus 6 includes a tubular housing 64 having a first end 66 for placement over an eyeequipped with the device 2 and a second opposite end 68 having at least one mark 70 arrangedsuch that, when the patient looks through the central sight hole 38 at the mark 70, the device2 is properly aligned with the actuation apparatus 6 and detecting arrangement 8.Preferably, the second end 68 includes an internal mirror surface 72 and the mark 70generally comprises a set of cross-hairs. Figure 3 illustrates the view seen by a patient throughthe central sight hole 38 when the device 2 is properly aligned with the actuation apparatus 6and detecting arrangement 8. When proper alignment is achieved, the reflected image 74 ofthe central sight hole 38 appears in the mirror surface 72 at the intersection of the two cross-hairs which constitute the mark 70. (The size of the image 74 is exaggerated in Figure 3 tomore clearly distinguish it from other elements in the drawing).Preferably, at least one light 75 is provided inside the tubular housing 64 to illuminatethe inside of the housing 64 and facilitate visualization of the cross-hairs and the reflected image74. Preferably, the internal mirror surface 72 acts as a mirror only when the light 75 is on, andbecomes mostly transparent upon deactivation of the light 75 due to darkness inside the tubularhousing 64. To that end, the second end 68 of the tubular housing 68 may be manufacturedusing "one-way glass" which is often found in security and surveillance equipment.Alternatively, if the device is to be used primarily by physicians, optometrists, or thelike, the second end 68 may be merely transparent. If, on the other hand, the device is to beused by patients for self-monitoring, it is understood that the second end 68 may merely includea mirror.The system also preferably includes an optical distance measuring mechanism forindicating whether the device 2 is spaced at a proper axial distance from the actuation apparatus6 and the detecting arrangement 8. The optical distance measurement mechanism is preferablyused in conjunction with the sighting arrangement.Preferably, the optical distance measuring mechanism includes a distance measurementbeam emitter 76 for emitting an optical distance measurement beam 78 toward the device 2.The device 2 is capable of reflecting the distance measurement beam 78 to produce a firstreflected distance measurement beam 80. Arranged in the path of the first reflected distance10202530CA 02264193 1999-02-26W0 98/09564 PCT/US97/1548925measurement beam 80 is a preferably convex mirror 82. The convex mirror 82 reflects the firstreflected distance measurement beam 80 to create a second reflected distance measurementbeam 84 and serves to amplify any variations in the first reflected beam's direction ofpropagation. The second reflected distance measurement beam 84 is directed generally towarda distance measurement beam detector 86. The distance measurement beam detector 86 isarranged so that the second reflected distance measurement beam 84 strikes a predeterminedportion of the distance measurement beam detector 86 only when the device 2 is located at theproper axial distance from the actuation apparatus 6 and the detecting arrangement 8. Whenthe proper axial distance is lacking, the second reflected distance measurement beam strikesanother portion of the beam detector 86.An indicator 88, such as an LCD or LED display, is preferably connected andresponsive to the beam detector 86 for indicating that the proper axial distance has beenachieved only when the reflected distance measurement beam strikes the predetermined portionof the distance measurement beam detector.Preferably, as illustrated in Figure 1, the distance measurement beam detector 86includes a multi-filter optical element 90 arranged so as to receive the second reflected distancemeasurement beam 84. The multi-filter optical element 90 contains a plurality of optical filters92. Each of the optical filters 92 filters out a different percentage of light, with thepredetermined portion of the detector 86 being defined by a particular one of the optical filters92 and a filtering percentage associated therewith.The distance measurement beam detector 86 further includes a beam intensity detectionsensor 94 for detecting the intensity of the second reflected distance measurement beam 84after the beam 84 passes through the multi-filter optical element 90, Since the multi-filteroptical element causes this intensity to vary with axial distance, the intensity is indicative ofwhether the device 2 is at the proper distance from the actuation apparatus 6 and the detectingarrangement 8.A converging lens 96 is preferably located between the multi-filter optical element 90and the beam intensity detection sensor 94, for focussing the second reflected distancemeasurement beam 84 on the beam intensity detection sensor 94 after the beam 84 passesthrough the multi-filter optical element 90.Preferably, the indicator 88 is responsive to the beam intensity detection sensor 94 sol0l5202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548926as to indicate what corrective action should be taken, when the device 2 is not at the properaxial distance from the actuation apparatus 6 and the detecting arrangement 8, in order toachieve the proper distance. The indication given by the indicator 88 is based on the intensityand which of the plurality of optical filters 92 achieves the particular intensity by virtue of afiltering percentage associated therewith.For example, when the device 2 is excessively far from the actuation apparatus 6, thesecond reflected distance measurement beam 84 passes through a dark one of the filters 92.There is consequently a reduction in beam intensity which causes the beam intensity detectionsensor 94 to drive the indicator 88 with a signal indicative of the need to bring the device 2closer to the actuation apparatus. The indicator 88 responds to this signal by communicatingthe need to a user of the system.Alternatively, the signal indicative of the need to bring the device 2 closer to theactuation apparatus can be applied to a computer which performs corrections automatically.In like manner, when the device 2 is excessively close to the actuation apparatus 6, thesecond reflected distance measurement beam 84 passes through a lighter one of the filters 92.There is consequently an increase in beam intensity which causes the beam intensity detectionsensor 94 to drive the indicator 88 with a signal indicative of the need to move the device 2farther from the actuation apparatus. The indicator 88 responds to this signal bycommunicating the need to a user of the system.In addition, computer-controlled movement of the actuation apparatus farther awayfrom the device 2 may be achieved automatically by providing an appropriate computer-controlled moving mechanism responsive to the signal indicative of the need to move the device2 farther from the actuation apparatus.With reference to Figure 3, the indicator 88 preferably comprises three LEDs arrangedin a horizontal line across the second end 68 of the housing 64. When illuminated, the lefi LED88a, which is preferably yellow, indicates that the contact device 2 is too far from the actuationapparatus 6 and the detecting arrangement 8. Similarly, when illuminated, the right LED 88b,which is preferably red, indicates that the contact device 2 is too close to the actuationapparatus 6 and the detecting arrangement 8. When the proper distance is achieved, the centralLED 88c is illuminated. Preferably, the central LED 88c is green. The LEDs 88a-88c areselectively illuminated by the beam intensity detection sensor 94 in response to the beam's152025CA 02264193 1999-02-26WO 98/09564 PCT/US97ll 548927intensity.Although Figure 1 illustrates an arrangement of filters 92 wherein a reduction inintensity signifies a need to move the device closer, it is understood that the present inventionis not limited to such an arrangement. The multi—filter optical element 90, for example, maybe reversed so that the darkest of the filters 92 is positioned adjacent the end 68 of the tubularhousing 64. When such an arrangement is used, an increase in beam intensity would signify aneed to move the device 2 farther away from the actuation apparatus 6.Preferably, the actuation apparatus 6 (or at least the coil 30 thereof) is slidably mountedwithin the housing 64 and a knob and gearing (e.g., rack and pinion) mechanism are providedfor selectively moving the actuation apparatus 6 (or coil 30 thereof) axially through the housing64 in a perfectly linear manner until the appropriate axial distance from the Contact device 2 isachieved. When such an arrangement is provided, the first end 66 of the housing 64 serves asa positioning mechanism for the contact device 2 against which the patient presses the facialarea surrounding eye to be examined. once the facial area rests against the first end 66, theknob and gearing mechanism are manipulated to place the actuation apparatus 6 (or coil 30thereof) at the proper axial distance from the contact device 2.Although facial contact with the first end 66 enhances stability, it is understood thatfacial contact is not an essential step in utilizing the present invention.The system also preferably includes an optical alignment mechanism for indicatingwhether the device 2 is properly aligned with the actuation apparatus 6 and the detectingarrangement 8. The optical alignment mechanism includes two alignment beam detectors48’,50' for respectively detecting the reflected beams 60,62 of light prior to any applanation.The alignment beam detectors 48’,50' are arranged so that the reflected beams 60,62 of lightrespectively strike a predetermined portion of the alignment beam detectors 48’,50' prior toapplanation only when the device 2 is properly aligned with respect to the actuation apparatus6 and the detecting arrangement 8. When the device 2 is not properly aligned, the reflectedbeams 60,62 strike another portion of the alignment beam detectors 48’,50', as will be describedhereinafter.The optical alignment mechanism further includes an indicator arrangement responsiveto the alignment beam detectors 48',50’. The indicator arrangement preferably includes a setof LEDs 98,100,lO2,104 which indicate that the proper alignment has been achieved only when102530CA 02264193 1999-02-26WO 98/09564 PCT/US97/ 1548928the reflected beams 60,62 of light respectively strike the predetermined portion of the alignmentbeam detectors 48',50' prior to applanation.Preferably, each of the alignment beam detectors 48',50' includes a respective multi-filter optical element 106,108. The multi-filter optical elements 106,108 are arranged so as toreceive the reflected beams 60,62 of light. Each multi—filter optical element 106,108 containsa plurality of optical filters 110,0-11090 (Figures 4 and 5), each of which filters out a differentpercentage of light. In Figures 4 and 5, the different percentages are labeled between 10 and90 percent in increments of ten percent. It is understood, however, that many otherarrangements and increments will suffice.For the illustrated arrangement, it is preferred that the centrally located filters 11050which filter out 50% of the light represent the predetermined portion of each alignment beamdetector 48',50'. Proper alignment is therefore deemed to exist when the reflected beams 60,62of light pass through the filters 1 10,0 and the intensity of the beams 60,62 is reduced by 50%.Each of the alignment beam detectors 48',50' also preferably includes a beam intensitydetector 1 12,1 14 for respectively detecting the intensity of the reflected beams 60,62 of lightafter the reflected beams 60,62 of light pass through the multi-filter optical elements 106,108.The intensity of each beam is indicative of whether the device 2 is properly aligned with respectto the actuation apparatus 6 and the detecting arrangement .A converging lens 116,118 is preferably located between each multi-filter opticalelement 106,108 and its respective beam intensity detector 112,114. The converging lens116,118 focusses the reflected beams 60,62 of light onto the beam intensity detectors 112,114afier the reflected beams 60,62 pass through the multi-filter optical elements 106,108.Each of the beam intensity detectors 1 12,1 14 has its output connected to an alignmentbeam detection circuit which, based on the respective outputs from the beam intensity detectors112,114, detennines whether there is proper alignment, and if not, drives the appropriate oneor ones of the LEDs 98,100,102,104 to indicate the corrective action which should be taken.As illustrated in Figure 3, the LEDs 98,100,102,104 are respectively arranged above,to the right of, below, and to the lefi of the intersection of the cross-hairs 70. No LEDS98,100,102,104 are illuminated unless there is a misalignment. Therefore, a lack of illuminationindicates that the device 2 is properly aligned with the actuation apparatus 6 and the detectingarrangement 8.152025CA 02264193 1999-02-26W0 98/09564 PCT/US97/1548929When the device 2 on the cornea 4 is too high, the beams 56,58 of light strike a lowerportion of the cornea 4 and because of the cornea's curvature, are reflected in a moredownwardly direction. The reflected beams 60,62 therefore impinge on the lower half of themulti—filter elements 106,108, and the intensity of each reflected beam 60,62 is reduced by nomore than 30%. The respective intensity reductions are then communicated to the alignmentdetection circuit 120 by the beam intensity detectors 112,114. The aligmnent detection circuit120 interprets this reduction of intensity to result from a misalignment wherein the device 2 istoo high. The alignment detection circuit 120 therefore causes the upper LED 98 to illuminate.Such illumination indicates to the user that the device 2 is too high and must be lowered withrespect to the actuation apparatus 6 and the detecting arrangement 8.Similarly, when the device 2 on the cornea 4 is too low, the beams 56,58 of light strikean upper portion of the cornea 4 and because of the cornea's curvature, are reflected in a moreupwardly direction. The reflected beams 60,62 therefore impinge on the upper half of themulti—filter elements 106,108, and the intensity of each reflected beam 60,62 is reduced by atleast 70%. The respective intensity reductions are then communicated to the alignmentdetection circuit 120 by the beam intensity detectors 112,114. The alignment detection circuit120 interprets this particular reduction of intensity to result from a misalignment wherein thedevice 2 is too low. The alignment detection circuit 120 therefore causes the lower LED 102to illuminate. Such illumination indicates to the user that the device 2 is too low and must beraised with respect to the actuation apparatus 6 and the detecting arrangement 8.With reference to Figure 1, when the device 2 is too far to the right, the beams 56,58strike a more leftward side of the cornea 4 and because of the comea's curvature, are reflectedin a more leftward direction. The reflected beams 60,62 therefore impinge on the left halvesof the multi-filter elements 106,108. Since the filtering percentages decrease from left to rightin multi—filter element 106 and increase from lefi to right in multifilter element 108, there willbe a difierence in the intensities detected by the beam intensity detectors 112,] 14. In particular,the beam intensity detector 1 12 will detect less intensity than the beam intensity detector 1 14The different intensities are then communicated to the alignment detection circuit 120 by thebeam intensity detectors 112,114. The alignment detection circuit 120 interprets the intensitydifference wherein the intensity at the beam intensity detector 114 is higher than that at thebeam intensity detector 112, to result from a misaligmnent wherein the device 2 is too far toCA 02264193 1999-02-26PCT/US 97/1543IPEA/Us 03 AUG 19981015202530the right in Figure 1 (too far to the lefi in Figure 3) . The alignment detection circuit 120therefore causes the left LED 104 to illuminate. Such illumination indicates to the user that thedevice 2 is too far to the left (in Figure 3) and must be moved to the right (left in Figure 1) withrespect to the actuation apparatus 6 and the detecting arrangement 8.Similarly, when the device 2 in Figure 1 is too far to the left, the beams 56,58 strike amore rightward side of the cornea 4 and because of the comea's curvature, are reflected in amore rightwardly direction. The reflected beams 60,62 therefore impinge on the right halvesof the multi-filter elements 106,108. Since the filtering percentages decrease fiom lefi to rightin multi-filter element 106 and increase from left to right in multifilter element 108, there willbe a difference in the intensities detected by the beam intensity detectors 1 12,114. In particular,the beam intensity detector 112 will detect more intensity than the beam intensity detector 114.The difi'erent intensities are then communicated to the alignment detection circuit 120 by thebeam intensity detectors 112,114. The alignment detection circuit 120 interprets the intensitydifference wherein the intensity at the beam intensity detector 114 is lower than that at thebeam intensity detector 112, to result from a misalignment wherein the device 2 is too far tothe lefi in Figure 1- (too far to the right in Figure 3) . The alignment detection circuit 120therefore causes the right LED 100 to illuminate. Such illumination indicates to the user thatthe device 2 is too far to the right (in Figure 3) and must be moved to the lefi (right in Figure1) with respect to the actuation apparatus 6 and the detecting arrangement 8.The combination of LEDs 98,100,102,104 and the alignment detection circuit 120therefore constitutes a display arrangement which is responsive to the beam intensity detectors112,114 and which indicates what corrective action should be taken, when the device 2 is notproperly aligned, ir1 order to achieve proper alignment. Preferably, the substantially transparentperipheral portion 36 of the movable central piece 16 is wide enough to permit passage of thebeams 56,58 to the cornea 4 even during misalignment.It is understood that automatic alignment correction may be provided via computer-controlled movement of the actuation apparatus upwardly, downwardly, to the right, and/orto the left, which computer-controlled movement may be generated by an appropriatecomputer-controlled moving mechanism responsive to the optical alignment mechanism.The optical alignment mechanism is preferably used in conjunction with the sightingarrangement, so that the optical alignment mechanism merely provides indications of minorAMENDED 3}-ff-rIO15CA 02264193 1999-02-26WO 98/09564 PCT/US97l1548931alignment corrections while the sighting arrangement provides an indication of major alignmentcorrections. It is understood, however, that the optical alignment mechanism can be used inlieu of the sighting mechanism if the substantially transparent peripheral portion 36 is madewide enough.Although the foregoing alignment mechanism uses the same reflected beams 60,62 usedby the detecting arrangement 8, it is understood that separate alignment beam emitters may beused in order to provide separate and distinct aligmnent beams. The foregoing arrangementis preferred because it saves the need to provide additional emitters and thus is less expensiveto manufacture.Nevertheless, optional alignment beam emitters 122,124 are illustrated in Figure 1. Thealignment mechanism using these optional alignment beam emitters 122,124 would operate inessentially the same manner as its counterpart which uses the reflected beams 60,62.In particular, each of the alignment beam emitters 122,124 emits an optical alignmentbeam toward the device 2. The alignment beam is reflected by the cornea 4 to produce areflected alignment beam. The alignment beam detectors 48',50' are arranged so as to receive,not the reflected beams 60,62 of light, but rather the reflected alignment beams when thealignment beam emitters 122,124 are present. More specifically, the reflected alignment beamsstrike a predetermined portion of each alignment beam detector 48',50' prior to applanationonly when the device 2 is properly aligned with respect to the actuation apparatus 6 and thedetecting arrangement 8. The rest of the system preferably includes the same components andoperates in the same manner as the system which does not use the optional. alignment beamemitters 122, 124.The system may further include an applicator for gently placing the contact device 2 onthe cornea 4. As illustrated in Figures SA-SF, a preferred embodiment of the applicator 127includes an annular piece 127A at the tip of the applicator 127. The annular piece 127Amatches the shape of the movable central piece 16. Preferably, the applicator 127 also includesa conduit l27CN having an open end which opens toward the annular piece 127A. Anopposite end of the conduit l27CN is connected to a squeeze bulb 127SB. The squeeze bulb127SB includes a one-way valve 127V which pennits the flow of air into the squeeze bulb127SB, but prevents the flow of air out of the squeeze bulb 127SB through the valve 127V.When the squeeze bulb 127SB is squeezed and then released, a suction effect is created at thel01525CA 02264193 1999-02-26WO 98109564 PCT/US97/1548932open end of the conduit 127CN as the squeeze bulb 127SB tries to expand to its pre-squeezeshape. This suction effect may be used to retain the contact device 2 at the tip of the applicator127.In addition, a pivoted lever system 127B is arranged to detach the movable central piece16 from the annular piece 127A when a knob 127C at the base of the applicator 127 is pressed,thereby nudging the contact device 2 away from the annular piece 127A.Alternatively, the tip of the applicator 127 may be selectively magnetized anddemagnetized using electric current flowing through the annular piece 127A. This arrangementreplaces the pivoted lever system 127B with a magnetization mechanism capable of providinga magnetic field which repels the movable central piece 16, thereby applying the contact device2 to the cornea 4.A preferred circuit arrangement for implementing the above combination of elementsis illustrated schematically in Figure 6. According to the preferred circuit arrangement, thebeam intensity detectors 112,114 comprise a pair of photosensors which provide a voltageoutput proportional to the detected beam intensity. The output from each beam intensitydetector 112,114 is respectively connected to the non-inverting input terminal of a filteringamplifier 126,128. The inverting terminals of the filtering amplifiers 126,128 are connected toground. The amplifiers 126,128 therefore provide a filtering and amplification effect.In order to determine whether proper vertical alignment exists, the output from thefiltering amplifier 128 is applied to an inverting input terminal of a vertical alignmentcomparator 130. The vertical alignment comparator 130 has its non-inverting input terminalconnected to a reference voltage Vrefl. The reference voltage Vref} is selected so that itapproximates the output from the filtering amplifier 128 whenever the light beam 62 strikes thecentral row of filters llO4(,_60 of the multi-filter optical element 108 (ie, when the propervertical alignment is achieved).Consequently, the output from the comparator 130 is approximately zero when propervertical alignment is achieved, is significantly negative when the contact device 2 is too high,and is significantly positive when the contact device 2 is too low. This output from thecomparator 130 is then applied to a vertical alignment switch 132. The vertical alignmentswitch 132 is logically arranged to provide a positive voltage to an AND-gate 134 only whenthe output from the comparator 130 is approximately zero, to provide a positive voltage to the15202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548933LED 98 only when the output from the comparator 130 is negative, and to provide a positivevoltage to the LED 102 only when the output from the comparator 130 is positive. The LEDs98,102 are thereby illuminated only when there is a vertical misalignment and each illuminationclearly indicates what corrective action should to be taken.In order to determine whether proper horizontal alignment exists, the output from thefiltering amplifier 126 is applied to a non-inverting input terminal of a horizontal alignmentcomparator 136, while the inverting input terminal of the horizontal alignment comparator 136is connected to the output from the filtering amplifier 128. The comparator 136 thereforeproduces an output which is proportional to the difference between the intensities detected bythe beam intensity detectors 112,114. This difference is zero whenever the light beams 60,62strike the central column of filters 1 1020, 1 1050, 1 IQO of the multi-filter optical elements106,108 (i.e., when the proper horizontal aligmnent is achieved).The output from the comparator 136 is therefore zero when the proper horizontalalignment is achieved, is negative when the contact device 2 is too far to the right (in Figure1), and is positive when the contact device 2 is too far to the lefl (in Figure 1) . This outputfrom the comparator 130 is then applied to a horizontal alignment switch 138. The horizontalalignment switch 138 is logically arranged to provide a positive voltage to the AND-gate 134only when the output from the comparator 136 is zero, to provide a positive voltage to theLED 104 only when the output from the comparator 136 is negative, and to provide a positivevoltage to the LED 100 only when the output from the comparator 136 is positive. The LEDs100, 104 are ‘thereby illuminated only when there is a horizontal misalignment and eachillumination clearly indicates what corrective action should be taken.In accordance with the preferred circuit arrangement illustrated in Figure 6, the beamintensity detection sensor 94 of the distance measurement beam detector 86 includes aphotosensor 140 which produces a voltage output proportional to the detected beam intensity.This voltage output is applied to the non-inverting input terminal of a filtering amplifier 142.The inverting terminal of the filtering amplifier 142 is connected to ground. Accordingly, thefiltering amplifier 142 filters and amplifies the voltage output from the photosensor 140. Theoutput from the filtering amplifier 142 is applied to the non-inverting input terminal of adistance measurement comparator 144. The comparator 144 has its inverting terminalconnected to a reference voltage Vrefz. Preferably, the reference voltage Vrefz is selected so1015202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/ 1548934as to equal the output of the filtering amplifier 142 only when the proper axial distanceseparates the contact device 2 from the actuation apparatus 6 and detecting arrangement 8.Consequently, the output from the comparator 144 is zero whenever the proper axialdistance is achieved, is negative whenever the second reflected beam 84 passes through a darkportion of the multi-filter optical element 90 (i.e., whenever the axial distance is too great), andis positive whenever the second reflected beam 84 passes through a light portion of the multi-filter optical element 90 (i.e., whenever the axial distance is too short).The output from the comparator 144 is then applied to a distance measurement switch146. The distance measurement switch 146 drives the LED 88c with positive voltage wheneverthe output from the comparator 144 is zero, drives the LED 88b only when the output fromthe comparator 144 is positive, and drives the LED 88a only when the output from thecomparator 144 is negative. The LEDs 88a,88b are thereby illuminated only when the axialdistance separating the contact device 2 from the actuation apparatus 6 and the detectingarrangement 8 is improper. Each illumination clearly indicates what corrective action shouldbe taken. Of course, when the LED 88c is illuminated, no corrective action is necessary.\Vrth regard to the detecting arrangement 8, the preferred circuit arrangement illustratedin Figure 6 includes the two light sensors 48,50. The outputs from the light sensors 48,50 areapplied to and added by an adder 147. The output from the adder 147 is then applied to thenon-inverting input terminal of a filtering amplifier 148. The inverting input terminal of thesame amplifier 148 is connected to ground. As a result, the filtering amplifier 148 filters andamplifies the sum of the output voltages from the light sensor 48,50. The output from thefiltering amplifier 148 is then applied to the non-inverting input terminal of an applanationcomparator 150. The inverting input terminal of the applanation comparator 150 is connectedto a reference voltage Vrefa. Preferably, the reference voltage Vref, is selected so as to equalthe output from the filtering amplifier 148 only when the predetermined amount of applanationis achieved (i.e., when the reflected beams 60,62 strike the light sensors 48,50). The outputfrom the applanation comparator 150 therefore remains negative until the predeterminedamount of applanation is achieved.The output from the applanation comparator 150 is connected to an applanation switch152. Th applanation switch 152 provides a positive output voltage when the output from theapplanation comparator 150 is negative and terminates its positive output voltage whenever1015202530CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548935the output from the applanation comparator 150 becomes positive.Preferably, the output from the applanation switch 152 is connected to an applanationspeaker 154 which audibly indicates when the predetermined amount of applanation has beenachieved. In particular, the speaker 154 is activated whenever the positive output voltage fromthe applanation, switch 152 initially disappears.In the preferred circuit of Figure 6, the coil 30 is electrically connected to the currentproducing circuitry 32 which, in turn, includes a signal generator capable of producing theprogressively increasing current in the coil 30. The current producing circuitry 32 is controlledby a start/stop switch 156 which is selectively activated and deactivated by an AND-gate 158.The AND-gate 158 has two inputs, both of which must exhibit positive voltages inorder to activate the start/stop switch 156 and current producing circuitry 32. A first input 160of the two inputs is the output from the applanation switch 152. Since the applanation switch152 normally has a positive output voltage, the first input 160 remains positive and the AND-gate is enabled at least with respect to the first input 160. However, whenever thepredetermined amount of applanation is achieved (i.e. whenever the positive output voltage isno longer present at the output from the applanation switch 152), the AND-gate 158deactivates the current producing circuitry 32 via the start/stop switch 156.The second input to the AND-gate 158 is the output from another AND-gate 162. Theother AND-gate 162 provides a positive output voltage only when a push-action switch 164is pressed and only when the contact device 2 is located at the proper axial distance from, andis properly aligned both vertically and horizontally with, the actuation apparatus 6 and thedetecting arrangement 8. The current producing circuitry 32 therefore cannot be activatedunless there is proper alignment and the proper axial distance has been achieved. In order toachieve such operation, the output from the AND-gate 134 is connected to a first input of theAND-gate 162 and the push-action switch 164 is connected to the second input of the AND-gate 162.A delay element 163 is located electrically between the AND-gate 134 and the AND-gate 162. The delay element 163 maintains a positive voltage at the first input terminal to theAND-gate 162 for a predetermined period of time after a positive voltage first appears at theoutput terminal of the AND-gate 134. The primary purpose of the delay element 163 is toprevent deactivation of the current producing circuitry 32 which would otherwise occur in10152025CA 02264193 1999-02-26WO 98/09564 PCT/US97ll 548936response to changes in the propagation direction of the reflected beams 60,62 during the initialstages of applanation. The predetermined period of time is preferably selected pursuant to themaximum amount of time that it could take to achieve the predetermined amount ofapplanation.According to the preferred circuitry illustrated in Figure 6, misalignment and improperaxial separation of the contact device 2 with respect to the actuation apparatus 6 and detectingarrangement 8 is audibly announced by a speaker 166 and causes deactivation of a display 167.The display 167 and speaker 166 are connected and responsive to an AND-gate 168. TheAND-gate 168 has an inverting input connected to the push-action switch 164 and anotherinput connected to a three-input OR-gate 170.Therefore, when the push-action switch 164 is activated, the inverting input terminalof the AND-gate 168 prevents a positive voltage from appearing at the output from the AND-gate 168. Activation of the speaker 166 is thereby precluded. However, when the push-actionswitch is not activated, any positive voltage at any of the three inputs to the OR-gate 170 willactivate the speaker 166. The three inputs to the OR-gate 170 are respectively connected tooutputs from three other OR-gates 172,174,176. The OR-gates 172,174,176, in turn, havetheir inputs respectively connected to the LEDs 100,104, LEDs 98,102, and LEDs 88a,88b.Therefore, whenever any one of these LEDs 88a, 88b, 98, 100, 102, 104 is activated, the OR-gate 170 produces a positive output voltage. The speaker 166, as a result, will be activatedwhenever any one of the LEDs 88a,88b,98,100,102,104 is activated while the push-actionswitch 164 remains deactivated.Turning now to the current producing circuitry 32, the output from the currentproducing circuitry 32 is connected to the coil 30. The coil 30, in turn, is connected to acurrent-to-voltage transducer 178. The output voltage from the current-to-voltage transducer178 is proportional to the current flowing through the coil 30 and is applied to the calculationunit 10.The calculation unit 10 receives the output voltage from the transducer 178 andconverts this output voltage indicative of current to an output voltage indicative of intraocularpressure. Initially, an output voltage from the filtering amplifier 142 indicative of the axialdistance separating the contact device 2 from the actuation apparatus 6 and the detectingarrangement 8, is multiplied by a reference voltage Vref} using a multiplier 180. The reference1015202530CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548937voltage Vref4 represents a distance calibration constant. The output from the multiplier 180is then squared by a multiplier 182 to create an output voltage indicative of distance squared(dz).The output from the multiplier 182 is then supplied to an input terminal of a divider184. The other input terminal of the divider 184 receives the output voltage indicative ofcurrent from the current-to-voltage transducer 178. The divider 184 therefore produces anoutput voltage indicative of the current in the coil 30 divided by the distance squared (I/dz).The output voltage from the divider 184 is then applied to a multiplier 186. Themultiplier 186 multiplies the output voltage from the divider 184 by a reference voltage Vref,.The reference voltage Vref, corresponds to a conversion factor for converting the value of(I/dz) to a value indicative of force in Newtons being applied by the movable central piece 16against the cornea 4. The output voltage from the multiplier 186 is therefore indicative of theforce in Newtons being applied by the movable central piece 16 against the cornea.Next, the output voltage from the multiplier 186 is applied to an input terminal of adivider 188. The other input terminal of the divider 188 receives a reference voltage Vrefé.The reference voltage Vrefs corresponds to a calibration constant for converting force (inNewtons) to pressure (in Pascals) depending on the surface area of the movable central piece'ssubstantially flat inner side 24. The output voltage from the divider 188 is therefore indicativeof the pressure (in Pascals) being exerted by the cornea 4 against the inner side of the movablecentral piece 16 in response to displacement of the movable central piece 16.Since ‘the pressure exerted by the cornea 4 depends upon the surface area of thesubstantially flat inner side 24, the output voltage from the divider 188 is indicative ofintraocular pressure only when the cornea 4 is being applanated by the entire surface area ofthe inner side 24. This, in turn, corresponds to the predetermined amount of applanation.Preferably, the output voltage indicative of intraocular pressure is applied to an inputterminal of a multiplier 190. The multiplier 190 has another input terminal connected to areference voltage Vref,. The reference voltage Vref; corresponds to a conversion factor forconverting pressure in Pascals to pressure in millimeters of mercury (mmHg). The voltageoutput from the multiplier 190 therefore is indicative of intraocular pressure in millimeters ofmercury (mml-lg) whenever the predetermined amount of applanation is achieved.The output voltage from the multiplier 190 is then applied to the display 167 which1015202530CA 02264193 1999-02-26W0 98I09564 PCT/U S97/ 1548938provides a visual display of intraocular pressure based on this output voltage. Preferably, thedisplay 167 or calculation unit 10 includes a memory device 33 which stores a pressure valueassociated with the output voltage from the multiplier 190 whenever the predetermined amountof applanation is achieved. Since the current producing circuitry 32 is automatically andimmediately deactivated upon achieving the predetermined amount of applanation, theintraocular pressure corresponds to the pressure value associated with the peak output voltagefrom the multiplier 190. The memory therefore can be triggered to store the highest pressurevalue upon detecting a drop in the output voltage from the multiplier 190. Preferably, thememory is automatically reset prior to any subsequent measurements of intraocular pressure.Although Figure 6 shows the display 167 in digital form, it is understood that thedisplay 167 may have any known form. The display 167 may also include the three LEDs40A,4OB,40C illustrated in Figure 1 which give a visual indication of pressure ranges which,in turn, are calibrated for each patient.As indicated above, the illustrated calculation unit 10 includes separate and distinctmultipliers 180,182,186, 190 and dividers 184,188 for converting the output voltage indicativeof current into an output voltage indicative of intraocular pressure in millimeters of mercury(mmHg). The separate and distinct multipliers and dividers are preferably provided so thatvariations in the system's characteristics can be compensated for by appropriately changing thereference voltages Vret], Vrefs, Vrefs and/or Vref,. It is understood, however, that when allof the system's characteristics remain the same (e.g., the surface area of the inner side 24 andthe desired distance separating the contact device 2 from the actuation apparatus 6 anddetecting arrangement 8) and the conversion factors do not change, that a single conversionfactor derived from the combination of each of the other conversion factors can be used alongwith a single multiplier or divider to achieve the results provided by the various multipliers anddividers shown in Figure 6.Although the above combination of elements is generally effective at accuratelymeasuring intraocular pressure in a substantial majority of patients, some patients haveunusually thin or unusually thick corneas. This, in turn, may cause slight deviations in themeasured intraocular pressure. In order to compensate for such deviations, the circuitry ofFigure 6 may also include a variable gain amplifier 191 (illustrated in Figure 7A) connected tothe output from the multiplier 190. For the majority of patients, the variable gain amplifier 191l0l52025CA 02264193 1999-02-26WO 98/09564 PCT/US97Il548939is adjusted to provide a gain (g) of one. The variable gain amplifier 191 therefore would haveessentially no effect on the output from the multiplier 190.However, for patients with unusually thick corneas, the gain (g) is adjusted to a positivegain less than one. A gain (g) of less than one is used because unusually thick corneas are moreresistant to applanation and consequently result in a pressure indication that exceeds, albeit bya small amount, the actual intraocular pressure. The adjustable gain amplifier 191 thereforereduces the output voltage from the multiplier 190 by a selected percentage proportional to thecomea's deviation from normal corneal thickness.For patients with unusually thin corneas, the opposite effect would be observed.Accordingly, for those patients, the gain (g) is adjusted to a positive gain greater than one sothat the adjustable gain amplifier 191 increases the output voltage from the multiplier 190 bya selected percentage proportional to the comea's deviation from normal corneal thickness.Preferably, the gain (g) is manually selected forneach patient using any known meansfor controlling the gain of a variable gain amplifier, for example, a potentiometer connected toa voltage source. As indicated above, the particular gain (g) used depends on the thickness ofeach patient's cornea which, in turn, can be determined using known corneal pachymetrytechniques. Once the corneal thickness is determined, the deviation from the normal thicknessis calculated and the gain (g) is set accordingly.Alternatively, as illustrated in Figure 7B, the gain (g) may be selected automatically byconnecting an output (indicative of corneal thickness) from a known pachymetry apparatus 193to a buffer circuit 195. The buifer circuit 195 converts the detected corneal thickness to a gainsignal associated with the detected thickness‘ deviation from the nonnal corneal thickness. Inparticular, the gain signal produces a gain (g) of one when the deviation is zero, produces again (g) greater than one when the detected corneal thickness is less than the normal thickness,and produces a gain (g) less than one when the detected corneal thickness is greater than thenormal thickness.Although Figures 7A and 7B illustrate a configuration which compensates only forcorneal thickness, it is understood that similar configurations can be used to compensate forcorneal curvature, eye size, ocular rigidity, and the like. For levels of corneal curvature whichare higher than normal, the gain would be less than one. The gain would be greater than onefor levels of corneal curvature which are flatter than normal. Typically, each increase in onel01525CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548940diopter of corneal curvature is associated with a 0.34 mm Hg increase in pressure. Theintraocular pressure rises 1 mm Hg for very 3 diopters. The gain therefore can be applied inaccordance with this general relationship.In the case of eye size compensation, larger than normal eyes would require a gainwhich is less than one, while smaller than normal eyes would require a gain which is greaterthan one.For patients with "stiiTer" than normal ocular rigidities, the gain is less than one, but forpatients with softer ocular rigidities, the gain is greater than one.As when compensating for corneal thickness, the gain may be manually selected foreach patient, or alternatively, the gain may be selected automatically by connecting theapparatus of the present invention to a known keratometer when compensating for cornealcurvature, and/or a known biometer when compensating for eye size.Despite not being illustrated, it is understood that the system includes a power supplymechanism for selectively powering the system using either batteries or household AC current.Operation of the preferred circuitry will now be described. Initially, the contact device2 is mounted on the corneal surface of a patient and tends to locate itself centrally at the frontofthe cornea 4 in essentially the same way as conventional contact lenses. The patient thenlooks through the central sight hole 38 at the intersection of the cross-hairs which define themark 70, preferably, while the light 75 provided inside the tubular housing 64 is illuminated tofacilitate visualization of the cross-hairs and the reflected image 74. A rough alignment isthereby achieved.Next, the preferred circuitry provides indications of misalignment or improper axialdistance should either or both exist. The patient responds to such indications by taking theindicated corrective action.Once proper alignment is achieved and the proper axial distance exists between theactuation apparatus 6 and the contact device 2, push-action switch 164 is activated and theAND-gate 158 and start/stop switch 156 activate the current producing circuitry 32. Inresponse to activation, the current producing circuitry 32 generates the progressively increasingcurrent in the coil 30. The progressively increasing current creates a progressively increasingmagnetic field in the coil 30. The progressively increasing magnetic field, in turn, causes axialdisplacement of the movable central piece 16 toward the cornea 4 by virtue of the magnetic10152030CA 02264193 1999-02-26W0 98/09564 PCT/US97/1548941field's repulsive effect on the magnetically responsive element 26. Since axial displacement ofthe movable central piece 16 produces a progressively increasing applanation of the cornea 4,the reflected beams 60,62 begin to swing angularly toward the light sensors 48,50. Such axialdisplacement and increasing applanation continues until both reflected beams 60,62 reach thelight sensors 48,50 and the predetermined amount of applanation is thereby deemed to exist.At that instant, the current producing circuit 32 is deactivated by the input 160 to AND-gate158; the speaker 154 is momentarily activated to give an audible indication that applanation hasbeen achieved; and the intraocular pressure is stored in the memory device 33 and is displayedon display 167.Although the above—described and illustrated embodiment includes various preferredelements, it is understood that the present invention may be achieved using various otherindividual elements. For example, the detecting arrangement 8 may utilize various otherelements, including elements which are typically utilized in the art of barcode reading.With reference to Figures 8A and 8B, a Contact device 2' may be provided with abarcode-like pattern 300 which varies in response to displacement of the movable central piece16'. Figure 8A illustrates the preferred pattern 300 prior to displacement of the movable centralpiece 16'; and Figure 8B shows the preferred pattern 300 when the predetermined amount ofapplanation is achieved. The detecting arrangement therefore would include a barcode readerdirected generally toward the contact device 2' and capable of detecting the differences in thebarcode pattern 300.Alternatively, as illustrated in Figures 9A and 9B, the contact device 2‘ may be providedwith a multi—color pattern 310 which varies in response to displacement of the movable centralpiece 16'. Figure 9A schematically illustrates the preferred color pattern 310 prior todisplacement of the movable central piece 16', while Figure 9B schematically shows thepreferred pattern 3 l0 when the predetermined amount of applanation is achieved. Thedetecting arrangement therefore would include a beam emitter for emitting a beam of lighttoward the pattern 310 and a detector which receives a reflected beam from the pattern 310 anddetects the reflected color to determine whether applanation has been achieved.Yet another way to detect the displacement of the movable central piece 16 is by usinga two dimensional array photosensor that senses the location of a reflected beam of light.Capacitive and electrostatic sensors, as well as changes in magnetic field can then be used to1520CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548942encode the position of the reflected beam and thus the displacement of the movable centralpiece 16.According to yet another alternative embodiment illustrated in Figure 10, a miniatureLED 320 is inserted into the contact device 2'. The piezoelectric ceramic is driven by ultrasonicwaves or is alternatively powered by electromagnetic waves. The brightness of the miniatureLED 320 is determined by the current flowing through the miniature LED 320 which, in turn,may be modulated by a variable resistance 330. The motion of the movable central piece 16'varies the variable resistance 330. Accordingly, the intensity of light from the miniature LED320 indicates the magnitude of the movable central piece's displacement. A miniature, low-voltage primary battery 340 may be inserted into the contact device 2' for powering theminiature LED 320.With regard to yet another preferred embodiment of the present invention, it isunderstood that a tear film typically covers the eye and that a surface tension resultingtherefrom may cause underestimation of the intraocular pressure. Accordingly, the contactdevice of the present invention preferably has an inner surface of hydrophobic flexible materialin order to decrease or eliminate this potential source of errorIt should be noted that the drawings are merely schematic representations of thepreferred embodiments. Therefore, the actual dimensions of the preferred embodiments andphysical arrangement of the various elements is not limited to that which is illustrated. Variousarrangements and dimensions will become readily apparent to those of ordinary skill in the art.The size of the movable central piece, for example, can be modified for use in animals orexperimental techniques. Likewise, the contact device can be made with smaller dimensionsfor use with infants and patients with eye lid abnormalities.One preferred arrangement of the present invention includes a handle portion extendingout from below the housing 64 and connected distally to a platform. The platform acts as abase for placement on a planar surface (e.g., a table), with the handle projecting up therefromto support the actuation apparatus 6 above the planar surface.TNDENTATIONThe contact device 2 and associated system illustrated in Figures I-5 may also be usedto detect intraocular pressure by indentation. When indentation techniques are used in10152025CA 02264193 1999-02-26W0 93/09564 PCT/US97/1548943measuring intraocular pressure, a predetermined force is applied against the cornea using anindentation device. Because of the force, the indentation device travels in toward the cornea,indenting the cornea as it travels. The distance travelled by the indentation device into thecornea in response to the predetermined force is known to be inversely proportional tointraocular pressure. Accordingly, there are various known tables which, for certain standardsizes of indentation devices and standard forces, correlate the distance travelled and intraocularpressure.In utilizing the illustrated arrangement for indentation, the movable central piece 16 ofthe contact device 2 fiinctions as the indentation device. In addition, the current producingcircuit 32 is switched to operate in an indentation mode. When switched to the indentationmode, the current producing circuit 32 supplies a predetermined amount of current through thecoil 30. The predetermined amount of current corresponds to the amount of current neededto produce one of the aforementioned standard forces.The predetermined amount of current creates a magnetic field in the actuation apparatus6. This magnetic field, in turn, causes the movable central piece 16 to push inwardly against thecornea 4 via the flexible membrane 14. Once the predetermined amount of current has beenapplied and a standard force presses against the cornea, it is necessary to determine how far themovable central piece 16 moved into the cornea 4.Accordingly, when measurement of intraocular pressure by indentation is desired, thesystem illustrated in Figure 1 further includes a distance detection arrangement for detectinga distance travelled by the movable central piece 16, and a computation portion 199 in thecalculation unit 10 for determining intraocular pressure based on the distance travelled by themovable central piece 16 in applying the predetermined amount of force.A preferred indentation distance detection arrangement 200 is illustrated in Figures 1 IAand 1 1B and preferably includes a beam emitter 202 and a beam sensor 204. Preferably, lenses205 are disposed in the optical path between the beam emitter 202 and beam sensor 204. Thebeam emitter 202 is arranged so as to emit a beam 206 of light toward the movable centralpiece 16. The beam 206 of light is reflected back from the movable central piece 16 to createa reflected beam 208. The beam sensor 204 is positioned so as to receive the reflected beam208 whenever the device 2 is located at the proper axial distance and in proper alignment withthe actuation apparatus 6. Preferably, the proper distance and alignment are achieved using all. ,.......,................_................................._.. . , . _H__...................-..,.,,.1015CA 02264193 1999-02-26WO 98/09564 PCT /US97/1548944or any combination of the aforementioned sighting mechanism, optical alignment mechanismand optical distance measuring mechanism.Once proper alignment and the proper axial distance are achieved, the beam 206 strikesa first portion of the movable central piece 16, as illustrated in Figure 11A. Upon reflectionof the beam 206, the reflected beam 208 strikes a first portion of the beam sensor 204. InFigure 11A, the first portion is located on the beam sensor 204 toward the right side of thedrawing.However, as indentation progresses, the movable central piece 16 becomes more distantfrom the beam emitter 202. This increase in distance is illustrated in Figure 11A. Since themovable central piece 16 moves linearly away, the beam 206 strikes progressively more to theleft on the movable central piece 16. The reflected beam 206 therefore shifis toward the lefiand strikes 204 at a second portion which is to the left of the first portion.The beam sensor 204 is arranged so as to detect the shifi in the reflected beam 206,which shift is proportional to the displacement of the movable central piece 16. Preferably, thebeam sensor 204 includes an intensity responsive beam detector 212 which produces an outputvoltage proportional to the detected intensity of the reflected beam 208 and an optical filterelement 210 which progressively filters more light as the light's point of incidence moves fromone portion of the filter to an opposite portion.In Figures 11A and 11B, the optical filter element 210 comprises a filter with aprogressively increasing thickness so that light passing through a thicker portion has a moresignificantly reduced intensity than light passing through a thinner portion of the filter.Alternatively, the filter can have a constant thickness and progressively increasing filteringdensity whereby a progressively increasing filtering effect is achieved as the point of incidencemoves across a longitudinal length of the filter.When, as illustrated in Figure 11A, the reflected beam 208 passes through a thinnestportion of the optical filter element 210 (e.g., prior to indentation) , the reflected beam‘ sintensity is reduced by only a small amount. The intensity responsive beam detector 212therefore provides a relatively high output voltage indicating that no movement of the movablecentral piece 16 toward the cornea 4 has occurred.However, as indentation progresses, the reflected beam 208 progressively shifts towardthicker portions of the optical filter element 210 which filter more light. The intensity of thel0202530CA 02264193 1999-02-26W0 93/09554 PCT/US97/1548945reflected beam 208 therefore decreases proportionally to the displacement of the movablecentral piece 16 toward the cornea 4. Since the intensity responsive beam detector 212produces an output voltage proportional to the reflected beam's intensity, this output voltagedecreases progressively as the displacement of the movable central piece 16 increases. Theoutput voltage from the intensity responsive beam detector 212 is therefore indicative of themovable central piece's displacement.Preferably, the computation portion 199 is responsive to the current producing circuitry32 so that, once the predetermined amount of force is applied, the output voltage from thebeam detectors 212 is received by the computation portion 199. The computation portion then,based on the displacement associated with the particular output voltage, determines intraocularpressure. Preferably, the memory 33 includes a memory location for storing a value indicativeof the intraocular pressure.Also, the computation portion 199 preferably has access to an electronically ormagnetically stored one of the aforementioned known tables. Since the tables indicate whichintraocular pressure corresponds with certain distances traveled by the movable central piece16, the computation portion I99 is able to determine intraocular pressure by merelydetermining which pressure corresponds with the distance traveled by the movable central piece16.The system of the present invention may also be used to calculate the rigidity of thesclera. In particular, the system is first used to determine intraocular pressure by applanationand then is used to determine intraocular pressure by indentation. The differences between theintraocular pressures detected by the two methods would then be indicative of the sclera'srigidity.Although the foregoing description of the preferred systems generally refers to acombined system capable of detecting intraocular pressure by both applanation and indentation,it is understood that a combined system need not be created. That is, the system capable ofdetermining intraocular pressure by applanation may be constructed independently from aseparate system for determining intraocular pressure by indentation and vice versa.l\/[EASURING HYDRODYNAIVHCS OF THE EYEThe indentation device of the present invention may also be utilized to non-invasively10152530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548946measure hydrodynamics of an eye including outflow facility. The method of the presentinvention preferably comprises several steps including the following:According to a first step, an indentation device is placed in contact with the cornea.Preferably, the indentation device comprises the contact device 2 illustrated in Figures 1 and2A-2D.Next, at least one movable portion of the indentation device is moved in toward thecornea using a first predetemiined amount of force to achieve indentation of the cornea. Whenthe indentation device is the contact device 2, the movable portion consists of the movablecentral piece 16.An intraocular pressure is then determined based on a first distance traveled toward thecornea by the movable portion of the indentation device during application of the firstpredetermined amount of force. Preferably, the intraocular pressure is determined using theaforementioned system for determining intraocular pressure by indentation.Next, the movable portion of the indentation device is rapidly reciprocated in towardthe cornea and away from the cornea at a first predetermined frequency and using a secondpredetermined amount of force during movement toward the cornea to thereby forceintraocular fluid out from the eye. The second predetermined amount of force is preferablyequal to or greater than the first predetermined amount of force. It is understood, however,that the second predetermined amount of force may be less than the first predetermined amountof force. The reciprocation, which preferably continues for 5 seconds, should generally notexceed 10 seconds induration.The movable portion is then moved in toward the cornea using a third predeterminedamount of force to again achieve indentation of the cornea.A second intraocular pressure is then determined based on a second distance traveledtoward the cornea by the movable portion of the indentation device during application of thethird predetermined amount of force. This second intraocular pressure is also preferablydetermined using the aforementioned system for determining intraocular pressure byindentation. Since intraocular pressure decreases as a result of forcing intraocular fluid out ofthe eye during the rapid reciprocation of the movable portion, it is generally understood that,unless the eye is so defective that no fluid flows out therefrom, the second intraocular pressurewill be less than the first intraocular pressure. This reduction in intraocular pressure is15202530CA 02264193 1999-02-26WO 98/09564 PCTIUS97/1548947indicative of outflow facility.Next, the movable portion of the indentation device is again rapidly reciprocated intoward the cornea and away from the cornea, but at a second predetermined frequency andusing a fourth predetermined amount of force during movement toward the cornea. The fourthpredetermined amount of force is preferably equal or greater than the second predeterminedamount of force. It is understood, however, that the fourth predetennined amount of force maybe less than the second predetermined amount of force. Additional intraocular fluid is therebyforced out from the eye. This reciprocation, which also preferably continues for 5 seconds,should generally not exceed 10 seconds in duration.The movable portion is subsequently moved in toward the cornea using a fifthpredetermined amount of force to again achieve indentation of the cornea.Thereafter, a third intraocular pressure is determined based on a third distance traveledtoward the cornea by the movable portion of the indentation device during application of thefilth predetermined amount of force.The differences are then preferably calculated between the first, second, and thirddistances, which differences are indicative of the volume of intraocular fluid which lefl: the eyeand therefore are also indicative of the outflow facility. It is understood that the differencebetween the first and last distances may be used, and in this regard, it is not necessary to usethe differences between all three distances. In fact, the difference between any two of thedistances will suffice.Although the relationship between the outflow facility and the detected differencesvaries when the various parameters of the method and the dimensions of the indentation devicechange, the relationship for given parameters and dimensions can be easily determined byknown experimental techniques and/or using known Friedenwald Tables.The method of the present invention is preferably carried out using an indenting surfacewhich is three millimeters in diameter and a computer equipped with a data acquisition board.In particular, the computer generates the predetermined forces via a digital-to-analog (D/A)converter connected to the current generating circuitry 32. The computer then receives signalsindicative of the first, second, and third predetermined distances via an analog-to-digital (A/D)converter. These signals are analyzed by the computer using the aforementioned relationshipbetween the differences in distance and the outflow facility. Based on this analysis, the1015202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/ 1548948computer creates an output signal indicative of outflow facility. The output signal is preferablyapplied to a display screen which, in turn, provides a visual indication of outflow facility.Preferably, the method fiirther comprises the steps of plotting the differences betweenthe first, second, and third distances to a create a graph of the differences and comparing theresulting graph of differences to that of a normal eye to determine if any irregularities inoutflow facility are present. As indicated above, however, it is understood that the differencebetween the first and last distances may be used, and in this regard, it is not necessary to usethe differences between all three distances. In fact, the difference between any two of thedistances will sufiice.Preferably, the first predetermined frequency and second predetermined frequency aresubstantially equal and are approximately 20 Hertz. Generally, any frequencies up to 35 Hertzcan be used, though frequencies below 1 Hertz are generally less desirable because the stressrelaxation of the eye's outer coats would contribute to changes in pressure and volume.The fourth predetermined amount of force is preferably at least twice the secondpredetermined amount of force, and the third predetermined amount of force is preferablyapproximately half of the first predetermined amount of force. It is understood, however, thatother relationships will suffice and that the present method is not limited to the foregoingpreferred relationships.According to a preferred use of the method, the first predetermined amount of forceis between 0.01 Newton and 0.015 Newton; the second predetermined amount of force isbetween 0.005 Newton and 0.0075 Newton; the third predetermined amount of force isbetween 0. 005 Newton and 0. 0075 Newton; the fourth predetermined amount of force isbetween 0.0075 Newton and 0.0125 Newton; the fifih predetermined amount of force isbetween 0.0125 Newton and 0.025 Newton; the first predetermined frequency is between 1Hertz and 35 Hertz; and the second predetermined frequency is also between 1 Hertz and 35Hertz. The present method, however, is not limited to the foregoing preferred ranges.Although the method of the present invention is preferably carried out using theaforementioned device, it is understood that various other tonometers may be used. Themethod of the present invention therefore is not limited in scope to its use in conjunction withthe claimed system and illustrated contact device.l0I5202530CA 02264193 1999-02-26WO 98/09564 PCT/US97l1548949ALTERNATIVE EMBODIIVIENTS OF THE CONTACT DEVICEAlthough the foregoing description utilizes an embodiment of the contact device 2which includes a flexible membrane 14 on the inside surface of the contact device 2, it is readilyunderstood that the present invention is not limited to such an arrangement, Indeed, there aremany variations of the contact device which fall well within the scope of the present invention.The contact device 2, for example, may be manufactured with no flexible membrane,with the flexible membrane on the outside surface of the contact device 2 (i.e., the side awayfiom the cornea), with the flexible membrane on the inside surface of the contact device 2, orwith the flexible membrane on both sides of the contact device 2.Also, the flexible membrane (s) 14 can be made to have an annular shape, thuspermitting light to pass undistorted directly to the movable central piece 16 and the cornea forreflection thereby.In addition, as illustrated in Figure 12, the movable central piece 16 may be formed witha similar annular shape so that a transparent central portion thereof merely contains air. Thisway, light passing through the entire contact device 2 impinges directly on the cornea withoutundergoing any distortion due to the contact device 2.Alternatively, the transparent central portion can be filled with a transparent solidmaterial. Examples of such transparent solid materials include polymethyl methacrylate, glass,hard acrylic, plastic polymers, and the like. According to a preferred arrangement, glass havingan index of refraction substantially greater than that of the cornea is utilized to enhancereflection of light by the cornea when the light passes through the contact device 2. Preferably,the index of refraction for the glass is greater than 1.7, compared to the typical index ofrefraction of 1.37 associated with the cornea.It is understood that the outer surface of the movable central piece 16 may be coatedwith an anti-reflection layer in order to eliminate extraneous reflections from that surface whichmight otherwise interfere with operation of the alignment mechanism and the applanationdetecting arrangement.The interconnections of the various components of the contact device 2 are also subjectto modification without departing from the scope and spirit of the present invention. It isunderstood therefore that many ways exist for interconnecting or otherwise maintaining theworking relationship between the movable central piece 16, the rigid annular member 12, and101520CA 02264193 1999-02-26WO 98109564 PCT/US97/1548950the membranes 14.When one or two flexible membranes 14 are used, for example, the substantially rigidannular member 12 can be attached to any one or both of the flexible membrane(s) 14 using anyknown attachment techniques, such as gluing, heat-bonding, and the like. Alternatively, whentwo flexible membranes 14 are used, the components may be interconnected or otherwisemaintained in a working relationship, without having to directly attach the flexible membrane14 to the substantially rigid annular member 12. Instead, the substantially rigid armular member12 may be retained between the two flexible membranes 14 by bonding the membranes to oneanother about their peripheries while the rigid annular member 12 is sandwiched between themembranes 14.Although the movable central piece 16 may be attached to the flexible membrane(s) 14by gluing, heat—bonding, and the like, it is understood that such attachment is not necessary.Instead, one or both of the flexible membranes 14 can be arranged so as to completely orpartially block the movable central piece 16 and prevent it from falling out of the hole in thesubstantially rigid annular member 12. When the aforementioned annular version of the flexiblemembranes 14 is used, as illustrated by way of example in Figure 12, the diameter of the holein at least one of the annular flexible membranes 14 is preferably smaller than that of the holein the substantially rigid annular member 12 so that a radially inner portion 14A of the annularflexible membrane 14 overlaps with the movable central piece 16 and thereby prevents themovable central piece 16 from falling out of the hole in the substantially rigid annular member12.As illustrated in Figure 13A, another way of keeping the movable central piece 16 fromfalling out of the hole in the substantially rigid annular member 12 is to provide arms 16Awhich extend radially out from the movable central piece 16 and are slidably received inrespective grooves 16B. The grooves 16B are formed in the rigid annular member 12. Eachgroove 16B has a longitudinal dimension (vertical in Figure 13) which is selectively chosen torestrict the range of movement of the movable central piece 16 to within predetermined limits.Although Figure 13 shows an embodiment wherein the grooves are in the substantially rigidannular member 12 and the arms extend out from the movable central piece 16, it is understoodthat an equally effective arrangement can be created by reversing the configuration such thatthe grooves are located in the movable central piece 16 and the arms extend radially in from1015202530CA 02264193 1999-02-26WO 98/09564 PCT/U S97] 1548951the substantially rigid annular member 12.Preferably, the grooves 16B include resilient elements, such as miniature springs, whichbias the position of the movable central piece 16 toward a desired starting position. In addition,the arms 16A may include distally located miniature wheels which significantly reduce thefriction between the arms 16A and the walls of the grooves 16B.Figure 13B illustrates another way of keeping the movable central piece 16 from fallingout of the hole in the substantially rigid annular member 12. In Figure 13B, the substantiallyrigid annular member 12 is provided with radially inwardly extending flaps 12F at the outersurface of the annular member 12. One of the aforementioned annular membranes 14 ispreferably disposed on the inner side of the substantially rigid annular member 12. Preferably,a portion of the membrane 14 extends radially inwardly past the walls of the rigid annularmember's hole. The combination of the annular membrane 14 and the flaps 12F keeps themovable central piece 16 from falling out of the hole in the substantially rigid annular member12. -The flaps 12F may also be used to achieve or facilitate actuation of the movable centralpiece 16. In a magnetically actuated embodiment, for example, the flaps 12F may bemagnetized so that the flaps 12F move inwardly in response to an externally applied magneticfield.With reference to Figure 14, an alternative embodiment of the contact device 2 is madeusing a soft contact lens material 12A having a progressively decreasing thickness toward itsouter circumference. A cylindrical hole 12B is formed in the soft contact lens material 12A.The hole 12B, however, does not extend entirely through the soft contact lens material 12A.Instead, the hole has a closed bottom defined by a thin portion 12C of the soft contact lensmaterial 12A. The movable central piece 16 is disposed slidably within the hole 12B, andpreferably, the thin portion 12C is no more than 0.2 millimeters thick, thereby allowing themovable central piece 16 to achieve applanation or indentation when moved against the closedbottom of the hole toward the cornea with very little interference from the thin portion 12C.Preferably, a substantially rigid annular member 12D is inserted and secured to the softcontact material 12A to define a more stable wall structure circumferentially around the hole12B. This, in turn, provides more stability when the movable central piece 16 moves in the hole12B.10152530CA 02264193 1999-02-26WO 98109564 PCT/US97/1548952Although the soft lens material 12A preferably comprises Hydrogel, silicone, flexibleacrylic, or the like, it is understood that any other suitable materials may be used. In addition,as indicated above, any combination of flexible membranes may be added to the embodimentof Figure 14. Although the movable central piece 16 in Figure 14 is illustrated as being annular,it is understood that any other shape may be utilized. For example, any of the previouslydescribed movable central pieces 16 would suffice.Similarly, the annular version of the movable central piece 16 may be modified byadding a transparent bottom plate (not illustrated) which defines a flat transparent bottomsurface of the movable central piece 16. When modified in this manner, the movable centralpiece 16 would have a generally cup-shaped appearance. Preferably, the flat transparentbottom surface is positioned toward the cornea to enhance the flattening effect of the movablecentral piece 16; however, it is understood that the transparent plate can be located on theoutside surface of the movable central piece 16 if desired.Although the movable central piece 16 and the hole in the substantially rigid annularmember 12 (or the hole in the soft contact lens material 12A) are illustrated as havingcomplementary cylindrical shapes, it is understood that the complementary shapes are notlimited to a cylinder, but rather can include any shape which permits sliding of the movablecentral piece 16 with respect to its surrounding structure.It is also understood that the movable central piece 16 may be mounted directly ontothe surface of a flexible membrane 14 without using a substantially rigid annular member 12.Although such an arrangement defines a working embodiment of the contact device 2, itsstability, accuracy, and level of comfort are significantly reduced compared to that of a similarembodiment utilizing the substantially rigid annular member 12 with a progressively taperingperiphery.Although the illustrated embodiments of the movable central piece 16 include generallyflat outside surfaces with well defined lateral edges, it is understood that the present inventionis not limited to such arrangements. The present invention, for example, can include a movablecentral piece 16 with a rounded outer surface to enhance comfort and/or to coincide with thecurvature of the outer surface of the substantially rigid annular member 12. The movablecentral piece can also be made to have any combination of curved and flat surfaces defined atits inner and outer surfaces, the inner surface being the surface at the cornea and the outer202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548953surface being the surface directed generally away from the cornea.With reference to Figure 15, the movable central piece 16 may also include a centrallydisposed projection 16P directed toward the cornea. The projection 16P is preferably createdby extending the transparent solid material in toward the cornea at the center of the movablecentral piece 16.ALTERNATIVE EMBODIMENT FORMEASURING INTRAOCULAR PRESSURE BY APPLANATIONWith reference to Figure 16, an alternative embodiment of the system for measuringintraocular pressure by applanation will now be described. The alternative embodimentpreferably utilizes the version of the contact device 2 which includes a transparent centralportion.According to the alternative embodiment, the schematically illustrated coil 30 of theactuation apparatus includes an iron core 30A for enhancing the magnetic field produced bythe coil 30. The iron core 30A preferably has an axially extending bore hole 30B(approximately 6 millimeters in diameter) which permits the passage oflight through the ironcore 30A and also permits mounting of two lenses L3 and L4 therein.In order for the system to operate successfully, the strength of the magnetic forceapplied by the coil 30 on the movable central piece 16 should be sufficient to applanate patients’corneas over at least the filll range of intraocular pressures encountered clinically (i.e. 5-50 mmHg). According to the illustrated alternative embodiment, intraocular pressures ranging from1 to over 100 mm of mercury can be evaluated using the present invention. The forcesnecessary to applanate against such intraocular pressures may be obtained with reasonablystraightforward designs and inexpensive materials as will be demonstrated by the followingcalculations:It is known that the force F exerted by an external magnetic field on a small magnetequals the magnet's magnetic dipole moment m multiplied by the gradient of the external field'smagnetic induction vector "grad B" acting in the direction of the magnet's dipole moment.F = m * grad B (1)The magnetic dipole moment m for the magnetic version of the movable central piece16 can be determined using the following formula:m = (B*V) /uo (2)l0152025CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548954where B is the magnetic induction vector just at the surface of one of the poles of themovable central piece 16, V is its volume, and uo is the magnetic permeability of freespace which has a value of 12.57 * 10” Henry/meter.A typical value of B for magnetized Alnico movable central pieces 16 is 0.5 Tesla. Ifthe movable central piece 16 has a thickness of 1 mm, a diameter of 5 mm, and 50% of itsinitial volume is machined away, its volume V = 9.8 cubic millimeters (9.8 * 109 cubic meters.Substituting these values into Equation 2 yields the value for the movable central piece’smagnetic dipole moment, namely, m = 0.00390 Amp* (Meter)?Using the foregoing calculations, the specifications of the actuation apparatus can bedetermined. The magnetic field gradient "grad B" is a function of the distance x measured fromthe front face of the actuation apparatus and may be calculated as follows:grad B= uo * X*N*l* (RAD)2* { [(x+L)2+RAD2]'3’2 - [x2+RAD2]'3’2}(3)2*Lwhere X is the magnetic susceptibility ofthe iron core, N is the number ofturns in thecoil's wire, I is the electric current carried by the wire, L is the length of the coil 30, andRAD is the radius ofthe coil 30.The preferred values for these parameters in the alternative embodiment are: X = 500,N = 200, I = 1.0 Amp, L = 0.05 meters, and RAD = 0.025 meters. It is understood, however,that the present invention is not limited to these preferred parameters. As usual, uo = 12.57 *10" Henry/meter.The force F exerted by the magnetic actuation apparatus on the movable central piece16 is found from Equation 1 using the aforementioned preferred values as parameters inEquation 3, and the above result for m = 0.00390 Amp*(Meter)2 . A plot of F as a functionof the distance x separating the movable central piece 16 from the pole of the magneticactuation apparatus appears as Figure 16A.Since a patient's cornea 4, when covered by the contact device 2 which holds themovable central piece 16, can be placed conveniently at a distance x = 2.5 cm (0.025 m) fromthe actuation apparatus, it is noted from Figure 16A that the magnetic actuation force isapproximately F = 0.063 Newtons.1015202530WO 98/09564CA 02264193 1999-02-26PCT/US97I1548955This force is then compared to F mm which is the force actually needed to applanatea cornea 4 over a typical applanation area when the intraocular pressure is as high as 50 mmHg. In Goldman tonometry, the diameter of the applanated area is approximately 3.1 mm andtherefore the typical applanated AREA will equal 7.55 mm2 . The typical maximum pressureof 50 mm Hg can be converted to metric form, yielding a pressure of 0.00666 Newtons/mmz.The value of Fmqmd then can be determined using the following equation:F,,q,,,,,d = PRESSURE * AREA (4)After mathematical substitution, Fm“,-M = 0.050 Newtons. Comparing the calculatedmagnetic actuation force F to the force required Fm”, it becomes clear that Fmmm, is less thanthe available magnetic driving force F. Therefore, the maximum force needed to applanate thecornea 4 for intraocular pressure determinations is easily achieved using the actuation apparatusand movable central piece 16 of the present invention.It is understood that, if a greater force becomes necessary for whatever reason (e. g, toprovide more distance between the contact device 2 and the actuation apparatus), the variousparameters can be manipulated and/or the current in the coil 30 can be increased to achieve asatisfactory arrangement. _In order for the actuation apparatus to properly actuate the movable central piece 16in a practical way, the magnetic actuation force (and the associated magnetic field) shouldincrease from zero, reach a maximum in about 0.01 sec., and then return back to zero inapproximately another 0. 01 sec. The power supply to the actuation apparatus thereforepreferably includes circuitry and a power source capable of driving a "current pulse" of peakmagnitude in the 1 ampere range through a fairly large inductor (i.e. the coil 30).For “single-pulse” operation, a DC-voltage power supply can be used to charge acapacitor C through a charging resistor. One side of the capacitor is grounded while the otherside ("high" side) may be at a 50 volt DC potential. The "high" side of the capacitor can beconnected via a high current-carrying switch to a "discharge circuit" consisting of the coil 30and a damping resistor R. This arrangement yields an R-L-C series circuit similar to that whichis conventionally used to generate large pulses of electrical current for such applications asobtaining large pulsed magnetic fields and operating pulsed laser power systems. Byappropriately choosing the values of the electrical components and the initial voltage of thecapacitor, a “current pulse” of the kind described above can be generated and supplied to the. . s._........._..«».........._.i.... .1015202530CA 02264193 1999-02-26WO 98/09564 PCTlUS97Il 548956coil 30 to thereby operate the actuation apparatus.It is understood, however, that the mere application of a current pulse of the kinddescribed above to a large inductor, such as the coil 30, will not necessarily yield a zeromagnetic field after the current pulse has ended. Instead, there is usually an undesirableresidual magnetic field from the iron-core 30A even though no current is flowing in the coil 30.This residual field is caused by magnetic hysteresis and would tend to produce a magnetic forceon the movable central piece 16 when such a force is not wanted.Therefore, the alternative embodiment preferably includes means for zeroing themagnetic field outside the actuation apparatus after operation thereof. Such zeroing can beprovided by a demagnetizing circuit connected to the iron-core 30A.Methods for demagnetizing an iron-core are generally known and are easy toimplement. It can be done, for example, by reversing the current in the coil repeatedly whiledecreasing its magnitude. The easiest way to do this is by using a step-down transformer wherethe input is a sinusoidal voltage at 60 Hz which starts at a "line voltage" of 110 VAC and isgradually dampened to zero volts, and where the output of the transformer is connected to thecoil 30.The actuation apparatus therefore may include two power circuits, namely, a "singlepulse" current source used for conducting applanation measurements and a "demagnetizationcircuit" for zeroing the magnetic field of the coil 30 immediately after each applanationmeasurement.As illustrated in Figures 16 and more specifically in Figure 17, the alternativeembodiment used for applanation also includes an alternative "optical alignment system.Alignment is very important because, as indicated by the graph of Figure 16A, the force exertedby the actuation apparatus on the movable central piece 16 depends very much on their relativepositions. In addition to the movable central piece's axial location with respect to the actuationapparatus (x-direction), the magnetic force exerted on the movable central piece 16 alsodepends on its lateral (y-direction) and vertical (z-direction) positions, as well as on itsorientation (tip and tilt) with respect to the central axis of the actuation apparatus.Considering the variation of force F with axial distance x shown in Fig. 16A, it is clearthat the movable central piece 16 should be positioned in the x-direction with an accuracy ofabout +/- 1 mm for reliable measurements. Similarly, since the diameter of the coil 30 is1015202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/ 1548957preferably 50 mm, the location of the movable central piece 16 with respect to the y and 2directions (i.e. perpendicular to the longitudinal axis of the coil 30) should be maintained towithin +/- 2 mm (a region where the magnetic field is fairly constant) of the coil's longitudinalaxis.Finally, since the force on the movable central piece 16 depends on the cosine of theangle between the coil's longitudinal axis and the tip or tilt angle of the movable central piece16, it is important that the ranggefithe patient's gaze with respect to the coil's longitudinal axisbe maintained within ab0lll{\‘fi,2 degrees for reliable measurements.In order to satisfy the foregoing criteria, the alternative optical alignment systemfacilitates precise alignment of the patient's corneal vertex (situated centrally behind themovable central piece 16) with the coil's longitudinal axis, which precise alignment can beachieved independently by a patient without the assistance of a trained medical technician orhealth care professional.The alternative optical alignment system functions according to how light reflects andrefracts at the corneal surface. For the sake of simplicity, the following description of thealternative optical alignment system and Figs. 16 and 17 does not refer specifically to the effectsof the movable central piece's transparent central portion on the operation of the optical system,primarily because the transparent central portion of the movable central piece 16 is preferablyarranged so as not to affect the behavior of optical rays passing through the movable centralpiece 16.Also, for the sake of simplicity, Figure 17 does not show the iron core 30A and itsassociated bore 30B, though it is understood that the alignment beam (described hereinafier)passes through the bored hole 30B and that the lenses L3 and L4 are mounted within the boredhole 30B.As illustrated in Figure 16, a point-like source 350 of light such as an LED is locatedat the focal plane of a positive (i.e., convergent) lens L1. The positive lens L1 is arranged soas to collimate a beam of light from the source 350. The collimated beam passes through abeam splitter BS1 and a transmitted beam of the collimated beam continues through the beamsplitter BS1 to a positive lens L2. The positive lens L2 focuses the transmitted beam to a pointwithin lens L3 located at the focal plane of a lens L4. The light rays passing through L4 arecollimated once again and enter the patient's eye where they are focused on the retina 5. The..... ,. nu... ..........................u.-...................t..__. .,1015202530CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548958transmitted beam is therefore perceived by the patient as a point-like light.Some of the rays which reach the eye are reflected from the corneal surface in adivergent manner due to the comea's preapplanation curvature, as shown in Fig. 18, and arereturned back to the patient‘s eye by a partially mirrored planar surface of the lens L4. Theserays are perceived by the patient as an image of the corneal reflection which guides the patientduring alignment of his/her eye in the instrument as will be described hereinafter.Those rays which are reflected by the convex cornea 4 and pass from right~to-leftthrough the lens L4 are made somewhat more convergent by the lens L4. From the perspectiveof lens L3, these rays appear to come from a virtual point object located at the focal point.Therefore, after passing through L3, the rays are once again collimated and enter the lens L2which focuses the rays to a point on the surface of the beam splitter BS1. The beam splitterBS1 is tilted at 45 degrees and consequently deflects the rays toward a lens L5 which, in turn,collimates the rays. These rays then strike the surface of a tilted reflecting beam splitter BS2.The collimated rays reflected from the beam splitter BS2 enter lens L6 which focuses them ontothe small aperture of a silicon photodiode which fiinctions as an alignment sensor D1.Therefore, when the curved cornea 4 is properly aligned, an electric current is producedby the alignment sensor D1. The aligmnent system is very sensitive because it is a confocalarrangement (i.e., the point image of the alignment light due to the corneal reflection - Purkinjeimage - in its fiducial position is conjugate to the small light-sensitive aperture of the siliconphotodiode). In this manner, an electrical current is obtained from the alignment sensor onlywhen the cornea 4 is properly aligned with respect to the lens L4 which, in turn, is preferablymounted at the end of the magnetic actuation apparatus. The focal lengths of all the lensesshown in Fig. 17 are preferably 50 mm except for the lens L3 which preferably has a focallength of 100 MM.An electrical circuit capable of operating the aligmnent sensor D1 is straight-forwardto design and build. The silicon photodiode operates without any bias voltage ("photovoltaicmode”) thus minimizing inherent detector noise. In this mode, a voltage signal, whichcorresponds to the light level on the silicon surface, appears across a small resistor spanningthe diode's terminals. Ordinarily this voltage signal is too small for display or subsequentprocessing; however, it can be amplified many orders of magnitude using a simpletransimpedance amplifier circuit. Preferably, the alignment sensor D1 is utilized in conjunction10CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548959with such an amplified photodiode circuit.Preferably, the circuitry connected to the aligmnent sensor D1 is arranged so as toautomatically activate the actuation apparatus immediately upon detecting via the sensor DIthe existence of proper alignment. If, however, the output from the alignment sensor D1indicates that the eye is not properly aligned, the circuitry preferably prevents activation of theactuation apparatus. In this way, the alignment sensor D1, not the patient, determines when theactuation apparatus will be operated.As indicated above, the optical alignment system preferably includes an arrangementfor guiding the patient during alignment of his/her eye in the instrument. Such arrangementsare illustrated, by way of example, in Figures 18 and 19.The arrangement illustrated in Figure 18 allows a patient to precisely position his/hereye translationally in all x-y-z directions. In particular, the lens L4 is made to include a planosurface, the plano surface being made partially reflective so that a patient is able to see amagnified image of his/her pupil with a bright point source of light located somewhere near thecenter of the iris. This point source image is due to the reflection of the incoming alignmentbeam from the curved corneal surface (called the first Purkinje image) and its subsequentreflection fiom the mirrored or partially reflecting plano surface of the lens L4. Preferably, thelens L4 makes the reflected rays parallel as they return to the eye which focuses them onto theretina 5.Although Fig. 18 shows the eye well aligned so that the rays are focused at a centrallocation on the surface of the retina 5, it is understood that movements of the eye toward oraway (x-direction) from the lens L4 will blur the image of the corneal reflection, and thatmovements of the eye in either the y or z direction will tend to displace the corneal reflectionimage either to the right/left or up/down.The patient therefore performs an alignment operation by gazing directly at thealignment light and moving his/her eye slowly in three dimensions until the point image of thecorneal reflection is as sharp as possible (x-positioning) and merges with the point image of thealignment light (y & z positioning) which passes straight through the cornea 4.As illustrated in Figure 19, the lens L4 need not have a partially reflective portion if theact of merely establishing a proper direction of gaze provides sufficient alignment.Once alignment is achieved, a logic signal from the optical alignment system activates2025CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548960the "pulse circuit" which, in turn, powers the actuation apparatus. After the actuationapparatus is activated, the magnetic field at the patient's cornea increases steadily for a timeperiod of about 0.01 sec. The effect of this increasing field is to apply a steadily increasingforce to the movable central piece 16 resting on the cornea which, in turn, causes the cornea4 to flatten increasingly over time. Since the size of the applanation area is proportional to theforce on the movable central piece 16 (and Pressure = Force/Area), the intraocular pressure(IOP) is found by determining the ratio of the force to the area applanated by the force.In order to detect the applanated area and provide an electrical signal indicative of thesize of the applanated area, the alternative embodiment includes an applanation sensor D2. Therays that are reflected from the applanated corneal surface are reflected in a generally parallelmanner by virtue of the flat surface presented by the applanated cornea 4. As the rays passfrom right-to-left through the lens L4, they are focused within the lens L3 which, in turn, is inthe focal plane ofthe lens L2. Consequently, after passing through the lens L2, the rays areonce again collimated and impinge on the surface of beam splitter BS1. Since the beam splitterBS1 is tilted at 45 degrees, the beam splitter BS1 deflects these collimated rays toward the lensL5 which focuses the rays to a point at the center of beam splitter BS2. The beam splitter BS2has a small transparent portion or hole in its center which allows the direct passage of the rayson to the lens L7 (focal length of preferably 50 mm). The lens L7 pertains to an applanationsensing arm of the alternative embodiment.The focal spot on the beam splitter BS2 is in the focal plane of the lens L7.Consequently, the rays emerging from the lens L7 are once again collimated. These collimatedrays impinge on the mirror M1, preferably at a 45 degree angle, and are deflected toward apositive lens L8 (focal length of 50 mm) which focuses the rays onto the small aperture of asilicon photodiode which defines the applanation sensor D2.It is understood that rays which impinge upon the cornea 4 slightly of center tend tobe reflected away from the lens L4 when the comea's curvature remains undisturbed. However,as applanation progresses and the cornea becomes increasingly flat, more of these rays arereflected back into the lens L4. The intensity of light on the applanation sensor D2 thereforeincreases, and as a result, an electric current is generated by the applanation sensor D2, whichelectric current is proportional to the degree of applanation.Preferably, the electrical circuit utilized by the applanation sensor D2 is identical orl5202530CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548961similar to that used by the alignment sensor D1.The electric signal indicative of the area of applanation can then be combined withsignals indicative of the time it takes to achieve such applanation and/or the amount of current(which, in turn, corresponds to the applied force) used to achieve the applanation, and thiscombination of information can be used to determine the intraocular pressure using theequation Pressure=Force/Area.The following are preferred operational steps for the actuation apparatus during ameasurement cycle:1) While the actuation apparatus is OFF, there is no magnetic field being directedtoward the contact device 2.2) When the actuation apparatus is turned ON, the magnetic field initially remains atzero.3) Once the patient is in position, the patient starts to align his/her eye with theactuation apparatus. Until the eye is properly aligned, the magnetic field remains zero.4) When the eye is properly aligned (as automatically sensed by the optical alignmentSensor), the magnetic field (driven by a steadily increasing electric current) starts to increasefrom zero.5) During the time period of the current increase (approximately 0.01 sec.), the forceon the movable central piece also increases steadily.6) In response to the increasing force on the movable central piece, the surface area ofthe cornea adjacent to the movable central piece is increasingly flattened.7) Light from the flattened surface area of the cornea is reflected toward the detectingarrangement which detects when a predetermined amount of applanation has been achieved.Since the amount of light reflected straight back from the cornea is proportional to the size ofthe flattened surface area, it is possible to determine exactly when the predetermined amountof applanation has been achieved, preferably a circular area of diameter 3.1 mm, of the cornea.It is understood, however, that any diameter ranging from 0.10 mm to 10 mm can be utilized.8) The time required to achieve applanation of the particular surface area (i.e, thepredetermined amount of applanation) is detected by a timing circuit which is part of theapplanation detecting arrangement. Based on prior calibration and a resulting conversion table,this time is converted to an indication of intraocular pressure. The longer the time required tol0152025CA 02264193 1999-02-26WO 98/09564 PCT/U S97! 1548962applanate a specific area, the higher the intraocular pressure, and vice versa.9) Afier the predetermined amount of applanation is achieved, the magnetic field isturned OFF.10) The intraocular pressure is then displayed by a readout meter, and all circuits arepreferably turned completely OFF for a period of 15 seconds so that the automaticmeasurement cycle will not be immediately repeated if the patient's eye remains aligned. It isunderstood, however, that the circuits may remain ON and that a continuous measurement ofintraocular pressure may be achieved by creating an automatic measurement cycle. The dataprovided by this automatic measurement cycle then may be used to calculate blood flow.ll) If the main power supply has not been turned OFF, all circuits are turned back ONafter 15 seconds and thus become ready for the next measurement.Although there are several methods for calibrating the various elements of the systemfor measuring intraocular pressure by applanation, the following are illustrative examples ofhow such calibration can be achieved:Initially, afier manufacturing the various components, each component is tested toensure the component operates properly. This preferably includes verifying that there is freepiston-like movement (no twisting) of the movable central piece in the contact device; verifyingthe structural integrity of the contact device during routine handling; evaluating the magneticfield at the surface of the movable central piece in order to determine its magnetic dipolemoment (when magnetic actuation is utilized); verifying that the electrical current pulse whichcreates the magnetic field that actuates the magnetically responsive element of the movablecentral piece, has an appropriate peak magnitude and duration, and ensuring that there is no"ringing"; verifying the efficacy of the "demagnetization circuit" at removing any residualmagnetization in the iron-core of the actuation apparatus after it has been pulsed; measuringthe magnetic field as a function of time along and near the longitudinal axis of the coil wherethe movable central piece will eventually be placed; determining and plotting grad B as afiinction of time at several x-locations (i.e., at several distances from the coil) ; and positioningthe magnetic central piece (contact device) at several x-locations along the coil's longitudinalaxis and determining the force F acting on it as a fiinction of time during pulsed-operation ofthe actuation apparatus.Next, the optical alignment system is tested for proper operation. When the optical20CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548963alignment system comprises the arrangement illustrated in Figures 16 and 17, for example, thefollowing testing and calibration procedure may be used:a) First, a convex glass surface (one face of a lens) having a radius of curvatureapproximately the same as that of the cornea is used to simulate the cornea and its surfacereflection. Preferably, this glass surface is placed in a micrometer—adjusted mountingarrangement along the longitudinal axis of the coil. The micrometer-adjusted mountingarrangement permits rotation about two axes (tip & tilt) and translation in three-dimensionalx-y—z space.b) With the detector DI connected to a voltage or current meter, the convex glasssurface located at its design distance of 25 mm from lens L4 will be perfectly aligned(tip/tilt/x/y/z) by maximizing the output signal at the read—out meter. 4c) After perfect alignment is achieved, the alignment detection arrangement is "detuned"for each of the positional degrees of freedom (tip/tilt/x/y/z) and curves are plotted for eachdegree of freedom to thereby define the system's sensitivity to alignment.d) The sensitivity to alignment will be compared to the desired tolerances in thereproducibility of measurements and also can be based on the variance of the magnetic forceon the movable central piece as a function of position.e) Thereafier, the sensitivity of the alignment system can be changed as needed by suchprocedures as changing the size of the aperture in the silicon photodiode which functions as thealignment sensor Dl, and/or changing an aperture stop at lens L4.Next, the detection arrangement is tested for proper operation. When the detectionarrangement comprises the optical detection arrangement illustrated in Figure 16, for example,the following testing and calibration procedure may be used:a) A flat glass surface (e.g., one face of a short polished rod) with a diameter ofpreferably 4-5 mm is used to simulate the applanated cornea and its surface reflection.b) A black, opaque aperture defining mechanism (which defines clear inner apertureswith diameters ranging from 0.5 to 4 mm and which has an outer diameter the same as that ofthe rod) is arranged so as to partially cover the face of the rod, thus simulating various stagesof applanation.c) The flat surfaced rod is placed in a mount along the longitudinal axis of the coil ina micrometer—adjusted mounting arrangement that can rotate about two axes (tip & tilt) and1015202530CA 02264193 1999-02-26WO 98/09564 PCTlUS97/ 1548964translate in three-dimensional x—y—z space.d) The applanation sensor D2 is then connected to a voltage or current meter, while therod remains located at its design distance of 25 mm from the lens L4 where it is perfectlyaligned (tip/tilt/x/y/z) by maximizing the output signal from the applanation sensor D2.Alignment, in this case, is not sensitive to x-axis positioning.e) After perfect alignment is achieved, the alignment is "detuned" for each of thepositional degrees of fieedom (tip/tilt/x/y/z) and curves are plotted for each degree of freedomthus defining the system's sensitivity to alignment. Data of this kind is obtained for thevariously sized apertures (i.e. different degrees of applanation) at the face of the rod.0 The sensitivity to alignment is then compared to the tolerances required forreproducing applanation measurements which depends, in part, on the results obtained in theaforementioned testing and calibration method associated with the alignment apparatus.g) The sensitivity of the applanation detecting arrangement is then changed as neededby such procedures as changing the size of the aperture in front of the applanation sensor D2and/or changing the aperture stop (small hole) at the beam splitter BS2.Further calibration and in-vitro measurements can be carried out as follows: After theaforementioned calibration and testing procedures have been carried out on the individualsubassemblies, all parts can be combined and the system tested as an integrated unit. For thispurpose, ten enucleated animal eyes and ten enucleated human eyes are measured in twoseparate series. The procedures for both eye types are the same. The eyes are mounted in non-magnetic holders, each having a central opening which exposes the cornea and part of thesclera. A 23 gauge needle attached to a short piece of polyethylene tubing is then insertedbehind the limbus through the sclera and ciliary body and advanced so that the tip passesbetween the lens and iris. Side ports are drilled in the cannulas about 2 mm from the tip to helpavoid blockage of the cannula by the iris or lens. This cannula is attached to a pressuretransducer with an appropriate display element. A normal saline reservoir of adjustable heightis also connected to the pressure transducer tubing system. The hydrostatic pressure appliedto the eye by this reservoir is adjustable between 0 and 50 mm Hg, and intraocular pressureover this range can be measured directly with the pressure transducer.In order to verify that the foregoing equipment is properly set up for each new eye, astandard Goldman applanation tonometer can be used to independently measure the eye'sU:1015202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/ 1548965intraocular pressure at a single height of the reservoir. The intraocular value measured usingthe Goldman system is then compared to a simultaneously determined intraocular pressuremeasured by the pressure transducer. Any problems encountered with the equipment can becorrected if the two measurements are significantly different.The reservoir is used to change in 5 mm Hg sequential steps the intraocular pressureof each eye over a range of pressures from 5 to 50 mm Hg. At each of the pressures, ameasurement is taken using the system of the present invention. Each measurement taken bythe present invention consists of recording three separate time-varying signals over the timeduration of the pulsed magnetic field. The three signals are: 1) the current flowing in the coilof the actuation apparatus as a fimction of time, labelled I (t), 2) the voltage signal as a functionof time from the applanation detector D2, labelled APPLN (t), and 3) the voltage signal as afunction of time from the alignment sensor Dl, labelled ALIGN (t). The three signals,associated with each measurement, are then acquired and stored in a computer equipped witha multi-input "data acquisition and processing" board and related sofiware.The computer allows many things to be done with the data including: 1) recording andstoring many signals for subsequent retrieval, 2) displaying graphs of the signals versus time,3) numerical processing and analyses in any way that is desired, 4) plotting final results, 5)applying statistical analyses to groups of data, and 6) labeling the data (e.g. tagging ameasurement set with its associated intraocular pressure).The relationship between the three time-varying signals and intraocular pressure are asfollows:1. I(t) is an independent input signal which is consistently applied as current pulse fromthe power supply which activates the actuation apparatus. This signal I (t) is essentiallyconstant from one measurement to another except for minor shot—to-shot variations. I (t) isa "reference" waveform against which the other waveforms, APPLN (t) and ALIGN (t) arecompared as discussed fi.1rther below.2. APPLN(t) is a dependent output signal. APPLN(t) has a value of zero when I(t) iszero (i.e. at the very beginning of the current pulse in the coil of the actuation apparatus. Thereason for this is that when I=0, there is no magnetic field and, consequently, no applanationforce on the movable central piece. As I (t) increases, so does the extent of applanation and,correspondingly, so does APPLN(t). It is important to note that the rate at which APPLN(t)l015CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548966increases with increasing I(t) depends on the eye's intraocular pressure. Since eyes with lowintraocular pressures applanate more easily than eyes with high intraocular pressures inresponse to an applanation force, it is understood that APPLN(t) increases more rapidly for aneye having a low intraocular pressure than it does for an eye having a high intraocular pressure.Thus, APPLN (t) increases from zero at a rate that is inversely proportional to the intraocularpressure until it reaches a maximum value when full applanation is achieved.3. ALIGN(t) is also a dependent output signal. Assuming an eye is aligned in thesetup, the signal ALlGN(t) starts at some maximum value when I(t) is zero (i.e. at the verybeginning of the current pulse to the coil of the actuation apparatus) . The reason for this is thatwhen I=0, there is no magnetic field and, consequently, no force on the movable central piecewhich would otherwise tend to alter the cornea‘s curvature. Since corneal reflection is whatgives rise to the alignment signal, as I(t) increases causing applanation (and, correspondingly,a decrease in the extent of corneal curvature), the signal ALIGN (t) decreases until it reacheszero at full applanation. It is important to note that the rate at which ALIGN (t) decreases withincreasing I(t) depends on the eye's intraocular pressure. Since extraocular pressure applanatemore easily than eyes with high intraocular pressure, it is understood that ALIGN (t) decreasesmore rapidly for an eye having a low intraocular pressure than for an eye having a highintraocular pressure. Thus, ALIGN(t) decreases from some maximum value at a rate that isinversely proportional to the intraocular pressure until it reaches zero when fiill applanation isachieved.From the foregoing, it is clear that the rate of change ofboth output signals, APPLNand ALIGN, in relation to the input signal I is inversely proportional to the intraocular pressureTherefore, the measurement of intraocular pressure using the present invention may depend ondetermining the SLOPE of the “APPLN versus 1” measurement data (also, although probablywith less certainty, the slope of the "ALIGN versus 1'' measurement data).For the sake of brevity, the following description is limited to the "APPLN versus I"data; however, it is understood that the "ALIGN versus I" data can be processed in a similarmanner.Plots of “APPLN versus I” can be displayed on the computer monitor for the variousmeasurements (all the different intraocular pressures for each and every eye) and regressionanalysis (and other data reduction algorithms) can be employed in order to obtain the "best fit"10CA 02264193 1999-02-26W0 93/09554 PCT/US97/1548967SLOPE for each measurement. Time can be spent in order to optimize this data reductionprocedure. The end result of a series of pressure measurements at different intraocularpressures on an eye (determined by the aforementioned pressure transducer) will be acorresponding series of SLOPE‘s (determined by the system of the present invention).Next, a single plot is prepared for each eye showing SLOPE versus intraocular pressuredata points as well as a best fitting curve through the data. Ideally, all curves for the 10 pigeyes are perfectly coincident — with the same being true for the curves obtained for the 10human eyes. If the ideal is realized, any of the curves can be utilized (since they all are thesame) as a CALIBRATION for the present invention. In practice, however, the ideal isprobably not realized.Therefore, all of the SLOPE versus intraocular pressure data for the l0 pig eyes issuperimposed on a single plot (likewise for the SLOPE versus intraocular pressure data for the10 human eyes). Such superimposing generally yields an "averaged" CALIBRATION curve,and also indication of the reliability associated with the CALIBRATION.Next, the data in the single plots can be analyzed statistically (one for pig eyes and onefor human eyes) which, in turn, shows a composite of all the SLOPE versus intraocularpressure data. From the statistical analysis, it is possible to obtain: 1) an averagedCALIBRATION curve for the present invention from which one can obtain the “most likelyintraocular pressure" associated with a measured SLOPE value, 2) the Standard Deviation (orVariance) associated with any intraocular pressure determination made using the presentinvention, essentially the present invention's expected "ability" to replicate measurements, and3) the "reliability" or "accuracy" of the present invention's CALIBRATION curve which isfound from a "standard-error-of-the mean" analysis of the data.In addition to data obtained with the eyes aligned, it is also possible to investigate thesensitivity of intraocular pressure measurements made using the present invention, totranslational and rotational misalignment.ALTERNATIVE EMBODIMENT FOR MEASURINGINTRAOCULAR PRESSURE BY INDENTATIONWith reference to Figures 20A and 20B, an alternative embodiment for measuringintraocular pressure by indentation will now be described.25CA 02264193 1999-02-26WO 98109564 PCT/US97/1548968The alternative embodiment includes an indentation distance detection arrangement andcontact device. The contact device has a movable central piece 16 of which only the outsidesurface is illustrated in Figures 20A and 20B. The outside surface of the movable central piece16 is at least partially reflective.The indentation distance detection arrangement includes two converging lenses L1 andL2; a beam splitter BS1; a light source LS for emitting a beam oflight having a width w; anda light detector LD responsive to the diameter of a reflected beam impinging on a surfacethereof.Figure 20A illustrates the alternative embodiment prior to actuation of the movablecentral piece 16. Prior to actuation, the patient is aligned with the indentation distancedetection arrangement so that the outer surface of the movable central piece 16 is located atthe focal point of the converging lens L2. When the movable central piece 16 is so located, thebeam of light fiom the light source LS strikes the beam splitter BS and is deflected through theconverging lens L1 to impinge as a point on the reflective outer surface of the movable centralpiece 16. The reflective outer surface of the movable central piece 16 then reflects this beamof light back through the converging lens Ll, through the beam splitter BS, and then throughthe converging lens L2 to strike a surface of the light detector LD. Preferably, the lightdetector LD is located at the focal point of the converging lens L2 so that the reflected beamimpinges on a surface of the light detector LD as a point of virtually zero diameter when theouter surface of the movable central piece remains at the focal point of the converging lens Ll.Preferably, the indentation distance detection arrangement is connected to a displaydevice so as to generate an indication of zero displacement when the outer surface of themovable central piece 16 has yet to be displaced, as shown in Figure 20A.By subsequently actuating the movable central piece 16 using an actuating device(preferably, similar to the actuating devices described above), the outer surface of the movablecentral piece 16 moves progressively away from the focal point of the converging lens L1, asillustrated in Figure 20B. As a result, the light beam impinging on the reflective outer surfaceof the movable central piece 16 has a progressively increasing diameter. This progressiveincrease in diameter is proportional to the displacement from the focal point of the converginglens L1. The resulting reflected beam therefore has a diameter proportional to the displacementand passes back through the converging lens Ll, through the beam splitter BS, through theIO15202530CA 02264193 1999-02-26W0 98/09564 PCT/US97/1548969converging lens C2 and then strikes the surface of the light detector LD with a diameterproportional to the displacement of the movable central piece 16. Since the light detector LDis responsive, as indicated above, to the diameter of the reflected light beam, any displacementof the movable central piece 16 causes a proportional change in output from the light detectorLD.Preferably, the light detector LD is a photoelectric converter connected to theaforementioned display device and capable of providing an output voltage proportional to thediameter of the reflected light beam impinging upon the light detector LD. The display devicetherefore provides a visual indication of displacement based on the output voltage from thelight detector LD.Alternatively, the output from the light detector LD may be connected to anarrangement, as described above, for providing an indication of intraocular pressure based onthe displacement of the movable central piece 16.ADDITIONAL CAPABHJTIESGenerally, the present apparatus and method makes it possible to evaluate intraocularpressure, as indicated above, as well as ocular rigidity, eye hydrodynamics such as outflowfacility and inflow rate of eye fluid, eye hemodynarnics such as the pressure in the episcleralveins and the pulsatile ocular blood flow, and has also the ability to artificially increaseintraocular pressure, as well as the continuous recording of intraocular pressure.With regard to the measurement of intraocular pressure by applanation, the foregoingdescription sets forth several techniques for accomplishing such measurement, including avariable force technique wherein the force applied against the cornea varies with time. It isunderstood, however, that a variable area method can also be implemented.The apparatus can evaluate the amount of area applanated by a known force. Thepressure is calculated by dividing the force by the amount of area that is applanated. Theamount of area applanated is determined using the optical means and/or filters previouslydescribed.A force equivalent to placing 5 gram of weight on the cornea, for example, willapplanate a first area if the pressure is 30 mmHg, a second area if the pressure is 20 mmHg, athird area if the pressure is 15 mmHg and so on. The area applanated is therefore indicativel0l530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548970of intraocular pressure.Alternatively, intraocular pressure can be measured using a non-rigid interface andgeneral applanation techniques. In this embodiment, a flexible central piece enclosed by themagnet of the movable central piece is used and the transparent part of the movable centralpiece acts like a micro-balloon. This method is based on the principle that the interfacebetween two spherical balloons of unequal radius will be flat if the pressures in the two balloonsare equal. The central piece with the balloon is pressed against the eye until the eye/centralpiece interface is planar as determined by the aforementioned optical means.Also, with regard to the previously described arrangement which measures intraocularpressure by indentation, an alternative method can be implemented with such an embodimentwherein the apparatus measures the force required to indent the cornea by a predeterminedamount. This amount of indentation is determined by optical means as previously described.The movable central piece is pressed against the cornea to indent the cornea, for example, 0.5mm-(though it is understood that virtually any other depth can be used). Achievement of thepredetermined depth is detected by the previously described optical means and filters.According to tables, the intraocular pressure can be determined thereafier from the force.Yet another technique which the present invention facilitates use of is the ballisticprinciple. According to the ballistic principle, a parameter of a collision between the knownmass of the movable central piece and the cornea is measured. This measured parameter is thenrelated theoretically or experimentally to the intraocular pressure. The following are exemplaryparameters:Impact accelerationThe movable central piece is directed at the cornea at a well definedvelocity. It collides with the cornea and, after a certain time of contact,bounces back. The time-velocity relationships during and after impact can bestudied. The applanating central piece may have a spring connecting to therigid annular member of the contact device. If the corneal surface is hard, theimpact time will be short. Likewise, if the corneal surface is sofi the impacttime will be longer. Optical sensors can detect optically the duration of impactand how long it takes for the movable central piece to return to its originalposition.1025CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548971Impact durationIntraocular pressure may also be estimated by measuring the durationof contact of a spring driven movable central piece with the eye. The amountof time that the cornea remains flattened can be evaluated by the previouslydescribed optical means.Rebound velocityThe distance traveled per unit of time after bouncing is also indicativeof the rebound energy and this energy is proportional to intraocular pressure.Vibration principleThe intraocular pressure also can be estimated by measuring thefrequency of a vibrating element in contact with the contact device and theresulting changes in light reflection are related to the pressure in the eye.TimeThe apparatus of the present invention can also be used, as indicatedabove, to measure the time that it takes to applanate the cornea. The harder thecornea, the higher the intraocular pressure and thus the longer it takes todeform the cornea. On the other hand, the softer the cornea, the lower theintraocular pressure and thus the shorter it takes to deform the cornea. Thus,the amount of time that it takes to deform the cornea is proportional to theintraocular pressure.Additional uses and capabilities of the present invention relate to alternative methodsof measuring outflow facility (tonography). These alternative methods include the use ofconventional indentation techniques, constant depth indentation techniques, constant pressureindentation techniques, constant pressure applanation techniques, constant area applanationtechniques, and constant force applanation techniques.1. conventional indentationWhen conventional indentation techniques are utilized, the movable central piece of thepresent invention is used to indent the cornea and thereby artificially increase the intraocularpressure. This artificial increase in intraocular pressure forces fluid out of the eye more rapidlythan normal. As fluid leaves the eye, the pressure gradually returns to its original level. Therate at which the intraocular pressure falls depends on how well the eye's drainage system isl0l5202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548972functioning. The drop in pressure as a fimction of time is used to calculated the C value orcoefficient of outflow facility. The C value is indicative of the degree to which a change inintraocular pressure will cause a change in the rate of fluid outflow. This, in turn, is indicativeof the resistance to outflow provided by the eye's drainage system. The various procedures fordetermining outflow facility are generally known as tonography and the C value is typicallyexpressed in terms of microliters per minute per millimeter of mercury. The C value isdetermined by raising the intraocular pressure using the movable central piece of the contactdevice and observing the subsequent decay in intraocular pressure with respect to time. Theelevated intraocular pressure increases the rate of aqueous outflow which, in turn, provides achange in volume. This change in volume can be calculated from the Friedehwald tables whichcorrelate volume change to pressure changes. The rate of volume decrease equals the rate ofoutflow. The change in intraocular pressure during the tonographic procedure can becomputed as an arithmetical average of pressure increments for successive ‘/2 minute intervals.The C value is derived then from the following equation: C= AV/t* (Pave-Po), in which t is theduration of the procedure, Pave is the average pressure elevation during the test and can bemeasured, P0 is the initial pressure and it is also measured, and AV is difference between theinitial and final volumes and can be obtained from known tables. The Flow (“F”) of fluid isthen calculated using the formula: F= C* (Po-Pv) , in which Pv is the pressure in the episcleralveins which can be measured and generally has a constant value of 10.2. constant depth indentationWhen constant depth indentation techniques are utilized, the method involves the useof a variable force which is necessary to cause a certain predetermined amount of indentationin the eye. The apparatus of the present invention is therefore configured so as to measure theforce required to indent the cornea by a predetermined amount. This amount of indentationmay be detected using optical means as previously described. The movable central piece ispressed against the cornea to indent the eye, for example, by approximately 0.5 mm. Theamount of indentation is detected by the optical means and filters previously described. Withthe central piece indenting the cornea using a force equivalent to a weight of 10 grams, a 0.5mm indentation will be achieved under normal pressure conditions (e. g. , intraocular pressureof 15 mm Hg) and assuming there is an average corneal curvature. With that amount ofindentation and using standard dimensions for the central piece, 2.5 mm3 of fluid will bel0152530CA 02264193 1999-02-26WO 98109564 PCT/U S97/ 1548973displaced. The force recorded by the present invention undergoes a slow decline and it levelsofi" at a more or less steady state value after 2 to 4 minutes. The decay in pressure is measuredbased on the difference between the value of the first indentation of the central piece and thefinal level achieved after a certain amount of time. The pressure drop is due to the return ofpressure to its normal value, after it has been artificially raised by the indentation caused by themovable central piece. A known normal value of decay is used as a reference and is comparedto the values obtained. Since the foregoing provides a continuous recording of pressure overtime, this method can be an important tool for physiological research by showing, for example,an increase in pressure during forced expiration. The pulse wave and pulse amplitude can alsobe evaluated and the pulsatile blood flow calculated.3.constant pressure indentationWhen constant pressure indentation techniques are utilized, the intraocular pressure iskept constant by increasing the magnetic field and thereby increasing the force against thecornea as fluid leaks out of the eye. At any constant pressure, the force and rate of outflow arelinearly related according to the Friedenwald tonometry tables. The intraocular pressure iscalculated using the same method as described for conventional indentation tonometry. Thevolume displacement is calculated using the tonometry tables. The facility of outflow (C) maybe computed using two different techniques. According to the first technique, C can becalculated from two constant pressure tonograms at different pressures according to theequation, C={[(AV,/t,) - (AV3/t2)]/ (P, - P2)}, in which 1 corresponds to a measurement at afirst pressure and 2 corresponds to a measurement at a second pressure (which is higher thanthe first pressure). The second way to calculate C is from one constant pressure tonogram andan independent measure of intraocular pressure using applanation tonometry (P_.,), in C=[(AV/t)/(P - P, - AP,)], where AP, is a correction factor for rise in episcleral venous pressurewith indentation tonometry and P is the intraocular pressure obtained using indentationtonometry.4. constant pressure applanationWhen constant pressure applanation techniques are utilized, the intraocular pressure iskept constant by increasing the magnetic field and thus the force as fluid leaks out of the eye.If the cornea is considered to be a portion of a sphere, a mathematical formula relates thevolume of a spherical segment to the radius of curvature of the sphere and the radius of the2030CA 02264193 1999-02-26WO 98/09564 PCT/U S97/ 1548974base of the segment. The volume displaced is calculated based on the formula V=A’/ (4*1t*R),in which V is volume, A is the area of the segment base, and R is the radius of curvature of thesphere (this is the radius of curvature of the cornea). Since A=weight/pressure, then V=W2/(4*'n:*R*P2). The weight is constituted by the force in the electromagnetic field, R is thecurvature of the cornea and can be measured with a keratometer, P is the pressure in the eyeand can be measured using the same method as described for conventional applanationtonometry. It is therefore possible to calculate the volume displaced and the C value or outflowfacility. The volume displaced, for example, can be calculated at 15 second intervals and isplotted as a fiinction of time.5. constant area applanation\Nhen constant area applanation techniques are utilized, the method consists primarilyof evaluating the pressure decay curve while the flattened area remains constant. Theaforementioned optical applanation detecting arrangements can be used in order to keepconstant the area flattened by the movable central piece. The amount of force necessary tokeep the flattened area constant decreases and this decrease is registered. The amount ofvolume displaced according to the different areas of applanation is known. For instance, a 5mm applanating central piece displaces 4.07 mm’ of volume for the average corneal radius of7.8 mm. Using the formula AV/At=l/ (R*AP), it is possible to calculate R which is thereciprocal of C. Since a continuous recording of pressure over time is provided, this methodcan be an important tool for research and evaluation of blood flow.6. constant force applanationWhen constant force applanation techniques are utilized, the same force is constantlyapplied and the applanated area is measured using any of the aforementioned opticalapplanation detection arrangements. Once the area flattened by a known force is measured,the pressure can be calculated by dividing the force by the amount of area that is applanated.As fluid leaves the eye the amount of area applanated increases with time. This methodconsists primarily of evaluating a resulting area augmentation curve while the constant forceis applied. The amount of volume displaced according to the different areas of applanation isknown. Using the formula AV/At=l/ (R*AP) , it is possible to calculate R which is thereciprocal of C.Still additional uses of the present invention relate to detecting the frequency response1015202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548975of the eye, using indentation tonometry. In particular, if an oscillating force is applied usingthe movable central piece 16, the velocity of the movable central piece 16 is indicative of theeye's frequency response. The system oscillates at the resonant frequency determined primarilyby the mass of the movable central piece 16. By varying the frequency of the force and bymeasuring the response, the intraocular pressure can be evaluated. The evaluation can be madeby measuring the resonant frequency and a significant variation in resonant frequency can beobtained as a function of the intraocular pressure.The present invention may also be used with the foregoing conventional indentationtechniques, but where the intraocular pressure used for calculation is measured usingapplanation principles. Since applanation virtually does not disturb the hydrodynamicequilibrium because it displaces a very small volume, this method can be considered moreaccurate than intraocular pressure measurements made using traditional indentation techniques.Another use of the present invention involves a time related way of measuring theresistance to outflow. In particular, the resistance to outflow is detected by measuring theamount of time necessary to transfigure the cornea with either applanation or indentation. Thetime necessary to displace, for example, 5 rnicroliters of eye fluid would be 1 second for normalpatients and above 2 seconds for glaucoma-stricken individuals.Yet another use of the present invention involves measuring the inflow of eye fluid. Inparticular, this measurement is made by applying the formula F=AP/R, in which AP is P - P,,,and P is the steady state intraocular pressure and P,, is the episcleral venous pressure which,for purposes of calculation, is considered constant at 10. R is the resistance to outflow, whichis the reciprocal of C that can be calculated. F, in units of volume/rnin, can then be calculated.The present invention is also useful at measuring ocular rigidity, or the distensibility ofthe eye in response to an increased intraocular pressure. The coefiicient of ocular rigidity canbe calculated using a nomogram which is based on two tonometric readings with differentweights. A series of conversion tables to calculate the coefficient of ocular rigidity wasdeveloped by Friedenwald. The technique for determining ocular rigidity is based on theconcept of differential tonometry, using two indentation tonometric readings with differentweights or more accurately, using one indentation reading and one applanation reading andplotting these readings on the nomogram. Since the present invention can be used to measureintraocular pressure using both applanation and indentation techniques, a more accuratel52025CA 02264193 1999-02-26WO 98/09564 PCT/US97/ 1548976evaluation of the ocular rigidity can be achieved.Measurements of intraocular pressure using the apparatus of the present invention canalso be used to evaluate hemodynamics, in particular, eye hemodynamics and pulsatile ocularblood flow. The pulsatile ocular blood flow is the component of the total ocular arterial inflowthat causes a rhythmic fluctuation of the intraocular pressure. The intraocular pressure varieswith each pulse due to the pulsatile influx of a bolus of arterial blood into the eye with eachheartbeat. This bolus of blood enters the intraocular arteries with each heartbeat causing atemporary increase in the intraocular pressure. The period of inflow causes a stretching of theeye walls with a concomitant increase in pressure followed by a relaxation to the previousvolume and a return to the previous pressure as the blood drains from the eye. If this processof expansion during systole (contraction of the heart) and contraction during diastole(relaxation of the heart) occurs at a certain pulse rate, then the blood flow rate would be theincremental change in eye volume times the pulse rate.The fact that intraocular pressure varies with time according to the cardiac cycle is thebasis for measuring pulsatile ocular blood flow. The cardiac cycle is approximately in the orderof 0.8 Hz. The present invention can measure the time variations of intraocular pressure witha frequency that is above the fundamental human heart beat frequency allowing the evaluationand recording of intraocular pulse. In the normal human eye, the intraocular pulse has amagnitude of approximately 3 mm Hg and is practically synchronous with the cardiac cycle.As described, measurements of intraocular pressure show a time variation that isassociated with the pulsatile component of arterial pressure. Experimental results providemeans of transforming ocular pressure changes into eye volume changes. Each bolus of bloodentering the eye increases the ocular volume and the intraocular pressure. The observedchanges in pressure reflect the fact that the eye volume must change to accommodate changesin the intraocular blood volume induced by the arterial blood pulse. This pulse volume is smallrelative to the ocular volume, but because the walls of the eye are stiff, the pressure increaserequired to accommodate the pulse volume is significant and can be measured. Therefore,provided that the relationship between the increased intraocular pressure and increased ocularvolume is known, the volume of the bolus of fluid can be determined. Since this relationshipbetween pressure change and volume change has been well established (Friedenwald 1937,McBain 1957, Ytteborg 1960, Eisenlohr 1962, McEwen 1965), the pressure measurements canl0l5CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548977be used to obtain the volume of a bolus of blood and thereby determine the blood flow.The output of the tonometer for the instantaneous pressure can be converted intoinstantaneous change in eye volume as a function of time. The time derivative of the changein ocular volume is the net instantaneous pulsatile component of the ocular blood flow. Underthese conditions, the rate of pulsatile blood flow through the eye can be. evaluated from theinstantaneous measurement of intraocular pressure. In order to rapidly quantify and analyzethe intraocular pulse, the signal from the tonometer may be digitalized and fed into a computer.Moreover, measurements of intraocular pressure can be used to obtain the intraocularvolume through the use of an independently determined pressure-volume relationship such aswith the Friedenwald equation (Friedenwald, 1937). A mathematical model based onexperimental data from the pressure volume relationship (Friedenwald 1937, McBain 1957,Eisenlohr 1962, McEwen 1965) can also be used to convert a change in ocular pressure intoa change in ocular volume.In addition, a model can also be constructed to estimate the ocular blood flow from theappearance of the intraocular pressure waveform. The flow curve is related to parameters thatcome from the volume change curve. This curve is indirectly measured since the intraocularpressure is the actual measured quantity which is transformed into volume change through theuse of the measured pressure-volume relation. The flow is then computed by taking the changein volume Vmax - Vmin multiplied by a constant that is related to the length of the time intervalof the inflow and the total pulse length. Known mathematical calculations can be used toevaluate the pulsatile component of the ocular blood flow. Since the present invention can alsobe used to measure the ocular rigidity, this parameter of coefiicient of ocular rigidity can beused in order to more precisely calculate individual differences in pulsatile blood flow.Moreover, since the actuation apparatus 6 and contact device 2 of the present inventionpreferably include transparent portions, the pulsatile blood flow can be directly evaluatedoptically to quantify the change in size of the vessels with each heart beat. A more preciseevaluation of blood flow therefore can be achieved by combining the changes in intraocularpulse with changes in vessel diameter which can be automatically measured optically.A vast amount of data about the vascular system of the eye and central nervous systemcan be obtained after knowing the changes in intraocular pressure over time and the amountof pulsatile ocular blood flow. The intraocular pressure and intraocular pulse are normally1525CA 02264193 1999-02-26WO 98/09564 PCTIU S97/ 1548978symmetrical in pairs of eyes. Consequently, a loss of symmetry may serve as an early sign ofocular or cerebrovascular disease. Patients afflicted with diabetes, macular degeneration, andother vascular disorders may also have a decreased ocular blood flow and benefit fromevaluation of eye hemodynamics using the apparatus of the present invention.The present invention may also be used to artificially elevate intraocular pressure. Theartificial elevation of intraocular pressure is an important tool in the diagnosis and prognosisof eye and brain disorders as well as an important tool for research.Artificial elevation of intraocular pressure using the present invention can beaccomplished in different ways. According to one way, the contact device of the presentinvention is modified in shape for placement on the sclera (white of the eye) . This arrangement,which will be described hereinafter, is illustrated in Figures 21-22, wherein the movable centralpiece 16 may be larger in size and is preferably actuated against the sclera in order to elevatethe intraocular pressure. The amount of indentation can be detected by the optical detectionsystem previously described.Another way of artificially increasing the intraocular pressure is by placing the contactdevice of the present invention on the cornea in the same way as previously described, but usingthe movable central piece to apply a greater amount of force to achieve deeper indentation.This technique advantageously allows visualization of the eye while exerting the force, sincethe movable central portion of the contact device is preferably transparent. According to thistechnique, the size of the movable central piece can also be increased to indent a larger area andthus create a higher artificial increase of intraocular pressure. Preferably, the actuationapparatus also has a transparent central portion, as indicated above, to facilitate directvisualization of the eye and retina while the intraocular pressure is being increased. When theintraocular pressure exceeds the ophthalmic arterial diastolic pressure, the pulse amplitude andblood flow decreases rapidly. Blood flow becomes zero when the intraocular pressure is equalor higher than the ophthalmic systolic pressure. Thus, by allowing direct visualization oftheretinal vessels, one is able to determine the exact moment that the pulse disappears and measurethe pressure necessary to promote the cessation of the pulse which, in turn, is the equivalentof the pulse pressure in the ophthalmic artery. The present invention thus allows themeasurement of the pressure in the arteries of the eye.Also, by placing a fixation light in a back portion of the actuation apparatus and askingl0152530CA 02264193 1999-02-26W0 98/09564 I’CT/US97/ 1548979the patient to indicate when he/she can no longer see the light, one can also record the pressureat which a patient's vision ceases. This also would correspond to the cessation of the pulse inthe artery of the eye. The pressure in which vessels open can also be determined by increasingintraocular pressure until the pulse disappears and then gradually decreasing the intraocularpressure until the pulse reappears. Thus, the intraocular pressure necessary for vessels to opencan be evaluated.It is important to note that the foregoing measurements can be performed automaticallyusing an optical detection system, for example, by aiming at light beam at the pulsating bloodvessel. The cessation of pulsation can be optically recognized and the pressure recorded. Anattenuation of pulsations can also be used as the end point and can be optically detected. Theapparatus also allows direct visualization of the papilla of the optic nerve while an increasedintraocular pressure is produced. Thus, physical and chemical changes occurring inside the eyedue to the artificial increase in intraocular pressure may be evaluated at the same time thatpressure is measured.Advantageously, the foregoing, test can be performed on patients with media opacitiesthat prevent visualization of the back of the eye. In particular, the aforementioned procedurewherein the patient indicates when vision ceases is particular useful in patients with mediaopacities. The fading of the peripheral vision corresponds to the diastolic pressure and fadingof the central vision corresponds to the systolic pressure.The present invention, by elevating the intraocular pressure, as indicated above and byallowing direct visualization of blood vessels in the back of the eye, may be used for tamponade(blockade of bleeding by indirect application of pressure) of hemorrhagic processes such asthose which occur, for example, in diabetes and macular degeneration. The elevation ofintraocular pressure may also be beneficial in the treatment of retinal detachments.As yet another use of the present invention, the aforementioned apparatus also can beused to measure outflow pressure of the eye fluid. In order to measure outflow pressure in theeye fluid, the contact device is placed on the cornea and a measurable pressure is applied to thecomea. The pressure causes the aqueous vein to increase in diameter when the pressure in thecornea equals the outflow pressure. The pressure on the cornea is proportional to the outflowpressure. The flow of eye fluid out of the eye is regulated according to Poiseuille's Law forlaminar currents. If resistance is inserted into the formula, the result is a formula similar to15202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/ 1548980Ohm's Law. Using these known formulas, the rate of flow (volume per time) can bedetermined. The change in the diameter of the vessel which is the reference point can bedetected manually by direct observation and visualization of the change in diameter or can bedone automatically using an optical detection system capable of detecting a change inreflectivity due to the amount of fluid in the vein and the change in the surface area. The actualcross-section of the vein can be detected using an optical detection system.The eye and the brain are hemodynarnically linked by the carotid artery and theautonomic nervous system. Pathological changes in the carotid, brain, heart, and thesympathetic nervous system can secondarily affect the blood flow to the eye. The eye and thebrain are low vascular resistance systems with high reactivity. The arterial flow to the brain isprovided by the carotid artery. The ophthalmic artery branches off of the carotid at a 90 degreeangle and measures approximately 0.5 mm in diameter in comparison to the carotid whichmeasures 5 mm in diameter. Thus, most processes that affect the flow to the brain will havea profound effect on the eye. Moreover, the pulsation of the central retinal artery may be usedto determine the systolic pressure in the ophthalmic artery, and due to its anatomic relationshipwith the cerebral circulatory system, the pressure in the brain's vessels can be estimated. Totalor partial occlusion of the vascular system to the brain can be determined by evaluating theocular blood flow. There are numerous vascular and nervous system lesions that alter theocular pulse amplitude and/or the intraocular pressure curve of the eye. These pathologicalsituations may produce asymmetry of measurements between the two eyes and/or a decreaseof the central‘ retinal artery pressure, decrease of pulsatile blood flow and alter the pulseamplitude.An obstruction in the flow in the carotid (cerebral circulation) can be evaluated byanalyzing the ocular pulse amplitude and area, pulse delay and pulse width, form of the waveand by harmonic analysis of the ocular pulse.The eye pulsation can be recorded optically according to the change in reflection of thelight beam projected to the cornea. The same system used to record distance traveled by themovable central piece during indentation can be used on the bare cornea to detect the changesin volume that occurs with each pulsation. The optical detection system records the variationsin distance from the surface of the cornea that occurs with each heart beat. These changes inthe position of the cornea are induced by the volume changes in the eye. From the pulsatile1015202530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548981character of these changes, the blood flow to the eye can be calculated.With the aforementioned technique of artificial elevation of pressure, it is possible tomeasure the time necessary for the eye to recover to its baseline and this recovery time is anindicator of the presence of glaucoma and of the coefficient of outflow facility.The present invention may also be used to measure pressure in the vessels on thesurface of the eye, in particular the pressure in the episcleral veins. The external pressurenecessary to collapse a vein is utilized in this measurement. The method involves applying avariable force over a constant area of conjunctive overlying the episcleral vein until a desiredend point is obtained. The pressure is applied directly onto the vessel itself and the preferredend point is when the vessel collapses. However, different end points may be used, such asblanching of the vessel which occurs prior to the collapse. The pressure ofthe end point isdetermined by dividing the force applied by the area of the applanating central piece in a similarway as is used for tonometry. The vessel may be observed through a transparent applanatingmovable central piece using a slit-lamp biomicroscope. The embodiment for this techniquepreferably includes a modified contact device which fits on the sclera (Figure 23) . Thepreferred size of the tip ranges from 250 micrometers to 500 micrometers. Detection of theend point can be achieved either manually or automatically.According to the manual arrangement, the actuation apparatus is configured for directvisualization of the vessel through a transparent back window of the actuation apparatus, andthe time of collapse is manually controlled and recorded. According to an automaticarrangement, an optical detection system is configured so that, when the blood stream is nolonger visible, there is a change in a reflected light beam in the same way as described abovefor tonometry, and consequently, the pressure for collapse is identifiable automatically. Theend point marking in both situations is the disappearance of the blood stream, one detected bythe operators vision and the other detected by an optical detection system. Preferably, in bothcases, the contact device is designed in a way to fit the average curvature of the sclera and themovable central piece, which can be a rigid or flexible material, is used to compress the vessel.The present invention may also be used to provide real-time recording of intraocularpressure. A built-in single chip microprocessor can be "made responsive to the intraocularpressure measurements over time and can be programmed to create and display a curve relatingpressure to time. The relative position of the movable central piece can be detected, as. . .........-u-nu.-a.-.__c... . . ..__. ....-r.........—..-.—........fl.....2025CA 02264193 1999-02-26WO 98/09564 PCT/US97Il548982indicated above, using an optical detection system and the detected position in combinationwith information regarding the amount of current flowing through the coil of the actuationapparatus can be rapidly collected and analyzed by the microprocessor to create theaforementioned curve.It is understood that the use of a microprocessor is not limited to the arrangementwherein curves are created. In fact, microprocessor technology may be used to create at leastthe aforementioned calculation unit 10 of the present invention. A microprocessor preferablyevaluates the signals and the force that is applied. The resulting measurements can be recordedor stored electronically in a number of ways. The changes in current over time, for example,can be. recorded on a strip-chart recorder. Other methods of recording and storing the datacan be employed. Logic microprocessor control technology can also be used in order to betterevaluate the data.Still other uses of the present invention relate to evaluation of pressure in defonnablematerials in industry and medicine. One such example is the use of the present invention toevaluate sofi tissue, such as organs removed from cadavers. Cadaver dissection is afundamental method of learning and studying the human body. The deformability of tissuessuch as the brain, liver, spleen, and the like, can be measured using the present invention andthe depth of indentation can be evaluated. In this regard, the contact device of the presentinvention can be modified to fit over the curvature of an organ. When the movable centralpiece rests upon a surface, it can be actuated to project into the surface a distance which isinversely proportional to the tension of the surface and rigidity of the surface to deformation.The present invention can also be used to evaluate and quantify the amount of cicatrization,especially in burn scar therapy. The present invention can be used to evaluate the firmness ofthe soar in comparison to normal skin areas. The scar skin tension is compared to the value ofnormal skin tension. This technique can be used to monitor the therapy of patients with burnscars allowing a numerical quantification of the course of cicatrization. This technique can alsobe used as an early indicator for the development of hypertrophic (thick and elevated) scarring.The evaluation of the tissue pressure and deformability in a variety of conditions such as: a)lymphoedema b) post-surgical effects, such as with breast surgery, and c) endoluminalpressures of hollow organs, is also possible with the apparatus. In the above cases, the piston-like arrangement provided by the contact device does not have to be placed in an element that202530CA 02264193 1999-02-26W0 98/09564 PCT/US97/ 1548983is shaped like a contact lens. To the contraiy, any shape and size can be used, with the bottomsurface preferably being flat and not curved like a contact lens.Yet another use of the present invention relates to providing a bandage lens which canbe used for extended periods of time. Glaucoma and increased intraocular pressure are leadingcauses for rejection of corneal transplants. Many conventional tonometers in the market areunable to accurately measure intraocular pressure in patients with corneal disease. For patientswith corneal disease and who have recently undergone corneal transplant, a thinner and largercontact device is utilized and this contact device can be used for a longer period of time. Thedevice also facilitates measurement of intraocular pressure in patients with corneal diseasewhich require wearing of contact lenses as part of their treatment.The present invention may also be modified to non-invasively measure infant intracranialpressure, or to provide instantaneous and continuous monitoring of blood pressure through anintact wall of a blood vessel. The present invention may also be used in conjunction with adigital pulse meter to provide synchronization with the cardiac cycle. Also, by providing acontact microphone, arterial pressure can be measured. The present invention may also be usedto create a dual tonometer arrangement in one eye. A first tonometer can be defined by thecontact device of the present invention applied over the cornea, as described above. Thesecond tonometer can be defined by the previously mentioned contact device which is modifiedfor placement on the temporal sclera. In using the dual tonometer arrangement, it is desirableto permit looking into the eye at the fundus while the contact devices are being actuated.Accordingly, at least the movable central piece of the Contact device placed over the cornea ispreferably transparent so that the fundus can be observed with a microscope.Although the foregoing illustrated embodiments of the contact device generally showonly one movable central piece 16 in each contact device 2, it is understood that more than onemovable central piece 16 can be provided without departing from the scope and spirit of thepresent invention. Preferably, the multiple movable central pieces 16 would be concentricallyarranged in the contact device 2, with at least one of the flexible membranes 14 interconnectingthe concentrically arranged movable central pieces 16. This arrangement of multiple movablecentral pieces 16 can be combined with any of the aforementioned features to achieve a desiredoverall combination.Although the foregoing preferred embodiments include at least one magnetically2025CA 02264193 1999-02-26W0 98l09564 PCT/US97/ 1548984actuated movable central piece 16, it is understood that there are many other techniques foractuating the movable central piece 16. Sound or ultrasound generation techniques, forexample, can be used to actuate the movable central piece. In particular, the sonic or ultrasonicenergy can be directed to a completely transparent version of the movable central piece which,in turn, moves in toward the cornea in response to the application of such energy.Similarly, the movable central piece may be provided with means for retaining a staticelectrical charge. In order to actuate such a movable central piece, an actuation mechanismassociated therewith would create an electric field of like polarity, thereby causing repulsionof the movable central piece away from the source of the electric field.Other actuation techniques, for example, include the discharge of fluid or gas towardthe movable central piece, and according to a less desirable arrangement, physically connectingthe movable central piece to a mechanical actuation device which, for example, may be motordriven and may utilize a strain gauge.Altematively, the contact device may be eliminated in favor of a movable central piecein an actuation apparatus. According to this arrangement, the movable central piece of theactuation apparatus may be connected to a slidable shaft in the actuation apparatus, which shaftis actuated by a magnetic field or other actuation means. Preferably, a physician applies themovable central piece of the actuation apparatus to the eye and presses a button whichgenerates the magnetic field. This, in turn, actuates the shaft and the movable central pieceagainst the eye. Preferably, the actuation apparatus, the shaft, and the movable central pieceof the actuation apparatus are appropriately arranged with transparent portions so that theinside of the patient's eye remains visible during actuation.Any of the above described detection techniques, including the optical detectiontechnique, can be used with the alternative actuation techniques.Also, the movable central piece 16 may be replaced by an inflatable bladder (not shown)disposed of the substantially rigid annular member 12. When inflated, the bladder extends outof the hole in the substantially rigid annular member 12 and toward the cornea.Similarly, although some of the foregoing preferred embodiments utilize an opticalarrangement for determining when the predetermined amount of applanation has been achieved,it is understood that there are many other techniques for determining when applanation occurs.The contact device, for example, may include an electrical contact arranged so as to make orl0152025CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548985break an electrical circuit when the movable central piece moves a distance corresponding tothat which is necessary to produce applanation. The making or breaking of the electrical circuitis then used to signify the occurrence of applanation.It is also understood that, after applanation has occurred, the time which it takes for themovable central piece 16 to return to the starting position after termination of the actuatingforce will be indicative of the intraocular pressure. when the intraocular pressure is high, themovable central piece 16 returns more quickly to the starting position. Similarly, for lowerintraocular pressures, it takes longer for the movable central piece 16 to return to its startingposition. Therefore, the present invention can be configured to also consider the return timeof the movable central piece 16 in determining the measured intraocular pressure.As indicated above, the present invention may be formed with a transparent centralportion in the contact device. This transparent central portion advantageously permitsvisualization of the inside of the eye (for example, the optic nerve) while the intraocularpressure is artificially increased using the movable central piece. Some of the effects ofincreased intraocular pressure on the optic nerve, retina, and vitreous are therefore readilyobservable through the present invention, while intraocular pressure is measuredsimultaneously.With reference to Figures 2] and 22, although the foregoing examples describeplacement of the contact device 2 on the cornea, it is understood that the contact device 2 ofthe present invention may be configured with a quasi-triangular shape (defined by thesubstantially rigid annular member) to facilitate placement of the contact device 2 on the scleraof the eye.With reference to Figures 23 and 24, the contact device 2 of the present invention maybe used to measure episcleral venous pressure. Preferably, when episcleral venous pressure isto be measured, the movable central piece 6 has a transparent centrally disposed frustoconicalprojection l6P. The embodiment illustrated Figure 24 advantageously permits visualization ofthe subject in through at least the transparent central portion of the movable central piece 16.Furthermore, as indicated above, the present invention may also be used to measurepressure in other parts of the body (for example, scar pressure in the context of plastic surgery)or on surfaces of various objects. The contact device of the present invention, therefore, is notlimited to the corneal-conforming curved shape illustrated in connection with the exemplary1015202530CA 02264193 1999-02-2686embodiments, but rather may have various other shapes including a generally flat configuration.ALTERNATIVE EMBODIMENT ACTUATEDBY CLOSURE OF THE EYE LIDWith reference to Figures 25-31, an alternative embodiment of the system will now bedescribed. The alternative apparatus and method uses the force and motion generated by theeye lid during blinking and/or closure of the eyes to act as the actuation apparatus and activateat least one transducer 400 mounted in the contact device 402 when the contact device 402 ison the cornea. The method and device facilitate the remote monitoring of pressure and otherphysiological events by transmitting the information through the eye lid tissue, preferably viaelectromagnetic waves. The information transmitted is recovered at a receiver 404 remotelyplaced with respect to the contact device 402, which receiver 404 is preferably mounted in theframe 408 of a pair of eye glasses. This alternative embodiment also facilitates utilization offorcefill eye lid closure to measure outflow facility. The transducer is preferably amicrominiature pressure-sensitive transducer 400 that alters a radio frequency signal in amanner indicative of physical pressure exerted on the transducer 400.Although the signal response from the transducer 400 can be communicated by cable,it is preferably actively or passively transmitted in a wireless manner to the receiver 404 whichis remotely located with respect to the contact device 402. The data represented by the signalresponse of th'e transducer 400 can then be stored and analyzed. Infonnation derived from thisdata can also be communicated by telephone using conventional means.According to the alternative embodiment, the apparatus comprises at least one pressure-sensitive transducer 400 which is preferably activated by eye lid closure and is mounted in thecontact device 402. The contact device 402, in turn, is located on the eye. In order to calibratethe system, the amount of motion and squeezing of the contact device 402 during eye lidmotion/closure is evaluated and calculated. As the upper eyelid descends during blinking, itpushes down and squeezes the contact device 402, thereby forcing the contact device 402 toundergo a combined sliding and squeezing motion.Since normal individuals involuntarily blink approximately every 2 to 10 seconds, thisalternative embodiment of the present invention provides frequent actuation of the transducer400. In fact, normal individuals wearing a contact device 402 of this type will experience anrm/Us 97/1548 9IPENUS 03 AUG 1998152025CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548987increase in the number of involuntary blinks, and this, in turn, tends to provide quasi-continuousmeasurements. During sleep or with eyes closed, since there is uninterrupted pressure by theeye lid, the measurements can be taken continuously.As indicated above, during closure of the eye, the contact device 402 undergoes acombined squeezing and sliding motion caused by the eye lid during its closing phase. Initiallythe upper eye lid descends from the open position until it meets the upper edge of the contactdevice 402, which is then pushed downward by approximately 0.5 mm to 2 mm. This distancedepends on the type of material used to make the structure 412 of the contact device 402 andalso depends on the diameter thereof.When a rigid structure 412 is used, there is little initial overlap between the lid and thecontact device 402. When a soft structure 412 is used, there is a significant overlap evenduring this initial phase of eye lid motion. After making this initial small excursion the contactdevice 402 comes to rest, and the eye lid then slides over the outer surface of the contactdevice 402 squeezing and covering it. It is important to note that if the diameter of thestructure 412 is greater than the lid aperture or greater than the corneal diameter, the upper lidmay not strike the upper edge of the contact device 402 at the beginning of a blink.The movement of the contact device 402 terminates approximately at the comeo-scleraljunction due to a slope change of about 13 degrees in the area of intersection between cornea(radius of 9 mm) and sclera (radius of 11.5 mm) . At this point the contact device 402, eitherwith a rigid or sofi structure 412, remains immobile and steady while the eye lid proceeds tocover it entirely.When a rigid structure 412 is used, the contact device 402 is usually pushed down 0.5mm to 2 mm before it comes to rest. When a soft structure 412 is used, the contact device 402is typically pushed down 0.5 mm or less before it comes to rest. The larger the diameter of thecontact device 402, the smaller the motion, and when the diameter is large enough there maybe zero vertical motion. Despite these differences in motion, the squeezing effect is alwayspresent, thereby allowing accurate measurements to be taken regardless of the size of thestructure 412. Use of a thicker structure 412 or one with a flatter surface results in anincreased squeezing force on the contact device 402.The eye lid margin makes a re—entrant angle of about 35 degrees with respect to thecornea. A combination of forces, possibly caused by the contraction of the muscle of Riolan152530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548988near the rim of the eye lid and of the orbicularis muscle, are applied to the contact device 402by the eye lid. A horizontal force (normal force component) of approximately 20,000 to25,000 dynes and a vertical force (tangential force component) of about 40 to 50 dynes isapplied on the contact device 402 by the upper eye lid. In response to these forces, the contactdevice 402 moves both toward the eye and tangentially with respect thereto. At the momentof maximum closure of the eye, the tangential motion and force are zero and the normal forceand motion are at a maximum.The horizontal lid force of 20,000 to 25,000 dynes pressing the contact device 402against the eye generates enough motion to activate the transducer 400 mounted in the contactdevice 402 and to permit measurements to be performed. This eye lid force and motion towardthe surface of the eye are also capable of sufficiently deforming many types of transducers orelectrodes which can be mounted in the contact device 402. During blinking, the eye lids arein fiill contact with the contact device 402 and the surface of each transducer 400 is in contactwith the cornea/tear film and/or inner surface of the eye lid.The microminiature pressure-sensitive radio frequency transducer 400 preferablyconsists of an endoradiosonde mounted in the contact device 402 which, in turn, is preferablyplaced on the cornea and is activated by eye lid motion and/or closure. The force exerted bythe eye lid on the contact device 402, as indicated above, presses it against the cornea.According to a preferred alternative embodiment illustrated in Figure 26, theendoradiosonde includes two opposed matched coils which are placed within a small pellet.The flat walls‘ of the pellet act as diaphragms and are attached one to each coil such thatcompression of the diaphragm by the eye lid brings the coils closer to one another. Since thecoils are very close to each other, minimal changes in their separation affect their resonantfrequency.A remote grid-dip oscillator 414 may be mounted at any convenient location near thecontact device 402, for example, on a hat or cap worn by the patient. The remote grid-diposcillator 414 is used to induce oscillations in the transducer 400. The resonant frequency ofthese oscillations is indicative of intraocular pressure.Briefly, the contact of the eye lid with the diaphragms forces a pair of parallel coaxialarchimedean-spiral coils in the transducer 400 to move closer together. The coils constitutea high-capacitance distributed resonant circuit having a resonant frequency that variesl015202530CA 02264193 1999-02-26WO 98109564 PCT/US97/1548989according to relative coil spacing. When the coils approach one another, there is an increasein the capacitance and mutual inductance, thereby lowering the resonant frequency of theconfiguration. By repeatedly scanning the frequency of an external inductively coupledoscillating detector of the grid-dip type, the electromagnetic energy which is absorbed by thetransducer 400 at its resonance is sensed through the intervening eye lid tissue.Pressure information from the transducer 400 is preferably transmitted by radio linktelemetry. Telemetry is a preferred method since it can reduce electrical noise pickup andeliminates electric shock hazards. FM (frequency modulation) methods of transmission arepreferred since FM transmission is less noisy and requires less gain in the modulation amplifier,thus requiring less power for a given transmission strength. FM is also less sensitive tovariations in amplitude of the transmitted signal.Several other means and transducers can be used to acquire a signal indicative ofintraocular pressure from the contact device 402. For example, active telemetry usingtransducers which are energized by batteries or using cells that can be recharged in the eye byan external oscillator, and active transmitters which can be powered from a biologic source canalso be used.The preferred method to acquire the signal, however, involves at least one of theaforementioned passive pressure sensitive transducers 400 which contain no internal powersource and operate using energy supplied from an external source to modify the frequencyemitted by the external source. Signals indicative of intraocular ocular pressure are based onthe frequency modification and are transmitted to remote extra-ocular radio frequencymonitors. The resonant frequency of the circuit can be remotely sensed, for example, by a grid-dip meter.In particular, the grip-dip meter includes the aforementioned receiver 404 in which theresonant frequency of the transducer 400 can be measured after being detected by externalinduction coils 415 mounted near the eye, for example, in the eyeglass frames near the receiveror in the portion of the eyeglass frames which surround the eye. The use of eyeglass framesis especially practical in that the distance between the external induction coils 415 and theradiosonde is within the typical working limits thereof. It is understood, however, that theexternal induction coils 415, which essentially serve as a receiving antenna for the receiver 404can be located any place that minimizes signal attenuation. The signal from the externall01530CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548990induction coils 415 (or receiving antenna) is then received by the receiver 404 for amplificationand analysis.When under water, the signal may be transmitted using modulated sound signalsbecause sound is less attenuated by water than are radio waves. The sonic resonators can bemade responsive to changes in temperature and voltage.Although the foregoing description includes some preferred methods and devices inaccordance with the alternative embodiment of the present invention, it is understood that theinvention is not limited to these preferred devices and methods. For example, many other typesof miniature pressure sensitive radio transmitters can be used and mounted in the contactdevice, and any rnicrominiature pressure sensor that modulates a signal from a radio transmitterand sends the modulated signal to a nearby radio receiver can be used.Other devices such as strain gauges, preferably piezoelectric pressure transducers, canalso be used on the cornea and are preferably activated by eye lid closure and blinking. Anydisplacement transducer contained in a distensible case also can be mounted in the contactdevice. In fact, many types of pressure transducers can be mounted in and used by the contactdevice. Naturally, virtually any transducer that can translate the mechanical deformation intoelectric signals is usable.Since the eye changes its temperature in response to changes in pressure, a pressure-sensitive transducer which does not require motion of the parts can also be used, such as athermistor. Alternatively, the dielectric constant of the eye, which also changes in response topressure changes, can be evaluated to determine intraocular pressure. In this case, a pressure-sensitive capacitor can be used. Piezoelectric and piezo-resistive transducers, silicon straingauges, semiconductor devices and the like can also be mounted and activated by blinkingand/or closure of the eyes.In addition to providing a novel method for performing single measurements,continuous measurements, and self-measurement of intraocular pressure during blinking or withthe eyes closed, the apparatus can also be used to measure outflow facility and otherphysiological parameters. The inventive method and device offer a unique approach tomeasuring outflow facility in a physiological manner and undisturbed by the placement of anexternal weight on the eye.In order to determine outflow facility in this fashion, it is necessary for the eye lid tol0152025CA 02264193 1999-02-26WO 98/09564 PCT/US97ll548991create the excess force necessary to squeeze fluid out of the eye. Because the present inventionpermits measurement of pressure with the patient's eyes closed, the eye lids can remain closedthroughout the procedure and measurements can be taken concomitantly. In particular, thisis accomplished by forcefiilly squeezing the eye lids shut. Pressures of about 60 mm Hg willoccur, which is enough to squeeze fluid out of the eye and thus evaluate outflow facility. Theintraocular pressure will decrease over time and the decay in pressure with respect to timecorrelates to the outflow facility. In normal individuals, the intraocular fluid is forced out ofthe eye with the forcefiil closure of the eye lid and the pressure will decrease accordingly;however, in patients with glaucoma, the outflow is compromised and the eye pressure thereforedoes not decrease at the same rate in response to the forceful closure of the eye lids. Thepresent system allows real time and continuous measurement of eye pressure and, since thesignal can be transmitted through the eye lid to an external receiver, the eyes can remain closedthroughout the procedure.Telemetry systems for measuring pressure, electrical changes, dimensions, acceleration,flow, temperature, bioelectric activity, chemical reactions, and other important physiologicalparameters and power switches to externally control the system can be used in the apparatusof the invention. The use of integrated circuits and technical advances occurring in transducer,power source, and signal processing technology allow for extreme miniaturization of thecomponents which, in turn, permits several sensors to be mounted in one contact device, asillustrated for example in Figure 28.Modern resolutions of integrated circuits are in the order of a few microns and facilitatethe creation of very high density circuit arrangements. Preferably, the modern techniques ofmanufacturing integrated circuits are exploited in order to make electronic components smallenough for placement on the eyeglass frame 408. The receiver 404, for example, may beconnected to various miniature electronic components 418, 419, 420, as schematicallyillustrated in Figure 31, capable of processing, storing, and even displaying the informationderived from the transducer 400.Radio frequency and ultrasonic micro-circuits are available and can be mounted in thecontact device for use thereby. A number of different ultrasonic and pressure transducers arealso available and can be used and mounted in the contact device. It is understood that furthertechnological advances will occur which will permit further applications of the apparatus of the10152025CA 02264193 1999-02-26WO 98/09564 PCT/US97/1 548992invention.The system may further comprise a contact device for placement on the cornea andhaving a transducer capable of detecting chemical changes in the tear film. The system mayfurther include a contact device for placement on the cornea and having a microminiature gas-sensitive radio frequency transducer (e.g., oxygen-sensitive) . A contact device having amicrominiature blood velocity-sensitive radio frequency transducer may also be used formounting on the conjunctiva and is preferably activated by eye lid motion and/or closure of theeye lid.The system also may comprise a contact device in which a radio frequency transducercapable or measuring the negative resistance of nerve fibers is mounted in the contact devicewhich, in turn, is placed on the cornea and is preferably activated by eye lid motion and/orclosure of the eye lid. By measuring the electrical resistance, the effects of microorganisms,drugs, poisons and anesthetics can be evaluated.The system of the present invention may also include a contact device in which arnicrominiature radiation-sensitive radio frequency transducer is mounted in the contact devicewhich, in turn, is placed on the cornea and is preferably activated by eye lid motion and/orclosure of the eye lid.In any of the foregoing embodiments having a transducer mounted in the contactdevice, a grid-dip meter can be used to measure the frequency characteristics of the tunedcircuit defined by the transducer.Besides using passive telemetry techniques as illustrated by the use of the abovetransducers, active telemetry with active transmitters and a microminiature battery mounted inthe contact device can also be used.The contact device preferably includes a rigid or flexible transparent structure 412 inwhich at least one of the transducers 400 is mounted in hole(s) fonned in the transparentstructure 412. Preferably, the transducers 400 is/are positioned so as to allow the passage oflight through the visual axis. The structure 412 preferably includes an inner concave surfaceshaped to match an outer surface of the cornea.As illustrated in Figure 29, a larger transducer 400 can be centrally arranged in thecontact device 402, with a transparent portion 416 therein preserving the visual axis of thecontact device 402.l01525CA 02264193 1999-02-26WO 98/09564 PCT/US97/1548993The structure 412 preferably has a maximum thickness at the center and a progressivelydecreasing thickness toward a periphery of the structure 412. The transducers is/are preferablysecured to the structure 412 so that the anterior side of each transducer 400 is in contact withthe inner surface of the eye lid during blinking and so that the posterior side of each transducer400 is in contact with the cornea, thus allowing eye lid motion to squeeze the contact device402 and its associated transducers 400 against the comea_Preferably, each transducer 400 is fixed to the structure 412 in such a way that only thediaphragms of the transducers experience motion in response to pressure changes. Thetransducers 400 may also have any suitable thickness, including matching or going beyond thesurface of the structure 412.The transducers 400 may also be positioned so as to bear against only the cornea oralternatively only against the inner surface of the eye lid. The transducers 400 may also bepositioned in a protruding way toward the cornea in such a way that the posterior part flattensa portion of the cornea upon eye lid closure. Similarly, the transducers 400 may also bepositioned in a protruding way toward the inner surface of the eye lid so that the anterior partof the transducer 400 is pressed by the eye lid, with the posterior part being covered by aflexible membrane allowing interaction with the cornea upon eye lid closure.A flexible membrane of the type used in flexible or hydrogel lenses may encase thecontact device 402 for comfort as long as it does not interfere with signal acquisition andtransmission. Although the transducers 400 can be positioned in a manner to counterbalanceeach other, as illustrated in Figure 28, it is understood that a counter weight can be used tomaintain proper balance.While the present invention has been described with reference to preferred embodimentsthereof, it is understood that the present invention is not limited to those embodiments, andby the scope of the appended claims.

Claims (8)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. ~A contact device for detecting intraocular pressure, said contact device comprising:
a contact structure shaped for placement on a patient's cornea, said contact structure having a flat inner portion which contacts said patient's cornea;

a transducer disposed in said contact structure, said transducer being responsive to pressure exerted on said transducer, so as to provide an output signal indicative of said pressure, said transducer being responsive to pressure generated by sliding and squeezing of said transducer by an eye lid during closure of the eye lid.

2. ~A contact device for detecting intraocular pressure, said contact device comprising:
a contact structure shaped for placement on a patient's cornea;

a flat structure mounted in a central opening of the contact structure and movable within the central opening of the contact structure;
a transducer disposed in said contact structure, said transducer being responsive to pressure exerted on said transducer, so as to provide an output signal indicative of said pressure, said transducer being responsive to pressure generated by sliding and squeezing of said transducer by an eye lid during closure of the eye lid.

3. ~A contact device for detecting intraocular pressure, said contact device comprising:
a contact structure shaped for placement on a patient's cornea: said contact structure comprising:

a substantially rigid annular member having an inner concave surface shaped to match an outer surface of a patient's cornea and having a hole defined therein;
and a movable central piece slidably disposed within said hole and having a substantially flat inner side for flattening a portion of the patient's cornea while the device is located on the cornea;
a transducer disposed in said contact structure, said transducer being responsive to pressure exerted on said transducer, so as to provide an output signal indicative of said pressure, said transducer being responsive to pressure generated by sliding and squeezing of said transducer by an eye lid during closure of the eye lid.

4. ~A method for detecting pressure using the contact device according to any one of claims 1 to 3 comprising the steps of:

mounting, on a surface of a cornea of an eye, a pressure sensitive transducer which is responsive to pressure generated by sliding and squeezing of said pressure sensitive transducer by an eye lid during closure of said eye lid associated with said eye; and activating said pressure sensitive transducer by sliding and squeezing of said pressure sensitive transducer by said eye lid during closure of said eye lid.

5. ~A method for detecting pressure according to claim 4, wherein signals indicative of pressure are transmitted through the eye lid by electromagnetic waves.

6. ~A contact device for detecting intraocular pressure, said contact device comprising:
a contact structure shaped for placement on a patient's cornea; said contact structure having a flat inner portion which contacts said patient's cornea;

a transducer disposed in said contact structure, said transducer being responsive to pressure exerted on said transducer, so as to provide an output signal indicative of said pressure; said transducer being a passive transducer having a resonant frequency which varies in accordance with said pressure.

7. ~A contact device for detecting intraocular pressure, said contact device comprising:
a contact structure shaped for placement on a patient's cornea;

a flat structure mounted in a central opening of the contact structure and movable within the central opening of the contact structure;
a transducer disposed in said contact structure, said transducer being responsive to pressure exerted on said transducer, so as to provide an output signal indicative of said pressure; said transducer being a passive transducer having a resonant frequency which varies in accordance with said pressure.

8. A contact device for detecting intraocular pressure, said contact device comprising:
a contact structure shaped for placement on a patient's cornea: said contact structure comprising:
a substantially rigid annular member having an inner concave surface shaped to match an outer surface of a patient's cornea and having a hole defined therein;
a movable central piece slidably disposed within said hole and having a substantially flat inner side for flattening a portion of the patient's cornea while the device is located on the cornea;
a transducer disposed in said contact structure, said transducer being responsive to pressure exerted on said transducer, so as to provide an output signal indicative of said pressure; said transducer being a passive transducer having a resonant frequency which varies in accordance with said pressure.