Tonometry Through The Ages

Transcription

1 Tonometry Through The Ages Tonometrie im Wandel der Zeit Habilitationsschrift zur Erlangung der venia legendi auf dem Gebiet der Ophthalmologie vorgelegt von Dr. Christoph Kniestedt Zürich 2007

2 Kniestedt, C. Tonometry Through The Ages 1 INTRODUCTION The definition of glaucoma has changed over the decades from a simple ocular pressure disease to a systemic disorder of multivariate etiology. Glaucoma may be defined for the individual eye as a chronic ocular disease with various underlying pathophysiologic disorders. Glaucoma represents a disturbance of the structural or functional integrity of the optic nerve that can usually be arrested or diminished by adequate lowering of the intraocular pressure. Therefore, elevated intraocular pressure (IOP) is still the most important risk factor for an untreated glaucomatous eye to progress to a more severe stage of the disease. As the main risk factor within therapeutic reach, IOP and its appropriate measurement deserves our ongoing interest. Not only has our understanding of the glaucomas changed but also our approach to the measurement of the IOP. In this article, a review is undertaken with the focus on the various developments in IOP measurement (tonometry) from the simple force-tonometers of the late 19 th century to the high-technology pressure-tonometers that were recently introduced for routine clinical use. Original articles are discussed from the perspective of the physical principles involved in tonometry.

3 Kniestedt, C. Tonometry Through The Ages 2 INTRAOCULAR PRESSURE Intraocular pressure is the result of a dynamic balance between aqueous humor formation and outflow, which are nearly equal under normal conditions. Aqueous formation (2 µl/min) has two components: a hydrostatic component, produced by passive leakage of fluid from the blood, and a secretory component, resulting from the active transport of sodium and other ions by the ciliary epithelium. 57,76,138 The aqueous is produced by the ciliary processes in the posterior chamber. It circulates throughout the eye and finally drains through the trabecular meshwork into Schlemm's canal, the collector channels, and episcleral veins. The uveoscleral or unconventional pathway contributes to a smaller proportion of aqueous humor outflow. 104,256 Figure 1. Liquid flow paths in the eye [From Davson (1969)] 41 Figure 1 shows diagrammatically the flow paths and the pressure produced. The aqueous fluid is produced from arterial blood flowing at pressure P ia (intraocular artery pressure) through the arteries in the ciliary body. Because there seems to be some metabolic work

4 Kniestedt, C. Tonometry Through The Ages 3 required to move fluid from the artery to the inside chambers of the eye, the location where such work is done is indicated as pump. The fluid leaves the eye via the canal of Schlemm and by percolation through the uveoscleral tract. The pressure in the episcleral veins reflects the central venous pressure. The episcleral venous pressure is the lower limit of the intraocular pressure in an intact eye if uveoscleral outflow is ignored. An increase in episcleral venous pressure makes it more difficult for the aqueous to drain and may result in increased IOP. 42,73 However, most common reasons for elevated IOP are due to an increase in trabecular resistance outflow whilst uveoscleral outflow may remain unchanged for a long time in the glaucomatous eye. 256 By applanation means, the normal IOP is around 16 mmhg with a Gaussian-like distribution but a tail towards higher IOP s in older individuums. An IOP between 7 and 21 mmhg is considered to be statistically normal. The upper cut-off value of 21 mmhg represents 2 standard deviations above the mean IOP of 16 mmhg in a population of white individuals. 18 The normal IOP is pulsatile, reflecting its cardio-vascular origin. 63,134,143,148,234 The pulses follow the arterial pulses, and a diagnosis of cardiac arrhythmia or a stenosis of the ipsilateral internal carotid artery can actually be made from a continuous measurement of the IOP with low pulsation. 15,151 On the other hand, pulsation may be greater if there is a large arterial pulse pressure, such as in hypertension or aortic regurgitation. 148

5 Kniestedt, C. Tonometry Through The Ages 4 MEASUREMENT OF INTRAOCULAR PRESSURE Three methods of evaluating the IOP are available: palpation (1.), manometry (2.) and tonometry (3.). Indentation (3.1.), applanation (3.2.), rebound (3.3.) and contour matching (3.4.) are the four physical principles of tonometers that are applicable in clinical practice today (Table 1). TABLE 1. INTRAOCULAR PRESSURE MEASUREMENT 1. Transpalpebral IOP Measurement 1.1. Digital palpation, Figure TGDc-01 and IGD (2003), Figures 3 a,b 1.3. Phosphene Tonometer 2. Manometry, Figure 4 3. Tonometry 3.1. Indentation Tonometers Von Graefe (1862), Figure 5 and Figure Coverpage Donders 47,48 (1863), Snellen 238 (1868), Figure 6 Monnik 168 (1868), Dor 49 (1869), Figure 7 Lazerat 147 (1885), Smith 237 (1887), Nicati 188 (1900) Schiøtz 217 (1905), Figure 8 McLean 162 (1914), Many 158 (1919), Brown 24 (1920) Bailliart 13 (1923), Figures 9 a and b, Wendt 257 (1925) Mueller 181 (1930), Giroux (1933) Recording Tonometer by Maurice 161 (1958), Figure 10 Electronic Tonometer by Mueller 180 (1960), Figure 11

6 Kniestedt, C. Tonometry Through The Ages Applanation - Fixed Force Tonometers Maklakoff 156 (1885), Figures Posner 203 (1965) Applanation Fixed Area Tonometers Weber 254 (1867), Figure 12 Fick 69 (1888), Figure 13 Goldmann and Schmidt (1955), Figures 17 a and b Draeger (1966) and Perkins 197 (1965), Figure 18 Noncontact (air puff) Tonometers, Figure 19 Reichert Ocular Response Analyzer 153 (2005), Figures 20 and 21 Dynamic Observing Tonometer 43,63 (1996), Figures 22 a and b Combined Indentation Applanation Tonometers MacKay-Marg 155 (1959) and TonoPen XL, Figure 23 Pneumatic Tonometer 145 (1969), Figure Rebound Tonometer 126 (1997), Figure Dynamic Contour Tonometer 107 (2005), Figures 26-29

7 Kniestedt, C. Tonometry Through The Ages 6 1. TRANSPALPEBRAL IOP MEASUREMENT 1.1. Digital Palpation Palpation is the oldest method of rough IOP evaluation. Johann Zacharias Platner was the first scientist to state that the glaucomatous eye was hard. For the examination, the patient is asked to close the eyes in downward gaze. The redundant skin of the upper eyelid is displaced, and the central meridian of the globe is balloted alternately with the tips of each index finger (Figure 2). By comparing tactile estimations of IOP to formal pressure measurements, the examiner's sense of touch can be calibrated to a limited extent. In 1862 Bowman suggested a classification of tension in nine grades 21 : Tn = normal tension T1? = questionable increased tension T1 T2 T3 -T1? = slightly raised tension = strongly raised tension = maximally raised tension = questionable reduced tension -T1 = slightly reduced tension -T2 = strongly reduced tension -T3 = extremely low tension This classification was meant to be the first trial of a quantitative estimation on pressure differences. Although palpation correlates poorly with Goldmann applanation readings, palpation may have a limited role in screening for marked elevations of IOP 16,68 or in cases when

8 Kniestedt, C. Tonometry Through The Ages 7 external tonometry is not possible, e.g. after penetrating keratoplasty or corneal scarring. 19,213 Palpation of the globe is the simplest, least expensive, and least accurate method of estimating IOP. 16,19 It is useful when other methods are unavailable or subject to gross error. Palpation may be the only feasible technique in patients who are unwilling or unable to undergo other methods of IOP measurement. 68 Palpation is best avoided in eyes with significant trauma or in certain postoperative conditions. 66,146,213 Figure 2. Digital palpation of the globe 1.2. and 1.3. Transpalpebral Tonometers Diaton (TGDc-01 and IGD-02). Efforts have been made to develop transpalpebral tonometers, such as the TGDc-01 and IGD-02 devices (Rajazan State Instrument- Making, Russia). These portable instruments measure the intraocular pressure through the eyelid (Figure 3a). The operation of both instruments is based on determining the acceleration of freely falling rod after its interaction with the elastic eye surface (Figure 3b). 187

9 Kniestedt, C. Tonometry Through The Ages 8 Figure 3a. The TGDc-01 (Diaton ) tonometer 1 = plastic body, 2 = tip, 3 = STOP button, 4 = rod, 5 = Operation button, 6 = display [mmhg], 7 = cap Figure 3b. Transpalpebral ballistic tonometers measure the elastic reaction of the globe caused by a free falling object with a definite weight. 1 = upper eye lid, 2 = tip of the TGDc-01, 3 = flat surface, 4 = cartilage of the upper eye lid Troost et al. demonstrated an increasing underestimation of IOP at elevated pressure levels when compared with Goldmann applanation tonometry. 182,246 Interobserver deviations using TGDc-01 tonometry and intraindividual deviations between TGDc-01 tonometry, Goldmann applanation tonometry, and palpation of IOP were found to be clinically relevant. 247 According to these results TGDc-01 could not be established as a substitute or diagnostic alternative method for Goldmann applanation tonometry. 142,152,211

10 Kniestedt, C. Tonometry Through The Ages 9 But as deviations between TGDc01 and applanation tonometry turned out smaller than between digital palpation of IOP and applanation tonometry, TGDc-01 seems to provide a better choice for tonometry in patients, in whom Goldmann applanation tonometry is not possible. 5,77,167,182,216,218,249 Proview Phosphene Tonometer. The Proview eye-pressure monitor (Bausch & Lomb, Rochester, NY, USA) was developed as a psychophysical test for self tonometry at home. The pencil-shaped instrument is pressed with its probe against the upper eye lid with increasing pressure until visual phenomenons are detected. These phosphenes should appear opposite to where the pressure was applied. As soon as the phosphene is detected, the tonometer should be removed from the eye lid and the measurement can be read on a scale with 2 mmhg intervals. The position of probe application can influence the measurement. Application of the probe to the nasal superior lid gives the most repeatable and accurate results. 94 Anesthetic eye drops are not required. The device is safe for self tonometry, noninvasive, portable and affordable. 185 By not applanating or indentating the cornea, this kind of tonometry may circumvent inaccuracies related to corneal scarring, edema, astigmatism and corneo-scleral rigidity. 92 However, the accuracy of the device has been questioned. Li et al. compared intraocular pressure values obtained by 86 patients using the Proview eye pressure monitor with those measured with the Goldmann applanation tonometer and with the TonoPen. The IOP s obtained with the Proview eye pressure monitor were significantly lower than those measured with both, the applanation tonometer and the TonoPen. Variations of the central corneal thickness did not contribute to the difference. 149 In another study, the sensitivity for detecting high IOP was low in a

11 Kniestedt, C. Tonometry Through The Ages 10 cohort of 137 patients and the agreement with Goldmann applanation tonometry was poor for some individuals. The Proview instrument gave quite reproducible results, but Alavarez et al. question the underlying assumption that a force proportional to the IOP generates phosphenes. 4

12 Kniestedt, C. Tonometry Through The Ages MANOMETRY Manometry is an invasive technique which precisely measures the pressure inside the eye. It is the reference pressure by which all other tonometers should be judged. The IOP is higher than the atmospheric pressure; therefore, if a small hollow needle is inserted into the anterior chamber, aqueous humor flows out through the needle. If the needle is attached to a reservoir of fluid that is raised just high enough to prevent any loss of aqueous, the height of the column of fluid, usually calibrated in centimeters of water or millimeters of mercury, reflects the IOP. Movement of the fluid column caused by changes in IOP can be detected by an electronic strain gauge. Manometry is most used as a laboratory technique in performing continuous pressure measurements over time, evaluating the effect of physiologic and pharmacologic manipulations on pressure, and studying aqueous humor dynamics in postmortem eyes. 62 Most widely used tonometers, such as Goldmann s applanation tonometry, Schiøtz indentation tonometry, Langham s pneumatonometry and Kanngiesser s dynamic contour tonometry have been calibrated and validated on human cadaver eyes against a manometric reference pressure (Figure 4). 84,86,122,123,145 Goldmann, for instance, experienced that with an applanation diameter of 4 millimeters capillary forces and rigidity forces most closely counterbalanced each other, assuming that normal corneal thickness was around 0.5 millimeters. 86 However, due to practicability reasons, a diameter of 3.06 millimeters was chosen in order that 1 gram of applanation force corresponds to 10 mmhg IOP. 177 Maurice realized that, when the eye was cannulated in

13 Kniestedt, C. Tonometry Through The Ages 12 the anterior chamber, there was a considerable difference between open and closed stopcock readings, but that this difference was almost negligible when the eye was cannulated in the vitreous body. Only results from eyes with cannulation in the anterior and in the posterior chamber and using both open and closed stopcock systems were accepted for the calibration of Maurice s recording tonometer. 161 Infusion bottle Operation microscope Pressure container h = p/mmhg * 1.316cm Laser Compensation container Catheter Threeway cock 2 Threeway cock 1 Reference sensor Figure 4. Manometry setting. The eye is cannulated and the IOP is measured with a reference pressure sensor. One can choose an open or closed bottle system for manometry. An open bottle system maintains a constant pressure during the entire set of consecutive IOP measurements taken on a given globe. With this set-up, the application of the tonometer tip does not result in an artificial pressure change and several measurements may be done without altering the IOP. In contrast, in a closed system such as a real living eye, any tonometer

14 Kniestedt, C. Tonometry Through The Ages 13 based on applanation or indentation will cause an immediate pressure rise corresponding to basic IOP plus an incremental pressure due to fluid displacement. Comparing applanation based tonometers with a contour matched tonometer, that hypothetically does not cause an artificial IOP elevation, should be done using an open tubing system to keep the IOP at a stable level. However, fluid displacement is in part dependent on how the globe is suspended. In the orbit, padded with soft tissue, forces acting on the globe are perfectly distributed. This situation cannot be modeled satisfactorily in an experimental setup with cadaver eyes. 122 Furthermore, practical experimental problems preclude use of a truly closed bottle system. Due to continuous leakage from cut vessels, manometric pressure in a closed system declines continuously, rendering a valid comparison of consecutive measurements difficult. 61,145,178 The ethical use of manometry in living human eyes is restricted to eyes undergoing enucleation or intraocular surgery. 20 This places constraints on the length of time manometry may be performed. It is always difficult to compare static tonometry with continuous tonometry or manometry due to missing definitions at what point of the pulse curve the static pressure should be compared to.

15 Kniestedt, C. Tonometry Through The Ages TONOMETRY Tonometers are the instruments for performing tonometry. Their purpose is to obtain an accurate measurement of the IOP with the least disturbance to the eye. There is a balanced production of aqueous into the globe and drainage of excess via the corneoscleral meshwork and the uveoscleral pathway. 104 The pressure that is a result of this homoeostasis, is equally transmitted to all points and in all directions (Principle of Blaise Pascal, ). So far, the cornea is the only structure of the eye that is accessible to external tonometry. Each technique has its advantages and disadvantages, and none is ideal. Indirect force tonometers work on the basis of indentation and applanation or a combination of each. Contour matching tonometry operates with an external piezo-electric pressure sensor and measures, in contrast to indentation and applanation, the pressure and not a force. 107 Over the ages, scientists had to deal with drawbacks in the development of an accurate external tonometer, such as the impossibility of measuring the IOP in an undisturbed globe or the displacement of fluid from the anterior chamber during the measurement procedure. 74 Until recently, the variable nature and flexibility of the sclera and the cornea were underestimated especially with the use of force tonometers. 50 Some general principles apply to any method of tonometry. Extraneous factors that influence the pressure reading must be avoided. 226 The fingers of the examiner can press on the eyelid or eye while holding the lids apart, artificially raising the IOP. Squeezing of the eyelids, eye movements, 34,131,255 accommodation, 8,17,160 a tight collar or necktie (increased venous pressure), 14,35,36,161,192,200 and repetitive measurements 133,179,241,261 can all falsely increase or decrease the IOP reading.

16 Kniestedt, C. Tonometry Through The Ages Indentation Tonometers The basic principle behind indentation tonometry is simple: a known force will indent a fluid or gas filled object to a greater degree if the internal pressure is low, compared with when the internal pressure is high. The force can be supplied by digital pressure or a known weight. In 1862 von Graefe was the first to describe an indentation tonometer for testing the eye pressure of a seated patient and reading it off a scale (Figure 5). Figure 5. Drawing of the construction of the first (transpalpebral) impression tonometer by A. von Graefe (1862) It is not known whether this instrument was ever demonstrated in public. A description of von Graefe s tonometer, given by J.A. Monnik in his thesis, makes this possible. 168 In the following years enormous efforts were undertaken at the Utrecht University by Monnik, Donders (1863), Snellen (1868, Figure 6) and Dor (1869, Figure 7) to develop impression tonometers that can be used on living human eyes.

17 Kniestedt, C. Tonometry Through The Ages 16 Figure 6. Tonometer by Snellen (1868) Figure 7. Tonometer by Dor (1869) All these tonometers comprised a cylinder with moving rods inside the hollow attached to a short straight steel spring on the side furthest from the cornea. 48,49,238 When the rod moved back into the cylinder during measurement, this spring moved away and at the same time its tension increased rapidly. The bending of the spring was shown enlarged on a scale, in grams, by means of a clock-type mechanism and/or a pointer needle.

18 Kniestedt, C. Tonometry Through The Ages 17 Schiøtz Tonometer. Hjalmar Schiøtz, the first director of the Eye Department at the Rijks Hospital in Oslo, developed a similar tonometer in 1905 (Figure 8). 217 His refined tonometer became the most widely used in the world and largely replaced the Maklakoff applanation tonometer. Figure 8. Schiøtz indentation tonometer (1905). A = Case, B = Scale, C = Concave foot with central plunger Because of its simplicity, reliability, and relative accuracy, it is the only mechanical indentation tonometer in widespread use today. 6 In the Schiøtz tonometer, which is used in supine position, gravity provides a known force on a weighted metal plunger. The plunger rides inside a metal cylinder attached to a footplate curved to match the average human corneal curvature. The top of the plunger rides along a curved lever that attaches to a pointer, which in turn rides along a scale. For

19 Kniestedt, C. Tonometry Through The Ages 18 each 0.05 mm that the plunger sinks below the level of the footplate, the pointer moves up 1 scale unit. Thus, the lower the IOP, the farther into the cornea the plunger sinks and the higher the scale reading. Scale readings can be converted to millimeters of mercury by conversion tables, based on the amount of weight placed on the plunger. Before each measurement, the tonometer is placed on a solid steel block, which should result in no plunger depression and a scale reading of zero. The scale measuring the amount of indentation is linear. The relation between the amount of indentation and intraocular pressure is not linear but logarithmic, so that the higher IOP values are compressed toward the lower end of the scale. 75 Below the scale reading of 3, it is not possible to get an accurate pressure reading other than to know that the pressure is elevated above the normal range. Therefore, additional weights of 2, 4.5, and 9.5 g, respectively, may be added to the plunger to give effective plunger weights of 7.5, 10, and 15 g, respectively. The heavier weights cause the plunger to sink deeper for a given intraocular pressure and to give a higher scale reading. In effect, the heavier weights expand the lower end of the scale. Original calibration was done by comparison with manometry in artificial and cadaver eyes. A comprehensive treatize on indentation tonometry was published by Römer in 1918 who worked on a promising prototype tonometer that never went into full-scale production. 214 Conversion tables to obtain P o (resting IOP) from P t (pressure with the tonometer on the eye) were developed from studies done on cadaver eyes by Friedenwald and confirmed by McBain. 75,164 The scale reading of the tonometer with each plunger

20 Kniestedt, C. Tonometry Through The Ages 19 weight was recorded. The volume of aqueous humor displaced by the weight of the tonometer was also measured. These observations were recorded and plotted on a logarithmic scale to yield the Friedenwald nomogram (Table 2)

21 Kniestedt, C. Tonometry Through The Ages 20 Table 2. Schiøtz Scale Readings - The Friedenwald Nomogram 74 Plunger Load Scale Reading 5.5g 7.5g 10g 15g According to Hook s Law, Schiøtz assumed constant ocular rigidity and he introduced elasticity constants to adequately correct the indentation reading. Friedenwald's tables for conversion of Schiøtz scale readings to IOP are calculated based on an average scleral rigidity. 163 In myopic eyes, scleral rigidity is lower than average, and the Schiøtz plunger sinks deeper into the cornea, compared with an eye with average scleral rigidity at the same IOP. The scale reading will be higher and the IOP will be underestimated. A

22 Kniestedt, C. Tonometry Through The Ages 21 diagnosis of glaucoma may be missed. Conversely, hyperopes and patients with scarred corneas have higher scleral rigidity, resulting in overestimation of their IOP.163 Bailliart Tonometer. In 1923 Bailliart proposed a completely novel type of indentation tonometer construction (Figure 9a). The instrument could be used both, on the sitting and lying patient. Bailliart did not use weights, but a spiral spring (Figure 9b). In this way the generally troublesome changing of weights was eliminated. Bailliart measured the tension of the spiral spring for known depths of impression. The hollow cylinder carried an exchangeable tip with a radius of 12 mm for corneal measurements and a radius of 14 mm for measurements on the sclera. Bailliart stated that measurements on the cornea lead to more accurate results than using the tonometer on the sclera. Bailliart described the limits of normal intraocular pressure between 18 and 20 mmhg. He considered ocular hypertension to start with certainty at 35 mmhg and he warned against establishing the diagnosis of glaucoma on solely tonometric results.13 Figure 9a. Tonometer by Bailliart (1923)

23 Kniestedt, C. Tonometry Through The Ages 22 Figure 9b. Cross section of Bailliart s Tonometer Maurice electrical tonometer. In 1958 Maurice described an electrical recording tonometer that measures the force that is necessary to indent the plunger 0.5 mm into the cornea. It is fixed to a patient s headband and is connected with an adjustable fixation mark for presentation to the other eye. The plunger is pressed against the cornea by a spring-loaded force of 10 gram and indents the cornea to a predetermined depth of 0.5 mm. The 10 gram force is split up into that required to give the plunger its indentation (0 to 8 gram according to the IOP) and the remainder (10 to 2 gram) that is supported by a conical foot, which, near its rim, rests on the cornea. The design of the instrument is shown in Figure 10. One end of the plunger indents the cornea, and the other bears against the pressure-sensitive element, which is connected to an amplifier and to any registration instrument. By a series of measurements on a number of healthy eyes, Maurice described a normal intraocular pressure of 19 mmhg. However, due to its complicated use and calibration for every single measurement, the device was not suitable for widespread use as a routine clinical instrument rather than a research tool.

24 Kniestedt, C. Tonometry Through The Ages 23 Figure 10. Electrical tonometer by Maurice (1958) Mueller s Electronic tonometer. In 1960 Mueller presented a tonometer with an electronic amplifier and a recorder in order to avoid mechanical errors (Figure 11). The tonometer head contained a double-coil inductor working on alternating current (A.C.) and a footplate with a plunger that was similar to the hardware of the Schiøtz tonometer. During the measurement the movable plunger provided a deflection from the equilibrium state that was registered and electronically amplified and altered to direct current (D.C.). The sensitivity of electronic indentation tonometers was described to be greater than comparable instruments with mechanical deflection. However, a new source of error was the calibration of the ampere-meter that needed to be done before each measurement and took up to 30 minutes. The introduction of these electronical tonometers enabled continuous IOP measurement, which was a milestone in the development of tonography.

25 Kniestedt, C. Tonometry Through The Ages 24 Figure 11. Mueller s recording tonometer (1969) 3.2. Applanation Tonometers Weber was not convinced of impression tonometry. He wrote to Snellen: With indentation you are measuring a tension which you have produced, but not one which was present beforehand. He suggested to flatten a small area of the cornea: It is possible to produce an instrument which will produce such a flattening, and show it at that moment when it has enlarged to such an extent that it is the base of the commencement of the sector of a sphere, and which will simultaneously register the necessary force. Only then will the task of measuring the hydrostatsic relationship of the globe on its own, be solved. In this way, Weber was the first to formulate the principle of applanation and in 1867 he presented the first tonometer that respected this novel physical principle (Figure 12). However, Weber stated that the size of the flattened area

26 Kniestedt, C. Tonometry Through The Ages 25 does not play an important role in the measurement. He accidentally chose a plunger with a diameter of 2 mm. Figure 12. Applanation tonometer by Weber (1867) Imbert and Fick continued to work on this hypothesis. They stated that the pressure inside a flexible sphere with thin walls can be closely approximated by knowing the force necessary to just flatten (applanate) a given area of the sphere. These parameters are related by the formula, pressure = force divided by the applanated area. 69,102 One can either measure the force necessary to flatten a fixed area (fixed area tonometers) or measure the area flattened by a fixed force (fixed force tonometers). Both methods have

27 Kniestedt, C. Tonometry Through The Ages 26 been used in designing tonometers. 57 Fick himself developed a simple mechanical tonometer based on his theoretical considerations (Figure 13). He presented a springloaded device which pushed a small metal plate against the cornea, and found it to be accurate in pig and sheep eyes. This early tonometer was never used on human eyes and was soon displaced by the Maklakoff tonometer that also came out in the late 19 th century. However, the Imbert-Fick law remains the physical basis of any kind of applanation tonometry. Figure 13. Fick s handheld tonometer (1888) Fixed-Force Tonometers The Maklakoff (Maklakov) Tonometer. Direct application of tonometers to the eye only became possible following introduction of topical anaesthetics in the form of cocaine drops. Graefes student, Alexei Maklakoff, was helped by the availability of

28 Kniestedt, C. Tonometry Through The Ages 27 localized anaesthesia. At the Moskow Eye Hospital, he developed the first practical applanation tonometer in 1885 (Figure 14). 136,156 Maklakoff stated that tonometry could be performed by applying a constant force to the eye and determining the volumetric displacement of the fluid produced by that force. He assumed that tonometry does only determine pressure changes in an individual eye and does not measure the absolute IOP of an individual eye. 156 Figure 14. First tonometer by Maklakoff (1885) In 1892 he revised his tonometer and presented an instrument with a metal cylinder of known weight with a flat bottom (Figures 15a and 15b). A dye was smeared on the cornea and with the patient in supine position, the cylinder was allowed to rest on the cornea. The applanated area transferred the dye to the tonometer, and the area of applanation could be calculated from the diameter of the circle of dye on the tonometer

29 Kniestedt, C. Tonometry Through The Ages 28 bottom (Figure 16). The pressure could be derived from the Imbert-Fick formula because the applanating force, i.e. the weight of the tonometer, was known. Figure 15a. The Maklakoff applanation Figure 15b. A metal cylinder of 10g tonometer from 1892 hanging in the handle applanated the central area of the cornea Figure 16. Applanation circles and ladder gauge for the Maklakoff tonometer Maklakoff was aware that his instrument was not yet perfect, but he was convinced that it was based on a correct principle. However, the Maklakoff tonometer had several disadvantages. The effect of the capillary forces of the tear film and the rigidity forces of the distorted cornea were neglected. Furthermore, the relatively large applanation area and the heavy weight of the tonometer itself raised the IOP above its resting state to a

30 Kniestedt, C. Tonometry Through The Ages 29 higher level during measurement. Also, the slightest movement of both the eye and the examiner smeared the ink spot, making it larger than the actual area of flattening. 118,205,207 In a recently published study, a high variation coefficient was found for IOP measurements with a Maklakoff tonometer. IOP was significantly underestimated compared to Goldmann applanation tonometry. 9 The Posner Tonometer (Applanometer). Posner revived this kind of fixed-force tonometry for clinical use in ,204 His version was disposable and plastic, which reduced its weight and the discrepancy between the undisturbed (P 0 ) and applanated IOP (P t ). 204 Ink was smeared on the tonometer footplate. When the tonometer rested briefly on the eye, the ink from the footplate was transferred to the flattened area of the cornea. The area on the footplate that was devoid of ink corresponded to the area of applanation. The footplate was then pressed onto a sheet of paper, and the diameter of the inkless area may be converted to the IOP. The Posner tonometer had the advantage of being inexpensive and disposable. It was developed for home use or whenever cleaning and sterilization of a tonometer was impractical Fixed-Area Tonometers The Goldmann Applanation Tonometer. In 1888, Fick devised a tonometer that maintained a fixed area of applanation (Figure 13). 69 The IOP was determined by measuring an adjustable force necessary to flatten this predetermined area of the corneal surface. Over the years, Fick s fixed-area principle was abandoned, since definite skill was required to obtain valid and reproducible tonometer readings. In 1955, Goldmann published his novel concept of fixed-area applanation tonometry and developed the

31 Kniestedt, C. Tonometry Through The Ages 30 tonometer that became the standard against which all others were judged until today.84,86,87,226 The applanating surface of the Goldmann tonometer has a diameter of 3.06 mm placed in the center of a plastic cylinder of 7 mm total diameter. The plastic cylinder is attached to an arm pushed forward through a spring-loaded knob. The amount of force on the cylinder is precisely controlled and can be read from a scale on the knob. The device is mounted on a slit-lamp biomicroscope (Figures 17a and 17b). Figure 17a. Goldmann applanation Figure 17b. Goldmann applanation tonometry (1955) tonometry (2005) To determine the IOP, topical anesthetic and fluorescein dye are placed in the eye. The dye mixes with the tears and fluoresces a brilliant yellowish green when activated by cobalt blue light. When the corneal surface is flattened by the plastic cylinder, the tear

32 Kniestedt, C. Tonometry Through The Ages 31 layer is squeezed out from the applanated surface, and the tear meniscus is seen through the clear center of the plastic cylinder as a ring of fluorescence. The force knob is adjusted until the applanated area is exactly 3.06 mm in diameter. The Goldmann tonometer uses an ingenious optical method to allow this adjustment to be precise: two prisms are positioned in the plastic cylinder, apex to apex, in such a way that the fluorescent ring of the tear meniscus is seen as two mires, one above and one below. The orientation and power of the prisms are such that the two mires are optically separated by exactly 3.06 mm. The force knob is turned until the inside edges of the end of each split ring just touch. Typically, the pulse pressure causes an oscillation of the mires. The force knob is adjusted until these oscillations are centered about the endpoint. When the endpoint is reached, the applanated area has a diameter of 3.06 mm. During applanation, corneal rigidity pushes back against the tonometer head. This force adds to the measured IOP and causes the IOP to be overestimated. The surface tension of the tears, however, creates a capillary attraction that pulls the tonometer surface toward the cornea, lowering the force required to applanate the cornea and causing the intraocular pressure to be underestimated. With an applanation diameter of exactly 3.06 mm and an assumed normal central corneal thickness of 0.5 millimeters, the forces of corneal rigidity and tear surface tension cancel out and the force of 1/10 th gram on an area of a circle of this diameter is equivalent to the pressure of 1 mmhg. 177 High corneal astigmatism (more than 3 diopters) can introduce significant errors in Goldmann tonometry, unless a modified measurement technique is used. 99 Schmidt

33 Kniestedt, C. Tonometry Through The Ages 32 averaged readings taken with the tonometer head oriented over the flat and steep meridians. 223 However, confirmed by the manometric pressure, a more accurate method involves rotating the tonometer prism to a 43 angle from the major axis of astigmatism, measured in minus cylinder. This position is indicated by a red line on the prism holder. If this is not done, a 2- to 3-mmHg error may be induced. 222 Alternatively, readings taken with the prism oriented horizontally and vertically can be averaged. 99 Goldmann used optical pachymetry in the calibration of the applanation tonometer. He assumed a corneal thickness of 0.5 mm and emphasized that theoretically the corneal thickness would influence the IOP reading. 86 In a major review article on Corneal Thickness and IOP, Doughty described a chronolgical shift in average CCT values as a result of changes in pachymeter use. 50 Over the years, ultrasound pachymetry widely replaced optical pachymetry that measured consistently lower (20-30 µm). The average reported CCT across all included 300 data sets was 534 µm. 50 All the more recent population based studies using ulrasound pachymetry give a range of central corneal thickness from 537 µm to 567 µm in healthy eyes. 7,23,140,186,230,262 The Rotterdam Eye Study described a mean CCT of 537 ± 4 µm, range of 193 µm, and a maximal difference between eyes of 42 µm. This study described an average IOP increase of 0.19 mmhg per 10 µm increase in CCT. 262 Other population based studies demonstrated a change in IOP between 0.32 mmhg and 0.11 mmhg per 10 µm change in CCT. 23,230 In these studies the eyes were classified as normals or ocular hypertensives based on the applanated IOP. A part of these eyes could bias the result and, thus, explain the variation of IOP change per µm change in these population groups due to artificially

34 Kniestedt, C. Tonometry Through The Ages 33 raised IOP measurements because of an increased CCT. 229 A review of the literature including studies comparing GAT values with the manometric reference pressure shows even greater variations ranging from 0.11 mmhg to 0.71 mmhg (with an average of 0.25 mmhg) for every 10 µm of CCT change. 59,60,212,230 A number of large and high powered studies such as the Ocular Hypertension Treatment Study (OHTS) have focused at the distribution of CCT according to diagnosis in ocular hypertensives. 22 OHTS reported a mean CCT of 573 ± 39 µm, and CCT appears to be thicker in patients with ocular hypertension, which may be explained, in part at least, by the fact that some of these eyes are misclassified owing to IOP overestimation. 23,105,230 In a clinical based single center study, Argus described a mean CCT in their ocular hypertension group of 610 ± 33 µm. 7 Subjects with primary open-angle glaucoma showed a slightly thinner CCT than that of control subjects. 38,230 Finally, normal-tension glaucoma is reported to be associated with CCT in the low 500 µm range. 169,230 Although many of these studies are differently designed and consist of variously large study populations, one must consider that individuals with excessively thin or thick corneas may lead to a misleading diagnosis of low-tension glaucoma or ocular hypertension. 60,90,93,105,245,259,260 Except CCT and scleral rigidity, there are other sources of error that may influence the accuracy of Goldmann applanation tonometry. 259 Corneas that are edematous or scarred have an abnormal elasticity, usually leading to underestimation of the true IOP. 122,177,235 Too much fluorescein or variable fluoresceine concentration may produce wider mires and result in an underestimation of the pressure. 88,176,226,244 Finding the endpoint may be

35 Kniestedt, C. Tonometry Through The Ages 34 difficult in a patient with an irregular cornea (which produces irregular mires) or wide pulse pressure. 111,166 Despite these limitations, the Goldmann applanation tonometer is considered to be the gold standard for clinical use. Unfortunately, it cannot be used without a slit lamp, is not portable, and requires the patient to be in a sitting position. Draeger and Perkins have each used the Goldmann principle to design tonometers that are handheld, portable, battery powered, and usable in the supine as well as sitting positions (Figure 18). 52,197 This brought applanation tonometry to screening clinics, the bedside, and the operating room. The Perkins applanation tonometer is still often used and particularly useful in measuring the IOP in young children, elderly and in obese patients, permitting measurements without having to position the child at a slit lamp. Figure 18. Current Perkins handheld applanation tonometer (introduced 1965)

36 Kniestedt, C. Tonometry Through The Ages 35 The spread of infection is possible through any contact tonometry unless the applanating prisms are disinfected against most ocular pathogens before each use. 124,154,183,189,190,224,225,248 Soaking the tonometer head for 5 minutes in 3% hydrogen peroxide, 0.5% sodium hypochlorite or 70% isopropyl alcohol meets the guidelines published by the Centers for Disease Control and Prevention (CDC) 1-3 and the American Academy of Ophthalmology (AAO). 150 However, wiping the tip with a 70% isopropyl alcohol swab is also described to be as effective in virus elimination as disinfectant immersion. 236 Alternatively, disposable tonometer tips or silicone shield over the Goldmann tonometer tip can be used. 12,117,208 Compared to uncovered GAT readings, a trend for overestimation of IOP using silicone shields and underestimation of IOP using disposable tips has been described. 157,194 Noncontact Air Puff Tonometer. The noncontact air puff tonometer works on the same basic principle as the Goldmann tonometer. A puff of air is directed to the cornea. The force of the air stream increases linearly over several milliseconds. The air puff is designed so that it hits the cornea with a known and reproducible area. The air pulse then progressively flattens the cornea and finally produces a slight concavity. The moment of applanation is determined by an optical sensor positioned so that an oblique light is reflected into the sensor only when the cornea is flat and acting as a plane mirror. At that precise moment, the sensor sends an electrical impulse to the air pulse generator, shutting it off. A microcomputer monitors the force of the air puff and records the force being generated at the moment of applanation. 71 The computer calculates the IOP from the

37 Kniestedt, C. Tonometry Through The Ages 36 force and the known area and displays it in digital form. Some patients find the air puff startling and mildly uncomfortable. However, painless measurements can be taken without anesthesia. The most recent models have sophisticated automatic monitoring, alignment, and measurement systems (NT 2000 and NT 4000 by Nidek, Aichi, Japan and AT 555 by Reichert, Depew, NY, USA). 202 This facilitates use in screening programs by non-medical personnel and in children. 65 Since the air puff tonometer does not touch the eye, transmission of infectious agents from eye to eye is unlikely. Most air puff tonometers are table mounted, not very portable, and must be used with the patient in the sitting position. However, there are also handheld models such as the Reichert PT 100 (Reichert, Depew, NY, USA, Figure 19) and the Pulsair EasyEye (Keeler, Windsor, UK) that consists of a base unit and a handset with the controls. The handheld models show similar repeatability and reproducibility compared to the table mounted devices. 32,250 However, all noncontact tonometers are rather expensive and require regular calibration. 10

38 Kniestedt, C. Tonometry Through The Ages 37 Figure 19. Handheld non-contact (air puff) tonometer (e.g. PT 100 by Reichert) A good correlation has been described in most studies comparing non-contact tonometers and Goldmann applanation tonometry. 70,91,100,137,175 Hansen measured the intraocular pressure in the right eye of 113 patients using both the non-contact tonometer and the Goldmann applanation tonometry, and found a mean difference of 0.92 mmhg, with noncontact having a smaller reading than applanation tonometry, using variance analyses to study the difference between the two tests. 91 Hollo et al. suggested that repeated noncontact tonometry had no significant effect on intraocular pressure, and that local anesthesia reduced mean difference of the tonometer readings and its standard deviation significantly. 100 Kretz and D ly studied and found a very good correlation in Goldmann applanation tonometry and noncontact measurements. 137 Similar to Goldmann applanation tonometry, noncontact tonometry seems to be dependent upon corneal thickness. 125 Recep et al. found a positive correlation between corneal thickness and the

39 Kniestedt, C. Tonometry Through The Ages 38 difference in measurements by noncontact and applanation tonometry. The magnitude of correlation was greater in cases with thicker corneas. 210 Applanation and Corneal Hysteresis (Reichert Ocular Response Analyser, ORA). It has long been suspected that corneal biomechanical properties influence the results and outcomes of various ocular measurements and procedures. Until recently, central corneal thickness was the only parameter of corneal biomechanics that was applicable to in-vivo measurements. All attempts failed to correct applanation based pressure values with solely central corneal thickness measurements. 120,121,193,230,242,243,262 Human corneal tissue is a complex visco-elastic structure. Viscous materials are defined by the relationship between deformation and apposition force depending upon time or rate, i.e. the resistance to the force that is applied to the cornea is positively correlated to the velocity at which the force is delivered. Elastic materials on the other hand, have a direct proportional relationship between deformation and force, depending upon the elastic modulus of the stressed material. Such as the non-contact airpuff tonometers, the Reichert Ocular Response Analyzer (ORA, Reichert, Depew, NY, USA, Figure 20) addresses these physical principles by utilizing a rapid air impulse and an electro-optical system to monitor the deformation of the cornea being caused by the air impact. 153 The rapid deformation of the cornea during the air impulse absorb energy that causes a time delay in the occurence of the applanation events (Hysteresis), which is, in other words, the result of viscous damping in the corneal tissue.

40 Kniestedt, C. Tonometry Through The Ages 39 Figure 20. Reichert Ocular Response Analyser, ORA (2005) A precisely-metered collimated-air-pulse causes the cornea to move inwards to applanation and even further into a slight concavity. Milliseconds after applanation, the air pump shuts off and the pressure declines in a smooth fashion. As the pressure decreases, the cornea begins to return to its normal configuration, again passing through an applanated state. The electro-optical applanation detection system monitors the corneal curvature in the central 3.0 mm diameter throughout the 20 ms measurement period. Two independent pressure values are derived from the INWARD and OUTWARD applanation events. Due to the dynamic nature of the air pulse and the viscoelastic properties of the cornea, the viscous corneal damping causes delays in the inward and outward applanation events, resulting in two different pressure values. 239 The average of these two pressure values provides the Goldmann-correlated IOP value (IOP G ). The difference between these two pressure values is described to be Corneal Hysteresis (CH, Figure 21). 153 Corneal Hysteresis is supposed to be a biological metric. CH values between right and left eyes are strongly correlated and do not show diurnal

41 Kniestedt, C. Tonometry Through The Ages 40 variation. 141 The instrument was calibrated based on the regression between IOP G and the corresponding Goldmann applanation tonometer value to provide (linear) calibration coefficients to report IOP and CH in millimeters of mercury. The regression is defined by the slope m and the intercept b. The inverse calculation (IOP G -b)/m is supposed to be the Corneal-Compensated IOP CC that utilizes information of individual corneal elasticity and viscosity. 153 Figure 21. Corneal Hysteresis (CH) Luce and Taylor described that IOP CC is less affected by corneal properties, such as central thickness. In a population of 182 normal eyes CCT was not significantly correlated with IOP CC, but in a significant manner with IOD G. So far, there is no published data available describing the accuracy of IOP CC compared to applanation

42 Kniestedt, C. Tonometry Through The Ages 41 tonometry, contour tonometry or manometry. As with dynamic contour tonometry, a comparison with invasive manometry needs to be done to confirm the tonometers absolute accuracy. However, Congdon et al. already worked with the ORA to investigate the impact of CCT and CH on various indicators of glauomca damage. 37 Both parameters were independently associated with features of glaucoma damage such as enlarged cup-todisc ratio or visual field defects. They conclude that thinner corneas give lower IOP readings misleading the practitioner to a wrong target pressure and withholding the eye from adequate IOP-lowering therapy. Alternatively, thinner and softer corneas might be a risk factor due to an association with the response of the corneoscleral shell to IOPinduced stress. The crucial difference to all other tonometers is, that the ORA instrument measures not only the pressure of the eye but also the deformability of human corneal tissue. The CH measurement may be useful in the identification of corneal diseases such as Keratoconus and Fuchs endothelial dystrophy. It also has potential for identifying refractive surgery candidates who are at higher risk of developing post-lasik ectasia. 92,209 In all these cases accurate tonometry is challenging and a reliable tonometer would be very valuable. However, with the current limited studies we do not know, whether corneal hysteresis corrected IOP is in close agreement with true IOP or not. Dynamic Observing Tonometry (DOT, SmartLens ). The dynamic observing tonometer by Robert is a diagnostic lens with which the practitioner measures the IOP and observes the posterior pole and the chamber angle at the same time ,63,108,109 The curved contact surface of the lens has a radius of 8.5 mm and a diameter of 11 mm. In the

43 Kniestedt, C. Tonometry Through The Ages 42 center of the curvature is a Mylar membrane-covered bore hole that provides a 2.5 mm diameter applanation zone. The cavity behind the membrane is filled with silicon oil with a continuity to a piezo-electric pressure sensor that is located in the housing of the lens (Figure 22 a and b). To avoid temperature drifts, the lens needs to be preheated in the base station before placing on the central cornea. 45,108 The view through the lens corresponds to that of the central 30º of a normal Goldmann three-mirror lens. Figure 22a. Cross-section of SmartLens (1996) 1 = interface controller, 2 = wireless transmitter, 3 = digital converter, 4 = observer tube, 5 = gonioscopic mirror, 6 = contact lens, 7 = rechargeable battery, 8 = antenna, 9 = pressure sensor SmartLens can be used at the slitlamp or in supine position. The investigator measures the intraocular pressure over a period of time and registers the intraocular pulse amplitude (OPA). In a study by Morgan et al., intraocular pressure measurements taken

44 Kniestedt, C. Tonometry Through The Ages 43 with the dynamic observing tonometer had a small positive bias compared with Goldmann applanation tonometry. Figure 22b. Base station with pressure sensing contact lens The pulse amplitude values correlated well with those obtained with a pneumatonometer and the repeatability of intraocular pressure measurements was similar to that found in other commercially available tonometers. 170 Other studies concluded that the dynamic observing tonometer is a reliable device in the hand of a skilled ophthalmologist, but it is difficult to learn and, thus, interobserver reliability can be low. 251 Thanks to the visibility of the optic nerve head vessels, different types of provocation tests were described giving indication to the pulsation of the optic nerve head being in proportion to the real or provocated intraocular pressure (Ophthalmodynanometry). 63 The pulsation of the central retinal artery can be observed by artificial elevation of the IOP by pressing the contact lens onto the eye. Information might be obtained about the pressure in the ophthalmic artery. In the past few years, clinical research with the dynamic observing tonometer was given up, since the manufacturer decided to pursue the

45 Kniestedt, C. Tonometry Through The Ages 44 development of the dynamic contour tonometer (DCT, PASCAL ) instead of the dynamic observing tonometer (DOT, SmartLens ) Combination Applanation-Indentation Tonometry The MacKay-Marg, TonoPen, and pneumatonometer instruments have properties of both applanation and indentation tonometers. The original MacKay-Marg tonometer is no longer manufactured and has been supplanted by a handheld and battery-operated version, the TonoPen XL. MacKay-Marg Tonometer. The MacKay-Marg tonometer uses a microplunger that protrudes a small amount from a flat footplate of a tubular handpiece. The microplunger is connected to a sensitive transducer, which converts plunger displacement into an electrical signal that is recorded on a paper chart, much like an electrocardiogram. 155 The shape of the tracing reflects the stages of applanating the cornea. As the plunger is pressed into the cornea, both intraocular pressure and corneal elasticity push back, as with the Schiøtz tonometer. During this phase of measurement, a rising trace is recorded. When the plunger no longer protrudes from the footplate, the footplate has applanated the cornea. The force of corneal elasticity is taken off the plunger, resulting in a slight drop in the trace. As the plunger and footplate are pressed farther into the cornea, the unit raises IOP by displacing aqueous humor, and a rise in the pressure is again recorded. The true IOP, P o, representing the point of applanation, is the bottom of the trough in the pressure recording.

46 Kniestedt, C. Tonometry Through The Ages 45 In a study by Augsburger, measurements of intraocular pressure using the noncontact tonometer and the MacKay-Marg tonometer were highly correlated, the NCT measures being lower by an average of 6.5 mmhg. 11 The mean values from the MacKay-Marg tonometer may be 1.5 to 3 mmhg higher than those from the Goldmann applanation tonometer on normal corneas. The MacKay-Marg tonometer may be a relatively more accurate tonometer in scarred or edematous corneas because the IOP reading is less independent of corneal rigidity and elasticity. 112,166,240 This has been confirmed manometrically in monkey eyes. 166 TonoPen XL. The TonoPen is a handheld, battery-operated version of the MacKay- Marg tonometer. The tip is covered by a disposable latex cover and applied perpendicularly to gently indent an anesthetized cornea (Figure 23). Each measurement requires several applanations. An acceptable applanation is indicated by an audible click after contact with the cornea. A microprocessor averages several acceptable waveforms and gives a digital readout of IOP on a liquid crystal display, with an estimate of the variability between the component readings. Figure 23. TonoPen XL

47 Kniestedt, C. Tonometry Through The Ages 46 Studies comparing the TonoPen with the manometric pressure or with an applanation tonometer revealed a sufficient correlation between the two methods in a physiologic pressure range. 33,55,95,96,98 Other investigators have confirmed this for the range 10 to 20 mmhg but report that at lower IOP (less than 9 mmhg), the TonoPen tends to give higher readings than the Goldmann applanation tonometer. Conversely, at higher IOPs (more than 21 mmhg) the TonoPen tends to underestimate the Goldmann reading. 72,110,130 Unlike Goldmann applanation or the original McKay-Marg, the TonoPen does not give any indication of the value around which IOP varies due to pulse and respiration. The TonoPen is useful for IOP measurement in a sitting and recumbent position. The results were found to be reproducible in 92% with the Goldmann applanation tonometer. 97 The overall agreement between the measurements of the two instruments was good but a small percentage of large difference (> or = +/-5 mm Hg in 7.4%) may be of concern in a population-based survey. The TonoPen, like the Mackay-Marg tonometer, is especially useful for obtaining IOP from scarred, edematous, irregular, or transplanted corneas. It can measure IOP through a bandage contact lens and with the patient in any position. 159,196 Its portability and ease of use are important advantages in screening situations. Pneumatic Tonometer. First developed by Durham et al. 58 and later refined by Langham et al. 144, the pneumatic tonometer allows a continuous IOP reading. This tonometer displays the intraocular pulse and makes a permanent record on a moving paper chart (Figure 24).

48 Kniestedt, C. Tonometry Through The Ages 47 Figure 24. Pneumatonometer Model 30 Classic, by Reichert, Depew, NY, USA (1969) The pneumatic tonometer uses a silicone membrane with a diameter of 5 mm as the applanating surface. The membrane is fixed to a light plastic tip attached to a plastic piston. The piston rides on a nearly frictionless air bearing and is driven against the eye by a carefully regulated gas flow. As the membrane is pressed against the cornea, the gas pressure in the handpiece increases until both the cornea and membrane are flat. At this point, the pressure in the handpiece equals the IOP and is measured by a transducer. No pressure from the hand holding the probe is transmitted to the eye because the pressure needed to push the tip against the eye is generated by the gas flow, and the piston rides on a frictionless bearing. Although the pneumatic tonometer was designed as an applanation device, it may display some of the properties of an indentation tonometer by deforming the cornea and displacing a significant amount of intraocular fluid. 178

49 Kniestedt, C. Tonometry Through The Ages 48 The tip of the pneumatic tonometer is held against the cornea for at least 5 to 10 seconds. This produces a pulsatile record on the graph paper, reflecting the pulsatile nature of the intraocular pressure. In a study, the pneumatic tonometer has been found to correlate fairly well with Goldmann tonometry in normal eyes. 61,215,258 On average, the intraocular pressure is overestimated by 2 to 4 mmhg with the pneumatic tonometer compared to Goldmann applanation tonometry. It is less accurate than the Mackay-Marg tonometer in diseased corneas. 25,258 There is also a suggestion that it begins to underestimate IOP at high pressure levels. 123 The real-time measurement of IOP can be used to calculate the pulsatile component of blood flow. 143,233 The pulsatile ocular blood flow device (POBF, Paradigm Inc.) is a pneumatonometer based on the physical principle that blood volume in the eye increases with the systolic pulse and decreases during diastole. When the blood volume in the choroidea increases, eye pressure increases as well. The IOP pulse wave is transformed into an ocular volume wave presuming the relationship between eye pressure and eye volume is identical for every eye. 234 The POBF device uses an air flow within the tip that increases its pressure until the cornea is indented. The patient sits at the slit lamp and fixates a red light within the center of the probe. The pulsation of the IOP can be heard, as well as observed on the POBF screen. The device is simple to perform and besides IOP measurement, functional parameters of the vascular and cardial system can be investigated. 232 However, POBF is an indirect measurement of blood flow. IOP is measured with applanation or indentation that is dependent of scleral rigidity. 89,172 The relationship between eye pressure and eye volume might not be uniform in all eyes and

50 Kniestedt, C. Tonometry Through The Ages 49 depends on variable parameters, such as axial length, 103,172 age, 82 gender, 28,29,79,82 systemic or topic medication, 80,81 and choroidal and systemic disorders. 30,31,171,174,219 A second disadvantage is that the true volume of blood entering the eye is not known as the rate of venous outflow is unknown and probabely varies among individual eyes. 134,165, Rebound Tonometer icare. Rebound tonometers are handheld ballistic devices that measure the returnbounce motion of an object impacting the cornea. Obbink introduced in 1931 this principle of tonometry and Dekking et al. developed in 1967 a hammer-like device for research purposes. He used an accelerator sensor and an electric contact method to detect the impact of the probe to the cornea. 46,191 The tonometer never reached widespread clinical use, since it was significantly dependent on corneal biomechanics and the tear film had a marked negative effect on the contact time. 135 The icare rebound tonometer (Tiolat, Helsinki, Finland) was first described in 1997 and validated and successfully used on mice eyes. 39,83,126,253 The hand-held device uses a projectile of stainless steel. One end is covered with a small mushroom-like plastic cap with a radius of 0.9 mm and a weight of 26.5 mg. The metallic end of the probe is held in place in the tonometer by a magnetic field that is activated when the instrument button is pressed and the extension spring is released. 83,128,129 The reading is performed by placing the adjustable rest on the patient s forehead. Once the measurement procedure is started, the probe hits the central cornea and the microprocessor analyses the deceleration of the probe following the impact. Deceleration is less at low than at high IOP s and, consequentely, the higher the

51 Kniestedt, C. Tonometry Through The Ages 50 IOP, the shorter the duration of the impact. No topical anesthetics are used and the probe can be exchanged after every patient (Figure 25). In a study with 46 healthy eyes of university students the rebound tonometer was compared to applanation tonometry.67 The icare overestimated the IOP value by 1.34 mmhg on average when compared with the Goldmann tonometer. icare was also compared to TonoPen XL, non-contact tonometry (Pulsair 3000) and TGDc-01. Measurements performed with the icare and the Tonopen XL were in good agreement with that of the Goldmann tonometer. Intraocular pressure (IOP) values measured with the TGDc-01 were significantly lower and showed more variability.127,249 Figure 25. Rebound Tonometer, icare (1997)

52 Kniestedt, C. Tonometry Through The Ages 51 A positive significant correlation to CCT was found. 26 On thick corneas, icare overestimated IOP even more than Goldmann applanation tonometry and TonoPen. 78,184 As with all applanation tonometers, pachymetry should always be taken into consideration. Intersessional repeatability of IOP taken with the icare is poorer than that of IOP taken with Goldmann applanation tonometry, but is comparable with that of TonoPen or Pulsair In all these studies, patient comfort was higher for icare when compared with the Tonopen or non-contact tonometry. Due to its simple use, the icare tonometer might be a good instrument for non-ophthalmologist or paramedical personel. In that circumstances, the icare tonometer may be helpful as a screening tool when Goldmann applanation tonometry is not applicable or not recommended, as it is able to estimate IOP within a range of +/-3.00 mmhg in more than 80% of the population Contour Tonometer Dynamic Contour Tonometry (DCT, PASCAL ). This kind of tonometry presents a novel technology for non-invasive and direct IOP measurement, and has been proposed to continuously and accurately measure the IOP irrespective of structural characteristics of the cornea and sclera. 107 Kanngiesser et al. experimentally showed that the contour adapted to the ideal cornea sufficiently matches the physiologically relevant range of human corneal shapes. 107,119 An actual dynamic contour tonometer head was designed and built that consists of a cylindrical tip with a surface contour that closely resembles the contour of the cornea

53 Kniestedt, C. Tonometry Through The Ages 52 when the pressure on both sides is equal. The centrally located piezo-resistive pressure sensor has the same surface contour as the surrounding tip (Figure 26). Figure 26. Principle of contour matching tonometry F = Forces F are equal on both sides of the cornea, P = Intraocular pressure, d = diameter of contour matching area, Rc = relaxed corneal radius, Rc = unrelaxed corneal radius The dynamic contour tonometer also allows the simultaneous measurement of the ocular pulse amplitude (OPA). The OPA is an indirect indicator for the choroidal perfusion and reflects the ocular blood flow corresponding to the heart pulse as a function of time. There is evidence that the OPA could play a role in the clinical course of glaucoma. 64,101,199,220,221,228 Perkins was the first to describe that in low-tension glaucoma and in myopia the amplitude of the ocular pulse is surprisingly low. 198 Three years later he published his observations that patients with low-tension glaucoma did not comprise a

54 Kniestedt, C. Tonometry Through The Ages 53 homogeneous population, but contained one group of patients with evidence of reduced choroidal blood flow and another group with pulse amplitudes similar to those found in primary open-angle glaucoma.199 Abnormally low pulse amplitudes were also found in exsudative age-related macular degeneration,173 in occlusive carotid disease,115 in sinus cavernosus fistulae116 and in eyes after trabeculectomy.121,252 A practical implementation of contour matching tonometry has been realized in the PASCAL tonometer (Figure 27a and 27b). PASCAL is a slit lamp mounted device and in its handling similar to the Goldmann applanation tonometer. Installed into the optical axis of the slit lamp, PASCAL provides to the examiner a view of the contact interface between the cornea and the tonometer tip (Figure 28). Figure 27a. Dynamic contour tonometer, Figure 27b. PASCAL PASCAL (2005) attached to slit-lamp

55 Kniestedt, C. Tonometry Through The Ages 54 A transparent pressure-sensing tip with a contoured contact surface applied to the center of the cornea with a constant force of 1 gram by a spring-loaded actuator. The piezoelectric pressure sensor built into the contoured contact surface generates an electric signal which is proportional to the IOP and proportional to an audio signal. The audible feedback indicates proper eye contact. The pressure signal is modulated by the pulsatile ocular blood flow. A good measurement takes about five seconds to achieve and is terminated by abruptly removing the tonometer head from the cornea. The software of the system computes IOP and its modulation caused by cardiac pulsations (OPA) from the digitized pressure-dependent electrical signal and from the baseline signal level corresponding to the atmospheric pressure. These signals are stored and processed by a microprocessor in the main unit of the tonometer. The pressure values are displayed on a LCD screen. Besides the numerical values of the mean IOP and the mean OPA, a quality score Q1 (good measurement) - Q5 (bad measurement) is also computed that is calculated from an evaluation of the number of valid data points, noise level, presence of artifacts, and regularity and shape of the pulsations. Q provides an indicator for trustworthiness of the results and reduces the probability of obtaining erroneous readings due to artifacts, poor data quality or agitation of the patient. However, good patient coorperation is required in order to achieve a reliable five second measurement with scores Q1 - Q3. Not all patients can maintain a steady eye and head position what is needed for the contour match measurement. In these cases, a number of attempts may be required to obtain an acceptable Q value, or it may even be impossible in some patients. There is a likelihood that the inter- and intra-observer variability may be reduced, 113,114 but conclusive studies need to be done in this regard.

56 Kniestedt, C. Tonometry Through The Ages 55 Figure 28. Contour matching area with central pressure sensor The PASCAL IOP is defined as the diastolic IOP. This must be noticed when comparing DCT pressure to Goldmann pressure as an estimate of mire pulsations. The difference between diastolic and systolic pressure is also obtained and displayed as OPA (Figure 29). PASCAL provides an indication for the range of pressure to which the optic nerve head is exposed over time. The pressure curve may be printed on an optional infrared connected printer for documentation purposes. Figure 29. PASCAL Print with Ocular Pulse Amplitude