Symposium: Glaucoma

TONOGRAPHY: PAST, PRESENT, AND FUTURE

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MORTON GRANT, MD BOSTON, MASSACHUSETTS

TONOGRAPHY is among the subjects chosen for this symposium which is designed to honor Paul A: Chandler and Peter C. Kronfeld because it has been a subject i~ which Kronfeld has long been interested, and to which he has repeatedly contributed new and valuable observations. Although Chandler has not personally been inyolved with tonography, he has saId that the combination of gonioscopy and tonography provided him the final proof of the need to distinguish subacute as well as acute angle-closure glaucoma from openangle glaucoma.l He said that this, added to earlier clinical observations, started him in the 1950s on a lecture tour, which almost amounted to a crusade, teaching proper means of diagnosis and managing subacute and acute angle-closure glaucoma.

ject, and is actively working on what may be called the "future" of tonography.2,3 The subject has, of course, involved a great many other people. To obtain a rough estimate of how many, I have made a sampling survey of the literature since 1950, and have found that approximately 1,000 articles have been published giving attention to tonography, and, of those, approximately 300 have been concerned principally with this subject. During the same period, at least six books or monographs have been published specifically on tonography. The "past" of tonography has already been reviewed by Kronfeld in a most scholarly manner in his de Schweinitz lecture of 1951. 4 For the purposes of this symposium, I inspected some of the historic background that he reviewed in that lecture, including some that I had never read before, and it was fascinating. I was most impressed by the length of time it can take to implement a simple basic concept.

Another reason for including discussion of tonography in this symposium is that one of the participants, Carl Kupfer, MD, has made valuable contributions to this subSubmitted for publication Jan 17, 1978. From the Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston. Presented in combination with the National Society for the Prevention of Blindness at the Eighty-second Annual Meeting of the American Academy of Ophthalmology and Otolaryngology, Dallas, Oct 2-6, 1977. Reprint requests to 243 Charles St, Boston, MA 02114.

Among the earliest works from which have come basic concepts of outflow of aqueous humor and associated ocular hydrodynamics are the observations made by Schwalbe more than 100 years ago. Schwalbe traced the outflow of aqueous humor to the episcleral veins by means of dyes .and fine particles. And, nearly as long ago Leber and his co-workers performed

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quantitative perfusion of the aqueous outflow system in excised eyes, measuring the German equivalent of "facility of aqueous outflow," showing that the facility of outflow was less in glaucomatous than in normal excised eyes. Those early experimenters probably wished they had a clinical means to m~asure facility of aqueous outflow, but this was probably not thought of until after development of the Schiotz tonometer. The idea of utilizing the Schiotz tonometer for obtaining information on facility of outflow in patients was clearly expressed by Polak-van Gelder in 1911,5 only six years after the Schiotz tonometer was introduced into widespread clinical use. The record shows that this idea appealed also to Ballantyne. 6 When he presented a paper at the International Congress of Medicine in 1913, he made the following statement, in which he said, in part, "It is well known that, if the application of the tonometer is continued for a number of seconds, there is a gradual fall of the pointer. The most plausible explanation of this is that the pressure has rendered the globe softer by expressing fluid through the normal filtration channels. There is, therefore, reason to hope that this phenomenon may provide us with a way of ascertaining the efficiency of the filtration." Thus, even before some of us were born, the potentiality of utilizing the Schiotz tonometer for obtaining information on the capacity of the aqueous outflow channels was clearly conceived. During a period of nearly 40 years, after the possibility was

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recognized, some investigators observed the fall of the pointer during continued application of the tonometer to the eye, while others applied the tonometer intermittently but repeatedly. However, it appears that those investigators who made observations on the rate at which the tonometer pointer fell utilized the phenomenon only for comparing one eye with another, or for comparing the performance of a given eye under different circumstances, without attempting to translate this into quantitative measures of outflow facility or rate of formation of aqueous humor. Among interesting examples of utilization of the phenomenon for comparative purposes prior to 1950 was a clinical study published by Seidel in 1928,7 in which he determined that when certain people with shallow anterior chambers, but normal intraocular pressure, were placed in a darkened room they had a considerable rise in pressure when their pupils semidilated. Seidel determined in these patients that when the intraocular pressure was elevated, the pointer of the tonometer fell much more slowly than when their pressure was normal. He concluded that in these special people when the pupil was semidilated there must be an obstruction to aqeuous outflow. Strangely, he did not mention closure of the angle by the iris as a possible cause. Kronfeld in 1934, with Bock and Stough,8 confirmed that in glaucomatous eyes in general there was a smaller drop in intraocular pressure than in nonglaucomatous eyes when a Schiotz tonometer with a 15-gm weight was applied for two minutes. In 1944 Kronfeld with

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Haas9 studied patients who developed glaucoma after they had had cataract extraction that was complicated by protracted flattening of the anterior chamber. In such cases they showed that peripheral anterior synechias were present and that the rate of fall of intraocular pressure under the Schiotz tonometer was abnormally slow. They concluded that the synechias were responsible for the obstruction to aqueous outflow, and that this was responsible for the elevation of intraocular pressure. Let us consider now the "present" of tonography, the period from 1950 to today, during which all of the articles and books mentioned in the introductory paragraphs of this discussion have been written. By 1950, circumstances had become particularly propitious for implementing the 40-year-old idea of using the tonometer for measuring facility of outflow, and for using this to calculate steady-state rate of aqueous flow. Everett Kinsey and his colleagues had provided evidence through chemical studies that the aqueous humor was not stagnant, and that there was truly a flow of aqueous humor through the eye. Jonas Friedenwald proposed fundamental concepts for the mechanism of formation of aqueous humor. Karl Ascher and Hans Goldmann actually saw in patients the outflow of aqueous humor in the aqueous veins that Schwalbe, Leber, and others recognized under experimental conditions. Goldmann 1o performed studies on the rate of flow of aqueous humor in patients, utilizing measurements of rate of change of concentration of fluorescein in the blood stream and in the anterior

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chamber, emphasizing how important it was to think about the relationships between intraocular pressure, episcleral venous pressure, rate of formation of aqueous humor, and resistance to aqueous outflow when one wanted to learn about the physiology, pathology, or pharmacology of intraocular pressure. The fluorescein method for estimating rate of flow was important for these pioneering investigational purposes, but it was too difficult for general clinical use. However, in 1950 it served importantly in helping to orient thinking into the quantitative relationships that regulate intraocular pressure. Propitiously for the development of tonography, Friedenwald and Kronfeld, as successive chairmen of the Academy's Committee on Standardization of Tonometers, developed calibration data for the Schiotz tonometer that permitted translating tonometer scale readings not only into units of mm Hg of intraocular pressure, but also units of microliters of volume of indentation, with associated formulas for relating the pressure of the eye to the volume of the eye. Conveniently, but fortuitously, the engineers for an instrument manufacturer devised an electronic counterpart of the mechanical Schiotz tonometer, primarily intended only to provide a larger and more easily readable tonometer scale, but fortunately also permitting easy adaptation to continuous recording of progressive fall of the pointer. With development of formulas to convert the recording into facility of outflow in units of microliters per minute per mm Hg intraocular pressure, and to calculate steadystate flow rate of aqueous humor in units of microliters per minute, the

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term "tonography" was coined, for what has become a standard clinical and investigative procedure. ll - l3 Where Goldmann's fluorometric method provided data on rate of aqueous flow from which facility of outflow could be calculated, taking into account intraocular pressure and episcleral venous pressure, tonography approached the relationships from another direction. It was anticipated that measuring facility of aqueous outflow by tonography, and taking into account intraocular pressure and episcleral venous pressure, would permit calculation of the rate of formation of aqueous humor, without having to resort to the complex and difficult procedures involved in Goldmann's fluorescein studies. As experience has since shown, tonography has proved to be relatively simple to carry out, but it has become quite evident that relationships between inflow and outflow, the pressures in the eye, and the episcleral vessels are much more complex than were known, or imagined, when the first approximations were made in 1950. Kronfeld has contributed repeatedly to our present fund of knowledge concerning both the technical aspects of the procedure and the clinical information that it yields. Kronfeld was one of the quickest to appreciate the quantitative advantages of tonographic analysis over the old comparative methods that were limited to observation of scale readings, and which did not attempt to quantify facility of outflow or rate of formation of aqueous humor. In his characteristically precise way, one of the first things that Kronfeld did with tonography was to evaluate its variability in

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individual eyes. 4.14 From his results he placed important emphasis on the need for multiple measurements under each condition that was being investigated. For instance, in study of the action of a drug, he emphasized the need for multiple measurements with and without the drug, a lesson that we should all remember. Also in making repeated measurements at different times of the day, he noted that the facility of outflow remained more stable than did the intraocular pressure, providing evidence that circadian variations of intraocular pressure are mainly attributable to variations in rate of formation of aqueous humor, an observation with which a number of other investigators have agreed. Kronfeld also provided an example of the way in which a technical advance can improve clinical information, in the course of his observations on glaucoma associated with peripheral anterior synechias from protracted flat anterior chamber after cataract extraction. Joseph Haas and he showed, in 1944, that in this type of glaucoma there was an abnormally slow rate of fall of the pointer of the Schiotz tonometer. When he reinvestigated this condition, however, in 1955 and calculated the facility of outflow, he was able to conclude that the severity of obstruction to aqueous outflow was approximately proportional to the circumferential extent of the peripheral anterior synechias. 15 The influences of acetazolamide, miotics, epinephrine, and corticosteroids on the facility of aqueous outflow and formation of aqueous humor have all been examined by Kronfeld,16-18 and he demonstrated

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a fundamental change in responsiveness of open-angle glaucomatous eyes to certain of these drugs after successful fistulizing operations. 19 He has shown that, whereas preoperatively one characteristically finds that miotics improve facility of outflow and that repeated application of corticosteroids increases obstruction to aqueous outflow, conditions are different when a successful fistulizing operation is accomplished. The better the filtering bleb, the less the miotics or corticosteroids influence aqueous outflow. This evidence suggests that the easier the outflow by way of the surgical fistula, the less the outflow by way of the regular aqueous outflow system.

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diagnosis of glaucoma and has contributed in many ways to our understanding of its pressure aspects of various types. Studies of large numbers of patients over many years, such as those recently reported by Roberts,21 have shown that the tonographic PolC ratio provides a little better indication of the likelihood of optic nerve damage than do isolated measurements of the tension. However, as constantly emphasized by Chandler, once tonometry or tonography has alerted us to the risk of glaucomatous damage of the optic nerve, it is the character of the appearance of the optic discs and the visual fields that become of paramount importance. Similarly when patients are under treatment for glaucoma, as Chandler taught, tonometry and tonography can serve only as warning indicators, and the true criteria of adequacy of treatment are determined by periodic evaluation of the appearance of the optic discs and the visual fields.

Most recently, Kronfeld has looked into the question of how much drinking water influences the facility of aqueous outflow, and he has substantiated that if one combines the data from a large number of patients there is significant decrease in facility of outflow within the hour after drinking a liter of water, but that in individual paThe present realities with regard tients the difference is so small to investigational use of tonography that it is not of practical impor- in study of physiology of the eye tance. 20 and particularly in study of the action of drugs, brings us face to Obviously a great many other face with the realization that there investigators have worked with is even more unknown today than tonography, as indicated by the was guessed at when present-day numbers of articles and books that tonography had its start more than I mentioned in the introductory 25 years ago. We have come to paragraphs, but this symposium realize that both the formation of honoring Kronfeld and Chandler aqueous humor and the aqueous includes their contributions in which outflow system are more complex we are most interested. than was guessed at then. From a variety of studies in the interim The present realities concerning we have come to realize that postonography that we see as a result sible suppression of aqueous formaof the work of all those concerned tion by tonography, and possible is that tonography has undoubtedly alteration of facility of outflow by contributed in various ways to the tonography, are just two of the

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factors that must be better evaluated and taken into account in studies on the physiologic, pharmacologic, and pathologic alterations of the eye in relation to glaucoma. Fundamental studies have shown in recent years that interesting things happen in the aqueous outflow system in response to elevation of intraocular pressure, and make us wish that we could evaluate facility of outflow with a method that would involve less disturbance of the pressure of the eye than does standard tonography. We are increasingly troubled and baffled by such clinical observations as failure of blood to reflux into Schlemm's canal when intraocular pressure is lower than episcleral venous pressure, making us realize that our knowledge of the details of aqueous outflow are still at a primitive stage. In the future of tonography, it appears that we have no immediately promising alternative for noninvasive clinical estimation of facility of aqueous outflow. Numerous modifications of tonography have been tried, including applanation and constant pressure tonography, but none of the modifications have as yet proved clearly superior. It appears that for the immediate future it will be important to try to analyze more thoroughly how to interpret tonographic data, to do as Kupfer, Gaasterland, and their colleagues have been doing 2 •3 and to try to evaluate and take into account factors such as pseudofacility. It will be important at the same time to pursue on a basic level our attempts to understand better the workings of the aqueous outflow system and the mecha-

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nisms involved in aqueous formation, so that they can be taken into account to help in interpretation of tonography. It seems now that one of the most fundamental needs is for an independent method that is noninvasive, accurate, and clinically applicable for measuring the rate of aqueous flow and for comparison with data provided by tonography. This comparison is much needed to help in assessing the validity of current interpretations of tonographic data, and to help in determining what kind of corrections may be needed. This would permit a basic test of present methods of estimating pseudofacility, aqueous flow, and episcleral venous pressure in connection with tonography in patients.

ACKNOWLEDGMENT This paper was supported by National Institutes of Health grant 5R01-EY00002 from the National Eye Institute.

REFERENCES 1. Chandler P A: Progress in the treatment of glaucoma in my lifetime. Surv Ophthalmol 21:412-428. 1977. 2. Kupfer C: Clinical significance of pseudofacility. Am J OphthalmoI75:193-204, 1973. 3. Kupfer C, Gaasterland D, Ross K: Studies of aqueous humor dynamics in man. V. Effects of acetazolamide and isoproterenol in young and old normal volunteers. Invest Ophthalmol 15:349-355, 1976. 4. Kronfeld PC: Tonography (de Schweinitz Memorial Lecture). Arch Ophthalmol 48:393-404, 1952. 5. Polak-van Gelder RES: Untersuchungen mit dem Tonometer von Schiotz. Klin Monatsbl Augenheilkd 49:592-605, 1911.

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6. Ballantyne AJ: Observations with the Schiotz tonometer. Transactions of the International Congress of Medicine, Section 9 (Ophthalmology), 1913, pp 197-211. 7. Seidel E: Zur Methodik der klinischen Glaukomforschung. Albrecht von Graefes Arch Klin Ophthalmol 119:15-21, 1928. 8_ Bock J, Kronfeld PC, Stough JT: Effect on intra-ocular tension of corneal massage with the tonometer of Schiotz. Arch Ophthalmol 11:797-806, 1934. 9. Kronfeld PC, Haas JS: Further study of the glaucoma due to peripheral anterior synechiae following delayed restoration of the anterior chamber after cataract operation. Trans Am Ophthalmol Soc 42:316-326, 1944. 10. Goldmann H: An analysis of primary glaucoma (Doyne Memorial Lecture). Trans Ophthalmol Soc UK 69:455-476, 1949.

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13. Grant WM: Clinical measurements of aqueous outflow. Arch Ophthalmol 46:113131, 1951. 14. Kronfeld PC: Some basic statistics of clinical tonography. Invest Ophthalmol 7: 319-327, 1968. 15. _ _ _. A tonographic study of the glaucoma due to delayed restoration of the anterior chamber after cataract extraction. Am J Ophthalmol 39:147-152, 1955. 16. _ _ _. Effects of acetazolamide on human aqueous dynamics. Arch Ophthalmol 68:442-445, 1962. 17. _ _ _. Dose-effect relationships as an aid in evaluation of ocular hypotensive drugs. Invest Ophthalmol 3:258-265, 1964. 18. _ _ _. Early effects of single and repeated doses of L-epinephrine in man. Am J Ophthalmol 72:1058-1072, 1971. 19. _ _ _. Functional characteristics of surgically produced outflow channels. Trans Am Acad Ophthalmol Otolaryngol 73:177193, 1969.

11. Grant WM: Tonographic method for measuring the facility and rate of aqueous flow in human eyes. Arch Ophthalmol 44: 204-214, 1950.

20. _ _ _. Water drinking and outflow facility. Invest Ophthalmol 14:49-52, 1975.

12. Moses RA, Bruno M: The rate of outflow of fl uid from the eye under increased pressure_ Am J OphthalmoI33:389-397, 1950.

21. Roberts W: Long-term handling of open-angle glaucoma: Tonography and other prognostic aids. Ann Ophthalmol 9:557·586, 1977.

Tonography: past, present, and future.

Symposium: Glaucoma TONOGRAPHY: PAST, PRESENT, AND FUTURE w. MORTON GRANT, MD BOSTON, MASSACHUSETTS TONOGRAPHY is among the subjects chosen for th...
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