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An Analysis of Some Concepts Concerning Chronic Simple Glaucoma
AN ANALYSIS O F SOME C O N C E P T S CONCERNING C H R O N I C SIMPLE GLAUCOMA HANS GOLDMANN,
M.D.
Berne, Switzerland
Whereas clinical research work in glau coma was often touched with speculation and fantasy 50 years ago, today we are disposed to look pragmatically at the problem. While mathematicians rack their brains over the foundations of prob ability calculus and statistics, clinical re search workers often simply accept the results of statistical manipulations with out further analysis and praise them as being the height of objectivity. Yet ques tions such as the following force them selves upon the mind: (1) How far is it justified to make a sharp distinction be tween ocular hypertension and beginning simple glaucoma? (2) Given two so-called glaucoma tests, one with 10% falsepositive and 12% false-negative results, the other with 20% false-positive and 15% false-negative results, is the first really better than the second? Analysis of the first problem only will be my concern in this paper. Glaucoma is the disease in which the intraocular pressure is too high for con tinued maintenance of visual function. The ultimate diagnostic aim in chronic glaucoma must be to determine the upper limit of nondamaging intraocular pres sure—the critical pressure—in every case. We are still far from this goal. However, there is an approach to it which is not so satisfactory but interesting by its implica tions. The probability of a damaging intra ocular pressure is high for a pressure of 32 mm Hg, low for a pressure of 20 mm Hg, but theoretically a probability of damage From the Department of Ophthalmology, Univer sity of Berne, Berne, Switzerland. Reprint requests to Hans Goldmann, M.D., De partment of Ophthalmology, University of Berne, Berne, Switzerland.
exists also for a pressure of 14 mm Hg. It is extremely small but is mathematically expressed as a positive figure. We have a distribution of frequency of intraocular pressure—Statistics 1. If we say that 2% of the population has an intraocular pres sure of between 21 and 25 mm Hg by applanation, it means that if we choose any one individual of the population, then the probability of finding that he has an ocular pressure of between 21 and 25 mm Hg is 1/50. Finding his pressure to have this value does not suggest that the probability of damage is 49/50. Other statistics should refer to the rela tionship between the intraocular pressure and probability of damage to the visual system (Statistics 2). The higher the intra ocular pressure the higher the probability of damage. This we know, but we do not know the characterizing figures as we do for Statistics 1. Only experience has taught us that the mean intraocular pres sures of 25 mm Hg and higher by applan ation are generally not tolerated without damage to the visual field for an indefi nite time. But we do not know if the probability of damage in the course of time is .8, .9 or .95 for a pressure of 25 mm Hg by applanation. Our knowledge of the distribution of frequency of the intraocular pressure being great and our knowledge of the distribution of damage with pressure being slight, other statistical relationships are almost unknown. For example, what is the average increase of a given intra ocular pressure in a given time (Statistics 3)? A certain correlation between this in crease and the actual increase of pressure has not been defined. 1 - 3 Such a correla tion must be slight. This finding has great theoretical and practical importance. For
409
410
AMERICAN JOURNAL OF OPHTHALMOLOGY
practical purposes there exist cases with pressures around 25 mm Hg by applanation that spontaneously exhibit lower mean pressures some years later. Was former treatment involved? Will pressure increase again later? Finally, still other statistics (4) would also be important: the statistics of the probable time from the onset of a given pressure until the appearance of a defined visual field damage. We only know that in cases with pressure values common in simple glaucomas, approximately one to two decades pass on an average before easily detectable scotomas are found. 4 Only because high intraocular pres sures have a greater probability of caus ing visual damage (Statistics 2) than lower ones and because higher values are rarer than lower values (Statistics 1) there is a correlation between rare (high) pres sures of Statistics 1 and frequency of damage (Statistics 2). Therefore, the opin ion is unfounded that low "normative" also means low critical pressure. In a case with high intraocular pressure but with out visual field defect, exists a great (exact data unknown) probability that this pres sure is above the damaging limit for this person (his critical pressure), that is, that it will in time (in which time? Statistics 4) cause a visual field defect. Therefore, only the diagnosis "suspicion of begin ning glaucoma" is justified. The diagno sis "ocular hypertension" as of a state essentially different from beginning glau coma would be justified only under two conditions: (1) If we know that the pre sent high pressure is below the critical pressure of the eye. But at the present moment we have no method by which to determine this. (2) If the patient dies many years later without having devel oped any visual field defect. Even then some doubts remain because of our poor knowledge of Statistics 4. From what we have hitherto said, two procedures are
SEPTEMBER, 1975
possible when we suspect a beginning glaucoma because of increased pressure without any visual field defect. 1. We believe that the probability of damage is high enough in time to justify treatment by means of drugs. 2. We wait and observe without treat ment until the first signs of damage (that is, a scotoma) appear. There is not much to be said about the first point of view. We ourselves endorse it and generally fix the pressure for intro ducing therapy by eyedrops at 25 mm Hg by applanation. (We keep patients with pressure values between 22 and 25 mm Hg applanation under observation.) "Generally" means that there may be co gent reasons influencing the ophthalmol ogist not to adhere to a rigid rule (patient's age, unsatisfactory effect of treatment, working conditions, psychical condition of the patient). But I wish to insist again that 25 mm Hg is an arbitrary value born of my experience as an oph thalmologist. If someone else insists on taking 27 mm Hg as his lower limit for action, nothing can be said against it, except personal experience and feeling. Correctly it should be. staled- As soon as the probability of dar"«gp dnp to a pres sure value is. let us sav. 85% we should begin jreatment even without visual field cJeiecL But it is still unknown if this probability is reached at 24, 26, or 28 mm Hg applanation, and even 85% would have to be fixed by agreement. The second procedure of the ophthal mologist, waiting for scotoma, is legalis tic in principle. As long as a defendant has not been judged it is illegal to call him a criminal. Defendant or suspect is equat ed with ocular hypertension; criminal with beginning glaucoma, that is, high pressure and visual field damage; judged or convicted is equated with appearance of scotoma. Such a juridical point of view, which is not a scientific one but accepted
VOL. 80, NO. 3, PART I
CHRONIC SIMPLE GLAUCOMA
at present by many ophthalmologists, does not solve the problem; it only shifts it. If the scotoma has appeared, treatment by drugs is begun. But now the question arises as to how far the pressure must be lowered to become ocular hypertension or normal, that is, what is the pressure that satisfies the ophthalmologist's demand for sufficient probability not to be damag ing. We have now reached the point where the supporters of the first proce dure were from the beginning. What is gained is a kind of "closed season" that is more or less trying for the patient because he has to remain under observation, and observed by a method which, to be can did, as carried out by many is still not satisfactory, perimetry. But the problem of perimetry is the same for ophthalmolo gists who do not postpone treatment until scotomas appear. I called waiting for scotomas a legalis tic, not a scientific, procedure. It is possi ble to disagree and to say waiting for scotoma is a scientific experiment. The experience of the research worker, the ophthalmologist, will be increased when the scotoma appears. Now he knows that the present pressure is too high. Put this way, it immediately becomes clear that the experiment is scientifically correct but as a form of medical behavior it seems open to doubt. Clearly a time-honored principle has been violated, primum non nocere. Where there is a great probability of doing more harm than good to a patient by any procedure this procedure must be avoided, even if it is a good scientific experiment. In cases of probably damaging pressure (without scotoma), there is no doubt that we diminish the danger of a later damage in such a case by lowering pressure by means of medication. But what if we do not succeed at all or succeed only insuffi ciently? Do we do more harm or more good to such a patient if we now proceed
411
to an operation or if we continue to wait with the best available medical treatment until a scotoma appears? Taking into con sideration that every operation has some risks, that almost every antiglaucomatous intervention is followed by a decrease of visual acuity, at least a transitory one, that many of these interventions accelerate the development of cataract, everyone will understand what we believe is the correct course in these cases: to wait for a small scotoma before proceeding to an opera tion. As can be seen, in principle we are in favor of the first procedure but we have often violated this principle because there are many uncertainties which the distinc tion between ocular hypertension and suspicion of beginning simple glaucoma does not remove. What really exists are pressures with greater or lesser probabili ty of damage. The unsatisfactory state of affairs will diminish but not disappear if we know the actual values of the proba bilities. Our ignorance cries out for knowledge of the critical pressure in every case either with or without scotoma, in cases with high or with low intraocular pressure. No so-called provocative test provides us with this knowledge. To return to Statistics 3, we only know that, until now, results have been unex pected. Unexpected because we believe that obstruction of the trabecular meshwork (or sometimes restriction of the out flow channels of Schlemm's canal) is the basis of increased resistance in simple glaucoma. That is a pathologic mecha nism that makes us expect a gradual in crease of resistance in the course of time. Undoubtedly there exist "secondary glau comas" caused by obstruction of the trabecular meshwork. However, the findings of Holmberg 5 and of Tripathi 6 showed that the passage of aqueous humor through the endothelium of Schlemm's canal is chiefly transcellular
412
AMERICAN JOURNAL OF OPHTHALMOLOGY
and not intercellular. The possibility sug gests itself that certain glaucomas are caused by some change in this mecha nism. It seems understandable that changes of this kind may proceed both in the direction of increased resistance and also in the direction of decreased resist ance from any given level of pressure. This would give just the results shown in Statistics 3. The practical conclusion for us in cases with pressure around 25 mm Hg applanation is to discontinue any medical treatment from time to time for some days to determine how the pressure responds in the untreated eye. In 1955 Gafner and Goldmann 7 pub lished a theory and its electrical model explaining why increased pressure would damage primarily the region of the optic disk, as found in glaucoma, because there are special conditions of the local circula tion (shunts). By fluoroangiophotography, Hayreh 8 showed that such condi tions probably exist. Therefore, we have reasons for admitting that the intraocular pressure damages the papillary tissue in fluencing the circulation of the blood in the papilla. Accordingly we may now change our definition of glaucoma. It is the disease in which the intraocular pres sure is too high for a sufficient circulation of the blood to be maintained in the papilla for the continued survival of its tissue. This definition implies that every drug that changes the circulation in the papilla independently of its influence on the aqueous dynamics also changes Sta tistics 2. Every pressure value will now have a probability of damage different from that before the use of the drug. Such constellations do exist. Heilmann 9 has shown that clonidine diminishes the in traocular pressure but at the same time also the general blood pressure. There fore, relative scotomas in a case of simple glaucoma diminish if the intraocular pressure is lowered by acetazolamide
SEPTEMBER, 1975
(Diamox) but do not diminish if the pres sure is lowered to the same degree by clonidine. Adrenalin 1 to 2% drops can damage the macular region not only in aphakic eyes 10 but also in phakic eyes, 1 1 apparently by disturbing the circulation of this region. These drugs may also in fluence the disk circulation, decreasing the critical pressure of the treated eye. We do not know it and we shall not know enough about it as long as we are unable to determine quantitatively the circula tion of the blood in the disk in every single case or to determine the individual critical pressure. Statistics and probabili ties are not sufficient. SUMMARY
Glaucoma is the disease in which the intraocular pressure is too high for con tinued maintenance of visual function. The upper limit of nondamaging pressure must be determined in each case. Our actual knowledge is restricted to some incomplete statistics correlating intraocu lar pressure to its probability to be dam aging to the optic nerve. Despite their scarcity these correlations allow us to draw conclusions of some theoretical and practical interest. REFERENCES
1. Armaly, M.: The Des Moines population study of glaucoma. Invest. Ophthalmol. 1:618, 1962. 2. : Ocular pressure and visual fields. A ten-year follow-up study. Arch. Ophthalmol. 81:25, 1969. 3. Linner, E., and Str8mberg, U.: The course of untreated ocular hypertension. A tonographic study. Acta Ophthalmol. 42:836, 1964. 4. Leydhecker, W.: Zur Verbreitung des Glauco ma simplex in der scheinbar gesunden, augenSrztlich nicht behandelten Bevolkerung. Doc. Ophthal mol. 13:359, 1959. 5. Holmberg, A. S.: Schlemm's canal and the trabecular meshwork. An electron microscopic study of the normal structure in man and monkey. Doc. Ophthalmol. 14:339, 1965. 6. Tripathi, R. C : Aqueous outflow pathways in normal and glaucomatous eyes. Br. J. Ophthalmol. 56:157, 1972.
VOL. 80, NO. 3, PART I
C H R O N I C SIMPLE GLAUCOMA
7. Gafner, F., and Goldmann, H.: Experimentelle Untersuchungen Uber den Zusammen^ang von Augendrucksteigerung und Gesichtsfeldschadigung. Ophthalmologica 130:357, 1955. 8. Hayreh, S. S.: Optic disc changes in glaucoma. Br. J. Ophthalmol. 65:175, 1972. 9. Heilmann, K.: Augendruck, Blutdruck und
413
Glaukomschaden. Biicherei des Augenarztes. Stutt gart, Enke, 1972, p. 61. 10. Kolker, A. E., and Becker, B.: Epinephrine maculopathy. Arch. Ophthalmol. 79:552, 1964. 11. Goldmann, H.: 1st Adrenalintherapie bei Glaucoma simplex harmlos. Arq. Oftalmol. 18:165, 1966.
M.D.
Berne, Switzerland
Whereas clinical research work in glau coma was often touched with speculation and fantasy 50 years ago, today we are disposed to look pragmatically at the problem. While mathematicians rack their brains over the foundations of prob ability calculus and statistics, clinical re search workers often simply accept the results of statistical manipulations with out further analysis and praise them as being the height of objectivity. Yet ques tions such as the following force them selves upon the mind: (1) How far is it justified to make a sharp distinction be tween ocular hypertension and beginning simple glaucoma? (2) Given two so-called glaucoma tests, one with 10% falsepositive and 12% false-negative results, the other with 20% false-positive and 15% false-negative results, is the first really better than the second? Analysis of the first problem only will be my concern in this paper. Glaucoma is the disease in which the intraocular pressure is too high for con tinued maintenance of visual function. The ultimate diagnostic aim in chronic glaucoma must be to determine the upper limit of nondamaging intraocular pres sure—the critical pressure—in every case. We are still far from this goal. However, there is an approach to it which is not so satisfactory but interesting by its implica tions. The probability of a damaging intra ocular pressure is high for a pressure of 32 mm Hg, low for a pressure of 20 mm Hg, but theoretically a probability of damage From the Department of Ophthalmology, Univer sity of Berne, Berne, Switzerland. Reprint requests to Hans Goldmann, M.D., De partment of Ophthalmology, University of Berne, Berne, Switzerland.
exists also for a pressure of 14 mm Hg. It is extremely small but is mathematically expressed as a positive figure. We have a distribution of frequency of intraocular pressure—Statistics 1. If we say that 2% of the population has an intraocular pres sure of between 21 and 25 mm Hg by applanation, it means that if we choose any one individual of the population, then the probability of finding that he has an ocular pressure of between 21 and 25 mm Hg is 1/50. Finding his pressure to have this value does not suggest that the probability of damage is 49/50. Other statistics should refer to the rela tionship between the intraocular pressure and probability of damage to the visual system (Statistics 2). The higher the intra ocular pressure the higher the probability of damage. This we know, but we do not know the characterizing figures as we do for Statistics 1. Only experience has taught us that the mean intraocular pres sures of 25 mm Hg and higher by applan ation are generally not tolerated without damage to the visual field for an indefi nite time. But we do not know if the probability of damage in the course of time is .8, .9 or .95 for a pressure of 25 mm Hg by applanation. Our knowledge of the distribution of frequency of the intraocular pressure being great and our knowledge of the distribution of damage with pressure being slight, other statistical relationships are almost unknown. For example, what is the average increase of a given intra ocular pressure in a given time (Statistics 3)? A certain correlation between this in crease and the actual increase of pressure has not been defined. 1 - 3 Such a correla tion must be slight. This finding has great theoretical and practical importance. For
409
410
AMERICAN JOURNAL OF OPHTHALMOLOGY
practical purposes there exist cases with pressures around 25 mm Hg by applanation that spontaneously exhibit lower mean pressures some years later. Was former treatment involved? Will pressure increase again later? Finally, still other statistics (4) would also be important: the statistics of the probable time from the onset of a given pressure until the appearance of a defined visual field damage. We only know that in cases with pressure values common in simple glaucomas, approximately one to two decades pass on an average before easily detectable scotomas are found. 4 Only because high intraocular pres sures have a greater probability of caus ing visual damage (Statistics 2) than lower ones and because higher values are rarer than lower values (Statistics 1) there is a correlation between rare (high) pres sures of Statistics 1 and frequency of damage (Statistics 2). Therefore, the opin ion is unfounded that low "normative" also means low critical pressure. In a case with high intraocular pressure but with out visual field defect, exists a great (exact data unknown) probability that this pres sure is above the damaging limit for this person (his critical pressure), that is, that it will in time (in which time? Statistics 4) cause a visual field defect. Therefore, only the diagnosis "suspicion of begin ning glaucoma" is justified. The diagno sis "ocular hypertension" as of a state essentially different from beginning glau coma would be justified only under two conditions: (1) If we know that the pre sent high pressure is below the critical pressure of the eye. But at the present moment we have no method by which to determine this. (2) If the patient dies many years later without having devel oped any visual field defect. Even then some doubts remain because of our poor knowledge of Statistics 4. From what we have hitherto said, two procedures are
SEPTEMBER, 1975
possible when we suspect a beginning glaucoma because of increased pressure without any visual field defect. 1. We believe that the probability of damage is high enough in time to justify treatment by means of drugs. 2. We wait and observe without treat ment until the first signs of damage (that is, a scotoma) appear. There is not much to be said about the first point of view. We ourselves endorse it and generally fix the pressure for intro ducing therapy by eyedrops at 25 mm Hg by applanation. (We keep patients with pressure values between 22 and 25 mm Hg applanation under observation.) "Generally" means that there may be co gent reasons influencing the ophthalmol ogist not to adhere to a rigid rule (patient's age, unsatisfactory effect of treatment, working conditions, psychical condition of the patient). But I wish to insist again that 25 mm Hg is an arbitrary value born of my experience as an oph thalmologist. If someone else insists on taking 27 mm Hg as his lower limit for action, nothing can be said against it, except personal experience and feeling. Correctly it should be. staled- As soon as the probability of dar"«gp dnp to a pres sure value is. let us sav. 85% we should begin jreatment even without visual field cJeiecL But it is still unknown if this probability is reached at 24, 26, or 28 mm Hg applanation, and even 85% would have to be fixed by agreement. The second procedure of the ophthal mologist, waiting for scotoma, is legalis tic in principle. As long as a defendant has not been judged it is illegal to call him a criminal. Defendant or suspect is equat ed with ocular hypertension; criminal with beginning glaucoma, that is, high pressure and visual field damage; judged or convicted is equated with appearance of scotoma. Such a juridical point of view, which is not a scientific one but accepted
VOL. 80, NO. 3, PART I
CHRONIC SIMPLE GLAUCOMA
at present by many ophthalmologists, does not solve the problem; it only shifts it. If the scotoma has appeared, treatment by drugs is begun. But now the question arises as to how far the pressure must be lowered to become ocular hypertension or normal, that is, what is the pressure that satisfies the ophthalmologist's demand for sufficient probability not to be damag ing. We have now reached the point where the supporters of the first proce dure were from the beginning. What is gained is a kind of "closed season" that is more or less trying for the patient because he has to remain under observation, and observed by a method which, to be can did, as carried out by many is still not satisfactory, perimetry. But the problem of perimetry is the same for ophthalmolo gists who do not postpone treatment until scotomas appear. I called waiting for scotomas a legalis tic, not a scientific, procedure. It is possi ble to disagree and to say waiting for scotoma is a scientific experiment. The experience of the research worker, the ophthalmologist, will be increased when the scotoma appears. Now he knows that the present pressure is too high. Put this way, it immediately becomes clear that the experiment is scientifically correct but as a form of medical behavior it seems open to doubt. Clearly a time-honored principle has been violated, primum non nocere. Where there is a great probability of doing more harm than good to a patient by any procedure this procedure must be avoided, even if it is a good scientific experiment. In cases of probably damaging pressure (without scotoma), there is no doubt that we diminish the danger of a later damage in such a case by lowering pressure by means of medication. But what if we do not succeed at all or succeed only insuffi ciently? Do we do more harm or more good to such a patient if we now proceed
411
to an operation or if we continue to wait with the best available medical treatment until a scotoma appears? Taking into con sideration that every operation has some risks, that almost every antiglaucomatous intervention is followed by a decrease of visual acuity, at least a transitory one, that many of these interventions accelerate the development of cataract, everyone will understand what we believe is the correct course in these cases: to wait for a small scotoma before proceeding to an opera tion. As can be seen, in principle we are in favor of the first procedure but we have often violated this principle because there are many uncertainties which the distinc tion between ocular hypertension and suspicion of beginning simple glaucoma does not remove. What really exists are pressures with greater or lesser probabili ty of damage. The unsatisfactory state of affairs will diminish but not disappear if we know the actual values of the proba bilities. Our ignorance cries out for knowledge of the critical pressure in every case either with or without scotoma, in cases with high or with low intraocular pressure. No so-called provocative test provides us with this knowledge. To return to Statistics 3, we only know that, until now, results have been unex pected. Unexpected because we believe that obstruction of the trabecular meshwork (or sometimes restriction of the out flow channels of Schlemm's canal) is the basis of increased resistance in simple glaucoma. That is a pathologic mecha nism that makes us expect a gradual in crease of resistance in the course of time. Undoubtedly there exist "secondary glau comas" caused by obstruction of the trabecular meshwork. However, the findings of Holmberg 5 and of Tripathi 6 showed that the passage of aqueous humor through the endothelium of Schlemm's canal is chiefly transcellular
412
AMERICAN JOURNAL OF OPHTHALMOLOGY
and not intercellular. The possibility sug gests itself that certain glaucomas are caused by some change in this mecha nism. It seems understandable that changes of this kind may proceed both in the direction of increased resistance and also in the direction of decreased resist ance from any given level of pressure. This would give just the results shown in Statistics 3. The practical conclusion for us in cases with pressure around 25 mm Hg applanation is to discontinue any medical treatment from time to time for some days to determine how the pressure responds in the untreated eye. In 1955 Gafner and Goldmann 7 pub lished a theory and its electrical model explaining why increased pressure would damage primarily the region of the optic disk, as found in glaucoma, because there are special conditions of the local circula tion (shunts). By fluoroangiophotography, Hayreh 8 showed that such condi tions probably exist. Therefore, we have reasons for admitting that the intraocular pressure damages the papillary tissue in fluencing the circulation of the blood in the papilla. Accordingly we may now change our definition of glaucoma. It is the disease in which the intraocular pres sure is too high for a sufficient circulation of the blood to be maintained in the papilla for the continued survival of its tissue. This definition implies that every drug that changes the circulation in the papilla independently of its influence on the aqueous dynamics also changes Sta tistics 2. Every pressure value will now have a probability of damage different from that before the use of the drug. Such constellations do exist. Heilmann 9 has shown that clonidine diminishes the in traocular pressure but at the same time also the general blood pressure. There fore, relative scotomas in a case of simple glaucoma diminish if the intraocular pressure is lowered by acetazolamide
SEPTEMBER, 1975
(Diamox) but do not diminish if the pres sure is lowered to the same degree by clonidine. Adrenalin 1 to 2% drops can damage the macular region not only in aphakic eyes 10 but also in phakic eyes, 1 1 apparently by disturbing the circulation of this region. These drugs may also in fluence the disk circulation, decreasing the critical pressure of the treated eye. We do not know it and we shall not know enough about it as long as we are unable to determine quantitatively the circula tion of the blood in the disk in every single case or to determine the individual critical pressure. Statistics and probabili ties are not sufficient. SUMMARY
Glaucoma is the disease in which the intraocular pressure is too high for con tinued maintenance of visual function. The upper limit of nondamaging pressure must be determined in each case. Our actual knowledge is restricted to some incomplete statistics correlating intraocu lar pressure to its probability to be dam aging to the optic nerve. Despite their scarcity these correlations allow us to draw conclusions of some theoretical and practical interest. REFERENCES
1. Armaly, M.: The Des Moines population study of glaucoma. Invest. Ophthalmol. 1:618, 1962. 2. : Ocular pressure and visual fields. A ten-year follow-up study. Arch. Ophthalmol. 81:25, 1969. 3. Linner, E., and Str8mberg, U.: The course of untreated ocular hypertension. A tonographic study. Acta Ophthalmol. 42:836, 1964. 4. Leydhecker, W.: Zur Verbreitung des Glauco ma simplex in der scheinbar gesunden, augenSrztlich nicht behandelten Bevolkerung. Doc. Ophthal mol. 13:359, 1959. 5. Holmberg, A. S.: Schlemm's canal and the trabecular meshwork. An electron microscopic study of the normal structure in man and monkey. Doc. Ophthalmol. 14:339, 1965. 6. Tripathi, R. C : Aqueous outflow pathways in normal and glaucomatous eyes. Br. J. Ophthalmol. 56:157, 1972.
VOL. 80, NO. 3, PART I
C H R O N I C SIMPLE GLAUCOMA
7. Gafner, F., and Goldmann, H.: Experimentelle Untersuchungen Uber den Zusammen^ang von Augendrucksteigerung und Gesichtsfeldschadigung. Ophthalmologica 130:357, 1955. 8. Hayreh, S. S.: Optic disc changes in glaucoma. Br. J. Ophthalmol. 65:175, 1972. 9. Heilmann, K.: Augendruck, Blutdruck und
413
Glaukomschaden. Biicherei des Augenarztes. Stutt gart, Enke, 1972, p. 61. 10. Kolker, A. E., and Becker, B.: Epinephrine maculopathy. Arch. Ophthalmol. 79:552, 1964. 11. Goldmann, H.: 1st Adrenalintherapie bei Glaucoma simplex harmlos. Arq. Oftalmol. 18:165, 1966.