PROGRESSIVE BILATERAL ESSENTIAL IRIS ATROPHY* BY Carl Kupfer, MD Muriel Kaiser-Kupfer, MD (BY INVITATION), AND (BY INVITATION) Toichiro Kuwabara, MD INTRODUCTION
ALTHOUGH PROGRESSIVE BILATERAL ESSENTIAL IRIS ATROPHY IS A RELATIVELY RARE
clinical entity, its clinical course and histopathology have been described."12.3 Despite such reports, the pathogenesis of this condition remains unknown. More recently, there has been increased interest in determining whether the iris atrophy is related to abnormalities of the vascular supply of the iris, as determined by fluorescein angiography.4 The purpose of this report is twofold: To report on the light and electron microscopic examination of iris tissue from an eye with advanced progressive essential iris atrophy, and to present fluorescein angiography before and after the first appearance of atrophic iris patches in the heretofore normal fellow eye. CASE HISTORY
R.P. (NIH #09 163 41), a 24-year-old white male, was referred to the Clinical Branch of the National Eye Institute with the diagnosis of progressive essential iris atrophy, left eye. The family history was completely normal with the respect to any eye abnormalities. The patient's general health was excellent, and extensive physical examination failed to reveal any skeletal or dental abnormalities. The present illness began three years previously when the patient noted a discolored spot on the left iris. This increased rapidly in size and the patient noted mild photophobia and intermittent left monocular diplopia. *From the Clinical Branch (Drs Kupfer and Kaiser-Kupfer) and the Laboratory of Vision Research (Dr Kuwabara), National Eye Institute, National Institutes of Health, Department of Health, Education, and Welfare, Bethesda, Maryland. TR. AM. OPHTH. Soc., vol. LXXIII, 1975
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When seen first in February 1972, the visual acuity of the right eye was 20/20 with a -3.00 + 0.75 x 12, and the entire examination was normal including iris transillumination (Figure 1A). This was performed by holding a hand light with a Finoff head directly against the conjunctiva in the region of the lateral scleral triangle. All positive findings were confined to the left eye. Visual acuity, left eye, was 20/30 with a -3.00 + 0.75 x 90. The conjunctiva was clear. The pupil was elliptical in shape and updrawn toward 11:30 o'clock position (Figure 1B). Some iris strands extended toward the 4:00, 6:00, 8:00 and 10:00 o'clock positions. Temporally, the remains of pigmented epithelium persisted in areas where stromal loss was complete. The pupil reacted briskly to light. Inferiorly, gross peripheral anterior synechae were apparent. On slit lamp examination, the cornea was clear, the anterior chamber deep without aqueous ray or keratic precipitates. The lens was clear. Goldmann applanation tension was 13 mm Hg. On gonioscopy, extensive peripheral anterior synechae were noted with two areas open to ciliary body band between the 12:30 and 2:00 o'clock positions (Figure 2A), and two additional areas inferiorly between the 4:00 and 6:30 o'clock positions (Figure 2B). As mentioned previously, the right eye had open angles with scattered fine iris processes (Figure 3). Ophthalmoscopy was normal. The impression was unilateral progressive essential iris atrophy, left eye. One month later, tonography was performed. The tension, right eye, was 17 mm Hg, with total facility of outflow 0.06 ,ul/min/mm Hg and the tension, left eye, was 21 mm Hg with total facility of outflow 0.13 ,ul/min/ mm Hg. On four subsequent tonography tests, the tension, right eye, was always between 10 and 18 mm Hg with total outflow facility values between 0.06 - 0.14 ,ul/min/mm Hg, the mean value being 0.09 ,ul/min/ mm Hg. Because of the consistently low outflow facility values in the right eye, it was decided to observe that eye for the earliest evidence of develop-
FIGURE 1 (opposite) A: Right eye in March 1972 which appeared normal. B: Left eye in March 1972 demonstrating marked iris atrophy.
FIGURE 2 (overleaf) A: Goniophotograph, left eye, March 1972 demonstrating the superior angle. Noteworthy is the open angle between 12:30 and 2:00 o'clock to the right and the peripheral anterior synechae seen on the left between 10:00 and 12:30 o'clock. B: Goniophotograph, left eye, March 1972 demonstrating the inferior angle. Peripheral anterior synechae are
prominent.
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FIGURE 3
Goniophotograph, right eye, March 1972 demonstrating fine iris processes and normal open angle.
ment of iris atrophy as determined by iris transillumination, and vascular abnormalities as observed by iris fluorescein angiography. From the time that the patient was first seen in February 1972 to February 1974, there was no evidence of iris atrophy in the right eye. In February 1975, iris fluorescein angiography was performed. The vessel pattern appeared normal and there was no evidence of new vessel formation or leakage of dye in either the early (Figure 4A) or late (Figure 4B) phases. In April 1974, definite iris transillumination was noted for the first time at the 4:00 o'clock position near the base of the iris. This was confirmed several times and photographed the following September 1974, at which time a repeat iris fluorescein angiogram was performed. Again the vascular pattern was normal including the area in the region in the lower temporal quadrant in both the early (Figure 4C) and late (Figure 4D) phases. Again no new vessel formation or dye leakage was noted. A review of goniophotographs of the 4:00 o'clock area of the anterior chamber angle indicated that no noticeable changes had taken place in the pattern of fine iris processes from August 1972 (Figure 5A),
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FIGURE 4
Fluorescein angiogram, right eye, February 1974. The pattern in the early (A) and late (B) phase is normal. September 1974 after the development of iris transillumination at 4:00 O'clock near the base of the iris. The early (C) and late (D) phases are still normal.
to September 1974 (Figure 5B), to as recently as February 1975 (Figure 5C). Returning to the left eye, the pattern of iris atrophy changed rapidly so that the peripheral anterior synechae became even more extensive
and the remaining iris, especially below, was more atrophic (Figure 6A). By October 1972 (Figure 6B), some eight months after the patient was first seen, the intraocular pressure in the left eye had become elevated into the thirties, requiring pilocarpine and epinephrine topically to which Diamox had to be added by June 1973. Despite maximal medical therapy, the tension in the left eye rose to the upper thirties and lower forties and there was intermittent corneal edema. An inconstant constriction of the lower nasal field became apparent on Goldmann perimetry. Accordingly, a trabeculectomy was performed on the left eye in July
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FIGURE 7
A: The iris tissue, left eye, has been curled during histological processing. The stroma is thin and its connective tissue is condensed. Many blood vessels are present in the atrophic area. Although their perivascular connective tissue is denser, the vessels are patent. B: Iris tissue, left eye. The epithelial cells are attenuated. The outer epithelial cell shows widened basal infoldings (x20,000).
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FIGURE 8
Iris tissue, left eye, stroma cells contain abundant fragmented pigment granules. Also, numerous histiocytes are present in the stroma (X 10,000).
1973, in which a large portion of iris was obtained from the 12:00 o'clock position. The iris specimen was studied by light and electron microscopy. In general, the iris was markedly thickened with excessive connective tissue surrounding the blood vessels which were patent (Figure 7A). Elsewhere, the stroma was fibrotic and there was increased compactness of the tissue. The epithelial cells were attenuated (Figure 7A) and the outer epithelial cells demonstrated widened basal infoldings (Figure 7B). Many histiocytes were noted and the stromal cells contained fragmented pigment granules (Figure 8). It was apparent that all basement membranes were markedly thickened. The dilator muscle basement membranes were two to three times normal diameter. The muscle fibers themselves were thin and small and no typical structures such as myofibrils were noted (Figures 9A, 9B). The iris stroma contained collagen fibers whose diameters were increased significantly. This thickened connective tissue surrounded the vessels. Finally, there was a general decrease in the number of nerve elements seen in the dilator muscle area (Figure 9A) and even in iris tissue at the edge of the atrophic focus, nerve elements were found infrequently (Figure 10).
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FIGURE 9
A: Markedly pathological iris tissue, left eye. The dilator muscle cells are atrophic and their basement membranes are extremely thick. No nerve elements are present in this area (x 12,000). B: Higher magnification of the atrophic muscle. The muscle elements are
attenuated (x21,000).
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FIGURE 10
Iris tissue, left eye, at the edge of the atrophic focus. The basement membrane of the dilator muscle is thickened but the muscle elements maintain the normal structure (x 10,000). The inset shows nerve elements (arrow) which arefound infrequently (x21,000).
DICUSSION
The two aspects of this case of particular interest are the relationship between the onset of iris atrophy and the integrity of the vascular supply to the iris in the right eye and the histopathology of the iris in the left eye. There appears to be no doubt that early stromal atrophy, as diagnosed by iris transillumination, occurred in the right eye in the absence of any discernable change in either the gonioscopic appearance of the anterior chamber angle or in the vascular pattern seen by iris fluorescein angiography. If there is vascular involvement in the pathogenesis essential iris atrophy as has been suggested,4 it does not appear to be a primary event and, at least over a period of some nine months, rubeosis has not been noted to develop. Of tangential interest is the persistenly low outflow facility in the right eye despite normal intraocular pressure. Since this value was confirmed on five separate occasions, it is necessary to consider the possibility that the glaucoma seen in progressive essential iris atrophy is not entirely explainable on the basis of peripheral anterior synechae but may involve a fundamental abnormality of the outflow
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channels. A review of both unilateral and bilateral cases of progressive essential iris atrophy reported in the literature has failed to reveal any tonographic data performed on eyes in which there was still a normal intraocular pressure. It is conceivable that the outflow channels are abnormal causing reduced outflow facility and that the onset of peripheral anterior synechae tip such eyes over into increased intraocular pressure. Concerning the histopathology of the left eye, there is no evidence for occulsive vascular disease although the vessels are surrounded by a large amount of connective tissue containing collagen fibers. If the basic histopathology were widespread vascular insufficiency with infarcted iris, one would expect to see a thin atrophic tissue rather than a thickened iris. The small muscle fibers have thickened basement membranes which would suggest that at one time, there was an active phase of whatever process was present and as the result ofsuch a chronic insult, the basement membranes increased in diameter. However, with time, the muscle elements themselves become atrophic. Along with the loss of neural elements, one is confronted with an end-stage picture of long-standing chronic disease and hence it is not possible to clarify the pathogenesis of this process from such material. SUMMARY
A case of bilateral progressive essential iris atrophy, more advanced in one eye than the other, has been studied. Histopathologic examination of the iris from the eye with the more advanced iris atrophy failed to find any vascular abnormalities in that the vessels were patent and appeared normal except for accumulated perivascular connective tissue. Fluorescein angiographic examination of the right eye which was undergoing the earliest changes of iris atrophy failed to show any vascular abnormalities. However, tonographic examination indicated a markedly decreased outflow facility. There does not appear to be any vascular abnormality involved in the pathogenesis of this case. REFERENCES 1. Chandler PA, Grant WM: Lectures on Glaucoma, Essential Atrophy of the Iris uith Glaucoma. Philadelphia, Lea & Febiger, 1965, p 278. 2. Duke-Elder S, Perldns ES (eds): System of Ophthalmology. St. Louis, CV Mosby Company, 1966, Vol. 9, p 687. 3. Cross HE, Maumenee AE: Progressive spontaneous dissolution of the iris. Survey Ophthalmol 18:186-199, 1973. 4. Jampol LM, Rosser MJ, Sears M: Unusual aspects of progressive essential iris atrophy. Am J Ophthalmol, 77:353-357, 1974.
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DR A. EDWARD MAUMENEE. Thank you, Mr President. I would like to thank Dr Kupfer and Dr Kaiser-Kupfer for bringing this very interesting case report to our attention. It is most important to establish the basic pathology of various ocular diseases. Since we usually do not have an opportunity to biopsy seeing eyes in the early stages of disease, we are ignorant of the early pathologic changes of many ocular problems. Drs Kupfer and Kaiser-Kupfer have brought to our attention this interesting case of bilateral essential iris atrophy occurring in a male. They have shown us the very interesting fluorescein angiography of the iris in the early lesion in the right eye and they have brought to our attention the observation that the facility of outflow was extremely low, even before there was actual blockage of the angle of the anterior chamber by peripheral anterior synechia. The problem of iris atrophy is a complicated one, primarily because it is extremely rare, and no one really has a large series of patients to study. [Slide] Dr Harold Cross, when he was at the Wilmer Institute, and I tried to put together the various conditions that had iris atrophy, some of which were frequently progressive and some which were rarely progressive. Reiger's syndrome is a condition that has dental abnormalities, changes in the face, umbilical hernia, and iris atrophy. Ordinarily this condition is nonprogressive, but there are progressive cases in the literature; and we have seen some progressive cases at the Wilmer Institute. Iridoschisis is difficult to differentiate from Chandler's syndrome, and I am not certain that these are two separate distinct entities. In most patients with iridoschisis the changes begin at around the age of 40 or older, and in Chandler's syndrome, of course, they have the endothelial changes as well as the progressive iris changes. The essential iris atrophy that we are all familiar with is that type which occurs in females, usually in the fourth, fifth, or sixth decade, is progressive, and uniocular. Essential iris atrophy has reportedly been observed in males and bilaterally. We have seen such cases of bilateral essential iris atrophy occurring in males and have considered the condition to be transmitted in a sexlinked abnormality. Whether they really should be divided into two separate groups is not clear. I don't think that there are enough cases in the literature to say one way or another. Drs Kupfer and Kaiser-Kupfer, I think, are the first to do a histopathologic study on this particular abnormality in males; although I can't say that with certainty since the ages and sex of Dr Parker Heath's original ten cases were not included in his article. The slide on the screen shows a biopsy of the iris taken from a female patient who had unilateral essential atrophy of the iris and secondary glaucoma. A trephine was done five years ago, which has controlled her intraocular pressure. The biopsy specimen, as in Dr Kupfer's case, shows no evidence of occlusive vascular disease in the iris. Dr Richard Green, our pathologist at Wilmer, reviewed five of the cases on file at the Armed Forced Institute of Pathology that Dr Parker Heath included in his report, and in none of these specimens did he find conclusive
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evidence of a vascular-occlusive etiology. He did not have access to Dr Parker Heath's other five cases in which he illustrated changes that looked like they were occlusive vascular diseases. It was of interest to read the discussion of Dr Health's paper by Drs Verhoeff and Friedenwald, both of whom were not fully convinced of the vascular etiology of essential iris atrophy. We have material from four cases on file at the Wilmer Institute, and none of these have shown the occlusive vascular disease; so that I think we can confirm what Dr Kupfer has said - that the cause of this condition is still a mystery. We have not found the occlusive vascular disease as has been suggested by some as the cause of this lesion in the literature. Dr Godfried Naumann, however, has recently observed vascular occlusion histopathologically in a specimen that he has studied. Fluorescein angiography of the anterior segment of the eye may be helpful in determining whether this is primarily a vascular disease or not. I would like to thank the authors again for bringing this most interesting case to our attention.
DR JAMES JERVEY. Mr President. Fellow Members and Guests. I have enjoyed this discussion very much indeed. I wish I had had the good sense to bring some photographs of a similar case I have been following for some 15 years. She is a beautiful young woman who began to have trouble with one eye when she was 30 years old. This one eye has gone along with the typical picture which has been presented on the screen today. I am here to point out that the American Ophthalmological Society was originally formed as a clinical society and very little has been said today about the management of the treatment in these cases. I have had so little experience that I feel some strangeness in being up here trying to say something to you about it. This young lady began to have trouble after about 12 years with elevated pressure which has been controlled very well with epinephrine and pilocarpine drops. She has not had diamox. Her pressure is well within normal limits. The opposite eye is not affected. I chiefly wanted to mention the treatment of the corneal edema which does accompany this condition. The use of 5% sodium chloride ointment is a very satisfactory treatment. DR ROBERT KENNEDY. Mr President. Ladies and Gentlemen. I have certainly enjoyed the Kupfers' paper. As Doctor Jervey points out, the name of the game to the man on the firing line is the clinical solution of this problem. We have very few guide lines because there are so few series reported. I think the overall picture that I get is that the fistulizing procedures seem to be the most successful. There is a reluctance to do very much to the iris. The following case illustrates such a patient operated upon 24 years ago with successful control despite progressive iris changes. A 59-year-old male with records available since age 24 was seen with a normal right eye and esotropia of the left eye with amblyopia and 2/200 vision in 1942. When seen in 1949, the pupil of his good right eye was slightly oval, and small areas of iris atrophy were noted. There was deep cupping and disk atrophy with a pressure of 50 Schi0tz. Essential atrophy of the iris was diagnosed and surgery advised since he was refractory to medical treatment.
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This was refused for 1% years when the man could then be shown the marked deterioration of his visual fields. A trephine operation was performed in January of 1951. The pressure has been 12 or less since surgery and there has been no further loss of field in the past 24 years. Iris atrophy has continued with the pupil becoming displaced to the angle [Slide] so that you see the pupil in the 4:00 to 5:00 o'clock position in the angle. He has marked iris atrophy and an obliterated angle gonioscopically. He was developed a cataract which has brought up the question of management or cataract surgery. A pars plana Roto-Extractor removal has been considered with the hopes of leaving a functional bleb. Any advice would be appreciated. I personally have given up doing corneal transplants. I've given up retinal detachments, and now that I have this man on my hands it might be time to give up doing cataract surgery. One swallow does not make a springtime but a single fistulizing procedure has certainly been effective in pressure control in this patient despite progressive iris atrophy for approximately a quarter of a century. Thank you. DR CARL KUPFER. I want to thank the discussants for their most interesting remarks. In such a rare occasion, it is very gratifying to have Doctor Maumenee be able to identify ten cases examined histopathologically and confirm the fact that, at least in this group of cases, there is no evidence for occlusive vascular disease. Doctor Jervey does bring up an extremely appropriate point: what we are concerned with is not only the diagnosis, but perhaps more important, the treatment. In these rare cases, it is very hard to have collective awareness of what is appropriate, and I think he rightly calls attention to the value of the 5% sodium chloride ointment for control of the corneal edema. We are using that in this young man. Interestingly enough, despite the fact that his pressures are now equalized, he does have intermittent corneal edema which is treated with the ointment as well as the hair dryer. Doctor Kennedy presents a very long-term followup of successful surgery, and I think that this is of particular value because it has been my impression that the younger these people are when surgery is done, the more aggressive one has to be. In this particular instance, we had to do two trabeculectomies plus a partial cyclodiathermy to bring the pressure down to the region of 12-15 mm of mercury, which it is at present. May I make one further comment? One of the roles of the National Eye Institute is to act as a referral center for these extremely rare cases with which we, as individual ophthalmologists, rarely can accumulate a large clinical experience in a lifetime. On the other hand, if these cases are referred to the clinical branch of the National Eye Institute, they can be collected and studied. As you know, this is a facility that does not charge the patient and, therefore, hospitalization is not accompanied by financial problems for the patient. We would welcome very much having patients with this condition, either unilateral or bilateral, referred to us. We would do a careful workup with full report back to the referring ophthalmologist. Thank you very much.
ALTHOUGH PROGRESSIVE BILATERAL ESSENTIAL IRIS ATROPHY IS A RELATIVELY RARE
clinical entity, its clinical course and histopathology have been described."12.3 Despite such reports, the pathogenesis of this condition remains unknown. More recently, there has been increased interest in determining whether the iris atrophy is related to abnormalities of the vascular supply of the iris, as determined by fluorescein angiography.4 The purpose of this report is twofold: To report on the light and electron microscopic examination of iris tissue from an eye with advanced progressive essential iris atrophy, and to present fluorescein angiography before and after the first appearance of atrophic iris patches in the heretofore normal fellow eye. CASE HISTORY
R.P. (NIH #09 163 41), a 24-year-old white male, was referred to the Clinical Branch of the National Eye Institute with the diagnosis of progressive essential iris atrophy, left eye. The family history was completely normal with the respect to any eye abnormalities. The patient's general health was excellent, and extensive physical examination failed to reveal any skeletal or dental abnormalities. The present illness began three years previously when the patient noted a discolored spot on the left iris. This increased rapidly in size and the patient noted mild photophobia and intermittent left monocular diplopia. *From the Clinical Branch (Drs Kupfer and Kaiser-Kupfer) and the Laboratory of Vision Research (Dr Kuwabara), National Eye Institute, National Institutes of Health, Department of Health, Education, and Welfare, Bethesda, Maryland. TR. AM. OPHTH. Soc., vol. LXXIII, 1975
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When seen first in February 1972, the visual acuity of the right eye was 20/20 with a -3.00 + 0.75 x 12, and the entire examination was normal including iris transillumination (Figure 1A). This was performed by holding a hand light with a Finoff head directly against the conjunctiva in the region of the lateral scleral triangle. All positive findings were confined to the left eye. Visual acuity, left eye, was 20/30 with a -3.00 + 0.75 x 90. The conjunctiva was clear. The pupil was elliptical in shape and updrawn toward 11:30 o'clock position (Figure 1B). Some iris strands extended toward the 4:00, 6:00, 8:00 and 10:00 o'clock positions. Temporally, the remains of pigmented epithelium persisted in areas where stromal loss was complete. The pupil reacted briskly to light. Inferiorly, gross peripheral anterior synechae were apparent. On slit lamp examination, the cornea was clear, the anterior chamber deep without aqueous ray or keratic precipitates. The lens was clear. Goldmann applanation tension was 13 mm Hg. On gonioscopy, extensive peripheral anterior synechae were noted with two areas open to ciliary body band between the 12:30 and 2:00 o'clock positions (Figure 2A), and two additional areas inferiorly between the 4:00 and 6:30 o'clock positions (Figure 2B). As mentioned previously, the right eye had open angles with scattered fine iris processes (Figure 3). Ophthalmoscopy was normal. The impression was unilateral progressive essential iris atrophy, left eye. One month later, tonography was performed. The tension, right eye, was 17 mm Hg, with total facility of outflow 0.06 ,ul/min/mm Hg and the tension, left eye, was 21 mm Hg with total facility of outflow 0.13 ,ul/min/ mm Hg. On four subsequent tonography tests, the tension, right eye, was always between 10 and 18 mm Hg with total outflow facility values between 0.06 - 0.14 ,ul/min/mm Hg, the mean value being 0.09 ,ul/min/ mm Hg. Because of the consistently low outflow facility values in the right eye, it was decided to observe that eye for the earliest evidence of develop-
FIGURE 1 (opposite) A: Right eye in March 1972 which appeared normal. B: Left eye in March 1972 demonstrating marked iris atrophy.
FIGURE 2 (overleaf) A: Goniophotograph, left eye, March 1972 demonstrating the superior angle. Noteworthy is the open angle between 12:30 and 2:00 o'clock to the right and the peripheral anterior synechae seen on the left between 10:00 and 12:30 o'clock. B: Goniophotograph, left eye, March 1972 demonstrating the inferior angle. Peripheral anterior synechae are
prominent.
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FIGURE 3
Goniophotograph, right eye, March 1972 demonstrating fine iris processes and normal open angle.
ment of iris atrophy as determined by iris transillumination, and vascular abnormalities as observed by iris fluorescein angiography. From the time that the patient was first seen in February 1972 to February 1974, there was no evidence of iris atrophy in the right eye. In February 1975, iris fluorescein angiography was performed. The vessel pattern appeared normal and there was no evidence of new vessel formation or leakage of dye in either the early (Figure 4A) or late (Figure 4B) phases. In April 1974, definite iris transillumination was noted for the first time at the 4:00 o'clock position near the base of the iris. This was confirmed several times and photographed the following September 1974, at which time a repeat iris fluorescein angiogram was performed. Again the vascular pattern was normal including the area in the region in the lower temporal quadrant in both the early (Figure 4C) and late (Figure 4D) phases. Again no new vessel formation or dye leakage was noted. A review of goniophotographs of the 4:00 o'clock area of the anterior chamber angle indicated that no noticeable changes had taken place in the pattern of fine iris processes from August 1972 (Figure 5A),
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FIGURE 4
Fluorescein angiogram, right eye, February 1974. The pattern in the early (A) and late (B) phase is normal. September 1974 after the development of iris transillumination at 4:00 O'clock near the base of the iris. The early (C) and late (D) phases are still normal.
to September 1974 (Figure 5B), to as recently as February 1975 (Figure 5C). Returning to the left eye, the pattern of iris atrophy changed rapidly so that the peripheral anterior synechae became even more extensive
and the remaining iris, especially below, was more atrophic (Figure 6A). By October 1972 (Figure 6B), some eight months after the patient was first seen, the intraocular pressure in the left eye had become elevated into the thirties, requiring pilocarpine and epinephrine topically to which Diamox had to be added by June 1973. Despite maximal medical therapy, the tension in the left eye rose to the upper thirties and lower forties and there was intermittent corneal edema. An inconstant constriction of the lower nasal field became apparent on Goldmann perimetry. Accordingly, a trabeculectomy was performed on the left eye in July
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FIGURE 7
A: The iris tissue, left eye, has been curled during histological processing. The stroma is thin and its connective tissue is condensed. Many blood vessels are present in the atrophic area. Although their perivascular connective tissue is denser, the vessels are patent. B: Iris tissue, left eye. The epithelial cells are attenuated. The outer epithelial cell shows widened basal infoldings (x20,000).
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FIGURE 8
Iris tissue, left eye, stroma cells contain abundant fragmented pigment granules. Also, numerous histiocytes are present in the stroma (X 10,000).
1973, in which a large portion of iris was obtained from the 12:00 o'clock position. The iris specimen was studied by light and electron microscopy. In general, the iris was markedly thickened with excessive connective tissue surrounding the blood vessels which were patent (Figure 7A). Elsewhere, the stroma was fibrotic and there was increased compactness of the tissue. The epithelial cells were attenuated (Figure 7A) and the outer epithelial cells demonstrated widened basal infoldings (Figure 7B). Many histiocytes were noted and the stromal cells contained fragmented pigment granules (Figure 8). It was apparent that all basement membranes were markedly thickened. The dilator muscle basement membranes were two to three times normal diameter. The muscle fibers themselves were thin and small and no typical structures such as myofibrils were noted (Figures 9A, 9B). The iris stroma contained collagen fibers whose diameters were increased significantly. This thickened connective tissue surrounded the vessels. Finally, there was a general decrease in the number of nerve elements seen in the dilator muscle area (Figure 9A) and even in iris tissue at the edge of the atrophic focus, nerve elements were found infrequently (Figure 10).
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FIGURE 9
A: Markedly pathological iris tissue, left eye. The dilator muscle cells are atrophic and their basement membranes are extremely thick. No nerve elements are present in this area (x 12,000). B: Higher magnification of the atrophic muscle. The muscle elements are
attenuated (x21,000).
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FIGURE 10
Iris tissue, left eye, at the edge of the atrophic focus. The basement membrane of the dilator muscle is thickened but the muscle elements maintain the normal structure (x 10,000). The inset shows nerve elements (arrow) which arefound infrequently (x21,000).
DICUSSION
The two aspects of this case of particular interest are the relationship between the onset of iris atrophy and the integrity of the vascular supply to the iris in the right eye and the histopathology of the iris in the left eye. There appears to be no doubt that early stromal atrophy, as diagnosed by iris transillumination, occurred in the right eye in the absence of any discernable change in either the gonioscopic appearance of the anterior chamber angle or in the vascular pattern seen by iris fluorescein angiography. If there is vascular involvement in the pathogenesis essential iris atrophy as has been suggested,4 it does not appear to be a primary event and, at least over a period of some nine months, rubeosis has not been noted to develop. Of tangential interest is the persistenly low outflow facility in the right eye despite normal intraocular pressure. Since this value was confirmed on five separate occasions, it is necessary to consider the possibility that the glaucoma seen in progressive essential iris atrophy is not entirely explainable on the basis of peripheral anterior synechae but may involve a fundamental abnormality of the outflow
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channels. A review of both unilateral and bilateral cases of progressive essential iris atrophy reported in the literature has failed to reveal any tonographic data performed on eyes in which there was still a normal intraocular pressure. It is conceivable that the outflow channels are abnormal causing reduced outflow facility and that the onset of peripheral anterior synechae tip such eyes over into increased intraocular pressure. Concerning the histopathology of the left eye, there is no evidence for occulsive vascular disease although the vessels are surrounded by a large amount of connective tissue containing collagen fibers. If the basic histopathology were widespread vascular insufficiency with infarcted iris, one would expect to see a thin atrophic tissue rather than a thickened iris. The small muscle fibers have thickened basement membranes which would suggest that at one time, there was an active phase of whatever process was present and as the result ofsuch a chronic insult, the basement membranes increased in diameter. However, with time, the muscle elements themselves become atrophic. Along with the loss of neural elements, one is confronted with an end-stage picture of long-standing chronic disease and hence it is not possible to clarify the pathogenesis of this process from such material. SUMMARY
A case of bilateral progressive essential iris atrophy, more advanced in one eye than the other, has been studied. Histopathologic examination of the iris from the eye with the more advanced iris atrophy failed to find any vascular abnormalities in that the vessels were patent and appeared normal except for accumulated perivascular connective tissue. Fluorescein angiographic examination of the right eye which was undergoing the earliest changes of iris atrophy failed to show any vascular abnormalities. However, tonographic examination indicated a markedly decreased outflow facility. There does not appear to be any vascular abnormality involved in the pathogenesis of this case. REFERENCES 1. Chandler PA, Grant WM: Lectures on Glaucoma, Essential Atrophy of the Iris uith Glaucoma. Philadelphia, Lea & Febiger, 1965, p 278. 2. Duke-Elder S, Perldns ES (eds): System of Ophthalmology. St. Louis, CV Mosby Company, 1966, Vol. 9, p 687. 3. Cross HE, Maumenee AE: Progressive spontaneous dissolution of the iris. Survey Ophthalmol 18:186-199, 1973. 4. Jampol LM, Rosser MJ, Sears M: Unusual aspects of progressive essential iris atrophy. Am J Ophthalmol, 77:353-357, 1974.
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DR A. EDWARD MAUMENEE. Thank you, Mr President. I would like to thank Dr Kupfer and Dr Kaiser-Kupfer for bringing this very interesting case report to our attention. It is most important to establish the basic pathology of various ocular diseases. Since we usually do not have an opportunity to biopsy seeing eyes in the early stages of disease, we are ignorant of the early pathologic changes of many ocular problems. Drs Kupfer and Kaiser-Kupfer have brought to our attention this interesting case of bilateral essential iris atrophy occurring in a male. They have shown us the very interesting fluorescein angiography of the iris in the early lesion in the right eye and they have brought to our attention the observation that the facility of outflow was extremely low, even before there was actual blockage of the angle of the anterior chamber by peripheral anterior synechia. The problem of iris atrophy is a complicated one, primarily because it is extremely rare, and no one really has a large series of patients to study. [Slide] Dr Harold Cross, when he was at the Wilmer Institute, and I tried to put together the various conditions that had iris atrophy, some of which were frequently progressive and some which were rarely progressive. Reiger's syndrome is a condition that has dental abnormalities, changes in the face, umbilical hernia, and iris atrophy. Ordinarily this condition is nonprogressive, but there are progressive cases in the literature; and we have seen some progressive cases at the Wilmer Institute. Iridoschisis is difficult to differentiate from Chandler's syndrome, and I am not certain that these are two separate distinct entities. In most patients with iridoschisis the changes begin at around the age of 40 or older, and in Chandler's syndrome, of course, they have the endothelial changes as well as the progressive iris changes. The essential iris atrophy that we are all familiar with is that type which occurs in females, usually in the fourth, fifth, or sixth decade, is progressive, and uniocular. Essential iris atrophy has reportedly been observed in males and bilaterally. We have seen such cases of bilateral essential iris atrophy occurring in males and have considered the condition to be transmitted in a sexlinked abnormality. Whether they really should be divided into two separate groups is not clear. I don't think that there are enough cases in the literature to say one way or another. Drs Kupfer and Kaiser-Kupfer, I think, are the first to do a histopathologic study on this particular abnormality in males; although I can't say that with certainty since the ages and sex of Dr Parker Heath's original ten cases were not included in his article. The slide on the screen shows a biopsy of the iris taken from a female patient who had unilateral essential atrophy of the iris and secondary glaucoma. A trephine was done five years ago, which has controlled her intraocular pressure. The biopsy specimen, as in Dr Kupfer's case, shows no evidence of occlusive vascular disease in the iris. Dr Richard Green, our pathologist at Wilmer, reviewed five of the cases on file at the Armed Forced Institute of Pathology that Dr Parker Heath included in his report, and in none of these specimens did he find conclusive
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evidence of a vascular-occlusive etiology. He did not have access to Dr Parker Heath's other five cases in which he illustrated changes that looked like they were occlusive vascular diseases. It was of interest to read the discussion of Dr Health's paper by Drs Verhoeff and Friedenwald, both of whom were not fully convinced of the vascular etiology of essential iris atrophy. We have material from four cases on file at the Wilmer Institute, and none of these have shown the occlusive vascular disease; so that I think we can confirm what Dr Kupfer has said - that the cause of this condition is still a mystery. We have not found the occlusive vascular disease as has been suggested by some as the cause of this lesion in the literature. Dr Godfried Naumann, however, has recently observed vascular occlusion histopathologically in a specimen that he has studied. Fluorescein angiography of the anterior segment of the eye may be helpful in determining whether this is primarily a vascular disease or not. I would like to thank the authors again for bringing this most interesting case to our attention.
DR JAMES JERVEY. Mr President. Fellow Members and Guests. I have enjoyed this discussion very much indeed. I wish I had had the good sense to bring some photographs of a similar case I have been following for some 15 years. She is a beautiful young woman who began to have trouble with one eye when she was 30 years old. This one eye has gone along with the typical picture which has been presented on the screen today. I am here to point out that the American Ophthalmological Society was originally formed as a clinical society and very little has been said today about the management of the treatment in these cases. I have had so little experience that I feel some strangeness in being up here trying to say something to you about it. This young lady began to have trouble after about 12 years with elevated pressure which has been controlled very well with epinephrine and pilocarpine drops. She has not had diamox. Her pressure is well within normal limits. The opposite eye is not affected. I chiefly wanted to mention the treatment of the corneal edema which does accompany this condition. The use of 5% sodium chloride ointment is a very satisfactory treatment. DR ROBERT KENNEDY. Mr President. Ladies and Gentlemen. I have certainly enjoyed the Kupfers' paper. As Doctor Jervey points out, the name of the game to the man on the firing line is the clinical solution of this problem. We have very few guide lines because there are so few series reported. I think the overall picture that I get is that the fistulizing procedures seem to be the most successful. There is a reluctance to do very much to the iris. The following case illustrates such a patient operated upon 24 years ago with successful control despite progressive iris changes. A 59-year-old male with records available since age 24 was seen with a normal right eye and esotropia of the left eye with amblyopia and 2/200 vision in 1942. When seen in 1949, the pupil of his good right eye was slightly oval, and small areas of iris atrophy were noted. There was deep cupping and disk atrophy with a pressure of 50 Schi0tz. Essential atrophy of the iris was diagnosed and surgery advised since he was refractory to medical treatment.
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This was refused for 1% years when the man could then be shown the marked deterioration of his visual fields. A trephine operation was performed in January of 1951. The pressure has been 12 or less since surgery and there has been no further loss of field in the past 24 years. Iris atrophy has continued with the pupil becoming displaced to the angle [Slide] so that you see the pupil in the 4:00 to 5:00 o'clock position in the angle. He has marked iris atrophy and an obliterated angle gonioscopically. He was developed a cataract which has brought up the question of management or cataract surgery. A pars plana Roto-Extractor removal has been considered with the hopes of leaving a functional bleb. Any advice would be appreciated. I personally have given up doing corneal transplants. I've given up retinal detachments, and now that I have this man on my hands it might be time to give up doing cataract surgery. One swallow does not make a springtime but a single fistulizing procedure has certainly been effective in pressure control in this patient despite progressive iris atrophy for approximately a quarter of a century. Thank you. DR CARL KUPFER. I want to thank the discussants for their most interesting remarks. In such a rare occasion, it is very gratifying to have Doctor Maumenee be able to identify ten cases examined histopathologically and confirm the fact that, at least in this group of cases, there is no evidence for occlusive vascular disease. Doctor Jervey does bring up an extremely appropriate point: what we are concerned with is not only the diagnosis, but perhaps more important, the treatment. In these rare cases, it is very hard to have collective awareness of what is appropriate, and I think he rightly calls attention to the value of the 5% sodium chloride ointment for control of the corneal edema. We are using that in this young man. Interestingly enough, despite the fact that his pressures are now equalized, he does have intermittent corneal edema which is treated with the ointment as well as the hair dryer. Doctor Kennedy presents a very long-term followup of successful surgery, and I think that this is of particular value because it has been my impression that the younger these people are when surgery is done, the more aggressive one has to be. In this particular instance, we had to do two trabeculectomies plus a partial cyclodiathermy to bring the pressure down to the region of 12-15 mm of mercury, which it is at present. May I make one further comment? One of the roles of the National Eye Institute is to act as a referral center for these extremely rare cases with which we, as individual ophthalmologists, rarely can accumulate a large clinical experience in a lifetime. On the other hand, if these cases are referred to the clinical branch of the National Eye Institute, they can be collected and studied. As you know, this is a facility that does not charge the patient and, therefore, hospitalization is not accompanied by financial problems for the patient. We would welcome very much having patients with this condition, either unilateral or bilateral, referred to us. We would do a careful workup with full report back to the referring ophthalmologist. Thank you very much.
