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The Late Stage of Serpiginous (Geographic) Choroiditis
AMERICAN JOURNAL OF OPHTHALMOLOGY VOLUME
82
SEPTEMBER, 1976
NUMBER
3
T H E LATE STAGE O F SERPIGINOUS (GEOGRAPHIC) C H O R O I D I T I S I. H. C H I S H O L M , F.R.C.S., J. D. M. G A S S , M.D., Miami,
The sudden development and slow res olution of each new lesion in serpiginous (geographic) choroiditis is well de scribed. 1 Attempts to identify the etiolo gy of the disease have failed to show any systemic abnormality or infective agent. 1 - 3 The disease is characterized by well-defined, gray lesions seen initially at the level of the pigment epithelium. 1 There is no change in the shape or size of each new lesion during its evolu tion but degeneration of the pigment epi thelium, 1 · 2 · 4 geographic atrophy of the choroid, 1 · 2,5 and in some patients subretinal scar formation occurs. 2 The disease progresses away from the region of the disk with more attacks in previously uninvolved areas. Visual acuity is only af fected if the central fovea is involved in an attack. 2 The fluorescein angiographie appearances of the different stages of the diseases are well described 1 · 2 · 6 and show primary involvement at the level of the choriocapillaris and pigment epithelium without evidence of neovascularization. Junius 7 examined a 39-year-old patient who had been observed for 14 years, but
A N D W. L. H U T T O N ,
M.D.
Florida
no other long-term follow-up has been available. No well-documented histologie study has been reported. We describe several patients who have had long-term follow-up or who had a condition that may represent the late stage of the dis ease. The diffuse atrophy without associ ated activity has an appearance that may be confused with that of an inherited dystrophic process such as central areolar choroidal sclerosis or diffuse choroidal sclerosis. SUBJECTS AND METHODS
The 20 white patients have been seen here since June 1966. At presentation, the 11 men and nine women averaged 47.5 years of age (range, 29 to 70 years) (Ta ble). The period of follow-up ranged from nine years to single visits. The average age at onset of symptoms in the first eye was 43.4 years (range, 22 to 70 years). The average time between onset of symptoms in the first eye and onset in the second eye was 5.1 years. Eight patients were asymp tomatic in the second eye when they were TABLE
From the Bascom Palmer Eye Institute, Depart ment of Ophthalmology, University of Miami, School of Medicine, Miami, Florida. This study was supported in part by National Eye Institute Public Health Service research grant EY-00338 and Public Health Service training grant EY-00028, National Institutes of Health; by the Camilla Samuel F u n d and the Medical Research Council, England (Dr. Chisholm); and by Seeing Eye, Inc., Morristown, New Jersey (Dr. Hutton). Reprint requests to I. H. Chisholm, F.R.C.S., Retinal Diagnostic Department, Moorflelds Eye Hospital, City Road, London, ECIV 2PD, England.
T H E A G E A T P R E S E N T A T I O N O F 20 P A T I E N T S W I T H SERPIGINOUS CHOROIDITIS
343
Age at Presentation, yrs
No. of Patients
30 or younger 31-40 41-50 51-60 60 or older
1 7 5 3 4
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first seen, although every patient had clin ical evidence of bilateral involvement. There was nothing in their general medi cal or family history, ocular history, or history of allergies to suggest a cause for their ocular problems. Stereoscopic fundus photography and fluorescein angiography were performed on all patients, and on each subsequent visit color photographs were taken. Electrophysiological studies using electroretinograms (ERG) and electro-oculograms (EOG) were carried out on 13 patients either on the first visit or on a subsequent one. Visual acuity in the better eye at pres entation was 6/6 (20/20) to 6/9 (20/30) in 14 eyes and between 6/12 (20/40) and 6/120 (20/400) in six eyes. Visual acuity in the poorer eye was 6/12 (20/40) to 6/15 (20/50) in four, 6/18 (20/60) to 6/24 (20/ 80) in three, 6/30 (20/100) to 6/60 (20/200) in five, and finger counting in eight eyes. Visual acuity during follow-up signifi cantly decreased in only three eyes (Fig. 1), the result of subsequent macular in volvement (Cases 1 and 2).
FINAL ACUITY
Fig. 1 (Chisholm, Gass, and Hutton). The visual acuity of each eye at presentation (ordinate) com pared with the latest acuity at follow-up visit (abscissa).
SEPTEMBER, 1976
None of the eyes was clinically in flamed but there was evidence in 15 eyes of small particles in the vitreous body that were indistinguishable from inflammato ry cells. In nine of these eyes there was evidence of active fundus disease when the cells were noticed. In the remaining eyes there was no evidence of vitreous cells even though three eyes showed evi dence of active chorioretinal disease at examination. New lesions were observed in ten pa tients during the follow-up period. We noted lesions at different stages of evolu tion in nine patients at presentation. The ERG was abnormal in three of the 26 eyes tested. Only the eye with the most extensive posterior pole involvement showed a marked reduction of the ERG. The E O G light rise ratio was normal in 17 eyes, moderately abnormal in one (1.45 to 1.65), and severely abnormal in eight (less than 1.45). The reduced levels of the E O G appeared to correlate well with the extent of the funduscopic change. Fluorescein angiography was per formed on every patient. The findings, which reflected the clinical stage of the disease, supported the diagnosis of serpiginous choroiditis in every case. In the acute stage there was relative hypofluorescence of the lesion that merged into the background fluorescence as the angiogram progressed. In the resolved lesion a hyperfluorescent border surrounded the area of hypofluorescence. The presence of pigment clumping, subretinal fibrous tis sue, and the degree of choroidal atrophy modified the fluorescein appearances. After the lesion resolved, ophthalmoscopic examination showed loss of the pigment epithelium and varying degrees of atrophy of the underlying choroid. The atrophy often had a scalloped appearance in contrast to the remaining normal pig ment epithelium. Sheets and, less often, mounds of white tissue, interpreted as fibrous tissue, developed between super-
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ficial choroid and retina in 19 eyes. In two eyes the fibrous tissue resembled a disciform scar. However, neither neovascularization nor subretinal hemorrhage was observed in the eyes examined. In every case lesions were present in the peripapillary region and appeared to spread peripherally as the disease pro gressed. Foveolar involvement appeared to occur during this stepwise centrifugal spread and did not occur once the mac ula had been passed. The outer limits of the involved area showed a pseudopod configuration. In nine patients there were discrete peripheral patches of atrophy that were not connected to the main areas of involvement. In every eye there were patches of pig ment hyperplasia scattered within the in volved area and on the edges of the atrophie processes. The unaffected areas of retina and pigment epithelium ap peared normal for the patient's age even in the eyes with extensive atrophy. The disks and retinal vessels appeared healthy. CASE REPORTS Case 1—A 44-year-old white woman was first seen here in 1967 with a two-year history of visual disturbance. She had been seen elsewhere in 1965 when a diagnosis of tuberculous chorioretinitis had been made on the basis of the fundus findings and a positive purified protein derivative test. Visual acu ity in 1967 was R.E.: 6/6-1 (20/20-1), and L.E.: finger counting. Ophthalmoscopic examination at that time revealed chorioretinal scars at the posterior pole and what appeared to be an active lesion above the left macula and evidence of subretinal fluid. No abnormality was found medically. Since then, there has been further involvement of the posterior pole with documented new lesions. In 1972, visual acuity was finger counting in the left eye and remains unchanged. In 1975, the areas of involvement were more extensive. There was atrophy of the pigment epithe lium throughout much of the posterior pole with patches of pigment hyperplasia. There were also isolated areas of atrophy in the retinal periphery. The uninvolved areas appeared normal. Many of the patches of atrophy appeared scalloped in relation to the surviving areas of pigment epithelium. In some areas, there was fibrous tissue deposition under the retina. There was no serous detachment of the
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retina. The ERG was normal in each eye. T h e E O G showed no light rise in the right eye and was severely abnormal (light rise ratio, 1.2) in the left eye (Figs. 2 and 3). Case 2—A 43-year-old white man was first seen in 1972 with a three-month history of waking with disturbed vision in his right eye. His left eye was asymptomatic. Visual acuity was R.E.: 6/12 (20/40) and L.E.: 6/6 (20/20). Ophthalmoscopic examina tion showed typical areas of pigment epithelial loss with patches of hyperpigmentation. In September 1973, he had a recurrence in his left eye that affected his central vision; visual acuity was 6/120 (20/400). There was a mild vitritis in each eye and an active lesion in the left macular region. In 1975, he had extensive involvement of both posterior poles with pseudopod formation and scalloped atrophie areas. There were also a few peripheral atrophie· patches and evidence of subretinal fibrous tissue. The ERG and E O G were normal (Figs. 4-7). Case 3—A 39-year-old white man was first seen in 1973 with blurred vision in the right eye of one month's duration. Vision in the left eye had been poor for ten years. Visual acuity was R.E.: 6/12 (20/40), and L.E.: 6/7.5 (20/25). There were no cells in the vitreous body. Ophthalmoscopic examination showed a typical lesion in the acute stage around the right macula and evidence of extensive previous involvement of both posterior poles. In 1975, there was marked loss of the pigment epithelium and choriocapillaris with preservation of the major choroidal vessels. At the posterior pole, the atrophy was confluent and locally resembled "choroidal sclerosis." The peripheral limits of the atrophie area showed typical pseudopod formation and discrete patches of atrophy. The area that was involved at first examination had become inactive and had merged into the general area of atrophy, but there was evidence that an area below the disk in the right eye had been active recently. There were patches of pigment hyperplasia throughout the involved area. Visual acuity was R.E.: 6/6 (20/20), and L.E.: 6/9 (20/30) eccentrically as a result of small residual islands of pigment epithelium in the center of the atrophie areas. T h e ERG was normal in each eye but the E O G was abnormal (light rise ratio, 1.3) in both eyes (Fig. 8). Case 4—A 34-year-old white woman was first seen in 1966 when she noticed that her right vision was poor. Visual acuity was R.E.: finger counting, and L.E. 6/6 (20/20). Ophthalmoscopic examination showed an active lesion in the right eye and one old lesion below the disk in the left eye. In 1974, the right eye showed an area of recent involvement temporal to the original lesion. Additionally, there were lesions in the left eye that had not been present. In both eyes'white tissue appeared at the level of and deep to the pigment epithelium. In October 1975, she had another attack in the left eye that decreased visual acuity to 6/9 (20/30). The ERG and E O G were normal in each eye (Figs. 9 and 10). Case 5—A 62-year-old white man was first seen in 1972 with an area of visual field loss in his left eye. He had been aware of poor vision in his right eye
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Fig. 2 (Chisholm, Gass, and Hutton). Case 1, right eye. In 1975, there was widespread involvement with peripheral pseudopod formation, isolated le sions, and pigment hyperplasia.
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Fig. 3 (Chisholm, Gass, and Hutton). Case 1, left eye. In 1975, fibrous tissue was present in both eyes under the retina. Some of the areas of atrophy had a scalloped appearance.
since 1961. Visual acuity was R.E.: finger counting, and L.E.: 6/9 (20/30) with a positive scotoma on Amsler testing. There were cells in the vitreous body in each eye. Ophthalmoscopic examination of the right eye showed extensive atrophy of the posterior
pole with pigmentary disturbance and pseudopod formation of the edge of the atrophie area. The left fundus showed fainter atrophie areas but a tongue of normal pigment epitelium extended to the macula. There was an area of activity below the macula. The
Fig. 4 (Chisholm, Gass, and Hutton). Case 2, left eye. In 1972, the macula was not involved.
Fig. 5 (Chisholm, Gass, and Hutton). Case 2, left eye. In September 1973, an attack involved the left macula. Visual acuity decreased to 6/120 (20/400).
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Fig. 6 (Chisholm, Gass, and Hutton). Case 2, left eye. In October 1973, the new lesions were resolv ing. The gray area was less swollen but more exten sive, and some hyperplasia of the pigment epitheli um occurred. There was a well-marked peripheral lesion in the superonasal quadrant. edges of the atrophie areas were somewhat rounded. An isolated peripheral lesion was present in the superotemporal quadrant. The disk and vessels ap peared healthy. In 1975, visual acuity was un changed, but the involvement in the left eye was more extensive. The area below the macula that had been active in 1972 was now atrophie. The pigment epithelium of the central macula was still intact. The
Fig. 8 (Chisholm, Gass, and Hutton). Case 3, left eye. In 1975, there was widespread involvement. The posterior pole had an appearance not unlike choroidal sclerosis but the periphery of the lesion shows typical pseudopods. Visual acuity was 6/9 (20/30).
347
Fig. 7 (Chisholm, Gass, and Hutton). Case 2, left eye. In 1975, there was considerable hyperplasia of the pigment epithelium and fibrous tissue deposi tion under the retina.
ERG and EOG in the right eye were abnormal but normal in the left eye (Figs. 11-13). DISCUSSION
Although we emphasized the ophthalmoscopic appearances, the diagnosis of
Fig. 9 (Chisholm, Gass, and Hutton). Case 4, left eye. In 1972, there was old involvement below the disk but the eye was otherwise normal.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 10 (Chisholm, Gass, and Hutton). Case 4, left eye. In November 1975, there were additional areas of involvement, a new area of activity between the disk and foveola, and marked fibrous tissue deposi tion above the disk (arrow).
serpiginous choroiditis was based on the fundus changes together with the charac teristic fluorescein angiographie findings and the observation of new lesions during the follow-up period. These new lesions
Fig. 11 (Chisholm, Gass, and Hutton). Case 5, right eye. In 1972, there was widespread atrophy of the posterior pole not unlike choroidal sclerosis. Peripheral pseudopods with pigment hyperplasia and the asymmetry (compare with Figs. 12 and 13) made the diagnosis of a primary dystrophic process most unlikely.
SEPTEMBER, 1976
Fig. 12 (Chisholm, Gass, and Hutton). Case 5, left eye. In 1972, there was an area of activity below the macula (arrow).
may be identified in the acute or subacute phase in a previously uninvolved area of retina, or inferred when an extension of the previous pattern is seen later. The existence of lesions at different stages of development at a single examination is also strong evidence for the diagnosis. 1
Fig. 13 (Chisholm, Gass, and Hutton). Case 5, left eye. In 1975, when there was a considerable increase in the area of involvement, visual acuity was 6/9 (20/30) due to a tongue of normal pigment epitheli um under the foveola.
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The gray swelling in the acute phase seems to lie deep to the retina at the level of the retinal pigment epithelium and choriocapillaris. Angiographically the le sion in the acute stage appeared initially hypofluorescent. The hypofluorescence is probably secondary to a primary closure of the choroidal blood vessels, 2 · 7 although it may be due to blocking of the choroidal fluorescence by the opaque pigment epi thelium. 1 The degree of choroidal atrophy seen in the late stage suggests that the choroidal blood vessels are primarily in volved. Schatz, Maumenee, and Patz 2 re ported an elevated retina in two of their patients. In three of our cases, there was a shallow serous detachment of the retina during the acute stage. Since there was no evidence of neovascular proliferation under the retina, the presence of serous detachment suggests that both the choroid and pigment epithelium are involved in the disease process. The degree of choroidal atrophy in this condition is not seen in acute posterior multifocal placoid pigment epitheliopathy in which the pigr ment epithelium is thought to be primari ly involved. 8 After the lesion resolves, there is atro phy of the choroid and pigment epitheli um with varying amounts of fibrous tis sue deposition and pigment hyperplasia. The degree of confluence of the atrophie areas varies so that in some patients there are recognizable islands of normal pig ment epithelium, and in others there is a marked resemblance to choroidal sclero sis. In all the patients with extensive disease, tongue-like projections or pseudopods with variable amounts of margin al pigmentation were seen around the main area of involvement. This feature does not occur in the primary choroidal atrophies. Peripheral to the main area of involve ment there were isolated discrete lesions that must have occurred separately rather than as creeping extensions of previous
349
lesions. The lesions probably originated at discrete patches of activity rather than spreading like a bush fire. The process seemed to begin in the region of the disk and subsequently involved more periph eral areas. Visual acuity was preserved when an island of normal pigment epithe lium lay at the foveola, and none of our patients lost central vision after the foveo la had been passed by the stepwise pro gression of the disease. The white tissue between the retina and affected choroid presumably was fi brous 2 ; this is supported by the clinicopathological report of a somewhat atypi cal case by Gass. 5 The tissue was slightly fluorescent during the early phase of angiography and stained during the later phases. Pigment hyperplasia appeared to occur at the same level as the fibrous tissue and masked any background fluo rescence. The appearance of both fibrous tissue and pigment at the level originally occupied by the pigment epithelium sug gests that the fibrous tissue developed as a result of pigment epithelial metaplasia or, less likely, astroglial proliferation rather than fibrous proliferation through Bruch's membrane. Subretinal hemor rhages did not occur in this condition. There was no evidence of subretinal neovascularization, which makes fibrous pro liferation through Bruch's membrane un likely. The atrophie areas were in sharp contrast to normal ones, giving an exca vated or scalloped appearance. The ret ina was separate from the underlying sciera and did not dip into the cavity, which is probably filled with transparent tissue. The retina and pigment epithelium out side the areas of involvement appeared clinically and angiographically normal. The retinal vessels were normal and the ERG was normal in 23 of the 26 eyes tested. The E O G findings agreed with those of Hamilton and Bird 1 in that they were only abnormal when there was ex-
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tensive disease present. Visual acuity in the eye with a markedly reduced ERG had been poor for 14 years (Case 5), and there was choroidal atrophy throughout the whole posterior pole. The disk ap peared healthy, and no other cause for the ERG changes could be identified. Krill and Archer 4 reported similar ERG chang es in one patient. None of the eyes showed marked vitre ous inflammation, but a few cells were seen in contradistinction to the findings of Hamilton and Bird. 1 These particles were indistinguishable from the cellular reaction in other forms of established inflammatory disease. All but two of the patients were treated with corticosteroids either locally or systemically at some stage of the disease. Although some of the patients felt that they had improved with this form of therapy, we had no objective evidence of improvement as a result of the use of corticosteroids. In four patients the lesion in the acute stage lay adjacent to the foveola, and there was an initial deterio ration of vision that improved as the le sion resolved. Since lesions resolve natur ally, it is difficult to be certain as to the efficacy of corticosteroids. There was nö rapid resolution of the lesion when these drugs were used. Photocoagulation was used in one patient in an attempt to halt progression toward the fovea, without success. Since the disease progresses in a stepwise manner, how photocoagulation can halt the progress of the disease is unknown. Hamilton and Bird 1 predicted that the final appearance in this disease would be well-demarcated atrophy of the pigment epithelium and choriocapillaris occupy ing the whole posterior fundus. One of our patients (Case 5) had this appearance in his right eye. The confluent atrophy with surrounding pseudöpods was simi lar to that seen in another patient (Case 3), although the atrophy was more extensive
SEPTEMBER, 1976
and resulted in ERG changes in addition to the È O G changes. The presence of pigment hypertrophy, the asymmetry be tween the two eyes, and the age at onset in Case 5 make it unlikely that the changes represent a primary choroidal sclerosis. The left eye became involved subjectively 11 years later due to an area of activity below the macula but has retained good vision. The atrophy extended and an iso lated peripheral lesion developed in the second eye, characterizing serpiginous choroiditis. The right eye, which has been involved since 1961, represents the late stage of the disease. Although the atrophy at the posterior pole might be mistaken for choroidal sclerosis, the diagnosis is serpiginous choroiditis, based on an over all consideration of the patient. These cases showed progressive stepwise involvement of the posterior pole and not the creeping kind of lesion that has been described. 9 The occurrence of discrete lesions supports the concept that each area of involvement is a new event and not an extension of a previous lesion. Our cases have the same features as those described by Hamilton and Bird 1 in geographic choroiditis and by Schatz, Maumenee, and Patz 2 in geographic helicoid peripapillary choroidopathy. Franceschetti 1 0 included a similar case in his presentation of helicoid peripapillary chorioretinal degeneration as did Krill and Archer 4 in their classification of the chorioretinal atrophies. The case original ly described by Gass 5 in 1970 is not included in our series as it does not have the characteristic features of the disease. Gass's patient had an exudative and hemorrhagic detachment of the retina with subretinal scarring and vascular ingrowth under the retina, an atypical example of the disease if it is the same disease. As all the descriptions seem to apply to the same disease, any attempt to distinguish be tween serpiginous and geographic cho roiditis is probably artifactual.
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SUMMARY
REFERENCES
Serpiginous and geographic choroiditis, one and the same disease, is charac terized by episodic involvement of the pigment epithelium and choroid. Each new lesion passes through an acute phase into an atrophie and scarring one. We observed 20 patients, some with longterm follow-up; some had eventual wide spread involvement of both posterior poles. There was no basis for the disease, and treatment did not affect its course. In the patients with long-term disease there was widespread atrophy of the choroid and pigment epithelium and variable amounts of pigment clumping and subretinal fibrous tissue deposition. In nine patients discrete peripheral patches of atrophy were also found. In some eyes the atrophy at the posterior pole had be come so confluent that the condition could have been mistaken superficially for a primary choroidal dystrophy. The uninvolved areas appeared to be normal. The electroretinogram and electrooculogram were only affected when ex tensive disease was present.
1. Hamilton, A. M., and Bird, A. C : Geographical choroidopathy. Br. J. Ophthalmol. 58:784, 1974. 2. Schatz, H., Maumenee, A. E., and Patz, A.: Geographic helicoid peripapillary choroidopathy. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:747, 1974. 3. Laatikainen, L., and Erkkila, H.: Serpiginous choroiditis. Br. J. Ophthalmol. 58:777, 1974. 4. Krill, A. E., and Archer, D.: Classification of the choroidal atrophies. Am. J. Ophthalmol. 72:562, 1971. 5. Gass, J. D. M.: Stereoscopic Atlas of Macular Disease. A Funduscopic and Angiographie Presen tation. St. Louis, C. V. Mosby, 1970, pp. 66 and 67. 6. Hyvarinen, L., Maumenee, A. E., George, T., and Weinstein, G. E.: Fluorescein angiography of the choriocapillaris. Am. J. Ophthalmol. 67:653, 1969. 7. Junius, P.: Seltene augenspiegelbilder zum klinischen phanomeh der retinitis exsudativa coats und der retino chorioditis "parapapillaris." Arch. Augenheilkd. 106:475, 1932. 8. Gass, J. D. M.: Acute posterior multifocal placoid pigment epitheliopathy. Arch. Ophthalmol. 80: 177, 1968. 9. Maumenee, A. E.: Clinical entities in uveitis. An approach to the study of intraocular inflamma tion. Trans. Am. Acad. Ophthalmol. Otolaryngol. 74:473, 1970. 10. Franceschetti, A.: A curious affection of the fundus oculi: helicoid peripapillar chorioretinal de generation. Its relation to pigmentary paravenous chorioretinal degeneration. Doc. Ophthalmol. 16:81, 1962.
82
SEPTEMBER, 1976
NUMBER
3
T H E LATE STAGE O F SERPIGINOUS (GEOGRAPHIC) C H O R O I D I T I S I. H. C H I S H O L M , F.R.C.S., J. D. M. G A S S , M.D., Miami,
The sudden development and slow res olution of each new lesion in serpiginous (geographic) choroiditis is well de scribed. 1 Attempts to identify the etiolo gy of the disease have failed to show any systemic abnormality or infective agent. 1 - 3 The disease is characterized by well-defined, gray lesions seen initially at the level of the pigment epithelium. 1 There is no change in the shape or size of each new lesion during its evolu tion but degeneration of the pigment epi thelium, 1 · 2 · 4 geographic atrophy of the choroid, 1 · 2,5 and in some patients subretinal scar formation occurs. 2 The disease progresses away from the region of the disk with more attacks in previously uninvolved areas. Visual acuity is only af fected if the central fovea is involved in an attack. 2 The fluorescein angiographie appearances of the different stages of the diseases are well described 1 · 2 · 6 and show primary involvement at the level of the choriocapillaris and pigment epithelium without evidence of neovascularization. Junius 7 examined a 39-year-old patient who had been observed for 14 years, but
A N D W. L. H U T T O N ,
M.D.
Florida
no other long-term follow-up has been available. No well-documented histologie study has been reported. We describe several patients who have had long-term follow-up or who had a condition that may represent the late stage of the dis ease. The diffuse atrophy without associ ated activity has an appearance that may be confused with that of an inherited dystrophic process such as central areolar choroidal sclerosis or diffuse choroidal sclerosis. SUBJECTS AND METHODS
The 20 white patients have been seen here since June 1966. At presentation, the 11 men and nine women averaged 47.5 years of age (range, 29 to 70 years) (Ta ble). The period of follow-up ranged from nine years to single visits. The average age at onset of symptoms in the first eye was 43.4 years (range, 22 to 70 years). The average time between onset of symptoms in the first eye and onset in the second eye was 5.1 years. Eight patients were asymp tomatic in the second eye when they were TABLE
From the Bascom Palmer Eye Institute, Depart ment of Ophthalmology, University of Miami, School of Medicine, Miami, Florida. This study was supported in part by National Eye Institute Public Health Service research grant EY-00338 and Public Health Service training grant EY-00028, National Institutes of Health; by the Camilla Samuel F u n d and the Medical Research Council, England (Dr. Chisholm); and by Seeing Eye, Inc., Morristown, New Jersey (Dr. Hutton). Reprint requests to I. H. Chisholm, F.R.C.S., Retinal Diagnostic Department, Moorflelds Eye Hospital, City Road, London, ECIV 2PD, England.
T H E A G E A T P R E S E N T A T I O N O F 20 P A T I E N T S W I T H SERPIGINOUS CHOROIDITIS
343
Age at Presentation, yrs
No. of Patients
30 or younger 31-40 41-50 51-60 60 or older
1 7 5 3 4
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first seen, although every patient had clin ical evidence of bilateral involvement. There was nothing in their general medi cal or family history, ocular history, or history of allergies to suggest a cause for their ocular problems. Stereoscopic fundus photography and fluorescein angiography were performed on all patients, and on each subsequent visit color photographs were taken. Electrophysiological studies using electroretinograms (ERG) and electro-oculograms (EOG) were carried out on 13 patients either on the first visit or on a subsequent one. Visual acuity in the better eye at pres entation was 6/6 (20/20) to 6/9 (20/30) in 14 eyes and between 6/12 (20/40) and 6/120 (20/400) in six eyes. Visual acuity in the poorer eye was 6/12 (20/40) to 6/15 (20/50) in four, 6/18 (20/60) to 6/24 (20/ 80) in three, 6/30 (20/100) to 6/60 (20/200) in five, and finger counting in eight eyes. Visual acuity during follow-up signifi cantly decreased in only three eyes (Fig. 1), the result of subsequent macular in volvement (Cases 1 and 2).
FINAL ACUITY
Fig. 1 (Chisholm, Gass, and Hutton). The visual acuity of each eye at presentation (ordinate) com pared with the latest acuity at follow-up visit (abscissa).
SEPTEMBER, 1976
None of the eyes was clinically in flamed but there was evidence in 15 eyes of small particles in the vitreous body that were indistinguishable from inflammato ry cells. In nine of these eyes there was evidence of active fundus disease when the cells were noticed. In the remaining eyes there was no evidence of vitreous cells even though three eyes showed evi dence of active chorioretinal disease at examination. New lesions were observed in ten pa tients during the follow-up period. We noted lesions at different stages of evolu tion in nine patients at presentation. The ERG was abnormal in three of the 26 eyes tested. Only the eye with the most extensive posterior pole involvement showed a marked reduction of the ERG. The E O G light rise ratio was normal in 17 eyes, moderately abnormal in one (1.45 to 1.65), and severely abnormal in eight (less than 1.45). The reduced levels of the E O G appeared to correlate well with the extent of the funduscopic change. Fluorescein angiography was per formed on every patient. The findings, which reflected the clinical stage of the disease, supported the diagnosis of serpiginous choroiditis in every case. In the acute stage there was relative hypofluorescence of the lesion that merged into the background fluorescence as the angiogram progressed. In the resolved lesion a hyperfluorescent border surrounded the area of hypofluorescence. The presence of pigment clumping, subretinal fibrous tis sue, and the degree of choroidal atrophy modified the fluorescein appearances. After the lesion resolved, ophthalmoscopic examination showed loss of the pigment epithelium and varying degrees of atrophy of the underlying choroid. The atrophy often had a scalloped appearance in contrast to the remaining normal pig ment epithelium. Sheets and, less often, mounds of white tissue, interpreted as fibrous tissue, developed between super-
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ficial choroid and retina in 19 eyes. In two eyes the fibrous tissue resembled a disciform scar. However, neither neovascularization nor subretinal hemorrhage was observed in the eyes examined. In every case lesions were present in the peripapillary region and appeared to spread peripherally as the disease pro gressed. Foveolar involvement appeared to occur during this stepwise centrifugal spread and did not occur once the mac ula had been passed. The outer limits of the involved area showed a pseudopod configuration. In nine patients there were discrete peripheral patches of atrophy that were not connected to the main areas of involvement. In every eye there were patches of pig ment hyperplasia scattered within the in volved area and on the edges of the atrophie processes. The unaffected areas of retina and pigment epithelium ap peared normal for the patient's age even in the eyes with extensive atrophy. The disks and retinal vessels appeared healthy. CASE REPORTS Case 1—A 44-year-old white woman was first seen here in 1967 with a two-year history of visual disturbance. She had been seen elsewhere in 1965 when a diagnosis of tuberculous chorioretinitis had been made on the basis of the fundus findings and a positive purified protein derivative test. Visual acu ity in 1967 was R.E.: 6/6-1 (20/20-1), and L.E.: finger counting. Ophthalmoscopic examination at that time revealed chorioretinal scars at the posterior pole and what appeared to be an active lesion above the left macula and evidence of subretinal fluid. No abnormality was found medically. Since then, there has been further involvement of the posterior pole with documented new lesions. In 1972, visual acuity was finger counting in the left eye and remains unchanged. In 1975, the areas of involvement were more extensive. There was atrophy of the pigment epithe lium throughout much of the posterior pole with patches of pigment hyperplasia. There were also isolated areas of atrophy in the retinal periphery. The uninvolved areas appeared normal. Many of the patches of atrophy appeared scalloped in relation to the surviving areas of pigment epithelium. In some areas, there was fibrous tissue deposition under the retina. There was no serous detachment of the
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retina. The ERG was normal in each eye. T h e E O G showed no light rise in the right eye and was severely abnormal (light rise ratio, 1.2) in the left eye (Figs. 2 and 3). Case 2—A 43-year-old white man was first seen in 1972 with a three-month history of waking with disturbed vision in his right eye. His left eye was asymptomatic. Visual acuity was R.E.: 6/12 (20/40) and L.E.: 6/6 (20/20). Ophthalmoscopic examina tion showed typical areas of pigment epithelial loss with patches of hyperpigmentation. In September 1973, he had a recurrence in his left eye that affected his central vision; visual acuity was 6/120 (20/400). There was a mild vitritis in each eye and an active lesion in the left macular region. In 1975, he had extensive involvement of both posterior poles with pseudopod formation and scalloped atrophie areas. There were also a few peripheral atrophie· patches and evidence of subretinal fibrous tissue. The ERG and E O G were normal (Figs. 4-7). Case 3—A 39-year-old white man was first seen in 1973 with blurred vision in the right eye of one month's duration. Vision in the left eye had been poor for ten years. Visual acuity was R.E.: 6/12 (20/40), and L.E.: 6/7.5 (20/25). There were no cells in the vitreous body. Ophthalmoscopic examination showed a typical lesion in the acute stage around the right macula and evidence of extensive previous involvement of both posterior poles. In 1975, there was marked loss of the pigment epithelium and choriocapillaris with preservation of the major choroidal vessels. At the posterior pole, the atrophy was confluent and locally resembled "choroidal sclerosis." The peripheral limits of the atrophie area showed typical pseudopod formation and discrete patches of atrophy. The area that was involved at first examination had become inactive and had merged into the general area of atrophy, but there was evidence that an area below the disk in the right eye had been active recently. There were patches of pigment hyperplasia throughout the involved area. Visual acuity was R.E.: 6/6 (20/20), and L.E.: 6/9 (20/30) eccentrically as a result of small residual islands of pigment epithelium in the center of the atrophie areas. T h e ERG was normal in each eye but the E O G was abnormal (light rise ratio, 1.3) in both eyes (Fig. 8). Case 4—A 34-year-old white woman was first seen in 1966 when she noticed that her right vision was poor. Visual acuity was R.E.: finger counting, and L.E. 6/6 (20/20). Ophthalmoscopic examination showed an active lesion in the right eye and one old lesion below the disk in the left eye. In 1974, the right eye showed an area of recent involvement temporal to the original lesion. Additionally, there were lesions in the left eye that had not been present. In both eyes'white tissue appeared at the level of and deep to the pigment epithelium. In October 1975, she had another attack in the left eye that decreased visual acuity to 6/9 (20/30). The ERG and E O G were normal in each eye (Figs. 9 and 10). Case 5—A 62-year-old white man was first seen in 1972 with an area of visual field loss in his left eye. He had been aware of poor vision in his right eye
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Fig. 2 (Chisholm, Gass, and Hutton). Case 1, right eye. In 1975, there was widespread involvement with peripheral pseudopod formation, isolated le sions, and pigment hyperplasia.
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Fig. 3 (Chisholm, Gass, and Hutton). Case 1, left eye. In 1975, fibrous tissue was present in both eyes under the retina. Some of the areas of atrophy had a scalloped appearance.
since 1961. Visual acuity was R.E.: finger counting, and L.E.: 6/9 (20/30) with a positive scotoma on Amsler testing. There were cells in the vitreous body in each eye. Ophthalmoscopic examination of the right eye showed extensive atrophy of the posterior
pole with pigmentary disturbance and pseudopod formation of the edge of the atrophie area. The left fundus showed fainter atrophie areas but a tongue of normal pigment epitelium extended to the macula. There was an area of activity below the macula. The
Fig. 4 (Chisholm, Gass, and Hutton). Case 2, left eye. In 1972, the macula was not involved.
Fig. 5 (Chisholm, Gass, and Hutton). Case 2, left eye. In September 1973, an attack involved the left macula. Visual acuity decreased to 6/120 (20/400).
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Fig. 6 (Chisholm, Gass, and Hutton). Case 2, left eye. In October 1973, the new lesions were resolv ing. The gray area was less swollen but more exten sive, and some hyperplasia of the pigment epitheli um occurred. There was a well-marked peripheral lesion in the superonasal quadrant. edges of the atrophie areas were somewhat rounded. An isolated peripheral lesion was present in the superotemporal quadrant. The disk and vessels ap peared healthy. In 1975, visual acuity was un changed, but the involvement in the left eye was more extensive. The area below the macula that had been active in 1972 was now atrophie. The pigment epithelium of the central macula was still intact. The
Fig. 8 (Chisholm, Gass, and Hutton). Case 3, left eye. In 1975, there was widespread involvement. The posterior pole had an appearance not unlike choroidal sclerosis but the periphery of the lesion shows typical pseudopods. Visual acuity was 6/9 (20/30).
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Fig. 7 (Chisholm, Gass, and Hutton). Case 2, left eye. In 1975, there was considerable hyperplasia of the pigment epithelium and fibrous tissue deposi tion under the retina.
ERG and EOG in the right eye were abnormal but normal in the left eye (Figs. 11-13). DISCUSSION
Although we emphasized the ophthalmoscopic appearances, the diagnosis of
Fig. 9 (Chisholm, Gass, and Hutton). Case 4, left eye. In 1972, there was old involvement below the disk but the eye was otherwise normal.
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Fig. 10 (Chisholm, Gass, and Hutton). Case 4, left eye. In November 1975, there were additional areas of involvement, a new area of activity between the disk and foveola, and marked fibrous tissue deposi tion above the disk (arrow).
serpiginous choroiditis was based on the fundus changes together with the charac teristic fluorescein angiographie findings and the observation of new lesions during the follow-up period. These new lesions
Fig. 11 (Chisholm, Gass, and Hutton). Case 5, right eye. In 1972, there was widespread atrophy of the posterior pole not unlike choroidal sclerosis. Peripheral pseudopods with pigment hyperplasia and the asymmetry (compare with Figs. 12 and 13) made the diagnosis of a primary dystrophic process most unlikely.
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Fig. 12 (Chisholm, Gass, and Hutton). Case 5, left eye. In 1972, there was an area of activity below the macula (arrow).
may be identified in the acute or subacute phase in a previously uninvolved area of retina, or inferred when an extension of the previous pattern is seen later. The existence of lesions at different stages of development at a single examination is also strong evidence for the diagnosis. 1
Fig. 13 (Chisholm, Gass, and Hutton). Case 5, left eye. In 1975, when there was a considerable increase in the area of involvement, visual acuity was 6/9 (20/30) due to a tongue of normal pigment epitheli um under the foveola.
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The gray swelling in the acute phase seems to lie deep to the retina at the level of the retinal pigment epithelium and choriocapillaris. Angiographically the le sion in the acute stage appeared initially hypofluorescent. The hypofluorescence is probably secondary to a primary closure of the choroidal blood vessels, 2 · 7 although it may be due to blocking of the choroidal fluorescence by the opaque pigment epi thelium. 1 The degree of choroidal atrophy seen in the late stage suggests that the choroidal blood vessels are primarily in volved. Schatz, Maumenee, and Patz 2 re ported an elevated retina in two of their patients. In three of our cases, there was a shallow serous detachment of the retina during the acute stage. Since there was no evidence of neovascular proliferation under the retina, the presence of serous detachment suggests that both the choroid and pigment epithelium are involved in the disease process. The degree of choroidal atrophy in this condition is not seen in acute posterior multifocal placoid pigment epitheliopathy in which the pigr ment epithelium is thought to be primari ly involved. 8 After the lesion resolves, there is atro phy of the choroid and pigment epitheli um with varying amounts of fibrous tis sue deposition and pigment hyperplasia. The degree of confluence of the atrophie areas varies so that in some patients there are recognizable islands of normal pig ment epithelium, and in others there is a marked resemblance to choroidal sclero sis. In all the patients with extensive disease, tongue-like projections or pseudopods with variable amounts of margin al pigmentation were seen around the main area of involvement. This feature does not occur in the primary choroidal atrophies. Peripheral to the main area of involve ment there were isolated discrete lesions that must have occurred separately rather than as creeping extensions of previous
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lesions. The lesions probably originated at discrete patches of activity rather than spreading like a bush fire. The process seemed to begin in the region of the disk and subsequently involved more periph eral areas. Visual acuity was preserved when an island of normal pigment epithe lium lay at the foveola, and none of our patients lost central vision after the foveo la had been passed by the stepwise pro gression of the disease. The white tissue between the retina and affected choroid presumably was fi brous 2 ; this is supported by the clinicopathological report of a somewhat atypi cal case by Gass. 5 The tissue was slightly fluorescent during the early phase of angiography and stained during the later phases. Pigment hyperplasia appeared to occur at the same level as the fibrous tissue and masked any background fluo rescence. The appearance of both fibrous tissue and pigment at the level originally occupied by the pigment epithelium sug gests that the fibrous tissue developed as a result of pigment epithelial metaplasia or, less likely, astroglial proliferation rather than fibrous proliferation through Bruch's membrane. Subretinal hemor rhages did not occur in this condition. There was no evidence of subretinal neovascularization, which makes fibrous pro liferation through Bruch's membrane un likely. The atrophie areas were in sharp contrast to normal ones, giving an exca vated or scalloped appearance. The ret ina was separate from the underlying sciera and did not dip into the cavity, which is probably filled with transparent tissue. The retina and pigment epithelium out side the areas of involvement appeared clinically and angiographically normal. The retinal vessels were normal and the ERG was normal in 23 of the 26 eyes tested. The E O G findings agreed with those of Hamilton and Bird 1 in that they were only abnormal when there was ex-
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tensive disease present. Visual acuity in the eye with a markedly reduced ERG had been poor for 14 years (Case 5), and there was choroidal atrophy throughout the whole posterior pole. The disk ap peared healthy, and no other cause for the ERG changes could be identified. Krill and Archer 4 reported similar ERG chang es in one patient. None of the eyes showed marked vitre ous inflammation, but a few cells were seen in contradistinction to the findings of Hamilton and Bird. 1 These particles were indistinguishable from the cellular reaction in other forms of established inflammatory disease. All but two of the patients were treated with corticosteroids either locally or systemically at some stage of the disease. Although some of the patients felt that they had improved with this form of therapy, we had no objective evidence of improvement as a result of the use of corticosteroids. In four patients the lesion in the acute stage lay adjacent to the foveola, and there was an initial deterio ration of vision that improved as the le sion resolved. Since lesions resolve natur ally, it is difficult to be certain as to the efficacy of corticosteroids. There was nö rapid resolution of the lesion when these drugs were used. Photocoagulation was used in one patient in an attempt to halt progression toward the fovea, without success. Since the disease progresses in a stepwise manner, how photocoagulation can halt the progress of the disease is unknown. Hamilton and Bird 1 predicted that the final appearance in this disease would be well-demarcated atrophy of the pigment epithelium and choriocapillaris occupy ing the whole posterior fundus. One of our patients (Case 5) had this appearance in his right eye. The confluent atrophy with surrounding pseudöpods was simi lar to that seen in another patient (Case 3), although the atrophy was more extensive
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and resulted in ERG changes in addition to the È O G changes. The presence of pigment hypertrophy, the asymmetry be tween the two eyes, and the age at onset in Case 5 make it unlikely that the changes represent a primary choroidal sclerosis. The left eye became involved subjectively 11 years later due to an area of activity below the macula but has retained good vision. The atrophy extended and an iso lated peripheral lesion developed in the second eye, characterizing serpiginous choroiditis. The right eye, which has been involved since 1961, represents the late stage of the disease. Although the atrophy at the posterior pole might be mistaken for choroidal sclerosis, the diagnosis is serpiginous choroiditis, based on an over all consideration of the patient. These cases showed progressive stepwise involvement of the posterior pole and not the creeping kind of lesion that has been described. 9 The occurrence of discrete lesions supports the concept that each area of involvement is a new event and not an extension of a previous lesion. Our cases have the same features as those described by Hamilton and Bird 1 in geographic choroiditis and by Schatz, Maumenee, and Patz 2 in geographic helicoid peripapillary choroidopathy. Franceschetti 1 0 included a similar case in his presentation of helicoid peripapillary chorioretinal degeneration as did Krill and Archer 4 in their classification of the chorioretinal atrophies. The case original ly described by Gass 5 in 1970 is not included in our series as it does not have the characteristic features of the disease. Gass's patient had an exudative and hemorrhagic detachment of the retina with subretinal scarring and vascular ingrowth under the retina, an atypical example of the disease if it is the same disease. As all the descriptions seem to apply to the same disease, any attempt to distinguish be tween serpiginous and geographic cho roiditis is probably artifactual.
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SUMMARY
REFERENCES
Serpiginous and geographic choroiditis, one and the same disease, is charac terized by episodic involvement of the pigment epithelium and choroid. Each new lesion passes through an acute phase into an atrophie and scarring one. We observed 20 patients, some with longterm follow-up; some had eventual wide spread involvement of both posterior poles. There was no basis for the disease, and treatment did not affect its course. In the patients with long-term disease there was widespread atrophy of the choroid and pigment epithelium and variable amounts of pigment clumping and subretinal fibrous tissue deposition. In nine patients discrete peripheral patches of atrophy were also found. In some eyes the atrophy at the posterior pole had be come so confluent that the condition could have been mistaken superficially for a primary choroidal dystrophy. The uninvolved areas appeared to be normal. The electroretinogram and electrooculogram were only affected when ex tensive disease was present.
1. Hamilton, A. M., and Bird, A. C : Geographical choroidopathy. Br. J. Ophthalmol. 58:784, 1974. 2. Schatz, H., Maumenee, A. E., and Patz, A.: Geographic helicoid peripapillary choroidopathy. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:747, 1974. 3. Laatikainen, L., and Erkkila, H.: Serpiginous choroiditis. Br. J. Ophthalmol. 58:777, 1974. 4. Krill, A. E., and Archer, D.: Classification of the choroidal atrophies. Am. J. Ophthalmol. 72:562, 1971. 5. Gass, J. D. M.: Stereoscopic Atlas of Macular Disease. A Funduscopic and Angiographie Presen tation. St. Louis, C. V. Mosby, 1970, pp. 66 and 67. 6. Hyvarinen, L., Maumenee, A. E., George, T., and Weinstein, G. E.: Fluorescein angiography of the choriocapillaris. Am. J. Ophthalmol. 67:653, 1969. 7. Junius, P.: Seltene augenspiegelbilder zum klinischen phanomeh der retinitis exsudativa coats und der retino chorioditis "parapapillaris." Arch. Augenheilkd. 106:475, 1932. 8. Gass, J. D. M.: Acute posterior multifocal placoid pigment epitheliopathy. Arch. Ophthalmol. 80: 177, 1968. 9. Maumenee, A. E.: Clinical entities in uveitis. An approach to the study of intraocular inflamma tion. Trans. Am. Acad. Ophthalmol. Otolaryngol. 74:473, 1970. 10. Franceschetti, A.: A curious affection of the fundus oculi: helicoid peripapillar chorioretinal de generation. Its relation to pigmentary paravenous chorioretinal degeneration. Doc. Ophthalmol. 16:81, 1962.