Retinal Vascular Changes in Congenital Hypertrophy of the Retinal Pigment Epithelium Salomon Y. Cohen, MD, Gabriel Quentel, MD, Brigitte Guiberteau, MD, Gabriel]. Coscas, MD Background: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a well-defined clinical entity with usually well-delineated, pigmented oval or round lesion with smooth or scalloped margins. Occasional retinal vascular changes have been reported previously. Purpose and Method: To assess the prevalence of these changes, the authors performed a retrospective analysis of 12 patients with CHRPE, for whom fluorescein angiography allowed visualization of the entire lesion and of the retinal vascular capillary bed. Results: Retinal vascular changes were found in 11 (91 %) of these 12 patients. The changes consisted of capillary rarefaction in all 11 patients, with areas of capillary non perfusion exceeding 1 disc diameter (~O) in three patients (25%), microaneurysmal capillary dilatations in three (25%), and chorioretinal anastomosis in one. Conclusion: These results suggest that the above changes could constitute clinical and angiographic characteristics of CHRPE and allow easy corroboration of its diagnosis, thus avoiding the need for further clinical investigations. Ophthalmology 1993;100:471-474
Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a well-defined clinical entity that usually appears in the form of a well-delineated, gray-brown to black, oval or round lesion with smooth or scalloped margins. 1.2 A halo of depigmentation often is seen just inside the outer edge of the lesion. Hypopigmented or depigmented lacunae may be present, particularly in older patients. The lesion is usually nonevolutive, but may exhibit discrete enlargement. 3,4 Retinal vascular changes, as shown by fluorescein angiography, have been reported to include areas of capillary nonperfusion, capillary microaneurysms, dye leakage, and chorioretinal anastomosis,5,6 but previously were only thought to occur occasionally.2 To assess their prevalence, we performed a retrospective analysis of the angiographic findings for CHRPE in our patients. Originally received: July 31, 1992. Revision accepted: November 19, 1992. From the Department of Ophthalmology, University of Paris XII, Creteil, France. Presented in part to the Paris Society of Ophthalmology, June 15, 1991 . Reprint requests to Gabriel J. Coscas, MD, Clinique OphtaImologique Universitaire, 40 Avenue de Verdun, F-940JO Creteil, France.
Patients and Methods Clinical and fluorescein angiographic charts for all the CHRPE patients examined from 1981 to 1990 at the Clinique Ophtalmologique Universitaire de Creteil were reviewed for a retrospective analysis. Clinical data regarding sex, age at diagnosis, and the involved eye were noted. Patients were included if fluorescein angiograms allowed visualization of the entire CHRPE lesion and of the retinal capillary bed. Angiographic pictures were analyzed by two independent observers in a search for capillary rarefaction and capillary nonperfusion areas, capillary microaneurysms, dye leakage, and chorioretinal anastomosis.
Results Congenital hypertrophy of the retinal pigment epithelium was diagnosed in 24 patients (20 females and 4 males) ranging in age from 17 to 79 years (mean, 40.6 years). The lesion was asymptomatic in all patients, and was discovered during routine fundus examination. There was
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no mention of retinal vascular changes in the clinical charts. In most cases, patients were referred to our department for suspected choroidal melanoma. fluorescein angiography was performed to eliminate this diagnosis. The right eye was involved in 13 patients and the left eye in 11. The lesion was always unilateral and solitary. The angiograms for 12 patients (50%) met the inclusion criteria. These patients comprised ten women and two men ranging in age from 22 to 49 years (mean, 34.7 years). The solitary lesion was located in the midperiphery in nine patients (75%) and at the posterior pole in three (25%), but never in the macular area. The size of the lesion varied: 1 disc diameter (~O) or less in five patients, 2 DD in one patient, 3 DO in four patients, and 4 DO or more in two patients. Retinal vascular changes were observed in the eyes of 11 patients (91 %), all of whom exhibited rarefaction of the retinal capillary bed. A capillary nonperfusion area greater than 1 DD was present in the eyes of three patients (25%). These anomalies were frequently observed in the
center of the pigmented lesions (Figs 1 and 2). Analysis of the retinal capillary bed disclosed capillary microaneurysms in the eyes of three patients (25%). Chorioretinal anastomosis was present in one eye (Fig 1). No fluorescein leakage was found.
Discussion Congenital hypertrophy of the retinal pigment epithelium is a benign and usually nonevolutive lesion. Nevertheless, cases of slight lesion enlargement have occasionally been reported. 3,4 Congenital hypertrophy of the retinal pigment epithelium lesions are usually asymptomatic and are diagnosed during routine fundus examination. They have been found at all ages and in both sexes. To our knowledge, however, the preponderantly female sex ratio of 4: 1, found in our study, has never been reported. The clinical features of CHRPE lesions are the following: they are well-delineated, round or oval, and gray-
Figure 1. Large lesion caused by congenital hypertrophy of the retinal pigment epithelium in a 32-year-old woman. A, red-free picture. Inhomogeneous pigmentation and scalloped margins. A whitish line is visible just inside the outer edge of the lesion. B, the arterial phase of the fluorescein angiography shows a central chorioretinal anastomosis (arrow). C, the arteriovenous phase of the fluorescein angiography shows (I) capillary rarefaction at the center of the lesion with a capillary nonperfusion area greater than 1 disc diameter, and (2) capillary microaneurysms (arrows).
Cohen et al . Retinal Vascular Changes in CHRPE
Figure 2. Lesion caused by CHRPE in a 40-year-old woman. The early arteriovenous phase of the fluorescein angiogram shows (1) central capillary rarefaction with a large area of capillary nonperfusion, and (2) capillary microaneurysms at the periphery of the lesion (arrows).
brown to black. A hypopigmented margin is frequently present inside the outer margin of the lesion, usually varying in size from 1 to 3 DD, but may be as large as one quadrant of the fundus. Hypopigmented lacunae are frequently observed, particularly in older patientsP Congenital hypertrophy of the retinal pigment epithelium may manifest itself as a solitary lesion, as in our patients, or be combined with other ocular or systemic anomalies including congenital-grouped pigmentation of the retinal pigment epithelium or "bear-tracks." These tracks comprise numerous pigment spots which are usually small but can vary in size, and may be combined with a typical CHRPE lesion. Their angiographic features are the blockage of choroidal fluorescence without retinal vascular changes. 8 Congenital hypertrophy of the retinal pigment epithelium has been reported to be present with choroidal melanoma, either in the same eye9 or in the opposite eye. 10 It also was observed together with retinitis pigmentosa. II In addition, CHRPE may be combined with Gardner's syndrome or with other forms of familial polyposis.1 2 •J3 When combined with Gardner's syndrome, CHRPE lesions are numerous and their shape differs from that of solitary CHRPE lesions. Moreover, a recent histopathologic study concluded that the fundus lesion was not hypertrophy of the RPE, but a hamartomatous lesion. 14 Results of histologic examination of typical CHRPE showed that the lesion consisted of a single hyperpigmented RPE cell layer. Its cells were larger than normal and the density of their pigment was estimated at 1.7 times the normal. 15 Cell proliferation (hyperplasia) was observed in some cases and may have caused the slight enlargement of some lesions. 15.16 Pigment epithelial cells were full of granules. Because these granules were not auto-fluorescent, their appearance did not suggest lipofuscin storage.
Degeneration of the overlying photoreceptors also was observed. 15 Solitary CHRPE lesions may be mistaken for the hemosiderin peripheral deposits observed in certain patients with sickle cell disease,17 or for choroidal melanomas. Although the echographic and angiographic features of melanomas are quite different, enucleations in the past have been performed to distinguish benign from malignant lesions. 18 Congenital hypertrophy of the retinal pigment epithelium lesions also may be mistaken for other benign conditions, such as choroidal melanocytic nevi or congenital hyperplasia of the retinal pigment epithelium. The angiographic features of these conditions do not include retinal vascular changes. 19.20 In CHRPE, retinal vascular changes were reported by Cleary et al 5 in five patients. Nonperfused areas were observed in three of these patients, and abnormal fluorescein leakage in two. One of these patients also presented with retino-choroidal anastomosis and a similar case of such anastomosis was reported in another study.6 However, careful analysis of the angiographic features of the current 12 patients disclosed a very high prevalence of these changes, because they were present in 11 (91 %) of 12 patients. The most frequent were capillary rarefaction, observed in all 11 patients, and microaneurysmal capillary ectasias, observed in 3 patients (25%). As capillary rarefaction was localized in one part of the lesion, the capillary network could be analyzed in the other part of the lesion. Consequently, the absence of capillary visualization detected was the result of localized nonperfusion, and could not be misinterpreted as a blockage secondary to pigment clumping. Retinochoroidal anastomosis only was observed in one patient. When the CHRPE lesion was located at the posterior pole or in its vicinity, the vascular changes were easily identified by fluorescein angiography, which was easier to perform. Certain authors considered these vascular changes secondary to an excessive concentration of oxygen in the inner retina. 5 In the current study, no information was available regarding the course of the vascular changes. They were observed in patients 22 to 49 years of age, and it was not possible to state whether the changes were acquired or congenital. There was no angiographic followup because the evolution of CHRPE is known to be benign. The diagnosis ofCHRPE is clinical. However, in atypical cases, fluorescein angiography may be useful in confirming the diagnosis. The occurrence of retinal vascular changes in 11 of our 12 patients suggests that these changes could be included among the angiographic characteristics of CHRPE, and that their presence might provide easy confirmation of the diagnosis of the disease, thus avoiding the need for additional investigations.
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2. Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment, 3rd ed. Vol. 2. St Louis: CV Mosby, 1987;606-11. 3. Norris JL, Cleasby GW. An unusual case of congenital hypertrophy ofthe retinal pigment epithelium. Arch Ophthalmol 1976;94:1910-1. 4. Boldrey EE, Schwartz A. Enlargement of congenital hypertrophy of the retinal pigment epithelium. Am J Ophthalmol 1982;94:64-6. 5. Cleary PE, Gregor Z, Bird AC. Retinal vascular changes in congenital hypertrophy of the retinal pigment epithelium. Br J Ophthalmol 1976;60:499-503. 6. Zografos L, KJainguti G. Les formes evolutives de l'hypertrophie congenitale de l'epithelium pigmentaire. Bull Mem Soc Fr Ophtalmol 1986;97:274-8. 7. Buettner H. Congenital hypertrophy of the retinal pigment epithelium. In: Ryan SJ, ed. Retina. Vol. 1: Basic Science and Inherited Retinal Disease. St. Louis: CV Mosby, 1989; chap. 34. 8. Morse PH. Fluorescein angiography of grouped pigmentation of the retina. Ann Ophthalmol 1973;5:27-30. 9. Purcell JJ Jr, Shields JA. Hypertrophy with hyperpigmentation ofthe retinal pigment epithelium. Arch Ophthalmol 1975;93: 1122-6. 10. Giuffre G. Sviluppo di melanoma coroideale in soggetto con ipertrofia congenita deH'epitelio pigmentato retinico. Boll OcuI1990;69:111-4. 11. De Laey JJ, Leys A, Van Hyfte R. Retinal pigment hyper-
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