Case ReportsCongenital hypertrophy of the retinal pigment epithelium complicatedby a choroidal neovascular membranePavlina Youhnovska, MD,

a Daniela Toffoli, MD,

b and Danny Gauthier, MDa

Author affiliations: aRetina Service, Ophthalmology Department, CHUM Hôpital Notre-Dame, Montreal, Quebec, Canada;bEmory Eye Center, Pediatric Ophthalmology Department, Atlanta Georgia

SummaryA 66-year-old woman presenting with a history of visual loss in her left eye was diagnosed with congenitalhypertrophy of the retinal pigment epithelium accompanied by a choroidal neovascular membrane(CNVM) affecting the macula. Visual acuity improved after 2 treatments of verteporfin photodynamic ther-apy. Recurrent CNVM in the same eye 3 years later was stabilized and vision slowly improved with a ser-ies of intravitreal bevacizumab injections.

IntroductionCongenital hypertrophy of the retinal pigment epithe-lium (CHRPE) is a benign clinical entity characterizedby round, flat, dark gray or dark brown plaques, whichare primarily found in the retinal mid-periphery but mayalso occur in more anterior locations or in the posteriorpole, including the macula.1,2 CHRPE lesions typicallyhave well-defined, scalloped edges and contain centrallacunae that appear “punched-out” in the retina. Addi-tionally, they often have a hypopigmented “halo” liningthe outer margins of the lesion. CHRPE typicallypresents as a solitary lesion; however, forms containingmultiple small lesions have been reported.3

CHRPE typically shows little progression, but long-termfollow-up studies have shown that the lesions occasion-ally grow slowly. Fluorescein angiography often revealsretinal vascular changes, including attenuation of the ret-inal capillary bed and the presence ofmicroaneurysms.2,4

Case ReportA 66-year-old woman presented to CHUM HôpitalNotre-Dame, Montréal (PQ), Canada, in July 2005 witha 3-month history of decreased visual acuity and a cen-tral “dark spot” in her left eye. She denied other ocularsymptoms, including metamorphopsia or micropsia. She

had no other systemic complaints and was in good gen-eral health. On ophthalmological examination, visualacuity was 20/30 in the right eye and 20/80 in the lefteye. Slit-lamp biomicroscopy was significant only formild bilateral cataracts. Examination of the right funduswas unremarkable (Figure 1A). There were no drusen orretinal pigment epithelium (RPE) changes compatiblewith age-related macular degeneration (ARMD). Exami-nation of the left fundus revealed a dark brown plaque,1.5 disc diameters in size, confined to the superotempo-ral vascular arcade. The plaque was fragmented and con-tained central atrophic spaces and lacunae. Three similarbut smaller lesions were observed adjacent to this pla-que. These lesions had smooth, well-defined marginsand were associated with atrophic changes. An area ofextrafoveal thickening, surrounded by a ring of lipidexudates and two small hemorrhages within the fovealavascular zone were noted. These latter findingsappeared compatible with the presence of a CNVM. Nosigns of ARMD were observed on left fundus examina-tion (Figure 1B).

On fluorescein angiography, the right fundus was nor-mal (Figure 2A). In the left eye, the pigmented lesionscreated a masking effect, corresponding to regions ofhypofluorescence, whereas window defects were seen atthe sites of atrophic changes. An area of extrafoveal

Published May 1, 2013.Copyright ©2013. All rights reserved. Reproduction in whole or in part in any form or medium without expressed written permission of theDigital Journal of Ophthalmology is prohibited.doi:10.5693/djo.02.2013.01.004Correspondence: Danny Gauthier MD, Retina Service, Ophthalmology Department, Hôpital Notre-Dame, 1560 Sherbrooke Street Est, Montreal,Quebec H2L 4M1 Canada (email: gaudan@sympatico.ca).

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hyperfluorescence was noted, arising immediately adja-cent to one of the edges of a satellite lesion. Progressivecapillary leakage was observed during the late phase offluorescein transit, consistent with a classic CNVM(Figure 2B–C).

The patient was diagnosed with CHRPE complicated bya CNVM and treated with verteporfin photodynamictherapy (PDT). Standard parameters for fluence and irra-diance were used for a total treatment time of 83 sec-onds. Following treatment, functional improvement wasnoted, with a visual acuity of 20/40 in the left eye at 6months’ follow-up. There was no leakage of fluoresceinnoted on angiography after treatment, consistent withfull regression of the CNVM (Figure 3). Clinical exami-nation performed following two PDT treatments 3months apart demonstrated a favorable response to thetherapy with resolution of subretinal fluid and lipid exu-dates. The patient required no further treatment duringthe 2-year follow-up period.

Two years after completing treatment, she presentedwith a new episode of decreased vision in the same eye.On ophthalmological examination, visual acuity was20/200 in the left eye. The fundus examination and thefluorescein angiography confirmed a recurrence of themacular CNVM. The patient was treated with intravi-treal bevacizumab 1.25mg/0.05ml. Following 5 consec-utive monthly injections, visual acuity stabilized at20/60 and no CNV activity was noted at last follow-up,2 years after her final injection.

DiscussionWe describe a patient with macular CHRPE associatedwith a CNVM. The membrane was treated with verte-porfin PDT and bevacizumab intravitreal injections. Toour knowledge, there is only one previous case ofCHRPE associated with neovascularization in the litera-ture,5 and this is the first report of CHRPE complicatedby a CNVM in the macular area.

Retinal vascular changes, as documented by fluoresceinangiography, may represent a sign of the CHRPE’s evo-lution in time. In a series of 12 patients, Cohen et al4reported vascular abnormalities in 91% of 12 cases andsuggested that the associated angiographic findingsshould be regarded as typical of the condition. Vascularchanges commonly observed include an attenuatedcapillary bed, microaneurysms, and chorioretinal anasto-moses. It has been proposed that capillary abnormalitiesoccur as a result of increased oxygen concentration inthe inner retina. Abnormal fluorescein leakage has onlybeen reported in 2 cases of CHRPE and in only 1 of thecases was fluorescein leakage noted at the margin of thelesion, increasing the suspicion of a CNVM.5

The precise etiology of the vascular changes noted inCHRPE have yet to be elucidated. Histological studiesof CHRPE lesions demonstrate an abnormal RPE, withan increase in the height of individual cells and anincrease in overall RPE cell density. Additionally, RPE

Figure 1. A, Color fundus photograph of the normal right eye. B, Color fundus photograph of the left eye showing a flat bi-fragmentedpigmented dark brown plaque and 3 smaller, similar adjacent lesions consistent with congenital hypertrophy of the retinal pigment epithelium(CHRPE). Lacunae are present within the plaque and retinal thickening with a ring of lipid exudates and 2 small hemorrhages are seen in themacular area.

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cells in CHRPE lesions contain multiple granules and show an increase in pigment density compared to theirnormal counterparts. Photoreceptors overlying theabnormal RPE are also noted to undergo degeneration, aprocess that may lead to a relative or absolute scotoma.Although RPE cells adjacent to the CHRPE lesion mayinitially appear to be normal, they may also undergochange. Unlike the increase in height of the RPE cells

seen within the CHRPE plaque, however, they tend tobroaden and flatten out. Some authors believe that theseflatter RPE cells may induce pressure on the hypertro-phic RPE cells present within the CHRPE lesion, creat-ing areas of micro-trauma at the junction between thetwo.2 Breaks in the RPE associated with these areas ofmicro-trauma may be associated with RPE cell migra-tion into the inner retina and may allow the subretinal

Figure 2. A, Fluorescein angiogram of the normal right eye at 6 minutes, 5seconds. B, Fluorescein angiogram of the left eye at 30.8 seconds. TheCHRPE lesions show blockage hypofluorescence. The atrophy at the lesion’smargins gives rise to an RPE window defect. Early hyperfluorescence adja-cent to the CHRPE plaque is seen in the juxtafoveal area. C, Fluoresceinangiogram at 7 minutes, 6 seconds. The dye transit progresses to a late retinalleakage consistent with a choroidal neovascular membrane. The lacunae showan RPE window defect within the CHRPE hypofluorescent plaques.

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fibrovascular growth associated with neovascular mem-branes. This may provide a possible explanation forCNV proliferation found at the junction of CHRPElesions and adjacent normal tissue.

In our case, the lesion was fragmented and associatedwith three satellite lesions, which may have resultedfrom breaks in the RPE and possibly Bruch’s membraneand subsequent migration of hypertrophic epithelialcells. This contrasts with the behavior of a typicalCHRPE plaque, where migration of RPE cells results inenlargement of atrophic lacunae with subsequent con-centric enlargement of the lesion. Other typical progres-sive CHRPE lesions include plaques with poorly pig-mented linear streaks. Chamot et al2 suggested that thesame mechanism could be a possible explanation for thenatural history of both forms.

When CHRPE presents with multiple lesions, it must bedifferentiated from the multifocal epithelial hypertrophy

Figure 3. Late frame of the control fluorescein angiogram afterverteporfin photodynamic therapy at 5 minutes, 46 seconds, show-ing an area of hyperfluorescence arising at the edge of the CHRPElesion with absence of late leakage.

associated with Gardner’s syndrome. The latter pathol-ogy presents with multiple, bilateral, variably pigmentedretinal lesions and is associated with familial adenoidalpolyposis. Any suspicion of Gardner’s syndromerequires further systemic work-up, including colono-scopy. Also to be included in the differential diagnosisof CHRPE is the congenital grouped hypertrophy of theRPE. This pathology typically presents with numerouspigmented retinal spots resembling “bear tracks” and isnot associated with vascular abnormalities on fluores-cein angiography. In some cases, it can be found along-side a typical solitary CHRPE.4 Finally, the angio-graphic and ultrasound characteristics of a choroidalmelanoma make it easy to differentiate from solitaryforms of CHRPE.

CHRPE is a clinical diagnosis. The lesion is usuallyasymptomatic and is found incidentally on routine oph-thalmoscopic examination. Progressive changes are nowconsidered to be a part of the natural history of CHRPE;the evolution is not a sign of malignancy since the lesionremains benign. Fluorescein angiography should be per-formed to reveal the presence of associated retinal vas-cular abnormalities, especially if a CNVM is suspected.CNVMs, particularly in the macular area, are anextremely rare complication of CHRPE. However, as inour case, CNV can be a vision-threatening condition andshould be identified and managed rapidly.

References1. Nishikatsu H, Shiono T. Congenital hypertrophy of the retinal pig-

ment epithelium in the macula. Ophthalmologica 1996;210:126-8.2. Chamot L, Zografos L, Klainguti G. Fundus changes associated

with congenital hypertrophy of the retinal pigment epithelium. Am JOphthalmol 1993;115:154-61.

3. Buettner H. Congenital hypertrophy of the retinal pigment epithe-lium. Am J Ophthalmol 1975;79:177-89.

4. Cohen SY, Quentel G, Guiberteau B, Coscas GJ. Retinal vascularchanges in congenital hypertrophy of the retinal pigment epithelium.Ophthalmology 1993;100:471-4.

5. Cleary PE, Gregor Z, Bird AC. Retinal vascular changes in congeni-tal hypertrophy of the retinal pigment epithelium. Br J Ophthalmol1976;60:499-503.

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