Congenital hypertrophy of the retinal pigment epithelium (CHRPE) usually presents as a stationary, flat, pigmented, unifocal lesion of the retinal pigment epithelium (RPE), located in the fundus midperiphery.1,2 Typically, smaller lesions are uniformly pigmented, whereas larger lesions contain pigmented areas with punched out hypopigmented lacunae.3 Commonly, lesions are surrounded by a double outline comprising an inner depigmented halo with an outer pigmented rim.3
CHRPE is considered to be a stable lesion, often present at birth.4 However, clinical studies have documented enlargement of this lesion in 74% to 83% cases with gradual enlargement of lacunae in 32% to 83% cases.2,3 We present a case of asymptomatic CHRPE with photographic documentation of gradual increase in size, deepening of color, and development of halo and lacunae over 22 years of follow-up.
A 2-year-old girl was found to have retinoblastoma in the right eye. On examination, visual acuity was no fix or follow in the right eye and fix and follow in the left eye. The right eye manifested 40 prism diopters of esotropia, leukocoria, iris neovascularization, and a large endophytic retinoblastoma with diffuse vitreous seeding, classified as group D. This eye was treated with enucleation. The left eye showed an inferonasal pinpoint RPE clump less than 0.5 mm diameter and classified as small CHRPE. This was documented clinically, but fundus photographs were not done.
When the patient was 12 years old, the CHRPE had enlarged to 2 mm diameter and a pigmented halo and lacunae had developed (Figure 1A). When the patient was 18 years old, the lesion measured 4 mm diameter and demonstrated both pigmented and nonpigmented halo, with darkening in central pigment (Figure 1B). When the patient was 24 years old, slight enlargement of the CHRPE to 4.25 mm in diameter and slight alteration in pigmentation was noted. Fundus autofluorescence showed marked hypofluorescence of the pigmented lesion and normofluorescence of the depigmented halo, consistent with CHRPE (Figures 1C–1D).
Figure 1. Evolution of congenital hypertrophy of the retinal pigment epithelium over 22 years. The lesion was noted when the patient was 2 years old as a tiny retinal pigment epithelium clump. (A) When the patient was 12 years old, the lesion was larger at 2 mm diameter and had pigmented halo. (B) When the patient was 18 years old, the lesion increased to 4 mm diameter and had slight darkening of color and noticeable peripheral depigmented and pigmented halo. (C) When the patient was 24 years old, a slight increase in base to 4.25 mm with more definitive halo was noted. (D) Fundus autofluorescence at age 24 years revealed intense hypofluoresence of the pigmented area and normofluorescence in the lacunae.
In 1975, Buettner reported progression of lacunae within CHRPE.5 In 1976, Norris et al. documented concentric enlargement of CHRPE.6 A subsequent study of 35 patients by Chamot et al. disclosed flat enlargement of CHRPE in 74%, with enlargement of lacunae in 83%.3 In that series, a marginal halo was present in 77%.3 In a series of 330 cases, Shields et al. reported enlargement of CHRPE in 83% and enlargement of lacunae in 32%.2 The median rate of enlargement was slow at 2 μm/mm basal dimension per month.2 Rarely, growth of CHRPE into nodular adenoma or adenocarcinoma has been documented in a few cases.7,8
The mechanism of CHRPE enlargement is not clear. Wirz et al. hypothesized that three groups of cells comprise a CHRPE lesion (hypertrophic, hyperplastic, and atrophic cells), with the ability to proliferate.9 The rim can represent a transition zone of expansion because histopathological reports have shown a mix between normal and CHRPE cellular features at this zone.9 Lloyd et al. believed enlargement was due to loss of contact inhibition.10 Chamot et al. postulated that the taller than normal RPE cells of CHRPE lack the ability to flatten out during the RPE aging process and compensate for the atrophied surrounding RPE, leading to “microlesions” and eventual lacunae.3
On histopathological examination of the hyperpigmented areas of CHRPE, a monolayer of hypertrophic RPE cells has been documented.5,10 Later investigations disclosed multiple layers of hypertrophic RPE in the hyperpigmented regions.9 Regardless, such reports have documented that the RPE cells vary in size from cuboidal to columnar, are packed with melanosomes, and end abruptly at the margin of the lesion and transition to normal RPE.5,9,10 In addition, within the CHRPE lesion, the RPE cells are 1.5 to 2 times denser than the normal surrounding RPE cells.10 In contrast, lacunae are completely devoid of RPE, with retina fused to Bruch’s membrane.9,10
Optical coherence tomography has been revealing in disclosing a lack of photoreceptors over the entire CHRPE lesion.11 Shields et al. found that the retina overlying CHRPE was 68% of normal thickness and the CHRPE lesion was 52% thicker than normal RPE.11 Electron microscopy confirms loss of outer photoreceptor segments in the overlying retina.9–11 The degree of retinal degeneration is more advanced in older patients, indicating progressive damage.11
Autofluorescence demonstrates intense hypoautofluorescence of pigmented CHRPE, with hypopigmented lacunae showing normofluorescence or slight hyperautofluorescence, as seen in our case.12 The intense hypoautofluorescence reflects the lack of lipofuscin from inability of the RPE cells to phagocytize outer segments of the photoreceptors.10 The lacunar autofluorescence is due to unmasking of underlying scleral fluorescence.12
We document a case of CHRPE that slowly evolved over 22 years. There was increase in diameter, deepening of color, and progression in the surrounding depigmented halo.
- Shields JA, Shields CL. Tumors and related lesions of the pigment epithelium. In: Shields JA, Shields CL. Atlas of Intraocular Tumors, 2nd ed. Philadelphia: Lippincott, Williams & Wilkins; 1998:287–288.
- Shields CL, Mashayekhi A, Ho T, et al. Solitary congenital hypertrophy of the retinal pigment epithelium: clinical features and frequency of enlargement in 330 patients. Ophthalmology. 2003;110:1968–1976. doi:10.1016/S0161-6420(03)00618-3 [CrossRef]
- Chamot L, Zografos L, Klainguti G. Fundus changes associated with congenital hypertrophy of the retinal pigment epithelium. Am J Ophthalmol. 1993;115:154–161.
- Champion R, Daicker BC. Congenital hypertrophy of the retinal pigment epithelium: microscopic and ultrasound findings in young children. Retina. 1989;9:44–48. doi:10.1097/00006982-198909010-00006 [CrossRef]
- Buettner H. Congenital hypertrophy of the retinal pigment epithelium. Am J Ophthalmol. 1975;79:177–189.
- Norris JL, Cleasby GW. An unusual case of congenital hypertrophy of the retinal pigment epithelium. Arch Ophthalmol. 1982;94:1910–1911. doi:10.1001/archopht.1976.03910040620008 [CrossRef]
- Shields JA, Eagle RC Jr, Shields CL, et al. Malignant transformation of congenital hypertrophy of the retinal pigment epithelium. Ophthalmology. 2009; 2213–2216. doi:10.1016/j.ophtha.2009.04.048 [CrossRef]
- Shields JA, Shields CL, Singh AD. Acquired tumors arising from congenital hypertrophy of the retinal pigment epithelium. Arch Ophthalmol. 2000;118:637–641. doi:10.1001/archopht.118.5.637 [CrossRef]
- Wirz K, Lee WR, Coaker T. Progressive changes in congenital hypertrophy of the retinal pigment epithelium. Graefes Arch Clin Exp Ophthalmol. 1982;219:214–221. doi:10.1007/BF00231238 [CrossRef]
- Lloyd WC, Eagle RC Jr, Shields JA, et al. Congenital hypertrophy of the retinal pigment epithelium: electron microscopic and morphometric observations. Ophthalmology. 1990;97:1052–1060.
- Shields CL, Materin MA, Walker C, et al. Photoreceptor loss overlying congenital hypertrophy of the retinal pigment epithelium. Ophthalmology. 2006;113;661–665. doi:10.1016/j.ophtha.2005.10.057 [CrossRef]
- Shields CL, Pirondini C, Bianciotto C, et al. Autofluorescence of congenital hypertrophy of the retinal pigment epithelium. Retina. 2007;27:1097–1100. doi:10.1097/IAE.0b013e318133a174 [CrossRef]