CHRPE and the Shadow Sign: Distinguishing Retinal Features

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a benign ocular finding that can sometimes be mistaken for more concerning retinal abnormalities. Recognizing its distinct characteristics is essential for accurate diagnosis and management, particularly when differentiating it from malignant lesions or other retinal conditions.

A key aspect of CHRPE evaluation involves identifying patterns and associated signs, such as the shadow sign, which helps distinguish it from similar findings. Understanding these features aids in clinical assessment and has implications for genetic associations and systemic health considerations.

Distinguishing Features

CHRPE appears as a well-defined, flat, pigmented lesion in the retina, typically dark gray to black with sharp borders. These lesions result from hypertrophy of the retinal pigment epithelium (RPE), leading to increased melanin density. Unlike choroidal nevi, which may have a mottled appearance and indistinct margins, CHRPE lesions maintain uniform pigmentation and are often surrounded by a depigmented halo due to atrophic changes in adjacent RPE cells.

Lesion size varies, with diameters ranging from a few hundred micrometers to several millimeters. Larger lesions may have irregular, scalloped edges. Over time, some develop lacunae—small depigmented areas caused by progressive RPE atrophy—distinguishing them from melanomas, which typically lack such internal depigmentation.

Another key characteristic is stability. Unlike malignant melanocytic lesions, which may grow or develop elevated components, CHRPE remains flat and unchanged over time. Optical coherence tomography (OCT) imaging confirms this distinction by revealing a hyperreflective RPE layer without choroidal disruption, a feature absent in neoplastic conditions.

Subtypes

CHRPE manifests in different forms, categorized by number, distribution, and morphology. Recognizing these subtypes aids in distinguishing CHRPE from other retinal lesions and understanding their clinical implications.

Solitary

A solitary CHRPE lesion appears as a single, well-demarcated pigmented spot, often in the mid-peripheral or peripheral fundus. These lesions are typically round or oval, with diameters ranging from a few millimeters to over a centimeter. Pigmentation is uniform, though some develop lacunae over time.

Solitary CHRPE is usually an incidental finding and does not affect vision unless near the macula. Unlike choroidal nevi, which may exhibit drusen or subretinal fluid, solitary CHRPE remains stable without secondary changes. OCT imaging shows a hyperreflective RPE layer with no choroidal disruption, further distinguishing it from neoplastic conditions. Given its benign nature, solitary CHRPE requires no treatment, though periodic monitoring may be recommended.

Grouped

Grouped CHRPE, or “bear tracks,” consists of multiple small, round pigmented lesions clustered in one retinal region. These lesions, generally smaller than solitary CHRPE, often measure less than a millimeter in diameter and appear in a linear or arcuate pattern.

Grouped CHRPE may be associated with systemic conditions, though most cases remain benign. The lesions share the well-defined borders and uniform pigmentation of solitary CHRPE, with occasional lacunae. Their clustered arrangement differentiates them from other pigmented retinal abnormalities, such as choroidal nevi or melanocytomas.

Fundoscopic examination and OCT imaging confirm their benign nature. These lesions remain stable and require no intervention, though their presence should prompt a thorough ocular examination to rule out systemic associations.

Multifocal

Multifocal CHRPE consists of multiple lesions scattered across different retinal regions, often affecting both eyes. These lesions vary in size and shape, with some appearing as small, round spots and others having irregular contours. Multifocal CHRPE is particularly notable for its association with familial adenomatous polyposis (FAP), an inherited condition linked to colorectal cancer.

Patients with FAP may develop bilateral, asymmetrical CHRPE lesions that differ from benign solitary or grouped forms. These lesions tend to be more numerous and irregular, sometimes exhibiting a fish-tail or comet-like shape. Unlike isolated CHRPE, which remains a localized retinal finding, multifocal CHRPE in FAP serves as an ophthalmic marker for an underlying genetic condition.

Ophthalmologists play a role in identifying these lesions and referring patients for genetic counseling if FAP is suspected. While CHRPE itself does not require treatment, its presence in a multifocal pattern warrants systemic evaluation.

The Shadow Sign

A key feature distinguishing CHRPE from other pigmented retinal abnormalities is the shadow sign, observed during ophthalmoscopic examination. This phenomenon occurs due to CHRPE’s interaction with light in imaging modalities like OCT and fundus photography. Unlike choroidal nevi or melanomas, which allow some light penetration due to their deeper location, CHRPE lesions are confined to the RPE, creating a stark contrast.

This shadowing effect is particularly evident in OCT scans, where CHRPE appears as a hyperreflective lesion with distinct light blockage beneath it. The underlying choroidal structures remain obscured due to the pigment density, a characteristic not typically seen in neoplastic lesions. In contrast, choroidal melanoma often presents with subretinal fluid or structural disruption, features absent in CHRPE.

Beyond OCT, the shadow sign is also visible in fundus autofluorescence (FAF), where CHRPE lesions appear hypoautofluorescent due to high melanin concentration. This further contributes to the shadowing effect, reinforcing the lesion’s superficial localization. In cases where differentiation remains challenging, fluorescein angiography (FA) can provide additional confirmation. CHRPE typically exhibits minimal to no fluorescein leakage, whereas neoplastic lesions often show hyperfluorescence due to vascular abnormalities.

Potential Genetic Links

While isolated CHRPE is usually a benign congenital finding, its presence in specific patterns has been linked to inherited syndromes. Familial adenomatous polyposis (FAP), an autosomal dominant disorder caused by APC gene mutations, is one of the most well-documented conditions associated with CHRPE. Studies show that individuals with FAP often develop bilateral, multifocal CHRPE lesions, sometimes with fish-tail or comet-like shapes. These retinal findings can precede colorectal polyps, making ophthalmologic screening a potential early indicator for at-risk individuals.

Genetic analysis has revealed that CHRPE lesions in FAP arise from somatic APC gene mutations in the RPE. Unlike sporadic CHRPE, which remains isolated to a single lesion, FAP-related CHRPE follows a widespread distribution, affecting both eyes asymmetrically. The presence of these multifocal lesions in young individuals has been proposed as a screening criterion for those with a family history of FAP, prompting genetic counseling and early intervention. Although CHRPE itself does not progress to malignancy, its association with an inherited cancer predisposition syndrome underscores its diagnostic significance.

Diagnostic Approaches

Identifying CHRPE relies on clinical examination and advanced imaging. Fundoscopic evaluation remains the first step, as the lesion’s pigmentation, well-defined borders, and potential lacunae provide strong diagnostic clues. Indirect ophthalmoscopy allows for detailed assessment, while slit-lamp biomicroscopy with a fundus lens provides higher magnification for closer inspection. Distinguishing CHRPE from choroidal nevi or malignant melanocytic lesions is a key focus.

Optical coherence tomography (OCT) enhances diagnostic accuracy by revealing structural details. A hallmark OCT feature of CHRPE is an intact, hyperreflective RPE layer with no choroidal disruption, contrasting with choroidal nevi, which often exhibit mild elevation and variable reflectivity. Fundus autofluorescence (FAF) further aids differentiation, as CHRPE appears hypoautofluorescent due to melanin absorption, whereas neoplastic lesions may show hyperautofluorescence. In ambiguous cases, fluorescein angiography (FA) provides confirmation, as CHRPE exhibits fluorescence masking without leakage, unlike malignant tumors with vascular abnormalities.

These imaging modalities allow clinicians to confidently distinguish CHRPE from other retinal lesions, ensuring appropriate management and follow-up strategies.