Unilateral Retinal Pigment Epithelium Dysgenesis-The Expanded Spectrum and New Insights From Multimodal Imaging.

PURPOSE: To describe the clinical spectrum, novel imaging features, and associations of unilateral retinal pigment epithelium dysgenesis (URPED), expanding its phenotypic and pathogenetic framework.

DESIGN

Retrospective, longitudinal, multicenter case series.

SUBJECTS: Ten eyes of ten patients with URPED and two eyes with combined hamartoma of the retina and retinal pigment epithelium (RPE) exhibiting URPED-like changes, examined between 2011 and 2025 at Luigi Sacco Hospital (Milan, Italy) and Macquarie University Hospital (Sydney, Australia).

METHODS

Comprehensive multimodal imaging was performed, including color fundus photography, near-infrared reflectance, short-wavelength fundus autofluorescence (SW-FAF), fluorescein and indocyanine green angiography (FA/ICGA), and spectral-domain optical coherence tomography (SD-OCT). Lesions were classified as overt, when diagnosis was achievable on noninvasive imaging alone, or covert, when ICGA was required. Near-infrared reflectance, SW-FAF, FA, and ICGA patterns were correlated with structural OCT findings. Lesion area was manually measured at baseline on SW-FAF and ICGA, and at last follow-up on SW-FAF.

MAIN OUTCOME MEASURES: URPED phenotypic patterns; multimodal imaging characteristics; frequency of associated hamartomatous lesions and other complications.

RESULTS

Seven eyes (70%) were classified as overt URPED, displaying scalloped (n = 4), mottled (n = 1), or mixed (n = 2) SW-FAF patterns; three eyes (30%) were categorized as covert URPED, detectable only on ICGA. The classic inverted SW-FAF/FA pattern occurred exclusively in overt scalloped or mixed lesions. SD-OCT consistently demonstrated Bruch membrane-RPE separation with overlying "sawtooth" changes (10/10, 100%). Evidence of iRORA/cRORA was present in six eyes (60%), and choroidal caverns in six eyes (60%). Hamartomatous lesions were identified in four eyes (40%), three retinal capillary hemangiomas, and one choroidal osteoma; all topographically colocalizing with URPED. Choroidal neovascularization developed in four eyes (40%), all responding favorably to anti-VEGF therapy. Lesion size remained largely stable over a median follow-up of 27.5 months, with excellent intergrader reproducibility (intraclass correlation coefficient = 0.98-0.99).

CONCLUSIONS

URPED encompasses a broader phenotypic continuum than previously recognized, ranging from overt to covert forms unified by Bruch membrane-RPE dysgenesis. The frequent coexistence with hamartomatous lesions supports a shared developmental origin. Multimodal imaging is essential for diagnosis and phenotypic classification, with ICGA playing a pivotal role in detecting covert forms.