High-Resolution Optical Coherence Tomography Correlates of Peau d'Orange in Pseudoxanthoma Elasticum.

Abstract

Pseudoxanthoma elasticum (PXE) is a rare inherited disorder marked by progressive calcification of Bruch membrane (BrM). Characteristic retinal features, such as peau d'orange and continuously calcified BrM (also called coquille d'œuf), reflect disease severity but lack reliable in vivo cross-sectional imaging correlates. To identify high-resolution optical coherence tomography (HR-OCT) correlates of peau d'orange and continuously calcified BrM in patients with PXE. This prospective case-control study was conducted at the Department of Ophthalmology, University Hospital, Bonn, Germany. HR-OCT imaging was performed in 37 eyes from 22 patients with PXE and 28 eyes from 16 healthy control participants between November 2024 and March 2025. These data were analyzed March 2025 to May 2025. Diagnosis of PXE based on clinical and genetic criteria. Healthy eyes served as controls. HR-OCT (axial resolution up to 3 μm) was measured in all study eyes. Identification of structural alterations in the retinal pigment epithelium (RPE)/BrM complex on HR-OCT that corresponded to peau d'orange or continuous BrM calcification visible on fundus photography and infrared imaging. A total of 42 eyes from 22 patients with PXE (mean age, 50.2 [SD, 13.6] years; range 25.4-77.9 years; 13 female and 9 male) and 28 healthy eyes from 16 control study participants (mean age, 56.4 [SD, 16.8] years; range 23.5-78.6 years; 11 female and 5 male) were examined. HR-OCT imaging revealed a consistent structural transition within peau d'orange zones: from a multilayered RPE/BrM complex, including distinct outer segment interdigitation zone and RPE bands, in unaffected retina to a condensed, hyperreflective monolayer overlying BrM, with hyporeflective separation. In more advanced disease, additional changes included BrM breaks, irregular RPE morphology, reticular pseudodrusen, and serous neurosensory retinal detachment in the absence of macular neovascularization. These features were absent in control eyes (0 of 28). In eyes with type 1 macular neovascularization, layer splitting confirmed anatomical identification of the RPE and BrM. Angioid streaks on fundus imaging corresponded to focal BrM disruptions on HR-OCT. This study demonstrated that HR-OCT can identify distinct in vivo correlates of Bruch membrane calcification in PXE. The observed transition from multilayered to monolayer RPE/BrM architecture with accompanying hyporeflective separation may serve as a sensitive imaging biomarker of disease progression in future clinical trials. These findings support HR-OCT as a valuable tool for diagnosis, monitoring, and clinical trial end point development in PXE.