This cross-sectional retrospective study was in adherence to the Declaration of Helsinki. Institutional review board approval (Ethikkommission, Medizinischen Fakultät, Rheinische Friedrich-Wilhelms-Universität Bonn) and patients' consent were obtained. Patients were recruited from a dedicated clinic for rare retinal diseases at the Department of Ophthalmology, University of Bonn, which is a German national referral center for PXE.
Inclusion criteria were the diagnosis of PXE based on genetic testing as described previously,
12,13 histopathologic findings in skin biopsies, and/or presence of characteristic ocular fundus alterations.
14 Out of the 302 eyes of 151 patients fulfilling the inclusion criteria, both eyes of 12 patients and one eye of two patients were excluded from further analysis due to insufficient quality of available fundus images, additional retinal pathologies unrelated to PXE, or prior vitreoretinal surgery. Eyes with previous intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors were not excluded.
All patients underwent a complete ophthalmologic examination including best corrected visual acuity (BCVA), slit lamp examination, indirect ophthalmoscopy with dilated pupils, and a dedicated imaging protocol. The imaging protocol included fundus color images (Zeiss Visucam, Zeiss, Oberkochen, Germany), fundus autofluorescence (AF), and near infrared (NIR) reflectance images with a confocal scanning laser ophthalmoscope (cSLO; Spectralis HRA, Heidelberg Engineering, Heidelberg, Germany), spectral-domain optical coherence tomography (SD-OCT) images (Spectralis HRA-OCT, Heidelberg Engineering), and in selected cases enhanced depth imaging (EDI) OCT, fluorescein (FA), and indocyanine green angiography (ICG-A).
All eligible eyes were graded for presence or absence of atrophy and CNV (independent from the CNV being active or inactive/fibrotic) at the posterior pole. Grading was based on color, NIR reflectance and AF fundus images, SD-OCT, and in selected cases on FA and ICG-A.