Ophthalmic, Systemic and Genetic Features in Wolfram Syndrome

To evaluate quantitative microvascular ocular features using optical coherence tomography angiography (OCTA) in patients with Wolfram syndrome (WFS) and compared it with healthy controls. This cross-sectional study included patients with WFS and healthy controls. Diagnosis of WFS was based on clinical presentation and identification of biallelic pathogenic variants in the WFS1 gene. Ophthalmic and systemic examinations were performed. Spectral Domain OCTA scans of the optic nerve head (ONH), peripapillary region, and macular area were analyzed in patients able to undergo the exam and compared to controls. Fifty-seven eyes were included: 22 eyes from 11 WFS patients and 35 eyes from 18 healthy controls, from six families with WFS. Optic atrophy (100%) and diabetes mellitus (90.9%) were the most common systemic findings, followed by neurologic, urologic, and psychiatric disorders (each 63.6%), neurosensorial deafness (54.5%), and diabetes insipidus (9.1%). Best-corrected visual acuity ranged from light perception to 0.1 logMAR, with a mean of 0.97 ± 0.69 logMAR. OCTA analysis revealed significantly lower whole-image vessel density (VD), inside-disc VD, and peripapillary VD in WFS patients compared to controls (<i>p</i> < .001). The macular region showed significantly reduced parafoveal superficial capillary plexus (SCP) vessel density (<i>p</i> < .001). Sectoral analysis showed decreased parafoveal SCP VD in the nasal, inferior, and superior sectors (<i>p</i> < .001). WFS is a progressive neurodegenerative disorder with severe ocular and systemic manifestations. OCTA demonstrated reduced vessel density in all examined regions in WFS patients, suggesting microvascular impairment may contribute to neurodegeneration and structural retinal changes.