Comprehensive genotypic and phenotypic analysis of Bietti crystalline dystrophy: insights from a large cohort study.

In this cross-sectional observational study, we conducted comprehensive ophthalmic evaluations, including fundus imaging, fundus autofluorescence (FAF), swept-source optical coherence tomography (SS-OCT), microperimetry, and electroretinography, in 164 patients with Bietti crystalline dystrophy (BCD) from 159 families. The mean age of onset was (29.9±8.9) years, with night blindness being the most common onset symptom (54.3%). FAF revealed diffuse hypoautofluorescence in 86.7% of eyes, and SS-OCT identified outer retinal tabulations (ORTs) in 69.9% of eyes, indicative of severe retinal pigment epithelium (RPE) dysfunction. Microperimetry demonstrated a gradual decline in retinal sensitivity and fixation stability with disease progression, particularly in advanced stages. We identified 34 distinct CYP4V2 variants, three of which were novel. Patients with biallelic truncating mutations experienced earlier disease onset and progressed to legal blindness at a younger age. These findings provide a comprehensive overview of structural and functional deterioration in BCD and underscore the significant impact of truncating mutations on disease progression.