Bietti’s crystalline dystrophy: genotyping and deep qualitative and quantitative phenotyping in preparation for clinical trials

Purpose To qualitatively and quantitatively characterise the genotypes and phenotypes of Bietti’s crystalline dystrophy (BCD) in a cohort of patients. Design Cross-sectional and observational study. Methods Clinically confirmed BCD patients were recruited for genotyping and phenotyping. Multiple retinal imaging modalities were employed. Atrophy in the fovea was adopted as major consideration for staging strategy, while percentage area of autofluorescence (AF) atrophy (PAFA) in the macula was determined for quantitation. Results In 74 clinically diagnosed BCD patients, c.802–8_810del17insGC was shown the predominant variant of the CYP4V2 gene (allele frequency 55.4%). Sixty-two cases (123 eyes) with full imaging data were classified according to a modified criterion into stages 1 (n=8, 6.50%), 2A (n=9, 7.32%), 2B (n=17, 13.82%), 3A (n=30, 24.39%) and 3B (n=59, 47.97%). The eyes of the stage 2B were particularly deemed ‘high risk’ due to atrophy near fovea, while in stage 3A, though with remarkable foveal atrophy, preserved retinal pigment epithelium/photoreceptor islands near the fovea were found in 14 eyes. A tendency of increase in PAFA with age was found (r s =0.31, p=0.014). Significant PAFA increase was shown through stages 1 to 3B, and best-corrected visual acuity (BCVA, Logarithm of the Minimum Angle of Resolution) was shown to moderately correlate with PAFA (r s =0.56, p<0.001). Conclusion The PAFA might be an efficient biomarker for BCD severities correlating with BCVA. The highly heterogeneous chorioretinopathy and BCVA of BCD cases appear to be associated with disease stages, progression types and patients’ ages. Foveal involvement should be of a major concern for consideration of potential therapeutic intervention.