Longitudinal structure-function analysis of molecularly-confirmed CYP4V2 Bietti Crystalline Dystrophy.

objectivesBietti Crystalline Dystrophy (BCD) is an autosomal recessive progressive retinal disease caused by mutations in CYP4V2. We have characterised the natural history including structural and functional measures to identify potential outcome metrics for future clinical trials.

methodsMolecularly-confirmed BCD patients with biallelic variants in CYP4V2 were retrospectively identified from Moorfields Eye Hospital (UK). Clinical details including results of molecular genetic testing, best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (OCT) scans were extracted. From OCT scans, ellipsoid zone (EZ) measures, foveal thickness of the whole retina, outer retina and choroid were measured. Age-related changes of clinical parameters were assessed with linear mixed models.

resultsTwenty-eight BCD patients were identified, with median age at baseline of 37 years (interquartile range [IQR]: 30-49.5). Median follow-up was 7.7 years (IQR: 3.4-14.5). Most patients (41.7%) showed chorioretinal atrophy at baseline. All OCT parameters showed significant age-related loss (p < 0.05), with EZ measures and choroidal thickness displaying the most rapid degeneration (2.3-3.3% per year vs 0.6-1.5% per year). Median BCVA was 0.2 LogMAR (IQR: 0-0.5) at baseline and showed small age-related loss ( + 0.016 LogMAR per year, p = 0.0019). Patients exhibited substantial phenotypic variability.

conclusionsBCD presents between age 25 and 40, and slowly progresses to an advanced chorioretinal atrophy and vision loss by age 60. BCVA may be preserved until late, and is seemingly poorly representative of disease progression. OCT parameters capturing EZ and choroid changes may afford more suitable trial outcome measures.