Abstract
PURPOSE: Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive progressive retinal degenerative disease due to mutations in the CYP4V2 gene. Best-corrected visual acuity (BCVA) is a common primary endpoint in clinical trials for retinal diseases, but the natural history of BCVA loss remains unclear because of the heterogeneity of manifestations in BCD patients. METHODS: Based on the individual data of untreated BCD patients, a disease progression model was established using the change in BCVA from baseline as an index, and covariates including age of onset, age, duration of disease, baseline BCVA, gender, race (East Asian/non-East Asian), genotype, and family history. Then, based on the final model, the natural disease progression characteristics of BCD were simulated. RESULT: A total of 14 studies met the inclusion criteria, with a total sample size of 117 cases, including 6 studies (N=80) with East Asian populations and 9 studies (N=37) with non-East Asian populations. The change of BCVA from baseline increased linearly with time, and the disease progression model of BCD was successfully established. BCVA increased by 0.06 logarithm of the minimum angle of resolution (LogMAR) per year in BCD patients. BCVA increased by 0.09 LogMAR per year in patients with BCVA≥0.5LogMAR and disease duration more than 10 years. CONCLUSIONS: For the first time, we successfully established a BCD disease progression model based on the change in BCVA from baseline. The mean visual acuity loss increased linearly with the progression of the disease. A sharper loss of BCVA may be expected in patients with BCVA≥0.5LogMAR and disease duration ≥10 years.