Best Vitelliform Macular Dystrophy Natural History Study Report 1: Clinical Features and Genetic Findings.

PurposeTo analyze the genetic findings, clinical spectrum and natural history of Best vitelliform macular dystrophy (BVMD) in a cohort of 222 children and adults.DesignSingle-center retrospective, consecutive, observational study.ParticipantsPatients with a clinical diagnosis of BVMD, from pedigrees with a likely disease-causing monoallelic sequence variant in the BEST1 gene.MethodsData were extracted from electronic and physical case notes. Electrophysiologic assessment and molecular genetic testing were analyzed.Main outcome measurementsMolecular genetic testing, clinical findings including best-corrected visual acuity (BCVA), choroidal neovascularization (CNV) rates, and electrophysiology parameters.Results222 patients (127 males and 95 females) from 141 families were identified, harboring 69 BEST1 variants, including 22 novel variants. Mean age at presentation was 26.8 years (range 1.3-84.8 years) and most patients (61.5%) presented with a deterioration of central vision. Major funduscopic findings at presentation included: 128 eyes (30.6%) with yellow vitelliform lesions, 78 eyes (18.7%) with atrophic changes, 49 eyes (11.7%) with fibrotic changes, 48 eyes (11.5%) with mild pigmentary changes and 43 eyes (10.3%) showing a vitelliruptive appearance. Mean BCVA was 0.37 LogMAR (20/47) for the right eye and 0.33 LogMAR (20/43) for the left eye at presentation, with a mean annual loss rate of 0.013 LogMAR and 0.009 LogMAR respectively over a mean follow-up of 9.6 years. 37 patients (17.3%) were diagnosed with CNV over a mean follow-up period of 8.0 years (range 0-55 years). Eyes with CNV that received treatment with anti-VEGF had a better mean VA compared to eyes that were not treated with anti-VEGF (0.28 LogMAR (20/38) versus 0.62 LogMAR (20/83). The majority of eyes exhibited a hyperopic refractive error (185/235, 78.7%) and 13 patients (6.1%) were diagnosed with amblyopia. Among the three most common variants, p.A243V was associated with a later age of onset, a better age-adjusted VA and less advanced Gass stages compared to p.R218C and p.R218H.ConclusionsBVMD shows a wide spectrum of phenotypic variability. The disease is very slowly progressive, and the observed phenotype-genotype correlations allow for more accurate prognostication and counselling.