Bestrophinopathies: Clinical Characteristics, Natural History, and Genetic Landscape

To investigate the clinical features, natural course, and genetic landscape of bestrophinopathies.

Retrospective case series.

A total of 134 patients from 115 families with disease-causing variants in the BEST1 gene.

Medical recordings, retinal imaging (color fundus photography, fundus autofluorescence, spectral-domain OCT), and genetic findings were assessed.

Ophthalmic characteristics, best-corrected visual acuity (BCVA), and BEST1 variants.

The 134 recruited patients included 60 patients from 48 families with best vitelliform macular dystrophy (BVMD) and 74 patients from 67 families with autosomal recessive bestrophinopathy (ARB). For the BVMD patients, 58 showed typical vitelliform or atrophic changes, and 2 displayed pattern dystrophy-like or irregular retinal pigment epithelium changes. For the ARB patients, 67 showed common scattered vitelliform lesions, and 5 demonstrated severe retinal detachment. Choroidal neovascularization (CNV) developed in 35.0% of the BVMD and 25.5% of the ARB eyes; these eyes exhibited significantly worse BCVA (P < 0.0001 in BVMD; P = 0.0102 in ARB). For the patients with ARB, 47.3% developed angle-closure glaucoma (ACG) and had worse BCVAs than the patients without ACG (P < 0.0001), with a median age of 32.1 years. In total, 43 patients (21 BVMD and 22 ARB) were followed up with a mean follow-up duration of 4.6 ± 2.3 years (range, 0.6-11.1 years). The mean rates of change in BCVA were 0.01 and 0.04 logarithm of the minimum angle of resolution/year for the patients with BVMD and ARB, respectively. Ninety-two distinct BEST1 variants were detected. The hotspot regions for the 2 diseases were different.

Our study delineated broad phenotypes, the natural disease course, and the genetic profile in bestrophinopathies. Patients with either BVMD or ARB showed a slow rate of BCVA decline, especially in the absence of CNV/ACG. These findings may facilitate the implementation of gene therapy in China.

The authors have no proprietary or commercial interest in any materials discussed in this article.