Natural history study of visual function in patients with BBS1 and BBS10-related Bardet-Biedl syndrome.

Abstract

Purpose : Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder where all patients have early, progressive photoreceptor degeneration. The natural history of visual function change has not been established. We explored changes in visual function for patients with biallelic mutations in most common BBS genotypes: BBS1 and BBS10.

Methods : Multicenter, retrospective longitudinal chart review of 40 Bardet-Biedl patients with 2 pathogenic variants in BBS1 (n=23) or BBS10 (n=17) genes. Parameters documented included best corrected visual acuity (BCVA), Goldmann perimetry (VF), electroretinography (ERG), full-field stimulus threshold (FST), and systemic phenotype. We used descriptive statistics to summarize observations (mean and range for continuous variables; counts and percentages for categorical variables).

Results : Mean age at first visit was 15.8 years (range 5.3 to 40.2 years), mean age at last visit was 28.6 years (range 8.5 to 47.8 years). Mean follow-up period was 12 years. 86% of all patients had systemic associations. 34 BBS patients had rod-cone dystrophy (n=21, BBS1; n=13 BBS10), 3 cone-rod dystrophy (n=3, BBS1) and 3 had cone dystrophy (n=3, BBS10). ERG was non-detectable in the majority of BBS10 patients by age 18. BBS10 patients with rod-cone dystrophy and BBS1 patients (either rod-cone or cone-rod dystrophy) had similar ocular phenotype: majority were myopic (70%), nyctalopia was present early (85%), however onset of cataract was observed earlier in BBS10 patients. BCVA most rapidly declined in BBS10 patients with rod-cone dystrophy. Similar trend was observed in VF progression over time leading to legal blindness by age 18 (61% of BBS1 patients and 100% of BBS10 patients with rod-cone dystrophy, n=27). FST in a 28 year old patient (BBS10, rod-cone dystrophy) showed residual rod mediated retinal function.

Conclusions : BBS-associated retinal degeneration is early and severe, usually leading to legal blindness by 18 years. Allelic heterogeneity may lead to different scales of severity. Documenting the course of change of visual function should be specific to the genetic subtypes to identify the optimal time of intervention.

This is a 2020 ARVO Annual Meeting abstract.