Purpose : Knowing the natural history of vision loss is key to select the appropriate endpoints and best interpret response to treatments. The purpose of this study was to compare the natural history of visual function change in a cohort of patients affected with retinal degeneration due to biallelic variants in BBS1 and BBS10 genes.
Methods : Design: Global, multicenter, retrospective chart review.
Patients were recruited from 9 participating academic centers from 6 countries (Belgium, Canada, France, New Zealand, Switzerland and USA). Inclusion criteria were: 1) female or male subjects with a clinical diagnosis of retinal dystrophy, 2) molecularly confirmed biallelic disease-causing variants in BBS1 or BBS10 and 3) measures of visual function for at least one visit. Retrospective data collected included age, onset of symptoms, visual acuity (VA) and genotypes. When possible we also collected data on refractive error, optical coherence tomography (OCT), kinetic perimetry (VF), electroretinography (ERG), and the systemic phenotype.
Results : 67 individuals had biallelic pathogenic variants in BBS1 (n=38; 20 females and 18 males); or BBS10 (n=29; 14 females and 15 males). Overall, the mean follow-up period was 10 years (range 0-33.9 years). Missense variants were the most common for BBS1-patients, and frameshift for BBS10. Extraocular signs were documented in 97% of BBS1-patients and in 92% of BBS10-patients. When ERGs were recordable, rod-cone dystrophy (RCD) was observed in 82% (23/28) of BBS1- and 73% (8/11) of BBS10-patients; cone-rod dystrophy (CORD) was seen in 18% of BBS1 only, and cone dystrophy (COD) was only seen in three BBS10-patients. ERGs were non-detectable earlier in BBS10-patients than in BBS1-patients. Similarly, VA and VF declined more rapidly in BBS10-compared to BBS1-patients.
Conclusions : Retinal degeneration appears earlier and is more severe in BBS10-patients compared to those with BBS1 variants. Non syndromic retinal degeneration was observed in both groups. The course of change of visual function appears to be related to genetic subtypes of BBS.