OCT characteristics associated with Bardet-Biedl syndrome (BBS) retinopathy

Abstract

Purpose : BBS is a rare multisystem ciliopathy affecting 1 in 100 000 in North America. Patterns of progression and prognosis of the retinal disease are poorly understood. There is no standardised clinical guideline to classify and grade BBS retinopathy using objective measures such as OCT. In this study we propose a clinically relevant grading system of OCT changes in BBS retinopathy, and evaluate potential genotype-phenotype correlation.

Methods : This was a retrospective analysis of clinical, imaging and genotypic data recorded of all BBS patients seen in the UK adult BBS service (Birmingham, UK) between 1st June 2013 and 1st Jan 2018. All clinical data was recorded prospectively using our established BBS Ophthalmic Assessment Tool. Imaging was performed with Spectralis SD-OCT (Heidelberg Engineering) aiming to obtain macular OCT (‘fast macular scan’ as standard; single line where needed), a retinal nerve fibre layer (‘RNFL’) OCT scan and macular Bluepeak Autofluorescence (BAF). Genotyping was performed through the regional genetic service based at Birmingham Womens’ and Childrens’ NHSFT.

Results :
88 scans, comprising both eyes of 44 cases, were analysed. 92% of patients with gradable scans showed symmetry of retinopathy between the two eyes.

Applying our OCT grading scale on a cross-sectional basis to this cohort ( 18 ungradable), the retinopathy patterns were a mixed central and peripheral retinopathy (CP) (31), rod-cone (RC) retinopathy (25), and a predominantly central cone-rod pattern (CR) (10); occasionally a Stargardt-like pattern was seen (4).
Stage of progression were as follows (79 scans, 9 ungradable): Grade 0 (4), Grade 1 (10), Grade 2 (34), Grade 3 (19), Grade 4 (12). 16 patients graded as ‘plus’ disease.
BBS1 gene mutation was the most common (25/44), followed by BBS10 (3/44), BBS2 (2/44), BBS5 (2/44), BBS12 (1/44), INPP5E (1/44) and no result in 10 cases.

Conclusions : We have described a novel grading system, based primarily on structural changes detected by standard SD-OCT. This grading system may help in measurement of structural progression and serve as a useful objective endpoint in clinical trials for BBS. Our OCT based grading system recognises a functional component since functional changes may predate the changes that can be seen with standard imaging systems.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Proposed OCT grading System for BBS Retinopathy