Foveal Hypoplasia in CRB1-Related Retinopathies

Abstract

The <i>CRB1</i> gene plays a role in retinal development and its maintenance. When disrupted, it gives a range of phenotypes such as early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) and macular dystrophy (MD). Studies in <i>CRB1</i> retinopathies have shown thickening and coarse lamination of retinal layers resembling an immature retina. Its role in foveal development has not yet been described; however, this retrospective study is the first to report foveal hypoplasia (FH) presence in a <i>CRB1</i>-related retinopathy cohort. Patients with pathogenic biallelic <i>CRB1</i> variants from Moorfields Eye Hospital, London, UK, were collected. Demographic, clinical data and SD-OCT analyses with FH structural grading were performed. A total of 15 (48%) patients had EOSRD/LCA, 11 (35%) MD, 3 (9%) CORD and 2 (6%) RP. FH was observed in 20 (65%; CI: 0.47-0.79) patients, all of whom were grade 1. A significant difference in BCVA between patients with FH and without was found (<i>p</i> = 0.014). BCVA continued to worsen over time in both groups (<i>p</i> < 0.001), irrespective of FH. This study reports FH in a <i>CRB1</i> cohort, supporting the role of <i>CRB1</i> in foveal development. FH was associated with poorer BCVA and abnormal retinal morphology. Nonetheless, its presence did not alter the disease progression.