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. 2023 Sep 11;24(18):13932.
doi: 10.3390/ijms241813932.

Foveal Hypoplasia in CRB1-Related Retinopathies

Ana Catalina Rodriguez-Martinez  1   2   3 , Bethany Elora Higgins  1   2 , Vijay Tailor-Hamblin  1   2   4 , Samantha Malka  1   2 , Riccardo Cheloni  1   2 , Alexander Mark Collins  1 , John Bladen  5 , Robert Henderson  1   2   3 , Mariya Moosajee  1   2   3   6
Affiliations

Foveal Hypoplasia in CRB1-Related Retinopathies

Ana Catalina Rodriguez-Martinez et al. Int J Mol Sci. .

Abstract

The CRB1 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 CRB1 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 CRB1-related retinopathy cohort. Patients with pathogenic biallelic CRB1 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 (p = 0.014). BCVA continued to worsen over time in both groups (p < 0.001), irrespective of FH. This study reports FH in a CRB1 cohort, supporting the role of CRB1 in foveal development. FH was associated with poorer BCVA and abnormal retinal morphology. Nonetheless, its presence did not alter the disease progression.

Keywords: Crumbs cell polarity complex component 1 gene (CRB1); LCA; cone-rod dystrophy (CORD); early-onset severe retinal dystrophy; foveal hypoplasia (FH); macular dystrophy (MD); optical coherence tomography (OCT); retinal dystrophy; retinitis pigmentosa (RP).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Multimodal imaging in representative patients: (A) 19-year-old patient with EOSRD/LCA with grade 1b FH; (B) 17-year-old patient with MD without FH.
Figure 2
Figure 2
(A) Best-corrected visual acuity (BCVA) scores in groups with and without FH. (B) Best-corrected visual acuity (BCVA) scores over a 10-year follow-up from baseline visit in both groups.
Figure 3
Figure 3
(A) Comparison of quantitative OCT imaging with normative data, showing an increase in thickness and volume of the fovea, inner ring thickness (IRT) and inner ring volume (IRV) in patients with FH, with no statistically significant differences between the two groups. (B) Retinal lamination showing a higher prevalence of worse retinal lamination (groups 2 and 3) in the FH group than those without FH.
See this image and copyright information in PMC

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Supplementary concepts