Genotype-Phenotype Correlations in Retinopathies: A Comprehensive Analysis of 36 Patients from the Oxford Eye Hospital, UK.

PURPOSE

To investigate genotype-phenotype correlations in -retinopathies in a cohort of 36 patients from the Oxford Eye Hospital and report on novel pathogenic variants.

METHODS

Clinical data, including best corrected visual acuities (BCVA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) imaging, were analysed. Genetic testing was performed using next-generation sequencing (NGS).

RESULTS

In this cohort, 26 different variants, including 8 novel variants, were identified. Variants were clustered in the D2 loop of the protein. A diverse range of phenotypes were observed: pseudo-Stargardt pattern dystrophy (PSPD) (47.2%), adult-onset vitelliform macular dystrophy (AVMD) (22.2%), pattern dystrophy (PD) (25.0%), atypical macular dystrophy (2.8%), and retinitis pigmentosa (RP) (2.8%). The mean age of symptom onset was 44.0 ± 14.4 years. Mean BCVA was 0.20 ± 0.54 logMAR OD and 0.14 ± 0.29 logMAR OS at baseline and 0.33 ± 0.40 logMAR OD and 0.32 ± 0.40 logMAR OS after a mean follow up duration of 6.0 ± 3.2 years (range 1-11 years). A thickened ellipsoid zone (EZ) was noted in 34/36 patients with a mean EZ thickness of 44.3 ± 11.3 µm OD and 42.7 ± 11.6 µm OS. No clear genotype-phenotype correlations were observed.

CONCLUSIONS

The significant phenotypic range described in this study is consistent with the previously reported phenotypic variability in retinopathy and emphasises the complexity of establishing genotype-phenotype correlations in this disease. The thickness of the EZ on OCT may serve as a useful biomarker in distinguishing retinopathy from other phenocopies. These findings contribute to improved understanding of retinopathy and help inform diagnosis and genetic counselling.