SD-OCT analysis in syndromic and non-syndromic forms of retinitis pigmentosa due to USH2A gene mutations

Introduction: This study aims to analyze macular structure by using SD-OCT in a cohort of patients affected by autosomal recessive retinitis pigmentosa and Usher syndrome, due to genetic variants in USH2A gene, and to correlate OCT parameters with functional and genetic data. Methods: The subjects of this study were 92 patients, 46 syndromic (Ush2) and 46 non-syndromic (arRP), with clinical and genetic diagnosis of USH2A-related retinal dystrophy, who underwent a complete ophthalmic examination and spectral domain OCT analysis. The study focused on evaluating the differences between the two groups in the following parameters: best corrected visual acuity (BCVA), ellipsoid zone width (EZ), presence of epiretinal membrane (ERM) and cystic macular lesions (CML). Variants in USH2A gene were divided in 3 categories, according to the expected impact (low/high) at protein level of the different variants on each allele. Results: BCVA and EZ width were significantly lower in Ush2 than in arRP patients (p < 0.0001 and p = 0.001). ERM was detected in 34.8% (16/46) of arRP patients and in 65.2% (30/46) of Ush2 patients (p = 0.003). CML was detected in 17.4% (8/46) of arRP patients and 30.4% (14/46) of Ush2 patients (p = 0.14). The allelic distribution was statistically different (p = 0.0003) by dividing the two diseases: for Ush2 patients it was 45.7% (high/high), 39.1% (low/high) and 15.2% (low/low); for arRP patients it was 8.7% (high/high), 56.5% (low/high) and 34.8% (low/low). The severity class of the variants significantly affected VA and EZ width parameters (p = 0.004 and p = 0.002, respectively). Conclusion: Retinal disease, as evaluated by means of SD-OCT, shows more advanced degeneration signs in the syndromic than the non-syndromic form of retinal dystrophy related to USH2A gene. Variant types and allelic profiles are determining factors for the onset of syndromic features. However, since the three allelic profiles can be found in both Usher and RP patients, other factors must necessarily play a determining role.