Spectral-Domain Optical Coherence Tomography Analysis in Syndromic and Nonsyndromic Forms of Retinitis Pigmentosa due to <b><i>USH2A</i></b> Genetic Variants

Abstract

<b><i>Introduction:</i></b> This study aimed to analyze macular structure by using spectral-domain optical coherence tomography (SD-OCT) in a cohort of patients affected by autosomal recessive retinitis pigmentosa and Usher syndrome, due to genetic variants in <i>USH2A</i> gene, and to correlate optical coherence tomography (OCT) parameters with functional and genetic data. <b><i>Methods:</i></b> The subjects of this study were 92 patients, 46 syndromic (Usher syndrome type IIa [Ush2]) and 46 nonsyndromic (autosomal recessive RP [arRP]), with clinical and genetic diagnosis of <i>USH2A</i>-related retinal dystrophy, who underwent a complete ophthalmic examination and spectral-domain OCT analysis. The study focused on evaluating the differences between the 2 groups in the following parameters: best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, presence of epiretinal membrane (ERM), and cystic macular lesions (CMLs). Variants in <i>USH2A</i> gene were divided into 3 categories, according to the expected impact (low/high) at protein level of the different variants on each allele. <b><i>Results:</i></b> BCVA and EZ width were significantly lower in Ush2 than in arRP patients (<i>p</i> &#x3c; 0.0001 and <i>p</i> = 0.001). ERM was detected in 34.8% (16/46) of arRP patients and in 65.2% (30/46) of Ush2 patients (<i>p</i> = 0.003). CML was detected in 17.4% (8/46) of arRP patients and 30.4% (14/46) of Ush2 patients (<i>p</i> = 0.14). The allelic distribution was statistically different (<i>p</i> = 0.0003) by dividing the 2 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 visual acuity and EZ width parameters (<i>p</i> = 0.004 and <i>p</i> = 0.002, respectively). <b><i>Conclusion:</i></b> Retinal disease, as evaluated by means of SD-OCT, shows more advanced degeneration signs in the syndromic than the nonsyndromic form of retinal dystrophy related to <i>USH2A</i> gene. Variant types and allelic profiles are determining factors for the onset of syndromic features. However, since the 3 allelic profiles can be found in both Usher and RP patients, other factors must necessarily play a determining role.