Clinical findings in Retinitis Pigmentosa related to CNGB1 variants

Abstract

Purpose : This study reports a longitudinal phenotypic analysis of patients with Retinitis Pigmentosa (RP) related to CNGB1 variants.

Methods : An Italian cohort of 13 RP patients with mutations in CNGB1 gene have been retrospectively evaluated. Medical records of each patient showed a detailed family history, complete ophthalmological evaluation, Color Fundus Photography, Optical Coherence Tomography (OCT) and full-field Electroretinography (ERG).

Results : The 13 patients included had a mean age at the time of first examination of 47.1 ± 21.8 years. The mean follow-up was 9.1 ± 8.6 years. At the first control, patients showed a mean Best Corrected Visual Acuity (BCVA) of 0.6 ± 1.0 LogMAR. All subjects presented a classic form of RP. OCT revealed cystoid macular edema (CME) in 9 eyes of 5 patients (34.6%). On average, excluding eyes with CME, mean macular thickness (MMT) was 247 ± 75 µm. Non-recordable ERG was reported in 9 patients (69.2%) whereas only the remaining 4 patients (30,8%) showed a deeply reduced rod responses with subnormal cone signals. Statistical analysis showed a significant worsening of BCVA with age (B: 0.017 logMAR / year; p-value < 0.001). No significant effect of age was observed on MMT (p-value = 0.868). The patients achieved low vision and blindness based on visual acuity at mean age of 75.4 ± 5.1 years and of 82.1 ± 4.5 years, respectively. Longitudinal analysis revealed a significant (p-value < 0.001) worsening of BCVA at mean annual rate of 0.010 logMAR /year (equivalent to about 0.5 ETDRS letters). Moreover, MMT decreased at a mean annual rate of 0.61 µm/year (p-value < 0.001).

Conclusions : The results from this study underline that RP secondary to CNGB1 variants presents a slowly progressive clinical pattern. Both visual acuity and foveal structure are frequently preserved in adulthood. These findings are valuable for patient counseling, but also for implications in design of gene therapy trials.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.