Unveiling Inflammation-Like Retinal Remodeling in CRB1-Associated Inherited Retinal Dystrophies: Insights From a Multicenter Study.

Abstract

To delineate the intricate interplay between inflammation, retinal remodeling, and genotype in CRB1-associated inherited retinal diseases (CRB1-IRDs). Retrospective, multicenter observational case series. We evaluated 66 CRB1-retinopathy patients from 61 unrelated families recruited from 4 tertiary hospitals in China between June 2016 and July 2024. Comprehensive medical records, ophthalmic examination and multimodal fundus imaging were obtained and reviewed. The main outcome measures included: inflammatory-like fundus characteristics, quantitative assessments of retinal thickness, and genotype-phenotype correlations regarding both inflammatory-like features and the severity of outer retinal disruption. Among 66 patients (59.1% male, aged 3-57 years), clinical diagnoses included retinitis pigmentosa (RP, 60.6%), Leber congenital amaurosis (LCA, 33.3%), and cone-rod dystrophy (6.1%). Several inflammatory-like fundus features were identified, including preserved para-arteriolar retinal pigment epithelium (PPRPE, 77.5%), yellow-white lesions (68.1%), vascular sheathing (48.9%), nummular pigmentation (26.6%) and Coats-like vasculopathy (3.2%). In CRB1-IRD retinas with residual outer nuclear layer (ONL), inner nuclear layer thickening was observed, whereas those with complete ONL loss exhibited progressive atrophy. Patients with biallelic loss-of-function variants exhibited significantly higher prevalence of PPRPE (88% vs 64.7%, P = .042), yellow-white lesions (80% vs 52.9%, P = .038), and greater outer retinal disruption compared to those with biallelic non-null mutations (outer plexiform layer continuity: 18.2% vs 50%, P = .014; ellipsoid zone retention: 13.6% vs 40%, P = .031). This study identifies retinal inflammation-like changes as core features of CRB1-IRD, might associated with retinal remodeling and genotype. These findings provide new insights into CRB1-IRD and establish references for diagnosis and future clinical trial design.