Detailed Comparison Between Two Main Phenotypes of CRB1-Related Retinal Dystrophy, Pan-retinopathy and Maculopathy

To conduct a comprehensive analysis of the distinct manifestations of two primary phenotypes of Crumbs cell polarity complex component 1 (CRB1)-related retinal dystrophy, pan-retinopathy, and maculopathy.

A cohort of 75 patients with biallelic pathogenic variants in the CRB1 gene was recruited. Clinical evaluations including visual acuity, refractive errors, fundus autofluorescence imaging, optical coherence tomography, visual field testing, and full-field ERG.

Genetic analysis identified 89 disease-causing CRB1 variants. Patients with biallelic loss-of-function variants were significantly more prevalent in the pan-retinopathy group (40.3%) than in the maculopathy group (7.1%) (P = 0.03). The proportion of patients harboring biallelic variants expressing wild-type CRB1-B was significantly higher in the maculopathy group (30.8%) than in the pan-retinopathy group (8.1%). In the pan-retinopathy group, visual function was significantly worse (P < 0.01). The pan-retinopathy group also showed marked hyperopia, shorter axial lengths, severe visual field impairment, and severely attenuated ERG responses (all P < 0.05). Initial visual acuity was better in the maculopathy group, but a critical decline occurred after 18.94 years. Optical coherence tomography and fundus autofluorescence imaging revealed distinct patterns: pan-retinopathy predominantly showed outer retinal atrophy (98.2%), parafoveal thickening (58.9%-60.7%), and diffuse hypofluorescence (87.5%), whereas maculopathy was characterized by macular edema/schisis (66.7%) and bilateral localized macular hypofluorescence (45.5%).

This study establishes CRB1-associated pan-retinopathy and maculopathy as clinically and genetically distinct entities. The maculopathy group initially has relatively stable vision but shows significant deterioration after adulthood.