Genotype-phenotype correlations in retinitis pigmentosa: structural and vascular insights using OCT and OCTA

This study aimed to identify disease-related genetic variants in 41 patients with retinitis pigmentosa (RP) and to evaluate their phenotypic effects on the retina and choroid.

Patients diagnosed with RP underwent targeted next-generation sequencing of RP-related genes and mitochondrial DNA analysis, with genetic counseling. Variants were classified according to ACMG guidelines. Central macular thickness (CMT), retinal nerve fiber layer thickness (RNFLT), subfoveal choroidal thickness (SfCT), foveal avascular zone area (FAZa), ellipsoid zone (EZ) integrity, and vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) were assessed using OCT and OCTA.

Patients were classified into three groups: Group 1 (USH2A; n = 11), Group 2 (other single-gene variants; n = 21), and Group 3 (multiple-gene variants; n = 9). There were no significant differences in age, sex, consanguinity, symptom onset, disease duration, best-corrected visual acuity, intraocular pressure, RNFLT, or EZ integrity. Pairwise comparisons showed a higher preserved EZ rate in Group 2 (66.7%) than in Group 3 (4.8%, p = 0.020). Mean SfCT was lower in Group 3 (147.9 ± 107.7 μm) than in Group 2 (243.9 ± 26.3 μm, p = 0.046). SCP and DCP FAZa and VD did not differ significantly; inferior-quadrant CC VD was lower in Group 3 than in Groups 1 and 2 (p ≤ 0.01).

RP patients harboring more than one variant showed reduced preserved EZ, SfCT, and inferior-quadrant CC VD compared to patients with a single variant. These findings require further investigation in larger cohorts, together with functional studies, to clarify their clinical and biological significance.