Comparative Analysis of Retinal Structure and Function in Female Carriers of Choroideremia and X-Linked Retinitis Pigmentosa.

PURPOSE: To characterize and compare structural and functional outcomes in female carriers of choroideremia (CHM) and RPGR-associated X-linked retinitis pigmentosa (XLRP), focusing on differences in disease severity and progression.

METHODS

Carriers of CHM (n = 20) and XLRP (n = 27) were identified retrospectively from a database of a single tertiary center. Visual acuity (best-corrected visual acuity [BCVA]), multimodal imaging including color fundus photography, short-wavelength autofluorescence, optical coherence tomography (OCT), and full-field electroretinography (ERG) were analyzed. Eyes were classified into severity phenotypes using previously published grading systems. Macular retinal thicknesses were measured, and progression was assessed over follow-up. Age-matched analyses were conducted to compare CHM and XLRP carriers.

RESULTS

CHM and XLRP carriers exhibited a broad spectrum of phenotypes from subclinical changes to severe, male-like disease. In both groups, greater disease severity correlated with younger age at symptom onset, worse baseline BCVA, thinner retinochoroidal layers, and diminished light-adapted 30-Hz flicker ERG amplitudes. CHM carriers demonstrated significantly faster retinal thinning in the outer macula (3-6 mm Early Treatment Diabetic Retinopathy Study [ETDRS]) and exhibited faster BCVA decline compared to XLRP carriers (P < 0.05). Although phenotypic progression based on grading scales was infrequent, quantitative OCT measurements revealed continuous structural thinning over time.

CONCLUSIONS

Compared to XLRP, CHM carriers experience accelerated retinal thinning. Severe phenotypes are associated with faster structural and functional decline. These findings underscore the need for careful monitoring and highlight female carriers as potential candidates for future gene therapy and therapeutic trials.

TRANSLATIONAL RELEVANCE: This study translates genetic and structural disease mechanisms in X-linked retinal degeneration into clinically relevant prognostic tools that may inform counseling, surveillance, and future gene therapy strategies for female carriers.