Retinitis Pigmentosa GTPase regulator–Associated Retinal Degeneration: Integrating Patient-Reported Outcomes, Genetic, and Structural Biomarkers

Purpose

To characterize the genetic, structural, and patient-reported visual function features in a multicenter cohort of patients with retinitis pigmentosa GTPase regulator (RPGR)–associated retinal degeneration.

Design

A cross-sectional, exploratory, international, multicenter study conducted across 3 academic centers.

Subjects

The study included 102 eyes from 51 patients (37.3% female) with genetically confirmed RPGR-associated retinal degeneration. Only male and female patients with a retinitis pigmentosa (RP) phenotype were included, as well as female carriers from RP pedigrees with retinal degeneration.

Methods

Genetic variants were identified and visual acuity (VA) was recorded. Retinal phenotype was classified using fundus autofluorescence. Structural retinal features were assessed using spectral-domain OCT to measure ellipsoid zone (EZ) area and width, central subfield thickness (CST), central point thickness (CPT), subfoveal outer nuclear layer (ONL) thickness, photoreceptor outer segment length (PROS), foveal outer segment pigment epithelial thickness (FOSPET), and FOSPET-PROS ratio. Patient-reported visual function was measured via the Michigan Retinal Degeneration Questionnaire (MRDQ).

Main Outcome Measures

Associations between genetic variant location, retinal structural parameters, and VA, as well as correlations between structural measures and MRDQ domain scores.

Results

Structural endpoints, including EZ area, CPT, PROS, and FOSPET, correlated significantly with all MRDQ domains, and higher disability scores on MRDQ were associated with more advanced retinal degeneration. There were no significant differences in VA or structural features between RPGR variants located in the open reading frame 15 region compared to exons 1 to 13. Eyes from male patients and female patients with an RP phenotype showed significantly decreased VA and structural features compared with eyes of female carriers with focal or radial pattern. A mixed model analysis found that VA was associated with several OCT features including CST, CPT, ONL thickness, EZ area, PROS, and FOSPET.

Conclusions

This study underscores the value of combining genetic, structural, and patient-reported outcome measures in understanding RPGR-associated retinal degeneration. Structural biomarkers provide valuable insights into disease severity and visual impairment, aligning closely with patient-reported visual function. This approach supports further development of patient-centered outcome measures for clinical trials and therapeutic interventions.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.