Peripheral Vascular Alterations in USH2A-Retinitis Pigmentosa and Relationship with Macular Involvement: A Cross-Sectional Study.

OBJECTIVE

To characterize peripheral retinal vascular alterations in USH2A-related retinitis pigmentosa (RP) using widefield OCT angiography (WF-OCTA) and to investigate their relationship with macular changes assessed by multimodal retinal imaging.

DESIGN

Cross-sectional observational study.

PARTICIPANTS

Thirty eyes of 30 patients with genetically confirmed USH2A-related RP and 30 age- and gender-matched healthy controls.

METHODS

We performed complete ophthalmologic examination and multimodal retinal imaging, including fundus autofluorescence (FAF), OCT, OCTA, AF-based macular pigment optical density, and 130° WF-OCTA. A quantitative WF-OCTA analysis pipeline was developed to assess peripheral perfusion through concentric fovea-centered retinal rings. The Concentric Peripheral Perfusion Index, peripheral perfusion loss gradient, and perfusion profile slope were calculated. Associations between peripheral vascular status and central retinal imaging biomarkers were analyzed.

MAIN OUTCOME MEASURES: WF-OCTA perfusion quantitative metrics.

RESULTS

Compared with controls, RP eyes showed significantly lower WF-OCTA perfusion indices across all eccentricity rings (all P < 0.05), with more pronounced perfusion loss in the outer retina and a steeper perfusion decline toward the periphery. Peripheral vascular impairment significantly correlated with visual field indices, preserved FAF area, retinal layer thicknesses, and macular vascular density, particularly at the intermediate capillary plexus. Eyes with bone spicule pigmentation or retinal vascular attenuation showed more severe peripheral vascular loss, whereas eyes with hyperautofluorescent ring demonstrated more preserved perfusion profiles. Autofluorescence-based macular pigment optical density values were reduced in RP and significantly associated with central vascular and structural parameters. Hyperreflective ganglion cell band was associated with more severe peripheral vascular impairment and worse macular vascular status.

CONCLUSIONS

USH2A-related RP is characterized by marked peripheral retinal vascular rarefaction, more evident at increasing eccentricities and closely associated with central retinal structural, vascular, and pigmentary alterations. These findings support the concept of RP as a diffuse neurovascular retinal disorder extending beyond the outer retina. Quantitative WF-OCTA may provide clinically meaningful biomarkers for disease characterization and monitoring.

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