Cone Structure and Function in RPGR- and USH2A-Associated Retinal Degeneration

Area of Science:

• Ophthalmology
• Genetics
• Retinal Degeneration

Background:

• Retinitis pigmentosa (RP) and Usher syndrome are inherited retinal diseases.
• RPGR and USH2A gene variants are known causes of these conditions.
• Understanding structural and functional differences is crucial for patient management.

Purpose of the Study:

• To compare cone structure and function in patients with RPGR-related X-linked retinitis pigmentosa (RPGR) and USH2A-related Usher syndrome (USH2) or autosomal recessive RP (ARRP).

Main Methods:

• A retrospective, observational study analyzed 13 eyes with RPGR, 15 with USH2, 16 with ARRP, and 7 normal eyes.
• Structural analysis used adaptive optics scanning laser ophthalmoscopy and optical coherence tomography (OCT).
• Cone function was assessed via fundus-guided microperimetry; choriocapillaris perfusion was evaluated using OCT angiography.

Main Results:

• RPGR eyes showed significantly reduced outer segment (OS), inner segment (IS), and outer nuclear layer (ONL) thickness compared to normal, USH2, and ARRP.
• Increased cone spacing was noted in RPGR and USH2 compared to normal.
• Choriocapillaris flow deficit was greater in RPGR than USH2, but regional sensitivity was similarly reduced across all disease groups.

Conclusions:

• RPGR-associated retinal degeneration exhibits more pronounced abnormalities in outer retinal structure and choriocapillaris perfusion compared to USH2A-associated degenerations.
• Despite structural differences, cone photoreceptor function, measured by regional sensitivity, was comparably impaired in RPGR and USH2A related conditions.