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Structure and function in retinitis pigmentosa patients with mutations in RHO vs. RPGR

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Abstract Number: 5169

AuthorBlock: Katharina G. Foote1,2, Jessica J. Wong2, Alexandra E. Boehm1, Ethan Bensinger1, Travis C. Porco2,3, Austin Roorda1, Jacque L. Duncan2
1School of Optometry and Vision Science Graduate Group, University of California, Berkeley, Berkeley, California, United States; 2Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States; 3Department of Ophthalmology, Francis I. Proctor Foundation, San Francisco, California, United States;

DisclosureBlock: Katharina G. Foote, Carl Zeiss Meditec, Inc. Code C (Consultant), Jessica J. Wong, None; Alexandra E. Boehm, None; Ethan Bensinger, C.Light Technologies Code C (Consultant), Travis C. Porco, None; Austin Roorda, USPTO#7,118,216, USPTO#6,890,076 (University of Rochester, University of Houston) Code P (Patent), C.Light Technologies Code I (Personal Financial Interest), Jacque L. Duncan, AGTC Code C (Consultant), Editas Medicine Code C (Consultant), Ionis Pharmaceuticals Code C (Consultant), Novelion Therapeutics Code C (Consultant), ProQR Therapeutics Code C (Consultant), SparingVision Code C (Consultant), Spark Therapeutics Code C (Consultant), Neurotech USA, Inc Code S (Non-remunerative)

Purpose
Retinitis pigmentosa (RP) causes death of rod, then cone photoreceptors. We measured cone structure and function with high-resolution in patients with mutations in rhodopsin (RHO), expressed only in rods, and patients with mutations in RPGR, expressed in both rods and cones.

Methods
8 RP patients (3 eyes with RHO mutations and 5 with RPGR mutations, mean age 32.5 ± 7.7 years) and 2 normal subjects (mean age 24.3 ± 1.7 years) were recruited for the study. Cone structure was studied with confocal and split detector adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain OCT. Cone function was measured with microperimetry using (i) fundus guided Scotopic-Macular Integrity Assessment (S-MAIA), performed in dark adapted conditions with a red (627 nm) stimulus (26 arcmin) and (ii) AOSLO microperimetry (AOMP) with a green (543 nm) stimulus (3.45 arcmin). Both systems were used to measure sensitivity of cone function at 1 deg intervals from fixation into the temporal retina. Cone density was measured as close as possible to each test location and the ratio of cone sensitivity to cone density was computed. Wilcoxon rank sum tests were used to compare this ratio between normal, RHO and RPGR patients.

Results
AOMP sensitivity/density ratios revealed RHO vs. RPGR to be significantly different from each other (P=0.003), and different from normal (normal vs. RHO P=0.034 and normal vs. RPGR P<0.001); sensitivity/cone was lowest in RPGR patients. Similarly, S-MAIA sensitivity/density was significantly lower in RHO and RPGR patients compared to normal (normal vs. RHO P=0.009 and normal vs. RPGR P<0.001), but RHO and RPGR patients were not significantly different from each other (P=0.11).

Conclusions
Normal subjects showed significantly greater sensitivity per cone compared with RP patients with RHO mutations, while sensitivity was even lower in patients with RPGR mutations. S-MAIA sensitivity/cone was also significantly lower in RP patients than normal, although results in patients with RHO and RPGR mutations were not significantly different. Cones in patients with RHO mutations retain better sensitivity than in patients with RPGR mutations, perhaps because cones express RPGR and degenerate primarily, while cones in eyes with RHO mutations die secondary to rod degeneration. High-resolution microperimetry can provide insight into mechanisms of cone degeneration in patients with different forms of RP.

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