Multimodal high-resolution imaging of retinal function in Retinitis Pigmentosa

Abstract

Purpose : Retinitis Pigmentosa (RP) is the most common inherited retinal disease and is characterized by progressive photoreceptor degeneration that leads to visual impairment. It remains unknown to what extent the diseased and surviving photoreceptors transduce light and support vision in RP. To address this, we correlated adaptive optics (AO) imaging of cone structure, AO microperimetry with retinally-tracked stimulus delivery, and AO-OCT based optoretinograms (ORGs) in the same RP subjects.

Methods : Three RP subjects (age 25-29) and 3 aged-matched controls were imaged with AO Scanning Laser Ophthalmoscopy (AOSLO) across the four cardinal meridians and the RP transition zone (TZ), which was verified using clinical OCT. Cones were counted in 100 by 100 micrometer regions of interest (ROI) spanning the TZ. Visual sensitivity was assessed by measuring increment thresholds for 543 nm, ½ Goldmann-I stimuli (3 arc-min), that were targeted to predetermined retinal locations via active eye tracking in the AOSLO. ORGs were measured at the same locations with line-field spectral domain AO-OCT to assess cone function. The change in optical path length (ΔOPL) between the cone outer segment tips and inner-outer segment junction reflections in AO-OCT were calculated following a 44% bleach of L/M-cones with 528 nm light stimulus.

Results : Cone density was reduced compared to controls in the majority of ROIs for all three RP subjects (p<0.05). Density reduction trended with TZ onset in Subject 1 (S1) and S2, while S3 had patches of reduced density throughout. ΔOPL was reduced in all 3 RP subjects in regions of reduced cone density compared to controls. There was an increased proportion of cones with reduced ΔOPL with increasing eccentricity in all RP subjects (p<0.05). Further, we observed a distinct subset (30%) of cones with reduced ΔOPL in a region with otherwise intact OCT outer retinal layers in S3. Interestingly, negative ΔOPLs were observed in the TZ of S1 and S2 (4.9% and 5.2% of cones). Despite significant deficits in cone density and ΔOPL, visual sensitivity to 3 arc-min retinal stimuli targeted to the same areas remained comparable to controls, with the exception of one test site in S1.

Conclusions : Multimodal high-resolution functional imaging enables a complementary picture of disease progression in RP, and shows that deficits in ORG-based measures of retinal function precede the reduction in visual sensitivity.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.