Objective measurement of local rod and cone function using gaze-controlled chromatic pupil campimetry in healthy subjects.

BackgroundVoretigene neparvovec is a gene therapeutic agent for treatment of retinal dystrophies caused by bi-allelic RPE65 mutations. In this study, we report on a novel and objective evaluation of a retinotopic photoreceptor rescue.MethodsSeven eyes of five patients (14, 21, 23, 24, 36 years, 1 male, 4 females) with bi-allelic RPE65 mutations have been treated with voretigene neparvovec. The clinical examinations included visual acuity testing, dark-adapted full-field stimulus threshold (FST), dark-adapted chromatic perimeter (DAC) with a 30-degree grid, and a 30 degrees grid scotopic and photopic chromatic pupil campimetry (CPC). All evaluations and spectral domain optical coherence tomography were performed at baseline, 1 month and 3 months.ResultsAll except the oldest patient had a measurable improvement of the rod function assessed via FST, DAC or scotopic CPC at 1 month. The visual acuity improved slightly or remained stable in all eyes. A cone function improvement as measured by photopic CPC was observed in three eyes. The gain of the dark-adapted threshold with blue FST and the DAC stimuli (cyan) average correlated strongly with age (R2>0.7). The pupil response improvement in the scotopic CPC correlated with the baseline local retinal volume (R2=0.5).ConclusionsThe presented protocols allow evaluating the individual spatial and temporal effects of gene therapy effects. Additionally, we explored parameters that correlated with the success of the therapy. CPC and DAC present new and fast ways to assess functional changes in retinotopic maps of rod and cone function, measuring complementary aspects of retinal function.

This work presents a quick clinical protocol for dark-adapted chromatic (DAC) perimetry as well as a novel clinical tool, scotopic chromatic pupil campimetry (CPC). The goal of the study was to explore the applicability of these methods in a clinical setting, their test-retest repeatability, and the congruence of the results. Local rod sensitivity was assessed at 36 locations within 30° eccentricity of the visual field in 15 healthy subjects (mean age 43 ± 16 years; 7 females and 8 males) with DAC perimetry (red and cyan stimuli) and CPC 2 times in repeated measurements. The duration of individual measurements was 370 ± 5 s for CPC and 366 ± 62 s for DAC perimetry. The intraclass correlation (ICC) coefficient was 0.53 for DAC perimetry cyan stimuli, 0.67 for red stimuli, and 0.93 for CPC. However, the spatial resolution of CPC was substantially smaller than in DAC perimetry. We did not find a correlation of DAC perimetry and CPC measurements on the global or the local level. In comparison to DAC perimetry, CPC shows a superior intervisit repeatability in detecting functional changes in the rod population in an objective way with lower spatial resolution. Our results also indicate that these 2 methods measure the rod function in different ways and could thus constitute complementary scotopic functional diagnostics.