Discriminating inherited retinal diseases based on photoreceptor-directed temporal contrast sensitivity measurements

Abstract

Purpose : In the past, we have published temporal contrast sensitivities (tCS) for circular, perifoveal stimuli directed at the different photoreceptor types in small cohorts of patients with retinitis pigmentosa (RP), Stargardt’s disease (STGD) and RP1L1-associated occult macular dystrophy (OMD). Here, we compare the three cohorts and analyzed the power of the pd tCS functions to discriminate them.

Methods : L-, M-, S-cone and rod-directed stimuli were created in a circular test field (2° inner, 12° outer diameter) using a 4-primary LED stimulator with triple-silent-substitution at temporal frequencies of 1, 2, 4, 6, 8, 10, 12, 16, 20 Hz. tCS deviation was calculated based on published normal values using an age-correction of 0.1 dB/year and then averaged across a range of neighboring temporal frequencies (temporal Contrast sensitivity Mean Deviation, tCMD). For L-cones, we used the frequency range 1-6 Hz (LMD_low; mediated by the red-green-opponency system) and 8-20 Hz (LMD_high; luminance system). For S-cones we used 1-6 Hz and for rods 6-12Hz (SMD/RMD). We performed classification tree analysis and ROC analyses using the R statistical programming language (packages rpart and pROC).

Results : Forty-nine subjects (normal: 9, RP: 15, STGD: 14, OMD: 11) were included. A recursive classification tree with a maximal depth of 2 branches and a minimum group size for splitting of 5 ended up using the parameter RMD for discriminating normal/OMD from STGD/RP, LMD_low for discriminating normal subjects from OMD patients, and SMD for discriminating RP from STGD, yielding an accuracy of 63% (p < 0.001). In the ROC analyses, the area-under-the-curve (AUC) was 0.84 for detecting abnormalities of the rod-driven function in RP and STGD (vs. normal/OMD), 0.91 for detecting abnormal L-cone-driven red-green-opponency in OMD patients (vs. normal subjects), and 0.64 for detecting poorer S-cone-driven tCS in RP (vs. STGD).

Conclusions : The ability of our technique to classify functional phenotypes was very good, particularly given the genotypical and phenotypical heterogeneity of the RP group. Thus, photoreceptor-directed tCMDs are a promising new tool for measuring visual function in IRDs.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.