Development and Validation of a Commercially Available Two Color Dark Adapted Perimetry to Assess Inherited Retinal...

This study aimed to develop and validate a commercially available 2-color dark-adapted full field perimetry (2cDAP) protocol to assess rod and cone function in patients with inherited retinal degenerations (IRDs), specifically retinitis pigmentosa (RP). The goal was to establish a widely accessible and reproducible method for measuring rod function for use in evaluating treatment efficacy in clinical trials.

We developed a 2cDAP protocol using the Octopus 900 Pro perimeter to measure thresholds to 450 nm (blue) and 610 nm (red) stimuli under dark-adapted conditions. The spectral sensitivity difference (SSD) between the stimuli was calculated to determine rod and cone mediation. A cohort of 35 RP patients and 14 normally sighted subjects underwent 2cDAP and standard light-adapted perimetry (LAP) across a standardized 78-point grid. Longitudinal data were collected from 12 RP patients over 12 months.

2cDAP demonstrated high repeatability in normally sighted subjects and consistent results across institutions. For normally sighted subjects, testing time was approximately 14.1 minutes for the red stimulus, 14.5 minutes for the blue stimulus, and 13.1 minutes for LAP. The testing time for patients with RP was approximately 13.3 minutes for the red stimulus, 13.2 minutes for the blue stimulus, and 12.1 minutes for LAP. The method detected rod-mediated function in retinal regions undetectable by LAP. Longitudinal data showed faster progression rates in rod-mediated loci compared to cone-mediated loci when measured under scotopic with a blue or red stimulus compared to standard white stimuli in mesopic conditions. For dark-adapted blue stimuli, the drop in mean sensitivity was from 25.8 dB to 20.4 dB in a year (a -5.4 dB change), compared to the dark-adapted red stimulus where mean sensitivity changed from 17.3 dB to 16.9 dB (a -0.4 dB change) and light-adapted perimetry with the white stimulus where mean sensitivity changed from 15.6 dB to 14.2 dB (a -1.4 dB change). These findings underscore the utility of 2cDAP in capturing early rod function loss, which is critical for evaluating emerging treatments.

Our 2cDAP protocol provides a robust, spatially resolved assessment of photoreceptor function in IRDs. Its ability to differentiate rod and cone contributions, coupled with its accessibility on commercially available equipment, makes it a promising tool for multicenter clinical trials. Future work will focus on refining the protocol, expanding normative databases, and validating the method in larger patient cohorts.