Photoreceptor-Specific Loss of Perifoveal Temporal Contrast Sensitivity in Retinitis Pigmentosa

Purpose: Inherited retinal diseases affect the L-, M-, S-cones and rods in distinct ways, which calls for new methods that enable quantification of photoreceptor-specific functions. We tested the feasibility of using the silent substitution paradigm to estimate photoreceptor-driven temporal contrast sensitivity (tCS) functions in patients with retinitis pigmentosa.

Methods: The silent substitution paradigm is based on substitution of lights of different spectral composition; this offers considerable advantage over other stimulation techniques. We used a four-primary LED stimulator to create perifoveal annular stimuli (2° inner, 12° outer diameters) and used a triple silent substitution to probe photoreceptor-selective tCS. Measurements were performed in a heterogeneous cohort of 15 patients with retinitis pigmentosa and related to those in a control group of nine color-normal healthy observers. Age differences between groups were addressed with a model of age-related normal contrast sensitivity derived from measurements in 20 healthy observers aged between 23 and 83 years.

Results: The age-related loss of tCS amounted to 0.1 dB/year in healthy subjects across all photoreceptor subtypes. In patients, tCS was decreased for every photoreceptor subtype; however, S-cone- and rod-driven sensitivities were most strongly affected. Postreceptoral mechanisms were not affected.

Conclusions: This feasibility study provides evidence that the silent substitution technique enables the estimation of photoreceptor-selective tCS functions and can serve as an accurate biomarker of photoreceptor-specific contrast sensitivity loss in patients with retinitis pigmentosa.

Translational relevance: We aim to develop tests of visual function for clinical trials of novel therapies for inherited retinal diseases from methods that can currently be used only in vision research labs.