Using Steady-State Visual Evoked Potentials to Characterize Wide-Ranging Retinopathy Linked to CRB1: Implications for...

Rapid advances in gene therapy are moving sight rescue treatments for inherited retinal diseases (IRDs) within reach, creating an urgent need to understand how these conditions affect neural signaling from the eye to the brain. However, capturing functional change across the diverse IRD sight-loss spectrum using a unified testing framework is challenging. Computational neuroimaging may help address this gap by exploiting known principles of visual-system tuning to derive more sensitive and computationally meaningful markers of visual function. This is particularly important in CRB1 retinopathy, an IRD with a strikingly wide phenotype range, where neural impacts across the full disease spectrum are not yet characterized. To investigate the functional impact of CRB1 retinopathy, we recorded steady-state visual evoked potentials (ssVEPs) in 72 eyes from 18 patients and 18 sighted controls using a patient-friendly, large-field protocol embedding phase-reversing sinusoidal gratings and full-screen flashes into age-appropriate videos. Fitting these data with neural tuning functions revealed significant ssVEP attenuation in patients, with the greatest reductions in those with generalized retinal degeneration, alongside shifts in spatial-frequency tuning toward lower frequencies. Our results show that with appropriate stimulus selection, ssVEPs offer a reliable response-free measure of visual function that correlates well with behavioral vision assessments and discriminates between CRB1 subgroups, with the optimally sensitive stimulus for detecting functional variation varying with the level of vision. Computational electroencephalogram-based neuroimaging thus provides quantitative insights across the wide spectrum of CRB1 pathology and represents a valuable complementary tool for evaluating disease progression and treatment outcomes in CRB1 retinopathy and related IRDs.