Kim Eliane Staeubli^1,2,3 (), Marc Pabst^1,2, Roni Maimon-Mor^1,2, Mariya Moosajee^1,3,4, H. Steven Scholte⁵, Tessa Dekker^1,2,3; ¹Institute of Ophthalmology, University College London, London, UK, ²Experimental Psychology, University College London, London, UK, ³Moorfields Eye Hospital NHS Foundation Trust, London, UK, ⁴The Francis Crick Institute, London, UK, ⁵Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands

Inherited retinal diseases (IRDs) are a leading cause of blindness worldwide. CRB1-related retinopathies are an IRD in which mutations to a single gene cause a wide range of sight loss profiles for reasons not well understood. With emerging gene therapies aiming to restore retinal gene function, we need to characterise the impacts of the disease on retino-cortical development and function, and establish objective clinical trial endpoints that can be used across disease phenotypes. So far, this has been challenging due to patients’ widely varying abilities and the associated variability in test feasibility and sensitivity. We used a child-friendly electroencephalography (EEG) paradigm to quantify retinocortical visual system function in a cohort of patients with CRB1-related retinopathy. This involved recording steady-state visual evoked potentials (ssVEPs) in response to flickering sinusoidal gratings and full-field flicker embedded in age-appropriate movies. Our results reveal significant ssVEP attenuation in patients with CRB1-related retinopathy compared to sighted controls, with the most pronounced reductions in those with generalised retinal involvement and milder reductions in those with isolated macular dystrophy. While ssVEP curve amplitude differed across CRB1 phenotypes, we found no significant differences in curve shape at the group level. Intra-session reliability was high across the sample, but lower in patients with severe impairment, likely due to fixation instability. Notably, full-field flicker stimuli elicited reliable responses in these patients, strongly correlating with visual acuity, suggesting that this stimulus is an important addition to phase-reversing patterns when assessing visual function in severe vision loss using VEPs. These findings highlight the utility of VEPs as a non-invasive, objective measure of visual function that can be applied across a broad spectrum of IRD phenotypes and visual abilities. VEPs thus provide a valuable complement to traditional assessments of visual function for characterising disease characteristics and assessing treatment efficacy in IRDs.

Acknowledgements: This research was supported by the Santen SenSyT studentship scheme.