Tracking Neural, Sensory, and Sensorimotor Adaptation to Progressive Vision Loss in Inherited Retinal Dystrophies: A Multimodal Longitudinal Study Protocol

Individuals with inherited retinal dystrophies (IRDs) undergo a slow, genetically heterogeneous loss of vision, yet how the visual cortex and non-visual sensory, motor, and psychological systems adapt to this deprivation remains poorly characterized. Existing evidence comes mainly from single-modality, cross-sectional studies that rarely account for genetic heterogeneity, making it hard to distinguish adaptive change from a direct, non-retinal mutation effect, since several IRD genes are not retina-specific. To address this gap, we designed an observational, longitudinal, multimodal protocol that combines ophthalmological, genetic, and in silico characterization with electrophysiological (steady-state visual evoked potentials and TMS-EEG), chemosensory, sensorimotor, and psycho-personological assessments. Patients aged 18 to 75 years with rod-cone (retinitis pigmentosa, Usher syndrome) or cone and cone-rod dystrophies will be assessed at baseline (T0) and at an 18-month follow-up (T1); sighted controls, matched for age, sex, and handedness, will complete the same battery once. Importantly, pairing genotypic with phenotypic data allows changes in non-visual domains to be interpreted against, rather than independently of, each patient’s molecular background. We expect individuals with IRDs to differ from controls in visual cortical responsiveness and in selected non-visual sensory and sensorimotor measures, with genotype-related differences explored where sample size permits. Given the rarity of IRDs, the design is exploratory and emphasizes effect sizes and individual variability over large-sample inference. The protocol was approved by the Ethics Committee of the University of Verona (CARP 08.R1/2024) and follows the Declaration of Helsinki and the GDPR; findings will be disseminated through peer-reviewed publications and shared with patients and IRD patient associations.