AbstractAchromatopsia (ACHM) is an inherited retinal disease characterised by complete loss of cone photoreceptor function from birth. In recent years, gene therapies have successfully been used to induce signal processing in dormant cones in animal models of ACHM, with greater functional benefits for younger animals. With several completed or on-going clinical trials of gene therapy for ACHM, preliminary evidence suggests that effects on visual function in adults with ACHM may be subtle. Given the known constraints of age on neural plasticity, it is possible that gene therapy earlier in life will have a greater impact. Sensitive, child-friendly tests of cone function are therefore needed to facilitate the optimisation of these treatment strategies. Here, we present a new method that leverages a multimodal approach, linking psychophysical estimates of cone function to cone-mediated signals in visual cortex, measured using fMRI. In a case study of two children with ACHM undergoing gene therapy, we find individual differences in recovery of cone function over time, with one child demonstrating strong concurrent evidence of improved cone function, and retinotopically organised responses in visual cortex to cone-selective stimuli. Integrated fMRI and psychophysical measures may provide insight into the utility of new sight-rescuing therapies at different stages of human development.
Methodological Challenges in the Economic Evaluation of a Gene Therapy for RPE65-Mediated Inherited Retinal Disease: The Value of Vision
