Patients with advanced IRDs that affect both rods and cones display a TPLR reduction of more than 5 log units, offering excellent dynamic range (Rukmini et al., 2019; Cideciyan et al., 2021b) and showed treatment-dependent improvement in phase 1 trials of RPE65 gene replacement therapy in LCA patients (Maguire et al., 2009). Here, RPE65 is linked to Leber congenital amaurosis.