PURPOSE: The purpose of this study was to characterize retinal structure in patients with late-stage inherited retinal diseases (IRD) for their suitability for optogenetic gene therapy. METHODS: This was a retrospective study using clinical data and spectral-domain optical coherence tomography (SD-OCT) images of patients with late-stage IRD (visual acuity ≤ 1.0), between December 2012 and 2023 from Oxford Eye Hospital, United Kingdom. Depending on the clinical phenotype and history, the patients were divided into three groups: rod-cone dystrophy (group 1), cone-rod/cone dystrophy (group 2), and macular dystrophy (group 3). SD-OCT structural parameters including total subfoveal thickness and, if possible, individual inner layers thickness were analyzed. RESULTS: 36 patients with late-stage IRD (11, 13, and 12 in groups 1, 2, and 3) and 54 eyes (18 per group) with mean age of 55.9 ± 9.8 years and mean visual acuity of 1.72 ± 0.66 were analyzed. Mean subfoveal thickness was reduced to 167.8 ± 54.3, 153.2 ± 65.3, and 138.1 ± 41.7 µm in groups 1, 2, and 3, respectively, with no significant difference among each group (P = 0.33). Twenty-five of 54 eyes had well-defined inner retinal layers with mean subfoveal thickness of nerve fiber, ganglion cell, inner plexiform, and inner nuclear layers were 12.6 ± 3.9, 17.3 ± 9.9, 18.6 ± 6.7, and 29.4 ± 11.3 µm, respectively. CONCLUSIONS: In our cohort, 46.3% of degenerate retinae had preservation of the inner retina, including nerve fiber, ganglion cell, and inner plexiform layers, and/or thickening of the inner nuclear layer and may benefit from targeted cell-specific optogenetic gene therapy. Patients with indiscernible or disrupted inner layers may be amenable to a non-cell-specific approach, to target all surviving neurons. TRANSLATIONAL RELEVANCE: SD-OCT structural characterization of different groups of late-stage IRD offers insight into vector selection and patient eligibility for optogenetic treatments.