Abstract
Purpose :
Outer retinal layer atrophy with preservation of inner retinal layer is a typical feature in most late-stage retinal degenerations. Optogenetics offer a potential gene-agnostic approach to restore vision in patients affected by these conditions by photosensitising residual inner retinal layer cells. Our study aims to characterise OCT structural parameters of these diseases, focusing on central inner retinal layers, for their suitability for optogenetic gene therapy.
Methods :
Cross-sectional study using clinical data and OCT images (Spectralis, Heidelberg Engineering, Heidelberg, Germany) of patients with late-stage inherited retinal degenerations (visual acuity≦1.0), from Oxford Eye Hospital, UK. Eyes were divided into rod (group 1), cone-rod/cone (group 2), and macular dystrophies (group 3). OCT scans were manually segmented to determine central subfield thickness. If possible, individual inner layer thickness (retinal nerve fibre layer, RNFL; ganglion cell layer, GCL; inner plexiform layer, IPL; inner nuclear layer, INL) were quantified. Statistical analyses were performed using SPSS V29.0 (Armonk, NY).
Results :
36 late-stage inherited retinal disease patients (11,13,12 in groups 1,2,3) 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 analysed. Manual re-segmentation was required in 50/54 scans. There was poor delineation of outer retinal layers in 54/54, INL/outer plexiform layer in 20/54, and inner retinal layers in 20/54 scans. Mean central subfield thickness were reduced at 167.8±54.3, 153±65.3, and 152±73.2μm in groups 1, 2, and 3 respectively with no significant difference between groups (p=0.334; normal≈280μm). 25/54 eyes had well-defined inner layers for sub-segmentation with mean central RNFL, GCL, IPL, and INL thickness of 12.6±3.9, 17.3±9.9, 18.6±6.7, and 29.4±11.3μm respectively.
Conclusions :
Extensive structural changes in late-stage inherited retinal degenerations represent a significant challenge to OCT assessment for optogenetics in clinical practice. In our cohort, 46% of degenerate retinas had preserved RNFL, GCL, IPL and thickening of INL and may benefit from optogenetic targeting of specific inner layer cells. Patients with indiscernible inner retinal layers may be amenable to a non-cell-specific approach with ubiquitous targeting of any surviving cells.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.