Effect of Human Central Nervous System Stem Cell Subretinal Transplantation on Progression of Geographic Atrophy Secondary to Non Neovascular Age-Related Macular Degeneration. Ophthalmology. Retina Nittala, M. G., Uji, A. n., Velaga, S. B., Hariri, A. H., Naor, J. n., Birch, D. G., Spencer, R. n., Leng, T. n., Capela, A. n., Tsukamoto, A. n., Ip, M. n., Sadda, S. R. 2020


To evaluate the effect of subretinally transplanted human central nervous system stem cells (HuCNS-SC) on progression of geographic atrophy (GA) in subjects with non-neovascular age-related macular degeneration (NNVAMD).Multicenter, prospective Phase I open-label clinical trial.Fifteen subjects with bilateral GA due solely to AMD.The eye with the worst best-corrected visual acuity from each subject was selected for treatment and considered the study eye; fellow eyes acted as controls. A total of 0.25 X 106 or 1.0 X 106 HuCNS-SC cells were directly infused into the subretinal space, superotemporal to the fovea near the junctional zone outside the area of GA. All subjects underwent spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging using the Spectralis HRA+OCT (Heidelberg Engineering Inc., Germany). Total GA area in both eyes was measured at baseline and month 12 by certified reading center graders using the Spectralis Region Finder software. Sectoral (clock hour)/directional radial GA progression rates with respect to the foveal center in both eyes were calculated using the polar transformation method in Image J. To facilitate comparative analysis across the cohort all eyes were transformed to a right eye orientation.Total GA area and sectoral/directional GA progression rates were compared in both study and control eyes.There was no statistically significant difference in mean change in total GA area at month 12 between study and fellow eyes (1.07 ± 0.84 vs. 2.08 ± 1.97 mm2, P=0.08). Whereas, the month 12 sectoral/directional radial GA growth rate for the superotemporal region (i.e. the location of HuCNS-SC cells transplantation) showed a significantly slower progression rate in study eyes than in fellow eyes (0.29 ± 0.58 vs. 1.08 ± 0.65 mm, P=0.007). The progression rate in the superotemporal quadrant of the study eye was significantly slower than in the other three quadrants combined (P=0.04) CONCLUSIONS: In this small pilot study, HuCNS-SC transplantation appeared associated with slower expansion of the GA lesion in the transplanted quadrant. Larger confirmatory studies are required. Sectoral or directional analysis of growth rates of GA may be a useful approach for assessing the efficacy of locally-delivered therapies.

View details for DOI 10.1016/j.oret.2020.06.012

View details for PubMedID 32562884