Effect of Human Central Nervous System Stem Cell Subretinal Transplantation on Progression of Geographic Atrophy Secondary to Nonneovascular Age-Related Macular Degeneration
Effect of Human Central Nervous System Stem Cell Subretinal Transplantation on Progression of Geographic Atrophy Secondary to Nonneovascular Age-Related Macular Degeneration
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DOI：
10.1016/j.oret.2020.06.012
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发表时间：
2021-01-04
影响因子：
4.5
通讯作者：
Sadda, Srinivas R.
中科院分区：
文献类型：
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作者：
Nittala, Muneeswar G.;Uji, Akihito;Sadda, Srinivas R.
目的：评价人中枢神经系统干细胞视网膜下移植的效果（HuCNS-SC）对非新生血管性年龄相关性黄斑变性（AMD）患者地图状萎缩（GA）进展的影响。设计：多中心、前瞻性、1期开放标签临床试验。参与者：15名仅因AMD而患双侧GA的患者。方法：从每例患者中选择最佳矫正视力最差的眼睛进行治疗，并将其视为研究眼睛;对侧眼睛作为对照。将总共0.25 x 10（6）或1.0 x 10（6）HuCNS-SC直接注入视网膜下腔，靠近连接区的中央凹颞上方，GA区域外。所有患者都使用Spectralis HRA+OCT（Heidelberg Engineering，Inc.，海德堡，德国）。在基线和第12个月时，由经认证的阅读中心分级员使用Spectralis RegionTM软件测量双眼中的总GA面积。使用Image J软件（National Institutes of Health，Bethesda，MD）中的极变换方法计算双眼中相对于中央凹中心的每个方向的径向GA进展速率的扇区（时钟小时）。为了便于整个队列的比较分析，所有的眼睛都转换为右眼orientation.Main结果Measures：总GA面积和部门每个方向GA进展率进行了比较，在研究和对照眼。在12个月时，研究眼和对侧眼的总GA面积的平均变化无统计学显著差异（1.07 ± 0.84 mm（2）vs. 2.08 ± 1.97 mm（2）; P = 0.08）。然而，第12个月的上颞区的每个方向的径向GA生长速率（即，HuCNS-SC移植的位置）显示研究眼的进展速率显著慢于对侧眼（0.29 +/- 0.58 mm对1.08 +/- 0.65 mm; P = 0.007）。研究眼的颞上象限的进展速率显著慢于其他3个象限的组合（P = 0.04）。结论：在这项小型试点研究中，HuCNS-SC移植似乎与移植象限中GA病变的缓慢扩张相关。需要更大规模的验证性研究。GA的生长率的部门或方向分析可能是一个有用的方法，用于评估局部递送疗法的疗效。(C)2020年美国眼科学会
Purpose: To evaluate the effect of subretinally transplanted human central nervous system stem cells (HuCNS-SC) on the progression of geographic atrophy (GA) in patients with nonneovascular age-related macular degeneration (AMD).Design: Multicenter, prospective, phase 1 open-label clinical trial.Participants: Fifteen patients with bilateral GA solely the result of AMD.Methods: The eye with the worst best-corrected visual acuity from each patient was selected for treatment and was considered the study eye; fellow eyes served as controls. A total of 0.25 x 10(6) or 1.0 x 10(6) HuCNS-SCs were infused directly into the subretinal space, superotemporal to the fovea near the junctional zone, outside the area of GA. All patients underwent spectral-domain OCT and fundus autofluorescence imaging using the Spectralis HRA+OCT (Heidelberg Engineering, Inc., Heidelberg, 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) per directional radial GA progression rates with respect to the foveal center in both eyes were calculated using the polar transformation method in Image J software (National Institutes of Health, Bethesda, MD). To facilitate comparative analysis across the cohort, all eyes were transformed to a right-eye orientation.Main Outcome Measures: Total GA area and sectoral per directional GA progression rates were compared in both study and control eyes.Results: No statistically significant difference was found in mean change in total GA area at month 12 between study and fellow eyes (1.07 +/- 0.84 mm(2) vs. 2.08 +/- 1.97 mm(2); P = 0.08). However, the month 12 sectoral per directional radial GA growth rate for the superotemporal region (i.e., the location of HuCNS-SC transplantation) showed a significantly slower progression rate in study eyes than in fellow eyes (0.29 +/- 0.58 mm 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 3 quadrants combined (P = 0.04).Conclusions: In this small pilot study, HuCNS-SC transplantation seems to be 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. (C) 2020 by the American Academy of Ophthalmology