Mustafic Nina, Ristoldo Federica, Nguyen Vuong, Fraser Clare L, Invernizzi Alessandro, Jamieson Robyn V, Grigg John R
The Discipline of Clinical Ophthalmology and Eye Health, Save Sight Institute, Sydney Eye Hospital, Faculty of Medicine and Health, The University of Sydney, 8 Macquarie Street, Sydney, NSW, 2001, Australia.
Department of Biomedical and Clinical Science 'L. Sacco', Luigi Sacco Hospital, University of Milan, Milan, Italy.
Doc Ophthalmol. 2020 Dec;141(3):205-215. doi: 10.1007/s10633-020-09765-0. Epub 2020 Apr 2.
To investigate the functional and structural biomarkers and their correlation with Usher syndrome (USH).
Medical records, imaging and electrophysiology test results of USH patients attending the Save Sight Institute between 2012 and 2017 were reviewed. Best corrected visual acuity (BCVA), ultra-widefield autofluorescence (UW-FAF), spectral-domain optical coherence tomography (SD-OCT), full-field electroretinogram and pattern electroretinogram (pERG) were performed. SD-OCT scans assessed central macular thickness (CMT), greatest linear diameter of preserved outer retinal layers-macular island (MI) and presence of cystoid macular edema (CME). UW-FAF images were qualitatively graded to identify hypo/hyperfluorescence patterns in the peripheral fundus.
Thirty-six eyes from 18 subjects were included. Mean BCVA was 0.22 ± 0.3 LogMAR. MI extent was significantly associated with better vision (β = - 0.175 per 1000 µm; R = 0.487; P = 0.002; Fig. 4). A higher pERG P50 was associated with a larger macular island (β = 782 per µV; R = 0.238; P = 0.025), while a higher pERG N95 was associated with a smaller macular island (β = - 499 per µV; R = 0.219; P = 0.030). Mean CMT was 271 ± 35 μm and was significantly associated with better vision (β = - 0.083 per 10 µm; R = 0.612; P < 0.001). CME was diagnosed in 47.2% (n = 17) eyes. There was no significant difference in mean BCVA for those with CME (0.19 ± 0.2 LogMAR) and without CME (0.40 ± 0.5; R = 0.081; P = 0.17). All patients had abnormal UW-FAF. Four main patterns of change were identified (granular 55%, annular 11%, bone spicule 17% and patchy 17%). Patients with the patchy pattern demonstrated worse BCVA in comparison with those with granular (P < 0.0001) and bone spicule (P = 0.0179) patterns.
Structural changes identified on OCT and UW-FAF correlated with BCVA and pERG in this cohort representing different stages of the disease. These parameters could represent reliable biomarkers in therapeutic clinical trials on USH.
研究功能性和结构性生物标志物及其与Usher综合征（USH）的相关性。
回顾了2012年至2017年在拯救视力研究所就诊的USH患者的病历、影像学和电生理检查结果。进行了最佳矫正视力（BCVA）、超广角自发荧光（UW-FAF）、光谱域光学相干断层扫描（SD-OCT）、全视野视网膜电图和图形视网膜电图（pERG）检查。SD-OCT扫描评估中心黄斑厚度（CMT）、保留的外层视网膜层-黄斑岛（MI）的最大线性直径以及黄斑囊样水肿（CME）的存在情况。对UW-FAF图像进行定性分级，以识别周边眼底的低/高荧光模式。
纳入了18名受试者的36只眼。平均BCVA为0.22±0.3 LogMAR。MI范围与更好的视力显著相关（每1000μmβ=-0.175；R=0.487；P=0.002；图4）。较高的pERG P50与较大的黄斑岛相关（每μVβ=782；R=0.238；P=0.025），而较高的pERG N95与较小的黄斑岛相关（每μVβ=-499；R=0.219；P=0.030）。平均CMT为271±35μm，与更好的视力显著相关（每10μmβ=-0.083；R=0.612；P<0.001）。47.2%（n=17）的眼睛诊断为CME。有CME的患者（0.19±0.2 LogMAR）和无CME的患者（0.40±0.5；R=0.081；P=0.17）的平均BCVA无显著差异。所有患者的UW-FAF均异常。识别出四种主要变化模式（颗粒状55%、环状11%、骨针状17%和斑片状17%）。与颗粒状（P<0.0001）和骨针状（P=0.0179）模式的患者相比，斑片状模式的患者BCVA更差。
在该代表疾病不同阶段的队列中，OCT和UW-FAF上识别出的结构变化与BCVA和pERG相关。这些参数可能代表USH治疗性临床试验中的可靠生物标志物。
