■我们调查了由于MYO7A基因变异导致的视网膜营养不良的自然史。
■53名患者(平均年龄,33.6±16.7年),归因于双等位基因的厄舍尔综合征,主要是致病性的,MYO7A变异体接受了基线和2次年度随访.最佳矫正视力(BCVA),半自动动态视野,全场视网膜电图,彩色眼底成像,显微视野,谱域光学相干层析成像,和眼底自发荧光进行了评估。
■在基线时,所有患者均表现为BCVA降低(66.4±17.9早期治疗糖尿病视网膜病变评分和59.5±21.7早期治疗糖尿病视网膜病变评分,在更好和更糟糕的眼睛里,分别),受限半自动动态视野(III4e区,3365.8±4142.1°2;4176.4±4400.3°2),黄斑敏感性降低(9.7±9.9dB;9.0±10.2dB)。谱域光学相干断层扫描显示黄斑中心厚度减小(259.6±63.0µm;250.7±63.3µm),椭球区带宽变窄(2807.5±2374.6µm;2615.5±2370.4µm)。纵向分析(50名患者)显示,在视力较好的眼睛中,BCVA显着降低,而在视力较差的眼睛中没有观察到任何参数的变化。BCVA,半自动动态视野(III4e和V4e)和黄斑敏感度与基线年龄显著相关.与高自发荧光环模式(22眼[43.1%])相比,高自发荧光中央凹贴片(16眼[31.4%])和异常中枢低自发荧光(9眼[17.6%])与更差的形态和功能读数显着相关。
■我们的欧洲多中心研究对迄今为止描述的最大的MYO7A患者队列之一进行了首次前瞻性纵向分析。确认疾病进展缓慢。更重要的是,这项研究强调了眼底自发荧光模式在视网膜损害分期中的关键作用,并主张将其作为未来基因治疗临床试验患者选择的客观生物标志物.
UNASSIGNED: We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene.
UNASSIGNED: Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed.
UNASSIGNED: At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]).
UNASSIGNED: Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.