Residual Foveal Cone Structure in CNGB3-Associated Achromatopsia.
Residual Foveal Cone Structure in CNGB3-Associated Achromatopsia.
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DOI：
10.1167/iovs.16-19313
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发表时间：
2016-08-01
影响因子：
4.4
通讯作者：
ACHM-001 Study Group
中科院分区：
文献类型：
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作者：
Langlo CS;Patterson EJ;Higgins BP;Summerfelt P;Razeen MM;Erker LR;Parker M;Collison FT;Fishman GA;Kay CN;Zhang J;Weleber RG;Yang P;Wilson DJ;Pennesi ME;Lam BL;Chiang J;Chulay JD;Dubra A;Hauswirth WW;Carroll J;ACHM-001 Study Group
先天性色盲(ACHM)是一种常染色体隐性遗传性疾病，视锥功能缺失或严重减退。ACHM动物模型的基因治疗显示了视锥功能的恢复，尽管这些结果在一定程度上依赖于治疗时存活的视锥感光细胞的存在。在这里，我们描述了CNGB3相关的ACHM受试者的残余视锥结构。对51例CNGB3相关的ACHM患者行高分辨率成像(光学相干断层扫描[OCT]和自适应光学扫描光检眼镜[AOSLO])。用分裂检测AOSLO测量中心凹的峰值视锥密度和视锥间距。在OCT图像中测量中心凹外核层厚度，并使用先前发表的OCT分级方案来评估光感受器层的完整性。51名受试者中有26人获得了中心凹视锥的可分析图像，眼球震颤是获得高质量图像的主要障碍。黄斑中心凹密度峰值为7,273~53,554个/mm~2，显著低于正常范围(84,733~234,391个/mm~2)，残存视锥呈连续或稀疏排列。峰值锥体密度与OCT完整性分级相关，但不同OCT分级之间密度范围存在重叠。CNGB3相关的ACHM患者的残留中心凹锥体结构的程度有很大的不同。这种测量方法可能有助于估计特定视网膜的治疗潜力，为受影响的个人和医生提供有价值的信息，以便在他们考虑参加实验性基因治疗试验时更准确地评估风险-收益比。(www.Clinicaltrials.gov，NCT01846052)
Congenital achromatopsia (ACHM) is an autosomal recessive disorder in which cone function is absent or severely reduced. Gene therapy in animal models of ACHM have shown restoration of cone function, though translation of these results to humans relies, in part, on the presence of viable cone photoreceptors at the time of treatment. Here, we characterized residual cone structure in subjects with CNGB3-associated ACHM. High-resolution imaging (optical coherence tomography [OCT] and adaptive optics scanning light ophthalmoscopy [AOSLO]) was performed in 51 subjects with CNGB3-associated ACHM. Peak cone density and inter-cone spacing at the fovea was measured using split-detection AOSLO. Foveal outer nuclear layer thickness was measured in OCT images, and the integrity of the photoreceptor layer was assessed using a previously published OCT grading scheme. Analyzable images of the foveal cones were obtained in 26 of 51 subjects, with nystagmus representing the major obstacle to obtaining high-quality images. Peak foveal cone density ranged from 7,273 to 53,554 cones/mm2, significantly lower than normal (range, 84,733–234,391 cones/mm2), with the remnant cones being either contiguously or sparsely arranged. Peak cone density was correlated with OCT integrity grade; however, there was overlap of the density ranges between OCT grades. The degree of residual foveal cone structure varies greatly among subjects with CNGB3-associated ACHM. Such measurements may be useful in estimating the therapeutic potential of a given retina, providing affected individuals and physicians with valuable information to more accurately assess the risk-benefit ratio as they consider enrolling in experimental gene therapy trials. (www.clinicaltrials.gov, NCT01846052.)