Retinal structure and function in achromatopsia: implications for gene therapy.
Retinal structure and function in achromatopsia: implications for gene therapy.
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DOI：
10.1016/j.ophtha.2013.08.017
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发表时间：
2014-01
期刊：
影响因子：
13.7
通讯作者：
Michaelides M
中科院分区：
文献类型：
--
作者：
Sundaram V;Wilde C;Aboshiha J;Cowing J;Han C;Langlo CS;Chana R;Davidson AE;Sergouniotis PI;Bainbridge JW;Ali RR;Dubra A;Rubin G;Webster AR;Moore AT;Nardini M;Carroll J;Michaelides M
探讨全色盲患者视网膜结构和功能的特点，为基因治疗的临床试验做准备。横断面研究。40例ACHM受试者。所有受试者均接受了光谱域光学相干断层扫描（SD-OCT）、微视野检查和分子遗传学检测。将SD-OCT上的中心凹结构分为5个不同类别：（i）连续内段椭圆体（ISe），（ii）ISe破坏，（iii）ISe缺失，（iv）存在低反射区（HRZ），以及（v）外部视网膜萎缩，包括视网膜色素上皮（RPE）丢失。测量中心凹和外核层（ONL）厚度，并确定是否存在发育不全。SD-OCT成像上的感光器外观;中心凹和ONL厚度;中心凹发育不全的存在;视网膜敏感性和固定稳定性;以及这些参数与年龄和基因型的关联。纳入了40例平均年龄为24.9岁（范围6 - 52岁）的受试者。在CNGA 3（n = 18）、CNGB 3（n = 15）、GNAT 2（n = 4）和PDE6C（n = 1）中发现致病变体。在2个个体中未发现变异。22.5%的受试者在中央凹处有连续的ISe层; 27.5%有ISe破坏; 20%有ISe层缺失; 22.5%有HRZ; 7.5%有外视网膜萎缩。在5个SD-OCT类别中，年龄（p = 0.77）、平均视网膜灵敏度（p = 0.21）或固视稳定性（p = 0.34）无显著差异。年龄与中心凹厚度之间（p = 0.84）或年龄与中心凹ONL厚度之间（p = 0.12）无显著相关性。ACHM视网膜结构或功能的破坏与年龄缺乏明确的相关性，这表明基因治疗干预的机会窗口在某些个体中比以前指出的更宽。因此，对于给定受试者的潜在益处可能通过感光器结构的特定测量而不是简单地通过年龄来更好地预测。利用SD-OCT和/或自适应光学成像直接评估锥光感受器保存的能力可能在选择未来试验的受试者和测量其影响方面证明是非常宝贵的。
To characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical trials of gene therapy. Cross-sectional study. Forty subjects with ACHM. All subjects underwent spectral domain optical coherence tomography (SD-OCT), microperimetry, and molecular genetic testing. Foveal structure on SD-OCT was graded into 5 distinct categories: (i) continuous inner segment ellipsoid (ISe), (ii) ISe disruption, (iii) ISe absence, (iv) presence of a hyporeflective zone (HRZ), and (v) outer retinal atrophy including retinal pigment epithelial (RPE) loss. Foveal and outer nuclear layer (ONL) thickness was measured, and presence of hypoplasia determined. Photoreceptor appearance on SD-OCT imaging; foveal and ONL thickness; presence of foveal hypoplasia; retinal sensitivity and fixation stability; and association of these parameters with age and genotype. Forty subjects with mean age of 24.9 years (range 6 to 52) were included. Disease-causing variants were found in CNGA3 (n=18), CNGB3 (n=15), GNAT2 (n=4), and PDE6C (n=1). No variants were found in 2 individuals. 22.5% of subjects had a continuous ISe layer at the fovea; 27.5% had ISe disruption; 20% had an absent ISe layer; 22.5% had a HRZ; and 7.5% had outer retinal atrophy. No significant differences in age (p=0.77), mean retinal sensitivity (p=0.21) or fixation stability (p=0.34) across the 5 SD-OCT categories were evident. No significant correlation was found between age and foveal thickness (p=0.84), or between age and foveal ONL thickness (p=0.12). The lack of clear association of disruption of retinal structure or function in ACHM with age suggests that the window of opportunity for intervention by gene therapy is wider in some individuals than previously indicated. Therefore the potential benefit for a given subject is likely to be better predicted by specific measurement of photoreceptor structure rather than simply by age. The ability to directly assess cone photoreceptor preservation with SD-OCT and/or adaptive optics imaging is likely to prove invaluable in selecting subjects for future trials and measuring their impact.
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影响因子：
1.8
作者：
McAllister, John T.;Dubis, Adam M.;Tait, Diane M.;Ostler, Shawn;Rha, Jungtae;Stepien, Kimberly E.;Summers, C. Gail;Carroll, Joseph
通讯作者：
Carroll, Joseph
影响因子：
4.4
作者：
Carroll, Joseph;Dubra, Alfredo;Michaelides, Michel
通讯作者：
Michaelides, Michel
影响因子：
--
作者：
Pang, Ji-Jing;Alexander, John;Lei, Bo;Deng, Wentao;Zhang, Keqing;Li, Qiuhong;Chang, Bo;Hauswirth, William W.
通讯作者：
Hauswirth, William W.
影响因子：
4
作者：
Aligianis, IA;Forshew, T;Maher, ER
通讯作者：
Maher, ER
影响因子：
13.7
作者：
Thomas, Mervyn G.;Kumar, Anil;Gottlob, Irene
通讯作者：
Gottlob, Irene