Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2 A Randomized Clinical Trial
Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2 A Randomized Clinical Trial
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DOI：
10.1016/j.ophtha.2018.09.041
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发表时间：
2019-04-01
期刊：
影响因子：
13.7
通讯作者：
Friedlander, Martin
中科院分区：
文献类型：
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作者：
Chew, Emily Y.;Clemons, Traci E.;Friedlander, Martin
目的：测试基于封装细胞的神经保护剂睫状神经营养因子（CNTF）的递送对 2 型黄斑毛细血管扩张症进展的影响，这是一种尚未被证实有效治疗的神经退行性疾病。设计：随机假对照临床试验。参与者：纳入了 67 名符合条件的参与者的 99 只研究眼。方法：从 2014 年 5 月到2017 年 4 月在美国和澳大利亚的 11 个视网膜专家临床中心进行。参与者以 1:1 的比例随机分配到玻璃体内持续递送人类 CNTF 的手术植入组与假手术组。 主要结果指标：主要结果是治疗组和未治疗组之间 24 个月时在谱域 (SD) OCT 图像上测量的椭球区破坏（或光感受器损失）面积所测量的神经变性面积的差异。次要结局包括治疗组之间视觉功能变化的比较。结果：在 67 名随机参与者（平均年龄 62 +/- 8.9 岁；41 名女性 [61%]；58 名白人 [86%]）中，65 名（97%）完成了研究。两名参与者（3 只研究眼睛）死亡，3 名参与者（4 只眼睛）被发现不符合资格。接受假治疗的眼睛比接受 CNTF 治疗的眼睛的神经退行性疾病进展要快 31%。 24 个月时，光感受器损失的平均面积差异为 0.05 +/- 0.03 mm(2) (P = 0.04)。使用显微视野测量法测量的视网膜敏感性变化与光感受器损失面积的变化高度相关（r = 0.86；P < 0.0001）。假手术组的平均视网膜敏感性损失比治疗组高 45%（下降 15.81 +/- 8.93 dB；P = 0.07）。假手术组的阅读速度下降（每分钟 13.9 个字），而治疗组则没有下降（P = 0.02）。假手术组 51 人中有 2 人 (4%) 发现了严重的眼部不良反应，治疗组 48 人中有 2 人 (4%) 出现了严重的眼部不良反应。 结论：在患有 2 型黄斑毛细血管扩张症的参与者中，与假手术相比，将 CNTF 释放到玻璃体腔中的手术植入物减缓了视网膜变性的进展。需要进一步研究来评估长期临床结果和安全性。 (C) 2018 年美国眼科学会
Purpose: To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF), on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy.Design: Randomized sham-controlled clinical trial.Participants: Ninety-nine study eyes of 67 eligible participants were enrolled.Methods: Single-masked randomized clinical trial of 24 months' duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a sham procedure.Main Outcome Measures: The primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral-domain (SD) OCT images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups.Results: Among the 67 participants who were randomized (mean age, 62 +/- 8.9 years; 41 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes. The difference in mean area of photoreceptor loss was 0.05 +/- 0.03 mm(2) (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly with the changes in the area of photoreceptor loss (r = 0.86; P < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than that of the treated group (decrease, 15.81 +/- 8.93 dB; P = 0.07). Reading speed deteriorated in the sham group (e13.9 words per minute) with no loss in the treated group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the sham group and 2 of 48 persons (4%) in the treated group.Conclusions: In participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety. (C) 2018 by the American Academy of Ophthalmology