Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy
Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy
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DOI：
10.1016/j.ophtha.2016.03.003
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发表时间：
2016-07-01
期刊：
影响因子：
13.7
通讯作者：
Stout, J. Timothy
中科院分区：
文献类型：
--
作者：
Weleber, Richard G.;Pennesi, Mark E.;Stout, J. Timothy
目的：初步评估表达RPE 65的重组腺相关病毒载体的安全性（rAAV 2-CB-hRPE 65）在患有由RPE 65突变引起的视网膜变性的成人和儿童中的应用。设计：非随机、多中心临床试验。参与者：8名成人和4名6至39岁的儿童，Leber先天性黑蒙（LCA）或严重的儿童期视网膜变性（SECORD）。患者在视力较差的眼睛中接受视网膜下注射rAAV 2-CB-hRPE 65，以2种剂量水平中的任一种，并在治疗后随访2年。主要安全性指标为眼部和非眼部不良事件。探索性疗效指标包括最佳矫正视力（BCVA）的变化，静态视野检查中心30度视野山（V30）和总视野山的视觉（VTOT），动态视野检查视野面积，并回答了生活质量questionnaire.Results：所有患者耐受视网膜下注射，并没有治疗相关的严重不良事件。常见的不良事件与外科手术相关，包括8例患者的结膜下出血和5例患者的眼部充血。在治疗眼中，5例患者BCVA增加，6例患者V30增加，5例患者VTOT增加，3例患者动态视野面积改善。1例患者BCVA下降，2例患者动态视野面积下降。结论：rAAV 2-CB-hRPE 65治疗与严重不良事件无关，12例患者中有9例观察到1项或多项视觉功能指标改善。在基线视力较好的年轻患者中观察到视力的最大改善。需要对更多患者进行评估，并进行更长时间的随访，以确定不常见或罕见副作用或安全性问题的发生率。(C)2016年美国眼科学会。
Purpose: To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations.Design: Nonrandomized, multicenter clinical trial.Participants: Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhoodeonset retinal degeneration (SECORD).Methods: Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment.Main Outcome Measures: The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30 degrees visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire.Results: All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area.Conclusions: Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns. (C) 2016 by the American Academy of Ophthalmology.