曲安奈德联合雷珠单抗玻璃体腔注射治疗老龄黄斑变性病:随机对照临床试验方案

Combined intravitreal injection of triamcinolone acetonide and ranibizumab for age-related macular degeneration: study protocol for a randomized controlled trial

背景:老龄性黄斑变性即老年人黄斑区出现的玻璃膜疣、视网膜色素上皮和脉络膜毛细血管的退行性改变,严重可致盲,目前多数医生给予患者抗氧化剂和扩张血管治疗,效果不明显。抗血管内皮生长因子融合蛋白雷珠单抗是一种血管生成抑制剂,目前已被用于治疗湿性(新生血管性)年龄相关性黄斑变性,但易出现眼内炎、孔源性视网膜脱离、视网膜撕裂和医源性外伤性白内障等不良反应。目的:试验设计了应用抗炎效果较强的糖皮质激素曲安奈德与雷珠单抗联合玻璃体腔注射治疗老龄性黄斑变性的随机对照试验,以观察其有效性及安全性。方法:试验计划纳入华中科技大学同济医学院附属荆州医院的老龄性黄斑变性患者80例,共160只眼,随机分为2组,对照组玻璃体腔内注射曲安奈德注射液,0.1 m L/次,1次/d;治疗组玻璃体腔注射曲安奈德注射液减量至0.025 m L/次基础上加用雷珠单抗眼用注射液,0.05 m L/次,1次/月,每组40例患者,80只眼。两组均连续治疗3个月,再进行6个月的随访。试验的主要观察指标为治疗前,治疗后6个月黄斑中心凹视网膜厚度;次要观察指标为治疗前,治疗后6个月最佳矫正视力、眼压值、生活质量评分变化及治疗后6个月不良反应发生率。试验经华中科技大学同济医学院附属荆州医院伦理委员会批准(审批单位:华中科技大学同济医学院附属荆州医院,伦理批准号:20170338)。研究符合世界医学会制定的《赫尔辛基宣言》的要求。参与者对试验方案和过程均知情同意,并签署知情同意书。试验于2018年1月开始进行患者招募,样本及数据收集时间为2018年1月至2018年6月,结果指标分析时间为2018年9月,试验于2018年9月结束。文章结果将以科学会议报告,或在同行评议的期刊上发表传播。试验已在中国临床试验注册中心注册(注册号:Chi CTR-IOR-17013865)。讨论:试验期望采用曲安奈德与雷珠单抗联合玻璃体腔注射在治疗老龄性黄斑变性方面显示出显著疗效及可靠的安全性。

BACKGROUND： Age-related macular degeneration is a condition that leads to the deterioration of the macula in the elderly, and is characterized by the presence of drusen and degenerative changes of the retinal pigment epithelium and choroidal capillaries. It is a major cause of blindness worldwide. The commonly used strategies, including antioxidant therapy and dilation of blood vessels, have shown undesired outcomes in clinical practice. Ranibizumab, an anti-vascular endothelial growth factor fusion protein, is an angiogenesis inhibitor that has been used to treat wet（neovascular） age-related macular degeneration; however, patients treated with ranibizumab are prone to develop endophthalmitis, rhegmatogenous retinal detachment, retinal tears, and iatrogenic traumatic cataract. OJECTIVE： To determine the efficacy and safety of intravitreal injection of combination of triamcinolone acetonide and ranibizumab in the treatment of age-related macular degeneration in a randomized controlled trial. METHODS： Eighty patients（160 eyes） with age-related macular degeneration admitted at Jingzhou Hospital Affiliated to Tongji Medical School of Huazhong University of Science and Technology, China will be recruited. These patients will be randomly assigned to control or treatment group at a 1：1 ratio. The patients in the control group will be treated with intravitreal injection of triamcinolone acetonide（0.1 m L, once daily）, while those in the treatment group will be treated with combined intravitreal injection of triamcinolone acetonide（0.025 m L, once daily） and ranibizumab（0.05 m L, once a month）. All patients will undergo continuous treatment for 3 months, followed by a 6-month follow-up. The primary outcome measure is foveal retinal thickness before and 6 months after treatment. The secondary outcome measures include best corrected visual acuity, intraocular pressure, quality of life scores before and 6 months after treatment, and the incidence of adverse events at 6 months after treatment. This study was approved by the Ethics Committee of the Jingzhou Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, China（approval No. 20170338）, and will be performed in accordance with the Declaration of Helsinki. The participants will be informed of the study protocol and procedures and asked to sign an informed consent. Participant recruitment will be initiated in January 2018. Sample and data collection will begin in January 2018 and end in June 2018. The analysis of outcome measures and the completion of trial will be in September 2018. The results of this study will be disseminated through presentations at scientific meetings and/or by publication in peer-reviewed journals. This trial was registered with the Chinese Clinical Trial Registry（registration No. Chi CTR-IOR-17013865）. DISCUSSION： We aim to confirm the safety and efficacy of the intravitreal injection of combination of triamcinolone acetonide and ranibizumab in the treatment of age-related macular degeneration.