Lek Jia Jia, Brassington Kate H, Luu Chi D, Chen Fred K, Arnold Jennifer J, Heriot Wilson J, Durkin Shane R, Chakravarthy Usha, Guymer Robyn H
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Victoria, Australia; Ophthalmology, University of Melbourne, Department of Surgery, Victoria, Australia.
Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, Perth, Western Australia, Australia; Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia.
Ophthalmol Retina. 2017 May-Jun;1(3):227-239. doi: 10.1016/j.oret.2016.12.001. Epub 2017 Jan 31.
The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is an investigation of the safety and efficacy of subthreshold nanosecond laser treatment to slow the progression of intermediate age-related macular degeneration (AMD). This report presents the novel study design and baseline characteristics.
Multicenter, double-masked, randomized controlled, medical device feasibility clinical trial.
Persons with bilateral drusen >125 μm within 1500 μm of the fovea, monocular best-corrected visual acuity (BCVA) ≥20/40, and microperimetric retinal sensitivity of <25 decibels (dB) in at least 1 location within central 6° in 1 eye. Signs of late AMD; choroidal neovascularization or geographic atrophy, or anatomic end points defined on multimodal imaging (MMI) as fundus autofluorescence-defined atrophy, spectral-domain OCT (SD-OCT)-defined atrophy, or nascent GA excluded participation.
Participants were randomized to nanosecond or sham laser treatment. Twelve laser or sham spots are applied to the macular region of the study eye. Participants are reviewed in visits every 6 months with functional testing and MMI for 36 months and are re-treated at each visit (until 30 months) if an end point is not reached in the study eye.
Progression to late AMD or MMI-defined anatomic end points in the study eye.
A total of 292 participants across 6 centers were enrolled, with 145 participants randomized to arm 1 and 147 participants randomized to arm 2. Population characteristics at baseline were as follows: median age 70 years, 73% female, 90% Anglo-Saxon, and 3% current smokers. Baseline ocular characteristics of the study eyes were BCVA of 83 letters (20/25); low luminance visual acuity (LLVA) of 68 letters (20/50); hyperpigmentation, 33%; reticular pseudodrusen, 23%; square root drusen area (SD-OCT), 0.77 mm; square root drusen area (color photographs), 0.92 mm; cube root drusen volume (SD-OCT), 0.26 mm; average retinal sensitivity, 26 dB; and worst point retinal sensitivity, 20 dB. Only lutein supplement use was significantly different between treatment arms.
The LEAD study uses novel inclusion/exclusion criteria and end points in an attempt to optimize our study design. Risk characteristics for progression to study end points are equally distributed between treatment arms.
年龄相关性黄斑变性早期激光干预（LEAD）研究旨在探讨阈下纳秒激光治疗延缓中度年龄相关性黄斑变性（AMD）进展的安全性和有效性。本报告介绍了该新颖的研究设计和基线特征。
多中心、双盲、随机对照、医疗器械可行性临床试验。
双眼黄斑中心凹1500μm范围内存在直径>125μm的玻璃膜疣，单眼最佳矫正视力（BCVA）≥20/40，且一只眼中中央6°范围内至少有1个位置的微视野视网膜敏感度<25分贝（dB）的患者。晚期AMD的体征；脉络膜新生血管或地图样萎缩，或多模态成像（MMI）定义的解剖学终点，如眼底自发荧光定义的萎缩、频域光学相干断层扫描（SD-OCT）定义的萎缩或新生地图样萎缩，均排除参与。
参与者被随机分配接受纳秒激光或假激光治疗。在研究眼的黄斑区应用12个激光或假激光光斑。每6个月对参与者进行一次随访，进行功能测试和MMI，为期36个月，如果研究眼未达到终点，则在每次随访时进行再次治疗（直至30个月）。
研究眼中进展为晚期AMD或MMI定义的解剖学终点。
6个中心共招募了292名参与者，145名参与者随机分配至第1组，147名参与者随机分配至第2组。基线时的人群特征如下：年龄中位数70岁，女性占73%，盎格鲁-撒克逊人占90%，当前吸烟者占3%。研究眼的基线眼部特征为BCVA为83个字母（20/25）；低亮度视力（LLVA）为68个字母（20/50）；色素沉着过度占33%；网状假性玻璃膜疣占23%；玻璃膜疣面积平方根（SD-OCT）为0.77mm；玻璃膜疣面积平方根（彩色照片）为0.92mm；玻璃膜疣体积立方根（SD-OCT）为0.26mm；平均视网膜敏感度为26dB；最差点视网膜敏感度为20dB。仅叶黄素补充剂的使用在治疗组之间存在显著差异。
LEAD研究采用了新颖的纳入/排除标准和终点，试图优化我们的研究设计。进展至研究终点的风险特征在治疗组之间均匀分布。
