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), 0.77mm; 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.
Read full abstract