Secondary and Exploratory Outcomes of the Subthreshold Nanosecond Laser Intervention Randomized Trial in Age-Related Macular Degeneration: A LEAD Study Report

Abstract

Purpose:To evaluate the secondary and exploratory outcomesof the Laser Intervention in Early Stages of Age-Related MacularDegeneration (LEAD) study, a 36-month trial of a subthresholdnanosecond laser (SNL) treatment for slowing the progression tolate age-related macular degeneration (AMD) in its early stages.Design:Multicenter, randomized, sham-controlled trial.Participants:Two-hundred ninety-two patients with bilaterallarge drusen.Methods:Participants were randomly assigned to receive SNLor sham treatment to the study eye at 6-month intervals.Main Outcome Measures:The secondary outcome measure ofthe LEAD study was the time to development of late AMD, definedby multimodal imaging in the nonestudy eye. The exploratoryoutcome measures were the rate of change in best-corrected visualacuity (BCVA), low-luminance visual acuity, microperimetric meansensitivity, drusen volume in the study and nonestudy eyes, andparticipant-reported outcomes based on the Night Vision Question-naire and Impact of Vision Impairment questionnaire.Results:Progression to late AMD in the nonestudy eye wasnot significantly delayed with SNL treatment (hazard ratio, 0.83;95% confidence interval, 0.40e1.71;P¼0.611). There was noevidence of effect modification based on the coexistence of retic-ular pseudodrusen; interactionP¼0.065). There was no signifi-cant difference between study groups in the rate of change of low-luminance visual acuity, microperimetric mean sensitivity, anddrusen volume in the study or nonestudy eyes, and Night VisionQuestionnaire and Impact of Vision Impairment questionnaire2 scores (allP 0.167). The rate of BCVA decline was slightlyhigher for participants in the SNL group compared with the shamtreatment group in the study eye (e0.54 and 0.23 letters/year,respectively;P<0.001) but not the nonestudy eye (e0.48 ande0.56 letters/year, respectively;P¼0.628).Conclusions:Subthreshold nanosecond laser treatment of oneeye did not have an effect on delaying progression to late AMD in thefellow eye and did not, in general, have an impact on the exploratorystructural, functional, and participant-reported outcomes.