Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration

Abstract

Purpose: There is an urgent need for a more effective intervention to slow or prevent progression of agerelated macular degeneration (AMD) from its early stages to vision-threatening late complications. Subthreshold nanosecond laser (SNL) treatment has shown promise in preclinical studies and a pilot study in intermediate AMD (iAMD) as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD.Design: The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is a 36month, multicenter, randomized, sham-controlled trial.Participants: Two hundred ninety-two participants with bilateral large drusen and without OCT signs of atrophy. Methods: Participants were assigned randomly to receive Retinal Rejuvenation Therapy (2RT Ò ; Ellex Pty Ltd, Adelaide, Australia) SNL or sham treatment to the study eye at 6-monthly intervals.Main Outcome Measures: The primary efficacy outcome was the time to development of late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events.Results: Overall, progression to late AMD was not slowed significantly with SNL treatment compared with sham treatment (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.33e1.14; P ¼ 0.122). However, a post hoc analysis showed evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; adjusted interaction P ¼ 0.002), where progression was slowed for the 222 participants (76.0%) without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09e0.59; P ¼ 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80e8.18; P ¼ 0.112) was observed for the 70 participants (24.0%) with RPD with SNL treatment. Differences between the groups in serious adverse events were not significant.Conclusions: In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RT Ò laser, but they should not be extrapolated to other short-pulse lasers.

Predicting risk of late age-related macular degeneration using deep learning

“…Making accurate time-based predictions of progression to late AMD is clinically critical. This would enable improved decision-making regarding: (i) medical treatments, especially oral supplements known to decrease progression risk, (ii) lifestyle interventions, particularly smoking cessation and dietary changes, and (iii) intensity of patient monitoring, e.g., frequent reimaging in clinic and/or tailored home monitoring programs 4 – 8 . It would also aid the design of future clinical trials, which could be enriched for participants with a high risk of progression events 9 .…”

Comparison of Drusen Volume Assessed by Two Different OCT Devices

“…Drusen are an important surrogate for progression of AMD [2] and hence techniques and tools to detect and analyze the area and volume [3] of drusen are important for long term follow-up of such patients. Additionally, quantitative drusen changes have been regularly assessed in trials as secondary or exploratory outcome parameters to prove efficacy of potential treatments and to follow disease progression of AMD [2]. Until now the increase of drusen area and the maximal drusen size were mainly assessed by color fundus photography [4,5].…”

Longitudinal Analysis of Structural and Functional Changes in Presence of Reticular Pseudodrusen Associated With Age-Related Macular Degeneration

“…In summary, recent findings underscore that eyes with predominantly RPD differ not only in terms of natural history and retinal function from eyes with soft drusen, but potentially also in terms of treatment response. 27 A subgroup analysis by Guymer et al 39 suggests that eyes with RPD treated by subthreshold nanosecond laser have an increased risk for progression to late-stage disease compared to eyes with without RPD.…”