Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration The LEAD Randomized Controlled Clinical Trial
Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration The LEAD Randomized Controlled Clinical Trial
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DOI：
10.1016/j.ophtha.2018.09.015
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发表时间：
2019-06-01
期刊：
影响因子：
13.7
通讯作者：
Luu, Chi D.
中科院分区：
文献类型：
--
作者：
Guymer, Robyn H.;Wu, Zhichao;Luu, Chi D.
目的：迫切需要一种更有效的干预措施来减缓或预防年龄相关性黄斑变性（AMD）从早期阶段发展为威胁视力的晚期并发症。阈下纳秒激光（SNL）治疗已在临床前研究和中期AMD（iAMD）的初步研究中显示出作为潜在治疗的前景。我们的目的是评估SNL治疗iAMD的安全性及其减缓进展为晚期AMD.Design的有效性：激光干预早期阶段的AMD相关黄斑变性（LEAD）研究是一项为期36个月，多中心，随机，假对照试验。参与者：292名双侧大玻璃疣和没有OCT萎缩迹象的参与者。参与者被随机分配接受视网膜再生治疗（2 RT（R）; Ellex Pty Ltd，阿德莱德，澳大利亚）SNL或假治疗，以6个月的间隔对研究眼进行治疗。结果：总体而言，与假手术治疗相比，SNL治疗并没有显著减缓晚期AMD的进展（调整后的风险比[HR]，0.61; 95%置信区间[CI]，0.33-1.14; P = 0.122）。然而，一项事后分析显示，基于网状假性玻璃疣的共存，（RPD;调整的相互作用P = 0.002），其中222名参与者的进展减慢（76.0%）基线时不存在RPD（校正HR，0.23; 95% CI，0.09-0.59; P = 0.002），而进展率增加在SNL治疗的70例RPD受试者（24.0%）中观察到（校正HR，2.56; 95% CI，0.80-8.18; P = 0.112）。各组之间的严重不良事件的差异并不显着。结论：在没有MMI检测到晚期AMD迹象的iAMD参与者中，接受SNL和假治疗的患者之间的晚期AMD总体进展率没有显着差异。然而，SNL治疗可能在减缓不存在RPD的患者的进展方面发挥作用，并且可能不适用于RPD患者，因此在考虑RPD临床表型的治疗时应谨慎。我们的发现为2 RT（R）激光的进一步试验提供了令人信服的证据，但它们不应该被外推到其他短脉冲激光器上。(C)2018年美国眼科学会。
Purpose: There is an urgent need for a more effective intervention to slow or prevent progression of age-related 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 36-month, 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 (R) ; 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], 0.33-1.14; P = 0.122). However, a post hoc analysis showed evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; adjusted interaction P = 0.002), where progression was slowed for the 222 participants (76.0%) without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09-0.59; P = 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80-8.18; P = 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 (R) laser, but they should not be extrapolated to other short-pulse lasers. (C) 2018 by the American Academy of Ophthalmology.