Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration The LEAD Randomized Controlled Clinical Trial

Laser Intervention Early Stages

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)829-838
Number of pages10
JournalOphthalmology
Volume126
Issue number6
DOIs
Publication statusPublished - Jun 2019

Cite this

@article{375f3e3513ce47b6a70bdb707f434782,
title = "Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration The LEAD Randomized Controlled Clinical Trial",
abstract = "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.",
keywords = "OPTICAL COHERENCE TOMOGRAPHY, VISION LOSS, DRUSEN, AUTOFLUORESCENCE, PSEUDODRUSEN, ATROPHY, EYES",
author = "{Laser Intervention Early Stages} and Guymer, {Robyn H.} and Zhichao Wu and Hodgson, {Lauren A. B.} and Emily Caruso and Brassington, {Kate H.} and Nicole Tindill and Aung, {Khin Zaw} and McGuinness, {Myra B.} and Fletcher, {Erica L.} and Chen, {Fred K.} and Usha Chakravarthy and Arnold, {Jennifer J.} and Heriot, {Wilson J.} and Durkin, {Shane R.} and Lek, {Jia Jia} and Harper, {Colin A.} and Wickremasinghe, {Sanjeewa S.} and Sandhu, {Sukhpal S.} and Baglin, {Elizabeth K.} and Pyrawy Sharangan and Sabine Braat and Luu, {Chi D.}",
year = "2019",
month = "6",
doi = "10.1016/j.ophtha.2018.09.015",
language = "English",
volume = "126",
pages = "829--838",
journal = "Ophthalmology: journal of the American Academy of Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier",
number = "6",

}

Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration The LEAD Randomized Controlled Clinical Trial. / Laser Intervention Early Stages.

In: Ophthalmology, Vol. 126, No. 6, 06.2019, p. 829-838.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration The LEAD Randomized Controlled Clinical Trial

AU - Laser Intervention Early Stages

AU - Guymer, Robyn H.

AU - Wu, Zhichao

AU - Hodgson, Lauren A. B.

AU - Caruso, Emily

AU - Brassington, Kate H.

AU - Tindill, Nicole

AU - Aung, Khin Zaw

AU - McGuinness, Myra B.

AU - Fletcher, Erica L.

AU - Chen, Fred K.

AU - Chakravarthy, Usha

AU - Arnold, Jennifer J.

AU - Heriot, Wilson J.

AU - Durkin, Shane R.

AU - Lek, Jia Jia

AU - Harper, Colin A.

AU - Wickremasinghe, Sanjeewa S.

AU - Sandhu, Sukhpal S.

AU - Baglin, Elizabeth K.

AU - Sharangan, Pyrawy

AU - Braat, Sabine

AU - Luu, Chi D.

PY - 2019/6

Y1 - 2019/6

N2 - 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.

AB - 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.

KW - OPTICAL COHERENCE TOMOGRAPHY

KW - VISION LOSS

KW - DRUSEN

KW - AUTOFLUORESCENCE

KW - PSEUDODRUSEN

KW - ATROPHY

KW - EYES

U2 - 10.1016/j.ophtha.2018.09.015

DO - 10.1016/j.ophtha.2018.09.015

M3 - Article

VL - 126

SP - 829

EP - 838

JO - Ophthalmology: journal of the American Academy of Ophthalmology

JF - Ophthalmology: journal of the American Academy of Ophthalmology

SN - 0161-6420

IS - 6

ER -