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

Zhichao Wu, Chi D. Luu, Lauren A. B. Hodgson, Emily Caruso, Kate H. Brassington, Nicole Tindill, Khin Zaw Aung, Colin A. Harper, Sanjeewa S. Wickremashinghe, Sukhpal S. Sandhu, Myra B. McGuinness, Fred K. Chen, Usha Chakravarthy, Jennifer J. Arnold, Wilson J. Heriot, Shane R. Durkin, Maximilian Wintergerst, Shekoufeh Gorgi Zadeh, Thomas Schultz, Robert Finger, Amy C. Cohn, Elizabeth K. Baglin, Pyrawy Sharangan, and Robyn H. Guymer
In: Ophthalmology Retina (2019)
 

Abstract

Purpose: To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its early stages.

Design: Multi-center, randomized, sham-controlled trial. Participants: Two-hundred and ninety-two participants with bilateral large drusen.

Methods: Participants were assigned randomly to receive SNL or sham treatment to the study eye at 6-monthly intervals.

Main Outcome Measures: The secondary outcome measure of the LEAD study was the time to development of late AMD defined by multimodal imaging in the non-study eye. The exploratory outcome measures were the rate of change in best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), microperimetric mean sensitivity (MS), drusen volume in the study and non-study eyes, and participant reported outcomes based on the Night Vision Questionnaire (NVQ-10) and Impact of Vision Impairment (IVI) questionnaire.

Results: Progression to late AMD in the non-study eye was not significantly delayed with SNL treatment (hazard ratio, 0.83; 95% confidence interval, 0.40-1.71; P=0.611). There was no evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; interaction P=0.065). There was no significant difference between study groups in the rate of change of LLVA, microperimetric MS and drusen volume in the study or non-study eyes, and NVQ-10 and IVI scores (all P≥0.167). The rate of BCVA decline was slightly higher for participants in the SNL compared to sham group in the study eye (-0.54 and 0.23 letters/year respectively; P<0.001), but not the non-study eye (-0.48 and -0.56 letters/year respectively; P=0.628).

Conclusions: SNL treatment of one eye did not have an effect on delaying progression to late AMD in the fellow eye and did not, in general, have an impact on the exploratory structural, functional and participant-reported outcomes.

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Bibtex

@ARTICLE{Wu:OR2019,
    author = {Wu, Zhichao and Luu, Chi D. and Hodgson, Lauren A. B. and Caruso, Emily and Brassington, Kate H. and
              Tindill, Nicole and Aung, Khin Zaw and Harper, Colin A. and Wickremashinghe, Sanjeewa S. and Sandhu,
              Sukhpal S. and McGuinness, Myra B. and Chen, Fred K. and Chakravarthy, Usha and Arnold, Jennifer J.
              and Heriot, Wilson J. and Durkin, Shane R. and Wintergerst, Maximilian and Gorgi Zadeh, Shekoufeh
              and Schultz, Thomas and Finger, Robert and Cohn, Amy C. and Baglin, Elizabeth K. and Sharangan,
              Pyrawy and Guymer, Robyn H.},
     title = {Secondary and Exploratory Outcomes of the Subthreshold Nanosecond Laser Intervention Randomized
              Trial in Age-Related Macular Degeneration: A LEAD Study Report},
   journal = {Ophthalmology Retina},
      year = {2019},
  abstract = {Purpose:
              To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of
              Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser
              (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its
              early stages.
              
              Design:
              Multi-center, randomized, sham-controlled trial. Participants: Two-hundred and ninety-two
              participants with bilateral large drusen.
              
              Methods:
              Participants were assigned randomly to receive SNL or sham treatment to the study eye at 6-monthly
              intervals.
              
              Main Outcome Measures:
              The secondary outcome measure of the LEAD study was the time to development of late AMD defined by
              multimodal imaging in the non-study eye. The exploratory outcome measures were the rate of change in
              best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), microperimetric mean
              sensitivity (MS), drusen volume in the study and non-study eyes, and participant reported outcomes
              based on the Night Vision Questionnaire (NVQ-10) and Impact of Vision Impairment (IVI)
              questionnaire.
              
              Results:
              Progression to late AMD in the non-study eye was not significantly delayed with SNL treatment
              (hazard ratio, 0.83; 95% confidence interval, 0.40-1.71; P=0.611). There was no evidence of effect
              modification based on the coexistence of reticular pseudodrusen (RPD; interaction P=0.065). There
              was no significant difference between study groups in the rate of change of LLVA, microperimetric MS
              and drusen volume in the study or non-study eyes, and NVQ-10 and IVI scores (all P≥0.167). The
              rate of BCVA decline was slightly higher for participants in the SNL compared to sham group in the
              study eye (-0.54 and 0.23 letters/year respectively; P<0.001), but not the non-study eye (-0.48 and
              -0.56 letters/year respectively; P=0.628).
              
              Conclusions:
              SNL treatment of one eye did not have an effect on delaying progression to late AMD in the fellow
              eye and did not, in general, have an impact on the exploratory structural, functional and
              participant-reported outcomes.},
       doi = {10.1016/j.oret.2019.07.008}
}