Abstract
Purpose
To determine clinical effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT) < 400 μm.
Design
Pragmatic, multicenter, allocation-concealed, double-masked, randomized, noninferiority trial.
Participants
Adults with center-involved DME < 400 μm and best-corrected visual acuity (BCVA) of > 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes.
Methods
Randomization 1:1 to 577 nm SML or SL treatment. Retreatments were allowed. Rescue with intravitreal anti–vascular endothelial growth factor therapies or steroids was permitted if 10 or more ETDRS letter loss occurred, CRT increased > 400 μm, or both.
Main Outcome Measures
Primary outcome was mean change in BCVA in the study eye at 24 months (noninferiority margin 5 ETDRS letters). Secondary outcomes were mean change from baseline to month 24 in binocular BCVA; CRT and mean deviation of Humphrey 10-2 visual field in the study eye; percentage meeting driving standards; EuroQoL EQ-5D-5L, 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), and Vision and Quality of Life Index (VisQoL) scores; cost per quality-adjusted life-years (QALYs) gained; adverse effects; and number of laser and rescue treatments.
Results
The study recruited fully (n = 266); 87% of SML-treated and 86% of SL-treated patients had primary outcome data. Mean ± standard deviation BCVA change from baseline to month 24 was –2.43 ± 8.20 letters and –0.45 ± 6.72 letters in the SML and SL groups, respectively. Subthreshold micropulse laser therapy was deemed not only noninferior but also equivalent to SL therapy because the 95% confidence interval (CI; –3.9 to –0.04 letters) lay wholly within both upper and lower margins of the permitted maximum difference (5 ETDRS letters). No statistically significant difference was found in binocular BCVA (0.32 ETDRS letters; 95% CI, –0.99 to 1.64 ETDRS letters; P = 0.63); CRT (–0.64 μm; 95% CI, –14.25 to 12.98 μm; P = 0.93); mean deviation of the visual field (0.39 decibels (dB); 95% CI, –0.23 to 1.02 dB; P = 0.21); meeting driving standards (percentage point difference, 1.6%; 95% CI, –25.3% to 28.5%; P = 0.91); adverse effects (risk ratio, 0.28; 95% CI, 0.06–1.34; P = 0.11); rescue treatments (percentage point difference, –2.8%; 95% CI, –13.1% to 7.5%; P = 0.59); or EQ-5D, NEI-VFQ-25, or VisQoL scores. Number of laser treatments was higher in the SML group (0.48; 95% CI, 0.18–0.79; P = 0.002). Base-case analysis indicated no differences in costs or QALYs.
Conclusions
Subthreshold micropulse laser therapy was equivalent to SL therapy, requiring slightly higher laser treatments.
To determine clinical effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT) < 400 μm.
Design
Pragmatic, multicenter, allocation-concealed, double-masked, randomized, noninferiority trial.
Participants
Adults with center-involved DME < 400 μm and best-corrected visual acuity (BCVA) of > 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes.
Methods
Randomization 1:1 to 577 nm SML or SL treatment. Retreatments were allowed. Rescue with intravitreal anti–vascular endothelial growth factor therapies or steroids was permitted if 10 or more ETDRS letter loss occurred, CRT increased > 400 μm, or both.
Main Outcome Measures
Primary outcome was mean change in BCVA in the study eye at 24 months (noninferiority margin 5 ETDRS letters). Secondary outcomes were mean change from baseline to month 24 in binocular BCVA; CRT and mean deviation of Humphrey 10-2 visual field in the study eye; percentage meeting driving standards; EuroQoL EQ-5D-5L, 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), and Vision and Quality of Life Index (VisQoL) scores; cost per quality-adjusted life-years (QALYs) gained; adverse effects; and number of laser and rescue treatments.
Results
The study recruited fully (n = 266); 87% of SML-treated and 86% of SL-treated patients had primary outcome data. Mean ± standard deviation BCVA change from baseline to month 24 was –2.43 ± 8.20 letters and –0.45 ± 6.72 letters in the SML and SL groups, respectively. Subthreshold micropulse laser therapy was deemed not only noninferior but also equivalent to SL therapy because the 95% confidence interval (CI; –3.9 to –0.04 letters) lay wholly within both upper and lower margins of the permitted maximum difference (5 ETDRS letters). No statistically significant difference was found in binocular BCVA (0.32 ETDRS letters; 95% CI, –0.99 to 1.64 ETDRS letters; P = 0.63); CRT (–0.64 μm; 95% CI, –14.25 to 12.98 μm; P = 0.93); mean deviation of the visual field (0.39 decibels (dB); 95% CI, –0.23 to 1.02 dB; P = 0.21); meeting driving standards (percentage point difference, 1.6%; 95% CI, –25.3% to 28.5%; P = 0.91); adverse effects (risk ratio, 0.28; 95% CI, 0.06–1.34; P = 0.11); rescue treatments (percentage point difference, –2.8%; 95% CI, –13.1% to 7.5%; P = 0.59); or EQ-5D, NEI-VFQ-25, or VisQoL scores. Number of laser treatments was higher in the SML group (0.48; 95% CI, 0.18–0.79; P = 0.002). Base-case analysis indicated no differences in costs or QALYs.
Conclusions
Subthreshold micropulse laser therapy was equivalent to SL therapy, requiring slightly higher laser treatments.
| Original language | English |
|---|---|
| Pages (from-to) | 14-27 |
| Number of pages | 14 |
| Journal | Ophthalmology |
| Volume | 130 |
| Issue number | 1 |
| Early online date | 19 Dec 2022 |
| DOIs | |
| Publication status | Published - Jan 2023 |
Access to Document
- Diabetic macular edema and diode subthreshold micropulse laser: A randomized double-masked noninferiority clinical trial
Copyright 2022 by the American Academy of Ophthalmology. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.