Lois Noemi, Campbell Christina, Waugh Norman, Azuara-Blanco Augusto, Maredza Mandy, Mistry Hema, McAuley Danny, Acharya Nachiketa, Aslam Tariq M, Bailey Clare, Chong Victor, Downey Louise, Eleftheriadis Haralabos, Fatum Samia, George Sheena, Ghanchi Faruque, Groppe Markus, Hamilton Robin, Menon Geeta, Saad Ahmed, Sivaprasad Sobha, Shiew Marianne, Steel David H, Talks James Stephen, Doherty Paul, McDowell Cliona, Clarke Mike
The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University, Belfast, United Kingdom.
The Northern Ireland Clinical Trials Unit (NICTU), Belfast, United Kingdom.
Ophthalmology. 2023 Jan;130(1):14-27. doi: 10.1016/j.ophtha.2022.08.012. Epub 2022 Aug 13.
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.
Pragmatic, multicenter, allocation-concealed, double-masked, randomized, noninferiority trial.
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.
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.
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.
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.
Subthreshold micropulse laser therapy was equivalent to SL therapy, requiring slightly higher laser treatments.
确定与标准激光（SL）相比，阈下微脉冲激光（SML）治疗中心视网膜厚度（CRT）<400μm的糖尿病性黄斑水肿（DME）的临床疗效、安全性和成本效益。
实用、多中心、分配隐藏、双盲、随机、非劣效性试验。
单眼或双眼患有累及中心的DME且最佳矫正视力（BCVA）>24个早期糖尿病性视网膜病变研究（ETDRS）字母、CRT<400μm的成年人。
1:1随机分配接受577nm SML或SL治疗。允许再次治疗。如果发生10个或更多ETDRS字母丢失、CRT增加>400μm或两者兼而有之，则允许采用玻璃体内抗血管内皮生长因子疗法或类固醇进行挽救治疗。
主要结局是研究眼在24个月时BCVA的平均变化（非劣效性界值为5个ETDRS字母）。次要结局包括从基线到第24个月双眼BCVA的平均变化；研究眼的CRT和Humphrey 10-2视野平均偏差；达到驾驶标准的百分比；欧洲五维度健康量表EQ-5D-5L、25项美国国立眼科研究所视觉功能问卷（NEI-VFQ-25）和视觉与生活质量指数（VisQoL）评分；每获得一个质量调整生命年（QALY）的成本；不良反应；以及激光治疗和挽救治疗的次数。
该研究招募满员（n = 266）；接受SML治疗的患者中有87%以及接受SL治疗的患者中有86%有主要结局数据。SML组和SL组从基线到第24个月BCVA的平均±标准差变化分别为-2.43±8.20个字母和-0.45±6.72个字母。阈下微脉冲激光疗法不仅被认为非劣效于而且等同于SL疗法，因为95%置信区间（CI；-3.9至-0.04个字母）完全落在允许的最大差异（5个ETDRS字母）的上下界范围内。在双眼BCVA（0.32个ETDRS字母；95%CI，-0.99至1.64个ETDRS字母；P = 0.63）、CRT（-0.64μm；95%CI，-14.25至12.98μm；P = 0.93）、视野平均偏差（0.39分贝（dB）；95%CI，-0.23至1.02dB；P = 0.21）、达到驾驶标准（百分点差异，1.6%；95%CI，-25.3%至28.5%；P = 0.91）、不良反应（风险比，0.28；95%CI，0.06 - 1.34；P = 0.11）、挽救治疗（百分点差异，-2.8%；95%CI，-13.1%至7.5%；P = 0.59）或EQ-5D、NEI-VFQ-25或VisQoL评分方面未发现统计学上的显著差异。SML组的激光治疗次数更高（0.48；95%CI，0.18 - 0.79；P = 0.002）。基础病例分析表明成本或QALY无差异。
阈下微脉冲激光疗法等同于SL疗法，只是所需的激光治疗次数略多。
