Owens S L, Bunce C, Brannon A J, Wormald R, Bird A C
Medical Retinal Service, Moorfields Eye Hospital, London, UK.
Eye (Lond). 2003 Jul;17(5):623-7. doi: 10.1038/sj.eye.6700442.
The Drusen Laser Study (DLS) of high-risk age-related maculopathy (ARM) is a randomised, controlled clinical trial designed to answer two questions: (1). Do drusen resolve after macular laser photocoagulation (2). Does macular laser photocoagulation prevent choroidal neovascularisation (CNV) in high-risk eyes? In this report, we present the results of the interim, pooled analysis of CNV prophylaxis for patients in the Unilateral Group of the DLS.
The DLS is a randomised controlled clinical trial of prophylactic macular photocoagulation for high-risk ARM. Patients in the Unilateral Group had a neovascular complication in the first eye; their fellow eye (Study Eye) had visual acuity of 6/12 or better and drusen. Following informed consent, patients were randomised to the Treatment Group or the No Treatment Group. Patients randomised to treatment received 12 light spots of argon laser photocoagulation to their Study Eye: four burns were placed 750 microm from the centre of the fovea at 12, 3, 6, and 9 o'clock, and the eight remaining burns were placed 1500 microm from the centre of the fovea at 12, 1:30, 3, 4:30, 6, 7:30, 9, and 10:30 o'clock. Drusen were treated directly only if they were present at the protocol treatment locations. All patients were followed in an identical fashion at regular intervals. Best-corrected visual acuity was measured and recorded by a masked observer. Fluorescein angiography was performed at baseline and yearly review, as well as nonprotocol visits if symptoms suggested CNV. Five clinical centres utilised and conformed to a common DLS protocol. Patient care and data collection methodologies were deemed sufficiently similar to permit a pooled data analysis.
There were 156 patients included in the interim analysis, and timed information was available on 153. CNV occurred in 21 of 81 (26%) patients in the Treatment Group and in 13 of 75 (17%) patients in the No Treatment Group (P=0.19). Kaplan-Meier survival analysis showed earlier onset of CNV in the Treatment Group compared to patients in the No Treatment Group (statistical significance not calculated). Visual acuity loss at 2 years occurred in nine of 54 (17%) patients in the Treatment Group compared to the two of 48 (4%) patients in the No Treatment Group (P=0.056).
We are only the second group to identify possible laser-induced CNV despite other similar studies in progress. Equipoise of the DLS investigators was lost, and recruitment was halted. We feel ethically bound to notify the ophthalmic community of this finding.
高危年龄相关性黄斑病变（ARM）的玻璃膜疣激光研究（DLS）是一项随机对照临床试验，旨在回答两个问题：（1）黄斑激光光凝术后玻璃膜疣是否消退？（2）黄斑激光光凝能否预防高危眼发生脉络膜新生血管（CNV）？在本报告中，我们呈现了DLS单侧组患者CNV预防的中期汇总分析结果。
DLS是一项针对高危ARM进行预防性黄斑光凝的随机对照临床试验。单侧组患者的一只眼睛出现了新生血管并发症；其对侧眼（研究眼）视力为6/12或更好且有玻璃膜疣。在获得知情同意后，患者被随机分为治疗组或非治疗组。随机分配至治疗组的患者其研究眼接受12个氩激光光凝光斑治疗：4个光斑位于距黄斑中心凹750微米处的12点、3点、6点和9点位置，其余8个光斑位于距黄斑中心凹1500微米处的12点、1:30、3点、4:30、6点、7:30、9点和10:30位置。仅当玻璃膜疣出现在方案规定的治疗位置时才直接对其进行治疗。所有患者均以相同方式定期随访。由一位不知情的观察者测量并记录最佳矫正视力。在基线、每年复查时以及出现CNV症状的非方案访视时进行荧光素血管造影。五个临床中心采用并遵循共同的DLS方案。患者护理和数据收集方法被认为足够相似，允许进行汇总数据分析。
中期分析纳入了156例患者，其中153例有定时信息。治疗组81例患者中有21例（26%）发生CNV，非治疗组75例患者中有13例（17%）发生CNV（P = 0.19）。Kaplan-Meier生存分析显示，与非治疗组患者相比，治疗组患者CNV发病更早（未计算统计学显著性）。治疗组54例患者中有9例（17%）在2年时出现视力下降，而非治疗组48例患者中有2例（4%）出现视力下降（P = 0.056）。
尽管其他类似研究正在进行，但我们是第二组发现可能由激光诱导CNV的研究团队。DLS研究者的 equipoise 已丧失，招募工作已停止。我们认为在伦理上有责任将这一发现告知眼科界。
