Abstract：
Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD.
Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis.
Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry.
Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy.
Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O\'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon.
A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified.
Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.
Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis.
Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry.
Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy.
Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O\'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon.
A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified.
Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.
摘要：
目的：增生性玻璃体视网膜病变（PVR）是原发性孔源性视网膜脱离（RRD）后手术失败的主要原因。到目前为止,尚无治疗方法可预防PVR。先前已经报道了在高风险眼睛中5-氟尿嘧啶（5-FU）和低分子量肝素（LMWH）的有希望的结果。该试验的目的是研究与安慰剂相比，5-FU和LMWH辅助玻璃体内治疗对原发性RRD高危患者PVR发生率的影响。
方法：随机化，双盲,控制,多中心，1个中期分析的介入试验。
方法：纳入被认为是PVR高风险的RRD患者。PVR的风险通过使用激光耀斑测光法的非侵入性房水耀斑测量来评估。
方法：患者被随机分为1：1，分别在常规平面玻璃体切除术中玻璃体内应用verum（200mg/ml5-FU和5IU/ml达肝素）和安慰剂（平衡盐溶液）。
方法：主要终点是术后12周内PVR等级CP（全厚度视网膜褶皱或位于赤道后方的时钟小时内的视网膜下链）1或更高的发展。对于分级，终点委员会评估眼底照片。次要终点包括最佳矫正视力和再脱离率。使用O\'Brien和Fleming边界应用具有1个中期分析的分组顺序设计。使用由外科医生分层的Mantel-Haenszel测试比较了增生性玻璃体视网膜病变CP等级的发生率。
结果：共有13个德国试验中心的325名患者被随机分配（verum，n=163；安慰剂，n=162）。在研究的眼睛，平均激光耀斑为31±26pc/ms。PVR率无显著差异。修改后的意向治疗人群结果的主要分析为：verum28％vs.安慰剂23%(包括不可评估的失败病例)；比值比[OR]，1.25；95%置信区间[CI]，0.76-2.08；P=0.77。符合方案的人群为：12％vs.12%；或，1.05；95%CI，0.47-2.34；P=0.47。在治疗组之间没有一个次要终点显示出任何显著差异。在学习期间,未发现相关安全风险。
结论：5-FU和LMWH辅助治疗与安慰剂治疗RRD眼的PVR率无差异。
方法：随机化，双盲,控制,多中心，1个中期分析的介入试验。
方法：纳入被认为是PVR高风险的RRD患者。PVR的风险通过使用激光耀斑测光法的非侵入性房水耀斑测量来评估。
方法：患者被随机分为1：1，分别在常规平面玻璃体切除术中玻璃体内应用verum（200mg/ml5-FU和5IU/ml达肝素）和安慰剂（平衡盐溶液）。
方法：主要终点是术后12周内PVR等级CP（全厚度视网膜褶皱或位于赤道后方的时钟小时内的视网膜下链）1或更高的发展。对于分级，终点委员会评估眼底照片。次要终点包括最佳矫正视力和再脱离率。使用O\'Brien和Fleming边界应用具有1个中期分析的分组顺序设计。使用由外科医生分层的Mantel-Haenszel测试比较了增生性玻璃体视网膜病变CP等级的发生率。
结果：共有13个德国试验中心的325名患者被随机分配（verum，n=163；安慰剂，n=162）。在研究的眼睛，平均激光耀斑为31±26pc/ms。PVR率无显著差异。修改后的意向治疗人群结果的主要分析为：verum28％vs.安慰剂23%(包括不可评估的失败病例)；比值比[OR]，1.25；95%置信区间[CI]，0.76-2.08；P=0.77。符合方案的人群为：12％vs.12%；或，1.05；95%CI，0.47-2.34；P=0.47。在治疗组之间没有一个次要终点显示出任何显著差异。在学习期间,未发现相关安全风险。
结论：5-FU和LMWH辅助治疗与安慰剂治疗RRD眼的PVR率无差异。
