Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy
Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy
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DOI：
10.1016/j.ophtha.2006.07.032
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发表时间：
2006-12-01
期刊：
影响因子：
13.7
通讯作者：
Zhi, Xin (Eric)
中科院分区：
文献类型：
--
作者：
Abraham, Prema;Adelman, Ron A.;Zhi, Xin (Eric)
目的：评价口服蛋白激酶Cβ(PKCβ)同工酶选择性抑制剂Ruboxistaurin对糖尿病患者视力丧失的影响。设计：36个月，随机、双盲、安慰剂对照、平行、多中心试验。参与者：随机选择70个临床站点的685例患者。采用早期治疗糖尿病视网膜病变研究(ETDRS)标准7野30色立体眼底照相，每6个月评估一次视网膜病变状态。糖尿病视网膜病变和糖尿病黄斑水肿的水平由2名独立的评分员确定，掩蔽到地点和治疗分配，并根据需要进行额外的独立裁决。在中重度至极重度非增殖性糖尿病视网膜病变患者中，符合条件的患者的最佳矫正视力(VA)评分=45个字母，视网膜病变水平=47A和=15个字母)。结果：接受安慰剂治疗的患者中有9.1%的患者出现持续的中度视力损失，而服用Ruboxistaurin的患者中有5.5%的患者持续中度视力损失(风险降低40%，P=0.034)。在接受Ruboxistaurin治疗的患者12个月后，平均视力较好。与安慰剂相比，服用Ruboxistaurin的患者从基线到终点的视力改善更频繁(4.9%比2.4%)，而>；=15个字母的恶化更少(6.7%比9.9%)(P=0.005)。当临床上显著的黄斑水肿发生在距黄斑中心100微米的基线范围内时，Ruboxistaurin治疗可减少水肿进展至100微米以内的几率(68%对50%，P=0.003)。服用Ruboxistaurin的患者首次激光治疗黄斑水肿的频率降低了26%(P=0.008)。结论：口服Ruboxistaurin治疗减少了非增殖性视网膜病变患者的视力损失、需要激光治疗和黄斑水肿进展，同时增加了视力改善的发生率。
Objective: To evaluate the effect of ruboxistaurin, an orally administered protein kinase C beta (PKC beta) isozyme-selective inhibitor, on vision loss in patients with diabetes.Design: Thirty-six-month, randomized, double-masked, placebo-controlled, parallel, multicenter trial.Participants: Six hundred eighty-five patients randomized at 70 clinical sites.Methods: Ophthalmologic examination was performed at screening and at each 3-month visit. Retinopathy status was assessed every 6 months with Early Treatment Diabetic Retinopathy Study (ETDRS) standard 7-field 30 color stereoscopic fundus photography. Levels of diabetic retinopathy and diabetic macular edema were determined by 2 independent graders masked to site and treatment assignment, with additional independent adjudication as required. Eligible patients had a best-corrected visual acuity (VA) score of >= 45 letters, retinopathy level >= 47A and = 15-letter decrease in ETDRS VA score maintained >= 6 months) in patients with moderately severe to very severe nonproliferative diabetic retinopathy.Results: Sustained moderate visual loss occurred in 9.1% of placebo-treated patients versus 5.5% of ruboxistaurin-treated patients (40% risk reduction, P = 0.034). Mean VA was better in the ruboxistaurin-treated patients after 12 months. Baseline-to-end point visual improvement of >= 15 letters was more frequent (4.9% vs. 2.4%) and >= 15-letter worsening was less frequent (6.7% vs. 9.9%) in ruboxistaurin-treated patients relative to placebo (P = 0.005). When clinically significant macular edema was > 100 p,m from the center of the macula at baseline, ruboxistaurin treatment was associated with less frequent progression of edema to within 100 mu m (68% vs. 50%, P = 0.003). Initial laser treatment for macular edema was 26% less frequent in eyes of ruboxistaurin-treated patients (P = 0.008).Conclusion: Oral ruboxistaurin treatment reduced vision loss, need for laser treatment, and macular edema progression, while increasing occurrence of visual improvement in patients with non proliferative retinopathy.