Aiello Lloyd Paul, Davis Matthew D, Girach Aniz, Kles Keri A, Milton Roy C, Sheetz Matthew J, Vignati Louis, Zhi Xin Eric
Beetham Eye Institute, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA.
Ophthalmology. 2006 Dec;113(12):2221-30. doi: 10.1016/j.ophtha.2006.07.032. Epub 2006 Sep 20.
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.
Thirty-six-month, randomized, double-masked, placebo-controlled, parallel, multicenter trial.
Six hundred eighty-five patients randomized at 70 clinical sites.
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 degrees 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 > or =45 letters, retinopathy level > or = 47A and < or = 53E, and no prior panretinal photocoagulation in at least one eye.
Effect of oral ruboxistaurin (32 mg/day) on reduction of sustained moderate visual loss (> or =15-letter decrease in ETDRS VA score maintained > or = 6 months) in patients with moderately severe to very severe nonproliferative diabetic retinopathy.
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 > or =15 letters was more frequent (4.9% vs. 2.4%) and > or =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 microm from the center of the macula at baseline, ruboxistaurin treatment was associated with less frequent progression of edema to within 100 microm (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).
Oral ruboxistaurin treatment reduced vision loss, need for laser treatment, and macular edema progression, while increasing occurrence of visual improvement in patients with nonproliferative retinopathy.
评估口服蛋白激酶Cβ（PKCβ）同工酶选择性抑制剂鲁比前列酮对糖尿病患者视力丧失的影响。
为期36个月的随机、双盲、安慰剂对照、平行、多中心试验。
70个临床地点的685名患者被随机分组。
在筛查时和每3个月的随访时进行眼科检查。每6个月用早期糖尿病性视网膜病变研究（ETDRS）标准的7视野30度彩色立体眼底摄影评估视网膜病变状况。糖尿病性视网膜病变和糖尿病性黄斑水肿的程度由两名对研究地点和治疗分配不知情的独立分级人员确定，必要时进行额外的独立判定。符合条件的患者最佳矫正视力（VA）得分≥45个字母，视网膜病变程度≥47A且≤53E，且至少一只眼睛未接受过全视网膜光凝治疗。
口服鲁比前列酮（32毫克/天）对中重度至重度非增殖性糖尿病性视网膜病变患者持续中度视力丧失（ETDRS VA得分下降≥15个字母且持续≥6个月）减少的影响。
安慰剂治疗的患者中有9.1%发生持续中度视力丧失，而鲁比前列酮治疗的患者中这一比例为5.5%（风险降低40%，P = 0.034）。12个月后，鲁比前列酮治疗的患者平均视力更好。与安慰剂相比，鲁比前列酮治疗的患者中基线至终点视力改善≥15个字母的情况更频繁（4.9%对2.4%），而视力恶化≥15个字母的情况更不频繁（6.7%对9.9%）（P = 0.005）。当基线时临床上显著的黄斑水肿距黄斑中心>100微米时，鲁比前列酮治疗与水肿进展至100微米内的频率较低相关（68%对50%，P = 0.003）。鲁比前列酮治疗的患者眼中黄斑水肿的初始激光治疗频率低26%（P = 0.008）。
口服鲁比前列酮治疗可减少非增殖性视网膜病变患者的视力丧失、激光治疗需求和黄斑水肿进展，同时增加视力改善的发生率。
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