Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, No.23, Boostan 9 St., Pasdaran Ave., 16666, Tehran, Iran.
Department of Ophthalmology, Torfeh Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Graefes Arch Clin Exp Ophthalmol. 2021 Oct;259(10):2949-2959. doi: 10.1007/s00417-021-05169-1. Epub 2021 Apr 15.
To evaluate the additional effect of ketorolac eye drops on therapeutic effects of intravitreal Bevacizumab in patients with diabetic macular edema (DME) METHODS: In a randomized clinical trial, 50 patients with center involved DME (macular thickness ≥ 300 microns accompanied by decreased VA (24 < BCVA ≤ 70 ETDRS letters) were enrolled consecutively and randomized 1:1 to receive either bevacizumab plus topical ketorolac (25 patients) or bevacizumab plus artificial tears (25 patients). Patients with proliferative diabetic retinopathy, history of intraocular surgery, intravitreal injection in less than three months, macular photocoagulation less than 6 months and any other concomitant ocular pathologies were excluded from the study. All the patients received three consecutive monthly injections of intravitreal bevacizumab (IVB). After that, patients were examined every 6 weeks and reinjection was administered based on the "as needed" protocol if macular thickness was 300 microns or more and VA was 70 ETDRS letters or less.. Patients also received either topical ketorolac or artificial tears three times a day over the study period (6 months). Changes in central subfield thickness (CST), best-corrected visual acuity (BCVA, ETDRS letters), and number of IVB injections were compared between the study groups.
Fifty eyes of 50 patients were included (25 eyes in each group). Mean CST was significantly decreased in both study groups at 14 week (-87 ± 98 µm, P = 0.012 and -100 ± 147 µm, P = 0.006 in bevacizumab plus ketorolac and bevacizumab plus artificial tears groups, respectively). Nevertheless, the changes of mean CST remained significant only in bevacizumab plus ketorolac group up to 26 week (-147 ± 124 µm, P < 0.001 and -51 ± 145 µm, P = 0.245, respectively). Comparing two groups, reduction of mean CST from baseline was significantly greater in bevacizumab plus ketorolac group compared with the control group at 26 week. (difference = -97 µm, 95%CI = -182 to -11, P = 0.017). In the study group, mean BCVA significantly increased at both 20 week (6.2 ± 10.1, P = 0.04) and 26 week (8.2 ± 10.9, P = 0.03). In contrast, visual acuity did not significantly improve at any time points in bevacizumab plus artificial tears group, While insignificant, the 26-week mean change of visual acuity from baseline was greater in bevacizumab plus ketorolac group (difference = 6.5 ETDRS letter; 95%CI = -14.4 to 1.4) Two groups were comparable regarding number of IVB injections (P = 0.99).
Topical ketorolac 0.5% three times a day could enhance and sustain the efficacy of intravitreal bevacizumab in the treatment of DME.
评估在患有糖尿病性黄斑水肿（DME）的患者中，使用酮咯酸滴眼液对玻璃体内贝伐单抗治疗效果的额外影响。
在一项随机临床试验中，连续纳入 50 例中心性 DME 患者（黄斑厚度≥300 微米，伴有视力下降（24<BCVA≤70 ETDRS 字母）），并将其随机分为 1:1 组，分别接受贝伐单抗联合局部酮咯酸（25 例）或贝伐单抗联合人工泪液（25 例）治疗。患有增殖性糖尿病性视网膜病变、眼内手术史、3 个月内玻璃体腔内注射、6 个月内黄斑光凝术和任何其他伴发性眼部疾病的患者被排除在研究之外。所有患者均接受连续 3 个月的玻璃体腔内贝伐单抗（IVB）注射。此后，每 6 周进行一次检查，如果黄斑厚度为 300 微米或以上，视力为 70 ETDRS 字母或以下，则根据“按需”方案进行再注射。在研究期间（6 个月），患者还接受了局部酮咯酸或人工泪液每日三次滴眼治疗。比较两组患者的中央视网膜厚度（CST）、最佳矫正视力（BCVA，ETDRS 字母）和 IVB 注射次数的变化。
纳入 50 例患者的 50 只眼（每组 25 只眼）。两组患者在第 14 周时 CST 均明显下降（贝伐单抗联合酮咯酸组为-87±98µm，P=0.012；贝伐单抗联合人工泪液组为-100±147µm，P=0.006）。然而，只有在贝伐单抗联合酮咯酸组，CST 的变化一直持续到第 26 周时仍有统计学意义（-147±124µm，P<0.001；-51±145µm，P=0.245）。与对照组相比，在第 26 周时，贝伐单抗联合酮咯酸组 CST 从基线的平均降低量显著更大（差异为-97µm，95%CI=-182 至-11，P=0.017）。在研究组中，BCVA 在第 20 周（6.2±10.1，P=0.04）和第 26 周（8.2±10.9，P=0.03）时均显著提高。相反，在贝伐单抗联合人工泪液组，视力在任何时间点均未显著改善，尽管不显著，但在贝伐单抗联合酮咯酸组，第 26 周时视力从基线的平均变化更大（差异为 6.5 ETDRS 字母；95%CI=-14.4 至 1.4）。两组患者的 IVB 注射次数相当（P=0.99）。
每日 3 次局部滴用 0.5%酮咯酸滴眼液可增强和维持玻璃体内贝伐单抗治疗 DME 的疗效。
