Topical ketorolac as an adjunctive treatment with intravitreal bevacizumab in the management of diabetic macular edema: A double-masked placebo-controlled randomized clinical trial

Abstract

Purpose: 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.

Results: Fifty eyes of 50 patients were included (25 eyes in each group). Mean CST was significantly decreased in both study groups at 14^th 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^th 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^th week. (difference = -97 µm, 95%CI = -182 to -11, P = 0.017). In the study group, mean BCVA significantly increased at both 20^th week (6.2 ± 10.1, P = 0.04) and 26^th 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).

Conclusion: Topical ketorolac 0.5% three times a day could enhance and sustain the efficacy of intravitreal bevacizumab in the treatment of DME.

Keywords: Bevacizumab; Diabetic macular edema; Macular thickness; Topical ketorolac; Visual acuity.