The effect of combination therapy with intravitreal bevacizumab and topical timolol-dorzolamide eye drops on diabetic macular edema: a double-blind randomized controlled trial.

BACKGROUND: The mainstay of treatment in diabetic macular edema (DME) is intravitreal administration of anti-vascular endothelial growth factors (anti-VEGFs). Aqueous depressants may enhance the effects of anti-VEGF agents by prolonging their clearance via aqueous outflow.

PURPOSE: To compare the anatomical and functional outcomes of treatment with intravitreal bevacizumab (IVB) and topical timolol-dorzolamide versus IVB alone.

METHOD: In this randomized placebo-controlled clinical trial, patients with center-involving DME (ci-DME) and best corrected visual acuity (BCVA) of 20/30 or less were enrolled and randomly allocated to two treatment arms. One group received three monthly IVB injections and timolol-dorzolamide eye drops twice a day (IVB + TD group); the other group received three monthly IVB injections and artificial tear drops as placebo (IVB group). Patients underwent ophthalmic evaluations and macular optical coherence tomography scans at baseline and 1 month after the third injection.

RESULT: Forty-six eyes from 46 patients with ci-DME were recruited. There was no intergroup difference regarding age, gender distribution, diabetic retinopathy stage, glycemic indices, BCVA, central macular thickness (CMT), or intraocular pressure at baseline. BCVA was significantly improved in the IVB + TD group (0.46 ± 0.18 to 0.36 ± 0.18 logarithm of the minimum angle of resolution [logMAR], p = 0.002), in contrast to IVB group (0.40 ± 0.17 to 0.35 ± 0.22 logMAR, p = 0.113). Similarly, the IVB + TD group showed a significant reduction in CMT (p < 0.001), unlike the IVB group (p = 0.086); and the CMT change in the former was greater than in the latter (- 0.57 ± 57.67 vs. - 25.52 ± 68.02 μm, p = 0.033).

CONCLUSION: Our findings support the short-term effectiveness of topical timolol-dorzolamide as adjunctive therapy to IVB injections in managing center-involving DME in terms of anatomical and visual outcomes.

TRIAL REGISTRATION: Clinicaltrials.gov NCT05083689 (October 19, 2021).