To evaluate topical dorzolamide hydrochloride-timolol maleate as an adjunct therapy to intravitreous anti-vascular endothelial growth factor injections in eyes with retinal vein occlusion resistant to treatment. Retinal vein occlusion patients with a history of persistent macular edema, despite fixed-interval intravitreous anti-vascular endothelial growth factor injections, were enrolled between April 4, 2016, and June 4, 2017. On enrollment, patients were instructed to administer one drop of topical dorzolamide-timolol twice daily for the duration of the study. They were maintained on the same anti-vascular endothelial growth factor drug and same interval between injections as preenrollment for the subsequent two visits. Primary outcome measures were change in central foveal thickness, central subfield thickness, and thickest macular cut at the final study visit. Eight patients (8 eyes) were eligible for enrollment and completed the study. There was a significant decrease in central foveal thickness (P = 0.02), central subfield thickness (P = 0.03), and thickest macular cut (P = 0.01) between the enrollment visit and the final visit. There was a decrease in mean (±SD) logarithm of the minimal angle of resolution from 0.52 (±0.35) (20/66, Snellen equivalent) at the enrollment visit to 0.41 (±0.35) (20/51, Snellen equivalent) at the final visit (P = 0.08). Topical dorzolamide-timolol may have a beneficial anatomical and functional effect in eyes with macular edema secondary to retinal vein occlusion resistant to treatment.