Switching Anti-VEGF Drug Can Improve Response in Diabetic Macular Edema

retina of diabetic retinophaty
A study shows improvements in diabetic macular edema with intravitreal ranibizumab in bevacizumab nonresponders.

Intravitreal ranibizumab therapy demonstrated both anatomical and functional improvements in patients with persistent diabetic macular edema who were previously incompletely responsive or unresponsive to intravitreal bevacizumab, according to research results published in Clinical Ophthalmology. They also found anatomical improvements switching to aflibercept, but were unable to confirm functional results.

Researchers conducted a single-center, retrospective, comparative study (NCT04018833) to evaluate the safety and efficacy of switching to either ranibizumab or aflibercept therapy after bevacizumab therapy in unresponsive eyes with diabetic macular edema. The total cohort included 56 eyes from 40 patients who met inclusion criteria. A total of 33 eyes were switched to ranibizumab while 23 were switched to aflibercept.

At baseline, investigators collected data on previous laser therapy, the number of previous intravitreal bevacizumab injections (1.25 mg/0.05 mL), central foveal thickness, and best-corrected visual acuity (BCVA). Following the switch, patients received 3 monthly, consecutive doses of either intravitreal ranibizumab (0.5 mg/0.05 mL) or intravitreal aflibercept (2.0 mg/0.05 mL).

Median central foveal thickness decrease was significantly different in both groups at 4 months compared with both the thickness before bevacizumab as well as thickness at the time of the switch (P <.001). No between-group differences were noted. BCVA improvements were only statistically significant in the ranibizumab group at 4-months after the switch. More patients increased by more than 15 letters in this group compared with patients who received aflibercept (18.2% vs 0%) at 4 months. 

Study limitations included the retrospective, nonrandomized nature, the small number of included eyes, the lack of a control group, a short follow-up duration, and the “difficulties inherent to the multifactorial nature of [diabetic macular edema].”

“[S]ignificant anatomical and functional improvement was observed with ranibizumab therapy,” compared with the previous unresponsive or incomplete response to bevacizumab, the study shows. “In the aflibercept group, the anatomical response was not followed by an improvement [in] BCVA. Novel biomarkers, other than visual acuity and [central foveal thickness] outcomes, should be pursued, to clarify these achievements and the real efficacy of each individual therapy.” 


Pessoa B, Malheiro L, Carneiro I, et al. Intravitreal ranibizumab or aflibercept after bevacizumab in diabetic macular edema: Exploratory retrospective analysis. Clin Ophthalmol. 2021;15:253-260. doi:10.2147/OPTH.S280644.