Diabetic Macular Edema Responds to Anti-VEGF Drugs Differently Based on Patient Age

Aflibercept may be preferable to ranibizumab for patients older than 60 years of age who have center-involved diabetic macular edema.

When comparing patients with diabetic macular edema (DME) treated with ranibizumab vs aflibercept, their age factors into the likelihood for success, according to data published in the International Journal of Retina and Vitreous. The study shows that individuals older than 60 years of age have superior outcomes when treated with  ranibizumab, while those younger than 60 had superior outcomes using aflibercept.

The study took into account 210 eyes of 121 participants; including a group of 48 patients 60 years of age and younger, and a group of 73 patients older than 60 years. After treatment during the period from 2016 to 2020, mean best-corrected visual acuity (BCVA) improved in the younger group as a whole by 5.64 Early Treatment of Diabetic Retinopathy Study (ETDRS) letter score, and the older group at 5.49, with no large difference by age (P =.5429).

Structurally, average central subfield thickness (CST) was reduced overall; -125.1 µm for those ≤60, and -94.0 µm in patients more than 60 years of age, with no significant statistical differences between sets (P =.08).

However, when comparing age groups treated with the 2 drugs, dissimilarities emerged. With ranibizumab, the younger group gained an average 19.13 ETDRS letter score vs the older group’s 4.18. In contrast, undergoing aflibercept injections, the younger set improved by 4.26 letter score, compared to the older group’s result of 5.70.

The results of the study showed that aflibercept could be used for all age groups of patients with no significant difference while the use of ranibizumab may be better restricted to younger patients.

The younger group’s mean CST decreased with ranibizumab by -228.13 µm compared with the older group’s reduction of -100.29 µm. With aflibercept, participants 60 years of age and younger displayed CST decrease of -117.21 µm, compared with those older than 60 years who showed CST improvement by -91.40 µm. These differences were significant for ranibizumab (P =.001), but not for aflibercept (P =.356). 

“In addition, we found [a] significant difference between CST and VA results for each anti-VEGF [agent] utilized where better results were significantly reported in patients treated with aflibercept than in patients treated with ranibizumab,” the researchers report. “The results of the study showed that aflibercept could be used for all age groups of patients with no significant difference while the use of ranibizumab may be better restricted to younger patients.”

Other overall cohort differences arose: significantly greater CST decrease occurred in eyes exhibiting disorganization of retinal inner layers (DRIL), as well as those with subretinal fluid (SRF). Participants with photoreceptor loss also achieved significantly better CST reduction. No large differences were detected by systemic comorbidities such as lipid disorder or hypertension.

Previous research has also shown greater CST change for individuals with baseline DRIL, SRF, and photoreceptor loss. Other investigations have agreed with the present paper on better anti-VEGF treatment results for younger participants. Analyses that evaluated differences in treating DME with various intravitreal drugs found good morphological results with aflibercept after weaker response with ranibizumab or bevacizumab, potentially due to longer length of DME.

The current study was conducted at a tertiary eye center in Saudi Arabia. Limitations of this analysis comprised a retrospective design that lacked records regarding diabetes mellitus duration for some individuals, potential selection bias including choice of anti-VEGF agent, and a small ranibizumab set; 8 eyes in the younger group and 17 older than 60 years of age. Conversely, investigators cited the strength of specific data from a real-world cohort of patients.


Alshalan HA, Arevalo JF, Alomary SI, et al. Effect of age on response to anti-VEGF agents in patients with center involving diabetic macular edema in a tertiary hospitalInt J Retin Vitr. Published online on December 13, 2022. doi:10.1186/s40942-022-00434-9