An analysis of 3 metrics  can help measure the treatment efficacy of anti-vascular endothelial growth factor (VEGF) injections for patients with neovascular age-related macular degeneration (nAMD), according to a study published in Clinical Ophthalmology.

The study sought to review results in the literature to compare the efficacy of VEGF inhibitors bevacizumab, ranibizumab, aflibercept, and brolucizumab, and develop metrics to standardize that comparison using the Advanced VitreoRetinal Analytics (AVRA) model, a method based on a logical mathematical derivation of Newtonian mechanics, according to the research team. 

Investigators searched records from 2 databases from 2000 to 2020 for all clinical trials that assessed subjects with nAMD and a history of using 1 of these 4 anti-VEGF agents. 

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“AVRA stipulates that the ideal VEGF inhibitor to treat nAMD would have a higher positive vision recovery velocity (more letters gained per unit time), low injection momentum (lower treatment burden requiring fewer interventions for a given visual acuity outcome), and vision recovery acceleration approximating zero (indicating stable vision over time),” report concludes. “AVRA allows comparisons across different trials to determine the optimal anti-VEGF agent for the treatment of nAMD.”

From this analysis, the researchers were able to extract that the agents with the most favorable vision recovery velocity are aflibercept and brolucizumab, with patients gaining approximately 0.44 and 0.56 letters per month, respectively. This is in contrast to 0.24 and 0.30 for bevacizumab and ranibizumab, respectively. 

Both aflibercept and brolucizumab require less frequent dosing than their competitors. This, researchers explain, is why they demonstrated the lowest injection momentum, at 4.13 and 3.61 injections, respectively. The researchers noted that they could achieve improved injection momentum for bevacizumab and ranibizumab with less-than-monthly dosing, but that this “came at a cost of vision recovery velocity.”

Finally, vision recovery acceleration was between -0.02 and -0.01 letters lost (negative value) per month squared for all 4 agents. This suggests that, with any of the agents, patients experience a negative direction to the vector quantity of VRA, indicating the likelihood of patients losing vision over time.

The study was limited in that there was likely heterogeneity with the studies in this analysis. Also, ARVA assesses treatment efficacy only, and doesn’t account for safety of treatment And lastly, cost-effectiveness is not included in ARVA.


Almeida DRP, Ruzicki J, Xu K, Chin EK. Vision recovery velocity, momentum and acceleration: advanced vitreoretinal analytics as measure of treatment efficacy for neovascular age-related macular degeneration. Clin Ophthalmol. 2021;15(1):189-194. doi:10.2147/OPTH.S288621.