Study Links Anti-VEGF Dose Frequency to Acuity Improvement

Macular degeneration treatment. 75-year-old female patient receiving an intra-ocular bevacizumab (Avastin) injection to treat macular degeneration and retinal vein thrombosis. Bevacizumab is an angiogenesis inhibitor, a drug that slows the growth of new blood vessels. It is usually used in chemotherapy to treat a number of cancers but here is being used to treat age-related eye conditions. Macular degeneration caused damage to the macula, the central area of the retina in the eye, which leads to a loss of vision in the central field of vision. Retinal vein thrombosis, or central retinal vein occlusion, is a blockage of the central retinal vein. As one of only two sources of blood supply to the eye, occlusion of the central retinal vein can lead to blindness.
Research shows a relationship between dose frequency and visual acuity change in patients with age-related macular degeneration.

A dose-response curve exists between treatment frequency and visual acuity change at 1 year in neovascular age-related macular degeneration (nAMD), a researcher found in a literature review published in Retina. The studies that dosed patients monthly had the best visual acuity gains, as well as the greatest injection frequency, while groups injected at variable or PRN frequencies had the lowest injection frequencies and the lowest acuity improvements.

The study sought to estimate the dose-response characteristics for the anti-vascular endothelial growth factor (VEGF) agents ranibizumab and aflibercept in the treatment of nAMD. The research includes observational studies since most systematic reviews of the treatment review a small number of core randomized controlled trials, which limits the ability of ophthalmologists to estimate outcomes.

The investigator recorded the number of patients treated, drug used, strategy employed, number of injections, and visual acuity results in the first year from studies in databases from January 1, 2006, to September 3, 2018. Treatment strategy was classified into 4 categories; fixed (fixed interval treatment), PRN protocol, variable (at physicians’ or patients’ and physicians’ discretion without stated protocol), and treat and extend(TRE). Visual acuity changes were calculated from logMAR visual acuity change. Group means were tested with 1-way ANOVA and Games-Howell posthoc test, and data were analyzed with univariate analysis of variance and least squares regression.

Of the 96 papers with 120 data points included in the review, 21 were in the fixed group (13 monthly and the remainder, less frequently), 59 PRN, 24 TE, and 16 variable. The mean number of injections varied from 3.5 injections to 13 injections annually.

The difference in the number of injections was significant (P <.05) between all pairwise comparisons, except for between the variable and PRN groups, which had the lowest injection frequencies and lowest acuity improvements.

The change in visual acuity by ETDRS equivalent letters ranged from -7.5 to +16.0 and showed a non-linear response with the injection frequency per year.

Lower injection frequencies were associated with higher costs per letter gained. The cost per letter gained reached a nadir at approximately 7 injections per year with a relatively flat cost function per letter through 13 injections per year.

“The burdens inherent in the disease should be weighed against concept-of-treatment burdens. There appears to be a trade-off between dosing frequency and outcome, calculating dollars saved by reduced dosing ignores the visual acuity costs,” the study says. “Thus, reported costs savings from using optical coherence tomography to guide personalized anti-VEGF treatment should be expanded to include expected gain in acuity vs the reduced treatment frequency since dollar costs are only half of the story.”

Limitations of the research included the heterogeneity of the studies included in the review.

Disclosure: The study author declared affiliations with the biotech and pharmaceutical industries. Please see the original reference for a full list of authors’ disclosures.


Spaide RF. Anti-vascular endothelial growth factor dosing and expected acuity outcome at 1 year. Retina. Published online January 11, 2021. doi:10.1097/IAE.0000000000003116