Study Explores Smoking, Intravitreal Anti-VEGF Injection Response in Wet AMD

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In a new study, the effect of smoking did not impact treatment response of anti-VEGF injection for patients with neovascular age-related macular degeneration.

A study led by Sophie Caspers of the Université Libre de Bruxelles in Brussels, Belgium did not find an effect of smoking on treatment response of intravitreal anti-vascular endothelial growth factor injection (anti-VEGF) in patients with neurovascular age-related macular degeneration (nAMD).1

Previous research suggested smoking has an association with nAMD. In a 2020 study, investigators found current smokers developed nAMD on average 5.5 years younger than non-smokers (P <0.00001) and 4.4 years younger than past smokers (P = 0.0008). Thus, if someone smoked, they were likely to develop nAMD at a younger age than someone who didn’t smoke or had stopped smoking.2

Then, in 2018, a retrospective, case-control study had already examined smoking’s effect on the outcome of VEGF therapy in Japanese patients with nAMD. The participants were divided into 2 categories: smokers and never-smokers. Patients were treated with ranibizumab or aflibercept for ≥1 year. The investigators measured the number of injections received, best-corrected visual acuity (BSVA), central retinal thickness (CRT) at the fovea, and choroidal thickness (SCT). The team found there were no statistically significant differences in BCVA, CRT, or SCT between smokers and non-smokers. Though, smokers with a history of heavy smoking received a higher number of injections.3

“Our results are consistent with the previous report of the harmful therapeutic effects of smoking in patients with nAMD,” the investigators of the 2018 study wrote. “The general population is unaware of the strong risk factor for the incidence of nAMD and the therapeutic effects for the patients with the disease; therefore, these hazards of smoking should be highlighted to the public.”3

Wanting to investigate the effect of smoking on the injection responses given to patients with nAMD, Caspers and colleagues conducted a cohort study in Belgium. Intravitreal treatment (IVT) was administered to 147 eyes of 131 patients. The team noted that 70% (n = 92) of the participants were female. The mean age at the time of the first injection was 79±9 years old.1

Like the 2018 study, the new study examined active smokers and non-smokers. At the start of the injections, 13% of the patients actively smoked. The smokers were, on average, 11 years younger than the non-smokers at the start of the IVT treatment. Ninety-four percent of the smokers had subretinal fluid, while only 65% of the non-smokers did.

Per findings from a binary logistic regression model, male patients reacted statistically worse to anti-VEGF IVT than female patients, with an odds ratio (OR) of 0.27.

The investigators also conducted Mann-Whitney analyses to compare the change in central macular thickness in smokers versus non-smokers.

“The change in logarithm of the minimum angle of resolution visual acuity between active smokers and non-smokers showed no significant difference in treatment response between both groups,” the investigators wrote. “Likewise, no significant difference was found when comparing treatment response between patients with less than 10 pack-years (PY) (including never-smokers) and patients with over 10 PY.”


  1. Caspers S, Abramowicz S, Pasteels B, Postelmans L. Smoking and short-term response to intravitreal anti-Vascular Endothelial Growth Factor injections in neovascular age-related macular degeneration [published online ahead of print, 2023 Oct 12]. J Fr Ophtalmol. 2023;S0181-5512(23)00411-4. doi:10.1016/j.jfo.2023.04.010
  2. Detaram HD, Joachim N, Liew G, et al. Smoking and treatment outcomes of neovascular age-related macular degeneration over 12 months. Br J Ophthalmol. 2020;104(7):893-898. doi:10.1136/bjophthalmol-2019-314849
  3. Kamao H, Goto K, Mito Y, Miki A, Kiryu J. Effects of Smoking on Outcomes of Antivascular Endothelial Growth Factor Therapy in Patients with Neovascular Age-Related Macular Degeneration Smoking and Anti-VEGF Therapy in nAMD. J Ophthalmol. 2018;2018:2353428. Published 2018 Nov 12. doi:10.1155/2018/2353428