Failed Compliance Remains Major Problem with Anti-VEGF

When you wake up, what is the thing you look forward to most for your upcoming day? Maybe  a run in the park? Or watching that latest TV show everyone has been talking about? From wherever you get life’s pleasures, one thing is for sure: Nobody looks forward to getting an eye injection.

We are not talking in abstract here — and occasionally, we all have to do things we don’t want to do. Nobody enjoys getting an injection to the eye, and while anti-VEGF treatment is a considerable medical breakthrough, patient compliance has proven difficult for many clinicians.

I Love the Smell of Anti-VEGF in the Morning

Anti-VEGF treatment is designed to block vascular endothelial growth factor (VEGF) and is used to treat conditions including age-related macular degeneration (AMD), a progressive disease with no current cure. According to the American Academy of Ophthalmology (AAO), anti-VEGF treatment improves the vision in about one-third of patients and in up to 90% of cases, it at least stabilizes vision.1 Anti-VEGF is also used to treat macular edema, diabetic retinopathy (DR), diabetic macular edema (DME) and retinal vein occlusion (RVO).

The description of how anti-VEGF is administered can send a shiver down the spines of the squeamish. A topical agent is applied to numb the eye, the patient’s eyelid is held back, and a small needle is injected into the white part of the eye, the sclera. Most people don’t want a needle in their eye, so it should therefore not come as a surprise that anti-VEGF has had significant problems with patient compliance.

A number of studies have been carried out on the issue and have found similar results from different countries and patient cohorts. One study from Turkey examined a group of 314 patients receiving anti-VEGF treatment for AMD, and a Jordanian study looked into 117 patients undergoing the same treatment, but for DME.

Failure to Comply Will Not Be Tolerated

Failed Compliance Remains Major Problem with Anti-VEGF

The Turkish study found that 57 patients (18.2%) did not attend monthly follow-up appointments over the following year after the first three months of injections. Overall, 39.8% of  patients were unable to fully comply with the anti-VEGF (ranibizumab) treatment after one year. The study also found that better visual acuity, smaller lesion size, living closer to the hospital, higher education and sociocultural level all led to patients being more likely to comply.2

The Jordanian study into DME patients reported that 85% of patients were compliant to their treatment and follow-up plan during the first year of management. However, while this study did take demographic, clinical and ocular characteristics into account, the study found that these factors were not significantly associated with patient compliance. The only independent variable was the subjective perception of visual improvement after three loading doses.3

Both studies showed a roughly 20% failure to comply rate, which in the Turkish study was significantly higher after one year. Even if the lowest figure is accepted, that still leaves a serious problem with patient compliance. So what can clinicians and doctors do to help improve this figure?

Eye Injections for Fun?

The psychological impact of anti-VEGF treatments was examined by a group of researchers primarily based in Manchester, England.4 They reviewed 14 different papers which considered this issue; unsurprisingly they found that patients focused on the potential anxiety and  pain caused by receiving regular intravitreal injections. They also reported that patients receiving anti-VEGF treatment showed a prevalence rate of depression between 20 and 26%, without attributing said depression to the treatment itself.

The researchers concluded that more research into the issue is required but still emphasized the efficacy and importance of anti-VEGF treatment, in general. In a similar study from  St. Franziskus Hospital in Munster, Germany, the researchers found that up to 30% of patients had unintentional termination. The main reason (38%) for an unintentional termination of examination and treatment was the frequent and long journey involved in the treatment process.5

The researchers concluded that “long-term therapy of AMD in the clinical routine can be achieved by a close relationship with the ophthalmologist, continuous follow-up controls and therapy cycles.” They also recommended telemedicine networking, as this is correlated with improved patient compliance. Given the explosion in telemedicine’s popularity since the beginning of the COVID-19 pandemic, this may prove to be an effective compliance tool.

No one is ever going to volunteer to have their eyes injected for fun, and while it’s easy to focus on medical progress, clinicians would do well to remember the psychological impact of treatment. More studies into anti-VEGF compliance would be welcome, and more importantly, so would practical solutions to improve this issue. After all, improved patient satisfaction is to the benefit of all.


  1. Anti-VEGF Treatments. The American Academy of Ophthalmology (AAO) Website. Available at Accessed on March 16, 2021.
  2. Polat O, İnan S, Özcan S, et al. Factors Affecting Compliance to Intravitreal Anti-Vascular Endothelial Growth Factor Therapy in Patients with Age-Related Macular Degeneration. Turk J Ophthalmol. 2017; 47(4): 205–210.
  3. Abu-Yaghi NE, Abed AM, Khlaifat DF et al. Factors Affecting Compliance to Anti-Vascular Endothelial Growth Factor Treatment of Diabetic Macular Edema in a Cohort of Jordanian Patients. Clin Ophthalmol. 2020; 14: 921–929.
  4. Senra H, Ali Z, Balaskas K, Aslam T. The Psychological Impact of anti-VEGF Treatments for Wet MAcular Degeneration – A Review. Graefes Arch Clin Exp Ophthalmol. 2016; 254(10): 1873–1880.
  5. Heimes B, Gunnemann F, Ziegler M, et al. Compliance of Age-Related Macular Degeneration Patients Undergoing anti-VEGF Therapy. Analysis and Suggestions for Improvement. [Article in German]. Ophthalmologe. 2016;113(11):925-932.
Notify of
Inline Feedbacks
View all comments