Access to Optimal Care Has Stymied Visual Acuity Gains in AMD With Anti-VEGF Treatment

The real-world visual acuity gains in age-related macular degeneration (AMD) after treatment have been inferior to those seen in clinical trials, explained a speaker during the American Academy of Ophthalmology 2021 meeting.

The real-world visual acuity gains in patients with age-related macular degeneration (AMD) treated with anti–vascular endothelial growth factor (VEGF) therapy have not matched those seen in clinical trials, explained Sophie J. Bakri, MD, chair, Department of Ophthalmology, Whitney and Betty MacMillan Professor of Ophthalmology in Honor of Robert R. Waller, MD, Mayo Clinic, during a session on AMD and accessibility of optimal care.

As the US population ages, the prevalence of AMD is expected to increase substantially between 2010 and 2050, particularly among the White population, and to a lesser degree in the Hispanic and Black populations.

The vision gains after VEGF therapy that have been experienced in the real world have been inferior to those seen in clinical trials, which have described visual acuity increases that plateau and are maintained. In the real world, visual acuity does increase, but it isn’t maintained and eventually it declines.1-3

According to Bakri, there are several unmet needs in neovascular AMD management:

  • Catching conversion to wet AMD when vision is still good
  • Avoiding undertreatment
  • Reducing treatment burden

In the United States, there is poor visual acuity at diagnosis of wet AMD. The IRIS Registry, from the American Academy of Ophthalmology, found that in all eyes, the mean visual acuity at diagnosis is 20/83, and it is 20/85 in first eyes and 20/79 in second eyes.4 When there is poor vision at diagnosis, there is limited potential for improvement, Bakri said. One study found after stratifying patients by their initial visual acuity that even with anti-VEGF therapy, “over time each group of patients stays in their visual acuity lane.”5

It is clear that more anti-VEGF injections translates to better visual acuity, she said. The dosing in clinical trials is more frequent than that in the real world. A review of multiple studies showed that in clinical trials, the mean number of injections per year in the first year of treatments was anywhere from 6 to 13; however, in the real world, the mean number of injections in year 1 was much lower and ranged between 4.3 and 6.9.

In the real world, most retina specialists and ophthalmologists use the treat and extend protocol in which they treat until disease activity is resolved and extend treatment in 2- to 4-week intervals. When disease activity is observed again, they decrease the treatment interval.

In the future, it’s possible that optical coherence tomography could be done at home, Bakri said. Some findings presented at the annual scientific meeting of the American Society of Retina Specialists in 2019 and 2020 have shown that most users can complete the test at home after a 2-minute video tutorial. In addition, using an analysis software has been shown to be accurate and on par with a retina specialist.

“So, this is not yet FDA approved, but we hope it could help access to care,” she said.

Anti-VEGF therapy is in high demand. In the United States, there are approximately 2500 retina specialists and 18,000 ophthalmologists who perform anti-VEGF injections. These injections cost Medicare $2.7 billion annually and account for more than 12% of the Medicare Part B budget.6 The busiest of retina specialists can perform as many as 50 injections each day, Bakri said.

A 10-year follow-up study that Bakri published found that patients were receiving 5 to 7 injections per year and that eyes that did not have a yearly injection had worse visual acuity compared with eyes that had an injection every year.7 The proportion of patients with ≥20/200 vision expanded from 15% at baseline to 38% at the end of the study.

“So, what we’ve learned is that the number of injections is really key to maintaining vision,” Bakri concluded. In addition, longer-term treatments and home monitoring could “increase access and reduce disparities in care.”


1. Schmidt-Erfurth U, Kaiser PK, Korobelnik J-F, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121(1):193-201. doi:10.1016/j.ophtha.2013.08.011

2. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012;119(7):1388-1398. doi:10.1016/j.ophtha.2012.03.053.

3. Holz FG, Tadayoni R, Beatty S, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol. 2015;99(2):220-226. doi:10.1136/bjophthalmol-2014-305327

4. Rao P, Lum F, Wood K, et al. Real-world vision in age-related macular degeneration patients treated with single anti-VEGF drug type for 1 year in the IRIS Registry. Ophthalmology. 2018;125(4):522-528. doi:10.1016/j.ophtha.2017.10.010

5. Writing Committee for the UK Age-Related Macular Degeneration EMR Users Group. The neovascular age-related macular degeneration database: multicenter study of 92 976 ranibizumab injections: report 1: visual acuity. Ophthalmology. 2014;121(5):1092-1101. doi:10.1016/j.ophtha.2013.11.031

6. Patel S. Medicare spending on anti-vascular endothelial growth factor medications. Ophthalmol Retina. 2018;2(8):785-791. doi:10.1016/j.oret.2017.12.006

7. Starr MR, Kung FF, Mejia CA, Bui YT, Bakri SJ. Ten-year follow-up of patients with exudative age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections. Retina. 2020;40(9):1665-1672. doi:10.1097/IAE.0000000000002668