Study Finds Up to 30% of Patients with Wet AMD Can Safely Stop Anti-VEGF Treatment

According to Johns Hopkins Medicine researchers, up to a third of people with "wet" age-related macular degeneration can safely stop eye injection treatment without further vision loss.

The findings, according to the researchers, do not provide a timeline for stopping treatment or a precise prediction of which patients can stop injections, but they say the results add to growing evidence that many people with the disease may not require the lifelong monthly medication that is currently recommended.

The preliminary study, which included 106 patients with wet macular degeneration, published in print Jan. 18 in the Journal of Clinical Investigation.

The findings, the investigators say, also point to specific proteins produced at different levels in the eyes of those who stopped therapy, which may lead to the development of a test to accurately identify who may be weaned off medication.

“Such a test could let us tell patients early on how well they would do and when they might be able to stop,” says Akrit Sodhi, M.D., Ph.D., The Branna and Irving Sisenwein Professor of Ophthalmology associate professor of ophthalmology at the Johns Hopkins University School of Medicine and Wilmer Eye Institute.

The root cause of vision loss in people over 50 is age-related macular degeneration (AMD). The "wet" form of the disease, which is characterized by abnormal blood vessel growth that leaks harmful fluids into the light-sensitive tissues of the eye, affects the majority of people who lose eyesight.

Wet AMD is treated with monthly or biweekly injections of anti-VEGF (anti-vascular endothelial growth factor) medicines into the eye. Anti-VEGF drugs can delay or stop the growth of leaky blood vessels, thus preventing additional vision loss in most cases.

However, the need to return to a physician's office or clinic each month for injections is a common barrier to care among patients, leading to missed treatments and potentially worsening vision.

The Study

Sodhi and his colleagues analyzed the treatment outcomes of 106 people with wet age-related macular degeneration who were treated at the Johns Hopkins Wilmer Eye Institute in East Baltimore and a satellite clinic in Maryland between 2013 and 2020.

Each patient had a personalized anti-VEGF injection schedule, with Sodhi monitoring response to therapy and determining whether patients needed another injection at each visit or if they could enter a treatment pause, where the injection would be held unless new disease activity was detected at the next visit.

After at least 30 weeks of monitoring, eyes without treatment that showed no signs of fluid accumulation or increasing vision loss were considered to be safely weaned off anti-VEGF therapy.

Up to a third of the patients had stopped anti-VEGF medications in at least one eye by the end of the year. That amounted to 38 of 122 (31%) of treated eyes. A smaller percentage of eyes still required monthly injections, amounting to treatments for 21 of 122 (17%) patients' eyes.

The remaining half of patients required treatment every 6 to 12 weeks; a small number of these individuals were eventually weaned off treatment by the end of year two.

Patients who stopped anti-VEGF treatments in at least one eye had the best outcome, with less fluid and better vision than those who needed injections to maintain their vision.

"Across the board, the patients who could enter a treatment pause did the best even though they were receiving no anti-VEGF drugs. They had better visual acuity, better gain of vision and less fluid in their retina," says Sodhi.

The researchers next looked for biomarkers that could reveal what distinguished these individuals from those who needed monthly injections to maintain their vision.

Before beginning treatment with anti-VEGF therapy using their treatment plan, Sodhi's team collected small amounts of fluid from the eyes of some of the patients, and continued collecting samples at subsequent clinic visits from many of the patients.

The researchers discovered differences in the amounts of 172 proteins in the fluids of patients who were able to end treatment vs those who needed monthly medication.

In a proof-of concept experiment, the researchers chose one of the 172 proteins to investigate further — apolipoprotein B100 — that other studies had demonstrated is an important part of drusen, the material that accumulates under the retina in all patients with AMD and was thought to promote early changes in dry AMD.

The researchers found that apolipoprotein B100 was present at much higher levels in the eyes of patients who had been weaned off anti-VEGF treatment.

They further observed that the levels of this protein were higher in patients who did not develop wet AMD compared with patients who did. The researchers hypothesized this protein may help protect patients from developing wet AMD.

The researchers next conducted tests on mice by inducing abnormal blood vessel growth in the retina, similar to what is found in humans with macular degeneration.

Mice genetically engineered with elevated apolipoprotein B100 levels had less abnormal blood vessel growth in the retina than mice with lower levels of this protein, suggesting the protein indeed has a protective effect against the retinal disorder.

Sodhi believes that among the 172 proteins, there may be others that might be used as biomarkers to predict responsiveness to anti-VEGF therapy. Some of these proteins, he says, could be used for the development of new macular degeneration treatments.

Before broader recommendations on halting anti-VEGF therapy can be developed, randomized clinical trials in a large group of individuals with wet macular degeneration must be conducted, according to Sodhi.

Other researchers involved in this study include Xuan Cao, Jaron Castillo Sanchez, Chuanyu Guo, Tapan Patel, Zhiyong Yang, Ming-Wen Hu, Danyal Malik, Kathleen Jee, Yassine Daoud, James T. Handa, Lijun Chen, Yuefan Wang, Hui Zhang, and Jiang Qian of the Johns Hopkins University School of Medicine; Silvia Montaner of the University of Maryland and Aumreetam Dinabandhu of the Johns Hopkins University School of Medicine and the University of Maryland.

This work was supported by the National Eye Institute, Research to Prevent Blindness, Inc., the Alcon Young Investigator Award from the Alcon Research Institute, the Robert Bond Welch Professorship, and the Branna and Irving Sisenwein Professorship in Ophthalmology.