A new study has shown up to a third of neovascular age-related macular degeneration (nAMD) patients may safely be able to stop intravitreal injections after a year, while also highlighting a potential biomarker to identify the best candidates.
In a preliminary study of 106 people with nAMD, Johns Hopkins Medicine researchers say while their findings fall short of setting a timeline for ending treatment or predicting which patients can stop injections, they have added to growing evidence that many patients may not need the lifelong monthly medication.
The findings 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,” Dr Akrit Sodhi, Associate Professor of Ophthalmology and the Branna and Irving Sisenwein Professor of Ophthalmology at the Johns Hopkins University School of Medicine and Wilmer Eye Institute, said.
For the study – published this month in Journal of Clinical Investigation – Sodhi and his team analysed treatment outcomes of 106 people with nAMD whom he treated.
Each patient had undergone a customised anti-VEGF injection schedule in which Sodhi monitored response to therapy and determined whether they needed another injection at each visit or if they could pause, in which the injection was held unless there was evidence of new disease activity at the next visit. Eyes without treatment that showed no signs of fluid accumulation or advancing vision loss after at least 30 weeks of monitoring were considered safely weaned off anti-VEGF therapy.
At the end of a year, up to a third of the patients had stopped anti-VEGF treatments in at least one eye. 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 other half required treatment every six to 12 weeks; a handful of these patients were also ultimately weaned from treatment at the end of year two.
Patients who stopped anti-VEGF treatments in at least one eye showed the best outcome, with less fluid and improved vision compared with those who required continued 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,” Sodhi said.
Deciphering who can stop treatment
The researchers next sought biomarkers that could show what distinguished these patients from those who required monthly injections to maintain their vision.
In fluid samples collected from patients, the researchers found differences in the amounts of 172 proteins between patients who were able to stop treatments compared with those who required monthly treatment.
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 researchers found 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. They hypothesised this protein may help protect patients from developing wet AMD.
The researchers then conducted tests in mice by inciting in the mouse retina abnormal blood vessel growth similar to that seen 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 said there were potentially other proteins among the 172 that could be used as biomarkers to predict the response to anti-VEGF therapies. He noted some of these proteins could be used for developing new macular degeneration treatments.