Real-World Treatment Choices for AMD

Poor adherence to anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) remains a major limitation of existing therapies, a review of a large clinical database showed.

Almost 40% of patients stopped treatment during the first year, rising to a majority by the end of the second year. By year 5, only about a quarter of patients remained on therapy. Visual acuity worsened with decreasing number of injections, reported Andrew Moshfeghi, MD, of Keck Medicine of USC in Los Angeles, at the recent American Society of Retina Specialists (ASRS) meeting.

“This real-world data tells us that the largest drop in anti-VEGF treatment adherence really occurs during the first year, with 40% of patients already going more than 180 days without an injection,” said Moshfeghi. “This declining injection frequency over time is associated with reduced durability of the early vision gains. Delayed treatment initiation was associated with poorer vision outcomes and greater likelihood of non-persistence.”

Anti-VEGF non-persistence was associated with worse fibrosis and atrophy at baseline as well as a more frequent treatment interval at latest follow-up.

A separate study of recent trends in use of anti-VEGF therapies showed a surge in bevacizumab (Avastin) use, increased use of biosimilars, and variation in therapy choices by indication.

Rapid Increase in Non-Persistence

Moshfeghi reported findings from an analysis of the Vestrum Health Retina Database, encompassing patients who had a diagnosis of nAMD from January 2015 through June 2025 and who received at least one anti-VEGF injection. The analysis excluded patients who had a history of diabetic retinopathy, diabetic macular edema, retinal vein occlusion, or myopic choroidal neovascularization.

The study included 201,768 eyes in 158,727 patients (mean age 80 years). The fellow eye had treated nAMD in 16.9% of cases and untreated nAMD in 24%.

Within 12 months after initiating anti-VEGF therapy, 38.9% of patients had become non-persistent, defined as no injection for more than 180 days. Non-persistence increased to 52.6% at the end of 2 years, 72.9% at 5 years, and 80.1% at 7 years. The steady increase in non-persistence came with a steady decline in number of intravitreal injections, from a mean of 8.4 during year 1 to 6.6 in year 2, and 6.2-6.3 for years 4 through 8. Non-persistent patients lost four times as many letters of visual acuity from baseline (-8.0 vs -2.1).

“Suboptimal long-term nAMD vision outcomes are driven by poor real-world anti-VEGF adherence, emphasizing the urgent need for longer-lasting, more durable therapies,” said Moshfeghi.

During a discussion, Vivienne Hau, MD, PhD, of Kaiser Permanente Bernard J. Tyson School of Medicine in Pasadena, California, noted: “The best drug is the one that the patient actually received. Your study demonstrated very well about how a lot of patients are not getting the medication. How do you think newer drugs coming out can change things?”

The problem is multifactorial, but newer drugs might help if they address one of the biggest issues: transportation for frequent treatment, said Moshfeghi.

“A lot of these patients can’t drive because they don’t have good vision,” he said. “They have to have a medical assistant or family member come with them, and that person often has to take time off from work. If we can do anything to remove some of these barriers, like having longer-lasting, more durable treatment … then they will have a lot more faith in the fact that the drug is still having the intended effect and less onus on the patient to come back and forth so frequently.”

Real-World Treatment Choices

A real-world study of recent trends in intravitreal therapy for nAMD showed that bevacizumab (Avastin) accounted for 30% of all injections in 2025, more than any other agent. Bevacizumab’s share of injections increased during the 3 years analyzed. In contrast, use of aflibercept 2 mg decreased by more than 50% from 2023 to 2025, but use of aflibercept 8 mg (Eylea) increased by 50% from 2024 to 2025, reported Anton Kolomeyer, MD, PhD, of NJRetina in Lawrenceville, New Jersey.

During the discussion, a member of the audience asked Kolomeyer about the potential reasons for the increased use of bevacizumab.

“Obviously the Good Days issue [with depletion of co-pay support] has been a big burden to the patients,” said Kolomeyer. “I keep having conversations with them, and they don’t understand why they now owe something for the injection, whereas before they didn’t. I never used to discuss this with patients.”

“I don’t think [bevacizumab is] our preference, as first line, but maybe we have to use it for a certain percentage of the population,” he added. “You definitely have to ask why the rate increased so dramatically in ’25 compared to ’23 and ’24.”

A study reported at the American Academy of Ophthalmology meeting in October supported Kolomeyer’s caution about switching to bevacizumab. An analysis of medical records for 177 eyes (152 patients) switched to treatment with bevacizumab showed a decline in visual acuity within 3 months of the switch, continuing out to 12 months. Retinal thickness initially increased before decreasing to a mean value below the baseline at 12 months. The frequency of intravitreal injections increased over time after the switch, which might explain the decline in retinal thickness, Adam Weiner, MD, of Associated Retinal Consultants and Corewell Health William Beaumont University Hospital in Royal Oak, Michigan, and colleagues reported in a poster presentation.

The findings were consistent with a report last year from an ASRS-supported analysis of treatment patterns involving more than 300,000 eyes. The study showed an increase in switching to bevacizumab for patients with AMD, diabetic macular edema (DME), and geographic atrophy. Based on Vestrum data, the analysis showed a decline in visual acuity after the switch in one-fourth of eyes treated for AMD and 19% of eyes treated for DME.

Kolomeyer’s analysis also involved records from the Vestrum database. The 2025 data encompassed 81 ophthalmology practices, 384 physicians, 930,606 patients, 2.8 million visits, and over 1.4 million intravitreal injections, a 6.1% increase in injections versus 2024 and 7.9% higher than 2023.

The most common indication for injection was nAMD (52.0%), followed by DME (28.3%), and retinal vascular occlusion (RVO) with ME (12.2%).

After bevacizumab, the next most commonly used agent was aflibercept 2 mg, at 21.9% in 2025 as compared with 36.9% in 2024 and 45.6% in 2023. Faricimab (Vabysmo) came in third at 18.9% (vs 18.4% in 2024 and 11.4% in 2023), followed by aflibercept 8 mg at 12.7% (vs 8.5% in 2024 and 0.6% in 2023, after an August 2023 approval). The biosimilar aflibercept-ayyh (Pavblu) accounted for 11.8% in 2025, an increase from 0.2% in 2024 (after an August approval).

An analysis of injections by indication showed that bevacizumab (23.6%) and faricimab (23.4%) accounted for almost half of all injections for nAMD. Bevacizumab (34.4%) and aflibercept 2 mg (24.7%) were used in a majority of injections for DME, and the same two drugs accounted for a majority of injections for RVO with ME (aflibercept 2 mg 35.9% and bevacizumab 26.5%).

Biosimilars accounted for 14.6% of all injections in 2025 (compared with 10.2% in 2024 and 3.5% in 2023), and the most common indication was nAMD (59% vs 70% in 2024). Aflibercept-ayyh was the biosimilar used in 80.8% of cases.