Early Anti-VEGF Isn't Worth Cost and Risk in Diabetic Retinopathy

Prophylactic aflibercept does not prevent vision loss in patients with diabetic retinopathy, according to new data presented at the 2023 annual meeting of the Association for Research in Vision and Ophthalmology.

Anti-vascular endothelial growth factor (anti-VEGF) treatments like aflibercept are proven interventions for patients with diabetic macular edema and proliferative diabetic retinopathy. However, aflibercept (Eylea) and drugs like it are indicated for all forms of diabetic retinopathy. So researchers, led by Raj Maturi, MD, ophthalmologist at Midwest Eye Institute in Indianapolis, set out to see if early treatment could protect vision in less severe forms of diabetic retinopathy.

"This study gives physicians very good data to say it is safe to wait until high-risk proliferative diabetic retinopathy or diabetic macular edema develop," Maturi told Medscape Medical News.

Maturi and colleagues conducted a head-to-head trial of early aflibercept vs a placebo injection in almost 400 eyes (328 patients) from 64 centers over 4 years. All patients had nonproliferative diabetic retinopathy (NPDR), good vision, and no center-involved diabetic macular edema (CI-DME). If participants advanced to high-risk prolific diabetic retinopathy or diabetic macular edema with vision loss, they were started on treatment with aflibercept.

After 4 years of up to quarterly injections, early intervention significantly improved signs of disease progression.

The four-year cumulative probability of developing prolific diabetic retinopathy or CI-DME with vision loss was 34% with aflibercept vs 57% for the sham group (adjusted hazard ratio, 0.40; 97.5% CI, 0.28 - 0.57; P < .001). Patients who received aflibercept also tended to have a lower probability of starting anti-VEGF injections for high-risk proliferative diabetic retinopathy or CI-DME within 4 years.

Vision outcomes, however, did not improve.

"It made no difference whatsoever in the level of visual acuity, even when you wait four years," Maturi told Medscape Medical News.

"Patients don't see with their anatomic outcomes, they see with their vision — and that's what we are ultimately interested in," said Lee Jampol, MD, professor of ophthalmology at Northwestern University Feinberg School of Medicine in Chicago, and a collaborator on the study. 

Patients' vision fared the same whether they received aflibercept early or once their disease progressed. The mean (standard deviation) change in visual acuity over 4 years in aflibercept vs placebo was -2.7 (6.5) vs. -2.4 (5.8) letters.

"If you are giving [intraocular] injections to prevent something you can easily treat, what's the point?" said Nimesh Patel, MD, a retina specialist at Mass Eye and Ear in Boston, who was not involved in the study. 

Patients who waited to receive aflibercept had the same visual acuity results with fewer treatments. The early treatment group ended up receiving an average of 13 injections, Maturi said. But the average for those who didn't get an injection until their condition worsened was only 8.7 injections. The placebo group overall averaged only 3.5 injections, he said. 

The anti-VEGF injections are expensive and time-intensive, requiring patients to come in frequently, according to Jampol. Plus giving the drug in the early stages of diseases, like NPDR, requires an intraocular injection into a healthy eye with good vision, Patel said, putting it at unnecessary risk for complications.

Maturi said the regimen of aflibercept in the study cost $1900 per dose.  

Clinicians must weigh the costs and risks of a preventive treatment in people who are healthy from a vision standpoint, Patel said. The prophylactic treatment adds cost and risk without producing a meaningful benefit to patient vision or quality of life.

Jampol said these findings were in line with what most retina specialists expected. The data  confirm the standard of care and demonstrate that "early is not necessarily better," he said. 

Regeneron Pharmaceuticals provided the aflibercept for the study and funds used by the DRCR Retina Network to offset the study's clinical costs. Maturi reports consultant work for Allegro Ophthalmics, Aiviva, Allergan, Allgenesis, Eli Lilly, Dutch Ophthalmic, Novartis, Neurotech, and Jaeb Center for Health Research. He reported receiving financial support from Allergan, Genentech, Ophthea, Kalvista, Samsung Bioepis, Graybug, Santen, ThromboGenics, Gyroscope, Gemini, Boehringer Ingelheim, Allegro, Senju, Ribomic, NGM Biopharmaceuticals, Unity, Graybug, and Clearside. Patel reports no relevant financial relationships.

Association for Research in Vision and Ophthalmology 2023 annual meeting: Abstract 2812. Presented April 25, 2023.

Donavyn Coffey is a Kentucky-based journalist reporting on healthcare, the environment, and anything that affects the way we eat. She has a master's degree from NYU's Arthur L. Carter Journalism Institute and a master's in molecular nutrition from Aarhus University in Denmark. You can see more of her work in Wired, Scientific American, Popular Science, and elsewhere.

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Cite this: Early Anti-VEGF Isn't Worth Cost and Risk in Diabetic Retinopathy - Medscape - Apr 25, 2023.