Methotrexate Could Reduce the Risk for Retinal Redetachment

Laird Harrison

July 20, 2022

NEW YORK — Intravitreal methotrexate injections can reduce the need for reoperation after surgery for retinal detachment, even in eyes with complex pathology, researchers say.

"The main goal of this study was to see if it may work in the sick diabetic patients," Alan Franklin, MD, PhD, a retina specialist at Diagnostic and Medical Clinic in Mobile, Alabama, told Medscape Medical News. "It worked very well."

The drug cut Franklin's rate of reoperation by 63%, he said, and he is now more optimistic in counseling patients about what he can do for them.

Methotrexate is used to treat cancer or autoimmune disorders. A phase 1b clinical trial of ADX-2191, an ophthalmic formulation, suggested it has potential for preventing proliferative vitreoretinopathy (PVR), and a phase 3 trial is nearing completion.

People with diabetes have a high rate of fibrosis, which can cause retinal detachment and make reattachment difficult, Franklin said.

To see if methotrexate could prevent fibrosis in these patients, Franklin and Lauren Gibson, MD, compared the records of 86 patients they had treated with methotrexate to 163 they had not. Those who received methotrexate got 200 µg intravitreally via the inferotemporal pars plana at postoperative weeks 1, 2, 4, 7, and 11.

The methotrexate group had a preoperative visual acuity of 20/400, while the non-methotrexate group had a visual acuity of 20/300.

The groups were divided similarly by diagnosis: proliferative diabetic retinopathy for the majority, proliferative vitreoretinopathy for one third of patients, and trauma for the rest.

In the methotrexate group, the average eye needed 0.41 reoperations 6 months after the operation, while in the group not receiving methotrexate the average eye needed 1.12 reoperations.

In the methotrexate group, visual acuity improved by almost 1.5 ETDRS lines, while in the group that did not get methotrexate visual acuity worsened by more than 1.5 lines.

Redness and irritation were similar in the two groups.

Franklin described a 53-year-old teacher who had lost vision in his right eye to retinal detachment. After multiple episodes of proliferative vitreoretinopathy in the man's left eye, Franklin was able to reattach the patient's retina using methotrexate.

Ten weeks after surgery, vision in his left eye was 20/40. "He's able to go back to work, no restrictions," Franklin said. "It'll be a normal life as opposed to going down the same road and there being no light perception in this second eye."

With methotrexate, Franklin said, his practice is using less silicone oil and more gas.

The study reinforced what others have shown, said session moderator Carl Awh, MD, president of Tennessee Retina in Nashville, Tennessee. "These methotrexate injections might be really the first thing that effectively reduces the incidence of PVR," he told Medscape Medical News. He speculated that more injections could be even more effective.

The success of methotrexate in patients with a high incidence of diabetes is encouraging, said Tomasz Stryjewski, MD, a retina specialist at Tallman Eye Associates in Lawrence, Massachusetts.

Stryjewski, who developed ADX-2191 with Dean Eliott, MD, a professor of ophthalmology at Harvard Medical School in Boston, Massachusetts, said the study provided a better understanding of which retinal reattachment patients are good candidates for methotrexate.

"Seeing that the drug was responsive in this population — which I think would kind of make sense, given that it's an anti-inflammatory and anti-proliferative — is another contribution to how this can be used and how it can be effective," he told Medscape Medical News.

Aldeyra Therapeutics plans to report the results of the phase 3 GUARD trial of ADX-2191 for proliferative vitreoretinopathy this year, Stryjewski said.

Franklin reported no relevant financial interests. Stryjewski reported a financial relationship with Aldeyra Therapeutics. Awh reported financial relationships with Adverum, Allergan, Apellis, Arctic DX, Bausch and Lomb, Genentech, GlaxoSmithKline, Hoffmann-La Roche, Katalyst Surgical, Kodiak Sciences, Merck Pharmaceuticals, Ophthotec, Regeneron, and Stealth Biotherapeutics.

American Society of Retina Specialists (ASRS). Presented July 18, 2022.

Laird Harrison writes about science, health, and culture. His work has appeared in national magazines, in newspapers, on public radio and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at or follow him on Twitter: @LairdH

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