Methotrexate Treat-and-Extend Tested for Vitreoretinopathy

Laird Harrison

July 27, 2020

A treat-and-extend regimen of methotrexate can be used to successfully treat proliferative vitreoretinopathy, according to a series of 50 eyes in which 96% of retinas were successfully reattached.

"I'm really a believer in it, based on my own personal experience," said Scott Walter, MD, from Retina Consultants in Hartford, Connecticut.

Proliferative vitreoretinopathy occurs when scars form after a retinal detachment repair or a traumatic injury. When the scar tissue contracts, it pulls on the retina and causes it to detach.

Methotrexate is an antimetabolite that slows the growth of unwanted cells in cancer and psoriasis and modulates the immune system in rheumatoid arthritis. It has not yet been approved for proliferative vitreoretinopathy by the US Food and Drug Administration, but compounding pharmacies can make it for off-label use.

The phase 3 GUARD trial is currently assessing methotrexate in patients with proliferative vitreoretinopathy. Researchers hope it can prevent scar tissue from forming around detached retinas.

In a previous study of vitreoretinopathy treated with an intensive methotrexate protocol — intravitreal injections administered weekly for 8 weeks, followed by one to four additional biweekly injections — the reattachment rate was 92%.

But "I started to get reluctance from patients when I described this weekly postoperative treatment," he explained when he presented the case series at the virtual American Society of Retina Specialists 2020 Annual Meeting. "So I started spacing things out — with my own trial-and-error — after the first injection and was continuing to have good results."

His case series consisted of 50 adults with a detached retina and grade C or severe grade B proliferative vitreoretinopathy treated with 25-gauge pars plana vitrectomy with membrane peeling or relaxing retinectomy. About 40% of the patients received steroids.

The patients had multiple risk factors, including previous vitrectomy (70%), hemorrhage (22%), hypotony (18%), giant retinal tears (14%), severe trauma (14%), and endophthalmitis or uveitis (10%). And their comorbidities included full-thickness macular hole (18%), retinal neovascularization (10%), amblyopia (6%), advanced glaucoma (4%), and choroidal neovascularization (4%).

Walter administered a median of five intravitreal injections (range, 3 - 11) of 400 µg/0.1 mL methotrexate to each of the 50 eyes. Most — 84% — received no more than six injections. But the dosing was front loaded; in the first 14 days — the loading phase — he administered a median of three injections each.

Overall, however, injections were administered at a median interval of 11.5 days.

Walter's 96% reattachment rate matched the 92% seen with the intensive protocol, and he reattached 88% of the retinas in a single operation.

This study was only preliminary, he cautioned, and there was no control group. But he has a "hunch" that he might have succeeded with one operation in about two-thirds of the patients if he hadn't used methotrexate, he told Medscape Medical News.

He also estimates that he used 60% fewer injections than he would have had he used the intensive protocol.

There was a significant improvement in vision in the eyes in his case series (P < .0005). However, 38% of patients developed some form of keratopathy, such as nonhealing corneal epithelial defects and vortex-like keratopathy.

Walters said he generally recognized these adverse events during the loading phase and was able to treat the eyes with lubrication, a bandage contact lens, or an extension of methotrexate dosing.

On the basis of this experience, he recommends an injection every 1 or 2 weeks until the retinal edge heals, then every 3 to 6 weeks until the silicone oil is removed. This means three or four injections in the first month, and then about two in the subsequent 2 to 3 months.

These results are encouraging but they are far from definitive, said Kourous Rezaei, MD, from Rush University Medical Center in Chicago. "This was a retrospective study and we have to wait and see what the results of the clinical trials show," he told Medscape Medical News.

And "we know steroids are also antiproliferative," so their use could have confounded the results, he added.

Walter is a consultant to Allergan, Castle Biosciences, and Genentech. Rezaei has disclosed no relevant financial relationships.

American Society of Retina Specialists (ASRS) 2020 Annual Meeting. Presented July 25, 2020.

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