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Intravitreal Methotrexate Reduces Reoperation After Retinal Detachment Repair

— Reoperation rate reduced by three fourths, use expanded to advanced diabetic retinopathy

MedpageToday

NEW YORK CITY -- Postoperative intravitreal methotrexate for retinal detachment led to a significant reduction in reoperation and improved visual acuity, a retrospective chart review showed.

The absolute difference in reoperation rate was small, greater than 1% without methotrexate versus 0.4% with three to five postoperative injections of the antiproliferative agent, but the difference translated into a 73% reduction in reoperation procedures. Patients who did not receive methotrexate had a mean vision loss of about 1.7 lines as compared with an improvement of about 1.2 lines with methotrexate.

Patients received an average of 4.2 methotrexate injections, substantially fewer than previously reported protocols, and adverse events were generally mild and similar between patients who received methotrexate and those who did not, reported Alan Franklin, MD, PhD, of Infirmary Health in Mobile, Alabama, at the American Society of Retina Specialists meeting.

"This was a retrospective study of patients with advanced disease, but I think the results are really clear-cut," said Franklin. "This has certainly changed the way that I approach both complicated retinal detachments and my diabetic patients."

Preclinical studies showed that methotrexate significantly inhibited cell growth in a (PVR). In a phase I clinical study plus additional patients from clinical practice, intravitreal methotrexate in patients with PVR and other ocular injuries.

The favorable early results in PVR and retinal fibrosis led Franklin and colleagues to expand clinical use of methotrexate to patients with various complex retinal detachments, advanced diabetic retinopathy, and trauma. He reported findings from a chart review of 249 patients with proliferative diabetic retinopathy (PDR), PVR, and retinal trauma.

The study population comprised 163 patients who had retinal surgery without methotrexate and 86 who received three to five intravitreal injections of methotrexate. PDR accounted for almost 60% of cases, followed by PVR (~35%), and was similar in the two groups. Preoperative visual acuity also was similar between the groups, 20/400 in the patients who received methotrexate and 20/300 in those who did not.

The results showed a statistically significant reduction in the frequency of reoperation (P<0.001). The 2.9-line cumulative difference in postoperative visual acuity also achieved statistical significance (P<0.001).

The most common adverse events were redness and irritation and were similar in the two patient groups. One patient in the methotrexate group had a corneal epithelial defect that was treated by micropuncture. The opposite eye of the same patient (which was not treated with methotrexate) required a penetrating keratoplasty for a nonhealing corneal epithelial defect. Another patient in the methotrexate group had a postinjection vitreous hemorrhage and six-line vision loss. The patient deferred treatment with bevacizumab (Avastin) or vitrectomy.

An early, for intravitreal methotrexate injection employed as many as 13 injections over 24 weeks. Franklin has reduced the number injections to five, and in selected cases patients receive only three injections. During a discussion that followed his presentation, Franklin said he is satisfied with the results observed with fewer injections and expressed reservations that more injections would produce better results.

In response to a question from the audience, Franklin said the results appear similar across the different types of patients included in the analysis.

"One of the reasons for this study is that we are seeing encouraging results with PVR and trauma, but I have a lot of diabetic patients that have a lot of fibrosis," he said. "We've really seen similar results with our diabetics, but we need to tabulate the subgroups."

A randomized trial comparing methotrexate injections, infusion, or both for primary rhegmatogenous retinal detachment repair will begin enrolling patients before the end of the year, Franklin added.

  • author['full_name']

    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined ֱ in 2007.

Disclosures

Franklin disclosed relationships with Alcon and ForwardVue Pharma.

Primary Source

American Society of Retina Specialists

Franklin A, et al "Intravitreal methotrexate reduces reoperation rate and improves vision after vitrectomy for retinal detachment, trauma, and proliferative diabetic retinopathy" ASRS 2022.