Q&A: Alan J. Franklin, MD, PhD, on postoperative methotrexate injections

At the 2025 meeting of the American Society of Retina Specialists, Alan J. Franklin, MD, PhD, FASRS, presented on using methotrexate to treat retinal detachments, particularly in diabetic patients. This presentation focused on a retrospective study of 251 patients showed a 57% reduction in reoperation rates. The treatment protocol evolved from weekly 13-week injections to a more flexible approach of 3-5 targeted injections at 200 micrograms.

The patient group included diabetics, complex retinal detachments, and trauma cases. Methotrexate's ability to inhibit scar tissue formation makes it effective in managing fibrotic proliferation.

Note: The following conversation has been lightly edited for clarity.

Modern Retina: Your presentation at the ASRS 2025 meeting is titled, "Postoperative methotrexate injections decrease reoperation rate and improve vision following vitrectomy for PDR and complex retinal detachments. Can you share about this study design and some of its highlights?

Alan J. Franklin, MD, PhD, FASRS: A lot of people have been using methotrexate for primary retinal detachment and PVR. We've got a very sick population and a lot of sick diabetics. So since methotrexate appears to inhibit scar tissue formation after surgery for standard rhegmatogenous retinal detachment, a lot of the mechanisms between PDR and PVR are somewhat similar. We tried it in our diabetic patients that had a fair amount of fibrotic proliferation or fibrovascular proliferation. It worked really well. We decreased our re-operation rate by about 57%.

This is an off-label, retrospective study. We have a little over 160 people in the non-treated eyes. We just looked at a similar cohort of patients prior to using methotrexate, and 91 in the methotrexate-treated arm. The methotrexate-treated arm contained about 2/3 diabetics, 1/3 complex retinal detachments, either giant tears or PVR, and then a small amount of trauma [cases]. And that was a similar breakdown amongst both groups.

MR: What was the treatment protocol used during this study?

Franklin: The initial methotrexate protocol was a shot-a-week for 13 weeks. My colleague and friend at Cincinnati Eye, Chris Riemann, was doing a limited injection protocol with 4 or 5 injections, and we adopted something similar to that, and then decreased the dose from 400 micrograms to 200 micrograms. So we were able to get most of our patients to do anywhere between 3 and 5 injections. It was an average of 4 injections. Kind of what we've evolved into is the patients with mild proliferation, or the ones that we're not too worried about. We do 3 injections, maybe week 2, 4, and 6 post-op, and the standard 5 injection is week 1, week 2, week 4, week 7, and week 11. So, 1 week between injections and 2 weeks, 3 weeks, and so on. I think it would be great to do, for the diabetics, a prospective study. That's something that we could do with the DRCR. Dr Riemann is actually going to report some findings from the FIXER study, which is a prospective study for primary retinal detachments.