Hi everybody. This is Chris Riemann from the Cincinnati Eye Institute, and I'm really happy to talk to you about the fixer methotrexate update that I gave at the ASRS meeting in Montreal this past week. What we started doing about two years ago is we decided the best way to treat PVR is to hopefully have it not happen in the first place. So what we did is we created a prospective randomized double mass trial where 10 surgeons at three different clinical sites in the Cincinnati area are randomizing adult patients presenting with primary retinal detachment and no PVR into four groups. And those four groups are our controls that get no methotrexate. Then there's one group that gets, and that's the SS group. Then there's the methotrexate methotrexate, the MM group, they get an infusion intraoperatively of methotrexate that we do by putting 40 milligrams of methotrexate in the BSS plus posterior segment infusaid.

Plus we give four postoperative injections post-op weeks, one, three, six, and 10. And that's the MM group. And then there's the SM group, they get a sham infusion and real injections. And then there's the MS group, they get a real intraoperative infusion and sham injections postoperatively. And we've been randomizing patients since March of 2024. And the primary endpoint for the study is six-month attachment rate, re-operations, and 12-month ETDRS visual acuity, as well as the incidence of epiretinal membranes and the incidence of PVR.

We reported a planned interim safety analysis last year when a hundred patients reached 10 weeks of follow-up. And this year we're reporting the planned interim safety and efficacy analysis when 200 patients reached four months of follow-up. And what we found was that over time, the incidence of recurrent retinal detachment, the incidence of PVD, and the incidence of epiretinal membrane all go up. They go up faster in patients in the SS group and the MS group, and they go up significantly slower in the MM group and the SM group. So what that means is that it appears that methotrexate is protective against PVR in the setting of primary retinal detachment repair. Now, these are interim analyses. The study is powered to need about a hundred patients per group, and we have about half that right now. So some of the differences that we are showing that are clinically very meaningful are approaching statistical significance.

So we're going to keep recruiting. We don't have enough evidence to start recommending prophylactic methotrexate in the setting of uncomplicated primary retinal detachment repair yet, but we are moving in that direction, we think. So what can we conclude as of right now? Methotrexate is probably, we have enough data to say that it's safe in the setting of vitrectomy for primary retinal detachment repair. Methotrexate may be indicated in primary retinal detachment repair. The optimal regimen still remains unclear whether it's methotrexate injections, methotrexate infusions. We're thinking probably both will be best. We're going to continue to recruit patients at the three Cincinnati sites. And given these favorable four-month interim safety and now efficacy results of the fixer methotrexate prospective randomized trial, we are opening the trial to our colleagues across the globe. If anyone is interested in participating in this unfunded labor of love, we would love to have more sites join us in pushing through this protocol.

Thanks so much everyone.