Use of Intravitreal Methotrexate Infusion in Complicated Retinal Detachment for Prevention of Proliferative Vitreoretinopathy in a Pilot Study

Abstract

Objective The objective of this pilot study was to evaluate the efficacy and safety of per-operative intravitreal methotrexate (MTX) infusion during vitrectomy in patients of retinal detachment (RD) with advanced grade proliferative vitreoretinopathy (PVR). Methods In this prospective interventional case series, we included patients with Grade C PVR, recurrent RD, and open globe trauma. All patients underwent standard single surgeon operated 23-gauge pars plana vitrectomy (PPV) with 80mg of MTX in 1000mL of irrigation fluid. All patients were followed up after four months to assess the final status of retinal attachment and visual acuity. Ethical review board permission was sought for this off-label use of MTX and all patients signed an informed consent form before this intervention. Results Thirty eyes of 30 patients with recurrent retinal detachment, open globe trauma, or grade C PVR at initial presentation were included in this study. After PPV, these patients were followed up after four months. A total of 24 (80%) patients maintained retinal attachment at four months. Mean preoperative best-corrected visual acuity (BCVA) was 1.35 logarithm of the minimum angle of resolution (logMAR) (range 0.5-3) and mean four months postoperative BCVA was 1.01 logMAR (range 0.3-3) (Student’s t -test; P -value <0.05). Seventeen (56.6%) eyes had pre-operative BCVA of 1.0 whereas 25 (83.3%) had BCVA of 1.0 at the end of the follow-up period. Six (20%) patients had preoperative BCVA of 0.7 whereas 12 (40%) patients had BCVA of 0.7 at four months postoperatively. Out of six (20%) eyes developing RD after this intervention, four eyes achieved retinal reattachment after a second surgery. We did not observe any MTX-related complications during the follow-up period of this study. Conclusion Intravitreal MTX infusion during PPV for complicated RD as an adjunctive therapy showed encouraging results and was found to be safe in its use. We need more rigorous and controlled studies to confirm the possible advantages of MTX and its role in the prevention of PVR.

Vitrectomy with Silicone Oil Tamponade and Single-Dose Intravitreal Methotrexate for Recurrent Retinal Detachment with Proliferative Vitreoretinopathy

“…Initial case series utilizing adjuvant MTX for PVR produced promising results [ 2 , 7 , 10 , 11 ]; moreover, the current ongoing GUARD (gain understanding against retinal detachment) trial employs a multiple-dose postoperative MTX regimen [ 14 ]. While results are pending, limitations of multiple MTX doses in the postoperative period are patient discomfort, need for more frequent visits, and addressing renumeration for procedures performed in the postoperative global period.…”

“…Methotrexate (MTX), a folate (vitamin B9) analog, and competitive dihydrofolate reductase inhibitor [ 2 , 7 , 8 ], prevents the regeneration of an essential cofactor (tetrahydrofolate) in the eukaryotic thymidine and purine ring synthesis pathways, resulting in halted DNA and RNA synthesis and subsequent cellular death, particularly for rapidly proliferating cells [ 9 ]. Intraocular preparations of MTX are typically concentrated to less than 400 μg/0.10 mL (usually in silicone oil) and have a therapeutic half-life of 3–5 days [ 2 , 7 , 10 , 11 ]. At this dosage, MTX inhibits cellular proliferation and suppresses immune cell-mediated cytokine production, which addresses the observed RPE EMT and immune cell proliferation observed in PVR [ 2 , 7 , 8 , 10 , 11 ].…”

“…Intraocular preparations of MTX are typically concentrated to less than 400 μg/0.10 mL (usually in silicone oil) and have a therapeutic half-life of 3–5 days [ 2 , 7 , 10 , 11 ]. At this dosage, MTX inhibits cellular proliferation and suppresses immune cell-mediated cytokine production, which addresses the observed RPE EMT and immune cell proliferation observed in PVR [ 2 , 7 , 8 , 10 , 11 ]. Current studies are assessing multiple-dose paradigms; however, our case is unique in the use of a single intraoperative intravitreal MTX application.…”

Translational and clinical advancements in management of proliferative vitreoretinopathy

“…Currently undergoing patient enrolment [78] Non controlled study of patients severe recurrent PVR and/or a history of severe ocular inflammation receiving intravitreal MTX infusion during PPV Low incidence of recurrent PVR and no significant safety issues [79] Non controlled study of grade C PVR, recurrent RD, and open globe trauma receiving intravitreal MTX infusion during PPV Favorable single surgery anatomic success rate (80%). No adverse events [80] factor is the timing of administration. Given that the peak onset of postoperative PVR occurs at a median of 2 months, there may be a need for repeated or sustained drug delivery [7].…”

Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice

“…Intravitreal (IVI) methotrexate injection has been extensively studied for PVR prevention recently. Although some promising results have been reported, the effect has not yet been proven in the clinical trials [ 18 , 19 , 20 , 21 ]. Many drugs, such as corticosteroids, retinoids, and glucosamine, might be useful for inhibiting PVR development at specific stages [ 1 , 22 , 23 , 24 ].…”