Abstract
Purpose To assess the anatomical and functional outcomes of intravitreal infusion of methotrexate (MTX) during pars plana vitrectomy (PPV) for proliferative vitreoretinopathy (PVR) associated with rhegmatogenous retinal detachment (RRD). Methods Comparative interventional nonrandomized study including consecutive patients who had vitrectomy for RRD. The study included six groups. Groups I (established PVR), II (high risk of PVR), and III (no risk of PVR) comprised prospectively recruited study eyes, which received PPV and adjuvant intravitreal MTX infusion equivalent to 400 μg/0.1 mL. Groups IA, IIA, and IIIA comprised retrospectively recruited control groups. Main outcome measures were retinal reattachment at the end of 6 months, visual outcome, and complications. Chi-square test or Fisher's exact test analyzed categorical variables. ANOVA test and Kruskal–Wallis test analyzed quantitative variables. Mann–Whitney U-test and independent t-test evaluated the difference between each group and its control. Comparison between two paired groups was done by Wilcoxon Rank test. The Kaplan–Meier method was used for survival analysis and the log-rank test estimated differences in event-free survival across the groups. P was significant at <0.05. Results The study included 190 eyes of 188 patients. Study Groups I, II, and III included 42, 35, and 24 eyes, respectively. Mean age was 45 years. Male gender constituted 70% of patients. Mean follow-up period was 6 months. Control Groups IA, IIA, and IIIA included 30, 30, and 29 eyes, respectively. Mean age was 50 years. Male gender constituted 50%. Mean follow-up period was 7 months. Median rate of retinal reattachment was 82% in the study eyes versus 86% in the control eyes. The difference in the retinal reattachment rates between each study group and its respective control was not statistically significant, Group I-IA (p= 0.2), Group II-IIA (p=0.07), and Group III-IIIA (p=0.07). BCVA improved by a mean of 4 lines in the study eyes versus 3 lines in the control eyes. The difference in visual outcome between each study group and its respective control was statistically significant between Groups II-IIA and III-IIIA, p=0.03, but not between Groups I-IA, p=0.07. We did not detect complications attributed to MTX use in the study eyes. Conclusion Intravitreal infusion of MTX during PPV is a safe adjuvant therapy in RRD patients with and without PVR. MTX yields superior functional outcomes in patients at high risk of PVR and in patients with no risk of PVR compared to PPV without MTX, but not in cases with established PVR. MTX did not confer an additional advantage in terms of retinal reattachment rate. Summary. Proliferative vitreoretinopathy is a major cause of failure in surgery for rhegmatogenous retinal detachment. Methotrexate as an adjuvant therapy blocks essential drivers in the pathogenetic cascade leading to PVR. Intravitreal infusion has the advantage of blocking the pathology in its nascence and obviates the need for repeated intravitreal injections of the drug.
Highlights
Proliferative vitreoretinopathy (PVR) represents a robust wound-healing response of the retina to injury produced by retinal detachment. e retinal cellular elements involved in this response are legion, and they work in tandem in a multipronged cascade that eventually establishes PVR. e pathogenetic process is based on three factors that are considered the hallmark of PVR
Intravitreal infusion of MTX during pars plana vitrectomy (PPV) has been reported to suppress PVR effectively. e rationale for this route is based on the easy penetrance of the low-molecular weight MTX into the retinal tissues, and the achievement of a stable tissue concentration that produces a uniform dosing of the drug as opposed to a single bolus delivered at the end of surgery [7]. e aim of this study is to assess the anatomical and functional outcomes of intravitreal infusion of MTX during PPV for PVR associated with retinal detachment
Significant differences were present between Groups I and IA in the status of the crystalline lens (p 0.01) and follow-up period (p 0.003), between Groups II and IIA in the follow-up period (p ≤ 0.001) and between Groups III and IIIA in gender distribution (p 0.001)
Summary
Proliferative vitreoretinopathy (PVR) represents a robust wound-healing response of the retina to injury produced by retinal detachment. e retinal cellular elements involved in this response are legion, and they work in tandem in a multipronged cascade that eventually establishes PVR. e pathogenetic process is based on three factors that are considered the hallmark of PVR. E aim of this study is to assess the anatomical and functional outcomes of intravitreal infusion of MTX during PPV for PVR associated with retinal detachment. Groups I, II, and III comprised prospectively recruited study eyes that received PPV and adjuvant intravitreal MTX infusion equivalent to 400 μg/0.1 mL. Group II (high risk of PVR) included eyes with recent-onset RRD ≤ 1-week duration and no clinical signs of PVR but with one or more risk factors for developing PVR. Groups IA, IIA, and IIIA comprised retrospectively recruited control eyes with established PVR, high risk of PVR, and no risk of PVR, respectively Patients in these groups had PPV without adjuvant intravitreal MTX infusion. A two-sided log-rank test with an overall sample size of 190 subjects (89 in the control group and 101 in the treatment group) achieves 80.0% power at a 0.050 significance level to detect a hazard ratio of 1.96 when the proportion surviving in the control group is 0.8950 with a difference in survival of 9%. e study lasts for 24 time periods, of which subject accrual (entry) occurs in the first 13 time periods
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