Anatomical and Functional Outcomes of Vitrectomy with/without Intravitreal Methotrexate Infusion for Management of Proliferative Vitreoretinopathy Secondary to Rhegmatogenous Retinal Detachment

Samir El Baha, Mahmoud Leila, Ahmed Amr, Mohamed M A Lolah, Samir El Baha, Mahmoud Leila, Ahmed Amr, Mohamed M A Lolah

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.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Copyright © 2021 Samir El Baha et al.

Figures

Figure 1
Figure 1
a-c. Six-month Kaplan–Meier survival curve for the study groups and their respective controls. Event refers to retinal redetachment within 6 months postoperatively.
Figure 2
Figure 2
Event-free survival across the study groups.

References

    1. Hiscott P. S., Grierson I., McLeod D. Natural history of fibrocellular epiretinal membranes: a quantitative, autoradiographic, and immunohistochemical study. British Journal of Ophthalmology. 1985;69(11):810–823. doi: 10.1136/bjo.69.11.810.
    1. Pastor J. C. Proliferative vitreoretinopathy. Survey of Ophthalmology. 1998;43(1):3–18. doi: 10.1016/s0039-6257(98)00023-x.
    1. Pennock S., Haddock L. J., Eliott D., Mukai S., Kazlauskas A. Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy? Progress in Retinal and Eye Research. 2014;40:16–34. doi: 10.1016/j.preteyeres.2013.12.006.
    1. Pastor J. C., Rojas J., Pastor-Idoate S., Di Lauro S., Gonzalez-Buendia L., Delgado-Tirado S. Proliferative vitreoretinopathy: a new concept of disease pathogenesis and practical consequences. Progress in Retinal and Eye Research. 2016;51:125–155. doi: 10.1016/j.preteyeres.2015.07.005.
    1. Sundaram V., Barsam A., Virgili G. Intravitreal low molecular weight heparin and 5-Fluorouracil for the prevention of proliferative vitreoretinopathy following retinal reattachment surgery. Cochrane Database of Systematic Reviews. 2013;(1):1–17. doi: 10.1002/14651858.CD006421.pub3.CD006421
    1. Lewis G. P., Sethi C. S., Linberg K. A., Charteris D. G., Fisher S. K. Experimental retinal reattachment: a new perspective. Molecular Neurobiology. 2003;28(2):159–176. doi: 10.1385/mn:28:2:159.
    1. Sadaka A., Sisk R., Osher J., Toygar O., Duncan M., Riemann C. Intravitreal methotrexate infusion for proliferative vitreoretinopathy. Clinical Ophthalmology. 2016;10:1811–1817. doi: 10.2147/opth.s111893.
    1. Benner J. D., Dao D., Butler J. W., Hamill K. I. Intravitreal methotrexate for the treatment of proliferative vitreoretinopathy. BMJ Open Ophthalmology. 2019;4(1) doi: 10.1136/bmjophth-2019-000293.e000293
    1. De Silva D. J., Kwan A., Bunce C., Bainbridge J. Predicting visual outcome following retinectomy for retinal detachment. British Journal of Ophthalmology. 2008;92(7):954–958. doi: 10.1136/bjo.2007.131540.
    1. Lewis H., Aaberg T. M., Abrams G. W. Causes of failure after initial vitreoretinal surgery for severe proliferative vitreoretinopathy. American Journal of Ophthalmology. 1991;111(1):8–14. doi: 10.1016/s0002-9394(14)76889-8.
    1. Lewis H., Aaberg T. M. Causes of failure after repeat vitreoretinal surgery for recurrent proliferative vitreoretinopathy. American Journal of Ophthalmology. 1991;111(1):15–19. doi: 10.1016/s0002-9394(14)76890-4.
    1. Silicone Study Group. Vitrectomy with silicone oil or perfluoropropane gas for eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone study report 2. Archives of Ophthalmology. 1992;110(6):780–792.
    1. Hardwig P. W., Pulido J. S., Erie J. C., Baratz K. H., Buettner H. Intraocular methotrexate in ocular diseases other than primary central nervous system lymphoma. American Journal of Ophthalmology. 2006;142(5):883–885. doi: 10.1016/j.ajo.2006.06.002.
    1. Amarnani D., Machuca-Parra A. I., Wong L. L., et al. Effect of methotrexate on an in vitro patient-derived model of proliferative vitreoretinopathy. Investigative Opthalmology and Visual Science. 2017;58(10):3940–3949. doi: 10.1167/iovs.16-20912.
    1. Hardwig P. W., Pulido J. S., Bakri S. J. The safety of intraocular methotrexate in silicone-filled eyes. Retina. 2008;28(8):1082–1086. doi: 10.1097/iae.0b013e3181754231.
    1. Nourinia R., Borna F., Rahimi A., et al. Repeated injection of methotrexate into silicone oil-filled eyes for grade C proliferative vitreoretinopathy: a pilot study. Ophthalmologica. 2019;242(2):113–117. doi: 10.1159/000500271.
    1. Falavarjani K. G., Hadavandkhani A., Parvaresh M. M., Modarres M., Naseripour M., Alemzadeh S. A. Intra-silicone oil injection of methotrexate in retinal reattachment surgery for proliferative vitreoretinopathy. Ocular Immunology and Inflammation. 2020;28(3):513–516. doi: 10.1080/09273948.2019.1597894.
    1. Asaria R. H. Y., Kon C. H., Bunce C., et al. Adjuvant 5-fluorouracil and heparin prevents proliferative vitreoretinopathy. Ophthalmology. 2001;108(7):1179–1183. doi: 10.1016/s0161-6420(01)00589-9.
    1. Schaub F., Hoerster R., Schiller P., et al. Prophylactic intravitreal 5-fluorouracil and heparin to prevent proliferative vitreoretinopathy in high-risk patients with retinal detachment: study protocol for a randomized controlled trial. Trials. 2018;19(1):p. 384. doi: 10.1186/s13063-018-2761-x.
    1. Charteris D. G. Proliferative vitreoretinopathy: revised concepts of pathogenesis and adjunctive treatment. Eye. 2020;34(2):241–245. doi: 10.1038/s41433-019-0699-1.
    1. Nussenblatt R. B. Philosophy, goals, and approaches to medical therapy. In: Nussenblatt R. B., Whitcup S. M., editors. Uveitis: Fundamentals and Clinical Practice. 4th. New York, NY, USA: Mosby - Elsevier; 2010. pp. 76–113.
    1. Velez G., Yuan P., Sung C., et al. Pharmacokinetics and toxicity of intravitreal chemotherapy for primary intraocular lymphoma. Archives of Ophthalmology. 2001;119(10):1518–1524. doi: 10.1001/archopht.119.10.1518.
    1. Ozkan E. B., Ozcan A. A., Sekeroglu H. T., Kuyucu Y., Ozgun H., Polat S. Intravitreal injection of methotrexate in an experimental rabbit model: determination of ultrastructural changes. Indian Journal of Ophthalmology. 2013;61(7):329–333. doi: 10.4103/0301-4738.109518.
    1. The Retina Society Terminology Committee. The classification of retinal detachment with proliferative vitreoretinopathy. Ophthalmology. 1983;90:121–125.
    1. Machemer R., Aaberg T. M., Freeman H. M., Alexander R. I., John S. L., Ronald M. M. An updated classification of retinal detachment with proliferative vitreoretinopathy. American Journal of Ophthalmology. 1991;112(2):159–165. doi: 10.1016/s0002-9394(14)76695-4.
    1. Grigoropoulos V. G., Benson S., Bunce C., Charteris D. G. Functional outcome and prognostic factors in 304 eyes managed by retinectomy. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2007;245(5):641–649. doi: 10.1007/s00417-006-0479-z.
    1. Charteris D. G., Aylward G. W., Wong D., Groenewald C., Asaria R. H. Y., Bunce C. A randomized controlled trial of combined 5-fluorouracil and low-molecular-weight heparin in management of established proliferative vitreoretinopathy. Ophthalmology. 2004;111(12):2240–2245. doi: 10.1016/j.ophtha.2004.05.036.
    1. Lam R. F., Cheung B. T. O., Yuen C. Y. F., Wong D., Lam D. S. C., Lai W. W. Retinal redetachment after silicone oil removal in proliferative vitreoretinopathy: a prognostic factor analysis. American Journal of Ophthalmology. 2008;145(3):527–533. doi: 10.1016/j.ajo.2007.10.015.
    1. Wickham L., Bunce C., Wong D., McGurn D., Charteris D. G. Randomized controlled trial of combined 5-fluorouracil and low-molecular-weight heparin in the management of unselected rhegmatogenous retinal detachments undergoing primary vitrectomy. Ophthalmology. 2007;114(4):698–704. doi: 10.1016/j.ophtha.2006.08.042.
    1. Znaor L., Medic A., Binder S., Vucinovic A., Marin Lovric J., Puljak L. Pars plana vitrectomy versus scleral buckling for repairing simple rhegmatogenous retinal detachments. Cochrane Database of Systematic Reviews. 2019;(3) doi: 10.1002/14651858.CD009562.pub2.CD009562

Source: PubMed

3
Sottoscrivi