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Abdi F, Mohammadi SS, Ghasemi Falavarjani K. Intravitreal Methotrexate. JOVR [Internet]. 2021Oct.25 [cited 2024Apr.25];16(4):657–669. Available from: https://knepublishing.com/index.php/JOVR/article/view/9756
https://doi.org/10.18502/jovr.v16i4.9756
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- Cited by 3 articles
authors
-
Fatemeh Abdi
Fatemeh Abdi
Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
-
S. Saeed Mohammadi
S. Saeed Mohammadi
Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
-
Khalil Ghasemi Falavarjani
Khalil Ghasemi Falavarjani
Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
Published Date
- Oct 25, 2021
Intravitreal Methotrexate
Abstract
Intravitreal methotrexate (MTX) has been proven to be an effective treatment for various intraocular diseases. In this article, a comprehensive review was performed on intravitreal applications of methotrexate. Different aspects of the administration of intravitreal MTX for various clinical conditions such as intraocular tumors, proliferative vitreoretinopathy, diabetic retinopathy, age-related macular degeneration, and uveitis were reviewed and the adverse effects of intravitreal injection of MTX were discussed. The most common indications are intraocular lymphoma and uveitis. Other applications remain challenging and more studies are needed to establish the role of intravitreal MTX in the management of ocular diseases.
Keywords:
Inflammation, Intraocular Tumor, Intravitreal Injection, Methotrexate, Proliferative Vitreretinopathy, Uveitis
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3. Green JM. Glucarpidase to combat toxic levels of methotrexate in patients. Ther Clin Risk Manag 2012;8:403–413.
4. Weinblatt ME. Methotrexate in rheumatoid arthritis: a quarter century of development. Trans Am Clin Climatol Assoc 2013;124:16–25.
5. Cronstein BN, Sitkovsky M. Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. Nat Rev Rheumatol 2017;13:41–51.
6. Crabtree MJ, Tatham AL, Hale AB, Alp NJ, Channon KM. Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitricoxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways. J Biol Chem 2009;284:28128–28136.
7. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 2010;142:409–419.
8. Malemud CJ. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther Adv Musculoskelet Dis 2018;10:117–127.
9. Spurlock CF, 3rd, Gass HMt, Bryant CJ, Wells BC, Olsen NJ, Aune TM. Methotrexate-mediated inhibition of nuclear factor kappaB activation by distinct pathways in T cells and fibroblast-like synoviocytes. Rheumatology 2015;54:178– 187.
10. Olsen NJ, Spurlock CF, 3rd, Aune TM. Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937. Arthritis Res Ther 2014;16:R17.
11. Brown PM, Pratt AG, Isaacs JD. Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers. Nat Rev Rheumatol 2016;12:731–742.
12. Chan ES, Cronstein BN. Mechanisms of action of methotrexate. Bull Hosp Jt Dis 2013;71: S5–S8.
13. Gangaputra S, Newcomb CW, Liesegang TL, Kaçmaz RO, Jabs DA, Levy-Clarke GA, et al. Methotrexate for ocular inflammatory diseases. Ophthalmology 2009;116:2188–2198 e2181.
14. Ericson L, Karlberg B, Rosengren BH. Trials of intravitreal injections of chemotherapeutic agents in rabbits. Acta Ophthalmol 1964;42:721–726.
15. Ozkan EB, Ozcan AA, Sekeroglu HT, Kuyucu Y, Ozgun H, Polat S. Intravitreal injection of methotrexate in an experimental rabbit model: determination of ultrastructural changes. Indian J Ophthalmol 2013;61:329–333.
16. Aly E, Ebrahim A. Apoptosis and electroretinogram after intravitreal injection of methotrexate in an experimental rabbit model. Gen Physiol Biophys 2016;35:231–236.
17. Tian XM, Zhu Y. Apoptosis of rabbit retinal cell after eyeball rupture. Asian Pac J Trop Med 2013;6:273–279.
18. Hara A, Niwa M, Kumada M, Aokie H, Kunisadae T, Oyamaa T, et al. Intraocular injection of folate antagonist methotrexate induces neuronal differentiation of embryonic stem cells transplanted in the adult mouse retina. Brain Res 2006;1085:33–42.
19. Palakurthi NK, Correa ZM, Augsburger JJ, Banerjee RK. Toxicity of a biodegradable microneedle implant loaded with methotrexate as a sustained release device in normal rabbit eye: a pilot study. J Ocul Pharmacol Ther 2011;27:151–156.
20. Sunalp M, Wiedemann P, Sorgente N, Ryan SJ. Effects of cytotoxic drugs on proliferative vitreoretinopathy in the rabbit cell injection model. Curr Eye Res 1984;3:619–623.
21. Dorr RT, Fritz WL. Cancer chemotherapy handbook. Elsevier; 1980.
22. Deng SX, Penland S, Gupta S, Fiscella R, Edward DP, Tessler HH, et al. Methotrexate reduces the complications of endophthalmitis resulting from intravitreal injection compared with dexamethasone in a rabbit model. Invest Ophthalmol Vis Sci 2006;47:1516–1521.
23. Abbaszadeh Hasiri M, Baghaei Moghaddam E, Khalili MR, Amini AH, Eghtedari M, Azizzadeh M, et al. Intra-vitreal injection of methotrexate in experimental endotoxininduced uveitis in rabbit. Vet Res Forum 2018;9:315–321.
24. Abramson DH, Schefler AC. Update on retinoblastoma. Retina 2004;24:828-848.
25. Hurwitz RL, Chevez-Barrios P, Boniuk M, Chintagumpala M, Hurwitz MY. Retinoblastoma: from bench to bedside. Expert Rev Mol Med 2003;5:1–14.
26. Shields CL, Shields JA. Diagnosis and management of retinoblastoma. Cancer Control 2004;11:317–327.
27. Shields CL, Mashayekhi A, Au AK, Czyz C, Leahey A, Meadows AT, et al. The International Classification of Retinoblastoma predicts chemoreduction success. Ophthalmology 2006;113:2276–2280.
28. Kivela T, Eskelin S, Paloheimo M. Intravitreal methotrexate for retinoblastoma. Ophthalmology 2011;118:1689, 1689 e1681–1686.
29. Frenkel S, Hendler K, Siegal T, Shalom E, Pe’er J. Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience. Br J Ophthalmol 2008;92:383–388.
30. Gorlick RG, Abramson DH, Sowers R, Mazza BA, Dunkel IJ. Impairments in antifolate transport are common in retinoblastoma tumor samples. Pediatr Blood Cancer 2008;50:573–576.
31. Chihara D, Dunleavy K. Primary central nervous system lymphoma: evolving biologic insights and recent therapeutic advances. Clin Lymphoma Myeloma Leuk 2020;21:73–79.
32. Shiels MS, Pfeiffer RM, Besson C, Clarke CA, Morton LM, Nogueira L, et al. Trends in primary central nervous system lymphoma incidence and survival in the U.S. Br J Haematol 2016;174:417–424.
33. Coupland SE, Damato B. Understanding intraocular lymphomas. Clin Exp Ophthalmol 2008;36:564–578.
34. Coupland SE, Heimann H, Bechrakis NE. Primary intraocular lymphoma: a review of the clinical, histopathological and molecular biological features. Graefes Arch Clin Exp Ophthalmol 2004;242:901–913.
35. Hoffman PM, McKelvie P, Hall AJ, Stawell RJ, Santamaria JD. Intraocular lymphoma: a series of 14 patients with clinicopathological features and treatment outcomes. Eye 2003;17:513–521.
36. Isobe K, Ejima Y, Tokumaru S, Shikama N, Suzuki G, Takemoto M, et al. Treatment of primary intraocular lymphoma with radiation therapy: a multi-institutional survey in Japan. Leuk Lymphoma 2006;47:1800–1805.
37. Teckie S, Yahalom J. Primary intraocular lymphoma: treatment outcomes with ocular radiation therapy alone. Leuk Lymphoma 2014;55:795–801.
38. Fishburne BC, Wilson DJ, Rosenbaum JT, Neuwelt EA. Intravitreal methotrexate as an adjunctive treatment of intraocular lymphoma. Arch Ophthalmol 1997;115:1152– 1156.
39. Smith JR, Rosenbaum JT, Wilson DJ, Doolittle ND, Siegal T, Neuwelt EA, et al. Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement. Ophthalmology 2002;109:1709–1716.
40. Goldberg S, Frenkel S, Blumenthal EZ, Solomon A, Pe’er J. Intraocular lymphoma. Ophthalmology 2007;114:1236–1237.
41. Kaur M, Sahu S, Sharma N, Titiyal JS. Femtosecond laserassisted cataract surgery in phakic intraocular lens with cataract. J Refract Surg 2016;32:131–134.
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