{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:19:56Z","timestamp":1773656396097,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,21]]},"DOI":"10.7759\/cureus.80958","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T16:07:45Z","timestamp":1742573265000},"source":"Crossref","is-referenced-by-count":1,"title":["Tolerability and Efficacy of Topical Methotrexate in Ocular Surface Disease"],"prefix":"10.7759","author":[{"given":"Nathan A","family":"Seto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Calvin W","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell  A","family":"Watsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W","family":"Yee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2016.60995","article-title":"Immunomodulation on the ocular surface: a review","volume":"41","author":"Ambroziak AM","year":"2016","unstructured":"Ambroziak AM, Szaflik J, Szaflik JP, Ambroziak M, Witkiewicz J, Skopi\u0144ski P. Immunomodulation on the ocular surface: a review. Cent Eur J Immunol. 2016, 41:195-208. 10.5114\/ceji.2016.60995","journal-title":"Cent Eur J Immunol"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.18240\/ijo.2022.05.20","article-title":"Inflammation and dry eye disease-where are we?","volume":"15","author":"Rao SK","year":"2022","unstructured":"Rao SK, Mohan R, Gokhale N, Matalia H, Mehta P. Inflammation and dry eye disease-where are we?. Int J Ophthalmol. 2022, 15:820-7. 10.18240\/ijo.2022.05.20","journal-title":"Int J Ophthalmol"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14303","article-title":"Characterization of AICAR transformylase\/IMP cyclohydrolase (ATIC) from Staphylococcus lugdunensis","volume":"284","author":"Verma P","year":"2017","unstructured":"Verma P, Kar B, Varshney R, Roy P, Sharma AK. Characterization of AICAR transformylase\/IMP cyclohydrolase (ATIC) from Staphylococcus lugdunensis. FEBS J. 2017, 284:4233-61. 10.1111\/febs.14303","journal-title":"FEBS J"},{"key":"ref4","article-title":"Methotrexate","author":"Hanoodi M","year":"2024","unstructured":"Hanoodi M, Mittal M. Methotrexate. StatPearls [Internet] (ed): StatPearls Publishing, Treasure Island (FL); 2024."},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1537689","article-title":"A review of clinical applications and side effects of methotrexate in ophthalmology","volume":"1","author":"Wang G","year":"2020","unstructured":"Wang G, Peng X. A review of clinical applications and side effects of methotrexate in ophthalmology. J. Ophthalmol. 2020, 1:1537689. 10.1155\/2020\/1537689","journal-title":"J. Ophthalmol"},{"key":"ref6","article-title":"A technique for obtaining sheets of intact rabbit corneal epithelium","volume":"23","author":"Gipson IK","year":"1982","unstructured":"Gipson IK, Grill SM. A technique for obtaining sheets of intact rabbit corneal epithelium. Invest Ophthalmol Vis Sci. 1982, 23:269-73.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2023.2241683","article-title":"A method for eliminating fibroblast contamination in mouse and human primary corneal epithelial cell cultures","volume":"48","author":"Chen Z","year":"2023","unstructured":"Chen Z, Lu X, Mylarapu N, Kuthyar S, Sakhalkar O, Watsky MA. A method for eliminating fibroblast contamination in mouse and human primary corneal epithelial cell cultures. Curr Eye Res. 2023, 48:981-91. 10.1080\/02713683.2023.2241683","journal-title":"Curr Eye Res"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59570-7","article-title":"Transient Cell Membrane Disruptions induce Calcium Waves in Corneal Keratocytes","volume":"10","author":"Chen Z","year":"2020","unstructured":"Chen Z, Lu X, McGee-Lawrence ME, Watsky MA. Transient Cell Membrane Disruptions induce Calcium Waves in Corneal Keratocytes. Sci Rep. 2020, 10:2840. 10.1038\/s41598-020-59570-7","journal-title":"Sci Rep"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(02)01125-9","article-title":"Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement","volume":"109","author":"Smith JR","year":"2002","unstructured":"Smith JR, Rosenbaum JT, Wilson DJ, et al.. Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement. Ophthalmology. 2002, 109:1709-16. 10.1016\/S0161-6420(02)01125-9","journal-title":"Ophthalmology"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2007.127928","article-title":"Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience","volume":"92","author":"Frenkel S","year":"2008","unstructured":"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, 92:383-8. 10.1136\/bjo.2007.127928","journal-title":"Br J Ophthalmol"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S111893","article-title":"Intravitreal methotrexate infusion for proliferative vitreoretinopathy","volume":"10","author":"Sadaka A","year":"2016","unstructured":"Sadaka A, Sisk RA, Osher JM, Toygar O, Duncan MK, Riemann CD. Intravitreal methotrexate infusion for proliferative vitreoretinopathy. Clin Ophthalmol. 2016, 10:1811-7. 10.2147\/OPTH.S111893","journal-title":"Clin Ophthalmol"},{"key":"ref12","article-title":"Conjunctiva-associated lymphoid tissue in the human eye","volume":"41","author":"Knop N","year":"2000","unstructured":"Knop N,  Knop E. Conjunctiva-associated lymphoid tissue in the human eye. Invest Ophthalmol Vis Sc. 2000, 41:1270-9.","journal-title":"Invest Ophthalmol Vis Sc"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2005.00394.x","article-title":"The role of eye-associated lymphoid tissue in corneal immune protection","volume":"206","author":"Knop E","year":"2005","unstructured":"Knop E, Knop N. The role of eye-associated lymphoid tissue in corneal immune protection. J Anat. 2005, 206:271-85. 10.1111\/j.1469-7580.2005.00394.x","journal-title":"J Anat"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2012.748052","article-title":"Dry eye as a mucosal autoimmune disease","volume":"32","author":"Stern ME","year":"2013","unstructured":"Stern ME, Schaumburg CS, Pflugfelder SC. Dry eye as a mucosal autoimmune disease. Int Rev Immunol. 2013, 32:19-41. 10.3109\/08830185.2012.748052","journal-title":"Int Rev Immunol"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e318030d259","article-title":"Hyperosmolarity-induced apoptosis in human corneal epithelial cells is mediated by cytochrome c and MAPK pathways","volume":"26","author":"Luo L","year":"2007","unstructured":"Luo L, Li DQ, Pflugfelder SC. Hyperosmolarity-induced apoptosis in human corneal epithelial cells is mediated by cytochrome c and MAPK pathways. Cornea. 2007, 26:452-60. 10.1097\/ICO.0b013e318030d259","journal-title":"Cornea"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.08.019","article-title":"JNK and ERK MAP kinases mediate induction of IL-1beta, TNF-alpha and IL-8 following hyperosmolar stress in human limbal epithelial cells","volume":"82","author":"Li DQ","year":"2006","unstructured":"Li DQ, Luo L, Chen Z, Kim HS, Song XJ, Pflugfelder SC. JNK and ERK MAP kinases mediate induction of IL-1beta, TNF-alpha and IL-8 following hyperosmolar stress in human limbal epithelial cells. Exp Eye Res. 2006, 82:588-96. 10.1016\/j.exer.2005.08.019","journal-title":"Exp Eye Res"},{"key":"ref17","article-title":"IL-6 induction in desiccated corneal epithelium in vitro and in vivo","volume":"17","author":"Higuchi A","year":"2011","unstructured":"Higuchi A, Kawakita T, Tsubota K. IL-6 induction in desiccated corneal epithelium in vitro and in vivo. Mol Vis. 2011, 17:2400-6.","journal-title":"Mol Vis"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1382","article-title":"Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium","volume":"47","author":"Corrales RM","year":"2006","unstructured":"Corrales RM, Stern ME, De Paiva CS, Welch J, Li DQ, Pflugfelder SC. Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium. Invest Ophthalmol Vis Sci. 2006, 47:3293-302. 10.1167\/iovs.05-1382","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-1145","article-title":"Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface","volume":"45","author":"Luo L","year":"2004","unstructured":"Luo L, Li DQ, Doshi A, Farley W, Corrales RM, Pflugfelder SC. Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. Invest Ophthalmol Vis Sci. 2004, 45:4293-301. 10.1167\/iovs.03-1145","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101442","article-title":"Ocular surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis","volume":"187","author":"Schaumburg CS","year":"2011","unstructured":"Schaumburg CS, Siemasko KF, De Paiva CS, Wheeler LA, Niederkorn JY, Pflugfelder SC, Stern ME. Ocular surface APCs are necessary for autoreactive T cell-mediated experimental autoimmune lacrimal keratoconjunctivitis. J Immunol. 2011, 187:3653-62. 10.4049\/jimmunol.1101442","journal-title":"J Immunol"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-2417","article-title":"Characterization of effector T cells in dry eye disease","volume":"50","author":"El Annan J","year":"2009","unstructured":"El Annan J, Chauhan SK, Ecoiffier T, Zhang Q, Saban DR, Dana R. Characterization of effector T cells in dry eye disease. Invest Ophthalmol Vis Sci. 2009, 50:3802-7. 10.1167\/iovs.08-2417","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.3.1247","article-title":"Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression","volume":"182","author":"Chauhan SK","year":"2009","unstructured":"Chauhan SK, El Annan J, Ecoiffier T, Goyal S, Zhang Q, Saban DR, Dana R. Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression. J Immunol. 2009, 182:1247-52. 10.4049\/jimmunol.182.3.1247","journal-title":"J Immunol"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1756-185X.2010.01564.x","article-title":"Low-dose and high-dose methotrexate are two different drugs in practical terms","volume":"13","author":"Malaviya AN","year":"2010","unstructured":"Malaviya AN, Sharma A, Agarwal D, Kapoor S, Garg S, Sawhney S. Low-dose and high-dose methotrexate are two different drugs in practical terms. Int J Rheum Dis. 2010, 13:288-93. 10.1111\/j.1756-185X.2010.01564.x","journal-title":"Int J Rheum Dis"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205023","article-title":"Methotrexate an old drug with new tricks","volume":"20","author":"Bedoui Y","year":"2019","unstructured":"Bedoui Y, Guillot X, S\u00e9lambarom J, et al.. Methotrexate an old drug with new tricks. Int J Mol Sci. 2019, 20:5023. 10.3390\/ijms20205023","journal-title":"Int J Mol Sci"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.5","article-title":"Methotrexate-how does it really work?","volume":"6","author":"Chan ES","year":"2010","unstructured":"Chan ES, Cronstein BN. Methotrexate-how does it really work?. Nat Rev Rheumatol. 2010, 6:175-8. 10.1038\/nrrheum.2010.5","journal-title":"Nat Rev Rheumatol"},{"key":"ref26","article-title":"Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells","volume":"6","author":"Cronstein BN","year":"1991","unstructured":"Cronstein BN, Eberle MA, Gruber HE, et al.. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci. 1991, 6:2441-5.","journal-title":"Proc Natl Acad Sci"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116884","article-title":"The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation","volume":"92","author":"Cronstein BN","year":"1993","unstructured":"Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest. 1993, 92:2675-82. 10.1172\/JCI116884","journal-title":"J Clin Invest"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e318157ac9e","article-title":"The development of validated bulbar redness grading scales","volume":"84","author":"Schulze MM","year":"2007","unstructured":"Schulze MM, Jones DA, Simpson TL. The development of validated bulbar redness grading scales. Optom Vis Sci. 2007, 84:976-83. 10.1097\/OPX.0b013e318157ac9e","journal-title":"Optom Vis Sci"}],"container-title":["Cureus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cureus.com\/articles\/329254-tolerability-and-efficacy-of-topical-methotrexate-in-ocular-surface-disease","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T16:08:01Z","timestamp":1742573281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cureus.com\/articles\/329254-tolerability-and-efficacy-of-topical-methotrexate-in-ocular-surface-disease"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,21]]},"references-count":28,"URL":"https:\/\/doi.org\/10.7759\/cureus.80958","relation":{},"ISSN":["2168-8184"],"issn-type":[{"value":"2168-8184","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3,21]]}}}