Losartan for Corneal Fibrosis

Summary

This is a prospective, randomized, double-blinded, controlled clinical trial designed to evaluate the efficacy and safety of topical losartan in improving visual acuity, contrast sensitivity and reducing corneal densitometry, corneal aberrations and corneal scarring severity in adult patients with corneal scars of different etiologies. Participants will be randomly assigned to receive either topical losartan 0.8 mg/mL or placebo eyedrops 6 times per day for six months.

Timeline

Start

2026-02-12

Primary completion

2027-02-11

Completion

2027-03-01

Publications

• Background COZAAR® (losartan potassium) tablets, for oral use Initial U.S. Approval: 1995 . FDA
• Background PLM. (n.d.). COZAAR - Comprimidos. Medicamentos PLM. Recuperado el 9 de febrero de 2025, de https://www.medicamentosplm.com/Home/productos/cozaar.comprimidos/128/101/77344/25
• Background Mauer M, Zinman B, Gardiner R, Suissa S, Sinaiko A, Strand T, Drummond K, Donnelly S, Goodyer P, Gubler MC, Klein R. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009 Jul 2;361(1):40-51. doi: 10.1056/NEJMoa0808400.
• Background Burnier M, Waeber B, Brunner HR. Clinical pharmacology of the angiotensin II receptor antagonist losartan potassium in healthy subjects. J Hypertens Suppl. 1995 Jul;13(1):S23-8. doi: 10.1097/00004872-199507001-00003.
• Background Zandbergen AA, Baggen MG, Lamberts SW, Bootsma AH, de Zeeuw D, Ouwendijk RJ. Effect of losartan on microalbuminuria in normotensive patients with type 2 diabetes mellitus. A randomized clinical trial. Ann Intern Med. 2003 Jul 15;139(2):90-6. doi: 10.7326/0003-4819-139-2-200307150-00008.
• Background Kubba S, Agarwal SK, Prakash A, Puri V, Babbar R, Anuradha S. Effect of losartan on albuminuria, peripheral and autonomic neuropathy in normotensive microalbuminuric type 2 diabetics. Neurol India. 2003 Sep;51(3):355-8.
• Background 45. Pucker AD, Frogozo M, Malooley MM, Harthan JS. Point-Counter Point: Treating Corneal Haze with 0.8 mg/mL Topical Losartan. Clinical Insights in Eyecare. 2024;2(5).
• Background Rodgers EG, Al-Mohtaseb Z, Chen AJ. Topical Losartan for Treating Corneal Haze After Ultraviolet-A/Riboflavin Collagen Cross-Linking. Cornea. 2024 Sep 1;43(9):1165-1170. doi: 10.1097/ICO.0000000000003527. Epub 2024 Mar 22.
• Background Sampaio LP, Hilgert GSL, Shiju TM, Murillo SE, Santhiago MR, Wilson SE. Topical losartan inhibits corneal scarring fibrosis and collagen type IV deposition after Descemet's membrane-endothelial excision in rabbits. Exp Eye Res. 2022 Mar;216:108940. doi: 10.1016/j.exer.2022.108940. Epub 2022 Jan 21.
• Background Sampaio LP, Villabona-Martinez V, Shiju TM, Santhiago MR, Wilson SE. Topical Losartan Decreases Myofibroblast Generation But Not Corneal Opacity After Surface Blast-Simulating Irregular PTK in Rabbits. Transl Vis Sci Technol. 2023 Sep 1;12(9):20. doi: 10.1167/tvst.12.9.20.
• Background Sampaio LP, Hilgert GSL, Shiju TM, Santhiago MR, Wilson SE. Losartan Inhibition of Myofibroblast Generation and Late Haze (Scarring Fibrosis) After PRK in Rabbits. J Refract Surg. 2022 Dec;38(12):820-829. doi: 10.3928/1081597X-20221026-03. Epub 2022 Dec 1.
• Background Sampaio LP, Hilgert GSL, Shiju TM, Santhiago MR, Wilson SE. Topical Losartan and Corticosteroid Additively Inhibit Corneal Stromal Myofibroblast Generation and Scarring Fibrosis After Alkali Burn Injury. Transl Vis Sci Technol. 2022 Jul 8;11(7):9. doi: 10.1167/tvst.11.7.9.
• Background Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC 3rd. Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. N Engl J Med. 2008 Jun 26;358(26):2787-95. doi: 10.1056/NEJMoa0706585.
• Background Rosenkranz S. TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res. 2004 Aug 15;63(3):423-32. doi: 10.1016/j.cardiores.2004.04.030.
• Background Gu L, Zhu Y, Lee M, Nguyen A, Ryujin NT, Huang JY, Pandit SK, Chamseddine S, Xiao L, Mohamed YI, Kaseb AO, Karin M, Shalapour S. Angiotensin II receptor inhibition ameliorates liver fibrosis and enhances hepatocellular carcinoma infiltration by effector T cells. Proc Natl Acad Sci U S A. 2023 May 9;120(19):e2300706120. doi: 10.1073/pnas.2300706120. Epub 2023 May 1.
• Background Junaid A, Rosenberg ME, Hostetter TH. Interaction of angiotensin II and TGF-beta 1 in the rat remnant kidney. J Am Soc Nephrol. 1997 Nov;8(11):1732-8. doi: 10.1681/ASN.V8111732.
• Background Dobaczewski M, Chen W, Frangogiannis NG. Transforming growth factor (TGF)-beta signaling in cardiac remodeling. J Mol Cell Cardiol. 2011 Oct;51(4):600-6. doi: 10.1016/j.yjmcc.2010.10.033. Epub 2010 Nov 6.
• Background Chen X, Lu H, Rateri DL, Cassis LA, Daugherty A. Conundrum of angiotensin II and TGF-beta interactions in aortic aneurysms. Curr Opin Pharmacol. 2013 Apr;13(2):180-5. doi: 10.1016/j.coph.2013.01.002. Epub 2013 Mar 12.
• Background Murphy AM, Wong AL, Bezuhly M. Modulation of angiotensin II signaling in the prevention of fibrosis. Fibrogenesis Tissue Repair. 2015 Apr 23;8:7. doi: 10.1186/s13069-015-0023-z. eCollection 2015.
• Background Wilson SE. Topical Losartan: Practical Guidance for Clinical Trials in the Prevention and Treatment of Corneal Scarring Fibrosis and Other Eye Diseases and Disorders. J Ocul Pharmacol Ther. 2023 Apr;39(3):191-206. doi: 10.1089/jop.2022.0174. Epub 2023 Mar 6.
• Background Pereira-Souza AL, Ambrosio R Jr, Bandeira F, Salomao MQ, Souza Lima A, Wilson SE. Topical Losartan for Treating Corneal Fibrosis (Haze): First Clinical Experience. J Refract Surg. 2022 Nov;38(11):741-746. doi: 10.3928/1081597X-20221018-02. Epub 2022 Nov 1.
• Background Chung JH, Kang YG, Kim HJ. Effect of 0.1% dexamethasone on epithelial healing in experimental corneal alkali wounds: morphological changes during the repair process. Graefes Arch Clin Exp Ophthalmol. 1998 Jul;236(7):537-45. doi: 10.1007/s004170050118.
• Background Mifflin MD, Betts BS, Frederick PA, Feuerman JM, Fenzl CR, Moshirfar M, Zaugg B. Efficacy and safety of a 3-month loteprednol etabonate 0.5% gel taper for routine prophylaxis after photorefractive keratectomy compared to a 3-month prednisolone acetate 1% and fluorometholone 0.1% taper. Clin Ophthalmol. 2017 Jun 12;11:1113-1118. doi: 10.2147/OPTH.S138272. eCollection 2017.
• Background Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, O'Brien KS, Glidden DV, Ray KJ, Oldenburg CE, Zegans ME, Whitcher JP, McLeod SD, Porco TC, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial. Am J Ophthalmol. 2014 Feb;157(2):327-333.e3. doi: 10.1016/j.ajo.2013.09.025. Epub 2013 Oct 1.
• Background Fung AT, Tran T, Lim LL, Samarawickrama C, Arnold J, Gillies M, Catt C, Mitchell L, Symons A, Buttery R, Cottee L, Tumuluri K, Beaumont P. Local delivery of corticosteroids in clinical ophthalmology: A review. Clin Exp Ophthalmol. 2020 Apr;48(3):366-401. doi: 10.1111/ceo.13702. Epub 2020 Jan 22.
• Background Mishima H, Nishida T, Otori T. Dexamethasone inhibition of phagocytosis by corneal keratocytes in culture. Arch Ophthalmol. 1988 Jul;106(7):978-80. doi: 10.1001/archopht.1988.01060140124038.
• Background Zhang T, Wang XF, Wang ZC, Lou D, Fang QQ, Hu YY, Zhao WY, Zhang LY, Wu LH, Tan WQ. Current potential therapeutic strategies targeting the TGF-beta/Smad signaling pathway to attenuate keloid and hypertrophic scar formation. Biomed Pharmacother. 2020 Sep;129:110287. doi: 10.1016/j.biopha.2020.110287. Epub 2020 Jun 12.
• Background Liu W, Wang DR, Cao YL. TGF-beta: a fibrotic factor in wound scarring and a potential target for anti-scarring gene therapy. Curr Gene Ther. 2004 Mar;4(1):123-36. doi: 10.2174/1566523044578004.
• Background Liu Y, Li Y, Li N, Teng W, Wang M, Zhang Y, Xiao Z. TGF-beta1 promotes scar fibroblasts proliferation and transdifferentiation via up-regulating MicroRNA-21. Sci Rep. 2016 Aug 24;6:32231. doi: 10.1038/srep32231.
• Background Sampaio LP, Martinez VV, Shiju TM, Hilgert GSL, Santhiago MR, Wilson SE. Cell Biology of Spontaneous Persistent Epithelial Defects After Photorefractive Keratectomy in Rabbits. Transl Vis Sci Technol. 2023 May 1;12(5):15. doi: 10.1167/tvst.12.5.15.
• Background Jester JV, Ho-Chang J. Modulation of cultured corneal keratocyte phenotype by growth factors/cytokines control in vitro contractility and extracellular matrix contraction. Exp Eye Res. 2003 Nov;77(5):581-92. doi: 10.1016/s0014-4835(03)00188-x.
• Background de Oliveira RC, Wilson SE. Fibrocytes, Wound Healing, and Corneal Fibrosis. Invest Ophthalmol Vis Sci. 2020 Feb 7;61(2):28. doi: 10.1167/iovs.61.2.28.
• Background Wilson SE. TGF beta -1, -2 and -3 in the modulation of fibrosis in the cornea and other organs. Exp Eye Res. 2021 Jun;207:108594. doi: 10.1016/j.exer.2021.108594. Epub 2021 Apr 22.
• Background Hong JW, Liu JJ, Lee JS, Mohan RR, Mohan RR, Woods DJ, He YG, Wilson SE. Proinflammatory chemokine induction in keratocytes and inflammatory cell infiltration into the cornea. Invest Ophthalmol Vis Sci. 2001 Nov;42(12):2795-803.
• Background Kwok SS, Shih KC, Bu Y, Lo AC, Chan TC, Lai JS, Jhanji V, Tong L. Systematic Review on Therapeutic Strategies to Minimize Corneal Stromal Scarring After Injury. Eye Contact Lens. 2019 Nov;45(6):347-355. doi: 10.1097/ICL.0000000000000584.
• Background Wilson SE. The corneal fibroblast: The Dr. Jekyll underappreciated overseer of the responses to stromal injury. Ocul Surf. 2023 Jul;29:53-62. doi: 10.1016/j.jtos.2023.04.012. Epub 2023 Apr 18.
• Background de Oliveira RC, Tye G, Sampaio LP, Shiju TM, DeDreu J, Menko AS, Santhiago MR, Wilson SE. TGFbeta1 and TGFbeta2 proteins in corneas with and without stromal fibrosis: Delayed regeneration of apical epithelial growth factor barrier and the epithelial basement membrane in corneas with stromal fibrosis. Exp Eye Res. 2021 Jan;202:108325. doi: 10.1016/j.exer.2020.108325. Epub 2020 Oct 22.
• Background Wilson SE, Sampaio LP, Shiju TM, Hilgert GSL, de Oliveira RC. Corneal Opacity: Cell Biological Determinants of the Transition From Transparency to Transient Haze to Scarring Fibrosis, and Resolution, After Injury. Invest Ophthalmol Vis Sci. 2022 Jan 3;63(1):22. doi: 10.1167/iovs.63.1.22.
• Background Flaxman SR, Bourne RRA, Resnikoff S, Ackland P, Braithwaite T, Cicinelli MV, Das A, Jonas JB, Keeffe J, Kempen JH, Leasher J, Limburg H, Naidoo K, Pesudovs K, Silvester A, Stevens GA, Tahhan N, Wong TY, Taylor HR; Vision Loss Expert Group of the Global Burden of Disease Study. Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis. Lancet Glob Health. 2017 Dec;5(12):e1221-e1234. doi: 10.1016/S2214-109X(17)30393-5. Epub 2017 Oct 11.
• Background Wang EY, Kong X, Wolle M, Gasquet N, Ssekasanvu J, Mariotti SP, Bourne R, Taylor H, Resnikoff S, West S. Global Trends in Blindness and Vision Impairment Resulting from Corneal Opacity 1984-2020: A Meta-analysis. Ophthalmology. 2023 Aug;130(8):863-871. doi: 10.1016/j.ophtha.2023.03.012. Epub 2023 Mar 22.
• Background Wilson SE. The Cornea: No Difference in the Wound Healing Response to Injury Related to Whether, or Not, There's a Bowman's Layer. Biomolecules. 2023 Apr 29;13(5):771. doi: 10.3390/biom13050771.
• Background Yam GHF, Riau AK, Funderburgh ML, Mehta JS, Jhanji V. Keratocyte biology. Exp Eye Res. 2020 Jul;196:108062. doi: 10.1016/j.exer.2020.108062. Epub 2020 May 19.
• Background 4. Oyster, C. W. (2006). The human eye: Structure and function (2006a ed.). Oxford University Press.
• Background Sridhar MS. Anatomy of cornea and ocular surface. Indian J Ophthalmol. 2018 Feb;66(2):190-194. doi: 10.4103/ijo.IJO_646_17.
• Background 2. Weisenthal, R. W. (2023b). 2023-2024 basic and clinical science courseTM, section 8: External disease and cornea. American Academy of Ophthalmology.
• Background Meek KM, Knupp C, Lewis PN, Morgan SR, Hayes S. Structural control of corneal transparency, refractive power and dynamics. Eye (Lond). 2025 Mar;39(4):644-650. doi: 10.1038/s41433-024-02969-7. Epub 2024 Feb 23.

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Indications