Eyecare providers face several challenges when it comes to treating corneal injury. Fortunately, new research initiatives have identified some of the many mechanisms at play when the cornea is injured, and exciting potential options to aid in wound healing are on the rise.

Losartan, a commonly used angiotensin II receptor blocker (ARB) for hypertension and heart failure, has been shown to aid in wound healing in animal models and may show promise in doing the same in humans for injuries and various diseases of the cornea.1-3 Topical losartan penetrates the intact corneal epithelium/epithelial basement membrane and full stroma to get to the endothelium, with little ocular surface toxicity noted in normal or fibrotic corneas.1,3 Losartan inhibits transforming growth factor (TGF)-stimulated stromal type IV collagen production and also inhibits myofibroblast development and fibrosis with four weeks of treatment.2,3 Since myofibroblast development is persistently dependent on ongoing TGF signaling, topical losartan should be effective for prophylaxis to prevent fibrosis and treatment when scarring fibrosis is already present.4

Corneal Management

Topical losartan has potential uses for any significant injury to the cornea by impeding TGF signaling.2 A list of potential uses includes thermal or chemical burns, microbial keratitis (bacterial, fungal, protozoan), herpetic keratitis, persistent epithelial defects (including neurotrophic keratitis) and other injuries such as lacerations or surgical complications of the cornea. Considering its mechanism of action, losartan may be suitable treatment for TGF ß-induced corneal dystrophies. Conjunctival fibrotic diseases such as ocular cicatricial pemphigoid and Stevens-Johnson syndrome are also part of a list of potential uses. 

Other uses may apply to glaucoma surgery (filtering and tube procedures) and even diabetic retinopathy or other fibrotic retinal diseases. Active infections will require concurrent antimicrobial therapies. Losartan could also help with existing scars and haze following late photorefractive keratectomy haze, breakthrough haze, as well as complicated LASIK, SMILE or corneal crosslinking haze.2,3 When there is significant inflammation, a topical steroid will enhance the process of healing.3

Depending on the corneal or conjunctival condition being treated, multi-drug therapy will undoubtedly be required when using losartan or another appropriate ARB agent. For example, a topical nerve growth factor can be used along with losartan for persistent epithelial defects. Topical netarsudil and losartan for deeper corneal injuries with endothelial cell damage (descemetorhexis, endotheliitis) have been shown to affect the healing response favorably.1,3 Also, losartan appears to have some efficacy in minimizing or improving corneal neovascularization.3 Topical sunitinib or axitinib, tyrosine kinase inhibitors, can be added to losartan if corneal neovascularization develops.4 As our retinal colleagues use them daily, these second-generation tyrosine kinase inhibitors work by blocking angiogenesis, tumor growth and metastases.

 Prior to any approved label indications for topical losartan in preventing and treating corneal scarring, large scale human trials are needed to provide reasonable assurance of safety and efficacy and to further evaluate recommendations for proper dosages and duration of treatment. Nevertheless, some providers are now ordering compounded losartan at a 0.8% concentration, which can be used six times a day for weeks to months, depending on the insult to the cornea without significant concerns for toxicity.3

To date, the results available from animal studies and limited human study appear to be exciting. Will losartan be the go-to topical agent for corneal haze, scarring or other ocular disease indications? We’ll see if this medication is picked up soon by a sponsor/manufacturer. Unfortunately, the cost to bring a product to market is overwhelmingly high, but I think we’ll see this topical option in the future. In the meantime, for those who like the research so far and are willing to use unapproved or off-label products, compounded losartan options are available. Personally, I’ll wait for additional studies beyond the rabbit. 

1. Sampaio LP, Villabona-Martinez V, Shiju TM, et al. Topical losartan decreases myofibroblast generation but not corneal opacity after surface blast-simulating irregular PTK in rabbits. Transl Vis Sci Technol. 2023;12(9):20.

2. 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; 39(3):191-206.

3. Wilson SE. Steven E. Wilson MD Cleveland Clinic, topical losartan treatment of corneal scarring and wound healing [Video]. YouTube. www.youtube.com/watch?v=XhhxG48CnBQ. October 24, 2022. Accessed April 17, 2024.

4. LP Sampaio, GS Hilgert, TM Shiju, et al. Topical losartan inhibits corneal scarring fibrosis and collagen type IV deposition after Descemet’s membrane-endothelial excision in rabbits. Exp Eye Res. 2022; 216(3):108940.