Eyeworld

SEPTEMBER 2023 | EYEWORLD | 51 C References 1. 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;39:191–206. 2. Sampaio LP, et al. Topical losartan inhibits corneal scarring fibrosis and collagen type IV deposition after Descem- et's membrane-endothelial excision in rabbits. Exp Eye Res. 2022;216:108940. 3. Sampaio LP, et al. Topical losartan and corticosteroid additively inhibit corneal stromal myofibroblast generation and scarring fibrosis after alkali burn injury. Transl Vis Sci Technol. 2022;11:9. 4. Pereira-Souza A, et al. Topical losartan for treating corneal fibrosis (haze): first clinical experience. J Refract Surg. 2022;38:741–746. drug that doesn't penetrate the epithelium and epithelial basement membrane is not going to be effective. "The study not only showed that lo- sartan was effective against corneal fibrosis but also that it could work in a cornea where the epithelium and epithelial basement membrane are intact." Dr. Wilson said there are dozens of compa- nies that have brainstormed ideas for drugs that will impact corneal fibrosis when given topically. Many have reached out for his opinion, and Dr. Wilson said the first question he asks is if it pen- etrates the epithelium and epithelial basement membrane. The answer is almost always no, but now it's been proven that losartan does. Dr. Wilson's work includes five studies in rabbits, three of which are published, one that is in review, and another that is being prepared for publication. One study was for descemetor- hexis, one was for alkali burns, 3 and a third was in PRK in rabbits. "One study simulated a blast injury to the cornea, and we used that with an irregular excimer laser ablation that simulates a very rough corneal surface, while the last study investigated the effect of losartan on incisions in rabbit corneas," he said. The Cleveland Clinic has submitted a patent covering losartan and all the other drugs in that group, Dr. Wilson said, adding that there are at least eight other angiotensin II receptor blockers. Losartan was the drug that was initially focused on because it has shown several advan- tages, with the first being that it's soluble in ba- sic buffers like balanced salt solution or normal saline. Most other drugs in that group are not soluble in aqueous solutions, so you'd have to use special vehicles. This adds more complexity for formulating it for patients. Losartan is also one of the most widely used oral drugs in the world, so the safety is assured, he said. It's now been used topically by hundreds of ophthalmologists throughout the world. Dr. Wilson has trained a number of Bra- zilian corneal and refractive surgeons and noted that the first in-human case report using losartan for a refractive surgery complication came from Renato Ambrosio Jr., MD, PhD, who contacted Dr. Wilson about one of his patients who he thought would benefit from this. 4 Since this first case, Dr. Wilson said he has heard from many other ophthalmologists with cases where they think losartan could be used. Dr. Wilson noted that a critical piece is that "you can't stop after 1 month of treatment and think that the patient failed." Some patients will start responding by 2 or 3 months. "In the vast majority, especially the more severe scarring fibrosis, it's going to take 4–6 months before you see that it's working," he said. He noted that patients may notice an improvement in vi- sion before physicians see it at the slit lamp. It's important to get a commitment from the patient to try this option for 6 months before giving up. Dr. Wilson noted that of the few patients who have been using it for almost a year, there have been no reports of toxicity. However, he cautioned that those interested in exploring this treatment option stick to the recommended and proven dosage of 0.8 mg/ mL. While many have asked if it would make sense to increase the dosage for the treatment to work faster, this could cause complications because you start interfering with normal functions that transforming growth factor beta controls in the cornea. "I encourage physicians not to use more than 0.8 mg/mL until animal studies show that higher concentrations are safe and effective. It's working so well now," he said. His research has shown that losartan is soluble up to more than 400 mg/mL in bal- anced salt solution, but when you get up to this amount, it becomes viscous like hyaluronic ac- id-containing solutions. "I don't want physicians applying that to corneas before higher doses have been tried in animals. My biggest concern is that people will start using higher concentra- tions with no data and end up with complica- tions that have not been reported with the 0.8 mg/mL dosage since transforming growth factor beta also regulates normal cellular functions in corneas," he said, emphasizing that he has yet to have any reports of complications in patients using it 6 times a day for months. continued on page 52

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