Eyeworld

52 | EYEWORLD | SEPTEMBER 2023 C ORNEA Contact Wilson: WILSONS4@ccf.org Relevant disclosures Wilson: Dr. Wilson and the Cleveland Clinic have submitted a patent on the use of topical losartan and other angiotensin II receptor blockers to prevent and treat corneal scarring fibrosis. Dr. Wilson pointed out that animal studies that have been done have so far have been pro- phylactic. But the human studies are in patients who already have the fibrosis and start treat- ment. This proves that the treatment could work either way. "It works prophylactically because transforming growth factor beta is required for the precursor cells to develop into myofibro- blasts," he said. "Or it works if the fibrosis is already there because the myofibroblasts that maintain the fibrosis are still dependent on an ongoing adequate supply of transforming growth factor beta signaling. If you cut that off with losartan, you'll cause those cells to under- go apoptosis, and when that happens, normal keratocytes and corneal fibroblasts can repop- ulate that area of the cornea and restore the normal transparent arrangement of the stromal tissue." This will require further research, as Dr. Wilson noted that patients who have been treated so far only had scarring for no more than a year or two. "The question is if it would still work on someone who had a terrible herpes simplex infection 10 years ago and has a scarred cornea," he said. Dr. Wilson said the use of losartan could have applications beyond the cornea as well, which makes it an exciting option to keep study- ing. He noted research being done by Victor Perez, MD, looking at losartan applications on different conjunctival fibrotic diseases, such as Stevens-Johnson syndrome, graft versus host disease, and bullous pemphigoid. None of these have very effective treatment, Dr. Wilson said, and the end pathology is transforming growth factor beta-mediated fibrosis of the conjunctiva. It may also be useful in glaucoma because one of the primary problems glaucoma surgeons face when patients need to have a conjunctival filtering bleb is that those procedures can fail by fibrosis caused by myofibroblasts. When using tubes, those can fail by myofibroblasts causing encapsulation of the tube. Losartan could pene- trate the conjunctiva and be effective for those, he said. He noted that it could be worth studying this as an option for proliferative vitreoreti- nopathy, which can occur in patients who have retinal detachments or diabetes, because that involves myofibroblast-driven fibrosis affecting the retina and vitreous. Extended delivery de- vices could potentially be studied as an option for giving losartan in these cases. Further research is needed on the appli- cations that Dr. Wilson is studying, as well as applications in other areas of ophthalmology. Instead of focusing on individual groups, Dr. Wilson wanted to encourage trials to ensure there is data to support the use and proper dos- age. "We need the trials, but there are patients out there right now who can benefit from this treatment, and there are no reported complica- tions," he said. When Dr. Wilson ends his lectures now- adays, he likes to reference his quest for the last 30 years to find a "magic bullet" to treat corneal fibrosis. "It was in my medicine cabinet all along," he said, noting that he's been on losartan for hypertension for around 20 years. He said it's interesting that this drug that is so widely used for other things can be repurposed as such an incredible option for the cornea. continued from page 51 "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." —Steven E. Wilson, MD

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