Topical Losartan: Practical Guidance for Clinical Trials in the Prevention and Treatment of Corneal Scarring Fibrosis and Other Eye Diseases and Disorders.

Abstract

Losartan is an angiotensin II receptor blocker (ARB) that impedes transforming growth factor (TGF) beta signaling by inhibiting activation of signal transduction molecule extracellular signal-regulated kinase (ERK). Studies supported the efficacy of topical losartan in decreasing scarring fibrosis after rabbit Descemetorhexis, alkali burn, and photorefractive keratectomy injuries, and in case reports of humans with scarring fibrosis after surgical complications. Clinical studies are needed to explore the efficacy and safety of topical losartan in the prevention and treatment of corneal scarring fibrosis, and other eye diseases and disorders where TGF beta has a role in pathophysiology. These include scarring fibrosis associated with corneal trauma, chemical burns, infections, surgical complications, and persistent epithelial defects, as well as conjunctival fibrotic diseases, such as ocular cicatricial pemphigoid and Stevens-Johnson syndrome. Research is also needed to explore the efficacy and safety of topical losartan for hypothesized treatment of transforming growth factor beta-induced (TGFBI)-related corneal dystrophies (Reis-Bu¨cklers corneal dystrophy, lattice corneal dystrophy type 1, and granular corneal dystrophies type 1 and type 2) where deposited mutant protein expression is modulated by TGF beta. Investigations could also explore the efficacy and safety of topical losartan treatments to reduce conjunctival bleb scarring and shunt encapsulation following glaucoma surgical procedures. Losartan and sustained release drug delivery devices could be efficacious in treating intraocular fibrotic diseases. Dosing suggestions and precautions that should be considered in trials of losartan are detailed. Losartan, as an adjuvant to current treatments, has the potential to augment pharmacological therapeutics for many ocular diseases and disorders where TGF beta plays a central role in pathophysiology.