Safety and efficacy of topically applied 0.5% and 1% pirfenidone in a canine model of subconjunctival fibrosis

Abstract

Objective To evaluate tissue levels, safety, and efficacy of topical ophthalmic 0.5% and 1% pirfenidone in decreasing subconjunctival fibrosis. Animal studied Twelve normal beagle dogs Procedures A 5 × 1 mm diameter silicone disk was implanted subconjunctivally in one eye, and then dogs were treated with topical 0.5% pirfenidone (n = 9) in artificial tears or artificial tears alone (n = 3) for 28 days. To evaluate tissue drug levels, a single sample of tears, conjunctiva, and aqueous humor was collected 30 (n = 3), 90 (n = 3), and 180 min (n = 3) following administration of the last drop of pirfenidone, respectively. Fibrous capsule thickness and staining for Ki67 and fibroblast activation protein alpha (FAPα) were evaluated histologically. After a 2‐week washout, the experiment was repeated in the opposite eye and using 1% pirfenidone. Results Treatment with pirfenidone resulted in thinner fibrous capsules and decreased staining for FAPα with no adverse effects. The implant in one dog treated with pirfenidone extruded. There was no difference in tissue levels, capsular thickness, or staining for Ki67 or FAPα between dogs treated with 0.5% or 1% pirfenidone. Conclusions Pirfenidone may decrease fibrosis following glaucoma shunt surgery and can potentially be used indefinitely due to minimal side effects.

Topical Pirfenidone-Loaded Liposomes Ophthalmic Formulation Reduces Haze Development after Corneal Alkali Burn in Mice

“…PFD has shown anti-fibrotic effects reducing TGF-β1 expression and ECM deposit in different organs [17]. Different preclinical studies have exhibited PFD therapeutic potential in the treatment of fibrotic and proliferative eye disorders including corneal chemical burns [13], conjunctival scarring [37][38][39], and choroidal neovascularization (CNV) [40]. It has been documented that PFD reduces αSMA expression, promotes epithelial restoration and suppresses infiltration by inflammatory cells in rat corneas [13].…”

Pirfenidone: A Promising Drug in Ocular Therapeutics

“…Pirfenidone's ability to counteract fibrosis was demonstrated in a live animal study conducted by Westermeyer and colleagues using a subconjunctival fibrosis model in beagle dogs and evaluated tissue pharmacokinetics, long term safety and efficacy [59] . Collectively, the findings indicate that pirfenidone has the potential to be efficacious in reducing the formation of fibrous tissue after the insertion of glaucoma shunts in canines.…”

“…The absence of negative consequences observed in relation to the topical administration suggests that pirfenidone may be utilized continuously for the management of fibrosis, without encountering the typical adverse effects associated with commonly prescribed medications like mitomycin-C (MMC) and 5-fluorouracil (5-FU). [59] Likewise, an experimental model was created to assess the effectiveness of pirfenidone in treating equine corneal fibrosis in a laboratory setting. These investigations were performed on cultured healthy primary equine corneal myofibroblast cells (ECMs).…”

A review of glaucoma surgical therapy

“…Revision of the “bleb” and removal of fibrosis with repeated use of antifibrotic agents is often performed weeks to months after the initial surgery. A recent study shows promise for pirfenidone and its efficacy in decreasing fibrosis following shunt surgery with minimal side effects 50 …”