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Safety and efficacy of topically applied 0.5% and 1% pirfenidone in a canine model of subconjunctival fibrosis
Author(s) -
Westermeyer Hans D.,
Salmon Beth,
Baynes Ronald,
Yeatts James,
Khattab Ahlam,
Oh Annie,
Mowat Freya
Publication year - 2019
Publication title -
veterinary ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.594
H-Index - 50
eISSN - 1463-5224
pISSN - 1463-5216
DOI - 10.1111/vop.12619
Subject(s) - pirfenidone , medicine , beagle , artificial tears , fibrosis , tears , conjunctiva , capsule , staining , surgery , ophthalmology , pathology , idiopathic pulmonary fibrosis , lung , botany , biology
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 ( FAP α) 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 FAP α 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 FAP α 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.