ABSTRACT
PURPOSE: This study compared the efficacy and safety of suberoylanilide hydroxamic acid (SAHA) and mitomycin C (MMC) up to 4 months in the prevention of corneal haze induced by photorefractive keratectomy (PRK) in rabbits in vivo. METHODS: Corneal haze in rabbits was produced with -9.00 diopter PRK. A single application of SAHA (25 µM) or MMC (0.02%) was applied topically immediately after PRK. Effects of the two drugs were analyzed by slit-lamp microscope, specular microscope, TUNEL assay, and immunofluorescence. RESULTS: Single topical adjunct use of SAHA (25 µM) or MMC (0.02%) after PRK attenuated more than 95% corneal haze and myofibroblast formation (P < .001). SAHA did not reduce keratocyte density, cause keratocyte apoptosis, or increase immune cell infiltration compared to MMC (P < .01 or .001). Furthermore, SAHA dosing did not compromise corneal endothelial phenotype, density, or function in rabbit eyes, whereas MMC application did (P < .01 or .001). CONCLUSIONS: SAHA and MMC significantly decreased corneal haze after PRK in rabbits in vivo. SAHA exhibited significantly reduced short- and long-term damage to the corneal endothelium compared to MMC in rabbits. SAHA is an effective and potentially safer alternative to MMC for the prevention of corneal haze after PRK. Clinical trials are warranted. [J Refract Surg. 2017;33(12):834-839.].
Subject(s)
Alkylating Agents/therapeutic use , Corneal Opacity/prevention & control , Disease Models, Animal , Histone Deacetylase Inhibitors/therapeutic use , Hydroxamic Acids/therapeutic use , Mitomycin/therapeutic use , Photorefractive Keratectomy/adverse effects , Alkylating Agents/adverse effects , Animals , Apoptosis , Cornea/surgery , Corneal Opacity/etiology , Fluorescent Antibody Technique, Indirect , Histone Deacetylase Inhibitors/adverse effects , Hydroxamic Acids/adverse effects , In Situ Nick-End Labeling , Mitomycin/adverse effects , Rabbits , Slit Lamp , Treatment Outcome , VorinostatABSTRACT
PURPOSE: This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFß1) -induced corneal fibrosis in vitro. METHODS: Corneal haze in rabbits was produced with -9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFß1. Vorinostat (25 µm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 µm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 hours for in vitro studies. Slit-lamp microscopy, TUNEL assay, and trypan blue were used to determined vorinostat toxicity, whereas real-time polymerase chain reaction, immunocytochemistry, and immunoblotting were used to measure its efficacy. RESULTS: Single 5-minute vorinostat (25 µm) topical application on the cornea following PRK significantly reduced corneal haze (P<.008) and fibrotic marker proteins (α-smooth muscle actin and f-actin; P<.001) without showing redness, swelling, or inflammation in rabbit eyes in vivo screened 4 weeks after PRK. Vorinostat reduced TGFß1-induced fibrosis in human and rabbit corneas in vitro in a dose-dependent manner without altering cellular viability, phenotype, or proliferation. CONCLUSIONS: Vorinostat is non-cytotoxic and safe for the eye and has potential to prevent laser-induced corneal haze in patients undergoing PRK for high myopia.
