Abstract
ABSTRACTAimThe aim of this study is to assess the effectiveness of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDI) with a broad spectrum epigenetic activity, in improving filtration bleb survival as an adjunct therapy to glaucoma filtration surgery (GFS) in the rabbit model.Materials and methodsEighteen New Zealand White rabbits underwent GFS in the left eye and were randomized to receive either a subconjunctival (SC) injection of 0.1 mL SAHA (9.25 μg/mL) or balanced saline solution (BSS) at the end of surgery, or a 3-minute intraoperative topical application of 0.4 mg/mL mitomycin-C (MMC). Bleb survival and histology were compared.ResultsBlebs of rabbits receiving injections of SAHA survived an average (mean ± SD) of 23.2 ± 2.7 days. SAHA rabbits showed a nonsignificant improvement over rabbits that received an injection of BSS, which had a mean survival time of 19.7 ± 2.7 days (p = 0.38) according to a one-way analysis of variance (ANOVA). Eyes receiving intraoperative topical MMC survived an average of 32.5 ± 3.3 days, which is significantly longer than both the control group treated with BSS (p = 0.01) and the experimental group treated with the SAHA (p = 0.0495). SAHA was well tolerated and showed no significant avascularity, necrosis, or conjunctival thinning.ConclusionAlthough it was well tolerated, a single intraoperative injection of SAHA did not significantly prolong bleb survival in the rabbit model.Clinical significanceEpigenetic adjuncts hold promise for improving GFS outcome; however, future studies must continue to examine different administration protocols and dosages to substantiate their efficacy.How to cite this articleRodgers CD, Lukowski ZL, et al. Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid. J Curr Glaucoma Pract 2019;13(1):37–41.
Highlights
When medication and laser treatment fail to reduce intraocular pressure (IOP), glaucoma filtration surgery (GFS) is the gold standard surgical procedure for patients with glaucoma.[1,2]In GFS, aqueous humor is rerouted from the anterior chamber of the eye to the subconjunctival (SC) space, forming a filtration bleb
This study evaluates the effect of a single intraoperative SC injection of suberoylanilide hydroxamic acid (SAHA) on ocular scarring following GFS in the rabbit model
It is well known that fibrosis in a glaucoma bleb increases resistance to aqueous flow and contributes to the elevated IOP seen in patients with failing filtration blebs
Summary
When medication and laser treatment fail to reduce intraocular pressure (IOP), glaucoma filtration surgery (GFS) is the gold standard surgical procedure for patients with glaucoma.[1,2]In GFS, aqueous humor is rerouted from the anterior chamber of the eye to the subconjunctival (SC) space, forming a filtration bleb. Excessive fibroblast and collagen accumulation along with increased angiogenesis often lead to scarring and subsequent filtration bleb failure.[3–5]In humans, the antimetabolites mitomycin C (MMC) and 5-fluorouracil (5-FU) are used to help reduce the scarring and failure of glaucoma filtration blebs following GFS. These compounds lack specificity and can endanger the bleb’s long-term structural integrity, increasing the risk of complications such as bleb leakage, hypotony, blebitis, endophthalmitis, and vision loss.2,4,6–9 there is a strong interest in finding an alternative anti-scarring therapy with a lower risk of toxicity.
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