Evaluation of valproic acid for bleb maintenance following experimental MicroShunt surgery

Abstract

Purpose : Bleb forming surgeries are effective ways to lower IOP in glaucoma. Subconjunctival collagen I deposition can lead to premature surgical failure. The use of adjunctive Mitomycin C can lead unhealthy avascular blebs with blinding complications. Valproic acid (VPA) has been shown to have anti-fibrotic properties and favourable post translational collagen I modification that could favour prolonged bleb function and survival in the presence of a glaucoma surgical device. The aim of the study is to evaluate the effect of VPA in maintaining bleb function after MicroShunt implantation.

Methods : Thirty New Zealand white rabbits underwent surgical implantation of the PRESERFLO MicroShunt (Santen). The animals were divided into 6 treatment groups: MMC 0.4mg/ml, MMC 0.1mg/ml (low dose), VPA 1mg/ml, MMC (0.1mg/ml) with VPA (1mg/ml). Comparison of administration of VPA by topical and subconjunctival injection route was also investigated in the combination treatment with low dose MMC (0.1mg/ml). Slit lamp photography of the blebs were taken weekly. Fibrotic gene and protein expression was analyzed in the harvested conjunctival blebs by qPCR and western blot respectively, and histology was performed on the eyes following sacrifice on D28.

Results : Combination of low dose MMC with VPA was associated with diffuse healthy blebs and prolonged bleb survival to D28. Reduced collagen 1 and fibronectin gene and protein expression (P<0.05) was observed. Extracellular matrix organisation within the bleb revealed fine immature collagen fibrils surrounding the MicroShunt shunt opening. Combination of low dose MMC with VPA treatment by either weekly subconjunctival injection or daily eyedrop was similarly effective in bleb maintenance to D28.

Conclusions : VPA is an effective adjunctive agent that can be used in combination of low dose MMC for maintaining favourable bleb morphology and function following MicroShunt implantation.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.