Safety of a novel biodegradable intracameral (IC) latanoprost free acid (LFA) implant for long-term intraocular pressure (IOP) control

Abstract

Purpose : Purpose: Continuous long-term IC drug release represents a promising solution to prevent accelerated progression of glaucomatous optic neuropathy due to low compliance rates for self-administration of IOP-lowering eye drops. PolyActiva cross-linked hydrogel glaucoma implants release LFA continuously for up to 34 wks. By varying the polymer chemistry, we have shown effective and selective control of IOP for 10, 20 or 34 wks in dogs with primary open-angle glaucoma by changing the period of implant biodegradation. The purpose of this study was to evaluate safety of the implants in these dogs.

Methods : Methods: LFA-releasing implants (220 ng/d) were administered IC via 27G cannula in 10 glaucomatous male and female dogs (ages: 2.8 +/- 1.1 yrs). The implants used 3 different biodegradation chemistries (PA5004: n=5 eyes; PA5108: n=5; PA5024: n=4) to set the implant treatment period. The implants had a common 0.2mm diameter and maximum segment lengths of 7mm. Safety was evaluated regularly by ophthalmic examination, pachymetry, visual acuity (obstacle course), and optical coherence tomography (OCT, Spectralis®, Heidelberg Engineering). Electroretinograms were recorded at the end of the study. Xalatan® (0.005% latanoprost) drops (n=4) administered topically q24h and IC blank implants (n=4) served as positive and negative controls, respectively.

Results : Results: Implants resided in the inferior iridocorneal angle with no evidence of migration. They were well tolerated with no clinical symptoms of intraocular inflammation. Moderate to mild conjunctival hyperemia was observed in a few dogs with LFA implants and Xalatan® drops. Central corneal thickness remained unchanged over the course of the study (PA5004: 602 ± 21 SEM µm baseline, 607 ± 16 SEM µm 24 wks; PA5108: 639 ± 9 SEM µm baseline, 648 ± 23 SEM µm 24 wks; PA5024: 613 ± 27 SEM µm baseline, 617 ± 18 SEM µm 24 wks). In 2 eyes, with longer implants, the implants were found to move and rub the corneal endothelium and induced focal corneal edema. Retinal thickness and optic nerve head measurements, electroretinograms, and visual performance did not reveal any treatment-related adverse effects.

Conclusions : Conclusions: Continuous IC LFA release via PolyActiva implants is a safe tool for long-term IOP control. The mechanical adverse effect on the cornea can be prevented by shortening the implants.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.