Long-term intraocular Pressure (IOP) control by means of a novel biodegradable intracameral (IC) latanoprost free acid (LFA) implant

Abstract

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 6-months. The purpose of this study was to evaluate long-term implant efficacy in dogs with primary open-angle glaucoma.

Methods : LFA implants (220 ng/d) were administered IC via 27G cannula in 10 glaucomatous male and female dogs (ages: 2.8 +/- 1.1 yrs) with IOPs of 24.3 +/- 3.6 SEM mmHg. These implants had 3 different chemistries (PA5004: n=5 eyes; PA5108: n=5; PA5024: n=4) a common diameter of 0.2 mm and maximum segment lengths of 7mm. The implants were evaluated for duration of efficacy and biodegradation. The dogs were followed by routine ophthalmic examination. The primary efficacy outcome measures were diurnal IOP (Icare® TONOVET) and pupil diameter. Xalatan® (0.005% latanoprost) drops (n=4) administered topically q24h and IC blank implants (n=4) served as positive and negative controls for 24 wks, respectively. Treatment effects were compared between groups and to baseline by Student’s t-test.

Results : All 3 LFA-implants lowered IOP comparable to Xalatan®; however, the implants reduced the diurnal IOP fluctuations. Degree of pupil constriction closely mirrored the IOP responses. For PA5024, IOPs were significantly lower than baseline at the primary time-points of 4 (11.7 +/- 2.9 SEM mmHg, p=0.003), 8 (12.3 +/- 1.7 SEM mmHg, p=0.003), 16 (13.9 +/- 1.8 SEM mmHg, p=0.007) and 24 wks (16.0 +/- 3.0 SEM mmHg, p=0.088), and IOP drop (≥30%) continued for 34 wks. With PA5004 and PA5108 this IOP-lowering effect lasted for 10 and 19 wks, respectively. Gonioscopy confirmed gradual implant biodegradation (PA5004: 10 wks; PA5108: 23 wks) coinciding with loss of therapeutic effect. Blank implants had no therapeutic effect. All implants were well tolerated with no clinical signs of intraocular inflammatory response.

Conclusions : Continuous IC LFA release is an effective and safe means for long-term, stable IOP control. The treatment period can be tailored by varying the implant chemistries. The accelerated biodegradation once drug release has subsided represents an ideal implant characteristic.

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