Using a Novel, Subconjunctival, Sustained-Release Mitomycin C Formulation in a Rabbit Model of Filtration Surgery with Gel Stent Implantation.

Purpose: To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Methods: Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. Results: Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. Conclusions: Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma.

Intraocular Pressure-Lowering Efficacy of a Sustained-Release Bimatoprost Implant in Dog Eyes Pretreated with Selective Laser Trabeculoplasty.

Purpose: To assess the intraocular pressure (IOP)-lowering effect of a biodegradable bimatoprost implant following selective laser trabeculoplasty (SLT) in a canine model. Methods: Unilateral SLT was performed in 11 normotensive, treatment-naive beagle dogs. IOP was measured at baseline (pre-SLT) and weekly post-SLT (≤10 weeks). After IOP returned to baseline or at 10 weeks (whichever occurred first), a sustained-release bimatoprost implant was administered bilaterally in the anterior chamber of each animal. IOP was measured weekly for 4 weeks and then every 2 weeks up to week 42. Results: The main outcomes included the IOP change (%) from baseline, calculated in both eyes in the overall population, SLT responder subgroup (defined by peak IOP reduction from baseline ≥3 mmHg or ≥15% for >1 week post-SLT), and SLT nonresponder subgroup (defined by peak IOP reduction from baseline <3 mmHg or <15%). The bimatoprost implant lowered IOP similarly in both the SLT-treated and fellow SLT-naive eyes. Following bimatoprost implant administration, the mean (standard deviation [SD]) peak IOP reduction from baseline was 34.4% (8.5%) in SLT-treated eyes and 35.7% (5.9%) in fellow SLT-naive eyes. The bimatoprost implant lowered IOP comparably (P > 0.17) in eyes that responded to SLT (mean [SD] peak IOP reduction, 34.6% [10.7%]; n = 6) and those that did not (mean [SD] peak IOP reduction, 34.1% [6.1%]; n = 5). Conclusion: The bimatoprost implant effectively lowered IOP in eyes pretreated with SLT, regardless of response to SLT. The current data suggest that eyes previously treated with SLT can still benefit from the intracameral bimatoprost implant.

Assessment of the differences in pharmacokinetics and pharmacodynamics between four distinct formulations of triamcinolone acetonide.

PURPOSE: To compare the durability of Kenalog, Trivaris, Triesence, and compounding pharmacy preservative-free triamcinolone acetonide in pigmented rabbits with syneretic vitreous using direct visualization, pharmacodynamics, and pharmacokinetics. METHODS: Twenty-five Dutch-belted rabbits were used. Pharmacokinetic experiment: Rabbits were intravitreally injected with one of four 4-mg triamcinolone acetonide formulations. Wide-field imaging was serially performed to document residual drug mass. Pharmacodynamics experiment: Four triamcinolone acetonide groups and one control group received intravitreal recombinant human vascular endothelial growth factor 165 every 2 weeks and were followed with fluorescein angiography to assess vascular endothelial growth factor retinal vasculopathy as a measure of residual steroid effect. Particle size of the formulations was measured with Mastersizer 2000. RESULTS: Remaining triamcinolone acetonide mass after 19 weeks: 12,091 ± 2,512 pixels for the Kenalog group, 1,307.36 ± 695.57 for Trivaris, 5577 ± 1477 for Triesence, and 1,535 ± 329 for compounded preservative-free triamcinolone acetonide. Kenalog suppressed recombinant human vascular endothelial growth factor-induced retinopathy more effectively than the other triamcinolone acetonide groups at Week 39, the final time point assessed. Particle size (90th percentile) was 47 µm for Kenalog, 26 µm for Triesence, and 22 µm for both compounded preservative-free triamcinolone acetonide and Trivaris. CONCLUSION: Triamcinolone acetonide formulations do not have the same pharmacokinetics/pharmacodynamics. Kenalog has the longest vitreous visibility and durability. Particle size appears to correlate with efficacy and durability.

Ocular changes after photodynamic therapy.

PURPOSE: The aim of this study was to identify the changes in the primate visual system after a single session of photodynamic therapy (PDT) in an intact nonhuman primate retina. METHODS: As part of a larger study, PDT (wavelength 689 nm, 50 J/cm2, 600 mW/cm2, 83 seconds, 4-mm spot size) with verteporfin (6 mg/m2 intravenous infusion) was performed in one eye each of two cynomolgus monkeys. Fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICG), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) were performed at baseline and 12 time points (1-283 days) after PDT. In addition, retinal histopathologic findings were evaluated at 9 months. RESULTS: Various morphologic changes, including whitening of the treated area, RPE proliferation, closure of the choroidal vasculature, and subretinal edema (followed by foveolar thinning) were observed. Most of the changes persisted and were detectable in histopathologic evaluation at 9 months. Reductions of the mfERG amplitude, followed by varying degrees of recovery from the treated and the border regions, were observed. This was accompanied by progressive delay of P1 peak time up to 3 months after treatment, followed by complete recovery at 9 months. In addition, the nontreated area showed amplitude and timing mfERG deficits, which underwent gradual (but not complete) recovery. CONCLUSIONS: In a primate model, under standard clinical parameters, a single PDT treatment resulted in various dynamic morphologic and functional retinal changes detectable for up to 9 months after treatment. The significance of the observed changes and possible ways of pharmacologic interference with PDT adverse effects are discussed.