PURPOSE: To compare the ocular hypotensive efficacy and safety of a fixed-dose combination (FDC) of the Rho kinase inhibitor netarsudil and latanoprost vs monotherapy with netarsudil or latanoprost. DESIGN: Three-month primary endpoint analysis of a randomized, double-masked, phase 3 clinical trial. METHODS: Adults with open-angle glaucoma or ocular hypertension (unmedicated intraocular pressure [IOP] >20 and <36 mm Hg at 8:00 AM) were randomized to receive once-daily netarsudil/latanoprost FDC, netarsudil 0.02%, or latanoprost 0.005% for up to 12 months. The primary efficacy endpoint was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3. RESULTS: Mean treated IOP ranged from 14.8-16.2 mm Hg for netarsudil/latanoprost FDC, 17.2-19.0 mm Hg for netarsudil, and 16.7-17.8 mm Hg for latanoprost. Netarsudil/latanoprost FDC met the criteria for superiority to each active component at all 9 time points (all P < .0001), lowering IOP by an additional 1.8-3.0 mm Hg vs netarsudil and an additional 1.3-2.5 mm Hg vs latanoprost. At month 3, the proportion of patients achieving mean diurnal IOP £15 mm Hg was 43.5% for netarsudil/ latanoprost FDC, 22.7% for netarsudil, and 24.7% for latanoprost. No treatment-related serious adverse events were reported; treatment-related systemic adverse events were minimal. The most frequent ocular adverse event was conjunctival hyperemia (netarsudil/latanoprost FDC, 53.4%; netarsudil, 41.0%; latanoprost, 14.0%), which led to treatment discontinuation in 7.1% (netarsudil/lata-noprost FDC), 4.9% (netarsudil), and 0% (latanoprost) of patients. CONCLUSIONS: Once-daily netarsudil/latanoprost FDC demonstrated IOP reductions that were statistically and clinically superior to netarsudil and latanoprost across all 9 time points through month 3, with acceptable ocular safety.
Glaucoma implants are designed to increase fluid outflow from the eye in order to decrease intraocular pressure and prevent damage to the optic nerve. The implant consists of a silicone tube that is inserted into the anterior chamber at one end and is attached at the other end to a silicone plate that is sutured to the outside of the globe beneath the conjunctiva. The glaucoma "implant" becomes a "drain" over the first 3 to 6 postoperative weeks as the silicone plate is enclosed by a fibrous capsule that allows a space to form into which fluid can drain and from which fluid can be absorbed by the surrounding tissues. Ideally, the size and thickness of the capsule (the filtering bleb) that surrounds the plate is such that the amount of fluid that passes through the capsule is identical to the amount of fluid produced by the eye at an intraocular pressure of 8 to 14 mmHg. The most common long-term complication of these implants is failure of the filtering bleb 2 to 4 years after surgery due to the formation of a thick fibrous capsule around the device. Micromovement of the smooth drainage plate against the scleral surface may be integral to the mechanism of glaucoma implant failure by stimulating low-level activation of the wound healing response, increased collagen scar formation, and increased fibrous capsule thickness. To test this hypothesis, we modified seven Baerveldt implants by adding porous cellular ingrowth material to the posterior surface of the drainage plate. Seven modified and five unmodified implants were placed in adult rabbit eyes. After 6 months, we found that the fibrous capsule around the modified implants was significantly thinner than the capsule surrounding the unmodified implants (p < 0.05), particularly on the surface between the porous ingrowth material and the sclera (p < 0.05). Although type I collagen predominated in the fibrous capsules around both types of implants, the amount of type III collagen in the capsules around the modified implants was significantly less than the amount around the unmodified implants (p < 0.05). We believe that these data suggest a reduction in the wound healing response to the modified implants, with greater stability of capsule thickness. Long-term studies are needed to verify that the stability of the capsules around the modified implants persists over a period of years, in which case this type of modification may prove useful in prolonging the functional life of these devices in the surgical treatment of glaucoma.
Thin (0.25 mm) E-PTFE patches were well tolerated in all rabbit eyes tested. Thin E-PTFE should be investigated further as a functional alternative to donor sclera for reinforcement in glaucoma drain surgery.
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