Vascular Endothelial Growth Factor Antagonists: Promising Players in the Treatment of Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (nAMD) treatment has been revolutionized by the introduction of vascular endothelial growth factor antagonists (anti-VEGF), but the need for frequent intravitreal injections poses a heavy burden to patients and physicians. Evolving anti-VEGF therapies include longer duration agents, approaches that target multiple pathways, topical anti-VEGF agents, sustained-release, and genetic therapies. Abicipar pegol, a designed ankyrin repeat protein (DARPin), demonstrated the ability to maintain stable visual acuity with 12-week dosing, but was not approved by the FDA due to higher than usual rates of intraocular inflammation. Conbercept, a recombinant anti-VEGF fusion protein, has been approved in China, and is in Phase 3 trials globally. KSI-301 is an anti-VEGF antibody biopolymer conjugate that allowed 66% of nAMD patients to maintain at least a 6-month treatment-free interval in Phase 1b studies. OPT-302, an inhibitor of VEGF-C/D, will be tested in phase 3 studies that compare anti-VEGF-A monotherapy against combination therapy with OPT-302. Faricimab is a bispecific anti-VEGF/Ang-2 antibody that upregulates the Tie-2 signaling pathway and promotes vascular stability; it is undergoing phase 3 trials with potential for 12- or 16-week dosing. PAN-90806 is a topical anti-VEGF agent that showed the ability to reduce injection frequency by 79% compared to ranibizumab monotherapy in a phase 1/2a trial. Sustained-release anti-VEGF therapies include the ranibizumab Port Delivery System (in phase 3 studies), GB-102 (Phase 2b), OTX-TKI (phase 1), and Durasert (preclinical). Suprachoroidal delivery of the tyrosine kinase inhibitor, axitinib, is in preclinical studies. Genetic therapies in phase 1 studies include RGX-314 and ADVM-022, which introduce a viral vector that modifies the retina's cellular apparatus to create an anti-VEGF biofactory, potentially serving as a one-time treatment. Further investigation is warranted for drugs and delivery systems that hope to advance visual outcomes and reduce treatment burden of nAMD.

Surgical Outcomes of Gonioscopy-assisted Transluminal Trabeculotomy (GATT) in Patients With Open-angle Glaucoma.

PURPOSE: To evaluate the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open-angle glaucoma. PARTICIPANTS AND METHODS: A retrospective chart review of adult patients who underwent GATT due to inadequately controlled intraocular pressure (IOP) or intolerance to medication. Main outcome measures were success rate, IOP, and number of glaucoma medications. Success was defined as IOP reduction >20% from baseline or IOP between 5 to 21 mm Hg, and no need for further glaucoma surgery. When success criteria were not met for any postoperative visit >3 months after surgery, failure was determined. RESULTS: In total, 66 patients, average age 62.9±14.9 years (50.8% female) were included in the analysis. Average follow-up was 11.9 months (range, 3 to 30 mo) and overall success rate was 63.0%. Mean IOP was 26.1±9.9 mm Hg preoperatively and 14.6±4.7 mm Hg at 12 months (44% IOP decrease; P<0.001). Mean number of medications decreased from 3.1±1.1 preoperatively to 1.2±0.9 at 12 months (P<0.001). No significant differences between patients with primary open-angle glaucoma and other types of glaucoma were found.The rate of hyphema at 1 week and 1 month postoperatively was 38% and 6%, respectively. Overall GATT success rate among white and black patients was 69% and 42%, respectively, which was statistically significant (P<0.05). CONCLUSIONS: The future of GATT as a minimally invasive glaucoma surgery in adults seems promising. This position is supported by its low rate of long-term complications and the conjunctiva-sparing nature of the surgery.