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.

A 37-year-old Indian male presented with a 3-year history of right eye blurred vision. Bilateral ophthalmic examinations revealed shallow, oval areas of macular subretinal fluid containing hypopion-like precipitates and central neurosensory retinal detachments with focal early-stage fluorescein leakage consistent with central serous chorioretinopathy (CSCR). Inadequate response to Eplerenone prompted reassessment yielding a positive BCG vaccine history. Latent tuberculosis infection (LTBI) was diagnosed by a positive interferon-γ response assay (IGRA) in the absence of pulmonary symptoms. Rifampin alone yielded only modest bilateral visual acuity increases and subretinal fluid decreases. Right eye focal macular laser was performed to stabilize vision with modest subretinal fluid decrease, but peripheral retinal lesions were noted on follow up. The patient has been unavailable for follow up evaluation and supportive anti-tuberculosis treatment (ATT) to date. The unresponsiveness to anti-corticosteroid medications in our case of CSCR secondary to LTBI, the reported detection of Mycobacterium tuberculosis DNA in CSCR subretinal fluid, and the resolution CSCR post ATT in 3 previous CSCR secondary to LTBI cases support a possible association of CSCR and LTBI. To our knowledge this is the fourth case of chronic CSCR in a patient with LTBI.