The purpose of this prospective interventional study is to assess whether adjunctive verteporfin photodynamic therapy (PDT) is effective for the treatment of persistent disease activity in neovascular age-related macular degeneration (NV AMD), as compared to anti-VEGF therapy (aflibercept) alone. This study will enroll individuals with NV AMD who have persistent disease activity in spite of either loading dose (initial 3-5 anti-VEGF treatments) or maintenance (established course) anti-VEGF therapy to determine whether PDT can improve disease activity, facilitate sustained visual acuity gains, and decrease burden of frequent anti-VEGF treatments for affected patients. Risks of study are related to treatment with study drugs: intravenous verteporfin, intravitreal triamcinolone acetonide, and intravitreal aflibercept. All have been studied extensively in clinical trials and are established treatments used routinely in NV AMD. Adverse events will be monitored by the principal investigator and study team.

Neovascular age-related macular degeneration (NV AMD) remains the leading cause of vision loss among people over 65. Intravitreal injections with drugs that block vascular endothelial growth factor (VEGF), a major protein mediator of angiogenesis and vascular leakage, have revolutionized treatment of NV AMD. This class of drugs includes the FDA-approved medications ranibizumab (Lucentis ®, Genentech) and aflibercept (Eylea ®, Regeneron), as well as bevacizumab (Avastin ®, Genentech), which is not FDA-approved for the treatment of NV AMD but is used off-label with demonstrated clinical efficacy. However, these therapies are not a cure. Even when effective, the vast majority of NV AMD patients require continued treatment with anti-VEGF drugs indefinitely for the rest of their lives, to sustain stable visual acuity. Further, in spite of continuous monthly anti-VEGF therapy, up to 40-50% of patients demonstrate persistent disease activity (PDA). Patients with persistent disease activity in spite of ongoing anti-VEGF therapy remain at increased risk for long-term vision loss. Persistent disease activity is defined as (1) unresolved intraretinal, subretinal, or sub-retinal pigment epithelium (RPE) fluid or exudation; (2) progressive lesion enlargement and fibrosis; and/or (3) persistent or new hemorrhage. Several large, multicenter, prospective clinical trials have demonstrated ~75% rate of PDA following loading dose therapy (i.e. three consecutive monthly injections), and ~ 40-50% PDA following one year of continued anti-VEGF therapy.

The treatment burden to sustain visual acuity for patients with PDA is especially high, since undertreatment or cessation of therapy assures visual decline. The PIER study assessed the efficacy of quarterly (i.e. every-three-months) anti-VEGF therapy with ranibizumab, following initiation with loading dose therapy. Patients who had resolution of disease activity following loading dose maintained visual acuity gains with subsequent quarterly therapy. In contrast, patients with PDA following loading dose had progressive loss of visual acuity gains when switched to subsequent quarterly therapy. Several subsequent clinical trials (CATT, IVAN, others) have demonstrated that patients with PDA typically require continued monthly therapy to sustain improved visual acuity. Though "do-able" in the short term, indefinite long-term therapy with monthly injections is often impractical for patients and for retina physicians, and as a result, undertreatment occurs with high frequency.

Verteporfin (Visudyne ®, Bausch + Lomb) PDT is an FDA-approved treatment for NV AMD that was initially approved over 10 years ago, prior to the advent of anti-VEGF therapy. As a first-line therapy, verteporfin PDT is much less effective than anti-VEGF therapy in improving vision for NV AMD patients. PDT has been studied as an adjunctive therapy in previously treatment-naïve patients receiving anti-VEGF therapy. It was not found to offer significant visual acuity benefit over anti-VEGF therapy alone, in this population. However, it is unknown whether adjunctive PDT may be effective in improving treatment response in patients with PDA in spite of anti-VEGF therapy. The investigators have performed several retrospective studies of NV AMD patients in the Duke Medical Retina practice to assess the role of adjunctive PDT in cases of PDA. Preliminary results indicate that adjunctive verteporfin PDT reduces disease activity (i.e. decreased fluid and exudation) in patients with PDA, facilitates treatment with fewer anti-VEGF injections (i.e. reduces treatment burden), and reduces risk of subsequent vision loss. However, no studies have prospectively evaluated the efficacy of adjunctive PDT in patients with PDA in spite of anti-VEGF therapy. The present study will assess the efficacy of adjunctive PDT for the treatment of PDA in NV AMD. The investigators will compare administration of anti-VEGF therapy with adjunctive PDT to the standard-of-care treatment approach, anti-VEGF monotherapy administered according to a "treat-and-extend" approach, where the interval between intravitreal injections is as short as every 1 month (approximately 4 weeks) but can be gradually lengthened to the longest interval between treatments that ensures disease quiescence.

Inclusion Criteria:

• Clinical diagnosis of either 1) NV AMD with PDA in spite of standard-of-care intravitreal anti-VEGF therapy, either loading dose or maintenance therapy or 2) Clinical diagnosis of NV AMD with Progressive Disease in spite of standard-of-care intravitreal anti-VEGF therapy, either loading dose or maintenance therapy
• Best-corrected visual acuity equivalent of 20/25-20/320
• Able to provide written informed consent
• Presence of discernible choroidal neovascular lesion by ICG angiography

Exclusion Criteria:

• History of porphyria or sensitivity to any component of verteporfin preparation
• Presence of systemic fungal infection or sensitivity to any component of triamcinolone acetonide preparation
• Presence of ocular or periocular infection or sensitivity to any component to aflibercept
• Prior vitrectomy surgery
• Prior thermal laser for macular photocoagulation
• Inability to avoid exposure of skin or eyes to direct sunlight or bright indoor light for 5 days following verteporfin PDT treatment sessions
• Presence of large submacular hemorrhage in association with choroidal neovascular lesion
• Known or suspected allergy to fluorescein and/or indocyanine green
• Known history of open angle glaucoma
• Known history of diabetic macular edema or macular edema attributable to central retinal vein occlusion
• Recent history (within prior 6 months) of cerebrovascular accident (i.e. stroke) or myocardial infarction.