Intravitreal Tumor Necrosis Factor-Alpha Inhibitors for Neovascular Age-Related Macular Degeneration Suboptimally Responsive to Antivascular Endothelial Growth Factor Agents: A Pilot Study from the Pan American Collaborative Retina Study Group Lihteh Wu, 1 J. Fernando Arevalo, 2,3 Erick Hernandez-Bogantes, 1 Caio V. Regatieri, 4 Jose ´ A. Roca, 5 and Michel E. Farah 4, * Abstract Purpose: To compare the short-term visual and anatomic outcomes after intravitreal injections of 2 different tumor necrosis factor-a inhibitors to continued antivascular endothelial growth factor (VEGF) therapy in eyes with choroidal neovascularization (CNV) secondary to age-related macular degeneration that responded suboptimally to anti-VEGF agents. Methods: Retrospective comparative case series of 26 eyes. Eyes were injected intravitreally with 1 mg infliximab, 2 mg infliximab, 2 mg adalimumab, or 1.25 mg bevacizumab. The main outcomes measured were the best-corrected visual acuity (BCVA) and the central macular thickness (CMT) at 3 months of follow-up. Results: The mean log minimal angle of resolution BCVA changed from 1.04 – 0.23 at baseline to 1.06 – 0.51 at 3 months (P = 0.9455) in the 1-mg infliximab group; 0.94 – 0.48 at baseline to 0.85 – 0.43 in the 2-mg infliximab group (P = 0.2802); 1.58 – 0.50 at baseline to 1.38 – 0.43 in the adalimumab group (P = 0.1116); and 1.08 – 0.1 at baseline to 1.03 – 0.16 in the bevacizumab group (P = 0.9928). The mean CMT changed from 387 – 54 mm at baseline to 342 – 108 mm(P = 0.1053) in the 1-mg infliximab group; 301 – 42 mm at baseline to 284 – 73 mm (P = 0.4854) in the 2-mg infliximab group; remained unchanged at 348 – 106 mm(P = 0.308) in the adalimumab group; and 362 – 66 mm to 340 – 27 mm in the bevacizumab group (P = 0.4622). Adverse events included uveitis in 37.5% (6/16) of eyes injected with infliximab. Conclusion: Intravitreal infliximab and adalimumab do not appear to benefit eyes with CNV that responded suboptimally to anti-VEGF agents. Intravitreal injections of infliximab may elicit a severe intraocular inflam- matory reaction. Introduction C horoidal neovascularization (CNV) is responsible for 80%–90% of cases of severe vision loss due to age- related macular degeneration (AMD). 1–3 The mechanisms of CNV formation in AMD are still being elucidated. Vascular endothelial growth factor (VEGF) has been shown to be a major player in the pathogenesis of CNV. The introduction of anti-VEGF therapy has marked a paradigm shift in the treatment of CNV secondary to AMD. Randomized clinical trials have shown that up to 41% of eyes treated with intravitreal ranibizumab achieved a gain of at least 15 letters of early treatment of diabetic retinopathy study (ETDRS) best- corrected visual acuity (BCVA) compared to 6.3% of the control eyes. Furthermore, up to 40% of eyes achieved a BCVA of ‡ 20/40. 4 A recent comparative trial demonstrated that at 1 year, intravitreal bevacizumab had similar effects on visual acuity as intravitreal ranibizumab. 5 Despite these advances in 1 Instituto de Cirugia Ocular, San Jose ´, Costa Rica. 2 King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia. 3 Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland. 4 Departamento de Oftalmologia, Instituto da Visa ˜ o, Universidade Federal de Sa ˜o Paulo, Sa ˜ o Paulo, Brazil. 5 Department of Ophthalmology, Clinica Ricardo Palma, Lima, Peru. *For a complete listing of participating members of PACORES please see Appendix. JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS Volume 29, Number 3, 2013 ª Mary Ann Liebert, Inc. DOI: 10.1089/jop.2012.0203 366