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July 2013

Growth of Type 1 Neovascularization Following Cessation of Anti–Vascular Endothelial Growth Factor Therapy as a Possible Explanation for Treatment Resistance

Author Affiliations
  • 1Vitreous-Retina-Macula Consultants of New York, New York, New York
  • 2Department of Ophthalmology, New York University School of Medicine, New York, New York
JAMA Ophthalmol. 2013;131(7):967-969. doi:10.1001/jamaophthalmol.2013.2120

Intravitreal anti–vascular endothelial growth factor (anti-VEGF) therapy is currently the standard of care for the treatment of neovascular age-related macular degeneration. Herein, we describe a mechanism by which some patients who initially show a robust response to treatment may later in their course become refractory to this therapy.

An 86-year-old woman received intravitreal ranibizumab in her left eye for type 1 (subretinal pigment epithelium) neovascularization associated with neovascular age-related macular degeneration1 (Figure 1A and B). Over the course of 4 monthly injections, there was complete resolution of subretinal pigment epithelium hemorrhage. Consolidation of the type 1 neovascular tissue and resolution of all fluid was noted with spectral-domain optical coherence tomography (SD-OCT) (Figure 1C). The patient was then switched to optical coherence tomography–guided therapy with pro re nata dosing. For the next 10 months, the type 1 vessels were noted to gradually increase in size, but because there was no visible hemorrhage and there was no fluid present on SD-OCT, injections were withheld. Approximately 11 months after her last injection, recurrent subretinal fluid was noted on SD-OCT (Figure 1D). Raster scans covering the entire lesion did not show evidence of polypoidal structures. At this time, she received an intravitreal ranibizumab injection followed by 1 additional injection 1 month later for persistent fluid. The next month, the patient was switched to intravitreal aflibercept as the fluid persisted. Despite 6 monthly aflibercept injections, SD-OCT imaging continued to show persistent fluid. The neovascular tissue appeared to have become partially refractory to anti-VEGF therapy (Figure 1E).