Retinal Nerve Fiber Layer Thickness in Patients Receiving Chronic Anti–Vascular Endothelial Growth Factor Therapy MICHAEL B. HORSLEY, NARESH MANDAVA, MARCO A. MAYCOTTE, AND MALIK Y. KAHOOK ● PURPOSE: To evaluate the effects of multiple intravit- real injections of anti–vascular endothelial growth factor (VEGF) agents on the thickness of the retinal nerve fiber layer (RNFL) in patients with wet age-related macular degeneration (ARMD). ● DESIGN: Retrospective, observational, consecutive case series of patients diagnosed with wet ARMD. ● METHODS: Forty-one eyes of 37 consecutive patients (25 female and 12 male; mean age 79.2  8.7 years) who underwent treatment with pegaptanib, bevacizumab, and/or ranibizumab for ARMD followed by sequential RNFL thickness measurement by optical coherence to- mography (OCT) were studied. Patients were included in the analyses if they had greater than 10 total anti-VEGF injections, RNFL measurements prior to the first injec- tion, and at least 12 months of follow-up. Patients were divided into 3 groups depending on which anti-VEGF agent(s) they received. The OCT RNFL measurements at the initial and final follow-up were used for analyses. ● RESULTS: Average follow-up for all patients was 27.0  9.7 months and they received an average of 16.0  5.5 intravitreal injections. The average RNFL thickness at presentation was 92.4  15.2 m and at last follow-up was 93.8  15.2 m(P  .68). There were no statistically significant differences in RNFL measure- ments when comparing between individual anti-VEGF treatment groups. ● CONCLUSION: Long-term treatment with anti-VEGF agents did not lead to significant changes in RNFL thickness in a patient population with wet ARMD. Despite the possibility of repeated intraocular pressure (IOP) fluctuations after intravitreal injections and known neurotrophic properties of VEGF in the eye, chronic therapy with intravitreal anti-VEGF agents does not appear to adversely affect RNFL thickness. Further prospective studies with longer follow-up are needed to corroborate the findings of this study. (Am J Ophthal- mol 2010;150:558 –561. © 2010 by Elsevier Inc. All rights reserved.) U PREGULATION OF VASCULAR ENDOTHELIAL GROWTH factor (VEGF) has been correlated with the choroidal neovascular membranes seen in patients with wet age-related macular degeneration (ARMD). 1 The use of intravitreal anti-VEGF agents has become the standard of care for patients with ARMD and these agents are now commonly used for various neovascular diseases of the eye. 2,3 The duration of efficacy of the anti-VEGF agents pegaptanib (Macugen; EyeTech Pharmaceuticals/Pfizer Inc, New York, New York, USA), bevacizumab (Avastin; Genentech, Inc, San Francisco, California, USA), and ranibizumab (Lucentis; Genentech, Inc) is limited. There- fore, repeated injections are required to maintain their anti-angiogenic effects. While the use of anti-VEGF agents in clinical practice has increased, long-term safety data are still being published, and the full implications of repeated injections of protein-based therapeutics into the vitreous cavity remain unclear. VEGF is known to be neurotrophic. 4 Theoretically, chronic suppression of a neurotrophic cytokine may result in deleterious downstream effects on the retinal nerve fiber layer (RNFL). In addition, there have been reports relating intravitreal injection of anti-VEGF agents to both tran- sient and sustained elevation of intraocular pressure (IOP). 5–10 The long-term effects of repeated anti-VEGF injections, as they relate to neurotrophic properties and IOP fluctuations, on RNFL thickness are not well known. The current study investigates the changes in RNFL measurements in ARMD patients treated with intravitreal pegaptanib, bevacizumab, and/or ranibizumab. METHODS THIS IS A RETROSPECTIVE, OBSERVATIONAL, CONSECUTIVE case series of patients who had received more than 10 intravitreal injections of pegaptanib sodium, bevacizumab, ranibizumab, or a combination of these anti-VEGF agents at the Rocky Mountain Lions Eye Institute, University of Colorado Department of Ophthalmology. All patients who had a diagnosis of ARMD receiving anti-VEGF therapy between June 2005 and January 2008 were identified and those with documented RNFL thickness measurement by optical coherence tomography (OCT) (Stratus Carl Zeiss Meditec, Inc, Dublin, California, USA) prior to their first Accepted for publication Apr 27, 2010. From the Rocky Mountain Lions Eye Institute, Department of Oph- thalmology, University of Colorado Denver School of Medicine, Aurora, Colorado. Inquiries to Malik Y. Kahook, Rocky Mountain Lions Eye Institute, University of Colorado Denver, 1675 Aurora Court, Mail Stop F-731, Aurora, CO 80045; e-mail: Malik.Kahook@gmail.com © 2010 BY ELSEVIER INC.ALL RIGHTS RESERVED. 558 0002-9394/$36.00 doi:10.1016/j.ajo.2010.04.029