Purpose: To evaluate outcome predictors of aflibercept in neovascular age-related macular degeneration pretreated with ranibizumab based on a treat-and-extend regimen (TER). Methods: We performed a retrospective evaluation of 18-month follow-up of 45 consecutive patients with limited response to ranibizumab. Results: At month 18, mean central retinal thickness and intraretinal fluid (IRF) height were significantly reduced. The recurrence-free treatment interval (RFTI) increased from 7.0 ± 1.8 to 8.5 ± 2.4 weeks (p = 0.01); visual acuity remained stable. At month 18, 58.1% of patients showed a longer RFTI. At month 12, eyes with baseline subretinal fluid (SRF) had a shorter RFTI than those without SRF (p = 0.032). Eyes with baseline IRF showed a longer RFTI than those without IRF (p = 0.037). Baseline hyperreflective foci (HRF) presence indicated improvement in SRF (p = 0.024) and IRF at month 12 (p = 0.049). Conclusion: Baseline HRF presence predicted better morphological outcome, while SRF predicted a shorter RFTI and IRF a longer RFTI after switching from ranibizumab to aflibercept within a TER.

Klein R, Peto T, Bird A, Vannewkirk MR: The epidemiology of age-related macular degeneration. Am J Ophthalmol 2004;137:486-495.
Rein DB, Zhang P, Wirth KE, Lee PP, Hoerger TJ, McCall N, Klein R, Tielsch JM, Vijan S, Saaddine J: The economic burden of major adult visual disorders in the United States. Arch Ophthalmol 2006;124:1754-1760.
Bloch SB, Larsen M, Munch IC: Incidence of legal blindness from age-related macular degeneration in Denmark: year 2000 to 2010. Am J Ophthalmol 2012;153:209-213.
Varano M, Eter N, Winyard S, Wittrup-Jensen KU, Navarro R, Heraghty J: Current barriers to treatment for wet age-related macular degeneration (wAMD): findings from the wAMD patient and caregiver survey. Clin Ophthalmol 2015;9:2243-2250.
Schmidt-Erfurth U, Chong V, Loewenstein A, Larsen M, Souied E, Schlingemann R, Eldem B, Monés J, Richard G, Bandello F: Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br J Ophthalmol 2014;98:1144-1167.
Mantel I, Deli A, Iglesias K, Ambresin A: Prospective study evaluating the predictability of need for retreatment with intravitreal ranibizumab for age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2013;251:697-704.
Freund KB, Korobelnik JF, Devenyi R, Framme C, Galic J, Herbert E, Hoerauf H, Lanzetta P, Michels S, Mitchell P, Monés J, Regillo C, Tadayoni R, Talks J, Wolf S: Treat-and-extend regimens with anti-VEGF agents in retinal diseases: a literature review and consensus recommendations. Retina 2015;35:1489-1506.
Dixon JA, Oliver SC, Olson JL, Mandava N: VEGF Trap-Eye for the treatment of neovascular age-related macular degeneration. Expert Opin Investig Drugs 2009;18:1573-1580.
Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, Pyles EA, Yancopoulos GD, Stahl N, Wiegand SJ: Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis 2012;15:171-185.
Stewart MW, Rosenfeld PJ: Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol 2008;92:667-668.
Bakall B, Folk JC, Boldt HC, Sohn EH, Stone EM, Russell SR, Mahajan VB: Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab. Am J Ophthalmol 2013;156:15-22.
Binder S: Loss of reactivity in intravitreal anti-VEGF therapy: tachyphylaxis or tolerance? Br J Ophthalmol 2012;96:1-2.
Eghoj MS, Sorensen TL: Tachyphylaxis during treatment of exudative age-related macular degeneration with ranibizumab. Br J Ophthalmol 2012;96:21-23.
Forooghian F, Cukras C, Meyerle CB, Chew EY, Wong WT: Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration. Retina 2009;29:723-731.
Schmidt-Erfurth U, Waldstein SM: A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration. Prog Retin Eye Res 2016;50:1-24.
European Agency for the Evaluation of Medicinal Products, International Conference on Harmonisation-World Health Organization: Guideline for Good Clinical Practice E6(R2). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002874.pdf (accessed January 26, 2017).
World Medical Association: Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. 52nd WMA General Assembly, Edinburgh, Scotland, October 2000. Last amended with Note of Clarification on Paragraph 29 by the WMA General Assembly, Washington 2002; and Note of Clarification on Paragraph 30 by the WMA General Assembly, Tokyo 2004. https://www.fda.gov/ohrms/dockets/dockets/06d0331/06D-0331-EC20-Attach-1.pdf (accessed January 26, 2017).
Lazzeri S, Ripandelli G, Sartini MS, Parravano M, Varano M, Nardi M, Di Desidero T, Orlandi P, Bocci G: Aflibercept administration in neovascular age-related macular degeneration refractory to previous anti-vascular endothelial growth factor drugs: a critical review and new possible approaches to move forward. Angiogenesis 2015;18:397-432.
De Massougnes S, Dirani A, Ambresin A, Decugis D, Marchionno L, Mantel I: Pigment epithelial detachment response to aflibercept in neovascular age-related macular degeneration refractory to ranibizumab: time course and drug effects. Retina 2016;36:881-888.
Bolz M, Schmidt-Erfurth U, Deak G, Mylonas G, Kriechbaum K, Scholda C; Diabetic Retinopathy Research Group Vienna: Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema. Ophthalmology 2009;116:914-920.
Abri Aghdam K, Pielen A, Framme C, Junker B: Correlation between hyperreflective foci and clinical outcomes in neovascular age-related macular degeneration after switching to aflibercept. Invest Ophthalmol Vis Sci 2015;56:6448-6455.
Chen KC, Jung JJ, Curcio CA, Balaratnasingam C, Gallego-Pinazo R, Dolz-Marco R, Freund KB, Yannuzzi LA: Intraretinal hyperreflective foci in acquired vitelliform lesions of the macula: clinical and histologic study. Am J Ophthalmol 2016;164:89-98.
Lee H, Lee J, Chung H, Kim HC: Baseline spectral domain optical coherence tomographic hyperreflective foci as a predictor of visual outcome and recurrence for central serous chorioretinopathy. Retina 2016;36:1372-1380.
Regatieri CV, Alwassia A, Zhang JY, Vora R, Duker JS: Use of optical coherence tomography in the diagnosis and management of uveitis. Int Ophthalmol Clin 2012;52:33-43.
Coscas G, De Benedetto U, Coscas F, Li Calzi CI, Vismara S, Roudot-Thoraval F, Bandello F, Souied E: Hyperreflective dots: a new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration. Ophthalmologica 2013;229:32-37.
Segal O, Barayev E, Nemet AY, Geffen N, Vainer I, Mimouni M: Prognostic value of hyperreflective foci in neovascular age-related macular degeneration treated with bevacizumab. Retina 2016;36:2175-2182.
Keane PA, Patel PJ, Liakopoulos S, Heussen FM, Sadda SR, Tufail A: Evaluation of age-related macular degeneration with optical coherence tomography. Surv Ophthalmol 2012;57:389-414.
Landa G, Su E, Garcia PM, Seiple WH, Rosen RB: Inner segment-outer segment junctional layer integrity and corresponding retinal sensitivity in dry and wet forms of age-related macular degeneration. Retina 2011;31:364-370.
Kim YM, Kim JH, Koh HJ: Improvement of photoreceptor integrity and associated visual outcome in neovascular age-related macular degeneration. Am J Ophthalmol 2012;154:164-173.
Waldstein SM, Wright J, Warburton J, Margaron P, Simader C, Schmidt-Erfurth U: Predictive value of retinal morphology for visual acuity outcomes of different ranibizumab treatment regimens for neovascular AMD. Ophthalmology 2016;123:60-69.
Schmidt-Erfurth U, Klimscha S, Waldstein SM, Bogunovic H: A view of the current and future role of optical coherence tomography in the management of age-related macular degeneration. Eye (Lond) 2017;31:26-44.
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