Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration

Sarah Mrejen, Jesse J Jung, Christine Chen, Samir N Patel, Roberto Gallego-Pinazo, Nicolas Yannuzzi, Luna Xu, Marcela Marsiglia, Sucharita Boddu, K Bailey Freund, Sarah Mrejen, Jesse J Jung, Christine Chen, Samir N Patel, Roberto Gallego-Pinazo, Nicolas Yannuzzi, Luna Xu, Marcela Marsiglia, Sucharita Boddu, K Bailey Freund

Abstract

With the advent of anti-vascular endothelial growth factor (VEGF) therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD), a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA) alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT) and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER) with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes) were followed over an average of 3.5 years (range 1-6.6) with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6) (± standard deviation) intravitreal anti-VEGF injections/year (range 4-13). The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.

Keywords: Treat and Extend Regimen; anatomical classification; choroidal neovascularization; fluorescein angiography classification; intravitreal anti-VEGF injections; neovascular age-related macular degeneration.

Figures

Figure 1
Figure 1
Mean visual acuity over time. The visual acuity is noted in logMAR and Snellen chart, as well as the number of eyes at each time point.
Figure 2
Figure 2
Mean visual change from baseline over time. The mean change in visual acuity from baseline is noted in logMAR and equivalent of lines.
Figure 3
Figure 3
Mean visual acuity in logMAR by neovascular subtype using the anatomic classification. The number of eyes for each neovascular subtype is reported at each time point.
Figure 4
Figure 4
Mean visual change from baseline in line equivalent by neovascular subtype using the anatomic classification.

References

    1. Friedman D.S., O’Colmain B.J., Munoz B., Tomany S.C., McCarty C., de Jong P.T., Nemesure B., Mitchell P., Kempen J. Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch. Ophthalmol. 2004;122:564–572.
    1. Ferris F.L., 3rd, Fine S.L., Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch. Ophthalmol. 1984;102:1640–1642. doi: 10.1001/archopht.1984.01040031330019.
    1. Rosenfeld P.J., Brown D.M., Heier J.S., Boyer D.S., Kaiser P.K., Chung C.Y., Kim R.Y., Group M.S. Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 2006;355:1419–1431. doi: 10.1056/NEJMoa054481.
    1. Brown D.M., Michels M., Kaiser P.K., Heier J.S., Sy J.P., Ianchulev T., Group A.S. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology. 2009;116:57–65. doi: 10.1016/j.ophtha.2008.10.018.
    1. Brown D.M., Regillo C.D. Anti-VEGF agents in the treatment of neovascular age-related macular degeneration: Applying clinical trial results to the treatment of everyday patients. Am. J. Ophthalmol. 2007;144:627–637. doi: 10.1016/j.ajo.2007.06.039.
    1. Cohen S.Y., Dubois L., Tadayoni R., Fajnkuchen F., Nghiem-Buffet S., Delahaye-Mazza C., Guiberteau B., Quentel G. Results of one-year’s treatment with ranibizumab for exudative age-related macular degeneration in a clinical setting. Am. J. Ophthalmol. 2009;148:409–413. doi: 10.1016/j.ajo.2009.04.001.
    1. Engelbert M., Zweifel S.A., Freund K.B. “Treat and extend” dosing of intravitreal antivascular endothelial growth factor therapy for type 3 neovascularization/retinal angiomatous proliferation. Retina. 2009;29:1424–1431. doi: 10.1097/IAE.0b013e3181bfbd46.
    1. Freund K.B., Korobelnik J.F., Devenyi R., Framme C., Galic J., Herbert E., Hoerauf H., Lanzetta P., Michels S., Mitchell P., et al. Treat-and-extend regimens with anti-VEGF inhibitors in retinal diseases: A consensus. Retina. 2014 Submitted.
    1. Comparison of Age-related Macular Degeneration Treatments Trials Research Group. Martin D.F., Maguire M.G., Fine S.L., Ying G.S., Jaffe G.J., Grunwald J.E., Toth C., Redford M., Ferris F.L., 3rd Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: Two-year results. Ophthalmology. 2012;119:1388–1398.
    1. Lalwani G.A., Rosenfeld P.J., Fung A.E., Dubovy S.R., Michels S., Feuer W., Davis J.L., Flynn H.W., Jr., Esquiabro M. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: Year 2 of the PrONTO Study. Am. J. Ophthalmol. 2009;148:43–58. doi: 10.1016/j.ajo.2009.01.024.
    1. Fung A.T., Kumar N., Vance S.K., Slakter J.S., Klancnik J.M., Spaide R.S., Freund K.B. Pilot study to evaluate the role of high-dose ranibizumab 2.0 mg in the management of neovascular age-related macular degeneration in patients with persistent/recurrent macular fluid <30 days following treatment with intravitreal anti-VEGF therapy (the LAST Study) Eye (Lond) 2012;26:1181–1187.
    1. Toalster N., Russell M., Ng P. A 12-month prospective trial of inject and extend regimen for ranibizumab treatment of age-related macular degeneration. Retina. 2013;33:1351–1358. doi: 10.1097/IAE.0b013e3182831265.
    1. Abedi F., Wickremasinghe S., Islam A.F., Inglis K.M., Guymer R.H. Anti-VEGF treatment in neovascular age-related macular degeneration: A Treat-and-Extend Protocol Over 2 Years. Retina. 2014;34:1531–1538. doi: 10.1097/IAE.0000000000000134.
    1. Gupta O.P., Shienbaum G., Patel A.H., Fecarotta C., Kaiser R.S., Regillo C.D. A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. Ophthalmology. 2010;117:2134–2140. doi: 10.1016/j.ophtha.2010.02.032.
    1. Shienbaum G., Gupta O.P., Fecarotta C., Patel A.H., Kaiser R.S., Regillo C.D. Bevacizumab for neovascular age-related macular degeneration using a treat-and-extend regimen: Clinical and economic impact. Am. J. Ophthalmol. 2012;153:468–473. doi: 10.1016/j.ajo.2011.08.011.
    1. Engelbert M., Zweifel S.A., Freund K.B. Long-term follow-up for type 1 (subretinal pigment epithelium) neovascularization using a modified “treat and extend” dosing regimen of intravitreal antivascular endothelial growth factor therapy. Retina. 2010;30:1368–1375. doi: 10.1097/IAE.0b013e3181d50cbf.
    1. Rayess N., Houston S.K., 3rd, Gupta O.P., Ho A.C., Regillo C.D. Treatment outcomes after 3 years in neovascular age-related macular degeneration using a treat-and-extend regimen. Am. J. Ophthalmol. 2015;159:3–8. doi: 10.1016/j.ajo.2014.09.011.
    1. Calvo P., Wang Y., Ferreras A., Lam W.C., Denevyl R., Brent M.H. Treat and extend versus treat and observe in wet age-related macular degeneration patients treated with ranibizumab: 3-year surveillance period. J. Clin. Exp. Ophthalmol. 2014;5:1–5.
    1. Oubraham H., Cohen S.Y., Samimi S., Marotte D., Bouzaher I., Bonicel P., Fajnkuchen F., Tadayoni R. Inject and extend dosing versus dosing as needed: A comparative retrospective study of ranibizumab in exudative age-related macular degeneration. Retina. 2011;31:26–30. doi: 10.1097/IAE.0b013e3181de5609.
    1. Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group. Arch. Ophthalmol. 1991;109:1220–1231.
    1. Grossniklaus H.E., Gass J.D. Clinicopathologic correlations of surgically excised type 1 and type 2 submacular choroidal neovascular membranes. Am. J. Ophthalmol. 1998;126:59–69. doi: 10.1016/S0002-9394(98)00145-7.
    1. Freund K.B., Zweifel S.A., Engelbert M. Do we need a new classification for choroidal neovascularization in age-related macular degeneration? Retina. 2010;30:1333–1349. doi: 10.1097/IAE.0b013e3181e7976b.
    1. Jung J.J., Chen C.Y., Mrejen S., Gallego-Pinazo R., Xu L., Marsiglia M., Boddu S., Freund K.B. The Incidence of Neovascular Subtypes in Newly Diagnosed Neovascular Age-Related Macular Degeneration. Am. J. Ophthalmol. 2014;158:769–779. doi: 10.1016/j.ajo.2014.07.006.
    1. Xu L., Mrejen S., Jung J.J., Gallego-Pinazo R., Thompson D., Marsiglia M., Freund K.B. Geographic Atrophy in Patients Receiving Anti-Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration. Retina. 2014;35:176–186. doi: 10.1097/IAE.0000000000000374.
    1. Yannuzzi L.A., Negrao S., Iida T., Carvalho C., Rodriguez-Coleman H., Slakter J., Freund K.B., Sorenson J., Orlock D., Borodoker N. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21:416–434. doi: 10.1097/00006982-200110000-00003.
    1. Rofagha S., Bhisitkul R.B., Boyer D.S., Sadda S.R., Zhang K., SEVEN-UP Study Group Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: A multicenter cohort study (SEVEN-UP) Ophthalmology. 2013;120:2292–2299. doi: 10.1016/j.ophtha.2013.03.046.
    1. Singer M.A., Awh C.C., Sadda S., Freeman W.R., Antoszyk A.N., Wong P., Tuomi L. HORIZON: An open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology. 2012;119:1175–1183. doi: 10.1016/j.ophtha.2011.12.016.
    1. Rasmussen A., Bloch S.B., Fuchs J., Hansen L.H., Larsen M., Lacour M., Lund-Andersen H., Sander B. A 4-year longitudinal study of 555 patients treated with ranibizumab for neovascular age-related macular degeneration. Ophthalmology. 2013;120:2630–2636. doi: 10.1016/j.ophtha.2013.05.018.
    1. Silva R., Axer-Siegel R., Eldem B., Guymer R., Kirchhof B., Papp A., Seres A., Gekkieva M., Nieweg A., Pilz S., et al. The SECURE study: Long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration. Ophthalmology. 2013;120:130–139. doi: 10.1016/j.ophtha.2012.07.026.
    1. Marcus D.M. Long-Term Follow-up of Intravitreal Injection for Neovascular Age-Related Macular Degeneration in an Open-Label Extension of the VIEW 1 Study; 4–8 May, 2014; Orlando, FL, USA. Abstract presented at: the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.
    1. Shah V.P., Freund K.B. Growth of type 1 neovascularization following cessation of anti-vascular endothelial growth factor therapy as a possible explanation for treatment resistance. JAMA Ophthalmol. 2013;131:967–969. doi: 10.1001/jamaophthalmol.2013.2120.
    1. Grunwald J.E., Daniel E., Huang J., Ying G.S., Maguire M.G., Toth C.A., Jaffe G.J., Fine S.L., Blodi B., Klein M.L., et al. Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2014;121:150–161. doi: 10.1016/j.ophtha.2013.08.015.
    1. McBain V.A., Kumari R., Townend J., Lois N. Geographic atrophy in retinal angiomatous proliferation. Retina. 2011;31:1043–1052. doi: 10.1097/IAE.0b013e3181fe54c7.
    1. Marsiglia M., Boddu S., Chen C.Y., Jung J.J., Mrejen S., Gallego-Pinazo R., Freund K.B. Correlation between neovascular lesion type and the clinical characteristics of non-neovascular fellow eyes in patients with unilateral neovascular age-related macular degeneration. Retina. 2015;35:966–974.
    1. Daniel E., Toth C.A., Grunwald J.E., Jaffe G.J., Martin D.F., Fine S.L., Huang J., Ying G.S., Hagstrom S.A., Winter K., et al. Risk of scar in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2014;121:656–666. doi: 10.1016/j.ophtha.2013.10.019.
    1. Green W.R. Histopathology of age-related macular degeneration. Mol. Vis. 1999;5:27.
    1. Grossniklaus H.E., Green W.R. Choroidal neovascularization. Am. J. Ophthalmol. 2004;137:496–503. doi: 10.1016/j.ajo.2003.09.042.
    1. Bhavsar K.V., Freund K.B. Retention of good visual acuity in eyes with neovascular age-related macular degeneration and chronic refractory subfoveal subretinal fluid. Saudi J. Ophthalmol. 2014;28:129–133. doi: 10.1016/j.sjopt.2014.03.001.
    1. Cohen S.Y., Creuzot-Garcher C., Darmon J., Desmettre T., Korobelnik J.F., Levrat F., Quentel G., Palies S., Sanchez A., de Gendre A.S., et al. Types of choroidal neovascularisation in newly diagnosed exudative age-related macular degeneration. Br. J. Ophthalmol. 2007;91:1173–1176. doi: 10.1136/bjo.2007.115501.
    1. Hoang Q.V., Tsuang A.J., Gelman R., Mendonca L.S., Della Torre K.E., Jung J.J., Freund K.B. Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial growth factor therapy. Retina. 2013;33:179–187. doi: 10.1097/IAE.0b013e318261a6f7.
    1. Hoang Q.V., Mendonca L.S., Della Torre K.E., Jung J.J., Tsuang A.J., Freund K.B. Effect on intraocular pressure in patients receiving unilateral intravitreal anti-vascular endothelial growth factor injections. Ophthalmology. 2012;119:321–326. doi: 10.1016/j.ophtha.2011.08.011.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner