helmholtzeyeinstituteРоссийский офтальмологический журналRussian Ophthalmological Journal2072-00762587-5760Real time Publishers10.21516/2072-0076-2017-10-2-103-111helmholtzeyeinstitute-102Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWSАфлиберцепт в лечении заболеваний сетчатки. Обзор клинических исследованийAflibercept for the therapy of retinal diseases. A review of clinical studiesОхоцимскаяТ. Д.OkhotsimskayaT. D.noemail@neicon.ruЗайцеваО. В.ZaitsevaO. V.noemail@neicon.ruФГБУ «Московский НИИ глазных болезней им. Гельмгольца» Минздрава РоссииРоссияHelmholtz Research Institute of Eye Diseases, Moscow, RussiaRussian Federation201703102018102103111Copyright © Охоцимская Т.Д., Зайцева О.В., 20182018Охоцимская Т.Д., Зайцева О.В.Okhotsimskaya T.D., Zaitseva O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://roj.igb.ru/jour/article/view/102

Афлиберцепт - гибридный белок - имитация рецептора VEGF, обладающий пролонгированной активностью. Описаны особенности строения молекулы афлиберцепта и его воздействие на патогенез заболеваний сетчатки. Приведены результаты клинических исследований по изучению эффективности и безопасности афлиберцепта при возрастной макулярной дегенерации (VIEW1, VIEW2), диабетическом макулярном отеке (VISTA, VIVID), макулярном отеке вследствие окклюзии центральной вены сетчатки (GALILEO, COPERNICUS) или ее ветвей (VIBRANT), а также при миопической хориоидальной неоваскуляризации (MYRROR) // Российский офтальмологический журнал, 2017; 2: 103-111.

Aflibercept is a hybrid protein-imitation of VEGF receptor with a prolonged activity. The review describes the structural properties of the Aflibercept molecule, the impact of the medication on the pathogenesis of retinal diseases, and the results of clinical studies into the safety and effectiveness of Aflibercept in the therapy of age related macular degeneration (VIEW1, VIEW2), diabetic macular oedema (VISTA, VIVID), macular oedema caused by the occlusion of the central retinal vein (GALILEO, COPERNICUS) or its branches (VIBRANT), and myopic choroidal neovascularization (MYRROR) Russian ophthalmological journal. 2017; 10 (2): 103-11. (in Russian). doi: 10.21516/2072-0076-2017-10-2-103-111.

макулярный отексосудистый эндотелиальный фактор роста (VEGF)афлиберцептmacular oedemavascular endothelial growth factor (VEGF)AfliberceptReferencesCiulla T.A., Amador A.G., Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 2003; 26 (9): 2653-64.Ciulla T.A., Amador A.G., Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 2003; 26 (9): 2653-64.Zechmeister-Koss I., Huic M. Vascular endothelial growth factor inhibitors (anti-VEGF) in the management of diabetic macular oedema: a systematic review. Br. J. Ophthalmol. 2012; 96 (2): 167-78.Zechmeister-Koss I., Huic M. Vascular endothelial growth factor inhibitors (anti-VEGF) in the management of diabetic macular oedema: a systematic review. Br. J. Ophthalmol. 2012; 96 (2): 167-78.Romero-Aroca. Current status in diabetic macular edema treatments. World J Diabetes. 2013; 4 (5): 165-9.Romero-Aroca. Current status in diabetic macular edema treatments. World J Diabetes. 2013; 4 (5): 165-9.Resnikoff S., Pascolini D., Etya’ale D., et al. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004; 82 (11): 844-51.Resnikoff S., Pascolini D., Etya’ale D., et al. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004; 82 (11): 844-51.Congdon N., O’Colmain B., Klaver C.C., et al. Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch. Ophthalmol. 2004; 122 (4): 477-85.Congdon N., O’Colmain B., Klaver C.C., et al. Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch. Ophthalmol. 2004; 122 (4): 477-85.Rogers S., McIntosh R.L., Cheung N., et al. The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology. 2010; 117 (2): 313.e1-319.e1.Rogers S., McIntosh R.L., Cheung N., et al. The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology. 2010; 117 (2): 313.e1-319.e1.Wong T.Y., Ferreira A., Hughes R., et al. Epidemiology and disease burden of pathologic myopia and myopic choroidal neovascularization: an evidence-based systematic review. Am. J. Ophthalmol. 2014; 157: 9-25.Wong T.Y., Ferreira A., Hughes R., et al. Epidemiology and disease burden of pathologic myopia and myopic choroidal neovascularization: an evidence-based systematic review. Am. J. Ophthalmol. 2014; 157: 9-25.VEGF Trap-Eye (aflibercept ophthalmic solution) briefing document. Ophthalmologic Drugs Advisory Committee. June 17, 2011. Tarrytown, NY: Regeneron Pharmaceuticals, Inc.; 2011.VEGF Trap-Eye (aflibercept ophthalmic solution) briefing document. Ophthalmologic Drugs Advisory Committee. June 17, 2011. Tarrytown, NY: Regeneron Pharmaceuticals, Inc.; 2011.Rudge J.S., Holash J., Hylton D., et al. VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade. Proc. Natl. Acad Sci USA. 2007; 104 (47): 18363-70.Rudge J.S., Holash J., Hylton D., et al. VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade. Proc. Natl. Acad Sci USA. 2007; 104 (47): 18363-70.Holash J., Davis S., Papadopoulos N., et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA. 2002; 99 (17): 11393-8.Holash J., Davis S., Papadopoulos N., et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA. 2002; 99 (17): 11393-8.Papadopoulos N., Martin J., Ruan Q., et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012; 15 (2): 171-85.Papadopoulos N., Martin J., Ruan Q., et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012; 15 (2): 171-85.Manual for using the EYLEA® LP-003544 for medical purposes of January 20, 2017.Manual for using the EYLEA® LP-003544 for medical purposes of January 20, 2017.Li X., Lee C., Tang Z., et al. VEGF-B: a survival, or an angiogenic factor? Cell AdhMigr. 2009; 3 (4): 322-7.Li X., Lee C., Tang Z., et al. VEGF-B: a survival, or an angiogenic factor? Cell AdhMigr. 2009; 3 (4): 322-7.Rakic J.M., Lambert V., Devy L., et al. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2003; 44 (7): 3186-93.Rakic J.M., Lambert V., Devy L., et al. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2003; 44 (7): 3186-93.Carmeliet P., Moons L., Luttun A., et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat. Med. 2001; 7 (5): 575-83.Carmeliet P., Moons L., Luttun A., et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat. Med. 2001; 7 (5): 575-83.Stewart M.W., Rosenfield P.J. Predicted biological activity of intravitreal VEGF Trap. Br. J. Ophthalmol. 2008; 92 (5): 667-8.Stewart M.W., Rosenfield P.J. Predicted biological activity of intravitreal VEGF Trap. Br. J. Ophthalmol. 2008; 92 (5): 667-8.Fauser S., Schwabecker V., Muether P.S. Suppression of intraocular vascular endothelial growth factor during aflibercept treatment of age-related macular degeneration. Am. J. Ophthalmol. 2014; 158 (3): 532-6.Fauser S., Schwabecker V., Muether P.S. Suppression of intraocular vascular endothelial growth factor during aflibercept treatment of age-related macular degeneration. Am. J. Ophthalmol. 2014; 158 (3): 532-6.Muether P.S., Hermann M.M., Dröge K., et al. Long-term stability of vascular endothelial growth factor suppression time under ranibizumab treatment in age-related macular degeneration. Am. J. Ophthalmol. 2013; 156 (5): 989-93.Muether P.S., Hermann M.M., Dröge K., et al. Long-term stability of vascular endothelial growth factor suppression time under ranibizumab treatment in age-related macular degeneration. Am. J. Ophthalmol. 2013; 156 (5): 989-93.Muether P.S., Dröge K., Fauser S. Vascular endothelial growth factor suppression times in patients with diabetic macular oedema treated with ranibizumab. Br. J. Ophthalmol. 2014; 98: 179-81.Muether P.S., Dröge K., Fauser S. Vascular endothelial growth factor suppression times in patients with diabetic macular oedema treated with ranibizumab. Br. J. Ophthalmol. 2014; 98: 179-81.Sarwar S., Bakbak B., Sadiq M.A., et al. Fusion Proteins: Aflibercept (VEGF Trap-Eye). Dev Ophthalmol. 2016; 55: 282-94.Sarwar S., Bakbak B., Sadiq M.A., et al. Fusion Proteins: Aflibercept (VEGF Trap-Eye). Dev Ophthalmol. 2016; 55: 282-94.Heier J.S., Brown D.M., Chong V., et al. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012; 119 (12): 2537-48.Heier J.S., Brown D.M., Chong V., et al. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012; 119 (12): 2537-48.Schmidt-Erfurth U., Kaiser P.K., Korobelnik J.F., et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six week results of the VIEW studies. Ophthalmology. 2014; 121 (1): 193-201.Schmidt-Erfurth U., Kaiser P.K., Korobelnik J.F., et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six week results of the VIEW studies. Ophthalmology. 2014; 121 (1): 193-201.CATT Research Group. Martin D.F., Maguire M.G., Ying G.S. et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 2011; 364: 1897-908.CATT Research Group. Martin D.F., Maguire M.G., Ying G.S. et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 2011; 364: 1897-908.Martin D.F., Maguire M.G., Fine S.L., et al. Comparison of Age related Macular Degeneration Treatments Trials (CATT) Research Group. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012; 119: 1388-98.Martin D.F., Maguire M.G., Fine S.L., et al. Comparison of Age related Macular Degeneration Treatments Trials (CATT) Research Group. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012; 119: 1388-98.Korobelnik J-F., Do D.V., Schmidt-Erfurth U., et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014; 121 (11): 2247-54.Korobelnik J-F., Do D.V., Schmidt-Erfurth U., et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014; 121 (11): 2247-54.Brown D.M., Schmidt-Erfurth U., Do D.V., et al. Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology. 2015; 122 (10): 2044-52.Brown D.M., Schmidt-Erfurth U., Do D.V., et al. Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology. 2015; 122 (10): 2044-52.Heier J.S., Korobelnik J.F., Brown D.M., et al. Intravitreal Aflibercept for Diabetic Macular Edema: 148-Week Results from the VISTA and VIVID Studies. Ophthalmology. 2016 Nov.; 123 (11): 2376-85.Heier J.S., Korobelnik J.F., Brown D.M., et al. Intravitreal Aflibercept for Diabetic Macular Edema: 148-Week Results from the VISTA and VIVID Studies. Ophthalmology. 2016 Nov.; 123 (11): 2376-85.DRCRnet, Wells J.A., Glassman A.R., et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N. Engl. J. Med. 2015; 372 (13): 1193-203.DRCRnet, Wells J.A., Glassman A.R., et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N. Engl. J. Med. 2015; 372 (13): 1193-203.Korobelnik J.F. Optimal Dose and Cost-effectiveness of Ranibizumab Treatment of Diabetic Macular Oedema. European Ophthalmic Review. 2016; 10 (2): 125-31.Korobelnik J.F. Optimal Dose and Cost-effectiveness of Ranibizumab Treatment of Diabetic Macular Oedema. European Ophthalmic Review. 2016; 10 (2): 125-31.Wells J.A., Glassman M.S., Avala A.R., et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trials. Ophthalmology. 2016; 123 (6): 1351-9.Wells J.A., Glassman M.S., Avala A.R., et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trials. Ophthalmology. 2016; 123 (6): 1351-9.Available at: http://www.peervoice.com/journal-club-decipheringlatest- data-improve-dme-treatment-choice.Available at: http://www.peervoice.com/journal-club-decipheringlatest- data-improve-dme-treatment-choice.Jampol L.M., Glassman A.R., Bressler N.M., et al. JAMA Ophthalmol. Published online October 6, 2016.Jampol L.M., Glassman A.R., Bressler N.M., et al. JAMA Ophthalmol. Published online October 6, 2016.Boyer D., Heier J., Brown DM., et al. Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology. 2012; 119 (5 May): 1024-32.Boyer D., Heier J., Brown DM., et al. Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology. 2012; 119 (5 May): 1024-32.Holz F.G., Roider J., Ogura Y., et al. VEGF Trap-Eye for macular oedema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br. J. Ophthalmol. 2013; 97 (3): 278-84.Holz F.G., Roider J., Ogura Y., et al. VEGF Trap-Eye for macular oedema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br. J. Ophthalmol. 2013; 97 (3): 278-84.Brown D.M., Heier J.S., Clark W.L., et al. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am. J. Ophthalmol. 2013; 155 (3): 429-37.Brown D.M., Heier J.S., Clark W.L., et al. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am. J. Ophthalmol. 2013; 155 (3): 429-37.Korobelnik J.F., Holz F.G., Roider J., et al. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study. Ophthalmology. 2014; 121 (1): 202-8.Korobelnik J.F., Holz F.G., Roider J., et al. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study. Ophthalmology. 2014; 121 (1): 202-8.Heier J.S., Clark W.L., Boyer D.S., et al. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology. 2014; 121 (7): 1414-20.Heier J.S., Clark W.L., Boyer D.S., et al. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology. 2014; 121 (7): 1414-20.Ogura Y., Roider J., Korobelnik J.F., et al. Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion: 18-month results of the phase 3 GALILEO study. Am. J. Ophthalmol. 2014; 158 (5): 1032-8.Ogura Y., Roider J., Korobelnik J.F., et al. Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion: 18-month results of the phase 3 GALILEO study. Am. J. Ophthalmol. 2014; 158 (5): 1032-8.Campochiaro P.A., Clark W.L., Boyer D.S., et al. Intravitreal aflibercept for macular edema following branch retinal vein occlusion: the 24-week results of the VIBRANT study. Ophthalmology. 2015; 122 (3 Mar.): 538-44.Campochiaro P.A., Clark W.L., Boyer D.S., et al. Intravitreal aflibercept for macular edema following branch retinal vein occlusion: the 24-week results of the VIBRANT study. Ophthalmology. 2015; 122 (3 Mar.): 538-44.Clark W.L., Boyer D.S., Heier J.S., et al. Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: 52-Week Results of the VIBRANT Study. Ophthalmology. 2016; 123 (2 Feb.): 330-6.Clark W.L., Boyer D.S., Heier J.S., et al. Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: 52-Week Results of the VIBRANT Study. Ophthalmology. 2016; 123 (2 Feb.): 330-6.Ikuno Y., Ohno-Matsui K., Wong T.Y., et al. Intravitreal Aflibercept Injection in Patients with Myopic Choroidal Neovascularization. The MYRROR Study. Ophthalmology. 2015; 122: 1220-7.Ikuno Y., Ohno-Matsui K., Wong T.Y., et al. Intravitreal Aflibercept Injection in Patients with Myopic Choroidal Neovascularization. The MYRROR Study. Ophthalmology. 2015; 122: 1220-7.

The authors declare that there are no conflicts of interest present.