Treatment for neovascular age-related macular degeneration: reasonable expectations of physicians and patients
DOI: 10.32364/2311-7729-2021-21-3-169-174
A.B. Durasov
Ophthalmology Clinic "Octopus" ("Tochka zreniya" Ltd), Samara, Russian Federation
Neovascular age-related macular degeneration (nAMD) is a progressive chronic multifactorial disease requiring long-term, lifelong anti-VEGF therapy. Treatment outcomes are not always in line with the results of randomized clinical trials and do not meet the expectations for therapy whose success is assessed differently by patients and physicians. Good functional and anatomical results are expected from antivasoproliferative therapy under certain conditions, e.g., accurate evaluation of some patient characteristics (baseline visual acuity, type of choroidal neovascularization, comorbidities, status of retinal fluid and its differentiation), timely (as early as possible) treatment initiation after verifying diagnosis, and strict adherence to a proactive personalized "Treat-and-Extend" (T&E) regimen that implies a required number of injections with individual intervals. Poor adherence to treatment (non-compliance or nonpersistence of anti-VEGF therapy) significantly affects treatment outcomes in real-world clinical practice. This paper reviews criteria which predict the response to antivasoproliferative therapy and improving treatment adherence. The authors describe four fundamental principles to be met by an ideal regimen of anti-VEGF therapy for nAMD.
Keywords: neovascular age-related macular degeneration, nAMD, "Treat-and-Extend", T&E, adherence, nonpersistence, anti-VEGF.
For citation: Durasov A.B. Treatment for neovascular age-related macular degeneration: reasonable expectations of physicians and patients. Russian Journal of Clinical Ophthalmology. 2021;21(3):169–174 (in Russ.). DOI: 10.32364/2311-7729-2021-21-3-169-174.
About the author:
Andrey B. Durasov — C. Sc. (Med.), ophthalmic surgeon; ORCID iD 0000-0002-5555-4217.
Ophthalmology Clinic "Octopus" ("Tochka zreniya" Ltd), 63, Karbyshev str., Samara, 443067, Russian Federation.
Contact information: Andrey B. Durasov, e-mail: andrey_durasov@mail.ru.
Financial Disclosure: the author has not a financial or property interest in any material or method mentioned.
There is no conflict of interests.
Received 02.08.2021.
2. Brown D.M., Kaiser P.K., Michels M. et al. ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1432–1444. DOI: 10.1056/NEJMoa062655.
3. 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):2537–2548.
4. Zhang K., Zhang L., Weinreb R.N. Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucomaNat Rev Drug Discov. 2012;11(7):541–559.
5. Rofagha S., Bhisitkul R.B., Boyer D.S. et al. 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.
6. Rasmussen A., Bloch S.B., Fuchs J. et al. A 4-year longitudinal study of 555 patients treated with ranibizumab for neovascular age-related macular degeneration. Ophthalmology. 2013;120:2630–2636.
7. Amoaku W.M., Chakravarthy U., Gale R. Defining response to anti-VEGF therapies in neovascular AMD. Eye. 2015;29:721–731. DOI: 10.1038/eye.2015.48.
8. Westborg I., Albrecht S., Rosso A. Risk for low visual acuity after 1 and 2 years of treatment with ranibizumab or bevacizumab for patients with neovascular age-related macular degeneration. Retina. 2017;37:2035–2046.
9. Ying G.-S., Maguire M.G., Daniel E. Association of Baseline Characteristics and Early Vision Response with Two-Year Vision Outcomes in the Comparison of AMD Treatments Trials (CATT) et al. Ophthalmology. 2015;122:2523–2531.
10. Stoller G.L., Kokame G.T., Dreyer R.F. et al. Patterns of Early and Delayed Visual Response to Ranibizumab Treatment for Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. 2016;134(5):545-553.
11. Li J., Xu J., Chen Y. et al. Efficacy comparison of intravitreal anti-VEGF therapy for three subtypes of neovascular age-related macular degeneration: a systematic review and meta-analysis. Hindawi Journal of Ophthalmology. 2018 Oct 23;2018:1425707. DOI: 10.1155/2018/1425707.
12. Ebneter A., Michels S., Pruenteet C. et al. Two-year outcomes of intravitreal aflibercept in a Swiss routine treat and extend regimen for patients with neovascular age-related macular degeneration. Sci Rep. 2020;10(1):20256. DOI: 10.1038/s41598-020-76354-1.
13. Sadda S.R., Tuomi LL., Ding B. et al. Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2018;125:878–886. DOI: 10.1016/j.ophtha.2017.12.026.
14. Фурсова А.Ж., Дербенева А.С., Васильева М.А. и др. Роль различных типов ретинальной жидкости как прогностических биомаркеров в выборе режима антиангиогенной терапии при возрастной макулярной дегенерации. Вестник офтальмологии. 2020;136(6):219–226. [Fursova A.Zh., Derbeneva A.S., Vasilyeva M.A. et al. The role of different types of retinal "fluid" as prognostic biomarkers in the choice of antiangiogenic therapy regimen for age-related macular degeneration. Bulletin of Ophthalmology. 2020;136(6):219–226. DOI: 10.17116/oftalma2020136062219 (in Russ.)].
15. Waldstein S.M., Simander C., Staurenghi G. et al. Morphology and Visual Acuity in Aflibercept and Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration in the VIEW Trials Ophthalmology. 2016;123:1521–1529. DOI: 10.1016/j.ophtha.2016.03.037.
16. Jaffe G.J., Martin D.F., Toth C.A. et al. Macular morphology and visual acuity in the comparison of age-related macular degeneration treatments trials. Ophthalmology. 2013;120(9):1860–1870. DOI: 10.1016/j.ophtha.2013.01.073.
17. Guymer R.H., Markey C.M., McAllister I.L. et al. Tolerating Subretinal Fluid in Neovascular Age-Related Macular Degeneration Treated with Ranibizumab Using a Treat-and-Extend Regimen: FLUID Study 24-Month Results. Ophthalmology. 2019;126(5):723–734. DOI: 10.1016/j.ophtha.2018.11.025.
18. Lim J.H., Wickremasinghe S.S., Xie J. Delay to Treatment and Visual Outcomes in Patients Treated With Anti-Vascular Endothelial Growth Factor for Age-Related Macular Degeneration. Am J Ophthalmol. 2012;153:678–686. DOI: 10.1016/j.ajo.2011.09.013.
19. Muether P.S., Hoerster R., Hermann M.M. et al. Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2013;251:453–458. DOI: 10.1007/s00417-012-2038-0.
20. Framme C., Eter N., Hamacher T. et al. Aflibercept for Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in Germany. Twelve-Month Outcomes of PERSEUS. Ophthalmology Retina. 2018;2:539–549. DOI: 10.1016/J.ORET.2017.09.017.
21. Файзрахманов Р.Р. Режимы назначения анти-VEGF-препаратов при терапии неоваскулярной возрастной макулярной дегенерации. Вестник офтальмологии. 2018;134(6):107–115. [Fayzrakhmanov R.R. Regimens for prescribing anti-VEGF drugs in therapy neovascular age-related macular degeneration. Bulletin of Ophthalmology. 2018;134(6):107–115. DOI: 10.17116/OFTALMA2018134061105 (in Russ.)].
22. Астахов Ю.С., Нечипоренко П.А. Режимы назначения ингибиторов ангиогенеза при лечении пациентов с неоваскулярной возрастной макулярной дегенерацией. Офтальмологические ведомости. 2019;12(2):47–56. [Astakhov Yu.S., Nechiporenko P.A. Regimens for the appointment of angiogenesis inhibitors in the treatment of patients with age-related neovascular macular degeneration. Ophthalmological statements. 2019;12(2):47–56. DOI: 10.17816/OV12247-56 (in Russ.)].
23. Hanemoto T., Hikichi Y., Kikuchi N., Kozawa T. The impact of different anti-vascular endothelial growth factor treatment regimens on reducing burden for caregivers and patients with wet age-related macular degeneration in a single-center real-world Japanese setting. PLoS ONE. 2017;12(12):e0189035. DOI: 10.1371/journal.pone.0189035.
24. Ross A.H., Downey L., Devonport H. Recommendations by a UK expert panel on an aflibercept treat-andextend pathway for the treatment of neovascular age-related macular degeneration. Eye. 2020;34:1825–1834. DOI: 10.1038/S41433-019-0747-X.
25. Lanzetta P., Loewenstein A. Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal anti–vascular endothelial growth factor therapy of macular diseases. Graefes Arch Clin Exp Ophthalmol. 2017;255:1259–1273. DOI: 10.1007/s00417-017-3647-4.
26. Okada M., Mitchell P., Finger R.P. et al. Nonadherence or Nonpersistence to Intravitreal Injection Therapy for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2021;128:234–247. DOI: 10.1016/j.ophtha.2020.07.060.
27. Droege K.M., Muether P.S., Hermann M.M. Adherence to ranibizumab treatment for neovascular age-related macular degeneration in real life. Graefes Arch Clin Exp Ophthalmol. 2013;251:1281–1284. DOI: 10.1007/s00417-012-2177-3.
28. Joko T., Nagai Y., Mori R. Patient Preferences for Anti-Vascular Endothelial Growth Factor Treatment for Wet Age-Related Macular Degeneration in Japan: A Discrete Choice Experiment. Patient Preference and Adherence. 2020;14:553–567. DOI: 10.2147/ppa.s228890.
29. Ohji M., Takahashi K., Okada A.A. et al. Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR. Adv Ther. 2020;37(3):1173–1187. DOI: 10.1007/s12325-020-01236-x.
30. Fauser S., Muether P.S. Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times. Br J Ophthalmol. 2016;0:1–5. DOI: 10.1136/bjophthalmol-2015-308264.
This work is licensed under a Creative Commons «Attribution» 4.0 License.
