Herausforderungen bei der Behandlung der neovaskulären altersbedingten Makuladegeneration

Zusammenfassung

Die altersbedingte Makuladegeneration (AMD) ist eine der Hauptursachen für Visusbeeinträchtigung und Erblindung von Menschen über 60 Jahren in entwickelten Ländern. Während für die trockene Spätform derzeit keine effektiven Therapieoptionen existieren, kann ein Fortschreiten der neovaskulären AMD (nAMD) bei einer regulären Behandlung mittels intravitrealer Applikation von Anti-VEGF-Substanzen zumeist verhindert werden. Neben den zugelassenen Wirkstoffen Ranibizumab, Aflibercept und seit Kurzem Brolucizumab werden andere Wirkstoffe wie Bevacizumab häufig Off-Label angewandt, um Kosten einzusparen. Auch das Behandlungsintervall wurde mehrfach weiterentwickelt, um die Frequenz der Injektionen bei Visuserhalt zu reduzieren und somit Kliniken und Patienten zu entlasten. Nach fix vorgegebenen Injektionsabständen etablierte sich das Pro-re-nata-Regime, bei dem anhand von festgelegten Kriterien in monatlichen Abständen entschieden wird, ob eine Injektion verabreicht wird. Bei dem Treat-and-extend-Protokoll erhalten Patienten an jedem Termin eine Injektion und die Abstände zwischen den Injektionen werden abhängig von klinischen Ergebnissen verändert. Das Observe-and-plan-Regime erlaubt als Erweiterung des Treat-and-extend-Protokolls eine blockweise Festlegung der Injektionsabstände für jeweils 3 aufeinanderfolgende Injektionen. Leider konnten die Ergebnisse in Real-World-Studien bei keinem der genannten Behandlungsschemata an die der Zulassungsstudien heranreichen. Hohe Terminanzahl und Angst vor dem Injektionsverfahren stellen Belastungen für Patienten dar. Angehörige beklagen Produktivitäts- und Einkommensverluste durch regelmäßige Betreuung der Patienten. Nicht zuletzt sind Gesundheitssysteme weltweit von den steigenden Behandlungszahlen und dem damit verbundenen Aufwand sowie den Kosten betroffen. Die Therapie der nAMD ist eine Errungenschaft der modernen Medizin, die stetig evaluiert und überarbeitet werden muss, um Patienten trotz Herausforderungen bestmöglich zu therapieren.

Schlüsselwörter

altersbedingte Makuladegeneration - choroidale Neovaskularisation - intravitreale Therapie - Gesundheitssystem

Publication History

Received: 06 October 2020

Accepted: 27 February 2021

Article published online:
01 July 2021

• References/Literatur

• 1 Flaxman SR, Bourne RRA, Resnikoff S. et al. Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. Lancet Glob Health 2017; 5: e1221-e1234 DOI: 10.1016/S2214-109X(17)30393-5.
• 2 Colijn JM, Buitendijk GHS, Prokofyeva E. et al. Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future. Ophthalmology 2017; 124: 1753-1763 DOI: 10.1016/j.ophtha.2017.05.035.
• 3 Schmidt-Erfurth UM, Richard G, Augustin A. et al. Guidance for the treatment of neovascular age-related macular degeneration. Acta Ophthalmol Scand 2007; 85: 486-494 DOI: 10.1111/j.1600-0420.2007.00979.x.
• 4 Boyle J, Vukicevic M, Koklanis K. et al. Experiences of patients undergoing repeated intravitreal anti-vascular endothelial growth factor injections for neovascular age-related macular degeneration. Psychol Health Med 2018; 23: 127-140 DOI: 10.1080/13548506.2016.1274040.
• 5 Baxter JM, Fotheringham AJ, Foss AJE. Determining patient preferences in the management of neovascular age-related macular degeneration: A conjoint analysis. Eye (Lond) 2016; 30: 698-704 DOI: 10.1038/eye.2016.18.
• 6 Grzybowski A, Told R, Sacu S. et al. 2018 Update on Intravitreal Injections: Euretina Expert Consensus Recommendations. Ophthalmologica 2018; 239: 181-193 DOI: 10.1159/000486145.
• 7 Sacu S, Michels S, Prager F. et al. Randomised clinical trial of intravitreal Avastin vs. photodynamic therapy and intravitreal triamcinolone: long-term results. Eye (Lond) 2009; 23: 2223-2227 DOI: 10.1038/eye.2008.423.
• 8 Maberley D. Pegaptanib for neovascular age-related macular degeneration. Issues Emerg Health Technol 2005; (76) 1-4 DOI: 10.1016/j.ajo.2005.02.003.
• 9 VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.). Chakravarthy U, Adamis AP, Cunningham jr. ET. et al. Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration. Ophthalmology 2006; 113: 1508.e1-1508.e25 DOI: 10.1016/j.ophtha.2006.02.064.
• 10 Brown DM, Kaiser PK, Michels M. et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006; 355: 1432-1444 DOI: 10.1056/NEJMoa062655.
• 11 Rosenfeld PJ, Brown DM, Heier JS. et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006; 355: 1419-1431 DOI: 10.1056/NEJMoa054481.
• 12 Heier JS, Brown DM, Chong V. et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 2012; 119: 2537-2548 DOI: 10.1016/j.ophtha.2012.09.006.
• 13 Martin DF, Maguire MG, Ying GS. et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 2011; 364: 1897-1908 DOI: 10.1056/NEJMoa1102673.
• 14 Bro T, Derebecka M, Jørstad ØK. et al. Off-label use of bevacizumab for wet age-related macular degeneration in Europe. Graefes Arch Clin Exp Ophthalmol 2020; 258: 503-511 DOI: 10.1007/s00417-019-04569-8.
• 15 Parikh R, Pirakitikulr N, Chhablani J. et al. A Multinational Comparison of Anti-Vascular Endothelial Growth Factor Use: The United States, the United Kingdom, and Asia-Pacific. Ophthalmol Retina 2019; 3: 16-26 DOI: 10.1016/j.oret.2018.08.002.
• 16 Singh SR, Dogra A, Stewart M. et al. Intravitreal Ziv-Aflibercept: Clinical Effects and Economic Impact. Asia Pac J Ophthalmol (Phila) 2017; 6: 561-568 DOI: 10.22608/APO.2017263.
• 17 Khanna S, Komati R, Eichenbaum DA. et al. Current and upcoming anti-VEGF therapies and dosing strategies for the treatment of neovascular AMD: A comparative review. BMJ Open Ophthalmol 2019; 4: e000398 DOI: 10.1136/bmjophth-2019-000398.
• 18 Ammar MJ, Hsu J, Chiang A. et al. Age-related macular degeneration therapy: a review. Curr Opin Ophthalmol 2020; 31: 215-221 DOI: 10.1097/ICU.0000000000000657.
• 19 Hufendiek K, Pielen A, Framme C. [Strategies of Intravitreal Injections with Anti-VEGF: “Pro re Nata versus Treat and Extend”]. Klin Monbl Augenheilkd 2018; 235: 930-939 DOI: 10.1055/s-0042-122340.
• 20 Mantel I, Niderprim SA, Gianniou C. et al. Reducing the clinical burden of ranibizumab treatment for neovascular age-related macular degeneration using an individually planned regimen. Br J Ophthalmol 2014; 98: 1192-1196 DOI: 10.1136/bjophthalmol-2013-304556.
• 21 Eleftheriadou M, Gemenetzi M, Lukic M. et al. Three-Year Outcomes of Aflibercept Treatment for Neovascular Age-Related Macular Degeneration: Evidence from a Clinical Setting. Ophthalmol Ther 2018; 7: 361-368 DOI: 10.1007/s40123-018-0139-5.
• 22 Rofagha S, Bhisitkul RB, Boyer DS. et al. 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.
• 23 Berg K, Roald AB, Navaratnam J. et al. An 8-year follow-up of anti-vascular endothelial growth factor treatment with a treat-and-extend modality for neovascular age-related macular degeneration. Acta Ophthalmol 2017; 95: 796-802 DOI: 10.1111/aos.13522.
• 24 Ozkaya A, Alagoz C, Garip R. et al. The role of indocyanine green angiography imaging in further differential diagnosis of patients with nAMD who are morphologically poor responders to ranibizumab in a real-life setting. Eye (Lond) 2016; 30: 958-965 DOI: 10.1038/eye.2016.71.
• 25 Ramos MS, Xu LT, Singuri S. et al. Patient-Reported Complications after Intravitreal Injection and Their Predictive Factors. Ophthalmol Retina 2020; DOI: 10.1016/j.oret.2020.09.024.
• 26 Falavarjani KG, Nguyen QD. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature. Eye (Lond) 2013; 27: 787-794 DOI: 10.1038/eye.2013.107.
• 27 Rosenfeld PJ, Browning DJ. Reply to Comment on: “Is this a 737 Max Moment for Brolucizumab?”. Am J Ophthalmol 2020; 223: 446-447 DOI: 10.1016/j.ajo.2020.06.034.
• 28 Daien V, Nguyen V, Essex RW. et al. Incidence and Outcomes of Infectious and Noninfectious Endophthalmitis after Intravitreal Injections for Age-Related Macular Degeneration. Ophthalmology 2018; 125: 66-74 DOI: 10.1016/j.ophtha.2017.07.005.
• 29 Droege KM, Muether PS, Hermann MM. et al. 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.
• 30 Chen X, Seth RK, Rao VS. et al. Effects of music therapy on intravitreal injections: A randomized clinical trial. J Ocul Pharmacol Ther 2012; 28: 414-419 DOI: 10.1089/jop.2011.0257.
• 31 Weyer-Wendl H, Walter P. Financial burden and quality of life of informal caregivers of patients with wet age-related macular degeneration. Health Econ Rev 2016; DOI: 10.1186/s13561-016-0116-4.
• 32 Hanemoto T, Hikichi Y, Kikuchi N. et al. 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: e0189035 DOI: 10.1371/journal.pone.0189035.
• 33 Williams G. IVT injections: health policy implications. Rev Ophthalmol 2014; 21: 62-64
• 34 Schwabe U, Paffrath D, Ludwig WD, Klauber J. Hrsg. Arzneiverordnungs-Report 2019. Berlin: Springer; 2019
• 35 Prenner JL, Halperin LS, Rycroft C. et al. Disease Burden in the Treatment of Age-Related Macular Degeneration: Findings from a Time-and-Motion Study. Am J Ophthalmol 2015; 160: 725-731.e1 DOI: 10.1016/j.ajo.2015.06.023.
• 36 Mulligan K, Seabury SA, Dugel PU. et al. Economic Value of Anti-Vascular Endothelial Growth Factor Treatment for Patients with Wet Age-Related Macular Degeneration in the United States. JAMA Ophthalmol 2019; 138: 40-47 DOI: 10.1001/jamaophthalmol.2019.4557.
• 37 Hollingworth W, Jones T, Reeves BC. et al. A longitudinal study to assess the frequency and cost of antivascular endothelial therapy, and inequalities in access, in England between 2005 and 2015. BMJ Open 2017; 7: e018289 DOI: 10.1136/bmjopen-2017-018289.
• 38 Starr MR, Barkmeier AJ, Engman SJ. et al. Telemedicine in the Management of Exudative Age-Related Macular Degeneration within an Integrated health care System. Am J Ophthalmol 2019; 208: 206-210 DOI: 10.1016/j.ajo.2019.03.021.
• 39 Andonegui J, Aliseda D, Serrano L. et al. Evaluation of a telemedicine model to follow up patients with exudative age-related macular degeneration. Retina 2016; 36: 279-284 DOI: 10.1097/IAE.0000000000000729.
• 40 Holekamp NM. Moving From Clinic to Home: What the Future Holds for Ophthalmic Telemedicine. Am J Ophthalmol 2018; 187: xxviii-xxxv DOI: 10.1016/j.ajo.2017.11.003.
• 41 Rim TH, Cheng CY, Kim DW. et al. A nationwide cohort study of cigarette smoking and risk of neovascular age-related macular degeneration in East Asian men. Br J Ophthalmol 2017; 101: 1367-1373 DOI: 10.1136/bjophthalmol-2016-309952.
• 42 Treder M, Eter N. [Chances of Artificial Intelligence and Big Data for the Diagnosis and Treatment of Age-related Macular Degeneration]. Klin Monbl Augenheilkd 2019; 236: 1418-1422 DOI: 10.1055/a-1012-2036.
• 43 Grassmann F, Mengelkamp J, Brandl C. et al. A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography. Ophthalmology 2018; 125: 1410-1420 DOI: 10.1016/j.ophtha.2018.02.037.
• 44 Schmidt-Erfurth U, Vogl WD, Jampol LM. et al. Application of Automated Quantification of Fluid Volumes to Anti–VEGF Therapy of Neovascular Age-Related Macular Degeneration. Ophthalmology 2020; 127: 1211-1219 DOI: 10.1016/j.ophtha.2020.03.010.
• 45 Hahn P, Eliott DE. 2020 Global Trends in Retina Survey. Am Soc Retin Spec 2020. Accessed May 5, 2021 at: https://www.asrs.org/content/documents/2020-global-trends-in-retina-survey-highlights-for-website.pdf
• 46 van Asten F, Michels CTJ, Hoyng CB. et al. The cost-effectiveness of bevacizumab, ranibizumab and aflibercept for the treatment of age-related macular degeneration–A cost-effectiveness analysis from a societal perspective. PLoS One 2018; 13: e0197670 DOI: 10.1371/journal.pone.0197670.
• 47 Cohen D. CCGs win right to offer patients Avastin for wet AMD. BMJ 2018; 362: k4035 DOI: 10.1136/bmj.k4035.
• 48 Simcock P, Kingett B, Mann N. et al. A safety audit of the first 10 000 intravitreal ranibizumab injections performed by nurse practitioners. Eye (Lond) 2014; 28: 1161-1164 DOI: 10.1038/eye.2014.153.
• 49 Toth CA, Decroos FC, Ying GS. et al. Identification of fluid on optical coherence tomography by treating ophthalmologists versus a reading center in the comparison of age-related macular degeneration treatments trials. Retina 2015; 35: 1303-1314 DOI: 10.1097/IAE.0000000000000483.
• 50 Bogunovic H, Waldstein SM, Schlegl T. et al. Prediction of Anti-VEGF Treatment Requirements in Neovascular AMD Using a Machine Learning Approach. Invest Ophthalmol Vis Sci 2017; 58: 3240-3248 DOI: 10.1167/iovs.16-21053.