Recommendations of the treat-and-extend regimen for neovascular age-related macular degeneration: 2020 updates

Authors

  • Alvin KH Kwok Hong Kong Sanatorium & Hospital
  • Wai-Ching Lam Department of Ophthalmology, The University of Hong Kong
  • Angie HC Fong Hong Kong Eye Hospital
  • Nicholas SK Fung Department of Ophthalmology, The University of Hong Kong
  • Mary Ho Department of Ophthalmology & Visual Sciences, Prince of Wales Hospital
  • Lawrence PL Iu Department of Ophthalmology & Visual Sciences, Prince of Wales Hospital
  • Callie KL Ko Department of Ophthalmology, Tung Wah Eastern Hospital
  • Shaheeda Mohamed Hong Kong Eye Hospital
  • Danny SC Ng Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong
  • Heather HY Tang Department of Ophthalmology, United Christian Hospital
  • Ian YH Wong Hong Kong Sanatorium & Hospital
  • Raymond LM Wong Hong Kong C-MER Dennis Lam & Partners Eye Center
  • Timothy YY Lai Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong
  • CT Tsoi

Keywords:

Macular degeneration, Retina, Subretinal fluid

Abstract

Anti-vascular endothelial growth factor (anti-VEGF) treatment is the gold standard of care for neovascular age-related macular degeneration (nAMD). To strike a balance between treatment burden and vision improvement, a treat-and-extend (T&E) regimen is the preferred approach to administer anti-VEGF treatment.

To facilitate implementation of the T&E regimen for nAMD in Hong Kong, a panel of retinal experts, with the support of Bayer Healthcare, held an online meeting on 15 September 2020 to discuss the latest published evidence and clinical experiences regarding the suitability and safety of anti-VEGF agents in the T&E regimen, patient selection, retreatment criteria, considerations for treatment discontinuation, and barriers to implementing the T&E regimen.

Compared with the 2019 recommendations, this 2020 version contains several major updates including differentiation of fluid compartments in retreatment criteria, additional considerations for patient selection, streamlined criteria for treatment cessation, and applicability of the T&E regimen in patients with polypoidal choroidal vasculopathy (PCV).

These updated recommendations are expected to facilitate implementation of the T&E regimen for nAMD including PCV in Hong Kong, with the aims of improving patient visual acuity, lowering treatment burden, and facilitating service capacity planning over the long term.

References

Cao Y. Positive and negative modulation of angiogenesis by VEGFR1 ligands. Sci Signal 2009;2:re1.

Chirco KR, Sohn EH, Stone EM, Tucker BA, Mullins RF. Structural and molecular changes in the aging choroid: implications for age-related macular degeneration. Eye (Lond) 2017;31:10-25.

Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2:e106-16.

LCQ14: Treatment for age-related macular degeneration. Available from: https://www.info.gov.hk/gia/general/201003/10/P201003100138_print.htm. Accessed 8 December 2020.

Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419-31.

Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-44.

Schmidt-Erfurth U, Chong V, Loewenstein A, et al. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br J Ophthalmol 2014;98:1144-67.

Chakravarthy U, Evans J, Rosenfeld PJ. Age related macular degeneration. BMJ 010;340:c981.

Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 2007;143:566-83.

Holz FG, Amoaku W, Donate J, et al. Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study. Ophthalmology 2011;118:663-71.

Jaffe GJ, Ying GS, Toth CA, et al. Macular morphology and visual acuity in year five of the comparison of age-related macular degeneration treatments trials. Ophthalmology 2019;126:252-60.

Chakravarthy U, Harding SP, Rogers CA, et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. Lancet 2013;382:1258-67.

Lanzetta P, Loewenstein A; Vision Academy Steering Committee. Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal antivascular endothelial growth factor therapy of macular diseases. Graefes Arch Clin Exp Ophthalmol 2017;255:1259-73.

Nguyen V, Vaze A, Fraser-Bell S, et al. Outcomes of suspending VEGF inhibitors for neovascular age-related macular degeneration when lesions have been inactive for 3 months. Ophthalmol Retina 2019;3:623-8.

Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, 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;120:2292-9.

Holz FG, Tadayoni R, Beatty S, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol 2015;99:220-6.

Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Maguire MG, Martin DF, et al. Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular agerelated macular degeneration: the comparison of age-related macular degeneration treatments trials. Ophthalmology 2016;123:1751-61.

Weber M, Velasque L, Coscas F, Faure C, Aubry I, Cohen SY. Effectiveness and safety of intravitreal aflibercept in patients with wet age-related macular degeneration treated in routine clinical practices across France: 12-month outcomes of the RAINBOW study. BMJ Open Ophthalmol 2019;4:e000109.

Richard G, Monés J, Wolf S, et al. Scheduled versus pro re nata dosing in the VIEW trials. Ophthalmology 2015;122:2497-503.

Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology 2014;121:193-201.

Silva R, Berta A, Larsen M, et al. Treat-and-extend versus monthly regimen in neovascular age-related macular degeneration: results with ranibizumab from the TREND study. Ophthalmology 2018;125:57-65.

Wykoff CC, Ou WC, Brown DM, et al. Randomized trial of treat-and-extend versus monthly dosing for neovascular age-related macular degeneration: 2-year results of the TREX-AMD Study. Ophthalmol Retina 2017;1:314-21.

Kim LN, Mehta H, Barthelmes D, Nguyen V, Gillies MC. Meta-analysis of real-world outcomes of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration. Retina 2016;36:1418-31.

Wong IY, Ng DS, Fung NS, et al. Treat-and-extend regimen for management of neovascular age-related macular degeneration: recommendations from the Hong Kong Retina Expert Panel. Hong Kong J Ophthalmol 2019;23:15-9.

Guymer RH, Markey CM, McAllister IL, 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;126:723-34.

Ohji M, Takahashi K, Okada AA, 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: a randomized controlled trial. Adv Ther 2020;37:1173-87.

Ross AH, Downey L, Devonport H, et al. Recommendations by a UK expert panel on an aflibercept treat-and-extend pathway for the treatment of neovascular age-related macular degeneration. Eye (Lond) 2020;34:1825-34.

Dugel PU, Holz FG, Hamilton RD, Jhaveri CD, Singh RP, Weissgerber G. Visual and expanded anatomical outcomes for brolucizumab versus aflibercept in patients with neovascular AMD: 96-week data from HAWK and HARRIER. Poster presented at the 13th Asia-Pacific Vitreo-Retina Society Congress; Shanghai, China. 22-24 November 2019.

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.

Eichenbaum DA. Association between early vision-related quality of life outcomes and anatomic dryness response in neovascular age-related macular degeneration (nAMD): a post-hoc analysis of VIEW trials. Invest Ophthalmol Vis Sci 2019;60:90.

Zarbin MA, Stoilov I, Hill L. Anti-VEGF resistant subretinal fluid is associated with reduced risk of macular atrophy and better visual acuity: drug-induced choroidal new vessel homeostasis? Invest Ophthalmol Vis Sci 2020;61:3503.

Souied EH, Holz FG, Hykin PG, et al. Efficacy of intravitreal aflibercept treat-and-extend regimen over 2 years for neovascular age-related macular degeneration: ARIES Study. Invest Ophthalmol Vis Sci 2020;61:4210.

Li A, Rieveschl NB, Conti FF, et al. Long-term assessment of macular atrophy in patients with age-related macular degeneration receiving anti-vascular endothelial growth factor. Ophthalmol Retina 2018;2:550-7.

Munk MR, Ceklic L, Ebneter A, Huf W, Wolf S, Zinkernagel MS. Macular atrophy in patients with long-term anti-VEGF treatment for neovascular age-related macular degeneration. Acta Ophthalmol 2016;94:e757-e764.

Sadda SR, Guymer R, Monés JM, Tufail A, Jaffe GJ. Antivascular endothelial growth factor use and atrophy in neovascular age-related macular degeneration: systematic literature review and expert opinion. Ophthalmology 2020;127:648-59.

Mehta H, Tufail A, Daien V, et al. Real-world outcomes in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor inhibitors. Prog Retin Eye Res 2018;65:127-46.

Hospital Authority. Drug formulary. Available from: https://www.ha.org.hk/hadf/Portals/0/Docs/HADF_List/EL_Full%20Ver_170708.pdf. Accessed 19 February 2021.

Novartis. Novartis completes safety review and initiates update to the Beovu® prescribing information worldwide. Available from: https://www.novartis.com/news/novartiscompletes-safety-review-and-initiates-update-beovuprescribing-information-worldwide. Accessed 15 October 2020.

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;15:171-85.

Gaudreault J, Gunde T, Floyd HS, et al. Preclinical pharmacology and safety of ESBA1008, a single-chain antibody fragment, investigated as potential treatment for age related macular degeneration. Invest Ophthalmol Vis Sci 2012;53:3025.

U.S. Food and Drug Administration. Drug approval package: Beovu® (brolucizumab-dbll); non-clinical review(s). Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125Orig1s000PharmR.pdf. Accessed 15 October 2020.

Do DV, Rhoades W, Nguyen QD. Pharmacokinetic study of intravitreal aflibercept in humans with neovascular age-related macular degeneration. Retina 2020;40:643-7.

Krohne TU, Liu Z, Holz FG, Meyer CH. Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans. Am J Ophthalmol 2012;154:682-6.e2.

Holz FG, Dugel PU, Weissgerber G, et al. Single-chain antibody fragment VEGF inhibitor RTH258 for neovascular age-related macular degeneration: a randomized controlled study. Ophthalmology 2016;123:1080-9.

Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF trap. Br J Ophthalmol 2008;92:667-8.

Muether PS, Hermann MM, Dröge K, Kirchhof B, Fauser S. Long-term stability of vascular endothelial growth factor suppression time under ranibizumab treatment in age-related macular degeneration. Am J Ophthalmol 2013;156:989-93.e2.

Fauser S, Schwabecker V, Muether PS. Suppression of intraocular vascular endothelial growth factor during aflibercept treatment of age-related macular degeneration. Am J Ophthalmol 2014;158:532-6.

Rittenhouse K, Ezzine S, Eissing T, Janer D, Katz T, Arbour J. Investigating molecular features of aflibercept and brolucizumab to clarify clinical results through pharmacokinetic simulations. Poster presented at the 19th European Society of Retina Specialists Congress; Paris, France. 5-8 September 2019.

Plyukhova AA, Budzinskaya MV, Starostin KM, et al. Comparative safety of bevacizumab, ranibizumab, and aflibercept for treatment of neovascular age-related macular degeneration (AMD): a systematic review and network meta-analysis of direct comparative studies. J Clin Med 2020;9:1522.

ALTAIR study published confirming efficacy of EYLEA® treat and extend dosing regimens for patients with wet AMD. Available from: https://www.bayer.com/en/ca/news/canadaaltair-study-confirming-efficacy-eylear-treat-extend-dosing. Accessed 2 November 2021.

Woo SJ, Cho GE, Cho JH. Short-term efficacy and safety of ranibizumab for neovascular age-related macular degeneration in the real world: a post-marketing surveillance study. Korean J Ophthalmol 2019;33:150-66.

Kunimoto D, Yoon YH, Wykoff CC, et al. Efficacy and safety of Abicipar in neovascular age-related macular degeneration: 52-week results of phase 3 randomized controlled study. Ophthalmology 2020;127:1331-44.

Dugel PU, Singh RP, Koh A, et al. HAWK and HARRIER: ninety-six-week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2021;128:89-99.

Monés J, Srivastava SK, Jaffe GJ, et al. Risk of inflammation, retinal vasculitis, and retinal occlusion-related events with brolucizumab: post hoc review of HAWK and HARRIER. Ophthalmology 2021;128:1050-9.

Avery RL, Castellarin AA, Steinle NC, et al. Systemic pharmacokinetics and pharmacodynamics of intravitreal aflibercept, bevacizumab, and ranibizumab. Retina 2017;37:1847-58.

Kitchens JW, Do DV, Boyer DS, et al. Comprehensive review of ocular and systemic safety events with intravitreal aflibercept injection in randomized controlled trials. Ophthalmology 2016;123:1511-20.

Cheung CMG, Lai TYY, Ruamviboonsuk P, et al. Polypoidal choroidal vasculopathy: definition, pathogenesis, diagnosis, and management. Ophthalmology 2018;125:708-24.

Lee WK, Iida T, Ogura Y, et al. Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy in the PLANET Study: a randomized clinical trial. JAMA Ophthalmol 2018;136:786-93.

Wong TY, Ogura Y, Lee WK, et al. Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy: two-year results of the aflibercept in polypoidal choroidal vasculopathy Study. Am J Ophthalmol 2019;204:80-9.

Ohji M, Kobayashi M, Okada AA, Terano Y, Takahashi K. Intravitreal aflibercept treat-and-extend dosing for wet age-related macular degeneration: ALTAIR 96-week results. Presentation at the 12th Asia-Pacific Vitreo-retina Society Congress; Seoul, South Korea. 14-16 December 2018.

Maruko I, Ogasawara M, Yamamoto A, et al. Two-year outcomes of treat-and-extend intravitreal aflibercept for exudative age-related macular degeneration: a prospective study. Ophthalmol Retina 2020;4:767-76.

Hosokawa M, Morizane Y, Hirano M, et al. One-year outcomes of a treat-and-extend regimen of intravitreal aflibercept for polypoidal choroidal vasculopathy. Jpn J Ophthalmol 2017;61:150-8.

Morimoto M, Matsumoto H, Mimura K, Akiyama H. Two-year results of a treat-and-extend regimen with aflibercept for polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophthalmol 2017;255:1891-7.

Morizane-Hosokawa M, Morizane Y, Kimura S, et al. Impact of polyp regression on 2-year outcomes of intravitreal aflibercept injections: a treat-and-extend regimen for polypoidal choroidal vasculopathy. Acta Med Okayama 2018;72:379-85.

Downloads

Published

2021-11-11

How to Cite

1.
Kwok AK, Lam W-C, Fong AH, Fung NS, Ho M, Iu LP, Ko CK, Mohamed S, Ng DS, Tang HH, Wong IY, Wong RL, Lai TY, Tsoi C. Recommendations of the treat-and-extend regimen for neovascular age-related macular degeneration: 2020 updates. Hong Kong J Ophthalmol [Internet]. 2021Nov.11 [cited 2024Dec.5];25(2). Available from: https://hkjo.hk/index.php/hkjo/article/view/306

Issue

Section

Position Paper

Most read articles by the same author(s)

1 2 3 4 > >>