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Editorial

Editorial on Treat-and-Extend Regimens for the Management of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy: Consensus and Recommendations from the Asia-Pacific Vitreo-retina Society

Mieler, William F. MD

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Asia-Pacific Journal of Ophthalmology: November-December 2021 - Volume 10 - Issue 6 - p 505-506
doi: 10.1097/APO.0000000000000454
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This review article from a consortium of 19 prominent authors from the Asia-Pacific region very nicely provides consensus recommendations from the Asia-Pacific Vitreo-retina Society (APVRS) regarding treat-and-extend (T&E) regimens for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). The results are intended to apply to the Asia-Pacific region, though have worldwide implications as well. The recommendations are based on a review of 27 studies from 31 publications, all containing at least 100 study eyes, identified through MEDLINE, EMBASE, and Cochrane databases, along with abstract databases from numerous worldwide ophthalmic organizations.

The recommendations are based on nAMD studies utilizing bevacizumab, ranibizumab, or aflibercept, and PCV studies utilizing aflibercept. All patients received at least 3 monthly loading doses of their respective anti–vascular endothelial growth factor (VEGF) agent, and when disease activity was felt to be stable, then the T&E treatment intervals could be extended by 2 to 4 weeks (up to 12 to 16 weeks) until an intraretinal fluid resolution was documented. Minimal subretinal fluid could be tolerated, if clinical conditions were stable. If intraretinal fluid returned, treatment intervals were shortened by a similar 2- to 4-week timeframe, and then could be re-extended once the fluid dissipated.

There typically are 3 approaches to the treatment of nAMD and PCV. All treatment regimens generally follow a loading dose of 3 or more monthly injections, and in that setting, one of the following regimens is employed: 1) a fixed dosing regimen employs treatment on a programmed schedule, generally every month or two, for a timeframe of at least 1 year; 2) a pro re nata (PRN) schedule requires routine, generally monthly appointments, with treatment applied only in the setting of active disease, while 3) a T&E regimen is started once the active disease process has been stabilized, and intervals between scheduled appointments and treatments are gradually extended by 2- to 4-week intervals. At each appointment, treatment is administered.

Worldwide in recent years, there does seem to be a preference toward T&E regimens,1,2 as this allows for the extension of treatment intervals, thereby potentially reducing the number of clinic visits, associated treatments and costs, in scenarios where resources may be limited.

Based on this review article, the authors likewise concur that T&E regimens are safe and efficacious for patients with nAMD and PCV, and these regimens can reduce the number of patent visits and minimalize the clinician and patient treatment burdens. They indicate that “meaningful visual outcomes” can be achieved. Previously published studies support this concept, in that studies such as TREND and CANTREAT3–5 show that T&E treatment regimens versus fixed monthly injections appear to offer comparable visual results. Even starting T&E regimens at week 52 versus week 16 as in the ARIES study, show comparable mean visual changes.6 Comparing T&E protocols with PRN dosing, generally shows more injections in the T&E protocols, with fewer patient visits, yet comparable vision.

I commend the authors for composing this impressive study on a very complex problem. It is difficult enough to get 19 authors to reach decisive conclusions on simple matters, yet alone, on very complex issues. The recommendations brought forth are based on up-to-date data and are very reasonable, especially for a region of the world, where in a number of areas, resources may be quite limited. This type of study aims to provide as much benefit for the majority of patients with nAMD and PCV. As indicated previously, the authors clearly indicate that they are trying to provide “meaningful visual outcomes” for their patients.

Of course, it is very important to acknowledge potential limitations of a review article such as this, especially with the relative paucity of head-to-head type of follow-up regimens (fixed, PRN, T&E) in the setting of nAMD and/or PCV. However, the authors have nicely summarized the trials that do exist. Comparing studies is also challenging, since studies have used different criteria to define disease activity (amount of subretinal and/or intraretinal fluid, timeframe to accumulation of such fluid, etc), and have had differing timeframes for follow-up evaluations. The authors of this review have not attempted to indicate if there is any difference in treatment outcomes based on the specific anti-VEGF agent which had been employed in the nAMD studies. Also, there is no level 1 data as to recommendations of how or when to proceed with treatment or monitoring beyond the 12- to 16-week T&E interval timeframe. The authors do suggest that perhaps with two 16-week timeframes and no disease activity, treatment could be indefinitely suspended, albeit with continued monitoring. The role of photodynamic therapy (PDT), especially in the setting of PCV, perhaps may still need to be integrated into treatment regimens, at least on occasion. Finally, the recent (and still ongoing) COVID-19 pandemic has made studies challenging in terms of missed appointments and follow-up examinations, which has potentially altered clinical trial results.

In summary, it is important to keep in mind that once one has decided to employ T&E guidelines in the management of nAMD and PCV, these are generalized recommendations. Still, these recommendations seem very reasonable and well thought out, at least for the majority of patients. It is also important to keep in mind that new treatment modalities currently in the pipeline (port delivery system, gene therapy, new therapeutic drugs, impact of home monitoring OCT devices, etc)7 will hopefully offer even more effective treatment and outcomes in the future, perhaps being more cost-effective as well. Once again, I commend the authors for undertaking this complex and fascinating study.

REFERENCES

1. Daien V, Finger RP, Talks JS, et al. Evolution of treatment paradigms in neovascular age-related macular degeneration: a review of real-world evidence. Br J Ophthalmol 2021; 105:1475–1479. Online ahead of print. doi:10.1136/bjophthalmol-2020-317434.
2. Stone T. ASRS Preferences and Trends Membership Survey. Chicago, IL: American Society of Retina Specialists; 2010; https://www.asrs.org
3. 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. Ophthalmol 2018; 125:57–65.
4. Kertes PJ, Galic IJ, Greve M, et al. Canadian treat-and-extend analysis trial with ranibizumab in patients with neovascular age-related macular disease: one-year results of the randomized Canadian treat-and-extend analysis trial with ranibizumab study. Ophthalmol 2019; 126:841–848.
5. Kertes PJ, Galic IJ, Greve M, et al. Efficacy of a treat-and-extend regimen with ranibizumab in patients with neovascular age-related macular disease: a randomized clinical trial. JAMA Ophthalmol 2020; 138:244–250.
6. Mitchell P, Souied EH, Midena E, et al. Efficacy of intravitreal aflibercept administered using treat-and-extend regimen over 2 years in patients with neovascular age-related macular degeneration: 1-year ARIES results. Invest Ophthalmol Vis Sci 2019; 60:117.
7. Samanta A, Aziz AA, Jhingan M, et al. Emerging Therapies in Neovascular Age-Related Macular Degeneration in 2020. Asia Pac J Ophthalmol (Phila) 2020; 9:250–259.
Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.