Japanese researchers have demonstrated that a treat-and-extend (TAE) regimen using aflibercept (Eylea, Regeneron Pharmaceuticals) successfully maintained baseline visual acuity (VA) and reduced central macular thickness (CMT) over a five-year period in patients with neovascular age-related macular degeneration (nAMD).
The multicenter study, led by Dr. Iori Wada from Kyushu University and Kyushu Medical Center in Fukuoka, Japan, provides important real-world evidence for the long-term efficacy of aflibercept in treating this sight-threatening condition.
Study Design and Patient Characteristics
Researchers retrospectively evaluated 126 consecutive treatment-naïve nAMD patients (126 eyes) who received a loading dose of at least three monthly intravitreal aflibercept (IVA) injections followed by a treat-and-extend regimen. Of these patients, 63 completed the full five-year follow-up period.
At baseline, patients presented with a mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) of 0.42 ± 0.036. The mean central macular thickness was 326.9 ± 10.8 μm, and the greatest linear dimension (GLD) was 4,037.3 ± 188.5 μm.
Key Visual Outcomes
The study revealed an interesting pattern in visual acuity outcomes. While BCVA significantly improved in all AMD cases (including type 3 macular neovascularization [MNV], type 1 or 2 MNV, and polypoidal choroidal vasculopathy) during the first year of treatment, it gradually declined thereafter, eventually returning to baseline levels.
By the five-year mark, mean BCVA had changed from 0.42 ± 0.036 logMAR at baseline to 0.36 ± 0.055 logMAR—a difference that did not reach statistical significance. This finding suggests that aflibercept treatment helped maintain vision over the long term, preventing the progressive vision loss typically associated with untreated nAMD.
Anatomical Improvements and Treatment Frequency
More encouragingly, the average CMT decreased significantly following treatment initiation and remained reduced throughout the entire follow-up period. This anatomical improvement indicates effective control of the underlying disease process.
The study also demonstrated that patients required fewer injections from the second year onward, with treatment frequency gradually decreasing during the follow-up period. This finding has important implications for patient burden and healthcare resource utilization.
Predictors of Long-Term Outcomes
Through multivariable analysis, researchers identified pretreatment GLD as the only independent risk factor for better vision after five years of treatment (p = 0.0024). Specifically, a smaller GLD was associated with superior visual outcomes, providing clinicians with a potential prognostic indicator.
Treatment Discontinuation and Recurrence
The IVA treatment was discontinued in 36 (44%) cases during the follow-up period. However, 12 of these eyes (33%) experienced disease recurrence. Notably, significant recurrence was observed in patients who had received a higher total number of aflibercept injections, suggesting a possible correlation between treatment intensity and recurrence risk.
Macular Atrophy Risk
An important secondary finding was that macular atrophy—a potential complication of long-term anti-VEGF therapy—was significantly more likely to develop in cases with occult MNV with subretinal hemorrhage compared to other forms of nAMD. This observation may help clinicians identify patients at higher risk for this complication.
Clinical Implications
Dr. Wada and colleagues concluded that "aflibercept monotherapy using the TAE regimen maintained baseline VA and reduced CMT for 5 years in Japanese patients with nAMD. A smaller GLD was independently associated with better VA."
These findings provide valuable real-world evidence supporting the long-term efficacy of aflibercept using a treat-and-extend approach, which aims to optimize treatment intervals while maintaining disease control. The study addresses an important knowledge gap, as previous large clinical trials of anti-VEGF drugs have reached varying conclusions about their ability to maintain or improve visual acuity over extended periods.
For ophthalmologists managing patients with nAMD, this study offers reassurance that a TAE regimen with aflibercept can provide sustained anatomical benefits and vision preservation over a five-year period, while potentially reducing treatment burden after the initial year of therapy.
