The XTEND study, the largest real-world prospective evaluation of intravitreal aflibercept (IVT-AFL) for neovascular age-related macular degeneration (nAMD), has released two-year results from its UK cohort, demonstrating the sustained effectiveness of proactive treatment regimens in routine clinical practice. The study, published in Nature, highlights both functional and anatomical improvements in patients treated with IVT-AFL 2mg.
Visual Acuity Improvements
The UK patient population experienced a mean change in best-corrected visual acuity (BCVA) from baseline of +3.4 letters at Month 12 and +1.3 letters at Month 24. Notably, patients with a baseline BCVA of less than 35 letters achieved a more significant improvement of +6.6 letters. While these gains were slightly lower than those observed in the global XTEND population (+4.3 and +2.3 letters at Months 12 and 24, respectively) and the VIEW randomized controlled trial (+7.6 letters by Week 96), a substantial proportion of patients with high baseline BCVA (≥70 letters) maintained their vision over the two-year period. The number of patients achieving ≥70 letters, the visual acuity required to legally drive in the UK, increased from 22.8% at baseline to 36.3% at Month 24.
Anatomical Outcomes
The study also demonstrated a significant improvement in central subfield thickness (CST) from baseline, with reductions of -105 μm at both Month 12 and Month 24. These CST improvements were consistent with those observed in the global XTEND cohort (-106 μm and -109 μm at Months 12 and 24, respectively) but less pronounced than in the VIEW study (-128 μm at Week 96). The researchers attribute this difference to the lower number of injections received by the UK cohort (7.4 and 10.7 injections by Months 12 and 24, respectively) compared to the VIEW trial (11.2 injections at Week 96).
Impact of COVID-19
The study period coincided with the COVID-19 pandemic, during which the Royal College of Ophthalmologists (RCOphth) issued guidance recommending that nAMD patients be maintained on 8-weekly anti-VEGF injections without clinical review. This resulted in a significant proportion of patients receiving IVT-AFL at 8-week intervals. While the number of injections administered in the UK and Global cohorts were similar, the strict COVID-19 restrictions reduced the flexibility for physicians to adjust treatment intervals based on individual patient needs. As the study mentions, "the T&E treatment paradigm may be preferred in routine clinical practice, as it allows the clinician to adjust treatment according to the needs of the patient, thereby, reducing treatment burden whilst achieving and maintaining robust visual gains."
Safety Profile
The safety profile of IVT-AFL in the UK cohort over 24 months was consistent with previous observational studies. Four deaths were reported during the study, coinciding with the COVID-19 pandemic.
Study Limitations
The authors acknowledge several limitations inherent to the observational, prospective design of the XTEND study, including the lack of randomization, the non-controlled design, and the heterogenous patient population. Information bias may have been introduced due to variations in visual acuity assessment methods. Additionally, all prescribing decisions were made at the discretion of the treating clinician, leading to diverse treatment patterns and variability in outcomes. The study also experienced some non-completion and missing data, which is typical in real-world evidence studies.
Clinical Implications
Despite these limitations, the XTEND study provides valuable real-world evidence supporting the effectiveness of proactive IVT-AFL treatment regimens for nAMD. The findings suggest that both fixed and treat-and-extend regimens can achieve clinically meaningful improvements in functional and anatomical outcomes, even during challenging circumstances such as the COVID-19 pandemic. The study underscores the importance of individualized treatment approaches to optimize visual outcomes and reduce treatment burden for patients with nAMD.
