Diabetic macular edema (DMO), a leading cause of vision loss in diabetic patients, affects a substantial and growing global population. Anti-vascular endothelial growth factor (VEGF) treatments, such as intravitreal aflibercept (IVT-AFL), have become first-line therapy. IVT-AFL offers a convenient treatment regimen, reducing the burden on patients and healthcare systems. Randomized controlled trials (RCTs) provide valuable data, but observational studies are crucial for understanding real-world effectiveness. The DRAKO study is the first UK-based prospective observational study to assess the effectiveness of standard-of-care IVT-AFL treatment in DMO patients across various centers. It aims to evaluate real-world outcomes, considering the variability in treatment adherence and local practices, offering a more representative picture of treatment efficacy compared to the highly controlled setting of RCTs.

Existing literature demonstrates the effectiveness of anti-VEGF treatments like IVT-AFL in improving visual acuity and anatomical parameters in DMO patients. However, most pivotal clinical trials (VIVID and VISTA) and observational studies (APOLLO) focused on patients with baseline visual acuity below 73 letters. Retrospective studies suggest lower injection frequencies and functional gains in real-world settings than those seen in RCTs. The relationship between baseline visual acuity and central subfield thickness (CST) and the response to anti-VEGF treatment is well-established, with greater improvements observed in patients with poorer baseline parameters. The need for a prospective, UK-based observational study like DRAKO is highlighted by the existing literature's limitations in capturing real-world treatment patterns and outcomes across diverse clinical practices.

DRAKO (NCT02850263) was a 24-month, prospective, observational, multicenter, non-randomized study. 750 patients with central-involving DMO were enrolled from 35 NHS hospitals across the UK between July 2016 and April 2018. Patients were divided into two cohorts: anti-VEGF treatment-naive (n=507) and non-treatment-naive (n=241). IVT-AFL treatment was administered according to local standard of care. Primary outcome measures were mean change from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) at month 12. Secondary and exploratory outcomes included changes in BCVA and CST stratified by baseline factors, vision-related quality of life (QoL) using the NEI VFQ-25, diabetic retinopathy (DR) score, glycated hemoglobin (HbA1c) levels, and the number of injections administered. Statistical analysis included descriptive statistics, frequency distributions, and assessment of correlations between letter gains/losses and injection numbers. Safety was also assessed.

At month 24, the treatment-naive cohort (C1) showed a mean change from baseline in BCVA of +10.7 letters and CST of -123.3 µm. The non-treatment-naive cohort (C2) showed a mean change from baseline in BCVA of +0.2 letters at 12 months and -0.3 letters at 24 months, and a CST change of -79.1 µm at 12 months and -91.6 µm at 24 months. In year 2, C1 and C2 patients received a mean of 3.7 and 4.3 injections, respectively. Patients with lower baseline BCVA and higher CST experienced the greatest improvements. High baseline QoL scores were maintained. DR assessments showed mostly stable or improved outcomes. Glycemic control, while good at baseline, could be improved. The correlation between the number of injections and visual acuity changes was low.

The DRAKO study confirms the effectiveness of IVT-AFL for DMO in real-world UK clinical practice, even with relatively low injection numbers. The maintenance of high baseline visual acuity and quality of life, along with continued anatomical improvements, highlight the treatment's positive impact. The observation that baseline measures were more predictive of outcomes than injection numbers suggests that treatment may be optimized by focusing on individualized patient needs and targeting treatment to achieve clinical goals. While the study showed high baseline visual acuity suggesting effective screening, suboptimal glycemic control provides an area for potential improvement to optimize patient outcomes.

The DRAKO study's 2-year findings reinforce the effectiveness of IVT-AFL in treating DMO in the UK. The maintenance of high baseline visual acuity and quality of life, coupled with continued anatomical improvements, supports the treatment's efficacy in real-world settings. However, exploring strategies for optimized glycemic control and individualized treatment approaches based on baseline factors could lead to further enhancements in patient care.

As with any observational study, DRAKO has limitations, including inconsistencies in treatment administration and the lack of defined clinical eligibility criteria. The inherent variability in real-world clinical practice might introduce confounders that limit the generalizability of findings. The study's prospective nature and large sample size across diverse centers mitigate these limitations to some extent.