Difficulty in Assessing the Systemic Adverse Effects of Intravitreal Anti–Vascular Endothelial Growth Factor Therapy

JAMA Ophthalmology Published online June 1, 2023

中文摘要

作者提到了Zafar等人進行的一項研究，該研究使用退伍軍人健康管理局數據庫評估接受玻璃體內anti-VEGF治療的2型糖尿病患者的全身不良事件。該研究發現與未接受治療的患者相比，接受anti-VEGF治療的患者在心肌梗塞、腦血管疾病和腎臟疾病等不良事件的風險增加。

作者承認已有文獻記錄了接受系統性anti-VEGF治療的癌症患者出現高血壓、蛋白尿和血栓栓塞等不良效應。然而，關於玻璃體內anti-VEGF治療的潛在全身不良效應的辯論仍在進行中，存在支持和反駁這些效應的證據。

評論討論了評估這些不良效應的研究面臨的挑戰，包括樣本量有限、難以找到適當的活性對照組、可能存在選擇偏差、時間混淆以及需要因果推斷。

作者建議使用時間更新的生存模型(time-updating survival modeling)，確保anti-VEGF劑量與不良效應之間的必要關聯。此外，提出使用糖尿病併發症嚴重程度指數作為評估潛在糖尿病嚴重程度並減少時間混淆的工具。

評論最後強調了使用各種研究設計進行進一步研究以達成對於玻璃體內anti-VEGF治療的全身不良效應的共識的重要性。

English Abstract

The author mentions a study conducted by Zafar and colleagues, which used the Veterans Health Administration database to assess systemic adverse events in patients with type 2 diabetes who received intravitreal anti-VEGF therapy. The study found an increased risk of adverse events, such as acute myocardial infarction, cerebrovascular disease, and kidney disease, in patients who received anti-VEGF therapy compared to unexposed patients.

The author acknowledges that adverse effects, including hypertension, proteinuria, and thromboembolic events, have been documented in patients with cancer who received systemic anti-VEGF therapy. However, the debate regarding the potential systemic adverse effects of intravitreal anti-VEGF therapy is ongoing, and evidence both supporting and contradicting these effects exists.

The commentary discusses the challenges in conducting studies to evaluate these adverse effects, including limited sample sizes, the difficulty in finding suitable active comparators, the potential for indication bias, confounding by time, and the need for causal inference.

The author suggests using time-updating survival modeling to ensure the necessary proximity of the anti-VEGF dose to the adverse effect. Additionally, the Diabetes Complications Severity Index is proposed as a tool to assess underlying diabetes severity and reduce confounding by time.

The commentary concludes by highlighting the importance of conducting further research using various study designs to achieve a consensus on the systemic adverse effects of intravitreal anti-VEGF therapy.