Pharmacokinetics of intravitreal anti-VEGF drugs in vitrectomized versus non-vitrectomized eyes

The review aims to discuss effects of vitrectomy on pharmacokinetics of anti-vascular endothelial growth factor (anti-VEGF) agents, and attempt to provide treatment guidance. Areas covered: An Embase search was conducted using the terms 'anti-VEGF', 'pegaptanib', 'ranibizumab', 'bevacizumab', 'aflibercept', 'pharmacokinetics', 'half-life', 'clearance', 'metabolism', 'vitrectomy', 'vitrectomized'. Published data regarding the pharmacokinetic properties of the above drugs and the effect of vitrectomy in animal and human eyes was reviewed. Expert opinion: There are limited studies on the effect of vitrectomy on pharmacokinetic properties of anti-VEGF drugs in human eyes. Most animal models indicate that intravitreal drugs have reduced half-lives and increased clearance in vitrectomized eyes. More studies, with carefully selected design, are required to explore this further. However, considering existing evidence, it is important to consider vitreous and lens status when monitoring and treating patients. Authors recommend fixed monthly dosing, with low threshold for increasing frequency of injection even to 2-weekly if required, as well as close monitoring of patients to establish individual response. There may be an increased role for slow-release steroid implants in vitrectomized eyes with DME or RVO. Longer acting substances currently under development such as brolucizumab or abicipar pegol, may become the treatment of choice in the future.