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

ABSTRACT

Introduction: 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.

KEYWORDS:

• Aflibercept (Eylea)
• anti-VEGF
• bevacizumab (Avastin)
• clearance
• half life
• metabolism
• pegaptanib sodium (Macugen)
• pharmacokinetics
• ranibizumab (Lucentis)
• vitrectomized
• vitrectomy

Article highlights

• The majority of available anti-VEGF pharmacokinetic data is from animal models. There are concerns about whether results of these studies can be extrapolated to human eyes due to anatomical and physiological differences, lack of animal disease models, and variability in study methodology.

• Faster vitreous clearance rates for medications in vitrectomized eyes have previously been observed for a number of pharmacological substances, and studies seem to confirm reduced half-life and efficacy of anti-VEGF agents in vitrectomized eyes.

• Increased clearance of anti-VEGF in vitrectomized eyes may have an important impact on dosing regimens (fixed, pro re nata, treat-and-extend), as well as the clinical burden of more frequent injections and monitoring of patients.

• It is difficult to draw definite conclusions from the available data in vitrectomized human eyes, as the majority of studies were retrospective, uncontrolled, and based on small numbers of patients.

• There is high inter-individual variation in functional and anatomical response to intravitreous anti-VEGF agents. Reasons for this are likely to be complex, and not simply associated with different molecular configurations of drugs.

This box summarizes key points contained in the article.

Acknowledgements

Thank you to Miss Rupal Morjaria for help in obtaining original papers from literature search.

Declaration of interest

M Edington has received Bayer travel grants, V Chong is employee for Boehringer Ingelheim and consultant for Quantel Medical. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. A reviewer on this manuscript has disclosed research support from Allergan and Regeneron as well as serving as a consultant for Bayer.

Additional information

Funding

This paper is not funded.