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

Abstract

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.

Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations

“…It also must be taken into account that these studies were performed in animal models and that its extrapolation to humans lacks of enough knowledge. However, it seems to be a general decrease in the half-life in humans and might affect the efficacy of the intravitreal drug, although this aspect is still under investigation [54].…”

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

“…While effective at controlling neovascularisation, vascular leakage and other pathological changes associated with retinal vascular diseases, anti-VEGF agents also have their Table 1 Available anti-VEGF compounds and their properties [28]. To date, alternative methods of administration have been unsuccessful.…”

“…However, anti-VEGF compounds have short half-lives in the posterior segment of the eye, necessitating the need for multiple injections. The half-life of current available anti-VEGF compounds range from~5-8 days (Table 1) [28]. This need for frequent injections not only exposes patients to the risk of endophthalmitis but also results in high treatment dropout rates.…”

A Randomized, Double-Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab versus Aflibercept in Patients with Visual Impairment due to Diabetic Macular Edema (KITE)

“…Bevacizumab (Avastin ® ) is an IgG1 antibody with a molecular weight of 149 kDa, while Aflibercept is a fusion protein weighing 97-115 kDa. Both are relatively large molecules compared to Ranibizumab, an antibody fragment with a molecular weight of 48 kDa, and Brolucizumab, only 26 kDa [3].…”