Pharmacokinetics of pars plana intravitreal injections versus microcannula suprachoroidal injections of bevacizumab in a porcine model
Open accessAbstract
PURPOSE: To compare the pharmacokinetics and tissue response between intravitreal and microcannulation injections into the suprachoroidal space using bevacizumab. METHODS: Sixty-two pigs were studied. Either a pars plana intravitreal bevacizumab or a viscoelastic-enhanced microcannula suprachoroidal injection was performed with either 1.25 mg (group 1) or 3 mg (group 2). In group 1, six animals were euthanatized at 0.5, 7, 30, 60, 90, and 120 days after injection (n = 36). In group 2, six animals were euthanatized at 0.5, 7, 14, and 32 days (n = 24). Eyes were enucleated, dissected, and snap-frozen, or they were fixed for histology. Analysis of drug tissue levels was performed at two separate laboratories using masked specimens. RESULTS: Both laboratories were confirmatory. Intravitreal bevacizumab pharmacokinetics demonstrated a gradual decline in tissue levels over 30 to 60 days in both groups 1 and 2. In addition, suprachoroidal bevacizumab tissue levels declined rapidly and were not measurable at or beyond 7 days. Vitreitis and granulomatous vasculitis were noted in 7 of 30 intravitreal injection eyes. Immunohistology suggested a distinctive drug distribution. CONCLUSIONS: Direct intravitreal injection of bevacizumab has a more sustained pharmacologic profile than does a similar dose delivered to the suprachoroidal space. Intravitreal injections distributed more to the inner retina, whereas suprachoroidal delivery occurred primarily at the choroid, retinal pigment epithelium, and photoreceptor outer segments. Sustained release formulation of larger biological molecules should be considered to optimize suprachoroidal delivery. Inflammation from injections is granulomatous, seen only with intravitreal injections, and may result from either an altered immune response or a dose-related effect.
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Bevacizumab (149 kDa) has been shown to effectively diffuse into the choroid, RPE, and photoreceptors through the suprachoroidal route.
“bevacizumab (149 kDa) has been shown to effectively diffuse into the choroid, RPE, and photoreceptors through this route [306].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [306]
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- Authors
- Olsen, T. W., Feng, X., Wabner, K., Csaky, K., Pambuccian, S., & Cameron, J. D.
- Affiliations
- University of Minnesota (US)
- National Eye Institute (US)
- Mayo Clinic (US)
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2011-06-30
- Volume
- 52
- Issue
- 7
- Pages
- 4749
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC3175963
- OpenAlex
- W1963720039
- Cited by
- 106
- References
- 26
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 10 · 2020: 8 · 2019: 5 · 2018: 9 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 8 · 2013: 8 · 2012: 5
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Research to Prevent Blindness
- Emory University
- University of Minnesota
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal and Macular Surgery
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- bevacizumab, intravitreal injection, suprachoroidal injection, pharmacokinetics, tissue drug distribution, sustained drug release, vitritis, granulomatous vasculitis, inner retina, choroid, retinal pigment epithelium, photoreceptor outer segments, porcine model, anti-VEGF therapy
- MeSH terms
- Bevacizumab, Animals, Antibodies, Monoclonal, Catheterization, Choroid, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Follow-Up Studies, Immunity, Cellular, Macular Degeneration, Miniaturization, Swine, Treatment Outcome, Retinal Pigment Epithelium, Retinal Photoreceptor Cell Outer Segment, Intravitreal Injections, Antibodies, Monoclonal, Humanized
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