Original articlePenetration of a Topically Administered Anti–Tumor Necrosis Factor Alpha Antibody Fragment into the Anterior Chamber of the Human Eye
Section snippets
Study Design
This interventional cohort study examined the intraocular penetration, biodistribution, safety, and apparent penetration coefficient (as primary outcomes of the study) of ESBA105 applied topically to 1 eye of otherwise healthy patients recruited from 2 eye clinics in Switzerland who were to undergo cataract surgery (cohorts I–III) or combined cataract surgery and vitrectomy owing to epiretinal fibroplasias (cohort IV). Cohorts I, II, and IV used an open-label, single-arm design, but patients in
Patient Disposition and Demographics
In total, 139 patients throughout Switzerland consented to be included in the study, which was initiated on December 9, 2008, and was completed on June 18, 2010. After screening examination, 60 patients were excluded owing to positive tuberculosis test (n = 43), previously unknown health problems (n = 7), withdrawal of consent (n = 7), or other reasons (n = 3). Overall participant flow is shown in Figure 1 (available online at http://aaojournal.org), and demographics are shown in Table 1. For
Discussion
The therapeutic efficacy of an intraocularly injected antibody fragment—ranibizumab, which is approved for the treatment of wet age-related macular degeneration, diabetic macular edema, and macular edema after retinal vein occlusion—has already been demonstrated, but this study is the first to our knowledge demonstrating therapeutic intraocular levels of an antibody fragment in humans after topical administration. Two different ESBA105 topical dosing regimens—8 hourly preoperative doses on the
Acknowledgments
The authors thank Alfons Schwarz as the Clinical Trial Manager for overseeing this study, and Mrs Edith Manuel, the study nurse at the Luzerner Kantonsspital. Jennifer Klem, PhD, provided medical writing assistance in drafting the manuscript, which was funded by Alcon Laboratories, Inc.
References (24)
- et al.
Mechanisms involved in the side effects of glucocorticoids
Pharmacol Ther
(2002) - et al.
Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye
J Pharm Sci
(1998) - et al.
Antigen-independent selection of stable intracellular single-chain antibodies
FEBS Lett
(2001) - et al.
Antigen-independent selection of intracellular stable antibody frameworks
Methods
(2004) - et al.
Molecular weight of recombinant human tumor necrosis factor-alpha
J Biol Chem
(1987) - et al.
Ocular complications of topical, peri-ocular, and systemic corticosteroids
Curr Opin Ophthalmol
(2000) - et al.
Topical ocular delivery of NSAIDs
AAPS J [serial online]
(2008) The role of NSAIDs in the management of postoperative ophthalmic inflammation
Drugs
(2007)Remicade [prescribing information]
(2011)Humira [prescribing information]
(2012)
Ranibizumab versus bevacizumab for the treatment of neovascular age-related macular degeneration
Curr Opin Ophthalmol
A protocol for the retina surgeon's safe initial intravitreal injections
Clin Ophthalmol
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Manuscript no. 2012-1307.
Financial Disclosure(s): The authors have made the following disclosures:
Dominik Escher: Employee, Stock Options—ESBATech.
Peter Lichtlen: Employee, Stock Options—ESBATech.
Annette Schmidt: Employee, Stock Options—ESBATech.
Supported by ESBATech, an Alcon Biomedical Research Unit (a member of the Novartis corporate group) located in Zurich, Switzerland. The sponsor participated in the design of the study, conducting the study, data collection, data management, data analysis, interpretation of the data, and preparation, review, and approval of the manuscript.