Monitoring Ocular Drug Therapy by Analysis of Aqueous Samples

Peter A. Campochiaro, David F. Choy, Diana V. Do, Gulnar Hafiz, Syed Mahmood Shah, Quan D. Nguyen, Roman Rubio, Joseph R. Arron

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49 Scopus citations

Abstract

Objective: To assess the value of sampling aqueous humor for measurement of potential molecular targets and for pharmacokinetic analysis. Design: Substudy within the context of clinical trials. Participants: Forty patients with macular edema caused by central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO), 11 patients with diabetic macular edema (DME), and 8 patients with neovascular age-related macular degeneration (NVAMD). Methods: Assays for potential molecular targets were performed on aqueous samples from patients participating in drug studies (CRVO, BRVO, and DME) or patients receiving standard care (NVAMD). Ranibizumab levels were measured in patients with CRVO or BRVO after the first and second injections of ranibizumab. Main Outcome Measures: Aqueous levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and ranibizumab. Results: Aqueous levels of VEGF were significantly higher in patients with DME than in patients with CRVO, which were significantly higher than those in patients with BRVO. Patients with NVAMD had aqueous VEGF levels in an intermediate range, significantly higher than those in patients with BRVO. One month after the second injection of ranibizumab, 27 of 39 patients with vein occlusions had no residual edema; mean aqueous levels of IL-6, IL-1β, and TNF-α were not greater in patients with residual edema; this provides a blueprint for definitive studies with larger cohorts. There was no significant difference in aqueous ranibizumab levels 1 month after the first injection of 0.5 mg versus injection of 0.3 mg, but 1 month after the second injection ranibizumab levels were significantly higher in eyes injected with 0.5 mg. There were substantial differences in levels among patients, but levels in the same patient at months 1 and 2 were highly correlated. No significant difference in aqueous ranibizumab levels was detected between phakic and pseudophakic patients who received the same dose. Conclusions: These data suggest that aqueous samples are useful for investigating potential involvement of molecular targets in various disease processes and for pharmacokinetic or pharmacodynamic studies. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Original languageEnglish (US)
Pages (from-to)2158-2164
Number of pages7
JournalOphthalmology
Volume116
Issue number11
DOIs
StatePublished - Nov 1 2009

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ASJC Scopus subject areas

  • Ophthalmology

Cite this

Campochiaro, P. A., Choy, D. F., Do, D. V., Hafiz, G., Shah, S. M., Nguyen, Q. D., Rubio, R., & Arron, J. R. (2009). Monitoring Ocular Drug Therapy by Analysis of Aqueous Samples. Ophthalmology, 116(11), 2158-2164. https://doi.org/10.1016/j.ophtha.2009.04.038