An intravitreal device providing sustained release of cyclosporine and dexamethasone

Laura B. Enyedi, P. Andrew Pearson, Paul Ashton, Glenn J. Jaffe

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Purpose. A device that releases cyclosporine and dexamethasone into the eye for extended periods of time might be beneficial in diseases such as proliferative vitreoretinopathy and uveitis. In this study we examine the pharmacokinetics and toxicity of cyclosporine and dexamethasone combined in an intravitreal sustained-release device and the toxicity of a similar device containing only dexamethasone in rabbits. Methods. Rabbits were divided into three groups for (1) evaluation of the drug tissue levels and device release kinetics following implantation of a device containing 100 μg of cyclosporine labeled with 2 μCi of 3H-cyclosporine and 2 mg of dexamethasone; (2) evaluation of the toxicity of this intravitreal device; and (3) evaluation of the toxicity of a similar device containing 2 mg of dexamethasone only. Cyclosporine was measured using a scintillation counter and dexamethasone was measured by high pressure liquid chromatography (HPLC). Toxicity was evaluated by electroretinography, clinical examination, and light microscopy. Results. Vitreous concentrations of cyclosporine (± standard deviation) averaged 0.06 (± 0.02) μg/ml over 10 weeks. The average dexamethasone concentration over the 10 week period was 2.9 (± 0.9) μg/ml. Devices containing cyclosporine and dexamethasone released each drug at rates similar to devices containing cyclosporine or dexamethasone alone. Devices containing both cyclosporine and dexamethasone caused reversible depressions in the b-wave amplitude of photopic and scotopic electroretinograms (ERG's). There was no evidence of toxicity associated with the devices containing dexamethasone only. There was no drug-related toxicity evident on clinical or histopathologic examination of eyes with devices containing the combination of cyclosporine and dexamethasone or dexamethasone alone. Conclusions. We conclude that the device maintains potentially therapeutic levels of both cyclosporine and dexamethasone in the vitreous. Reversible electroretinographic abnormalities are attributable to cyclosporine. A sustained-release device containing cyclosporine and dexamethasone may be useful for reducing inflammation in diseases such as proliferative vitreoretinopathy and uveitis.

Original languageEnglish
Pages (from-to)549-557
Number of pages9
JournalCurrent Eye Research
Issue number5
StatePublished - 1996

Bibliographical note

Funding Information:
This study was supported by the Heed Ophthalmic Fellowship (PAP), the Adler Foundation, Research to Prevent Blindness, EY09106 (GJJ) and EYO 9973 (PA, GJJ).


  • Cyclosporine
  • Dexamethasone
  • Intravitreal drug delivery
  • Proliferative vitreoretinopathy
  • Rabbit
  • Uveitis

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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