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An intravitreal device providing sustained release of cyclosporine and dexamethasone.

Publication ,  Journal Article
Enyedi, LB; Pearson, PA; Ashton, P; Jaffe, GJ
Published in: Curr Eye Res
May 1996

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 micrograms of cyclosporine labeled with 2 microCi 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) microgram/ml over 10 weeks. The average dexamethasone concentration over the 10 week period was 2.9 (+/- 0.9) micrograms/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.

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Published In

Curr Eye Res

DOI

ISSN

0271-3683

Publication Date

May 1996

Volume

15

Issue

5

Start / End Page

549 / 557

Location

England

Related Subject Headings

  • Vitreous Body
  • Vitreoretinopathy, Proliferative
  • Uveitis
  • Time Factors
  • Rabbits
  • Ophthalmology & Optometry
  • Male
  • Female
  • Drug Implants
  • Dexamethasone
 

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Enyedi, L. B., Pearson, P. A., Ashton, P., & Jaffe, G. J. (1996). An intravitreal device providing sustained release of cyclosporine and dexamethasone. Curr Eye Res, 15(5), 549–557. https://doi.org/10.3109/02713689609000766
Enyedi, L. B., P. A. Pearson, P. Ashton, and G. J. Jaffe. “An intravitreal device providing sustained release of cyclosporine and dexamethasone.Curr Eye Res 15, no. 5 (May 1996): 549–57. https://doi.org/10.3109/02713689609000766.
Enyedi LB, Pearson PA, Ashton P, Jaffe GJ. An intravitreal device providing sustained release of cyclosporine and dexamethasone. Curr Eye Res. 1996 May;15(5):549–57.
Enyedi, L. B., et al. “An intravitreal device providing sustained release of cyclosporine and dexamethasone.Curr Eye Res, vol. 15, no. 5, May 1996, pp. 549–57. Pubmed, doi:10.3109/02713689609000766.
Enyedi LB, Pearson PA, Ashton P, Jaffe GJ. An intravitreal device providing sustained release of cyclosporine and dexamethasone. Curr Eye Res. 1996 May;15(5):549–557.
Journal cover image

Published In

Curr Eye Res

DOI

ISSN

0271-3683

Publication Date

May 1996

Volume

15

Issue

5

Start / End Page

549 / 557

Location

England

Related Subject Headings

  • Vitreous Body
  • Vitreoretinopathy, Proliferative
  • Uveitis
  • Time Factors
  • Rabbits
  • Ophthalmology & Optometry
  • Male
  • Female
  • Drug Implants
  • Dexamethasone