Inflammatory ocular disease is an important cause of
blindness and uveitis accounts for 1.0% of blind patients
in Canada.¹ This disease can be particularly troublesome to
treat, because the nature of the causal factor or factors
and mechanisms of progressi n are usually unknown.
Non-specific anti - inflammatory agents have been used
orally and systemically with some success to treat
uveitis, ²⁻⁸ but they may produce serious side effects both
locally and elsewhere in the body.⁹̛¹²̛¹⁴ With prolonged
use tolerance to these drugs may develop , making them
ineffective. Recently a powerful immuno suppressive agent,
Cyclosporine (Cy), used orally and systemically in the
treatment of uveitis has shown promising results.¹⁶⁻¹⁹̛²⁸
However, its routine use is limited because of a narrow
therapeutic index and renal toxicity. Several studies have shown that subconjunctival injection of a number of antineoplastic agents enhanced
ocular absorption ²⁰⁻²⁴ in a traditional pharmacological
sanctuary,¹³̛¹⁴ and circumvented the associated systemic
side effects. Therefore, if Cy were administered
subconjunctivally it might be possible to avoid the side
effects associated with the oral and systemic routes, and
at the same time provide higher levels of Cy to the eye.
A protocol for the administration of Cy subconjunctivally was developed in New Zealand white rabbits, to study toxicity, ocular pharmacokinetics following equidose administration subconjunctivally and systemically and the effects of Cy on an animal model of uveitis. Subconjuntival administration of 5mg of Cy in O.lcc (Sandimmune I.V.(R) 50 mg/ml) weekly was found to be the maximum tolerated dose by the rabbitsˈ eye, and was superior to intravenous injection for ocular penetration while minimizing systemic exposure. The uveitis model showed that Cy was effective in reducing the inflammatory response and the earlier the application of Cy the milder the uveitis.
The results from our study support the contention that local administration of Cy would lead to higher levels of Cy absorption and circumvent the side effects of systemic administration. This may facilitate the routine use of Cy in ocular inflammatory disease. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/26422 |
| Date | January 1986 |
| Creators | Kalsi, Gursharan Singh |
| Publisher | University of British Columbia |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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