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L. H. Lombardi, S. Pasadhika, K. T. Galster, T. Diebel, D. Choi, S. R. Planck, J. T. Rosenbaum; Do Mydriatics Worsen Anterior Uveitis? Data From an Animal Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4746.
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Intraocular inflammation has been shown to be modulated in part through systemic cholinergic pathways mediated through the vagus nerve. Recent studies have demonstrated that cholinergic stimulation inhibits endotoxin-induced uveitis in rats (IOVS, 48:2719, 2007). However, in the clinical treatment of uveitis, current therapy includes anti-cholinergic agents such as atropine or cyclopentolate. This study was designed to assess whether anti-cholinergic therapy exacerbates uveitis.
Female Spraque-Dawley rats were injected intraperitoneally (IP) with 1500 micrograms per kilogram of lipopolysaccharide (LPS) (E. coli 055:B5) to induce acute anterior uveitis. Pilot studies were performed to determine the optimum dosage of this LPS preparation. The rats were divided into three cohorts (n=6); 1) control group with intraperitoneal (IP) saline at time 0 (T=0), and saline eye drops every 6 hours (q6hr); 2) intraperitoneal atropine (5mg/kg) at T=0, and saline drops q6hrs; or 3) IP saline at T=0, and atropine 1% eye drops q6hrs. Inflammation was measured by slit lamp biomicroscopic exam and graded for conjunctival and iris injection, anterior chamber (AC) cell count, AC fibrin, AC flare, and keratic precipitates. The rats were then euthanized and AC fluid was analyzed for cell counts and protein.
Anterior segment inflammation as measured by biomicroscopy, showed more inflammation in the intraperitoneal atropine group (p<0.1 by Wilcoxon rank sum using an average for each animal, p<0.03 based on each eye as an independent variable). The IP atropine group also had a 50% increase in average cell count, which was not statistically significant. Cell counts and protein analysis showed wide variability within each group. There was a trend toward increased inflammation in the topical atropine group, which did not reach statistical significance.
Systemic atropine may have the potential to alter the inflammatory response as seen by clinical exam in a model of acute endotoxin-induced uveitis in rats. Exacerbation of inflammation showed borderline statistical significance such that the study requires validation. However, topical atropine did not demonstrate the same effect. The data are reassuring with regard to the use of dilating drops in an inflamed eye, but the data also suggest that systemic medications with anti-cholinergic effects could potentially worsen uveitis.
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