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J. L. Simpson, C. Nien Shy, K. J. Flynn, S. Cherqui, D. J. Brown, J. V. Jester; Quantitative in vivo Confocal Microscopy Assessment of Topical Cysteamine Treatment in the Cystinosin Knockout Mouse. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4652.
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Cystinosin knockout mice (ctns-/-) develop cystine corneal crystals beginning at 3 months of age and increase in density until 7-12 months, at which time animals begin to succumb to the disease and corneas become scarred and neovascularized. The purpose of this study was to assess the ability of quantitative in vivo confocal microscopy to detect changes in crystal volume in ctns -/- corneas that undergo treatment with cysteamine eye drops compared to those that do not.
Five month old ctns-/- mice were used in this study. Twenty eyes of 10 ctns-/- mice were divided into 2 groups. Ten eyes received topical cysteamine eye drops 0.55% (Leiter Pharmacy, CA) qid for 4 weeks and 10 eyes were used as control. Scans in 4 different regions per eye were performed before and after the treatment using a tandem scanning confocal microscope. The volume of cystine crystals in the cornea was calculated before and after treatment using Metamorph Image Processing Software (Molecular Devices, Downington, PA). Stromal regions were extracted and threshold to include all high intensity pixels representing light scattering from the cystine crystals. Pixels within the threshold region were then counted for all planes in the image stack and the crystal volume recorded. The extracted stromal volume was calculated and the crystal volume was divided by the stromal volume multiplied by 100 to provide a % crystal volume index (CVI).
There was no significant difference in the CVI between untreated and treated groups at baseline (0.82% and 0.70% respectively, p=0.78). After 4 weeks, 3 eyes in the untreated group became scarred and could not be evaluated for crystal deposition. The remaining untreated eyes showed a significant 173% increase in the CVI (0.82% vs 1.41%, p≤0.04). In the cysteamine treated group, there was a 15% increase in the CVI (0.70% before and 0.83% after treatment respectively, p=ns) which was significantly less than the untreated group (p<0.0001).
Cysteamine eye drops appear to inhibit the progression of corneal cystinosis by preventing further accumulation of cystine crystals in the ctns-/- mouse. These findings are similar to those seen in humans with corneal cystinosis treated with cysteamine drops. Further development of the ctns -/- mouse model may allow for more rapid and cost effective screening of potential alternative therapies for corneal cystinosis.
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