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B. Fortune, L. Wang, G. Cull, G. A. Cioffi; Intravitreal Colchicine Causes Decreased Retinal Nerve Fiber Layer Thickness Measured by Scanning Laser Polarimetry but Not by Optical Coherence Tomography in Non-Human Primates. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2877.
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To test the hypothesis that longitudinal differences between scanning laser polarimetry (SLP) and optical coherence tomography (OCT) measurements of retinal nerve fiber layer thickness (RNFLT) are informative about the state of axonal degeneration.
Colchicine was injected into the vitreous cavity of one eye in each of six vervet monkeys (Chlorocebus sabaceus; estimated vitreal concentration: 1 mM, n=3; 2 mM, n=1; 10 mM, n=2); an equivalent volume (~0.1 ml) of saline was injected into fellow control eyes. RNFLT was measured by SLP (GDx VCC, Carl Zeiss Meditec, Inc) prior to injection, and every 10 min after injection for two hours. RNFLT was also measured by OCT (Stratus, Carl Zeiss Meditec, Inc) prior to injection and 2 hours later. After isolating each retina, biopsies were obtained from the infero-temporal arcuate region, ~2 mm from the center of the optic disc, using a 2.5 mm trephine and processed for transmission electron microscopy (TEM). Retinas were then flat-mounted and stained with an antibody against polymerized beta-tubulin (SMI-62R, Covance Research Products).
RNFLT measured by SLP decreased over time in all 6 colchicine-injected eyes, reaching a plateau ~100 minutes after injection of -20 ± 7% (p<0.0001). The change in vehicle injected control eyes was -3 ± 3% (ns). RNFLT change measured by OCT was +1 ± 4% (ns) in colchicine-injected eyes and -3 ± 6% (ns) in control eyes. There were no significant differences between quadrants and no apparent dose effect. There was no evidence of macular edema by fundus biomicroscopy, stereo fundus photography or OCT. Flat-mounted retinas stained with an antibody against polymerized beta-tubulin showed mild-to-moderate reduction of peripapillary stain intensity in the colchicine-injected eyes as compared with controls. TEM revealed disorganization of microtubules, swelling of mitochondria and axons, and blurred axonal membrane borders in colchicine-injected eyes.
Intravitreal injection of colchicine caused microtubule disruption within the axons of the RNFL in non-human primate eyes. This was manifest as a reduction of RNFLT when measured by SLP, but not by OCT, suggesting that such discrepancies can be informative about the status of axonal degeneration.
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