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18 February 2009Optical coherence tomography in estimating molecular diffusion of drugs and analytes in ocular tissues
Aside from other ocular drug delivery methods, topical application and follow up drug diffusion through
the cornea and sclera of the eye remain the favored method, as they impose the least pain and discomfort to the
patient. However, this delivery route suffers from the low permeability of epithelial tissues and drug washout, thus
reducing the effectiveness of the drug and ability to reach its target in effective concentrations. In order to better
understand the behavioral characteristics of diffusion in ocular tissue, a method for noninvasive imaging of drug
diffusion is needed. Due to its high resolution and depth-resolved imaging capabilities, optical coherence
tomography (OCT) has been utilized in quantifying the molecular transport of different drugs and analytes in vitro in
the sclera and the cornea. Diffusion of Metronidazole (0.5%), Dexamethasone (0.2%), Ciprofloxacin (0.3%),
Mannitol (20%), and glucose solution (20%) in rabbit sclera and cornea were examined. Their permeability
coefficients were calculated by using OCT signal slope and depth-resolved amplitude methods as function of time
and tissue depth. For instance, mannitol was found to have a permeability coefficient of (8.99 ± 1.43) × 10-6 cm/s in
cornea (n=4) and (6.18 ± 1.08) × 10-6 cm/s in sclera (n=5). We also demonstrate the capability of OCT technique for
depth-resolved monitoring and quantifying of glucose diffusion in different layers of the sclera. We found that the
glucose diffusion rate is not uniform throughout the tissue and is increased from approximately (2.39 ± 0.73) × 10-6
cm/s at the epithelial side to (8.63 ± 0.27) × 10-6 cm/s close to the endothelial side of the sclera. In addition,
discrepancy in the permeability rates of glucose solutions with different concentrations was observed. Such diffusion
studies could enhance our knowledge and potentially pave the way for advancements of therapeutic and diagnostic
techniques in the treatment of ocular diseases.
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Mohamad G. Ghosn, Valery V. Tuchin, Kirill V. Larin, "Optical coherence tomography in estimating molecular diffusion of drugs and analytes in ocular tissues," Proc. SPIE 7163, Ophthalmic Technologies XIX, 71631H (18 February 2009); https://doi.org/10.1117/12.810635