Since 1980, with increasing patient exposure through overnight wear, contact lens use has become the leading cause of infectious keratitis. Since overnight use is the dominant risk factor identified with lens wear for this complication, attention is focused on the role of overnight lens- induced hypoxia in determining bacterial corneal binding. The purpose of this proposal is: 1) to investigate the hypothesis that daily or overnight contact lens wear produces graded hypoxic injury to the corneal epithelium in inverse proportion to the oxygen transmissibility of the lens (Dk/l(total)); and that the resulting degree of hypoxic damage determines the amount of bacterial binding with Pseudomonas aeruginosa (PA), one of the most important organisms associated with lens related infectious keratitis in man, and, 2) to determine the role of lens-type in PA binding and investigate the hypothesis that hydrogel contact lenses cause significantly higher degrees of corneal damage and hence pose different risks in promoting bacterial corneal adhesion than rigid lenses. To achieve these purposes, the following experimental aims are proposed in human and rabbit studies: (1) To establish the clinical correlation between oxygen transmissibility,lens-induced corneal epithelial desquamation, and tear lactate dehydrogenase (LDH) measurements in the right eyes of human patients for four rigid and four hydrogel lenses worn for periods of 8 hours (daily wear) and 24 hours to three months (extended wear) using in vivo tandem scanning confocal microscopy (TSCM). (2) To establish the clinical correlation in vivo between oxygen transmissibility and tear LDH, and binding of Pseudomonas aeruginosa to exfoliated human surface corneal cells collected from the left eyes of the same test lens- wearing groups and wearing regimens. (3) To measure contact lens-induced total corneal binding of Pseudomonas aeruginosa and determine the relative contributions of binding to exfoliated surface epithelial cells and binding to the residual desquamated corneal surface in the in vivo rabbit model and correlate PA binding with Dk/L(total) for both rigid and hydrogel lens wear. (4) To establish clinically the role of hypoxia alone in promoting increased epithelial desquamation using in vivo TSCM, elevated tear LDH levels, and associated increased Pseudomonas binding to exfoliated surface corneal cells in human patients following variable nitrogen-CO2 exposure beneath tightly fitted goggles.
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