Castroviejo Lecture 2009: 40 Years in Search of the Perfect Contact Lens

Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA.
Cornea (Impact Factor: 2.36). 10/2010; 29(10):1075-85. DOI: 10.1097/ICO.0b013e3181d103bb
Source: PubMed

ABSTRACT To identify the pathophysiological changes produced by contact lens wear that predispose the cornea to infection and search for prospective modifiable risk factors that could reduce the incidence of this critical complication in millions of patients worldwide.
Significant experimental and clinical publications are reviewed, and the results of ongoing studies are presented.
Pseudomonas aeruginosa (PA) is the most common pathogen causing lens-related infectious keratitis over 3 decades. Contact lens wear can increase the risk of infection by increasing surface cell PA binding, thereby promoting invasion between broken tight junctions and initiating direct intracellular invasion mediated by lens-induced membrane lipid rafts. Prevention of upregulation of specific surface-binding receptors for PA with concomitant increase in infection risk is a zero damage game where independent interactions among lens type, mode of wear, oxygen transmissibility, polymer, and toxic effects of associated care solutions ideally should collectively produce no increased ability for PA to attach and/or to invade, thus minimizing the risk for lens-associated infections. The specific hypothesis tested is, "no increased epithelial surface damage... no increased PA binding or invasion... no increased risk for infection." Testing of this new paradigm has been performed in vitro and in animal and human clinical trials and correlated clinically with relative risk results from robust current epidemiological studies. Results to date clearly support the use of lens-related increases in PA binding (bench) as a noninvasive clinical predictor of risk for lens-related infection in subsequent large-scale population studies (bedside). Currently, results suggest that use of common commercial multipurpose lens care solutions with soft lenses may alone significantly increase infection risk by enhancing lens-related PA binding as compared with use of nonpreserved solutions (hydrogen peroxide). Clinical testing also shows that only peroxide solutions show significant disinfection capability against amoebic cysts. Further case-control studies to examine relative risk for infection by lens type and lens care solution are urgently needed.
Millions of patients are dependent on contact lenses for vision worldwide; over 3 decades, lens use has increased, although risk for lens-related infection has remained stubbornly unchanged. Unfortunately, recent introduction of a new generation of hyper-oxygen transmissible lenses used with traditional multipurpose lens care solutions has not lowered overall risks for lens-related infections; however, similar lenses used with nonpreserved care solutions (peroxide) recently demonstrated no significant increases in PA binding in a 1-year clinical trial. Collectively, these findings along with the urgent need for amoebic cysticidal disinfection have led to a current recommendation to patients to use nonpreserved (hydrogen peroxide) care solutions in soft lens wear.

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    ABSTRACT: Purpose: To establish a rabbit model of infectious P. aeruginosa keratitis using ultra high oxygen transmissible rigid lenses; and characterize the frequency and severity of infection when compared to a non-oxygen transmissible lens material. Methods: Rabbits were fit with rigid lenses composed of ultra high and non-oxygen transmissible materials. Prior to wear, lenses were inoculated with an invasive corneal isolate of P. aeruginosa stably conjugated to GFP. Corneas were examined before and after lens wear using a modified HRT in vivo confocal microscope. Viable bacteria adherent to unworn and worn lenses were assessed by standard plate counts. The presence of P. aeruginosa-GFP and myeloperoxidase-labeled neutrophils in infected corneal tissue was evaluated using laser scanning confocal microscopy. Results: The frequency and severity of infectious keratitis was significantly greater with inoculated ultra high oxygen transmissible lenses. Infection severity was associated with increasing neutrophil infiltration and in severe cases, corneal melting. In vivo confocal microscopic analysis of control corneas following lens wear confirmed that hypoxic lens wear was associated with mechanical surface damage, whereas no ocular surface damage was evident in the high oxygen lens group. Conclusions: These data indicate that in the absence of adequate tear clearance, the presence of P. aeruginosa trapped under the lens overrides the protective effects of oxygen on surface epithelial cells. These findings also suggest that alternative pathophysiological mechanisms exist whereby changes under the lens in the absence of frank hypoxic damage result in P. aeruginosa infection in the otherwise healthy corneal epithelium.
    Investigative Ophthalmology &amp Visual Science 08/2014; 55(9). DOI:10.1167/iovs.14-14235 · 3.66 Impact Factor
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    ABSTRACT: Purpose: To evaluate the effects of a chemically-preserved multipurpose contact lens care solution (MPS) on the corneal epithelial surface and Pseudomonas aeruginosa (PA) internalization in the rabbit corneal epithelium. Methods: Rabbits were fit in one eye with a silicone hydrogel lens (balafilcon A, Bausch & Lomb) soaked overnight in a borate-buffered MPS (BioTrue, Bausch & Lomb). The contralateral eye was fit with a lens removed directly from the blister pack containing borate buffered saline (control). Lenses were worn for two hours. Upon lens removal, corneas were challenged ex vivo with invasive PA strain 6487 and assessed for PA internalization. Ultrastructural changes were assessed using scanning electron (SEM) and transmission electron microscopy (TEM). Results: SEM showed frank loss of surface epithelium in MPS-exposed eyes, while control eyes exhibited occasional loss of surface membranes but retention of intact junctional borders. TEM data supported and extended SEM findings, demonstrating the presence of epithelial edema in MPS-treated eyes. There was a 12-fold increase in PA uptake into the corneal epithelium following wear of the MPS-treated lens compared to control (p=0.008). Conclusions: These data demonstrate that corneal exposure to MPS during lens wear damages the surface epithelium and are consistent with our previous clinical data showing an increase in bacterial binding to exfoliated epithelial cells following MPS use with resultant increased risk for lens-mediated infection. These findings also demonstrate that the PA invasion assay may provide a highly sensitive quantitative metric for assessing the physiological impact of lens-solution biocompatibility on the corneal epithelium.
    Investigative Ophthalmology &amp Visual Science 05/2014; 55(7). DOI:10.1167/iovs.14-14513 · 3.66 Impact Factor
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    ABSTRACT: Tear exchange beneath a contact lens facilitates ongoing fluid replenishment between the ocular surface and the lens. This exchange is considerably lower during the wear of soft lenses compared with rigid lenses. As a result, the accumulation of tear film debris and metabolic by-products between the cornea and a soft contact lens increases, potentially leading to complications. Lens design innovations have been proposed, but no substantial improvement in soft lens tear exchange has been reported. Researchers have determined post-lens tear exchange using several methods, notably fluorophotometry. However, due to technological limitations, little remains known about tear hydrodynamics around the lens and, to-date, true tear exchange with contact lenses has not been shown. Further knowledge regarding tear exchange could be vital in aiding better contact lens design, with the prospect of alleviating certain adverse ocular responses.
    Journal of Optometry 01/2015; 8(1). DOI:10.1016/j.optom.2014.12.001

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