Tear mixing; Epithelial barrier function; corneal physiology; Contact lens extended wear
My laboratory focuses on human clinical research and explores the effects of disease, drugs, contact lenses, and the environment on
human corneal structure and function. During the past 30 years we have made several interesting and potentially important discoveries
about the etiology and amelioration of some of the adverse effects of contact lenses on the eye. These findings would not have been
possible without many strong and productive collaborative relationships, both with Berkeley scientists (Irv Fatt, Bob Mandell, Mort
Sarver, Richard Brand, Robert Fusaro, and Clay Radke), and with investigators not on the Berkeley campus, such as William Bourne (Mayo
Clinic), Brien Holden (University of New South Wales, Australia), Joe Bonnano (Indiana University), Nancy McNamara (University of
California, San Francisco), Michel Guillon (City University, London), and Des Fonn (University of Waterloo). Listed below are some
brief descriptions of the current research in the laboratory. Additional information can be found at my web site:
http://vision.berkeley.edu/polse/
Tear mixing under a Soft Lens: Measurement and Model
Soft Contact Lens Extended Wear (SCLEW) may lead to corneal complications, including substantial vision loss. Although one factor is
corneal hypoxia during eye closure, not all complications can be eliminated with high-oxygen transmissibility lenses. In overnight
wear there is an accumulation of debris trapped at the tear-lens interface, and once the eye is open, it may take several hours for
the debris to be eliminated. Persistent trapped debris due to inadequate tear exchange under the contact lens contributes to SCLEW
complications. In collaboration with Richard Brand we pioneered a method using fluorophometry, which allows us to estimate the rate of
tear mixing under a lens by monitoring the change in concentration of a high molecular weight (FITC-Dextran) dye. We then apply those
intensity data to a composite exponential model that gives the time required to deplete 95% of the dye from under the lens. We can now
describe the exponential rate at which the dye flows from the post-lens compartment, thus providing an expression for tear mixing under
the lens.
In collaboration with the Clay Radke research team (UCB Chemical Engineering), we have worked to develop and refine a hydrodynamic model
that helps explain many factors controlling tear exchange under a lens. Mixing due to fluid flow is proposed to originate from dispersion,
a combination of diffusion, lens movement, and parallel tear flow under the lens, and is termed dispersive mixing. This model displays an
exponential decay of tracer concentration and is in agreement with the FITC-Dextran data obtained with the fluorophometry technique. The
dispersive mixing model can be used to explore the role of various lens and ocular factors that affect tear flow under the lens. Ultimately
the model may be used to develop new materials and lens designs that will provide improved tear flow under soft contact lenses. In addition,
the dispersive mixing model predicted that the thicker the post-lens tear film, the greater the tear exchange. In response, we have
developed a new technique for measuring the post-lens tear thickness.
Epithelial Barrier Function
Many serious complications associated with contact lens wear involve changes to the structure and function of the corneal epithelium.
Nancy McNamara, Robert Fusaro, and I developed a clinical technique for quantifying epithelial integrity through the measurement of
epithelial permeability (Pdc). This technique is very powerful because it measures changes in the epithelium that are not
detectable by standard slit lamp clinical assessment. Using this new and highly sensitive technique, we first explored the effects of
1 hour of closed-eye and overnight soft lens wear and showed that contact lens-induced hypoxic closed-eye wear can cause a 40% to 150%
increase in Pdc. We then investigated whether these changes in Pdc were a direct result of hypoxia. Subjects wore
gas goggles that exposed their eyes to a hypoxic environment, similar to that under SCLEW, but without the mechanical influence of the
lens. We found that hypoxia alone did not lead to changes in Pdc, indicating that the changes must be the result of a
combination mechanical and hypoxic factors. In a follow-up study, we exposed eyes to 100% hypoxia during contact lens wear with the eyes
open. Surprisingly, there were again no changes in Pdc We were then able to develop a model showing that changes in epithelial
barrier function require the combination of a closed-eye state, hypoxia, and contact lens wear. These experiments have been crucial to the
investigation of mechanisms associated with a loss of epithelial structure and function, and they will also be useful in exploring new lens
designs that may eliminate loss of epithelial integrity during extended wear.
The Berkeley Contact Lens Extended Wear Study (CLEWS)
Contact lens extended wear has been associated with various contact lens associated keratopathies (CLAK) or complications, some of which
can cause permanent visual impairment. While previous studies provide some evidence for a hypoxic mechanism, we lacked a clear demonstration
of a link between hypoxia and either the incidence of complications or the ability to maintain successful extended wear (EW) with rigid
gas-permeable (RGP) lenses. A team of clinicians, biostatisticians, and basic scientists developed a protocol to test the hypothesis that,
when compared to EW with medium oxygen-permeable RGP lenses, EW with high-oxygen rigid lenses reduces the incidence of CLAK while increasing
the rate of success in maintaining EW. Our analysis shows that although the incidence of adverse events was equal for the two groups, the
number of complications leading to termination was substantially greater for the lower-oxygen group, indicating that the type of adverse
response or the inability to reverse a complication was different for the lower-oxygen group. Thus the level of oxygen available to the
cornea has a significant impact on maintaining successful RGP EW. We also demonstrated that overnight corneal swelling response was not a
good predictor of ocular complications associated with RGP EW. Lenses that cause little or no corneal edema are not necessarily safer for
overnight wear. In addition, we showed that corneal epithelial permeability increases with hypoxia, and that epithelial barrier function is
impaired by overnight lens wear. preventative treatments.
Selected Publications
Lin MC, Graham AD, Polse KA, McNamara NA, Tieu TG: The effects of one-hour wear of high oxygen permeable soft lenses on corneal pH and epithelial permeability. CLAO J, 2000; 26(3): 130-33.
Fusaro, RE, Polse, KA, Graham AD, Gan CM, Rivera RK, Lin MC, Sanders TL, McNamara NA, Chan JS: The Berkeley contact lens extended wear study: Part I – Study design. Ophthalmol 2001; 108(8): 1381-88.
Polse KA, Fusaro RE, Graham AD, Gan CM, Rivera RK, Lin MC, Sanders TL, McNamara NA, Chan JS: The Berkeley contact lens extended wear study: Part II – Clinical results. Ophthalmol 2001; 108(8): 1389-99.
Graham AD, Fusaro RE, Polse KA, Lin MC, Giasson CJ: Predicting extended wear complications from overnight corneal swelling. Invest Ophthalmol Vis Sci, 2001; 42(13): 3150-57.
Lin MC, Graham AD, Polse KA, Fusaro RE. The Impact of Rigid Contact Lens Extended Wear on Corneal Epithelial Barrier Function. Invest Ophthalmol Vis Sci, 2002; 43(4): 1019-1024.
Miller KL, Polse KA, and Radke CJ. Black-line formation and the "perched" human tear film. Current Eye Research, 2002; 25(3):155-162.
Miller KL, Polse KA, and Radke CJ. Fenestrations enhance tear mixing under soft contact lenses. Invest Ophthalmol Vis Sci, 2003; 44(1):60-67.
Lin MC, Chen YQ, Polse KA: The effects of ocular and lens parameters on the post-lens tear thickness. Eye & Contact Lens, Suppl, 2003, 29(15):S33-S36.
Lin MC, Soliman GN, Song MJ, Smith JP, Lin CT, Chen YQ, Polse KA: Soft contact lens extended wear affects corneal epithelial permeability: Hypoxic or mechanical etiology? CL & Anterior Segment 2003; 26:11-16.
Lin, MC, Soliman GN, Lim VA, Giese ML, Wofford LE, Marmo C, Radke C, Polse KA: Scalloped Channels Enhance Tear Mixing Under Hydrogel Contact Lenses. Invest Ophthalmol Vis Sci, accepted for publication Nov. 2006.
Links
Polse website
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