This year's ARVO abstracts provide fresh data in familiar areas, such as managing contamination, while profiling advances in everything from measurement tools, lens comfort and drug delivery to improved vision. In addition, they offer new insights into the ways in which contact lens wear affects our eyes. (Unless otherwise noted, studies received no commercial support.)
Advances in Lens Technology
Because internal wetting agents have been shown to decrease protein uptake and increase the comfort of contact lens materials, researchers at McMaster University and the University of Waterloo in Ontario, Canada, investigated using hyaluronic acid (HA) as a wetting agent in conventional and silicone hydrogel contact lens materials (pHEMA, pHEMA/ TRIS and DMAA/TRIS), in terms of its impact on lysosome adsorption and denaturation. Models of conventional hydrogel lenses were synthesized using UV polymerization, with varying molecular weights of HA covalently incorporated into the materials. Photocrosslinkable HA was also incorporated into some pHEMA hydrogels.
Lysozyme adsorption and in vitro lysozyme activity were then measured.
• Mean percentage of active lysozyme adsorbed varied between 37.3 ±2.1 and 85.2 ±11 percent, depending on the molecular weight of HA used.
• All molecular weights of HA decreased lysozyme denaturation.
• The presence of HA significantly reduced lysozyme adsorption (p<0.05) in pHEMA hydrogels; they adsorbed only 10 to 16 percent of the amount taken up by control lenses. Similarly, protein associated with the pHEMA/ TRIS hydrogels decreased significantly (p<0.001); they adsorbed only 16 percent as much as the control lenses.
• The percentage of active lysozyme varied between 50.7 ±1.4 and 51.2 ±21 percent for the HA-containing hydrogels—significantly higher than the controls.
• pHEMA hydrogels containing photocrosslinkable HA also adsorbed less lysozyme than pHEMA controls (p<0.05).
The authors conclude that incorporating HA as an internal wetting agent significantly reduces lysozyme adsorption and leads to lower denaturation of the sorbed protein, which could result in increased contact lens comfort.5651
Researchers working at multiple centers in Massachusetts have created a prototype contact lens able to provide extended, controlled release of a drug onto the cornea. The lens consists of a thin polylactic-co-glycolic acid (PLGA) film containing test compounds (encapsulated fluorescein or ciprofloxacin), coated with polyhydroxyethyl methacrylate (pHEMA) using ultraviolet light polymerization.
To test the drug release rates, the lenses were subjected to continuous shaking in phosphate-buffered saline at 37 degrees C. An antimicrobial assay was also used to verify the antimicrobial effectiveness of the ciprofloxacin eluted from the lenses. After a minimal initial release burst, both compounds were released slowly and steadily with zero-order release kinetics under infinite sink conditions for multiple weeks. Data showed that the rate of drug release can be controlled by changing either the ratio of drug to PLGA or the molecular weight of the PLGA employed; it is also affected by the presence or absence of PLGA and pHEMA in the configuration (see chart, facing page). Ciprofloxacin released from the lenses inhibited ciprofloxacin-sensitive Staphylococcus aureus at all time-points tested.5638
Researchers at Indiana University have used a recently developed technique called ocular wavefront tomography to design a contact lens that may be able to correct optical refractive errors even in the periphery of vision. (They note that this could impact not only day-to-day vision, but also refractive development and diagnostic imaging of the retina.) OWT has been used to create model eyes that mimic the expected off-axis wavefront aberrations of a real eye; here it was adapted for contact lens design.
The study authors optimized an aspheric contact lens to correct a wide-angle model eye with three different levels of foveal myopia (-2 D, -4 D and -6 D). Designs were based on two different goals: to fully correct central vision while also improving optical quality peripherally; and to fully correct central vision while introducing a degree of peripheral myopia in order to slow myopia progression. The OWT technique was able to generate multiple contact lenses that produced the desired refractive states over a wide field of view.5641
Researchers at the University of Manchester in the United Kingdom have developed a new device designed to measure the contact angle of contact lenses in vivo using a sessile drop method. The instrument consists of a manual microliter syringe unit attached to a flexible nylon dosing tube mounted on a custom-made base that allows it to be moved in three dimensions.
The subject lies supine in a reclining chair with the instrument mounted above the headrest. A 1.5-µl drop of 0.4 percent sodium hyaluronate mixed with 2 percent sodium fluorescein (to allow visualization of the drop under UV light) is formed at the tip of the dosing tube; the device is lowered towards the contact lens until contact is made with the lens surface. A two-camera digital system records video of the drop being dispensed onto the lens surface. (See image, below.) This ensures accurate centration of the drop on the contact lens, and makes it possible to measure contact angles and the rate at which the drop spreads across the lens surface.
Initial results of pilot investigations suggest that different lens materials produce different contact angles and that rate of spread of the drop may also provide useful information about the wetting characteristics of the contact lens.5645
Managing Bacteria
Researchers at Abbott Medical Optics in Santa Ana, Calif., conducted a study to investigate the propensity of contact lenses and storage cases to become contaminated, which bacteria were most common, how effective multi-purpose solutions were at eradicating them, and how they interacted with Acanthamoeba.
Storage cases from asymptomatic lens wearers were used for the study; subjects used three different MPS. After one month's use, lens cases were collected. The contents were cultured and isolates identified using the Biolog system. Some of the isolates were then tested for resistance to the MPS the wearer had been using.
Significant levels of case contamination were found. Of 460 case solutions and lenses examined, 43 percent showed bacterial contamination, with Stenotrophomonas maltophilia being most frequently isolated (23.9 percent). The three solutions used (not identified by name) showed contamination rates of 34, 41 and 55 percent, respectively. The solution with the highest contamination rate was found to contain Chryseobacterium (19.4 percent), Acidovorax (10.5 percent), Raoutella (9 percent), and Flavobacterium (4.5 percent); the specific bacteria appear to be determined by the type of antimicrobial disinfectant in the MPS being used. Biocidal testing of these isolates against the solution used by these wearers produced only 0 to 1.8 log kill after six hours. Furthermore, the bacteria were found to support Acanthamoeba encystment and trophozoite replication.5661
In a prospective, randomized, masked clinical trial supported by Alcon, researchers in Fort Worth, Texas, and the Victorian College of Optometry in Melbourne, Australia, studied the time course of the development of case and contact lens contamination during daily wear of silicone hydrogel CLs. Seventy-three subjects were fitted with senofilcon A contact lenses and randomly assigned to use a lens-care solution containing preservatives polyquaternium-1 and MAPD (solution A) or one containing PHMB (solution B) on a contralateral basis. They were assigned to return for follow-up in one week (group one), two weeks (group two) or 30 days (group three). At those times, contact lenses and cases were cultured for bacterial contamination and levels of contamination.
Overall, 59 percent of cases and 34 percent of contact lenses were contaminated at the follow-up visits. The data showed:
• Contact lenses had significantly less contamination than cases (p<0.05). Most contaminated contact lenses showed only trace levels of contamination. However, case and lens contamination levels were significantly correlated (rs=0.22, p<0.05).
• Gram-positive bacteria were found in 47 percent of cases; gram-negative bacteria were found in 21 percent of cases.
• Gram-positive bacteria were found on 30 percent of contact lenses; gram-negative bacteria were found on 5 percent.
• There were no significant differences in type of bacteria between follow-up groups or solution types (p>0.05). However, there was a trend towards reduced gram-positive contamination of solution A cases compared to solution B cases (p=0.10); and in group three, lenses disinfected with solution A had significantly less gram-positive contamination than those disinfected with solution B (p<0.05).6352
A grant-financed study conducted by five researchers at two universities in Florida compared the efficacy of commercial contact lens disinfecting solutions—Ultra Care, Opti-free, Aquify, Renu and Complete—against two isolates of Acanthamoeba. (Two of the researchers have had commercial relationships with AMO.)
The Acanthamoeba isolates were grown on non-nutrient amoeba saline agar streaked with live E. coli as prey. Blocks of agar about 2 mm2 containing about 50 trophozoites and cysts were placed in 1 mL of multipurpose solution; an amoeba saline test was used as a control. Cells were tested for viability after three, six and 24 hours of exposure to the multi-purpose solutions. After exposure, the agar blocks were placed in Difco Dey/Engley broth for five minutes; then rinsed twice to remove the broth; then placed trophozoite side down on NNAS agar plates streaked with E. coli, which were sealed and incubated at room temperature for three weeks. Trophozoite migration from the agar block was measured.
Some solutions showed increased efficacy over time; others showed the reverse. (See chart, below.)5653
The Impact of Contact Lens Wear
To determine how contact lens wear might affect the expression of corneal inflammatory cytokines, researchers at CIBA Vision exposed eyes of mice who had intact corneas, scarred corneas or had worn lotrafilcon B contact lenses in one eye for two weeks, to lipopolysaccharide (LPS, derived from Pseudomonas aeruginosa, serotype 10), which can contaminate contact lenses or topical solutions.
Once initial conditions were met, the eyes were challenged with contact lenses soaked in either endotoxin-free water or LPS; three different concentrations of LPS were tested.
After 24 hours, real-time reverse transcription-polymerase chain reaction was used to evaluate the corneal response and determine which, if any, cytokines were upregulated.
The intact mouse eyes that had not worn contact lenses before the challenge showed no more cytokine upregulation than the control group. Mice that had worn a contact lens for two weeks, however, showed significant upregulation of TNF-a and CINC-1, regardless of the concentration of LPS they were exposed to. (Levels of IL-1‚ IL-6, TGF-1, TLR-4 and MyD88 were not different from controls.) Scarified corneas showed no upregulation in response to a very light concentration of LPS (0.02 µg/ µl), but all cytokines tested were significantly upregulated in response to a more significant dose (2 µg/µl).5635
Researchers at Anglia Ruskin University in Cambridge, England, with partial support from UltraVision, conducted a study to determine whether wavefront aberration variability during the interblink period increases in response to contact lens wear or duration of lens wear, and if so, which aberrations were affected.
Ocular wavefront aberrations were measured at two-second intervals from two to 10 seconds after a blink in 10 subjects before lens insertion, after insertion and after five to six hours of lens wear, using the COAS-HD aberrometer (Wavefront Sciences). Analysis was done based on 5-mm pupil aperture. Three lens types were worn on separate days (silicone hydrogel, balafilcon A and nelfilcon A). Mean aberrations were calculated for each lens and each condition; variability was assessed by calculating the standard deviation of the mean aberrations across the full 10-second period.
The data showed that spherical aberration increased significantly and changed sign from positive to negative during the after-blink interval after insertion of lenses (p=0.013) and also after five to six hours of wear, compared to without lenses (p=0.001). Coma and third-order RMS showed higher standard deviations than spherical aberration and fourth-order terms for both lens-wearing conditions, but there was no significant difference in the standard deviation of any aberration term with lenses compared to pre-insertion. (Lens type had no significant effect.)
The authors conclude that variability in aberrations across the inter-blink period was not adversely affected by contact lens wear. However, the absolute magnitude of spherical aberration was consistently higher.6339
The same group of researchers also conducted a study to see whether the wavefront aberrations of a contact lens in vitro, added to the aberrations of the eye, would equal the aberrations found when the contact lens is on the eye. The study used three contact lenses of different optical designs and materials (silicone hydrogel, balafilcon A and nelfilcon A). Aberrometer measurements for 10 subjects were analyzed for a 5-mm aperture. Data for the individual elements and lens on the eye were compared in terms of spherical aberration, coma, third- and fourth-order aberrations, and total RMS aberrations.
The data showed no significant differences in spherical aberration between the lens on eye and off eye for any lens type (p>0.05). However, third-order RMS aberrations differed significantly for the silicone hydrogel lens (p=0.004). For nelfilcon A, the third-order (p=0.031) and total RMS (p=0.025) aberrations differed significantly. The authors conclude that spherical aberration correction will probably have the expected effect on the optical system, but other aberrations may be more difficult to correct for because of lens decentration, drape and changes in tear film properties when the lens is worn.6346
Researchers at the University of Maastricht in the Netherlands and the University of New South Wales in Sydney, Australia, conducted a study of tear meniscus height in rigid gas permeable contact lens wearers to determine whether it differs from meniscus height in those who wear no lenses. They also investigated possible associations with lens-fit variables and eyes with significant 3 o'clock and 9 o'clock staining.
A CCD camera made a video recording of the tear meniscus on the lower eyelid in 26 subjects who did not wear lenses and 55 subjects who wore GP lenses, with and without staining. The video allowed measurement of TMH on a computer screen.
TMH in GP lens wearers was significantly smaller than in those who wore no contact lenses: 0.20 ±0.08 mm vs. 0.28 ±0.10 mm (p<0.01). No statistically significant differences in TMH were found in relation to lens fit variables or staining. The study authors conclude that this data support the hypothesis that gas permeable lenses withhold tear volume from the anterior ocular surface in the lens edge meniscus.904
Creating a Better Questionnaire
A clinical trial conducted by researchers in Atlanta, Bloomington, Ill., and Jacksonville, Fla., with support from Vistakon, CIBA Vision, Alcon and Johnson & Johnson, aimed to create a streamlined, more user-friendly version of the Contact Lens Dry Eye Questionnaire, which is intended to reflect the status of a patient's opinion of contact lens performance.
Thirty-eight healthy current contact lens wearers who had been in their current lens type for at least six months, and were participating in a four-week, randomized, crossover daily-wear contact lens trial, took part in the study. They completed the CLDEQ along with a question on overall opinion of contact lens performance at baseline, and at one and two weeks after crossover to silicone hydrogel lenses.
Individual items from the CLDEQ were first tested to determine those which best correlated to overall opinion. From that group of highly correlated items, a subset of eight questions was tested to establish its ability to reflect change in overall opinion after refitting.
A new, eight-question version of the test, scored by summing the questions regarding frequency and late-day intensity of dryness, discomfort and blurry vision that clears with a blink, the frequency of closing the eyes to rest them, and removing CLs to relieve discomfort, significantly reflected the change in overall opinion regarding CL performance among the silicone hydrogel wearers.6337
Dr. Asbell is a professor of ophthalmology and director of cornea and refractive surgery at the Mount Sinai School of Medicine.