Extended-wear Contact Research Articles

Polyclonal human antibodies reduce bacterial attachment to soft contact lens and corneal cell surfaces

Bacterial keratitis due to Pseudomonas aeruginosa is a potentially serious complication of extended-wear contact lens use. Adhesion of P. aeruginosa to soft contact lens materials or corneal endothelial cells in the presence of pooled human immunoglobulins and/or neutrophils in artificial tear fluid was studied in vitro as a potential method to treat contact lens-associated infection. Soft hydrophilic contact lens materials equilibrated in sterile saline were soaked in artificial tear fluid for 18 h prior to use. P. aeruginosa IFO 3455 was added to groups of lenses or confluent cultured bovine corneal endothelial cells with varying amounts of human polyclonal immunoglobulin (IgG) and human blood neutrophils or serum albumin as a control. After 2 or 4 h incubation, adherent viable bacteria on lenses were quantified. Fluorescence microscopy was used to assess bacterial adherence to bovine corneal endothelial cells in the presence and absence of IgG and neutrophils. Various concentrations of albumin had no effect on adhesion. Human immunoglobulin solutions (25 mg/ml) reduced P. aeruginosa adhesion by nearly 1 log and 2 logs after 2 and 4 h incubations, respectively. Neutrophils in combination with 25 mg/ml IgG reduced bacterial adhesion approximately 1 log over reduction in adhesion by neutrophils alone. Diluted human IgG (10 mg/ml) did not significantly decrease bacterial adhesion after 2 or 4 h, but did reduce adhesion in combination with human neutrophils at both time points. Similar reductions in amounts of fluorescently labeled bacteria adhered to cultured monolayers of corneal endothelial cells under these conditions were qualitatively observed.

Confocal microscopic observations of stromal keratocytes during extended contact lens wear

Background: The aim of this study was to monitor changes in keratocyte density during extended contact lens wear and to explore the possible role of hypoxia and oedema in any changes observed. Methods: Twenty‐three neophyte myopic subjects wore a high Dk/t lens (Pure Vision) in one eye and a low Dk/t lens (Acuvue 2) in the other eye on an extended wear basis for six months. Slit‐scanning confocal microscopy and ultrasonic pachometry were performed on both eyes at baseline (before lens wear), after three and six months of lens wear, and one week after cessation of lens wear (the ‘post‐cessation’ visit). Results: No differences were established between die two lenses or between the three study visits for anterior stromal keratocyte density (KD). Posterior stromal KD was similar for the two lenses throughout the study. However, there was an overall drop in posterior KD of 14 per cent in bodl eyes at the six‐month visit, compared to die initial visit. Posterior KD at die six‐mondi visit was no different from diat at die post‐cessation visit. Corneal thickness was similar for die two lenses at die initial and post‐cessation visits, but was diree per cent greater for the eye wearing die Acuvue 2 lens at die six‐month visit. Conclusion: Extended contact lens wear causes a loss of keratocytes; diis loss cannot be attributed to contact lens‐induced hypoxia and/or oedema, or to an artifact of confocal microscopy relating to presence of residual oedema. It is postulated diat lens‐induced keratocyte loss may be related to die physical presence of contact lenses creating some mechanical effect.

Oxygen permeability of hydrogel contact lenses with organosilicon moieties

Oxygen transport through two extended wear (day and night) hydrogel contact lenses that contain organosilicon moieties (balafilcon A and lotrafilcon A) was studied in the hydrate (hydrogel) and dry (xerogel) states. The water uptake increased the oxygen permeability [( Dk) app] and transmissibility [ Dk/ L av] coefficients of the dry materials by about 70%. The ( Dk) app for the hydrated lenses was determined following the so-called stack procedure. The values obtained were 107±4 barrer for balafilcon A and 141±5 barrer for lotrafilcon A, about 5–10 times larger than those previously reported for conventional (without organosilicon moieties) extended wear hydrogels contact lenses. The Dk/ L av for −3.00 diopter lenses (harmonic average thickness, L av=75±2 μm for lotrafilcon, and 85±2 μm for balafilcon) was 123±6 barrer/cm for balafilcon A and 183±8 barrer/cm for lotrafilcon A. The minimum oxygen transmissibility 87 barrer/cm stipulated by Holden and Mertz to avoid corneal edema with extended wear contact can be easily achieved with lotrafilcon and balafilcon lenses of diverse dioptric powers if the central and peripheral thickness of the lenses are kept below the critical level of oxygen transmissibility.

Contact lens-induced papillary conjunctivitis is associated with increased albumin deposits on extended wear hydrogel lenses.

Contact lens papillary conjunctivitis (CLPC) may be a combination of immunological and mechanical responses to contact lenses and their deposits, resulting in a hypersensitivity reaction.1 Enlarged papillae on the tarsal conjunctiva, redness, itching, increased mucus, and decreased contact lens tolerance are typical symptoms. 2 CLPC is a major reason for discontinuing contact lens wear; 3 however, the link between lens deposits, mechanical trauma, the immunological response and ultimate discontinuation of lens wear is still unclear. In view of the known immunological aspects of CLPC, our aim was to determine the levels of human serum albumin (HSA), secretory IgA (sIgA, a constitutive protein) and lactoferrin (a regulated protein) on extended wear contact lenses (EWCL).

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Pseudomonas aeruginosa corneal infection affects cholinergic enzymes in rat lacrimal gland.

Since the increased use of extended-wear contact lenses, Pseudomonas aeruginosa has emerged as a primary etiological agent of ulcerative keratitis. Clinical isolates have been classified into two types: cytotoxic and non-cytotoxic. This study revealed significant immune and neuro-enzymatic changes elicited by the two types of P. aeruginosa in the lacrimal gland of rats. The humoral immune response in the lacrimal gland to the non-cytotoxic strain was significantly lower than to the cytotoxic strain, possibly due to the immunogenicity of the extracellular toxin; however, the same effect was not seen in the serum. Choline acetyltransferase and acetylcholinesterase are known to be responsible for synthesis and degradation of acetylcholine, respectively, binding receptors on acini and plasma cells, modulating their activity, and constituting the principle regulator of tear secretion. Following infection, neuro-enzyme activities were significantly modified to reduce the concentration of acetylcholine and therefore potentially reduce secretion from the glands. The data lead to the hypothesis that P. aeruginosa may have the potential to reduce the protective barrier provided by the lacrimal gland to benefit pathogenicity. It was also observed that the neuro-enzyme response of the lacrimal glands of uninfected eyes of the test animals was the same as that of infected eyes, implying that the signal may be relayed by common lymphoidal tissue or the central nervous system and a measurable response returned to both eyes.

The performance of the refractive status and vision profile survey in a contact lens clinical trial

To evaluate the Refractive Status and Vision Profile (RSVP) questionnaire in a contact lens clinical trial and to assess the feasibility of its use in future trials. Randomized, crossover clinical trial and survey. The RSVP was administered to 50 contact lens-wearing participants recruited from a large contact lens clinic. RSVP scores were calculated for subjects at three outcome visits: (1) baseline, (2) after wearing daily disposable contact lenses, and (3) after wearing disposable extended wear contact lenses. One-sample t tests were used to compare baseline survey scores with those previously reported for the instrument. The relation of survey scores within and between subjects was assessed with repeated measures analysis of variance. Statistical power and sample size calculations were performed to determine the number of subjects required in future studies to detect differences in RSVP subscale scores. Eight subscale scores (concern, driving, expectations, glare, optical problems, physical and social functioning, problems with corrective lenses, and symptoms) and the overall RSVP score were calculated on the basis of guidelines reported for scoring of the instrument. Five of eight mean subscale scores (concern, expectations, driving, optical problems, and problems with corrective lenses) and the overall score were significantly lower than those previously reported. No differences were found in the following subscales after contact lens treatment: concern, expectations, physical and social functioning, driving, optical problems, problems with corrective lenses, or the overall RSVP score. Significant differences were found on the symptoms (P = 0.03) and glare (P = 0.05) subscales; post hoc testing revealed that the significant differences in these scores occurred between baseline and daily disposable lens wear and not between treatment modalities (daily disposable and disposable extended wear). A sample size of 420 would be required to find clinically relevant significant differences (25%) for all subscales in a similar one-sample clinical trial. A more restrictive difference (10%) would require more than 1100 subjects for four of the nine subscales. The RSVP questionnaire may not be the appropriate quality-of-life instrument for use in a contact lens clinical trial. The instrument seems to lack sensitivity and discriminative validity in evaluating contact lens treatments.

Staphylococcus aureus causes acute inflammatory episodes in the cornea during contact lens wear

The aim of this investigation was to determine the ability of Staphylococcus aureus to cause keratitis during contact lens wear in the rabbit. Rabbits were fitted with hydrogel lenses and wore them on an extended wear schedule for 7 weeks. At the end of each week of wear, one drop of S. aureus was added to the eyes, and the eyes were monitored using slit lamp bio-microscopy, with subsequent microbial and histological studies of the cornea. In the presence of S. aureus, keratitis occurred after 3 weeks of lens wear, a condition that was characterized by diffuse infiltration of the peripheral cornea and limbal redness. In the absence of bacteria, there was no infiltration until week 6. Contact lens wear also prolonged the retention of bacteria in the eye. Extended contact lens wear and S. aureus caused non-ulcerative keratitis in a rabbit model, and disturbances in the ability of the eye to remove bacteria.

Proposed performance criteria for extended wear contact lenses

The introduction of silicone-hydrogel materials has changed expectations for the response to contact lenses used in extended wear. In keeping with this technology shift, we have re-evaluated the criteria by which practitioners judge the performance of extended wear lenses. Attendees at the 1999 Annual Clinical Conference of the British Contact Lens Association were surveyed. The proportion of respondents who considered it appropriate to fit selected patients with conventional, disposable and silicone-hydrogel soft lenses for extended wear was 63%, 67% and 86%, respectively. Only 11% of respondents did not fit extended wear because of personal experience with infectious keratitis, and over 50% relied on educators' advice in avoiding this practice. Fifteen per cent of practitioners reported fitting extended wear on occasions. Ninety-five per cent of respondents thought that the relative risk of infectious keratitis with daily wear compared with no lens wear should be ten or less, which was reduced to 60% when it was revealed that the current relative risk is estimated to be 60. A strong preference for a relative risk of infection with extended wear compared to daily wear of less than five times was indicated, which is consistent with current estimates. A minority of respondents were prepared to accept an overnight oedema level of over 6% with extended wear, although silicone-hydrogel materials have been shown to induce less than 4%. A wide variety of microcyst responses were considered reasonable, with many respondents accepting up to 40 per cornea; again, this result contrasted with early research data suggesting a level of 10 microcysts or less occurring with silicone-hydrogel materials. Interpretation of these findings has led us to the following proposals for safe extended wear: (i) extended wear fitting should preferably be done with silicone-hydrogel materials, rather than conventional hydrogels, where the available parameter ranges overlap; (ii) the relative risk of corneal infection with extended wear compared to daily wear should be two to five times, providing the relative risk of daily wear compared to the no lens wear'situation is reduced to 20 times, and (iii) extended wear lenses should produce an average of no more than 4% overnight oedema and no more than 10 microcysts per eye in the long term.

Assessing the in vitro cell based ocular compatibility of contact lens materials

A series of in vitro assays for determining the biocompatibility of ocular biomaterials have been developed and used to assess the differences in performance of omafilcon A, etafilcon A and nelfilcon A contact lens materials. The assays assessed bacterial attachment, macrophage adhesion, granulocyte adhesion and activation, epithelial cell adhesion and corneal cell contact damage. Overall, omafilcon A was found to be more biocompatible than the other materials although there was no significant difference between the epithelial cell adhesion and granulocyte adhesion and activation on any of the hydrogels. Etailcon A performed less well compared to nelfilcon A and omafilcon A with respect macrophage adhesion and bacterial adhesion. The results indicate that these biological assays can be successfully applied for the testing of contact lens materials and may be particularly useful in the in vitro screening of new extended wear contact lens materials where cell adhesion and activation may have a greater influence on clinical performance.

Extended-wear contact lenses, microbial keratitis, and public health

Extended-wear soft contact lenses (lenses worn continuously for more than 24 h and in many cases for 1–4 weeks) are being relaunched in several countries. This move follows a decade of their restriction by licensing authorities and by contact-lens practitioners because the incidence of microbial keratitis is greater with extended-wear than with daily-wear, soft hydrogel lenses.1,2 Why are extended-wear lenses being revisited and what might be the implications for public health?

Secretory IgA epitopes in basal tears of extended-wear soft contact lens wearers and in non-lens wearers.

To determine secretory IgA epitopes in tears of extended-wear soft contact lens wearers and non-wearing controls. We developed enzyme-linked immunosorbent assays (ELISA) to determine the tear concentrations of two epitopes of secretory IgA, the IgA alpha-chain and the secretory component. These epitopes were measured in basal tears of 20 individuals in 6 nights of extended wear of etafilcon A soft contact lenses and in 19 non-lens-wearing individuals. Levels of IgA alpha-chain immunoreactivity were significantly decreased in the lens-wearing group compared to non-lens wearers. However, the level of secretory component immunoreactivity was not significantly different between groups. IgA alpha-chain and secretory component immunoreactvity were highly correlated; however, some samples showed a marked variation between these two values. Tear concentrations of sIgA epitopes are significantly reduced in extended-wear contact lens wearers, and may contribute to the increased susceptibility to ocular infection seen in this group.

Changes in corneal thickness after daily and extended wear of hydrogel lenses: a comparison of optical and ultrasonic pachometry

Central corneal thickness of both eyes of 18 normal subjects was measured in a study comparing a Haag-Streit optical pachometer and an ultrasonic pachometer (Teknar Ophthasonic, preset velocity 1630 m/sec). All subjects were awake for 3 hours before measurements to reduce swelling of the cornea from overnight eye closure. Reliability was assessed by a three-way analysis of variance between repeated measurements for the optical and ultrasonic pachometers. The former revealed a systematic right–left difference, the left cornea being significantly thicker. The correlation coefficient indicates that the link between the two variables is 0.92 and 0.88 for right and left eyes, respectively. It is concluded that, for clinical purposes, optical and ultrasonic pachometry techniques are comparable. The effect of the daily and extended-wear contact lenses on central corneal thickness also was studied. The degree of change (morning vs evening) in corneal thickness of the polymacon group was lower and decreased with the wear, whereas in the etafilcon A group the change was greater and almost constant with the time of wear.

The temporal correlation of elevated tear IgE levels with the onset of symptoms in patients wearing daily-wear and extended-wear contact lenses

Fourteen patients wearing a disposable contact lens as a daily-wear lens in one eye and as an extended-wear lens in the other eye had tear immunoglobulin (Ig)E levels measured at a baseline visit and at 13 follow-up visits over a 31-day period. Multivariate regression analyses were performed for tear IgE levels against numerous independent variables, including a history of allergies and the level and progression of various symptoms. Although there was a significantly higher level of symptoms in the extended-wear vs. the daily-wear eyes ( p = 0.05), no significant difference in tear IgE levels between the extended-wear and daily-wear eyes was observed. However, tear IgE levels were consistently higher in allergic patients vs. nonallergic patients ( p = 0.02), regardless of the wearing type. A simultaneous bilateral elevation in the tear IgE levels had a 100% correlation with patients reporting a positive history of environmental allergies. Periodic lag analysis revealed that increased symptoms in the extended-wear eyes correlated ( p = 0.003) with elevated tear IgE levels three periods (6.5 days) prior. This pilot study suggests a potential predictive value for tear IgE with regard to contact lens symptomatology. It also revealed a strong correlation between a history of allergies and elevated tear IgE in all types of contact lens wearers.

Extended wear in perspective.

Convenience and safety are major motivating factors in the choice of a mode of correction for refractive errors. Extended wear of contact lenses is associated with greater convenience than daily wear, but questions remain concerning the safety and risks associated with this modality. This paper investigates the hurdles that have rendered extended wear an unfavorable option thus far and seeks to identify strategies to overcome these obstacles. We review the history of extended contact lens wear, focusing on soft extended wear for cosmetic use. Results of incidence and relative risk studies for the major complications are scrutinized. The factors that are associated with increased risk together with mechanisms which have been proposed on based on scientific research are analyzed to derive strategies for preventing adverse reactions in extended wear. Infectious keratitis associated with extended wear of contact lenses has been identified by the community as a major issue, although the degree of concern may be disproportionate. Current perceptions of the relative risk of extended wear versus daily wear in the context of the risk for nonwearers may be misplaced, and the role of eye closure versus consistency and duration of wear remains open to debate. In the minds of practitioners and patients, other adverse reactions may be of greater significance in rejecting extended wear. Nonetheless, the potential extent of injury from infection demands attention. Studies collectively attest that corneal hypoxia during extended wear is a potential causative mechanism in infectious keratitis, suggesting that the provision of higher oxygen levels to the cornea will reduce morbidity rates from this unwanted complication. However, the issues of stagnation of the post-lens tear film during eye closure, mechanical properties of the lens, and lens movement remain unresolved and may prove to be contributing factors to adverse responses. Attention to oxygen permeability and mechanical properties of soft contact lenses should solve the remaining problems with extended wear. Materials currently under development promise to meet at least some of the desired properties and may lead to the long-awaited advent of safe extended wear.

Heme oxygenase induction with attenuation of experimentally induced corneal inflammation

Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular levels of heme and hemeproteins; certain of the latter, i.e. cytochrome P450s, generate pro-inflammatory products from endogenous substrates. Two HO isozymes, the products of distinct genes, have been described; HO-1 is the inducible one, whereas HO-2 is believed to be constitutively expressed. We studied the inducing effects of several metal compounds [CoCl 2, SnCl 2, ZnCl 2, heme, and cobalt protoporphyrin (CoPP)]on HO-1 mRNA content and enzyme activity in cultures of rabbit corneal epithelial (RCE) cells; these metal compounds are known to induce HO in other tissues. Additionally, we studied HO-1 expression in an experimental model of ocular inflammation produced in rabbit corneas by extended contact lens wear, and the relation of HO expression to the induced inflammatory process. SnCl 2 added to RCE cells in vitro produced marked time- and concentration-dependent increases in HO-1 mRNA and HO-1 enzyme activity; CoCl 2, ZnCl 2, and CoPP were inducers of HO as well, though to a lesser degree than SnCl 2. Corneas treated for 6 days with contact lenses impregnated with SnCl 2 displayed substantially less corneal inflammation, swelling, and new vessel invasion than did controls; attenuation of ocular inflammation was paralleled by SnCl 2-induced increases in HO mRNA and HO activity in corneal epithelial cells from treated eyes. It is suggested that amelioration of the inflammatory response produced by extended contact lens wear is due, in part, to the induction of high levels of HO-1 activity by SnCl 2, which results in diminished production of pro-inflammatory mediators generated through heme-dependent metabolic processes. Regulation of HO activity in this manner may have clinical applications.

SHORT COMMUNICATION: Detection of complement regulatory proteins on soft contact lenses

PURPOSE. To determine whether the regulators of complement activation, decay-accelerating factor (DAF) and CD59, which have been identified on the cornea and conjunctiva and in soluble forms in tears and lacrimal secretions, are transferred to soft contact lenses worn by normal subjects. METHODS. Following overnight wear of group 4 extended-wear hydrophilic contact lenses by five normal subjects, we examined the lenses immunohistochemically for decay-accelerating factor (DAF) and CD59, two regulators which interfere with the complement cascade at the C3 and C9 steps, respectively. RESULTS. Both proteins were detected on all worn lenses but not on controls. CONCLUSIONS. These findings raise the question of whether these proteins, as do other contact lens-bound proteins, have deleterious effects, or to the contrary, if they maintain their natural activity, might they have protective functions for contact lens wearers.

Immunoglobulin A antibodies against Pseudomonas aeruginosa in the tear fluid of contact lens wearers

Purpose. Pseudomonas aeruginosa is the most important cause of contact lens-associated ulcerative keratitis, especially for those who use extended-wear lenses. Until now, the presence of specific anti-P. aeruginosa immunoglobulin A (IgA) antibodies in the tears of contact lens wearers has not been investigated and is the purpose of the current study. Methods. The levels of specific IgA antibodies against P. aeruginosa and total secretory IgA (sIgA) concentrations were measured in tears of various groups of contact lens and non-contact lens wearers using enzyme-linked immunosorbent assays. Contact lens groups were divided into the following categories: daily-wear rigid gas-permeable lenses (n = 23), daily-wear soft lenses (n = 22), extended-wear soft lenses (n = 17), and non-contact lens wearers (n = 23). As a positive control group, we tested tears obtained from patients with cystic fibrosis (n = 5) because the respiratory tract of these persons often are colonized by P. aeruginosa. Results. The percentage of nonresponders (<15 U/ml) varied between 9% in daily-wear rigid gas-permeable contact lens users to 23% in daily-wear soft contact lens users. The percentage of nonresponders in controls was 13%. The frequency of nonresponders was not significantly different among the different groups tested. All patients with cystic fibrosis showed a very high anti-P. aeruginosa IgA response in their tears. When analyzing the mean anti-P. aeruginosa IgA response, a significandy lower level was found in extended-wear contact lens users (38 U/ml) compared to non-contact lens wearers (82 U/ml). Total s-IgA levels in die tears of the various groups tested were not significandy different. Conclusions. A substantial number of persons in the population of contact lens wearers tested lack detectable IgA antibodies against P. aeruginosa in their tears and may be susceptible to P. aeruginosa keratitis if die physiological condition of dieir cornea is compromised. Invest Ophthalmol Vis Sci. 1996; 37:2081-2088.

Risk of infection from sleeping with contact lenses on: causes of risk.

Although the risks associated with extended wear contact lenses are well-known, there has not been an adequate explanation of why sleeping with the lenses on increases the risk of infection. It is contended that the reduction in the available oxygen caused by contact lenses does not in itself explain the high rate of corneal infection caused by wearing the lenses while sleeping. This paper examines the contribution that the mechanism of sleep itself makes to the risk of infection, based on patient studies in two optometric practices. The results show that the risk of ocular infection, particularly corneal ulcers, is substantially increased with overnight wear of lenses. A review of the role of oxygen deprivation, atmospheric pollution, bacterial survival strategies, infection-resistant defenses during wakefulness, and patterns of sleep indicates that oxygen deprivation of the cornea is not the only factor in the increased risk associated with wearing the lenses while sleeping. It is suggested that the combination of the introduction of airborne pollutants to the contact lens during the day, the reduced oxygen transmission through contact lenses and closed lids, and the lack of eye and lid movement during sleep together create the conditions in which bacterial infection is most likely to occur.

Recent advances in the design of polymers for contact lenses

AbstractThree approaches for the design of polymers for extended wear contact lenses possessing high oxygen permeability are described. These approaches include the design of high strength, high water content hydrogels, the design of low water content fluorosilicone based materials and the design of hydrogels based on methacrylate end capped hydrophilic side chain siloxanes.