Fiona Stapleton

Contact lenses and other risk factors in microbial keratitis

Microbial keratitis is a potentially binding disease that is rare in normal eyes unless associated with contact lens (CL) wear. To assess the risks of CL use, and other major causes, for keratitis, a case-control study of 91 cases of keratitis including 60 CL users was done. Relative risks (RR) and population attributable risk percentages (PAR%) for keratitis were estimated for different causes and for the different types of CL. The RR (95% confidence intervals) for CL wear was 80 (38-166) and for trauma cases 14 (6-32) compared with cases of keratitis without a predisposing condition. The PAR% for microbial keratitis attributed to CL wear was 65%. The RR for overnight wear soft lenses was 21 (7-60), for daily-wear soft lenses 3.6 (1-14), and for polymethylmethacrylate hard lenses 1.3 (0-9) compared with gas-permeable hard lenses. Continuous periods of CL wear for more than 6 days was associated with increased risk. CL wear is now the commonest cause, and has the highest risk, for new cases of microbial keratitis at Moorfields Eye Hospital. Soft CLs, especially extended-wear lenses, carry a significantly higher risk than do hard lenses for this disease.

In vivo confocal microscopy of the human cornea

Aims: To describe the optics of in vivo confocal microscopy, its advantages over previous methods, and to summarise the literature that arose from its use for the observation of the human cornea. A critical review of the clinical usefulness of this new technology for the corneal examination is undertaken. Methods: Confocal microscopes obtain increased resolution by limiting the illumination and observation systems to a single point. Rapid scanning is used to reconstruct a full field of view and allows for “real time” viewing. Results: Coronal sections of the in situ epithelium, Bowman’s membrane, stroma, and endothelium can be visualised at a resolution of 1–2 μm. A backscattered light intensity curve allows objective measurements of sublayer thickness and corneal haze to be taken. In vivo confocal microscopy is therefore particularly useful in the areas of infective keratitis, corneal dystrophies, refractive surgery, and contact lens wear, where it aids in differential diagnosis and detection of subtle short and long term changes. Real time endothelial cell assessment can also be performed. Conclusion: Because of their ability to visualise living tissue at cellular levels, confocal microscopes have proved useful additions to the current clinical tools.

Risk factors and causative organisms in microbial keratitis.

Purpose: To establish the risk factors, causative organisms, levels of antibiotic resistance, patient demographics, clinical presentations, and clinical outcomes of microbial keratitis at a tertiary hospital in Australia. Methods: Patients who had a corneal scraping for culture over a 5-year period were identified through the local microbiology database, and a retrospective audit of their medical records was carried out. Clinical information was gathered from medical records, and smear, culture, and antibiotic resistance results were from the microbiology database. An index of disease severity was calculated for each patient from scores for the magnitude of the epithelial defect and anterior-chamber reaction and the location of the lesion. Associations between risk factors for keratitis and variables such as patient demographics, causative organism and antibiotic resistance, disease severity, and outcome were analyzed by using analysis of variance and χ2 tests with appropriate correction for multiple comparisons. Results: Two hundred fifty-three cases of microbial keratitis in 231 patients were included. Sixty percent of patients were men, and there was a bimodal distribution in the age of presentation. Common risk factors for keratitis were contact lens wear (53; 22%), ocular surface disease (45; 18%), ocular trauma (41; 16%), and prior ocular surgery (28; 11%). Gram stains were positive in 33%, with a sensitivity of 53% and specificity of 89%. Cultures of corneal scrapings were positive in 65% of cases, and Pseudomonas aeruginosa (44; 17%), coagulase-negative staphylococci (22; 9%), Staphylococcus aureus (19; 8%), and fungi (7; 3%) were commonly recovered. P. aeruginosa was more common than other culture results in contact lens-related cases (55% vs. 0%-23%; P < 0.001), and S. aureus was more common than other culture results in ocular surgery-related cases (29% vs. 0%-21%; P < 0.001). Patients with keratitis related to prior ocular surface disease had more severe keratitis at the time of scraping (P = 0.037). Cultures positive for Fusarium, P. aeruginosa, and other Gram-negative organisms had statistically significantly more severe keratitis at the time of scraping, whereas patients with negative cultures had milder keratitis (P = 0.030). Only 2% of all bacterial isolates were resistant to ciprofloxacin, 20% of Gram-positive isolates were resistant to cephalothin, and no Gram-negative isolates were resistant to gentamicin. Conclusions: In this series, the most common risk factor for keratitis was contact lens wear and the most commonly isolated organism was P. aeruginosa.

Risk Factors for Microbial Keratitis with Contemporary Contact Lenses : A Case-Control Study

OBJECTIVE To assess the relative risks (RR) of microbial keratitis (MK) for contemporary contact lens (CL) types and wearing schedules. DESIGN A 2-year prospective case-control study begun in December 2003. PARTICIPANTS Cases were 367 CL wearers attending Moorfields Eye Hospital with proven or presumed MK. Controls were 1069 hospital controls, who were CL wearers with a disorder unrelated to CL wear, and 639 population-based controls who were CL wearers randomly selected from the Moorfields catchment area. Hospital patients completed a self-administered questionnaire; population-based controls were interviewed by telephone. TESTING Multivariate analysis was done both for all cases of MK, and for the moderate and severe MK subgroups alone. MAIN OUTCOME MEASURES The RR for developing MK, and vision loss, for all lens types compared with planned replacement soft lenses (the referent). RESULTS Compared with planned replacement soft lenses (the referent), the RR of MK was significantly increased with daily disposable (DD) CLs (RR, 1.56x [95% confidence interval (CI), 1.1-2.1]; P = 0.009) and differed between different brands of DD lens, was reduced for rigid lenses (RR, 0.16x [95% CI, 0.06-0.4]; P<0.001), and no different for silicone hydrogel or other types of soft lens. Although the risk of MK was higher overall among DD lens users, the risk of vision loss was less than for planned replacement soft CL users (P = 0.05); no DD lens users lost vision to the level of >or=20/40. The RR for overnight wear, for any lens type, was 5.4 times higher (95% CI, 3.3-10.9; P<0.001). Comparison of the DD soft CL types with planned replacement soft lenses (the referent), showed significant differences between brands for the risk of MK. CONCLUSIONS The risk of MK has not been reduced in users of DD and silicone hydrogel CLs. However, vision loss is less likely to occur in DD than in reusable soft CL users. Different brands of CL may be associated with significantly different risks of keratitis; understanding these differences should lead to the development of safer soft lenses. These findings suggest that lens/ocular surface interactions may be more important in the development of corneal infection than oxygen levels and CL case contamination.

Bacterial biofilm on contact lenses and lens storage cases in wearers with microbial keratitis

Bacterial biofilm formation on contact lenses (CLs), and CL storage cases may be a risk factor for CL‐associated corneal infection and may explain the persistence of organisms in CL storage cases. This study evaluated biofilm formation on, and microbial contamination of, CLs and CL storage cases from patients with microbial keratitis. Contact lenses and CL storage cases from 20 wearers with microbial keratitis were sampled microbiologically and visualized using scanning electron microscopy (SEM). Culture results from the cornea were also noted. Bacterial biofilm was present more frequently (P < 0·05) on CL storage case surfaces (17/20) compared with CL surfaces (11/20) and biofilm density was significantly greater on case surfaces (P < 0·05). There was no association between poor compliance and microbial contamination of the CL storage case, nor between poor compliance and biofilm formation or density on the CL or CL storage case. Biofilm formation occurred equally frequently with hydrogen peroxide and chlorine release care systems. Microbial keratitis in CL wearers is frequently associated with bacterial biofilm in the CL storage case. Despite the use of current CL disinfection systems, the CL storage case is a favourable environment for proliferation of certain organisms. Biofilm on CLs may prolong the retention time of organisms at the ocular surface and increase their potential pathogenicity.

The epidemiology of contact lens related infiltrates.

With estimated numbers of contact lens wearers worldwide exceeding 140 million, even complications with a low incidence will affect a significant number of individuals. Although contact lenses clearly have many advantages for wearers, certain risks have been associated with their use. Differences in risk for different types of contact lenses and wearing patterns have been demonstrated for both rare and common lens related complications. This review particularly focuses on the incidence and etiology of contact lens related corneal infection and inflammation. An understanding of the risks and contributory factors to these conditions is important for practitioners and will enable an informed choice of safer lens wear modalities, wear schedules, and hygiene regimes to be made.

Silicone Hydrogel Contact Lenses and the Ocular Surface

For 30 years, contact lens research focused on the need for highly oxygen-permeable (Dk) soft lens materials. High Dk silicone hydrogel contact lenses, made available in 1999, met this need. The purpose of this review is to examine how silicone hydrogel lens wear affects the ocular surfaces and to highlight areas in which further research is needed to improve biocompatibility. Silicone hydrogel lenses have eliminated lens-induced hypoxia for the majority of wearers and have a less pronounced effect on corneal homeostasis compared to other lens types; however, mechanical interaction with ocular tissue and the effects on tear film structure and physiology are similar to that found with soft lens wear in general. Although the ocular health benefits of silicone hydrogel lenses have increased the length of time lenses can be worn overnight, the risk of infection is similar to that found with other soft lens types, and overnight wear remains a higher risk factor for infection than daily wear, regardless of lens material. Future contact lens research will focus on gaining a better understanding of the way in which contact lenses interact with the corneal surface, upper eyelid, and the tear film, and the lens-related factors contributing to infection and inflammatory responses.

Contact lens-related microbial keratitis: how have epidemiology and genetics helped us with pathogenesis and prophylaxis

Contact lens wear is a common predisposing factor in microbial keratitis and is one of the two preventable risk factors for corneal infection in a working age population. Our understanding of the prevention and prophylaxis of contact lens-related corneal infection is informed by recent epidemiological studies describing the incidence of and risk factors for the disease, the effect of causative organism on disease severity, and an appreciation of individual immune profiles in susceptibility to and severity of the disease. Although contemporary contact lenses have not reduced the overall incidence of keratitis, a reduction in morbidity may be achievable through recognition of appropriate risk factors in severe disease, including avoiding delays in presenting for appropriate treatment, and attention to storage case hygiene practise. Severe keratitis is most commonly associated with an environmental causative organism, and daily disposable lenses are associated with less severe disease. Pseudomonas aeruginosa remains the commonest cause of contact lens-related corneal infection probably because of its unique virulence characteristics and ability to survive in the contact lens/storage case/ocular environment. In two recent outbreaks of contact lens-related infections, there has been a strong association demonstrated with particular contact lens solutions. Since the recall of these specific contact lens solutions, the rate of Acanthamoeba keratitis has remained above the expected baseline, indicating unidentified risk factors that may include environmental exposures. Individual differences in susceptibility to microbial keratitis may be partly explained by differences in single-nucleotide polymorphisms in certain cytokine genes, particularly those with a proven protective role in corneal infection.

Biofilm-related infections in ophthalmology

A biofilm is a functional consortium of microorganisms organised within an extensive exopolymer matrix. Organisms within a biofilm are difficult to eradicate by conventional antimicrobial therapy and can cause indolent infections. This paper reviews the pathophysiology of biofilms and their application of ophthalmology. Under certain environmental conditions such as nutrient limitation, some bacteria may secrete and reside in an exopolysaccharide glycocalyx polymer. This confers relative protection from humoral and cellular immunity, antibiotics and surfactants. Biofilms occur in natural aquatic ecosystems, on ship hulls, in pipelines and on the surface of biomaterials. They cause clinical infections of prosthetic hip joints, heart valves and catheters. Biofilm formation may occur rapidly on contact lenses and their cases and hence contribute to the pathogenesis of keratitis. Formation of biofilms is also implicated in delayed post-operative endophthalmitis and crystalline keratopathy. Bacteria within biofilms are 20-1000 times less sensitive to antibiotic than free-living planktonic organisms. Existing experimental methods for modifying biofilm include the use of macrolide antibiotics that specifically impair biofilm production, and the use of enzymes to digest it. These may have clinical applications, as potential adjunctive therapies to antibiotic treatment, for these resistant infections. In conclusion, biofilm is an important cause of infections associated with biomaterials. Novel strategies are needed to deal with these.

Risk factors for moderate and severe microbial keratitis in daily wear contact lens users

OBJECTIVE To establish risk factors for moderate and severe microbial keratitis among daily contact lens (CL) wearers in Australia. DESIGN A prospective, 12-month, population-based, case-control study. PARTICIPANTS New cases of moderate and severe microbial keratitis in daily wear CL users presenting in Australia over a 12-month period were identified through surveillance of all ophthalmic practitioners. Case detection was augmented by record audits at major ophthalmic centers. Controls were users of daily wear CLs in the community identified using a national telephone survey. TESTING Cases and controls were interviewed by telephone to determine subject demographics and CL wear history. Multiple binary logistic regression was used to determine independent risk factors and univariate population attributable risk percentage (PAR%) was estimated for each risk factor. MAIN OUTCOME MEASURES Independent risk factors, relative risk (with 95% confidence intervals [CIs]), and PAR%. RESULTS There were 90 eligible moderate and severe cases related to daily wear of CLs reported during the study period. We identified 1090 community controls using daily wear CLs. Independent risk factors for moderate and severe keratitis while adjusting for age, gender, and lens material type included poor storage case hygiene 6.4× (95% CI, 1.9-21.8; PAR, 49%), infrequent storage case replacement 5.4× (95% CI, 1.5-18.9; PAR, 27%), solution type 7.2× (95% CI, 2.3-22.5; PAR, 35%), occasional overnight lens use (<1 night per week) 6.5× (95% CI, 1.3-31.7; PAR, 23%), high socioeconomic status 4.1× (95% CI, 1.2-14.4; PAR, 31%), and smoking 3.7× (95% CI, 1.1-12.8; PAR, 31%). CONCLUSIONS Moderate and severe microbial keratitis associated with daily use of CLs was independently associated with factors likely to cause contamination of CL storage cases (frequency of storage case replacement, hygiene, and solution type). Other factors included occasional overnight use of CLs, smoking, and socioeconomic class. Disease load may be considerably reduced by attention to modifiable risk factors related to CL storage case practice.