Risk Factors for Bacterial Keratitis and Severe Disease in Hydrogel Contact Lens Users: A Multicenter Case-Control Study and Case-Only Analysis.

PURPOSE: To assess risk factors for contact lens (CL)-related bacterial keratitis, cases and high-risk controls were enrolled. Using high-risk controls can help elucidate whether certain CL types or modalities are attributable to disease burden if risky wear patterns are similar between the cases and controls. This analysis identified whether such CL factors were associated with the occurrence of bacterial keratitis. In addition, a case-only analysis determined CL factors associated with severe disease. METHODS: From 2018 to 2021, 158 controls were enrolled at University Hospitals of Cleveland Eye Institute, and 153 bacterial keratitis cases were enrolled across 14 sites in the United States. Cases were soft CL wearers with either culture-proven bacterial keratitis or a corneal infiltrate with an overlying epithelial defect within the central 4 mm of the cornea, uveitis, or significant pain. Fungal, protozoan, or nonsoft CL wear-related microbial keratitis cases were excluded. Controls were recruited from high-risk CL wearers with no history of disease. All participants completed a questionnaire related to demographics, type of CL used, wearing schedule, lens handling practices, and storage case handling. Cases with ulcer/infiltrate size ≥2 mm in size, presence of hypopyon, or had fortified antibiotics prescribed were classified as severe keratitis. Univariate and multivariable logistic regression was used to assess association of CL variables with the occurrence of bacterial keratitis as well as occurrence of severe disease among the cases only. RESULTS: Compared with the control cohort, cases were older (mean age 45.6 vs. 38.9 years), had more males (42.5% vs. 23.6%), and had more current or former smokers (41.7% vs. 12.9%). There were no significant associations between CL material (silicone hydrogel vs. not) or CL type (daily disposable vs. reusable) and occurrence of bacterial keratitis. More than two-thirds (67.3%) of cases were classified as severe. Among cases only, univariate analyses found current smokers to have increased risk of severe disease (OR=2.87; 95% CI 1.13-7.26, P=0.03). Adjusting for age, sex, and smoking among the cases only, daily disposable lenses were protective against severe disease (OR=0.32; 95% CI 0.11-0.89, P=0.03). Reusable lenses increased risk of severe microbial keratitis between 3.0- and 4.4-fold compared with compliant daily disposability. DISCUSSION/CONCLUSION: Compared with a high-risk control cohort, no specific lens factors were associated with occurrence of CL-associated bacterial keratitis. Among cases only, current smokers and patients wearing reusable lenses are at increased risk of severe keratitis. Daily disposable lenses were protective even when noncompliance to daily disposability was considered.

Contact Lens Safety for the Correction of Refractive Error in Healthy Eyes.

ABSTRACT: Contact lenses are a safe and effective method for correction of refractive error and worn by an estimated 45 million Americans. Because of the widespread availability and commercial popularity of contact lenses, it is not well appreciated by the public that contact lenses are U.S. Food and Drug Administration (FDA)-regulated medical devices. Contact lenses are marketed in numerous hard and soft materials that have been improved over decades, worn in daily or extended wear, and replaced in range of schedules from daily to yearly or longer. Lens materials and wear and care regimens have impact on the risks of contact lens-related corneal inflammatory events and microbial keratitis. This article reviews contact lens safety, with specific focus on the correction of refractive error in healthy eyes.

n-3 Fatty Acid Supplementation for the Treatment of Dry Eye Disease.

BACKGROUND: Dry eye disease is a common chronic condition that is characterized by ocular discomfort and visual disturbances that decrease quality of life. Many clinicians recommend the use of supplements of n-3 fatty acids (often called omega-3 fatty acids) to relieve symptoms. METHODS: In a multicenter, double-blind clinical trial, we randomly assigned patients with moderate-to-severe dry eye disease to receive a daily oral dose of 3000 mg of fish-derived n-3 eicosapentaenoic and docosahexaenoic acids (active supplement group) or an olive oil placebo (placebo group). The primary outcome was the mean change from baseline in the score on the Ocular Surface Disease Index (OSDI; scores range from 0 to 100, with higher scores indicating greater symptom severity), which was based on the mean of scores obtained at 6 and 12 months. Secondary outcomes included mean changes per eye in the conjunctival staining score (ranging from 0 to 6) and the corneal staining score (ranging from 0 to 15), with higher scores indicating more severe damage to the ocular surface, as well as mean changes in the tear break-up time (seconds between a blink and gaps in the tear film) and the result on Schirmer's test (length of wetting of paper strips placed on the lower eyelid), with lower values indicating more severe signs. RESULTS: A total of 349 patients were assigned to the active supplement group and 186 to the placebo group; the primary analysis included 329 and 170 patients, respectively. The mean change in the OSDI score was not significantly different between the active supplement group and the placebo group (-13.9 points and -12.5 points, respectively; mean difference in change after imputation of missing data, -1.9 points; 95% confidence interval [CI], -5.0 to 1.1; P=0.21). This result was consistent across prespecified subgroups. There were no significant differences between the active supplement group and the placebo group in mean changes from baseline in the conjunctival staining score (mean difference in change, 0.0 points; 95% CI, -0.2 to 0.1), corneal staining score (0.1 point; 95% CI, -0.2 to 0.4), tear break-up time (0.2 seconds; 95% CI, -0.1 to 0.5), and result on Schirmer's test (0.0 mm; 95% CI, -0.8 to 0.9). At 12 months, the rate of adherence to treatment in the active supplement group was 85.2%, according to the level of n-3 fatty acids in red cells. Rates of adverse events were similar in the two trial groups. CONCLUSIONS: Among patients with dry eye disease, those who were randomly assigned to receive supplements containing 3000 mg of n-3 fatty acids for 12 months did not have significantly better outcomes than those who were assigned to receive placebo. (Funded by the National Eye Institute, National Institutes of Health; DREAM ClinicalTrials.gov number, NCT02128763 .).

American Academy of Optometry Microbial Keratitis Think Tank.

SIGNIFICANCE: Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies. PURPOSE: The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting. METHODS: Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. RESULTS: The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed. CONCLUSIONS: The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain.

Technical Report: Guidelines for Handling of Multipatient Contact Lenses in the Clinical Setting.

SIGNIFICANCE: Standardized guidelines that are clinically practical are needed to assist the prescriber in minimizing the risk of conveying infection through multiuse diagnostic contact lens use and reuse.Contact lens prescribers face the specter of transferring potential pathogens from one patient to another when reusing diagnostic (trial) contact lenses on multiple patients because infectious organisms have been recovered from worn contact lenses, although there is no evidence of transmission through this mechanism. These pathogens can be introduced into the system from one patient to another, or they may be introduced by clinician lens handling, storage, or both. These pathogens can cause acute or chronic systemic or ocular infection that can lead to significant morbidity (temporary or permanent) that includes vision loss.

Lipid Analysis on Block Copolymer-containing Packaging Solution and Lens Care Regimens: A Randomized Clinical Trial.

SIGNIFICANCE: Lotrafilcon B lenses packaged in and cared for with block copolymer-containing (polyoxyethylene-polyoxybutylene; EOBO) lens care solutions resulted in lower cholesterol extraction than each of the habitual silicone hydrogel lens/multipurpose solution (MPS) regimens tested. PURPOSE: This study aimed to compare the extracted cholesterol of lotrafilcon B lenses packaged in and cared for with EOBO-containing lens care solutions with the extracted cholesterol of habitual silicone hydrogel lenses cared for with MPS not containing EOBO. METHODS: In this prospective, randomized, observer-masked parallel study, habitual wearers of senofilcon C, senofilcon A, comfilcon A, and samfilcon A contact lenses using a non-EOBO MPS were randomized 1:1 to lotrafilcon B lenses packaged in and cared for with EOBO-containing solutions or to their habitual lenses and MPS. Subjects randomized to lotrafilcon B were further randomized to one of two EOBO-containing lens care solutions, OPTI-FREE PUREMOIST or CLEAR CARE PLUS with HydraGlyde (Alcon Laboratories, Inc., Fort Worth, TX). A subset of right eye lenses was collected after wear, and total cholesterol was extracted and measured using a fluorometric enzymatic assay. RESULTS: Of 143 lenses analyzed, 95 were from subjects randomized to their habitual lenses/MPS and 48 to lotrafilcon B + EOBO lenses plus CLEAR CARE PLUS with HydraGlyde or OPTI-FREE PUREMOIST. The mean amounts of cholesterol extracted from lotrafilcon B + EOBO lenses cared for with CLEAR CARE PLUS with HydraGlyde (0.28 ± 0.18 µg/lens) and OPTI-FREE PUREMOIST (0.28 ± 0.48 µg/lens) were significantly lower than those extracted from senofilcon C (4.18 ± 3.25 µg/lens), senofilcon A (2.19 ± 2.69 µg/lens), comfilcon A (2.17 ± 1.47 µg/lens), and samfilcon A (2.07 ± 1.48 µg/lens) lenses used with MPS (P < .0001 each). CONCLUSIONS: Cholesterol sorption was significantly lower in wearers of lotrafilcon B lenses cared for with polyoxyethylene-polyoxybutylene-containing lens care solutions than in users of habitual silicone hydrogel lenses cared for with non-polyoxyethylene-polyoxybutylene MPS.

Postoperative Endothelial Cell Density Is Associated with Late Endothelial Graft Failure after Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To determine whether preoperative endothelial cell density (ECD) and postoperative ECD after Descemet stripping automated endothelial keratoplasty (DSAEK) are associated with late endothelial graft failure (LEGF) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter, randomized clinical trial. PARTICIPANTS: A total of 1007 individuals (1223 study eyes), mean age 70 years, undergoing DSAEK for Fuchs' dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE) (6% of eyes) and followed for up to 5 years. METHODS: Central ECD was determined by a central image analysis reading center. Preoperative ECD was determined for 1209 eyes that did not fail and 14 eyes that experienced LEGF. The ECD at 6 and 12 months after DSAEK, the change in ECD from preoperative to 6 and 12 months, surgeon-reported operative complications, and postoperative graft dislocation were investigated for an association with LEGFs unrelated to other postoperative events. Univariable and multivariable Cox proportional hazards regression models were used to assess associations. MAIN OUTCOME MEASURES: Late endothelial graft failure and its associations with pre- and postoperative ECD and operative complications. RESULTS: The cumulative probability of LEGF was 1.3% (95% confidence interval [CI], 0.8%-2.4%). Median (interquartile range [IQR]) preoperative ECDs were similar for eyes with LEGF (2523; 2367-3161) cells/mm2) and eyes without failure (2727; 2508-2973) cells/mm2) (P = 0.34). The ECD at 6 months was associated with LEGF (P < 0.001) in time-to-event analyses, whereas preoperative ECD was not (P = 0.55). The cumulative incidence (95% CI) of LEGF was 6.5% (3.0%, 14.0%) for 97 grafts with a 6-month ECD less than 1200 cells/mm2, 0.3% (0.0%, 2.4%) for 310 grafts with a 6-month ECD between 1200 and 2000 cells/mm2, and 0.6% (0.1%, 2.7%) for 589 grafts with a 6-month ECD greater than 2000 cells/mm2. In multivariable analyses, ECD at 6 months and operative complications were both associated with LEGF (P = 0.002 and P = 0.01, respectively), whereas graft dislocation was not (P = 0.61). CONCLUSIONS: In eyes undergoing DSAEK, preoperative ECD is unrelated to LEGF, whereas lower ECD at 6 months is associated with LEGF. Early endothelial cell loss after DSAEK and intraoperative complications should be minimized to improve graft survival.

Impact of Dry Eye on Visual Acuity and Contrast Sensitivity: Dry Eye Assessment and Management Study.

SIGNIFICANCE: Identification of the association of specific signs of dry eye disease with specific visual function deficits may allow for more targeted approaches to treatment. PURPOSE: The purpose of this study was to explore the association of dry eye signs and symptoms with visual acuity (VA) and contrast sensitivity in the Dry Eye Assessment and Management study. METHODS: Baseline data from participants in the Dry Eye Assessment and Management study were used in this secondary cross-sectional analysis. Standardized procedures were used to obtain results on the Ocular Surface Disease Index (OSDI), high-contrast logMAR VA, contrast sensitivity, tear film debris, tear breakup time (TBUT), corneal fluorescein staining, meibomian gland evaluation, conjunctival lissamine green staining, and Schirmer test scores. Generalized linear models that included age, refractive error status, and cataract status were used to assess the association between VA and contrast sensitivity with OSDI score and each dry eye sign. The Hochberg procedure was used to account for multiple comparisons. RESULTS: Among 487 participants (974 eyes), worse VA was associated with worse mean score on the OSDI vision subscale (39.4 for VA 20/32 or worse vs. 32.4 for VA 20/16 or better; adjusted linear trend, P = .02); scores were not associated with contrast sensitivity. Severe meibomian gland plugging and abnormal secretions were associated with worse mean log contrast sensitivity (1.48 for severe vs. 1.54 for not plugged [P = .04] and 1.49 for obstructed vs. 1.57 for clear [P = .002], respectively). Longer TBUT was associated with better mean log contrast sensitivity (1.57 for TBUT >5 seconds and 1.51 for TBUT ≤2 seconds, P < .0001). CONCLUSIONS: Worse VA rather than worse contrast sensitivity drives vision-related symptoms in dry eye. Greater tear film instability was associated with worse contrast sensitivity.

The Case for Using Hydrogen Peroxide Contact Lens Care Solutions: A Review.

Despite their established disinfection and safety benefits, the use of hydrogen peroxide (H2O2) lens care systems among today's wearers of reusable contact lenses remains low in comparison with multipurpose solution (MPS) use. Multipurpose solution systems, however, present several potential drawbacks that may impact patient outcomes, including the use of chemical preservatives for disinfection, biocompatibility issues, and challenges with respect to lens care compliance. Given their unique composition and mechanism of action, one-step H2O2 systems offer the opportunity to avoid many of the challenges associated with MPS use. This article reviews the evolution of H2O2 lens care systems and examines the current scientific and clinical evidence regarding the relative ease of use, lens and tissue compatibility, disinfection efficacy, and ocular surface safety of H2O2 systems. Evaluation of the available data indicates that in comparison with MPS, one-step H2O2 systems tend to promote more favorable compliance, efficacy, comfort, and ocular surface outcomes for a wide range of contact lens-wearing patients. Based on the current published evidence, the authors recommend that eye care practitioners consider making one-step H2O2 systems their first-line contact lens care recommendation for most wearers of reusable lenses.

Diversity of Ocular Surface Bacterial Microbiome Adherent to Worn Contact Lenses and Bacterial Communities Associated With Care Solution Use.

PURPOSE: This study assessed microbiome adherent to contact lenses and defined the bacterial communities associated with use of lens care solutions. METHODS: Among 84 lenses screened for adherent ocular surface bacterial microbiome using 16S rRNA molecular amplification, 63 (75%) generated bacterial-specific amplicons processed using the Ion Torrent Personal Genome Machine workflow. Data were stratified by solution use (peroxide vs. polyhexamethylene biguanide [PHMB]-preserved multipurpose solution [MPS]). Diversity of lens-adherent microbiome was characterized using Shannon diversity index and richness index. Data were analyzed using principal components analysis and Kruskal-Wallis tests. RESULTS: We identified 19 phyla and 167 genera of bacteria adherent to the lenses. Proteobacteria was the most abundant phyla, followed by Firmicutes and Actinobacteria. The most abundant bacterial genera (>1% abundance) were Ralstonia, Enterococcus, Streptococcus, Halomonas, Corynebacterium, Staphylococcus, Acinetobacter, Shewanella, Rhodococcus, and Cobetia. Sixteen of 20 lenses (80%) negative for bacterial DNA were worn by participants using peroxide solutions while only 4 (20%) were MPS-treated lenses (P=0.004). Genera diversity of lens-adherent microbiome showed a significant increase in MPS-treated lenses compared with peroxide (P=0.038). Abundance of Corynebacterium, Haemophilus, and Streptococcus were increased 4.3-, 12.3-, and 2.7-fold, respectively, in the MPS group compared with peroxide (P=0.014, 0.006, 0.047, respectively). CONCLUSIONS: Commensal, environmental, and pathogenic bacteria known to be present in the conjunctival microbiome can be detected on worn contact lenses. Although most contact lenses worn by asymptomatic wearers harbor bacterial DNA, compared with peroxide, lenses stored in a PHMB-preserved MPS have more quantifiable, abundant, and diverse bacterial communities adherent to them.

Donor, Recipient, and Operative Factors Associated with Graft Success in the Cornea Preservation Time Study.

PURPOSE: To associate donor, recipient, and operative factors with graft success 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter, double-masked, randomized clinical trial. PARTICIPANTS: One thousand ninety individuals (1330 study eyes) with a median age of 70 years undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE; 6% of eyes). METHODS: Eyes undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (n = 675) or 8 to 14 days (n = 655). Donor, recipient, and operative parameters were recorded prospectively. Graft failure was defined as regraft for any reason, a graft that failed to clear by 8 weeks after surgery, or an initially clear graft that became and remained cloudy for 90 days. Failure in the first 8 weeks was classified further as primary donor failure or early failure, in the absence or presence of operative complications, respectively. Proportional hazards and logistic regression models were used to estimate risk ratios (RR) and 99% confidence intervals (CIs) for graft failure. MAIN OUTCOME MEASURES: Graft success at 3 years. RESULTS: One thousand two hundred fifty-one of 1330 grafts (94%) remained clear at 3 years and were considered successful. After adjusting for PT, tissue from donors with diabetes (RR, 2.35; 99% CI, 1.03-5.33) and operative complications (RR, 4.21; 99% CI, 1.42-12.47) were associated with increased risk for primary or early failure. Preoperative diagnosis of PACE (RR, 3.59; 99% CI, 1.05-12.24) was associated with increased risk for late failure by 3 years after surgery compared with Fuchs dystrophy. Graft success showed little variation among other factors evaluated, including donor age (RR, 1.19 per decade; 99% CI, 0.91-1.56 per decade), preoperative donor endothelial cell density (RR, 1.10 per 500 cells; 99% CI, 0.74-1.63 per 500 cells), graft diameter (RR, 1.22 per 1 mm; 99% CI, 0.39-3.76 per 1 mm), and injector use for graft insertion (RR, 0.92; 99% CI, 0.40-2.10). CONCLUSIONS: Descemet stripping automated endothelial keratoplasty success in the early and entire postoperative period is more likely when the donor did not have diabetes and was without operative complications and in the long-term postoperative period in recipients with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success after DSAEK warrant further study.

Daily Wear Contact Lenses Manufactured in Etafilcon A Are Noninferior to Two Silicone Hydrogel Lens Types With Respect to Hypoxic Stress.

PURPOSE: This study hypothesized that a traditional high-water contact lens of moderate oxygen transmissibility (Dk/t) is noninferior to common silicone hydrogel (SH) lenses worn for daily wear with respect to measures of hypoxic stress. METHODS: Thirty-six habitual contact lens wearers completed wear of three lens types worn in a randomized order: etafilcon A (ACUVUE 2, control), lotrafilcon B (Air Optix Aqua), and comfilcon A (Biofinity). Central corneal thickness (CT) and limbal hyperemia were measured >2 hr after waking and after 6 to 8 hr of wear on days 1 and 7. Endothelial bleb formation was measured on day 1 of each lens type. Noninferiority of etafilcon A, with respect to the other two lens types, was assumed if the following difference margins of equivalence were met: <1.5% for corneal swelling, <0.5 grade for limbal hyperemia, and <1% area of endothelial blebs. Outcomes were modeled using generalized linear mixed modeling techniques. RESULTS: All lenses showed reductions in least-square mean estimates of CT on both days: etafilcon A -0.26% at day 1 and -0.31% at day 7; lotrafilcon B -1.11% at day 1 and -1.06% at day 7; comfilcon A -0.63% at day 1 and -0.84% at day 7. The difference in mean swelling between etafilcon A and lotrafilcon B was 0.85% at day 1 (95% confidence interval [0.4%-1.3%]) and 0.75% at day 7 (0.3%-1.2%). The difference in mean swelling between etafilcon A and comfilcon A was 0.37% at day 1 (-0.1% to 0.8%) and 0.53% at day 7 (0.1%-1.0%). For limbal redness, etafilcon A fell within 0.1 grade of lotrafilcon B and 0.18 grade of comfilcon A. For endothelial bleb formation, etafilcon A fell within 0.45% of lotrafilcon B and 0.23% of comfilcon A. CONCLUSION: The etafilcon A control lens resulted in corneal deswelling throughout the day as did the SH lens types. Limbal hyperemia and endothelial bleb formation with all lenses were negligible, and noninferiority assumptions were met between the lens types for all outcomes. Equivalence of etafilcon A with respect to the two SH lenses for three measures of hypoxic stress was demonstrated.

Mucin Balls Influence Corneal Infiltrative Events.

PURPOSE: To determine whether mucin ball (MB) formation is protective against corneal infiltrative events (CIEs) as previously reported. METHODS: Two hundred eighty-two eligible participants were enrolled at three sites in the USA. Participants began a 1-month continuous wear run-in period with high modulus lotrafilcon A lenses to assess their ability to form MBs (phase 1). Subsequently, they were stratified by this characteristic and randomized to balafilcon A or comfilcon A lenses for 7-day extended wear and followed for 1 year (phase 2). MB formation in each phase was defined as repeated presence of any MBs on a person level. Multivariable Cox proportional hazards regression was used to model the probability of a CIE as a function of MB formation in each phase and other covariates. RESULTS: Of the 282 participants who entered phase 1, 218 of them entered the phase 2 randomized trial during which 33 CIEs occurred. Overall, 74%, 61%, and 79% of participants repeatedly produced MBs in lotrafilcon A, balafilcon A, and comfilcon A lenses, respectively. Early repeated MB presence in phase 1 with lotrafilcon A lenses significantly increased the rate of CIEs in phase 2 (12-month follow-up) by 466% (HR 4.66, 95% confidence interval 1.10-19.79, P = .0372). Repeated, longer-term MB presence during wear of balafilcon A or comfilcon A in phase 2 did not significantly reduce the incidence of CIEs; however, it significantly decreased the rate of CIEs by 62% (hazard ratio (HR) 0.380, 95% confidence interval 0.145-0.998, P = .0494). CONCLUSIONS: The overarching hypothesis that MB formation is protective against CIEs throughout extended wear was not supported. Although a protective effect of longer-term MB presence on rate of CIEs was detected, early-onset MB formation substantially increased the hazard for CIE in subsequent wear with different lens types.

A genome-wide association study identifies a potential novel gene locus for keratoconus, one of the commonest causes for corneal transplantation in developed countries.

Keratoconus is a condition in which the cornea progressively thins over time, and is a major cause for cornea transplantation. To identify keratoconus susceptibility regions, we performed a comprehensive genome-wide association study (GWAS) using a discovery and replication design. A discovery panel of 222 keratoconus Caucasian patients and 3324 Caucasian controls was genotyped using Illumina 370K beadchips. Further associated and fine-mapping single nucleotide polymorphisms (SNPs) (n= 4905) were genotyped in an independent replication case-control panel of 304 cases and 518 controls and a family panel of 307 subjects in 70 families. Logistic regression models implemented in PLINK were performed to test associations in case-control samples with and without principal component (PC) adjustments. Generalized estimation equation models accounting for familial correlations implemented in GWAF were used for association testing in families. No genome-wide associations were identified in the discovery GWAS panel. From the initial testing without adjustments for PCs, the top three SNPs located at 3p26 (rs6442925), 2q21.3 (rs4954218) and 19q13.3 (rs1428642) were identified with unadjusted P-values of 6.5 × 10(-8), 2.4 × 10(-7) and 3.1 × 10(-7), respectively. After adjustments for PCs, rs1428642 became the most significant through the genome with a P-value of 1.4 × 10(-6), while rs6442925 and rs4954218 were less significant (P= 1.9 × 10(-5) and 2.6 × 10(-4)). SNP rs4954218 was confirmed in two independent replication panels with P-values of 0.004 and 0.009, respectively. Meta-analysis revealed a highest association at rs4954218 with adjusted P= 1.6 × 10(-7) (unadjusted P= 1.2 × 10(-9)). These findings suggest SNP rs4954218, located near the RAB3GAP1 gene, previously reported to be associated with corneal malformation, is a potential susceptibility locus for keratoconus.

Corneal inflammatory events with daily silicone hydrogel lens wear.

PURPOSE: This study aimed to determine the probability and risk factors for developing a corneal inflammatory event (CIE) during daily wear of lotrafilcon A silicone hydrogel contact lenses. METHODS: Eligible participants (n = 218) were fit with lotrafilcon A lenses for daily wear and followed up for 12 months. Participants were randomized to either a polyhexamethylene biguanide-preserved multipurpose solution or a one-step peroxide disinfection system. The main exposures of interest were bacterial contamination of lenses, cases, lid margins, and ocular surface. Kaplan-Meier (KM) plots were used to estimate the cumulative unadjusted probability of remaining free from a CIE, and multivariate Cox proportional hazards regression was used to model the hazard of experiencing a CIE. RESULTS: The KM unadjusted cumulative probability of remaining free from a CIE for both lens care groups combined was 92.3% (95% confidence interval [CI], 88.1 to 96.5%). There was one participant with microbial keratitis, five participants with asymptomatic infiltrates, and seven participants with contact lens peripheral ulcers, providing KM survival estimates of 92.8% (95% CI, 88.6 to 96.9%) and 98.1% (95% CI, 95.8 to 100.0%) for remaining free from noninfectious and symptomatic CIEs, respectively. The presence of substantial (>100 colony-forming units) coagulase-negative staphylococci bioburden on lid margins was associated with about a five-fold increased risk for the development of a CIE (p = 0.04). CONCLUSIONS: The probability of experiencing a CIE during daily wear of lotrafilcon A contact lenses is low, and symptomatic CIEs are rare. Patient factors, such as high levels of bacterial bioburden on lid margins, contribute to the development of noninfectious CIEs during daily wear of silicone hydrogel lenses.

Risk factors for contact lens-induced papillary conjunctivitis associated with silicone hydrogel contact lens wear.

BACKGROUND: Contact lens-induced papillary conjunctivitis (CLPC) continues to be a major cause of dropout during extended wear of contact lenses. This retrospective study explores risk factors for the development of CLPC during extended wear of silicone hydrogel lenses. METHODS: Data from 205 subjects enrolled in the Longitudinal Analysis of Silicone Hydrogel Contact Lens study wearing lotrafilcon A silicone hydrogel lenses for up to 30 days of continuous wear were used to determine risk factors for CLPC in this secondary analysis of the main cohort. The main covariates of interest included substantial lens-associated bacterial bioburden and topographically determined lens base curve-to-cornea fitting relationships. Additional covariates of interest included history of adverse events, time of year, race, education level, gender, and other subject demographics. Statistical analyses included univariate logistic regression to assess the impact of potential risk factors on the binary CLPC outcome and Cox proportional hazards regression to describe the impact of those factors on time-to-CLPC diagnosis. RESULTS: Across 12 months of follow-up, 52 subjects (25%) experienced CLPC. No associations were found between the CLPC development and the presence of bacterial bioburden, lens-to-cornea fitting relationships, history of adverse events, gender, or race. Contact lens-induced papillary conjunctivitis development followed the same seasonal trends as the local peaks in environmental allergens. CONCLUSIONS: Lens fit and biodeposits, in the form of lens-associated bacterial bioburden, were not associated with the development of CLPC during extended wear with lotrafilcon A silicone hydrogel lenses.

Risk factors for microbial bioburden during daily wear of silicone hydrogel contact lenses.

PURPOSE: To assess risk factors associated with substantial microbial bioburden of lids, conjunctivae, contact lenses, and storage cases during daily wear of silicone hydrogel contact lenses. METHODS: Two hundred eighteen patients were fit to lotrafilcon A lenses, randomized to use either a multipurpose solution or a hydrogen peroxide care system, and followed up for 1 year. Lenses, lens transport saline, lids, conjunctivae, and storage cases were cultured and considered to have substantial microbial bioburden when they harbored high levels of commensal or pathogenic organisms. Univariate and multivariate logistic regression analyses were conducted to examine which demographic covariates were associated with significant bioburden at each location while controlling for solution use. RESULTS: In multivariate analyses, smoking trended toward an association with lens bioburden (odds ratio [OR]=2.15, 95% confidence interval [CI]: 0.95-4.88). Clerical occupations were found to be associated with more frequent overall storage case contamination (OR=3.51, 95% CI: 1.15-10.70) and, specifically, higher gram-positive storage case contamination (OR=5.57, 95% CI: 1.82-17.06). The peroxide system was associated with more frequent storage case contamination (OR=7.6, 95% CI: 3.79-15.19). Coagulase-negative staphylococci (CNS) were the most frequently cultured organisms within storage cases, and in multivariate analyses, CNS were more frequently found in storage cases of peroxide users (OR=6.12, 95% CI: 2.91-13.09). CONCLUSIONS: Clerical occupations were associated with increased microbial bioburden of storage cases during daily wear of silicone hydrogel lenses. Smoking may increase the risk of lens contamination. Storage cases are most frequently contaminated with normal skin flora, and peroxide cases were associated with more frequent contamination. However, the solution type was not associated with lid or lens contamination nor with corneal infiltrative events in this study.