Loretta Szczotka-Flynn

Cedars-Sinai Medical Center, Los Angeles, CA, United States

Are you Loretta Szczotka-Flynn?

Claim your profile

Publications (32)71.5 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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). 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.
    Optometry and vision science: official publication of the American Academy of Optometry 11/2013; · 1.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: UV-blocking contact lenses were evaluated to determine if they could provide adequate ocular protection during narrowband UVB phototherapy treatment. Theoretical safe exposure durations for the crystalline lens, cornea and conjunctiva were determined. A Cary 500 spectrophometer generated transmittance data for six UV-blocking and two non-UV-blocking contact lenses. An IL-1700 radiometer measured the lenses' radiation transmittance within the NB-UVB phototherapy unit. The lenses were exposed to a 1500-mJ/cm(2) dose of radiation from a 308-nm excimer laser to determine if the radiation would alter their protective properties. Theoretical safe exposure durations for eye structures were calculated using previous human and animal study data. All UV-blocking contact lenses showed less than 1E-7 W/cm(2) of radiation transmittance within the narrowband phototherapy unit. The excimer laser did not significantly alter the lenses' UV-blocking capabilities. The safe exposure durations for the cornea and crystalline lens were greater than 11 min with UV-blocking lenses, and that for the unprotected conjunctiva was approximately 11 s. Some UV-blocking contact lenses potentially provide sufficient ocular protection during narrowband UVB phototherapy treatment, as the crystalline lens and cornea are adequately protected should a patient open his or her eyes for a short time.
    Photodermatology Photoimmunology and Photomedicine 10/2013; 29(5):253-60. · 1.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Single nucleotide polymorphisms (SNPs) located near or within the COL5A1 gene, at 9q34.2-q34.3 chromosomal region have been reported in association with central corneal thickness (CCT). Using family linkage analysis, we identified a keratoconus susceptibility locus at 9q34. These findings led us to perform an association study between COL5A1 variation and keratoconus susceptibility. METHODS: A Caucasian case-control cohort of 222 keratoconus patients and 3324 controls was selected as the discovery panel. An independent case-control panel of 304 cases and 518 controls and a family panel of 186 subjects were replicated for genotyping and association. Forty-four SNPs (21 for discovery and 23 for fine-mapping) spanning 300 KB in and around COL5A1 were genotyped and tested for genetic association. Logistic regression models implemented in PLINK were used to test for association in case-controls. Generalized estimating equation models accounting for familial correlations implemented in GWAF were used for association testing in families. RESULTS: Two CCT associated SNPs (rs1536482 and rs7044529 near and within COL5A1), were identified in the keratoconus discovery cohort (p values of 6.5×10(-3) and 7.4×10(-3)). SNP rs1536482 was replicated in the second case-control sample (p=0.02), and SNP rs7044529 was replicated in keratoconus family panel (p=0.03). Meta p values of rs1536482 and rs7044529 in the keratoconus cohorts were 1.5×10(-4) (OR=1.30) and 2.9×10(-3) (OR=1.39). After Bonferroni correction, the association of SNP rs1536482 remained significant (p=6.5×10(-3)). CONCLUSIONS: SNPs in the COL5A1 region, which regulate normal variation in CCT, may play a role in the thinning associated with keratoconus.
    Investigative ophthalmology & visual science 03/2013; · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE:: Keratoconus (KC) is a genetically heterogeneous corneal dystrophy. Previously, we performed 2 genome-wide linkage scans in a 4-generation autosomal dominant pedigree and repeatedly mapped a KC locus to a genomic region located on chromosome 5q overlapping the gene encoding the inhibitor of calpains, calpastatin (CAST). To test whether variants in CAST gene are involved in genetic susceptibility to KC, we performed genetic testing of polymorphic markers in CAST gene in family and case-control panels of patients with KC. METHODS:: We genotyped single-nucleotide polymorphisms (SNPs) located in CAST gene in 262 patients in 40 white KC families and in a white case-control panel with 304 cases and 518 controls. Generalized estimating equation models accounting for familial correlations implemented in GWAF program were used for association testing in families. Logistic regression models implemented in PLINK were performed to test the associations in case-control samples. RESULTS:: Genetic testing of the first set of 7 SNPs in familial samples revealed 2 tentative nominally significant markers (rs4869307, P = 0.03; rs27654, P = 0.07). Additional genotyping of 12 tightly spaced SNPs identified CAST SNP rs4434401 to be associated with KC in both familial and case-control panels with P values of 0.005 and 0.05, respectively, and with combined meta P value of familial and case-control cohorts of 0.002 or after Bonferroni correction of 0.04. CONCLUSIONS:: Linkage analysis and genetic association support involvement of CAST gene in the genetic susceptibility to KC. In silico analysis of CAST expression suggests differential regulation of calpain/calpastatin system in cornea as a potential mechanism of functional defect.
    Cornea 02/2013; · 1.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Microbial infections of the cornea frequently cause painful, blinding and debilitating disease that is often difficult to treat and may require corneal transplantation. In addition, sterile corneal infiltrates that are associated with contact lens wear cause pain, visual impairment and photophobia. In this article, we review the role of Toll-Like Receptors (TLR) in bacterial keratitis and sterile corneal infiltrates, and describe the role of MD-2 regulation in LPS responsiveness by corneal epithelial cells. We conclude that both live bacteria and bacterial products activate Toll-Like Receptors in the cornea, which leads to chemokine production and neutrophil recruitment to the corneal stroma. While neutrophils are essential for bacterial killing, they also cause tissue damage that results in loss of corneal clarity. These disparate outcomes, therefore, represent a spectrum of disease severity based on this pathway, and further indicate that targeting the TLR pathway is a feasible approach to treating inflammation caused by live bacteria and microbial products. Further, as the P. aeruginosa type III secretion system (T3SS) also plays a critical role in disease pathogenesis by inducing neutrophil apoptosis and facilitating bacterial growth in the cornea, T3SS exotoxins are additional targets for therapy for P. aeruginosa keratitis.
    International Reviews Of Immunology 01/2013; 32(1):4-18. · 5.73 Impact Factor
  • Loretta Szczotka-Flynn, Robin Chalmers
    [Show abstract] [Hide abstract]
    ABSTRACT: Contact lens-associated corneal infiltrative events (CIEs) are presumed sterile events that have complicated contact lens wear for more than 30 years. There is consistent evidence that silicone hydrogel soft contact lenses increase CIE risk by twofold compared with low Dk hydrogel materials. The incidence of CIEs during silicone hydrogel extended wear ranges from 2% to 6% for symptomatic events and from 6% to 25% when asymptomatic events are included. For daily wear, with silicone hydrogels, the incidence of CIEs ranges from 2% to 3% for symptomatic events and from 7% to 20% when asymptomatic events are included. Despite the increased rate of CIEs with silicone hydrogels, the benefits of these lenses largely outweigh this risk for many patients. Most risk factors for CIEs observed with silicone hydrogels are consistent with CIE risk factors reported earlier with hydrogel lenses, such as bacterial bioburden on lens surfaces, and young age among others. Limiting the transfer of bacterial bioburden from the skin to lenses, lens cases and eventually to the eye is an obvious step forward for the prevention of CIEs across all lens types.
    Eye & contact lens 11/2012;
  • Source
    Rong Zhou, Rui Zhang, Yan Sun, Sean Platt, Loretta Szczotka-Flynn, Eric Pearlman
    [Show abstract] [Hide abstract]
    ABSTRACT: Serratia marcescens is frequently isolated from lenses of patients with contact lens-associated corneal infiltrates. In the current study, we examined the role of toll-like receptors (TLRs) and interleukin-1 receptor type 1 (IL-1R1) in S. marcescens-induced corneal inflammation and infection. The central corneal epithelium of C57BL/6 and gene knockout mice was abraded, and 1 × 10(7) S. marcescens were added in the presence of a silicone hydrogel contact lens, and we examined corneal inflammation by confocal microscopy and neutrophil enumeration. Viable bacteria were quantified by colony-forming units (CFU). S. marcescens induced neutrophil recruitment to the corneal stroma, and increased corneal thickness and haze in C57BL/6 mice. Conversely, CFU was significantly lower by 48 hours post infection. In contrast, MyD88(-/-), IL-1R(-/-), TLR4(-/-), and TLR4/5(-/-) corneas infected with S. marcescens had significantly increased CFU, indicating impaired clearance. However, there was no significant difference in CFU among C57BL/6, TIRAP(-/-), and TRIF(-/-) mice. Tobramycin-killed S. marcescens induced corneal inflammation in C57BL/6 mice, which was impaired significantly in MD-2(-/-) mice and in C57BL/6 mice pretreated topically with the MD-2 antagonist eritoran tetrasodium. S. marcescens induces corneal inflammation by activation of TLR4/MD-2/MyD88 and the IL-1R1/MyD88 pathways, which are potential therapeutic targets for inhibition of S. marcescens-induced corneal inflammation.
    Investigative ophthalmology & visual science 10/2012; 53(11):7382-8. · 3.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Keratoconus is a bilateral noninflammatory progressive corneal disorder with complex genetic inheritance and a common cause for cornea transplantation in young adults. A genomewide linkage scan in keratoconus families identified a locus at 5q23.2, overlapping the gene coding for the lysyl oxidase (LOX). LOX encodes an enzyme responsible for collagen cross-linking in a variety of tissues including the cornea. Corneal collagen cross-linking with long-wave ultraviolet light and riboflavin is a promising new treatment for keratoconus. To determine whether LOX is a genetic determinant of the pathogenesis of keratoconus, we analyzed association results of LOX polymorphisms in two independent case-control samples and in keratoconus families. Association results were analyzed of single-nucleotide polymorphisms (SNPs) in the LOX gene from a Genome-Wide Association Study (GWAS) investigation in two independent panels of patients with keratoconus and controls and in keratoconus families. Evidence of association was found at SNPs rs10519694 and rs2956540 located in intron 4 of LOX in the GWAS discovery case-control panel with P values of 2.3×10(-3) and 7×10(-3), respectively. The same two SNPs were found to be associated with keratoconus by family-based association testing with P values of 2.7×10(-3) and 7.7×10(-4), respectively. Meta P values of 4.0×10(-5) and 4.0×10(-7) were calculated for SNPs rs10519694 and rs2956540 by analyzing case-control and family samples simultaneously. Sequencing of LOX exons in a subset of keratoconus patients identified two polymorphisms, rs1800449 and rs2288393, located in LOX transcripts I and II, associated with keratoconus in case-control and family samples with a meta P value of 0.02. Results provided strong genetic evidence that LOX variants lead to increased susceptibility to developing of keratoconus.
    Investigative ophthalmology & visual science 06/2012; 53(7):4152-7. · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE:: To assess the effect of topical taprenepag isopropyl on each layer of the cornea by confocal microscopy. METHODS:: Thirty-two ocular hypertensive or glaucoma patients were randomized into a 2-period, crossover study of 14 days of 0.1% taprenepag alone and in unfixed combination with 0.005% latanoprost (combination therapy). Baseline and sequential slit-lamp biomicroscopy, fluorescein staining, central ultrasonic pachymetry, and confocal microscopy were performed. Confocal images were analyzed for the density of the central superficial and basal epithelium, midstromal keratocytes, and endothelium, as well as endothelial coefficient of variation and percentage of hexagonal cells, and reflectivity of anterior stromal and midstromal layers. RESULTS:: Corneal staining increased from baseline, reaching a peak at day 13 (69% and 63% of subjects treated with monotherapy and combination therapy, respectively), which resolved by day 35. A statistically significant increase in mean corneal thickness for both eyes and both treatments occurred on days 7 and 13 (range, 20-27 μm; P < 0.001) but recovered (≤6 μm) by day 35. No statistically significant changes were observed in the basal epithelial, midstromal, or endothelial cells. Mean ratio of average reflectivity of anterior stroma to midstroma increased on days 13 and 35 in period 1 for each treatment (range, 1.2-1.9; P < 0.001), and this increase persisted during period 2. CONCLUSIONS:: Anterior stromal reflectivity may remain increased even when biomicroscopic and confocal images of corneal layers remain normal or have recovered after topical taprenepag. This subclinical measure may be useful to detect a persistent adverse effect of a topical agent on the cornea.
    Cornea 04/2012; · 1.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to assess the effect of lens wear on the formation of soft contact lens-associated Fusarium biofilms and to determine the efficacy of marketed contact lens care products against such biofilms. Using an established in vitro soft contact lens-Fusarium biofilm model, two clinical Fusarium isolates (F. solani B6914 and F. oxysporum B8996) were incubated with three different types (lotrafilcon A, etafilcon A, and balafilcon A) of worn contact lenses under conditions that facilitate biofilm formation. Unworn lenses were used as internal controls for biofilm formation. Biofilm was quantified using a tetrazolium XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) assay. In addition, susceptibilities of the fungal biofilm growth phases to the five most common multipurpose contact lens care solutions available at the time of study (three polymeric biguanide-preserved and two polyquaternium-preserved) and two hydrogen peroxide care solutions were assessed. Both Fusarium strains formed dense biofilms on each of the contact lens types tested. Worn lenses showed no differences in the ability of biofilm to form compared with unworn lenses except worn etafilcon A lenses which formed more biofilm with F. oxyspourm B8996 compared with unworn controls. Lens material did not influence biofilm formation. The biofilms of F. solani on all three lens types were consistently susceptible to both hydrogen peroxide care systems (growth reduction of 84 to 97%, p ≤ 0.001) and two of the five multipurpose solutions (MPSs) (growth reduction of 62 to 85% for a biguanide-preserved MPS, p ≤ 0.05; growth reduction of 92 to 96% for a polyquaternium-myristamidopropyl dimethylamine preserved MPS, p < 0.001). The biofilms of F. oxysporum on all three lens types were consistently susceptible to both hydrogen peroxide care systems (growth reduction of 79 to 99%, p ≤ 0.001) and one of the five MPSs (growth reduction of 93 to 96% for a polyquaternium-myristamidopropyl dimethylamine preserved MPS, p ≤ 0.001). F. solani and F. oxysporum form biofilms on lotrafilcon A, etafilcon A, and balafilcon A worn contact lenses, which are resistant to the antifungal activity of several soft contact lens care products. Only the hydrogen peroxide care systems and one polyquaternium-myristamidopropyl dimethylamine-preserved solution consistently demonstrated effective antifungal activity against both Fusarium strains on all three lens types.
    Optometry and vision science: official publication of the American Academy of Optometry 03/2012; 89(4):382-91. · 1.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Human Molecular Genetics 01/2012; 21(2):421-9. · 7.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Keratoconus is a progressive disorder of the cornea that can lead to severe visual impairment or blindness. Although several genomic regions have been linked to rare familial forms of keratoconus, no genes have yet been definitively identified for common forms of the disease. Two genome-wide association scans were undertaken in parallel. The first used pooled DNA from an Australian cohort, followed by typing of top-ranked single-nucleotide polymorphisms (SNPs) in individual DNA samples. The second was conducted in individually genotyped patients, and controls from the USA. Tag SNPs around the hepatocyte growth factor (HGF) gene were typed in three additional replication cohorts. Serum levels of HGF protein in normal individuals were assessed with ELISA and correlated with genotype. The only SNP observed to be associated in both the pooled discovery and primary replication cohort was rs1014091, located upstream of the HGF gene. The nearby SNP rs3735520 was found to be associated in the individually typed discovery cohort (P = 6.1 × 10(-7)). Genotyping of tag SNPs around HGF revealed association at rs3735520 and rs17501108/rs1014091 in four of the five cohorts. Meta-analysis of all five datasets together yielded suggestive P values for rs3735520 (P = 9.9 × 10(-7)) and rs17501108 (P = 9.9 × 10(-5)). In addition, SNP rs3735520 was found to be associated with serum HGF level in normal individuals (P = 0.036). Taken together, these results implicate genetic variation at the HGF locus with keratoconus susceptibility.
    Investigative ophthalmology & visual science 10/2011; 52(11):8514-9. · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the association between mucin ball formation and corneal infiltrative events (CIEs) during continuous wear with lotrafilcon A silicone hydrogel contact lenses. Subjects (n = 205) in the Longitudinal Analysis of Silicone Hydrogel Contact Lens Study wore lotrafilcon A contact lenses for 12 months of continuous wear. The primary outcome was a CIE. Kaplan-Meier methods were used to estimate the unadjusted cumulative incidence of remaining CIE free stratified by mucin ball presence. Cox proportional hazards regression was used to model the hazard of developing a CIE as a function of mucin ball formation and other covariates. Over half (54.2%) of the subjects displayed some presence of mucin balls during at least 1 visit and about one third (32.8%) displayed repeated episodes. Mucin ball scores were correlated between the 2 eyes and weakly correlated with corneal curvature (P ≤ 0.005). Univariate analyses revealed that the relative hazard for a CIE was 0.35 [95% confidence interval (CI), 0.19-0.68] if a single episode of mucin balls was detected and 0.17 (95% CI, 0.06-0.43) if repeated episodes were detected. Upon multivariate analysis, repeated presence of mucin balls was associated with an 84% decreased hazard of experiencing a CIE (hazard ratio: 0.16; 95% CI, 0.06-0.44). The presence of mucin balls is significantly associated with a decreased incidence of CIEs, and the effect is greatest when they are repeatedly present over time. We hypothesize that the mucin ball presence represents a more concentrated or viscous mucus layer, which prevents upregulation of the immune response against bacterial ligands.
    Cornea 12/2010; 30(5):535-42. · 1.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study determined which microbiologic, clinical, demographic, and behavioral factors are associated with corneal infiltrative events (CIEs) during continuous wear of silicone hydrogel (SH) contact lenses. Subjects (n = 205) were fitted with lotrafilcon A lenses for continuous wear and observed for 1 year. The main exposures of interest were corneal staining and bacterial lens contamination. Kaplan-Meier (KM) plots were used to estimate the cumulative unadjusted probability of remaining CIE free, and Cox proportional hazards regression was used to model the hazard of having a CIE, as a function of key predictor variables. The KM-unadjusted cumulative probability of remaining CIE free was 73.3%. Approximately 53% of subjects had repeated episodes of corneal staining (mild or greater), and 11.3% had repeated episodes of moderate or greater corneal staining. Corneal staining was not associated with the development of a CIE. The frequency of substantial bacterial bioburden on worn lenses at the time of a CIE was 64.7%, compared with only 12.2% during uncomplicated wear. The presence of substantial lens bacterial bioburden was associated with the development of a CIE (adjusted hazards ratio [HR], 8.66; 95% confidence interval [CI], 2.88-26.01). Smoking was also associated with a CIE (adjusted HR, 4.13; 95% CI, 1.27-13.45). Corneal staining is common during continuous wear of SH lenses, but it is not associated with the development of a CIE. Smoking and substantial lens bacterial bioburden pose prominent risks of a CIE. In this study, more than 70% of the total risk of CIE in those with substantial lens bioburden is attributable to this exposure. (ClinicalTrials.gov number, NCT00727402).
    Investigative ophthalmology & visual science 11/2010; 51(11):5421-30. · 3.43 Impact Factor
  • Source
    Loretta B Szczotka-Flynn, Eric Pearlman, Mahmoud Ghannoum
    [Show abstract] [Hide abstract]
    ABSTRACT: A contact lens (CL) can act as a vector for microorganisms to adhere to and transfer to the ocular surface. Commensal microorganisms that uneventfully cohabitate on lid margins and conjunctivae and potential pathogens that are found transiently on the ocular surface can inoculate CLs in vivo. In the presence of reduced tissue resistance, these resident microorganisms or transient pathogens can invade and colonize the cornea or conjunctiva to produce inflammation or infection. The literature was reviewed and used to summarize the findings over the last 30 years on the identification, enumeration, and classification of microorganisms adherent to CLs and their accessories during the course of normal wear and to hypothesize the role that these microorganisms play in CL infection and inflammation. Lens handling greatly increases the incidence of lens contamination, and the ocular surface has a tremendous ability to destroy organisms. However, even when removed aseptically from the eye, more than half of lenses are found to harbor microorganisms, almost exclusively bacteria. Coagulase-negative Staphylococci are most commonly cultured from worn lenses; however, approximately 10% of lenses harbor Gram-negative and highly pathogenic species, even in asymptomatic subjects. In storage cases, the incidence of positive microbial bioburden is also typically greater than 50%. All types of care solutions can become contaminated, including up to 30% of preserved products. The process of CL-related microbial keratitis and inflammation is thought to be preceded by the presence or transfer or both of microorganisms from the lens to the ocular surface. Thus, this detailed understanding of lens-related bioburden is important in the understanding of factors associated with infectious and inflammatory complications. Promising mechanisms to prevent bacterial colonization on lenses and lens cases are forthcoming, which may decrease the incidence of microbially driven CL complications.
    Eye & contact lens 02/2010; 36(2):116-29.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fusarium solani and F. oxysporum were the causative organisms of the 2005/2006 outbreak of contact lens-associated fungal keratitis in the United States. The present study was an investigation of the ability of F. oxysporum grown as a biofilm on silicone hydrogel contact lenses to induce keratitis. A clinical isolate of F. oxysporum was grown as a biofilm on lotrafilcon A contact lenses, and a 2-mm diameter punch was placed on the abraded corneal epithelium of either untreated or cyclophosphamide-treated C57BL/6 mice or of IL-1R1(-/-), MyD88(-/-), TLR2(-/-), or TLR4(-/-) mice. After 2 hours, the lens was removed, and corneal opacification, colony forming units (CFUs), and histopathology were evaluated. C57BL/6 mice developed severe corneal opacification within 24 hours and resolved after four days. In contrast, corneal opacification progressed in cyclophosphamide-treated mice, and was associated with unimpaired fungal growth in the cornea, and with hyphae penetrating into the anterior chamber. The phenotype of MyD88(-/-) and IL-1R(-/-) mice was similar to that of cyclophosphamide-treated animals, with significantly impaired cellular infiltration and fungal clearance. Although TLR4(-/-) mice developed a cellular infiltrate and corneal opacification similar to C57BL/6 mice, the CFU count was significantly and consistently higher. Fusarium grown as a biofilm on silicone hydrogel contact lenses can induce keratitis on injured corneas, with disease severity and fungal killing dependent on the innate immune response, including IL-1R1, MyD88, and TLR4.
    Investigative ophthalmology & visual science 10/2009; 51(3):1511-6. · 3.43 Impact Factor
  • Source
    Loretta B Szczotka-Flynn, Saralee Bajaksouzian, Michael R Jacobs, Alfred Rimm
    [Show abstract] [Hide abstract]
    ABSTRACT: Microbial contamination of contact lenses is associated with corneal infection and inflammation. This study determined the microbiological, clinical, and demographic factors that are associated with bacterial contamination of a silicone hydrogel contact lens when worn for continuous wear (CW). Two hundred five healthy subjects were enrolled in the Longitudinal Analysis of Silicone Hydrogel Contact Lens Study and were fitted with lotrafilcon A lenses for monthly CW and followed for 1 year. Lenses were aseptically removed after 1 week and 4 months of wear and cultured using an agar sandwich technique. Lids and conjunctiva were routinely cultured at baseline and after 1 week and 4 months of CW. Lenses and ocular sites were considered to have substantial microbial bioburden when they harbored pathogenic organisms or high levels of commensal organisms. Univariate and multivariate logistic regression analyses were conducted to examine whether substantial conjunctival or lid bioburden, subject demographics, lens-wearing history, symptoms, and biomicroscopic signs were associated with lens bioburden. About one third (32.4%) of subjects had substantial bacterial bioburden in either eye across multiple visits. Over half (53.2%) and about one tenth (11.7%) of subjects had substantial lid and conjunctival bioburden, respectively, and 11.2% discontinued because of discomfort. The adjusted odds ratios (and 95% confidence intervals) for presence of substantial lens bioburden were 2.49 (1.17-5.30), 4.24 (1.45-12.40), and 4.11 (1.17-14.46) for substantial lid bioburden, substantial conjunctival bioburden, and lens discomfort, respectively. Bacterial contamination of silicone hydrogel contact lenses is common during CW. Substantial lens bioburden is associated with discomfort precluding successful CW. The presence of substantial lid and conjunctival bioburden is associated with a 2.5-fold and more than fourfold greater risk of substantial lens bioburden and is likely the major route of contamination.
    Optometry and vision science: official publication of the American Academy of Optometry 09/2009; 86(11):1216-26. · 1.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine if clinical and reference strains of Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus form biofilms on silicone hydrogel contact lenses and ascertain antimicrobial activities of contact lens care solutions. Clinical and American Type Culture Collection reference strains of P. aeruginosa, S. marcescens, and S. aureus were incubated with lotrafilcon A lenses under conditions that facilitate biofilm formation. Biofilms were quantified by quantitative culturing (colony-forming units, CFUs), and gross morphology and architecture were evaluated using scanning electron microscopy and confocal microscopy. Susceptibilities of the planktonic and biofilm growth phases of the bacteria to 5 common multipurpose contact lens care solutions and 1 hydrogen peroxide care solution were assessed. Pseudomonas aeruginosa, S. marcescens, and S. aureus reference and clinical strains formed biofilms on lotrafilcon A silicone hydrogel contact lenses, as dense networks of cells arranged in multiple layers with visible extracellular matrix. The biofilms were resistant to commonly used biguanide-preserved multipurpose care solutions. Pseudomonas aeruginosa and S. aureus biofilms were susceptible to a hydrogen peroxide and a polyquaternium-preserved care solution, whereas S. marcescens biofilm was resistant to a polyquaternium-preserved care solution but susceptible to hydrogen peroxide disinfection. In contrast, the planktonic forms were always susceptible. Pseudomonas aeruginosa, S. marcescens, and S. aureus form biofilms on lotrafilcon A contact lenses, which in contrast to planktonic cells are resistant to the antimicrobial activity of several soft contact lens care products.
    Cornea 09/2009; 28(8):918-26. · 1.75 Impact Factor
  • Loretta Szczotka-Flynn, Rouzbeh Ahmadian, Mireya Diaz
    [Show abstract] [Hide abstract]
    ABSTRACT: In 1995, Myers and Weiss published an article comparing the risk of ulcerative keratitis related to low oxygen permeability (Dk) extended contact lens wear to other life risks. This article updates the risks associated with silicone hydrogel (SH) extended wear contact lens use and some comparative life risks, to provide a current perspective within the hierarchy of life risks. A comparative ratio was defined as the incidence of microbial keratitis in a population of SH extended wear contact lens users divided by the incidence of other disease or occurrence in a given population at risk. The risk of SH lens-related microbial keratitis is about 1.5 to 16 times less risky than certain nonfatal disruptive occurrences in the general population, and about the same as the risk of developing breast cancer. Compared with other ocular conditions, the risk of microbial keratitis with SH lenses is about the same as developing late-stage age-related macular degeneration or retinal detachment after cataract extraction on an annual basis; it is over 200 times greater than developing eye or orbit cancer; it is about 7, 20, or more than 30 times less than proceeding to penetrating keratoplasty in keratoconus, developing nuclear cataract, or experiencing a corneal inflammatory event during low-Dk extended wear, respectively. Although the risk of microbial keratitis with modern day SH contact lens extended wear has not changed since the 1980s, when put in perspective with other life risks, it is a relatively rare occurrence.
    Eye & contact lens 04/2009; 35(2):69-75.
  • Loretta B Szczotka-Flynn, Shamil Patel
    [Show abstract] [Hide abstract]
    ABSTRACT: The tisilfocon A (Menicon Z) rigid gas permeable (RGP) contact lens polymer has the highest oxygen permeability (Dk) value of any RGP lens material. To our knowledge there is no published literature documenting the success of this material in fitting contact lenses to highly irregular and diseased corneas. A retrospective medical record review of 40 consecutive patients (64 eyes) who had worn lenses made in the Menicon Z RGP material was performed. All patients had some form of corneal pathology and were fitted in a single tertiary care hospital-based contact lens service. Menicon Z contact lenses were fit to 33 eyes of 20 patients with keratoconus (KC) and 31 eyes of 23 patients with irregular corneas. The irregular cornea group comprised 28 eyes of 21 patients after corneal surgery, 1 eye with ocular cicatricial pemphigoid and 2 eyes of 1 patient with chronic staphylococcal blepharo-keratoconjuncitivitis. Treatment goals included acceptable corneal physiology, comfort, and visual acuity. In the KC group, there was an 82% (27/33 eyes) success rate as measured by the treatment goals. Mean duration of wear for successful patients was 2.5 years (0.5-5 years). Only 12% (4/33 eyes) failed directly due to inability of the Menicon Z material to perform adequately while another material was acceptable. In the irregular surface group (surgical and ocular surface disease), there was a 74% (23/31 eyes) success rate. Mean duration of wear for successful patients in this group is 2.79 years (3 months-7 years). Only 3% (1/31 eyes) failed directly due to inability of the Menicon Z material to perform adequately while another material was acceptable. The tisilfocon A hyper Dk lens material maintains clinically acceptable corneal health and clinically acceptable visual acuity for patients with KC and irregular corneal surfaces. In this series of patients with complicated corneal disease, the most failures were due to design issues and discomfort not related to the Menicon Z material. The Menicon Z material was inadequate in only 8% of eyes, whereas another RGP material was successful. Most patients with irregular corneas in a tertiary care center can be successfully fit with the tisilfocon A RGP material for visual rehabilitation.
    Eye & contact lens 10/2008; 34(5):254-60.

Publication Stats

423 Citations
71.50 Total Impact Points

Institutions

  • 2012–2013
    • Cedars-Sinai Medical Center
      • Cedars Sinai Medical Center
      Los Angeles, CA, United States
    • San Diego Regenerative Medicine Institute
      San Diego, California, United States
  • 2004–2012
    • Case Western Reserve University
      • • Department of Ophthalmology and Visual Sciences (University Hospitals Case Medical Center)
      • • Department of Epidemiology and Biostatistics
      Cleveland, Ohio, United States
  • 2004–2008
    • Case Western Reserve University School of Medicine
      • Department of Dermatology
      Cleveland, Ohio, United States