Publications by authors named "Penny A Asbell"

98 Publications

Effect of Omega-3 on HLA-DR Expression by Conjunctival Cells and Tear Cytokine Concentrations in the Dry Eye Assessment and Management Study.

Eye Contact Lens 2022 Jun 30. Epub 2022 Jun 30.

Department of Ophthalmology (N.S.R.), Weill Cornell Medicine, New York, NY; Department of Ophthalmology (Y.Y., G.Y., M.G.M.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and Department of Ophthalmology (P.A.A.), Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN.

Objectives: To determine effect of omega-3 supplementation on conjunctival cell HLA-DR expression and tear concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, interferon-γ, and tumor necrosis factor-α in dry eye disease patients in the Dry Eye Assessment and Management study.

Methods: Patients were randomized to receive a daily dose of eicosapentaenoic and docosahexaenoic acids (ω3) or refined olive oil (placebo) for 12 months. At baseline, 6 and 12 months, HLA-DR expression in conjunctival total, epithelial, and white blood cells and cytokine concentration in tears were determined. Differences in change from baseline between treatment groups were assessed using generalized estimating equations (HLA-DR) or Wilcoxon rank-sum test (cytokines).

Results: No differences were observed in HLA-DR expression in total, epithelial, or white blood cells between ω3 and placebo groups at 6 months (n=435) or 12 months (n=436). The median concentration percent change differed between ω3 and placebo groups at 6 months for IL-6 (-36.6 vs. 24.5%, P=0.02, n=75) and for IL-8 (3.7% vs. 72.6%, P=0.02, n=68); at 12 months, they did not differ (P≥0.18). No other differences between the treatment groups were detected.

Conclusions: ω3 supplementation did not consistently affect ocular inflammatory status as measured by the frequency of HLA-DR expressing conjunctival cells or tear cytokines.
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http://dx.doi.org/10.1097/ICL.0000000000000916DOI Listing
June 2022

Another Disappointment for ω-3 Fatty Acid and Dry Eye Disease.

JAMA Ophthalmol 2022 07;140(7):714-715

Department of Ophthalmology, University of Pennsylvania, Philadelphia.

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http://dx.doi.org/10.1001/jamaophthalmol.2022.1821DOI Listing
July 2022

Lirentelimab for severe and chronic forms of allergic conjunctivitis.

J Allergy Clin Immunol 2022 Apr 4. Epub 2022 Apr 4.

Massachusetts Eye Research & Surgery Institution, Waltham, Mass. Electronic address:

Background: Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells.

Objective: We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study.

Methods: Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed.

Results: Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions.

Conclusions: Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.
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http://dx.doi.org/10.1016/j.jaci.2022.03.021DOI Listing
April 2022

Assessing the Quality, Reliability, and Readability of Online Information on Dry Eye Disease.

Cornea 2022 Aug 24;41(8):1023-1028. Epub 2022 Mar 24.

Department of Ophthalmology, Hamilton Eye Institute-University of Tennessee, Memphis, TN.

Purpose: The purpose of this study was to assess the quality, reliability, readability, and technical quality of web sites relating to dry eye disease.

Methods: A cross-sectional study was conducted that evaluated the first 75 web sites on a Google Search by using the keyword "dry eyes." Each web site was evaluated by 2 independent reviewers using the DISCERN, HONcode, and JAMA criteria to assess quality and reliability. Interrater reliability was also analyzed. Readability was assessed using the Flesch-Kincaid readability tests and the Gunning fog, Simple Measure of Gobbledygook, Coleman-Liau, and automated readability indices. Technical quality was determined by the presence of 10 specific features. Web sites were further categorized into institutional (academic centers, medical associations, and government institutions) and private (private practices) categories.

Results: There was no significant difference in scoring observed between the 2 reviewers. The overall mean DISCERN score ± standard error (SE) was 3.2 ± 0.1, the mean HONcode score (±SE) was 9.3 ± 0.3, and the mean JAMA score (±SE) was 1.9 ± 0.1. Institutional web sites had a higher DISCERN score (3.4 ± 0.1 vs. 3.1 ± 0.1; P < 0.05) and HONcode score (10.3 ± 0.5 vs. 8.8 ± 0.4; P < 0.05) than private sites. Technical quality was higher in institutional web sites compared with private web sites ( P < 0.05). Readability was poor among all web sites, with most web sites not achieving below a ninth grade reading level.

Conclusions: Quality, reliability, and readability scores were low for most web sites. Although institutional web sites achieved higher scores than private web sites, revision is warranted to improve their overall quality of information and readability profile.
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http://dx.doi.org/10.1097/ICO.0000000000003034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273298PMC
August 2022

Antibiotic susceptibility of bacterial pathogens isolated from the aqueous and vitreous humour in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) Surveillance Study: 2009-2020 update.

J Glob Antimicrob Resist 2022 Jun 23;29:236-240. Epub 2022 Mar 23.

Scripps Health, La Jolla, California.

Objectives: We evaluated antibiotic resistance among intraocular isolates obtained from presumed endophthalmitis cases collected from 2009 through 2020 in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) study, the only ongoing nationwide surveillance study tracking in vitro resistance in ocular pathogens.

Methods: Presumed endophthalmitis isolates obtained from the aqueous humour and vitreous humour were collected from participating centres, and minimum inhibitory concentrations were determined and interpreted per Clinical and Laboratory Standards Institute methods and available breakpoints.

Results: A total of 307 presumed endophthalmitis isolates (aqueous humour, n = 88; vitreous humour, n = 219) were obtained from 43 clinical sites, including 188 coagulase-negative staphylococci (CoNS), 61 Staphylococcus aureus, 31 Streptococcus pneumoniae, 14 Pseudomonas aeruginosa, and 13 Haemophilus influenzae isolates. Of the CoNS isolates, 47.9% (90/188) were methicillin resistant, 58.0% (109/188) were azithromycin resistant, and 46.3% (87/188) were ciprofloxacin resistant. Of the S. aureus isolates, 45.9% (28/61) were methicillin resistant, 57.4% (35/61) were azithromycin resistant, and 44.3% (27/61) were ciprofloxacin resistant. Multidrug resistance (MDR; i.e., resistance to ≥3 antibiotic classes) was prevalent among staphylococci, particularly methicillin-resistant strains, of which >70% exhibited MDR. Resistance among S. pneumoniae isolates was notable for azithromycin and penicillin, each 38.7% (12/31), and for polymyxin B among P. aeruginosa 100.0% (14/14), whereas no resistance was observed for H. influenzae isolates to the antibiotics tested.

Conclusion: In vitro antibiotic resistance was common among presumed endophthalmitis isolates collected in the ARMOR surveillance study. These data could inform antibiotic selection for infection prophylaxis and/or treatment of intraocular infections.
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http://dx.doi.org/10.1016/j.jgar.2022.03.010DOI Listing
June 2022

A Systematic Review of Multi-decade Antibiotic Resistance Data for Ocular Bacterial Pathogens in the United States.

Ophthalmol Ther 2022 Apr 3;11(2):503-520. Epub 2022 Feb 3.

Department of Ophthalmology, Hamilton Eye Institute, The University of Tennessee Health Science Center, 20 Madison Ave, Memphis, TN, 38163, USA.

Introduction: Since 2009, the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study has been assessing in vitro antibiotic resistance for bacterial isolates sourced from ocular infections in the US. The main goal of this systematic review was to compare in vitro resistance data for ocular pathogens from published US studies with the most recently published data from the ARMOR study (2009-2018) and, where possible, to evaluate trends in bacterial resistance over time over all studies.

Methods: A literature search was conducted using MEDLINE®, BIOSIS Previews®, and EMBASE databases (1/1/1995-6/30/2021). Data were extracted from relevant studies and antibiotic susceptibility rates for common ocular pathogens (Staphylococcus aureus, coagulase-negative staphylococci [CoNS], Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae), longitudinal changes in susceptibility, and multidrug resistance (MDR) were compared descriptively.

Results: Thirty-two relevant studies were identified. High in vitro resistance was found among S. aureus and CoNS to fluoroquinolones, macrolides, and methicillin/oxacillin across studies, with high rates of MDR noted, specifically among methicillin-resistant staphylococci. Data from studies pre-dating or overlapping the early years of ARMOR reflected increasing rates of S. aureus resistance to fluoroquinolones, macrolides, methicillin/oxacillin, and aminoglycosides, while the ARMOR data suggested slight decreases in resistance to these classes between 2009 and 2018. Overall, methicillin-resistant S. aureus (MRSA) prevalence peaked from 2005 to 2015 with a possible decreasing trend in more recent years.

Discussion And Conclusions: Data from local and regional US datasets were generally consistent with data from the national ARMOR surveillance study. Continued surveillance of ocular bacterial pathogens is needed to track trends such as methicillin resistance and MDR prevalence and any new emerging antibiotic resistance phenotypes. Susceptibility data from ARMOR can inform initial choice of therapy, especially in practice areas where local antibiograms are unavailable.
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http://dx.doi.org/10.1007/s40123-021-00449-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8927494PMC
April 2022

In Vitro Antibiotic Resistance among Bacteria from the Cornea in the Antibiotic Resistance Monitoring in Ocular MicRoorganisms Surveillance Study.

Optom Vis Sci 2021 09;98(9):1113-1121

University of Tennessee Health Science Center, Knoxville, Tennessee.

Purpose: This study aimed to report on in vitro susceptibility patterns among corneal isolates collected in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) study.

Methods: Each year, from 2009 to 2019, Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae isolates cultured from patients with ocular infections at participating ARMOR sites were submitted to a central laboratory for species confirmation and antibiotic susceptibility testing. In this analysis of corneal isolates, odds ratios for concurrent resistance were based on sample proportions, one-way ANOVA was used to evaluate resistance by patient age, and Cochran-Armitage tests were used to examine changes in antibiotic resistance over time.

Results: A total of 1499 corneal isolates were collected from 61 sites over the 11-year period. Overall, 34.5% (148 of 429) of S. aureus and 41.9% (220 of 525) of CoNS isolates were methicillin resistant and had higher odds ratios for concurrent resistance to azithromycin (17.44 and 5.67), ciprofloxacin (39.63 and 12.81), and tobramycin (19.56 and 19.95), respectively, relative to methicillin-susceptible isolates (P < .001, all); also, a high proportion of methicillin-resistant S. aureus (85.1%) and methicillin-resistant CoNS (81.8%) were multidrug resistant (at least three classes of antibiotics). Resistance among S. pneumoniae isolates was highest for azithromycin (33.1%), whereas P. aeruginosa and H. influenzae isolates demonstrated low resistance overall. Among staphylococci, antibiotic resistance differed by patient age (S. aureus: F = 6.46, P < .001; CoNS: F = 4.82, P < .001), and few small changes in resistance (≤3.60% per year), mostly decreases, were observed over time.

Conclusions: Although rates of in vitro antibiotic resistance among presumed keratitis isolates obtained in ARMOR seemed stable between 2009 and 2019, resistance among staphylococci and pneumococci remains high (and should be considered when treating keratitis).
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http://dx.doi.org/10.1097/OPX.0000000000001768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505161PMC
September 2021

Correlation of Measures From the OCULUS Keratograph and Clinical Assessments of Dry Eye Disease in the Dry Eye Assessment and Management Study.

Cornea 2022 Jul 21;41(7):845-851. Epub 2021 Jul 21.

Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA.

Purpose: The purpose of this study was to compare objective, noninvasive assessments of tear function using the OCULUS Keratograph with the corresponding clinical assessments [tear break-up time (TBUT), Schirmer test, and bulbar erythema] among patients with moderate-to-severe dry eye disease.

Methods: Participants in the Dry Eye Assessment and Management study at centers having an OCULUS Keratograph were assessed using standardized procedures. Associations between the assessments from the Keratograph [noninvasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and bulbar redness (BR)] and clinical examination (TBUT, Schirmer test, and bulbar erythema) and between these test results and Ocular Surface Disease Index (OSDI) scores were summarized with Spearman correlation coefficients (r s ); 95% confidence intervals (95% CI) accounted for intereye correlation.

Results: Among 288 patients (576 eyes), the mean (standard deviation) age was 56.6 (13.8) years, 78.1% were female, and the mean baseline OSDI score was 44.3 (14.0). The mean was 2.9 (1.5) seconds for TBUT and 8.2 (5.7) seconds for NIKBUT (their correlation r s = 0.18, 95% CI = 0.09-0.28). The mean was 10.6 (7.6) mm for the Schirmer test and 0.3 (0.2) mm for TMH (r s = 0.15, 95% CI = 0.04-0.25). The median clinical grade redness was mild, and the mean BR score was 1.1 (0.5) (r s = 0.25, 95% CI = 0.15-0.35). Correlation between results of each of the 6 tests and OSDI scores was low (r s from -0.07 to 0.05).

Conclusions: In the Dry Eye Assessment and Management study, NIKBUT, TMH, and BR were weakly correlated with their clinical counterparts. No measurements were correlated with the OSDI score.
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http://dx.doi.org/10.1097/ICO.0000000000002804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782916PMC
July 2022

Ocular Discomfort and Quality of Life Among Patients in the Dry Eye Assessment and Management Study.

Cornea 2021 Jul;40(7):869-876

Departments of Ophthalmology; and.

Purpose: To assess the association of severity of ocular discomfort with measures of quality of life among patients with moderate to severe dry eye disease (DED).

Methods: This is a prospective, observational, cohort study within a randomized clinical trial. Patients (N = 535) in the Dry Eye Assessment and Management study with moderate to severe DED completed the Ocular Surface Disease Index on DED symptoms, the SF-36 on quality of life, and the Brief Ocular Discomfort Inventory questionnaire and had a comprehensive ophthalmic assessment by a study-certified clinician. The ocular discomfort on average over the past week was scored on an 11-point scale (0 for no discomfort and 10 for discomfort as bad as you can imagine).

Results: The average ocular discomfort scores for patients ranged from 0 to 10, with a mean of 4.28. Discomfort scores did not vary with demographic characteristics, signs of DED, self-reported depression, or self-reported nonocular pain conditions. Ocular discomfort scores did correlate moderately to strongly with total Ocular Surface Disease Index scores (Spearman correlation coefficient, rs, 0.47-0.67) and with measures of interference with activities of daily living [general activity level, mood, walking ability, ability for normal work, relations with other people, sleep, and enjoyment of life (rs = 0.39-0.65)].

Conclusions: Among patients in the Dry Eye Assessment and Management study, worse ocular discomfort was associated with worse overall DED symptoms and interfered to a greater degree with activities of daily living. Ocular discomfort is an important part of the assessment of patients with DED.
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http://dx.doi.org/10.1097/ICO.0000000000002580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175479PMC
July 2021

Association of Severity of Dry Eye Disease with Work Productivity and Activity Impairment in the Dry Eye Assessment and Management Study.

Ophthalmology 2021 06 15;128(6):850-856. Epub 2020 Oct 15.

Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Purpose: To evaluate the association of dry eye disease (DED) severity with work productivity and activity impairment.

Design: Longitudinal, observational study within a randomized clinical trial.

Participants: People with moderate to severe DED who enrolled in the multicenter Dry Eye Assessment and Management (DREAM) study.

Methods: Participants completed the Work Productivity and Activity Impairment questionnaire at 0, 6, and 12 months and were assessed in parallel for symptoms and signs (conjunctival and corneal staining, tear film break-up time [TBUT], and Schirmer test) of DED. Associations of work productivity and activity impairment with symptom and signs were evaluated with linear regression models using generalized estimating equations and controlling for demographics and comorbidities.

Main Outcome Measures: Work productivity (employment, absenteeism, presenteeism, overall work impairment) and activity impairment.

Results: Among 535 participants at baseline, 279 (52%) were employed, and mean activity impairment was 24.5%. Among those employed, the mean score was 2% for absenteeism, 18% for presenteeism, and 19.6% for overall work impairment. Higher Ocular Surface Disease Index (OSDI) symptom scores were associated with greater absenteeism, presenteeism, and activity impairment. Overall work impairment and activity impairment were greater by 4.3% and 4.8%, respectively, per 10-unit difference in OSDI score (P < 0.001). Longitudinal increases (worsening) in OSDI scores were associated with increasing impairment in work and non-work-related activity: 2.0% and 3.1% per 10 units in OSDI, respectively (P < 0.01). Worse corneal staining and TBUT were associated with higher overall work impairment and activity level (P ≤ 0.04). However, longitudinal changes in these two signs were not associated with changes in work productivity or activity impairment.

Conclusions: Worse symptoms of DED are associated with decreased work productivity and activity level, both cross-sectionally (interindividually) and longitudinally within person (intraindividually). Corneal staining and TBUT are associated with interindividual differences but not intraindividual changes in work productivity and activity impairment.
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http://dx.doi.org/10.1016/j.ophtha.2020.10.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046838PMC
June 2021

Association of meibomian gland morphology with symptoms and signs of dry eye disease in the Dry Eye Assessment and Management (DREAM) study.

Ocul Surf 2020 10 25;18(4):761-769. Epub 2020 Aug 25.

Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA.

Purpose: To describe associations between symptoms and signs of dry eye disease (DED) and meibomian gland (MG) morphology.

Methods: Cross-sectional study utilizing data from the Dry Eye Assessment and Management (DREAM) Study. Readers graded MG features in the middle third of upper and lower lids on infrared meibography images. Associations with signs and symptoms of DED were evaluated with adjustment for age and sex.

Results: Among 268 patients, no MG features were associated with symptom scores (p > 0.08). Among 394 upper eyelids, better tear break-up times (<2, >2- <3.2and ≥ 3.2 s) were associated with more tortuous glands (mean (SD) 0.58(0.95), 0.83(1.2) and 1.14 (1.4), p = 0.01) and with higher scores on a composite score of MG features (21.90 (9.76), 23.29 (9.50), 26.26 (10.27); p = 0.02). Longer Schirmer test wetting lengths (0-5, >5-10, and >10 mm) were associated with increasing composite scores (22.02 (9.29), 23.80 (10.34), 24.96 (9.96), p = 0.03). Patients with Sjogren syndrome compared to other patients had fewer distorted MGs (mean 3.4 (2.3) vs 4.3 (2.3), p = 0.03) and fewer ghost glands (mean 0.33 (0.88) vs 0.89 (1.8), p = 0.006) in the upper lid.

Conclusion: In the DREAM study, most MG morphologic features were not associated with the severity of DED symptoms or signs. Tortuous glands and a higher composite score for MG features were associated with longer tear break-up times and longer Schirmer test length in the upper eyelid only. Patients with Sjogren syndrome had fewer distorted and ghost glands.
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http://dx.doi.org/10.1016/j.jtos.2020.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686056PMC
October 2020

Climatic and Environmental Correlates of Dry Eye Disease Severity: A Report From the Dry Eye Assessment and Management (DREAM) Study.

Transl Vis Sci Technol 2020 04 29;9(5):25. Epub 2020 Apr 29.

Department of Ophthalmology, Mayo Clinic, Scottsdale, AZ, USA.

Purpose: Correlate climate, weather parameters, and environmental exposures with the severity of symptoms and signs of dry eye disease (DED) in Dry Eye Assessment and Management (DREAM) study participants.

Methods: Participants from five distinct climates completed the Ocular Surface Disease Index (OSDI) and were examined for corneal and conjunctival staining, tear breakup time (TBUT), and Schirmer's testing at baseline, 3, 6, and 12 months. Climate, weather parameters, and pollutants including ozone (O), carbon monoxide (CO), nitrous oxides (NO, NO, NO), sulfur dioxide (SO), particulate matter, and optical depth were obtained from governmental databases. Multivariate analysis and partial correlation coefficients (ρ) were used to assess associations, adjusted for age, sex, and the presence of Sjögren disease.

Results: Among 535 participants, 81% were female and mean age was 58 years. Participants from the Mediterranean climate demonstrated better corneal fluorescein staining, better TBUT, and higher Schirmer's test scores throughout the calendar year (each < 0.0001). Greater corneal fluorescein staining was associated with lower humidity ( < 0.0038). TBUT measurements positively correlated with temperature, humidity, and dewpoint and inversely correlated with NO levels ( < 0.0038). Paradoxically, some airborne pollutants were associated with less severe signs of dry eye ( < 0.0038). Windspeed was not correlated with signs of DED, and OSDI scores did not correlate with individual environmental exposures.

Conclusions: Dry eye signs differed between climates and local humidity levels. With the exception of NO, airborne pollutants were not associated with detrimental dry eye features.

Translational Relevance: These results support limiting dry air exposure for patients with DED.
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http://dx.doi.org/10.1167/tvst.9.5.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401914PMC
April 2020

Pediatric versus Adult Corneal Collagen Crosslinking: Long-term Visual, Refractive, Tomographic and Aberrometric Outcomes.

Curr Eye Res 2021 01 26;46(1):14-22. Epub 2020 Jun 26.

Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center , Memphis, Tennessee, USA.

Purpose: To comparatively evaluate the long-term visual, refractive, topographic and aberrometric outcomes of conventional corneal collagen crosslinking (CXL) in the management of pediatric versus adult progressive keratoconus patients.

Materials And Methods: Retrospective, cross-sectional review of consecutive progressive keratoconus cases of corneal standard CXL using a standardized protocol for treatment and examinations was performed. Best spectacle-corrected distance visual acuity (CDVA), manifest refraction, slit lamp biomicroscopy, corneal tomography, corneal aberrometry and endothelial cell counts were evaluated at baseline and yearly at all postoperative follow-up examinations after month-12. The outcomes were analyzed by dividing the patients into 2 age groups; pediatric (≤18 years) versus adult (>18 years).

Results: Eighty-eight eyes (54 patients) in the pediatric and 104 eyes (68 patients) in the adult age groups completed 3 years follow-up. Compared to baseline, the mean CDVA, manifest refraction, keratometric readings, tomographic and aberrometric parameters improved statistically significantly in both groups at postoperative year-3 and year-4, without any statistically significant between-group differences. No change in the mean endothelial cell density ( > .05), or no sight threating complication was encountered in any patient eye in either group. In a subset of patients who were followed for 4 years (71 eyes in the pediatric and 70 eyes in the adult age groups), the outcome analyses were again similar between-groups.

Conclusion: Conventional corneal CXL effectively halts the progression of keratoconus in both pediatric and adult age groups in long-term follow-up with similar visual, refractive, tomographic and aberrometric efficacy in both groups.
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http://dx.doi.org/10.1080/02713683.2020.1782940DOI Listing
January 2021

Trends in Antibiotic Resistance Among Ocular Microorganisms in the United States From 2009 to 2018.

JAMA Ophthalmol 2020 05;138(5):439-450

Pharmaceutical Medical Affairs, Bausch + Lomb, Rochester, New York.

Importance: Antibiotic resistance in ocular infections can affect treatment outcomes. Surveillance data on evolving antibacterial susceptibility patterns inform the treatment of such infections.

Objective: To assess overall antibiotic resistance profiles and trends among bacterial isolates from ocular sources collected during 10 years.

Design, Setting, And Participants: This cross-sectional study of longitudinal data from the ongoing, nationwide, prospective, laboratory-based surveillance study, the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) study, included clinically relevant isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae cultured from patients with ocular infections at US centers from January 1, 2009, to December 31, 2018.

Main Outcomes And Measures: Minimum inhibitory concentrations were determined for various combinations of antibiotics and species. Odds ratios (ORs) were determined for concurrent antibiotic resistance; analysis of variance and χ2 tests were used to evaluate resistance rates by patient age and geographic region; Cochran-Armitage tests identified changing antibiotic susceptibility trends over time.

Results: A total of 6091 isolates (2189 S aureus, 1765 CoNS, 590 S pneumoniae, 767 P aeruginosa, and 780 H influenzae) from 6091 patients were submitted by 88 sites. Overall, 765 S aureus (34.9%) and 871 CoNS (49.3%) isolates were methicillin resistant and more likely to be concurrently resistant to macrolides (azithromycin: S aureus: OR, 18.34 [95% CI, 13.64-24.67]; CoNS: OR, 4.59 [95% CI, 3.72-5.66]), fluoroquinolones (ciprofloxacin: S aureus: OR, 22.61 [95% CI, 17.96-28.47]; CoNS: OR, 9.73 [95% CI, 7.63-12.40]), and aminoglycosides (tobramycin: S aureus: OR, 18.29 [95% CI, 13.21-25.32]; CoNS: OR, 6.28 [95% CI, 4.61-8.56]) compared with methicillin-susceptible isolates (P < .001 for all). Multidrug resistance was observed among methicillin-resistant S aureus (577 [75.4%]) and CoNS (642 [73.7%]) isolates. Antibiotic resistance among S pneumoniae isolates was highest for azithromycin (214 [36.3%]), whereas P aeruginosa and H influenzae isolates showed low resistance overall. Differences in antibiotic resistance were found among isolates by patient age (S aureus: F = 28.07, P < .001; CoNS: F = 11.46, P < .001) and geographic region (S aureus: F = 8.03, P < .001; CoNS: F = 4.79, P = .003; S pneumoniae: F = 8.14, P < .001; P aeruginosa: F = 4.32, P = .005). Small changes in antibiotic resistance were noted over time (≤2.5% per year), with decreases in resistance to oxacillin/methicillin (oxacillin: -2.16%; 95% CI, -3.91% to -0.41%; P < .001) and other antibiotics among S aureus isolates, a decrease in ciprofloxacin resistance among CoNS (-1.38%; 95% CI, -2.24% to -0.52%; P < .001), and an increase in tobramycin resistance among CoNS (0.71%; 95% CI, -0.29% to 1.71%; P = .03). Besifloxacin retained consistently low minimum inhibitory concentrations.

Conclusions And Relevance: Antibiotic resistance may be prevalent among staphylococcal isolates, particularly among older patients. In this study, a few small differences in antibiotic resistance were observed by geographic region or longitudinally.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.0155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146550PMC
May 2020

Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis.

Ophthalmology 2020 04;127(4S):S5-S18

Purpose: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis.

Methods: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization.

Results: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups.

Conclusions: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.
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http://dx.doi.org/10.1016/j.ophtha.2020.01.037DOI Listing
April 2020

Potential Biomarkers for Allergic Conjunctival Diseases.

Eye Contact Lens 2020 Mar;46 Suppl 2:S109-S121

Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN.

Allergic conjunctival diseases (ACDs) are a group of ocular allergies that include allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Although a large body of information exists on the pathophysiology of ACDs, this has not yet lead to the development of clear recommendations and guidelines for the diagnosis of ACDs or development of conclusive and objective diagnostic tools. Identification of objectively measurable biomarkers that represent the molecular and cellular mechanisms associated with ACDs will be an important step toward achieving these aims. This is a comprehensive review of biological markers that have the potential to become "biomarker(s)" for ACDs and aid in the classification, diagnosis, and development of new therapeutic strategies for these group of allergic conditions.
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http://dx.doi.org/10.1097/ICL.0000000000000688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122043PMC
March 2020

Associations Between Systemic Omega-3 Fatty Acid Levels With Moderate-to-Severe Dry Eye Disease Signs and Symptoms at Baseline in the Dry Eye Assessment and Management Study.

Eye Contact Lens 2021 Jan;47(1):2-7

Ophthalmology (E.J.K., K.Y.K., P.A.A.), Icahn School of Medicine at Mount Sinai, New York, NY; Private Practice (M.M.H.), Azusa, CA; Ophthalmology (G.-S.Y., M.G.M.), University of Pennsylvania, Philadelphia, PA; Clinical Research Center (M.C.L.), University of California, Berkeley, CA; Program in Integrative Nutrition & Complex Diseases (R.S.C.), Texas A&M University, College Station, TX; Kennedy Krieger Institute (R.J., A.M.), Baltimore, MD; and Ophthalmology (P.A.A.), University of Tennessee, Memphis, TN.

Purpose: Omega-3 (n-3) fatty acid supplementation is used to treat systemic inflammatory diseases, but the role of n-3 in the pathophysiology and therapy of dry eye disease (DED) is not definitive. We evaluated the relationship of systemic n-3 levels with signs and symptoms at baseline in the Dry Eye Assessment and Management (DREAM) Study.

Methods: Blood samples from participants at baseline were analyzed for n-3 and n-6, measured as relative percentage by weight among all fatty acids in erythrocytes. Symptoms were evaluated using the Ocular Surface Disease Index. Signs including conjunctival staining, corneal staining, tear breakup time (TBUT), and Schirmer's test with anesthesia were also evaluated.

Results: There was no correlation between the systemic n-3 levels and DED symptoms. When the associations with signs of DED were assessed, lower DHA levels were associated with higher conjunctival staining, with mean scores of 3.31, 2.96, and 2.82 for low, medium, and high levels of DHA, respectively (linear trend P=0.007). None of the other signs were associated with DHA or the other measures of n-3.

Conclusion: Previous studies have found varying results on the role of n-3 supplementation with the signs and symptoms of DED. Among patients with DED enrolled in the DREAM Study, lower systemic n-3 levels were not associated with worse symptoms and most signs of DED.
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http://dx.doi.org/10.1097/ICL.0000000000000687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483206PMC
January 2021

An Evaluation of Staphylococci from Ocular Surface Infections Treated Empirically with Topical Besifloxacin: Antibiotic Resistance, Molecular Characteristics, and Clinical Outcomes.

Ophthalmol Ther 2020 Mar 15;9(1):159-173. Epub 2019 Nov 15.

Department of Ophthalmology, Hamilton Eye Institute, University Health Science Center, Memphis, TN, USA.

Introduction: Understanding antibiotic resistance and toxin profiles among staphylococcal isolates in ocular infections can aid in therapeutic management and infection prevention strategies. We evaluated in vitro antibiotic resistance patterns and molecular traits of staphylococci isolated from patients with ocular surface infections. We also report on clinical outcomes for these patients following empirical treatment with topical besifloxacin ophthalmic suspension 0.6%.

Methods: This was a small observational study. Participating investigators from three clinical sites collected an initial ocular culture from the affected eye of patients presenting with ocular surface infections with presumed staphylococcal etiology. Clinical outcome data for patients with confirmed staphylococcal infections were collated later through retrospective review of patient medical records. Staphylococcal species identification in ocular cultures, in vitro antibiotic susceptibility testing, and PCR-based determination of methicillin resistance cassettes and toxin genotypes were conducted at a central laboratory. Isolates were categorized as susceptible or resistant based on systemic breakpoints, where available.

Results: Cultures were collected from 43 patients, and staphylococcal infections were confirmed in 25 patients. Two isolates of Staphylococcus aureus and 27 isolates of Staphylococcus epidermidis were identified. Both S. aureus isolates were methicillin-susceptible, lacked the gene encoding Panton-Valentine leukocidin, and carried few enterotoxin genes. Eight (30%) S. epidermidis were methicillin-resistant (MRSE), and 10 (37%) were ciprofloxacin-resistant. All but two MRSE isolates demonstrated multidrug resistance (MDR), and the staphylococcal cassette chromosome mec (SCCmec) type IVa was detected in five of the eight MRSE isolates. Clinical resolution of the ocular surface infection was reported in all 25 patients following treatment with besifloxacin.

Conclusions: In this study, S. aureus contained few toxins, while SCCmec IVa and MDR was predominant among MRSE from ocular surface infections. Despite significant in vitro fluoroquinolone resistance, there were no cases of treatment failure with topical besifloxacin ophthalmic suspension 0.6%.

Funding: Bausch Health US, LLC.
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http://dx.doi.org/10.1007/s40123-019-00223-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054570PMC
March 2020

Authors' Response.

Optom Vis Sci 2019 11;96(11):892

Case Western Reserve University, Department of Ophthalmology and Visual Sciences, Cleveland, OH Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA School of Optometry, University of California, Berkeley, Berkeley, CA Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Cambridge, MA Department of Ophthalmology, University of Tennessee, Health Science Center, Memphis, TN.

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http://dx.doi.org/10.1097/OPX.0000000000001450DOI Listing
November 2019

ISOPT Hot Topic Panel Discussion on Cornea Anterior Segment Disease.

J Ocul Pharmacol Ther 2019 Oct;35(8):447-456

Department of Ophthalmology, Ankara University School of Medicine, Ankara, Turkey.

The cornea and its adnexa pose a unique situation of a tightly defined set of requirements for its function. This includes: transparency, perfect built to obtain appropriate refractive power, protective barrier from microbial invaders. Moreso, the cornea also endures extreme external physical conditions (temperature, high and low humidity, winds and alike). All these functions are maintained while preserving a constant state of homogenous wetting. Toward that end the cornea is equipped with an elaborated network of sensory neural network. While enabling the blinking reflex and maintaining the physiological steady state of wetting, this neural network also makes the cornea prone to the discomfort that with or without associated changes seen on medical examination. ISOPT Clinical 2018 discussion touched upon this hypercomplex situation, addressing the role of inflammation and its resulting discomfort in dry eye conditions. The discussion also engulfed the emerging neuropathic pain syndrome that is recently gaining more attention. Another related topic was the utilization of autologous serum tears and its ability to provide amelioration to desperate patients. Finally, the panel discussed the issue of treating corneal infection, including when and how to utilize steroids in the course of therapy. We assume the reader will find interest in this discussion that directly addresses issues seen day in and day out in our busy clinics.
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http://dx.doi.org/10.1089/jop.2019.0023DOI Listing
October 2019

Conjunctival HLA-DR Expression and Its Association With Symptoms and Signs in the DREAM Study.

Transl Vis Sci Technol 2019 Jul 21;8(4):31. Epub 2019 Aug 21.

Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, 930 Madison Avenue, Memphis, TN, USA.

Purpose: Evaluation of dry eye disease (DED) relies on subjective symptoms and signs. We examined HLA-DR expression (HLA-DR%) in conjunctival cells, a minimally invasive biomarker with objective metrics, as an alternative method.

Methods: Dry Eye Assessment and Management (DREAM) study participants completed the Ocular Surface Disease Index questionnaire. Clinicians evaluated tear volume, tear breakup time, and corneal and conjunctival staining. Conjunctival impression cytology samples ( = 1049) were assessed for HLA-DR% in total cells (TCs), epithelial cells (ECs), and white blood cells (WBCs). Associations (categorized into <5%, 5%-15%, >15%-25%, and >25%) with symptoms and signs were evaluated.

Results: The HLA-DR% varied markedly across samples. Over 40% had <5 HLA-DR% positive cells in TCs and ECs and under 23% in WBCs. Higher HLA-DR% was associated with higher conjunctival staining for ECs (mean score 2.77 for <5% and 3.28 for >25%, linear trend = 0.009) and TCs (mean score 2.82 for <5% and 3.29 for >25%, linear trend = 0.04) and in TCs was associated with higher corneal staining (mean score 3.59 for <5% and 4.46 for >25%, linear trend = 0.03). HLA-DR% in WBCs did not correlated with signs (all ≥ 0.58), and in TCs, ECs or WBCs were not associated with symptoms ( > 0.06).

Conclusions: The distribution of HLA-DR% in conjunctival cells reflects the heterogeneity of disease in DREAM participants. High percentages of samples with <5% positive cells indicate that HLA-DR% may not be a sensitive marker for DED in all patients.

Translational Relevance: High HLA-DR% in ECs in association with high conjunctival staining may identify a subgroup of DED patients prone to epithelial disease and possibly need a different approach from current standards of treatment.
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http://dx.doi.org/10.1167/tvst.8.4.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707226PMC
July 2019

Effects of Omega-3 Supplementation on Exploratory Outcomes in the Dry Eye Assessment and Management Study.

Ophthalmology 2020 01 25;127(1):136-138. Epub 2019 Jul 25.

Hamilton Eye Institute, University of Tennessee Health Science Center (UTHSC), Memphis Tennessee.

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http://dx.doi.org/10.1016/j.ophtha.2019.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926153PMC
January 2020

The Dry Eye Assessment and Management (DREAM) extension study - A randomized clinical trial of withdrawal of supplementation with omega-3 fatty acid in patients with dry eye disease.

Ocul Surf 2020 01 16;18(1):47-55. Epub 2019 Aug 16.

Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN, USA.

Purpose: To determine effects of continued or discontinued use of omega-3 (ω3) fatty acid supplements through a randomized withdrawal trial among patients assigned to ω3 supplements in the first year of the DREAM study.

Methods: Patients who were initially assigned to ω3 (3000 mg) for 12 months in the primary trial were randomized 1:1 to ω3 active supplements or placebos (refined olive oil) for 12 more months. The primary outcome was change in the Ocular Surface Disease Index (OSDI) score. Secondary outcomes included change in conjunctival staining, corneal staining, tear break-up time, Schirmer test, and adverse events.

Results: Among 22 patients assigned to ω3 and 21 to placebo supplements, the mean change in OSDI score between month 12 and 24 was similar between treatment groups (mean difference in change -0.6 points, 95% confidence interval [CI], (-10.7, 9.5), p = 0.91). There were no significant differences between groups in mean change in conjunctival staining (difference in mean change -0.5 points; 95% CI (-1.2, 0.3)), corneal staining (-0.3 points; 95% CI (-1.2, 0.3)), tear break-up time (-0.8 s; 95% CI (-2.6, 0.9)) and Schirmer test (0.6 mm, 95% CI (-2.0, 3.2)). Rates of adverse events were similar in both groups.

Conclusion: Among patients who received ω3 supplements for 12 months in the primary trial, those discontinuing use of ω3 for an additional 12 months did not have significantly worse outcomes compared to those who continued use of ω3. ClinicalTrials.gov number NCT02128763.
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http://dx.doi.org/10.1016/j.jtos.2019.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004875PMC
January 2020

Why DREAM should make you think twice about recommending Omega-3 supplements.

Ocul Surf 2019 10 12;17(4):617-618. Epub 2019 Aug 12.

Perelman School of Medicine, University of Pennsylvania, USA.

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http://dx.doi.org/10.1016/j.jtos.2019.08.003DOI Listing
October 2019

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

Optom Vis Sci 2019 06;96(6):387-396

Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee

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.
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http://dx.doi.org/10.1097/OPX.0000000000001387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544497PMC
June 2019

Grading and baseline characteristics of meibomian glands in meibography images and their clinical associations in the Dry Eye Assessment and Management (DREAM) study.

Ocul Surf 2019 07 22;17(3):491-501. Epub 2019 Apr 22.

Hamilton Eye Institute, University of Tennessee Health Science Center (UTHSC), Memphis, TN, USA.

Purpose: To describe and evaluate a comprehensive grading system for meibomian gland (MG) digital infrared images developed for the Dry Eye Assessment and Management (DREAM) Study.

Methods: Cross-sectional study. Reading Center (RC) certified readers independently evaluated MG features of both lids from meibography images of dry eye disease subjects. Dropout areas were measured using planimetry software. Inter-reader and grade-regrade agreement and comparison of meiboscale scores (Meiboscale; Pult) from clinical centers to RC percent dropout and of MG features with clinical parameters were evaluated.

Results: Among 551 eyes of 277 patients at baseline, 62 (11%) upper lid and 5 (1%) lower lid images were missing. Lid eversion was poor in 63 (13%) of upper lids compared to 15 (3%) of lower lids. Intraclass correlation for inter-reader and grade-regrade agreement was moderate to substantial for most MG features. MG features were more frequent in the upper lid (p < 0.001), except for dropout glands, gaps, fluffy gland areas and dropout areas. Clinic meiboscale score was associated with RC percent dropout (p < 0.001), a clinic score of 0% having a mean RC score of 19%, and a clinic score of >75% having a mean RC score of 66%. MG plugging was associated with ghost glands (p = 0.009), dropout glands (p < 0.001) and a composite severity score (p = 0.02); turbid and absent secretions were associated with ghost glands (p = 0.046).

Conclusion: RC readers identified MG features with good reproducibility. Upper lids had more MG features. RC dropout areas correlated well with clinic meiboscale scores. Ghost glands were associated with paste like and absent meibomian secretions.
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http://dx.doi.org/10.1016/j.jtos.2019.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708483PMC
July 2019

It's Been Fun and Productive Too.

Authors:
Penny A Asbell

Eye Contact Lens 2019 May;45(3):151

Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN.

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http://dx.doi.org/10.1097/ICL.0000000000000600DOI Listing
May 2019

Antibiotic resistance among ocular pathogens: current trends from the ARMOR surveillance study (2009-2016).

Clin Optom (Auckl) 2019 12;11:15-26. Epub 2019 Mar 12.

Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN, USA.

Background: The Antibiotic Resistance Monitoring in Ocular micRoorganisms study is an ongoing surveillance study that tracks antibiotic resistance among bacterial isolates from ocular infections across the United States. We report antibiotic resistance rates and trends from 2009 through 2016.

Materials And Methods: , coagulase-negative staphylococci (CoNS), , , and from various ocular infections were obtained from participating United States centers. Isolates were sent to a central laboratory for determination of antibiotic resistance profiles. Minimum inhibitory concentrations were determined by broth microdilution according to the Clinical and Laboratory Standards Institute for drugs from more than ten antibiotic classes, and isolates were classified as susceptible or resistant based on systemic breakpoints, wherever available. Resistance rates were also evaluated based on decade of patient life and longitudinally over the 8-year time period.

Results: A total of 1,695 . , 1,475 CoNS, 474 . , 586 , and 599 . were collected from 87 sites. Resistance was high among staphylococci and pneumococci, with methicillin resistance detected in 621 (36.6%) . and 717 (48.6%) CoNS isolates. Multidrug resistance (≥3 drug classes) was observed among staphylococci, particularly in methicillin-resistant (MR) isolates (MR [MRSA]: 76.2%; MR CoNS [MRCoNS]: 73.5%). Differences in methicillin resistance among staphylococci were observed based on patient age, with higher rates observed in older patients (<0.0001). For certain organism-antibiotic combinations, there were significant changes in resistance over time, including a decrease in methicillin resistance among (but not CoNS); no notable trends were observed for .

Conclusion: Antibiotic resistance was prevalent among gram-positive organisms, and MR staphylococcal isolates were more likely to be multidrug resistant. Although a small decrease in methicillin resistance was observed among over time, the continued high prevalence of in vitro methicillin resistance should be considered when treating patients with ocular infections.
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http://dx.doi.org/10.2147/OPTO.S189115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419597PMC
March 2019

Antibiotic resistance among bacterial conjunctival pathogens collected in the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study.

PLoS One 2018 18;13(10):e0205814. Epub 2018 Oct 18.

Bausch + Lomb, Rochester, New York, United States of America.

The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) surveillance study evaluates in vitro antibiotic resistance among Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae isolates from ocular infections. Here we report resistance rates and trends among conjunctival-sourced ocular isolates collected across the US from 2009 through 2016. A total of 1198 conjunctival isolates (483 S. aureus, 305 CoNS, 208 H. influenzae, 118 S. pneumoniae, and 84 P. aeruginosa) were collected from patients with presumed bacterial conjunctivitis from 57 sites across 40 states. A large proportion of staphylococci demonstrated resistance to oxacillin and azithromycin, while resistance was low against the majority of antibiotics tested for S. pneumoniae, P. aeruginosa, and H. influenzae. Multidrug resistance (≥3 antibiotic classes) was found in 30.2% of S. aureus and 39.0% of CoNS isolates, and methicillin resistance more than doubled the rate of multi-drug resistance (methicillin-resistant S. aureus [MRSA], 76.5%; methicillin-resistant CoNS isolates, 72.8%). There was a pattern of increasing mean percent resistance with increasing age by decade of life among S. aureus, MRSA, and CoNS (P≤0.038). Over the eight-year study period, there were small yet significant decreases in resistance rates among S. aureus to azithromycin, ciprofloxacin, tobramycin, trimethoprim, and oxacillin (P≤0.003), and among CoNS and P. aeruginosa (both P<0.05) to ciprofloxacin. These data indicate that antibiotic resistance is high, but did not increase, among conjunctival-sourced isolates collected in the US from 2009 through 2016. For certain antibiotic/pathogen combinations, there was a trend of decreased resistance, including a decrease in oxacillin resistance among S. aureus.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205814PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193682PMC
March 2019

Antibiotic Resistance Among Pediatric-Sourced Ocular Pathogens: 8-Year Findings From the Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) Surveillance Study.

Pediatr Infect Dis J 2019 02;38(2):138-145

Pharmaceutical Medical Affairs, Bausch + Lomb, Rochester, New York.

Background: The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) study is a nationwide longitudinal antibiotic resistance surveillance program specific to bacterial pathogens commonly encountered in ocular infections. We evaluated in vitro resistance rates and trends among isolates obtained from pediatric patients (≤17 years of age).

Methods: Clinical centers across the United States were invited to submit ocular isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa to a central laboratory. Minimum inhibitory concentrations for various antibiotic classes were determined by broth microdilution per Clinical and Laboratory Standards Institute guidelines and interpreted as susceptible, intermediate or resistant based on available breakpoints. Longitudinal trends were analyzed using a Cochran-Armitage test for linear trends in a proportion.

Results: Of 4829 isolates collected from January 2009 to December 2016, 995 isolates, sourced primarily from hospitals and referral centers, were obtained from pediatric patients (n = 286 H. influenzae, n = 284 S. aureus, n = 213 CoNS, n = 150 S. pneumoniae and n = 62 P. aeruginosa). With few exceptions, P. aeruginosa and H. influenzae were generally susceptible to the antibiotics tested. Of S. aureus and CoNS isolates, respectively, 56% and 72% were resistant to azithromycin and 24% and 47% were methicillin-resistant (MR); concurrent resistance to other drug classes and multidrug resistance (≥3 drug classes) were prevalent among MR staphylococci. Of S. pneumoniae isolates, 38% and 35% demonstrated resistance to azithromycin and penicillin, respectively. Besifloxacin had the lowest minimum inhibitory concentration against the Gram-positive isolates.

Conclusions: These in vitro data suggest antibiotic resistance is common among staphylococcal and pneumococcal isolates collected from pediatric patients with ocular infections. Methicillin resistance was prevalent among staphylococci with many strains demonstrating multidrug resistance. These findings may not be representative of resistance trends in community-based practices.
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http://dx.doi.org/10.1097/INF.0000000000002206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343952PMC
February 2019
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