Association of Systemic Markers of Inflammation with Signs and Symptoms of Dry Eye Disease and Sjogren's Syndrome in the Dry Eye Assessment and Management (DREAM©) Study.

PURPOSE: To evaluate the possible role of systemic inflammation in dry eye disease (DED) via systemic inflammatory marker associations with DED signs and symptoms, and an analysis of a subgroup with Sjogren's Syndrome (SS). METHODS: Participant serums were analyzed using line immunoassays (LIAs) for the presence of antibodies against 34 systemic inflammatory markers. Using the 2012 American College of Rheumatology definition, the 481 participants were categorized into group 1 (SS; n = 52), group 2 (autoimmune disease not including SS; n = 66), or group 3 (control, i.e. no autoimmune disease; n = 363). RESULTS: 3 markers were positive in ≥10% of participants: Ro52 (19.3%), Scl-70 (15.0%), CN-1A (14.2%). 2 markers were positively associated with symptoms: PM-Scl100 (p = 0.02), Sm (p = 0.009). 5 markers were positively associated with signs: U2SnRNP A', Ro52, La, DNA, Ro60. SS participants showed significantly higher positivity for 4 markers compared to participants with no autoimmune disease: PL-7 (p = 0.02), Ro52 (p < 0.0001), La (p < 0.0001), Ro60 (p < 0.0001). SS participants showed significantly higher positivity for 3 markers compared to participants with another autoimmune disease: Ro52 (p < 0.0001), La (p = 0.002), Ro60 (p < 0.0001). CONCLUSIONS: This study did not show evidence of significant systemic inflammation in participants with moderate-to-severe DED, based on the markers tested. PM-Scl100 and Sm may be associated with more severe DED symptoms. U2SnRNP A', Ro52, La, DNA, and Ro60 may be associated with more severe ocular surface disease. Ro52 and PL-7 may be diagnostic markers for SS. Future research evaluating these relationships and their clinical significance is needed.

Association between systemic medication use and severity of dry eye signs and symptoms in the DRy eye assessment and management (DREAM) study.

PURPOSE: Some systemic medications are reported to be associated with dry eye disease (DED), yet their associations with the severity of DED signs and symptoms are not well studied. To evaluate these associations, we performed a secondary analysis of data from the DRy Eye Assessment and Management (DREAM) Study. METHODS: Participants (N = 535) were assessed for DED signs using tear break-up time (TBUT), Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, meibomian gland dysfunction (MGD), and tear osmolarity and DED symptoms using the Ocular Surface Disease Index (OSDI). We derived a composite signs severity score from the 6 DED signs and categorized participant-reported systemic medications into antidepressants, antihistamines, aspirin, corticosteroids, diuretics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors, statins, vitamin D3, and medications for diabetes mellitus, hypertension, hypothyroidism, migraine, and seizure. Generalized linear models were used to compare DED symptom and sign scores between medication users and non-users, with adjustment for factors associated with DED severity. RESULTS: Compared to non-users, antihistamine users had lower TBUT (p = 0.01) and higher OSDI score (p = 0.02); aspirin users had lower TBUT (p = 0.02); corticosteroid users had lower TBUT (p = 0.02), lower Schirmer test scores (p = 0.03), higher cornea fluorescein staining (p = 0.01), higher composite severity score (p = 0.01), and higher OSDI score (p = 0.03); seizure medication users had higher composite severity score (p = 0.02); vitamin D3 users had lower TBUT (p = 0.001) and greater MGD (p = 0.03); and diuretic users had less MGD (p = 0.03). CONCLUSIONS: Certain systemic medications may be associated with more severe DED. This may guide prescription practices in patients with DED.

A latent profile analysis of tear cytokines and their association with severity of dry eye disease in the Dry Eye Assessment and Management (DREAM) study.

This study is to identify subgroups of DED patients with different tear cytokine profiles and compare their DED symptoms and signs among subgroups. Baseline tear cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-17A, IFN-γ and TNF-α) were measured using a magnetic bead assay. DED symptoms were assessed by Ocular Surface Disease Index (OSDI) and signs were assessed by corneal and conjunctival staining, tear break-up time (TBUT), Schirmer's test, tear osmolarity and meibomian gland dysfunction (MGD). Latent profile analysis was performed to identify subgroups, and their scores of DED symptoms and signs were compared using generalized linear regression. Among 131 patients with total tear volume > 4 µl from both eyes, subgroup 1 (n = 23) significantly higher in IL-6 and IL-8 (all p < 0.001) and subgroup 2 (n = 108) significantly higher in IL-10 (p = 0.03), IL-17A (p < 0.001), and IFN-γ (p < 0.001). Both subgroups were similar in demographics and DED symptoms, but subgroup 1 had significantly more severe DED signs: higher conjunctival staining (3.38 vs. 2.69, p = 0.04), corneal staining (4.26 vs. 3.03, p = 0.03), lower Schirmer's test score (8.20 vs. 13.72, p < 0.001), and higher composite severity score of DED sign (0.62 vs. 0.45, p = 0.002). We identified two DED subgroups with different profiles of tear cytokines. Patients in these subgroups differed significantly in DED signs, supporting the inflammation's role in DED development and progression.

Association of Tear Cytokine Ratios with Symptoms and Signs of Dry Eye Disease: Biomarker Data from the Dry Eye Assessment and Management Study.

PURPOSE: To assess the relationship between tear inflammatory cytokine ratios (CRs) and signs and symptoms of dry eye disease (DED) to investigate the possible use of tear CRs, which may better address the complexity of cytokine interactions than absolute cytokine levels, as a DED biomarker. METHODS: Tear concentrations of IL-1b, IL-6, IL-8, IL-10, IL-17A, IFN-g, and TNF-a were measured using standardized procedures, as were DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)]. Ratios between pro-inflammatory (IL-1b, IL-8, IL-17A, IFN-g, and TNF-a) and anti-inflammatory (IL-10) cytokines were calculated. Given its opposing roles in inflammation, IL-6 was tested as both a pro- and anti-inflammatory cytokine. Correlations between CR and DED symptoms and signs were calculated using Spearman correlation coefficients (rho). RESULTS: At baseline, 131 patients, 80.2% female and mean age 54.2 years (SD 14.1, range 20-82), from 10 sites of the Dry Eye Assessment and Management study had sufficient tear volumes ≥4 µL for analysis. IL-6:IL-10, IL-8:IL-10, and TNF-a:IL-10 had some significant correlations, mostly with conjunctival or corneal staining or the composite sign severity score (IL-8:IL-10 and conjunctival staining: rho = 0.19, p = 0.03; IL-6:IL-10 and corneal staining: rho = 0.31, p < 0.001; IL-8:IL-10 and corneal staining: rho = 0.21, p = 0.01; IL-6:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; IL-8:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; TNF-a:IL-10 and corneal staining: rho = 0.29, p < 0.001; TNF-a:IL-10 and Schirmer test: rho = -0.23, p = 0.009). CRs had no significant correlation with DED symptoms. All significant correlations using IL-6 in the denominator (anti-inflammatory) produced counterintuitive results based on clinical understanding of the disease. CONCLUSIONS: Pro- to anti-inflammatory CR was weakly correlated with some DED signs and not with symptoms, as measured by OSDI. Future studies in different dry eye populations are needed and should address sampling biases and tear collection techniques.

Antibiotic resistance of bacterial pathogens isolated from the conjunctiva in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) surveillance study (2009-2021).

Antibiotic resistance in bacterial ocular infections is of significant clinical concern and may affect treatment outcomes. We report on in vitro antibiotic susceptibility rates and trends among conjunctival-sourced isolates collected in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) surveillance study. A total of 2214 conjunctival isolates (918 Staphylococcus aureus, 589 coagulase-negative staphylococci [CoNS], 194 Streptococcus pneumoniae, 171 Pseudomonas aeruginosa, and 342 Haemophilus influenzae) obtained between 2009-2021 were analyzed. Staphylococci were commonly resistant to azithromycin (≥54.8%) and oxacillin (≥29.3%). Resistance among S. pneumoniae isolates was notable for azithromycin (34.0%) and penicillin (28.9%), while P. aeruginosa and H. influenzae isolates were highly susceptible to most tested antibiotics. Methicillin-resistant staphylococci demonstrated greater concurrent resistance to other antibiotics than methicillin-susceptible isolates and exhibited high rates of multidrug resistance (≥74.0%). Among staphylococci, antibiotic resistance increased with patient age, and there were small decreases in resistance to several drugs over the 13-year period. These findings indicate that resistance to antibiotics routinely used in ophthalmic practice remains high among conjunctival isolates.

Association of Ocular Surface Immune Cells With Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study.

Purpose: Dry eye disease (DED) is a multifactorial, heterogeneous disease of the ocular surface with one etiology being ocular surface inflammation. Studies using animal models demonstrate the role of ocular surface immune cells in the inflammatory pathway leading to DED, but few have evaluated humans. This study described the white blood cell population from the ocular surface of patients with DED and assessed its association with DED signs and symptoms in participants of the Dry Eye Assessment and Management (DREAM) study. Methods: Participants were assessed for symptoms using the Ocular Surface Disease Index, signs via corneal staining, conjunctival staining, tear break-up time, and Schirmer test, and Sjögren's syndrome (SS) based on the 2012 American College of Rheumatology classification criteria. Impression cytology of conjunctival cells from each eye was evaluated using flow cytometry: T cells, helper T cells (Th), regulatory T cells (Tregs), cytotoxic T cells, and dendritic cells. Results: We assessed 1049 eyes from 527 participants. White blood cell subtype percentages varied widely across participants. Significant positive associations were found for Th and conjunctival staining (mean score of 2.8 for 0% Th and 3.1 for >4.0% Th; P = 0.007), and corneal staining (mean score of 3.5 for 0% Th and 4.3 for >4.0% Th; P = 0.01). SS was associated with higher percent of Tregs (median 0.1 vs. 0.0; P = 0.01). Conclusions: Th were associated with more severe conjunctival and corneal staining, possibly indicating their role in inflammation leading to damage of the ocular surface. There is no consistent conclusion about Tregs in SS, but these results support that Tregs are elevated in SS.

Update on Dry Eye Disease Treatment: Evidence From Randomized Controlled Trials.

ABSTRACT: Although the ultimate goal of dry eye disease (DED) management is to restore the ocular surface and tear film homeostasis and address any accompanying symptoms, addressing this is not an easy task. Despite the wide range of current treatment modalities targeting multiple aspects of DED, the available DED management literature is quite heterogeneous, rendering evaluation or comparison of treatment outcomes hard or almost impossible. There is still a shortage of well-designed, large-scale, nonsponsored, randomized, controlled trials (RCTs) evaluating long-term safety and efficacy of many targeted therapies individually or used in combination, in the treatment of identified subgroups of patients with DED. This review focuses on the treatment modalities in DED management and aims to reveal the current evidence available as deduced from the outcomes of RCTs.

Association of Dry Eye Symptoms and Signs in Patients with Dry Eye Disease.

PURPOSE: To determine the correlations among symptoms and signs of dry eye disease (DED) in the Dry Eye Assessment and Management (DREAM) study. METHODS: A total of 535 patients with moderate-to-severe DED were assessed for symptoms using the Ocular Surface Disease Index (OSDI) and four DED signs in both eyes (conjunctival lissamine green staining, corneal fluorescein staining, Schirmer's testing, and tear break-up time (TBUT)) following standardized protocols at baseline and follow-up visits (months 3, 6, and 12). Spearman correlation coefficients (rho) were calculated for correlations among symptoms and signs of DED at baseline and among changes in symptoms and signs from baseline at 12 months. The confidence intervals and p-values for correlation coefficients were calculated using a cluster bootstrapping to account for inter-eye correlation. RESULTS: At baseline, OSDI total score was not correlated with signs; however, OSDI subscale score of ocular symptoms was weakly correlated with corneal staining score (rho = 0.14, p = .002) and Schirmer test score (rho = 0.11, p = .01). There were statistically significant correlations among the four signs (p < .001), with absolute correlation coefficient ranging from 0.14 (conjunctival staining score vs. TBUT) to 0.33 (conjunctival staining score vs. cornea staining score). The correlations among changes in symptoms and signs were weaker, with the highest correlation between change in conjunctival staining and corneal staining (rho = 0.21, p < .001). CONCLUSIONS: Consistent with previous studies, among DREAM participants with moderate-to-severe DED at baseline, correlations of DED symptoms with signs were low and correlations among four objective signs were low to moderate. The correlations among changes in symptoms and signs were even weaker.

Age Associations with Dry Eye Clinical Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study.

Purpose: To evaluate how increasing age is associated with dry eye disease (DED) signs and symptoms in the Dry Eye Assessment and Management (DREAM) study. This study was undertaken to better understand how DED signs and symptoms differ across decades of life with goals to help assess detection and treatment of DED. Design: Secondary analysis of the DREAM study. Subjects: One hundred twenty, 140, 185, and 90 participants aged < 50, 50 to 59, 60 to 69, and ≥ 70 years, respectively. Methods: We performed a secondary analysis of data from the DREAM study, a multicenter randomized clinical trial, to evaluate the effect of omega-3 fatty acid supplementation for the treatment of DED. At baseline, 6 months, and 12 months follow-up, participants underwent an assessment of DED symptoms and signs using Ocular Surface Disease Index, Brief Pain Inventory, tear break-up time (TBUT) (in seconds), Schirmer test with anesthesia (mm/5 minutes), conjunctival staining, corneal staining, meibomian gland dysfunction evaluation, and tear osmolarity (mOsm/l). Multivariable generalized linear regression models were used to compare DED symptoms and signs across the 4 age groups among all participants and by sex. Main Outcome Measures: Scores of DED symptoms, individual signs, and composite scores of DED signs. Results: Among 535 patients with DED, increasing age was significantly associated with worse TBUT (P = 0.01), corneal staining (P < 0.001), a composite severity score of DED signs (P = 0.007), and tear osmolarity (P = 0.001). Similar significant differences were found across 4 age groups of 334 women in TBUT, corneal staining score, composite severity score of DED signs, and tear osmolarity (all P < 0.05) but not in men. Conclusion: We found that corneal staining, TBUT, tear osmolarity, and a composite severity score of DED signs were significantly more severe with increasing age in women but not in men; worsening symptoms did not increase with increasing age. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association of Tear Cytokine Concentrations with Symptoms and Signs of Dry Eye Disease: Baseline Data from the Dry Eye Assessment and Management (DREAM) Study.

PURPOSE: To describe tear concentrations of IL-1ß, Il-6, IL-8, IL-10, IL-17A, IFNγ and TNFα in tears, collected by microcapillaries, and their correlation with symptoms and signs in subjects with dry eye disease (DED) in the DREAM Study. METHODS: Cytokine levels of patients with moderate to severe DED were determined using a magnetic bead assay. Scores for Ocular Surface Disease Index, corneal and conjunctival staining, tear break-up time (TBUT), and Schirmer's test were obtained using standardized procedures. Associations of cytokines with each other and signs/symptoms were assessed with Spearman correlation coefficients (r). RESULTS: Assay results from 131 patient samples from 10 sites with tear volumes ≥ 4 ul were analyzed. Cytokine concentrations did not correlate with each other in a generally acknowledged pro-inflammatory/anti-inflammatory pattern, such as proinflammatory IL-17A and IFNγ were not inversely correlated to anti-inflammatory cytokine IL-10, and cytokines did not correlate with DED symptoms. Lower corneal staining was correlated with higher concentrations of IL-17A (r= -0.24, p = 0.006), IL-10 (r= -0.25, p = 0.005) and IFNγ (r= -0.33, p = 0.0001). Higher concentrations of IFNγ were associated with lower conjunctival staining (r= -0.18, p = 0.03). Higher concentrations of IL-17A were associated with higher TBUT scores (r = 0.19 p = 0.02). CONCLUSIONS: Cytokines IL-10, IL-17A and IFNγ were highly correlated with each other but weakly correlated with some DED signs. No key cytokines or definitive expression patterns were identified in this study of moderate to severe DED patients. Further studies addressing various biases, including methodological and sampling biases, and standardization of methodology for inter-laboratory consistency are needed to confirm and establish pathological and clinical relevance of tear cytokines in DED.

Association of Tear Osmolarity With Signs and Symptoms of Dry Eye Disease in the Dry Eye Assessment and Management (DREAM) Study.

Purpose: To determine the relationships of (1) tear osmolarity (TO) levels with the severity of signs and symptoms of dry eye disease (DED) and (2) changes in TO with changes in signs and symptoms. Methods: Patients (N = 405) with moderate to severe DED in the Dry Eye Assessment and Management (DREAM) Study were evaluated at baseline and at six and 12 months. Associations of TO with signs and symptoms were evaluated using Pearson correlation coefficient (r) and regression models. Results: The mean (standard deviation [SD]) TO was 303 (16) mOsm/L at baseline and 303 (18) mOsm/L at both six and 12 months. TO was higher in older patients (306 mOsm/L for ≥70 years vs. 300 mOsm/L for <50 years; P = 0.01) and those with Sjögren's disease (311 vs. 302 mOsm/L; P < 0.0001). TO did not differ between patients randomized to placebo and omega-3 fatty acid supplementation. TO was weakly correlated with conjunctival (r = 0.18; P < 0.001) and corneal staining scores (r = 0.17; P < 0.001), tear film break-up time (r = 0.06; P = 0.03), and Schirmer test score (r = -0.07; P = 0.02) but not with Ocular Surface Disease Index scores (r = 0.03; P = 0.40). Changes in signs and were not significantly correlated with change in TO at six or 12 months. Conclusions: Within DREAM, TO was weakly correlated with DED signs, explaining <5% variability in signs. Changes in tear osmolarity were not associated with changes in signs and symptoms of DED, indicating that the association may not be causal.

Dry Eye Subtypes in the Dry Eye Assessment and Management (DREAM) Study: A Latent Profile Analysis.

Purpose: Dry eye disease (DED) is a heterogeneous condition with poorly characterized subtypes. The DREAM study was a large multicenter randomized clinical trial that did not find omega-3 to be more effective than placebo in treating symptomatic DED. We performed secondary analysis of DREAM data to characterize DED subtypes and their omega-3 response. Methods: A total of 535 patients with moderate-to-severe DED were randomized to omega-3 or placebo treatment for one year. We used latent profile analysis to identify subtypes based on baseline Ocular Surface Disease Index, tear break-up time (TBUT), anesthetized Schirmer's test, corneal and conjunctival staining, and meibomian gland dysfunction (MGD). We evaluated omega-3's effect for each subtype using generalized linear regression. Results: Five clinically meaningful DED subtypes were identified. They differed significantly in sex (P < 0.001) and race (P = 0.02). Subtype 1 had the most severe DED signs yet milder symptoms and was associated with more Sjögren's syndrome (21%, P < 0.001). Subtype 2 had the mildest DED signs except MGD. Subtype 3 had the most severe symptoms, out of proportion to DED signs. Subtype 4 had relatively milder symptoms and MGD. Subtype 5 had severe MGD and TBUT and was associated with rosacea (29%, P = 0.04). Omega-3 was not significantly more beneficial than placebo for any subtype. Conclusions: Five clinically meaningful DED subtypes differed significantly in demographics, symptoms, signs, and systemic disease associations. Omega-3 was not significantly more effective than placebo for any subtype. Translational Relevance: T3 translational research identifying subtypes in the DREAM study can improve DED clinical classification and targeted management.

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

OBJECTIVES: To determine effect of omega-3 supplementation on conjunctival cell HLA-DR expression and tear concentrations of interleukin (IL)-1ß, 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.

Lirentelimab for severe and chronic forms of allergic conjunctivitis.

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.

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.

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.

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

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.

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

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.

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

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.