381 results on '"Zegans, Michael"'
Search Results
2. Cefiderocol Is an Effective Topical Monotherapy for Experimental Extensively Drug-Resistant Pseudomonas aeruginosa Keratitis
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Romanowski, Eric G., Mumper, Sonya M., Shanks, Hazel Q., Yates, Kathleen A., Mandell, Jonathan B., Zegans, Michael E., and Shanks, Robert M.Q.
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- 2024
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3. Clinical metagenomics for infectious corneal ulcers: Rags to riches?
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Ung, Lawson, Bispo, Paulo JM, Doan, Thuy, Van Gelder, Russell N, Gilmore, Michael S, Lietman, Thomas, Margolis, Todd P, Zegans, Michael E, Lee, Cecilia S, and Chodosh, James
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Infectious Diseases ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,Good Health and Well Being ,Communicable Diseases ,Corneal Ulcer ,High-Throughput Nucleotide Sequencing ,Humans ,Metagenomics ,Clinical metagenomics ,Next generation sequencing ,Infectious corneal ulcers ,Microbial keratitis ,Opthalmology and Optometry ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
The emergence of clinical metagenomics as an unbiased, hypothesis-free approach to diagnostic testing is set to fundamentally alter the way infectious diseases are detected. Long envisioned as the solution to the limitations of culture-based conventional microbiology, next generation sequencing methods will soon mature, and our attention will inevitably turn to how they can be applied to areas of medicine which need it most urgently. In ophthalmology, the demand for this technology is particularly pressing for the care of infectious corneal ulcers, where current diagnostic tests may fail to identify a causative organism in over half of cases. However, the optimism found in the budding discourse surrounding clinical metagenomics belies the reality that clinicians and scientists will soon be inundated by oppressive volumes of sequencing data, much of which will be foreign and unfamiliar. Therefore, our success in translating clinical metagenomics is likely to hinge on how we make sense of these data, and understanding its implications for the interpretation and implementation of sequencing into routine clinical care. In this consortium-led review, we provide an outline of these data-related issues and how they may be used to inform technical workflows, with the hope that we may edge closer to realizing the potential of clinical metagenomics for this important unmet need.
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- 2020
4. Infectious corneal ulceration: a proposal for neglected tropical disease status
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Ung, Lawson, Acharya, Nisha R, Agarwal, Tushar, Alfonso, Eduardo C, Bagga, Bhupesh, Bispo, Paulo JM, Burton, Matthew J, Dart, John KG, Doan, Thuy, Fleiszig, Suzanne MJ, Garg, Prashant, Gilmore, Michael S, Gritz, David C, Hazlett, Linda D, Iovieno, Alfonso, Jhanji, Vishal, Kempen, John H, Lee, Cecilia S, Lietman, Thomas M, Margolis, Todd P, McLeod, Stephen D, Mehta, Jod S, Miller, Darlene, Pearlman, Eric, Prajna, Lalitha, Prajna, N Venkatesh, Seitzman, Gerami D, Shanbhag, Swapna S, Sharma, Namrata, Sharma, Savitri, Srinivasan, Muthiah, Stapleton, Fiona, Tan, Donald TH, Tandon, Radhika, Taylor, Hugh R, Tu, Elmer Y, Tuli, Sonal S, Vajpayee, Rasik B, Van Gelder, Russell N, Watson, Stephanie L, Zegans, Michael E, and Chodosh, James
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Anti-Bacterial Agents ,Bacterial Infections ,Corneal Ulcer ,Developing Countries ,Global Health ,Health Promotion ,Humans ,Leprosy ,Neglected Diseases ,Onchocerciasis ,Ocular ,Trachoma ,Medical and Health Sciences ,Tropical Medicine - Published
- 2019
5. Characteristics of Prescreened Patients Who Did Not Participate in the Zoster Eye Disease Study
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Maja, Ayodele K., primary, Gu, Darren, additional, Ge, Lily, additional, Lopez-Jimenez, Carlos, additional, Cohen, Elisabeth J., additional, and Zegans, Michael E., additional
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- 2024
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6. Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis
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Singh, Rohan Bir, Das, Sujata, Chodosh, James, Sharma, Namrata, Zegans, Michael E., Kowalski, Regis P., and Jhanji, Vishal
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- 2022
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7. The Significance of Repeat Cultures in the Treatment of Severe Fungal Keratitis
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Ray, Kathryn J, Prajna, N Venkatesh, Lalitha, Prajna, Rajaraman, Revathi, Krishnan, Tiruvengada, Patel, Sushila, Das, Manoranjan, Shah, Ranjeet, Dhakhwa, Kavita, McLeod, Stephen D, Zegans, Michael E, Acharya, Nisha R, Lietman, Thomas M, Rose-Nussbaumer, Jennifer, and Group, Mycotic Ulcer Treatment Trial
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Eye Disease and Disorders of Vision ,Clinical Research ,Clinical Trials and Supportive Activities ,Eye ,Administration ,Oral ,Adult ,Antifungal Agents ,Bacteriological Techniques ,Corneal Perforation ,Corneal Ulcer ,Double-Blind Method ,Eye Infections ,Fungal ,Female ,Fungi ,Humans ,India ,Keratoplasty ,Penetrating ,Male ,Middle Aged ,Nepal ,Re-Epithelialization ,Risk Assessment ,Treatment Outcome ,Vision Disorders ,Visual Acuity ,Voriconazole ,Mycotic Ulcer Treatment Trial Group ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
PURPOSE:To identify fungal keratitis patients who are at risk of a poor outcome and may benefit from closer follow-up or more aggressive treatment. DESIGN:Secondary analysis of randomized clinical trial data. METHODS:We compared the clinical outcomes of patients who had positive 6-day fungal cultures with those who did not, using backward stepwise regression with covariates for all baseline clinical characteristics. SUBJECTS:Patients presenting with a smear-positive filamentous fungal ulcer and visual acuity of 20/400 or worse, and who subsequently had a 6-day fungal culture performed at the Aravind Eye Care system (India), Lumbini Eye Hospital (Nepal), or Bharatpur Eye Hospital (Nepal). MAIN OUTCOME MEASURES:The primary outcome is rate of corneal perforation and/or the need for therapeutic penetrating keratoplasty. Secondary outcomes include 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate and/or scar size, and rate of re-epithelialization. RESULTS:Patients who tested positive at their 6-day culture had twice the hazard of experiencing a corneal perforation or the need for therapeutic penetrating keratoplasty (P = .002) than those who tested negative, even after controlling for baseline ulcer characteristics. These patients also had on average 0.26 logMAR lines worse BSCVA at 3 months (P = .001). Culture positivity at day 6 was not a statistically significant predictor of 3-month infiltrate/scar-size (-0.24 mm1; P = .45) or time to re-epithelialization (hazard ratio = .81; P = .31). CONCLUSIONS:Here we identify a uniquely valuable clinical tool, day 6 culture results, for the treatment of severe fungal keratitis. Risk stratification based on repeat culture positivity is an objective way to assess response to medical therapy and identify patients who are at high risk of a poor clinical outcome. This establishes a new standard of care for severe fungal keratitis management.
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- 2018
8. Out of sight, but not out of mind: Zoster sine herpete case study and survey of Zoster Eye Disease Study (ZEDS) Group
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Sanchez, George, primary, Tsougranis, Gregory, additional, Zheng, Heavenly, additional, Miller, Donald M., additional, Phan, Cong, additional, Jeng, Bennie H., additional, Cohen, Elisabeth, additional, and Zegans, Michael E., additional
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- 2024
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9. Predictors of Corneal Perforation or Need for Therapeutic Keratoplasty in Severe Fungal Keratitis: A Secondary Analysis of the Mycotic Ulcer Treatment Trial II
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Prajna, N Venkatesh, Krishnan, Tiruvengada, Rajaraman, Revathi, Patel, Sushila, Shah, Ranjeet, Srinivasan, Muthiah, Das, Manoranjan, Ray, Kathryn J, Oldenburg, Catherine E, McLeod, Stephen D, Zegans, Michael E, Acharya, Nisha R, Lietman, Thomas M, and Rose-Nussbaumer, Jennifer
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Clinical Research ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Eye Disease and Disorders of Vision ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Eye ,Administration ,Oral ,Adult ,Antifungal Agents ,Corneal Perforation ,Corneal Ulcer ,Double-Blind Method ,Drug Therapy ,Combination ,Eye Infections ,Fungal ,Female ,Humans ,Keratoplasty ,Penetrating ,Male ,Middle Aged ,Mycoses ,Natamycin ,Suppuration ,Visual Acuity ,Voriconazole ,Mycotic Ulcer Treatment Trial Group ,Opthalmology and Optometry ,Ophthalmology & Optometry - Abstract
ImportanceIdentifying patients with infectious keratitis who are at risk of experiencing a poor outcome may be useful to allocate resources toward high-risk patients, particularly in resource-poor settings.ObjectiveTo determine baseline patient and ulcer characteristics that predict a high risk of developing corneal perforation and/or the need to undergo therapeutic penetrating keratoplasty (TPK).Design, setting, and participantsThis is a secondary analysis of Mycotic Ulcer Treatment Trial II, a multicenter, double-masked, placebo-controlled randomized clinical trial that enrolled 240 patients with smear-positive filamentous fungal corneal ulcers who enrolled between May 2010 and August 2015. Participants had a baseline visual acuity of 20/400 or worse and were randomized to receive oral voriconazole or a placebo (all participants received topical voriconazole, 1%). After 39 participants (16.3%) were enrolled, topical natamycin, 5%, was also added.Main outcomes and measuresThe primary outcome of this secondary analysis was the rate of corneal perforation or the need to undergo TPK.ResultsThe mean (SD) age at enrollment was 49 (13) years, 104 participants (43.3%) were women, and all were of Southeast Asian descent. The presence of hypopyon at baseline indicated 2.28 times the odds of the patient developing corneal perforation and/or needing TPK (95% CI, 1.18-4.40; P = .01). Study participants whose infiltrate involved the posterior one-third had a 71.4% risk of developing corneal perforation and/or needing TPK. For each 1-mm increase in the geometric mean of the infiltrate, there was 1.37 (95% CI, 1.12-1.67; P = .002) increased odds of developing perforation and/or needing TPK. Other clinical features such as visual acuity, baseline culture positivity, type of filamentous fungal organism and duration of symptoms, and demographic characteristics, such as sex and occupation, were not significant predictors in the multivariable regression analysis.Conclusions and relevanceThese results suggest that risk stratification from baseline ulcer characteristics can identify those at highest risk for developing corneal perforation and/or needing TPK.Trial registrationclinicaltrials.gov Identifier: NCT00996736.
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- 2017
10. Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II): A Randomized Clinical Trial
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Prajna, N Venkatesh, Krishnan, Tiruvengada, Rajaraman, Revathi, Patel, Sushila, Srinivasan, Muthiah, Das, Manoranjan, Ray, Kathryn J, O’Brien, Kieran S, Oldenburg, Catherine E, McLeod, Stephen D, Zegans, Michael E, Porco, Travis C, Acharya, Nisha R, Lietman, Thomas M, and Rose-Nussbaumer, Jennifer
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Infectious Diseases ,Clinical Trials and Supportive Activities ,Clinical Research ,Eye Disease and Disorders of Vision ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Administration ,Oral ,Adult ,Aged ,Antifungal Agents ,Cornea ,Corneal Ulcer ,Dose-Response Relationship ,Drug ,Double-Blind Method ,Eye Infections ,Fungal ,Female ,Follow-Up Studies ,Humans ,Male ,Middle Aged ,Retrospective Studies ,Treatment Outcome ,Voriconazole ,Mycotic Ulcer Treatment Trial II Group ,Ophthalmology and optometry - Abstract
ObjectiveTo compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis.Design, setting, and participantsThe Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis.InterventionsStudy participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%.Main outcomes and measuresThe primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use.ResultsA total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup analyses comparing treatment effects among organism subgroups, there was some suggestion that Fusarium species might have a decreased rate of perforation or TPK in the oral voriconazole-treated arm; however, this was not a statistically significant finding after Holms-Šidák correction for multiple comparisons (effect coefficient, 0.49; 95% CI, 0.26-0.92; P = .03). Patients receiving oral voriconazole experienced a total of 58 adverse events (48.7%) compared with 28 adverse events (23.1%) in the placebo group (P
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- 2016
11. Environmentally Endemic Pseudomonas aeruginosa Strains with Mutations in lasR Are Associated with Increased Disease Severity in Corneal Ulcers
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Hammond, John H, Hebert, Wesley P, Naimie, Amanda, Ray, Kathryn, Van Gelder, Rachel D, DiGiandomenico, Antonio, Lalitha, Prajna, Srinivasan, Muthiah, Acharya, Nisha R, Lietman, Thomas, Hogan, Deborah A, and Zegans, Michael E
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Microbiology ,Biological Sciences ,Infectious Diseases ,Genetics ,Rare Diseases ,Eye Disease and Disorders of Vision ,Aetiology ,2.2 Factors relating to the physical environment ,2.1 Biological and endogenous factors ,Infection ,Anr ,bacterial keratitis ,corneal ulcer ,CupA ,eye infection ,LasR ,Pseudomonas aeruginosa ,quorum sensing ,SCUT - Abstract
The Steroids for Corneal Ulcers Trial (SCUT) was a multicenter, international study of bacterial keratitis in which 101 Pseudomonas aeruginosa infections were treated. Twenty-two of 101 P. aeruginosa isolates collected had a colony morphology characteristic of a loss-of-function mutation in lasR, the gene encoding a quorum-sensing master regulator. Ulcers caused by these 22 strains were associated with larger areas of corneal opacification, worse vision, and a lower rate of vision recovery in response to treatment than ulcers caused by the other isolates. The lasR sequences from these isolates each contained one of three nonsynonymous substitutions, and these strains were deficient in production of LasR-regulated protease and rhamnolipids. Replacement of lasR with either of the two most common lasR alleles from the SCUT isolates was sufficient to decrease protease and rhamnolipid production in PA14. Loss of LasR function is associated with increased production of CupA fimbriae, and the LasR-defective isolates exhibited higher production of CupA fimbriae than LasR-intact isolates. Strains with the same lasR mutation were of the same multilocus sequence type, suggesting that LasR-deficient, environmental P. aeruginosa strains were endemic to the area, and infections caused by these strains were associated with worse patient outcomes in the SCUT study. (This study has been registered at ClinicalTrials.gov under registration no. NCT00324168.) IMPORTANCE The LasR transcription factor is an important regulator of quorum sensing in P. aeruginosa and positively controls multiple virulence-associated pathways. The emergence of strains with lasR loss-of-function alleles in chronic disease is well described and is thought to represent a specific adaptation to the host environment. However, the prevalence and virulence of these strains in acute infections remain unclear. This report describes observations revealing that lasR mutants were common among isolates from a large, multicenter clinical study of keratitis and were associated with worse clinical outcomes than LasR-intact strains despite reduced production of LasR-regulated factors. Additionally, these lasR mutants were closely related strains or clones, as determined by molecular analysis. Because bacterial keratitis is community acquired, these data indicate infection by endemic, LasR-deficient strains in the environment. These results suggest that the conventional paradigm regarding the role for LasR-mediated regulation of virulence is more complex than previously appreciated.
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- 2016
12. Changing Azole Resistance: A Secondary Analysis of the MUTT I Randomized Clinical Trial.
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Prajna, N Venkatesh, Lalitha, Prajna, Rajaraman, Revathi, Krishnan, Tiruvengada, Raghavan, Anita, Srinivasan, Muthiah, O'Brien, Kieran S, Zegans, Michael, McLeod, Stephen D, Acharya, Nisha R, Keenan, Jeremy D, Lietman, Thomas M, Rose-Nussbaumer, Jennifer, and Mycotic Ulcer Treatment Trial Group
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Mycotic Ulcer Treatment Trial Group ,Humans ,Fungi ,Corneal Ulcer ,Eye Infections ,Fungal ,Mycoses ,Natamycin ,Antifungal Agents ,Microbial Sensitivity Tests ,Double-Blind Method ,Drug Resistance ,Multiple ,Fungal ,Visual Acuity ,Adult ,Middle Aged ,Female ,Male ,Voriconazole ,Eye Disease and Disorders of Vision ,Infectious Diseases ,Prevention ,Clinical Trials and Supportive Activities ,Clinical Research ,Infection ,Good Health and Well Being ,Opthalmology and Optometry ,Ophthalmology & Optometry - Abstract
ImportanceThe development of multiple triazole resistance in pathogenic filamentous fungi has become an increasing clinical concern and has been shown to increase the risk for treatment failure.ObjectiveTo determine whether antifungal resistance increased during the Mycotic Ulcer Treatment Trial I (MUTT I), as measured by minimum inhibitory concentrations (MICs) in baseline cultures.Design, setting, and participantsThis secondary analysis of a double-masked, multicenter, randomized clinical trial included patients with culture- or smear-positive filamentous fungal corneal ulcer and a baseline visual acuity of 20/40 to 20/400. Culture-positive samples with susceptibility testing were included in this analysis. The patients were treated at multiple locations of the Aravind Eye Care Hospital system in South India. Data were collected from April 3, 2010, to December 31, 2011, and analyzed from July 15 to September 1, 2015.InterventionsCorneal smears and cultures were obtained from all study participants at baseline. Susceptibility testing was performed for each culture-positive specimen.Main outcomes and measuresMinimum inhibitory concentration of voriconazole and natamycin in baseline cultures.ResultsOf 323 participants with smear-positive specimens (183 men [56.7%]; 140 women [43.3%]; median [interquartile range] age, 47 [38-56] years), fungal-positive cultures were obtained for 256 (79.3%). The MIC data were available for 221 of 323 participants (68.4%), because 35 samples had no growth during susceptibility testing. A 2.14-fold increase per year (95% CI, 1.13-4.56; P = .02) in voriconazole MICs after controlling for the infectious organism was found. This association was not found when looking at natamycin MICs of baseline cultures after controlling for the infectious organism (1.26; 95% CI, 0.13-12.55; P = .85).Conclusions and relevanceSusceptibility to voriconazole appeared to decrease during the relatively short enrollment period of the clinical trial. This decrease may be more related to increased resistance of environmental fungi rather than previous treatment with azoles, because presenting with azole treatment was not a risk factor for resistance.Trial registrationclinicaltrials.gov Identifier: NCT00996736.
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- 2016
13. Surgery Versus Interferon Alpha-2b Treatment Strategies for Ocular Surface Squamous Neoplasia
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Siedlecki, Andrew N, Tapp, Stephanie, Tosteson, Anna NA, Larson, Robin J, Karp, Carol L, Lietman, Thomas, and Zegans, Michael E
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Cancer ,Clinical Research ,Adult ,Aged ,Antineoplastic Agents ,Carcinoma ,Squamous Cell ,Combined Modality Therapy ,Conjunctival Neoplasms ,Decision Support Techniques ,Female ,Humans ,Interferon alpha-2 ,Interferon-alpha ,Male ,Neoplasm Recurrence ,Local ,Ophthalmologic Surgical Procedures ,Probability ,Prospective Studies ,Recombinant Proteins ,Reoperation ,Sensitivity and Specificity ,eye neoplasms ,decision analysis ,ocular surface squamous neoplasia ,interferon alpha-2b ,Clinical Sciences ,Opthalmology and Optometry ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
PurposeTo compare treatment strategies for ocular surface squamous neoplasia (OSSN), ranging from surgical excision to empiric topical interferon alpha-2b (IFN-α2b).MethodsA decision model was constructed to determine which of 4 treatment strategies minimized expected persistence/recurrence of disease in patients with OSSN: excision followed by repeat excision for positive surgical margins, excision followed by IFN-α2b for positive margins, incisional biopsy followed by IFN-α2b for positive biopsies, and empiric treatment with IFN-α2b. Probabilities were estimated from literature published between 1983 and 2015. Expected values for the probability of recurrence could range from 0 (no persistence/recurrence) to 1 (persistence/recurrence). Sensitivity analyses were performed for each variable.ResultsExcision followed by IFN-α2b for positive margins was estimated to minimize persistence/recurrence of OSSN (expected value 0.13 versus 0.17 for empiric IFN-α2b, 0.22 for excision-only, and 0.30 for incisional biopsy-directed IFN-α2b). The optimal strategy was sensitive to 3 variables: efficacy of IFN-α2b, recurrence after negative surgical margins, and accuracy of excisional biopsy.ConclusionsIn our decision analysis using studies published between 1983 and 2015, surgical excision followed by IFN-α2b for positive margins is the favored strategy for minimizing persistence/recurrence of OSSN. Future prospective studies would add to the certainty of these conclusions.
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- 2016
14. Association of Artificial Tears with Ocular and Systemic Infection: Carbapenem-resistant Pseudomonas aeruginosa (VIM-GES-CRPA) Outbreak
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Velcani, Frida, primary, Kuo, Irene C., additional, Shanks, Robert M.Q., additional, Chodosh, James, additional, Garg, Prashant, additional, Amescua, Guillermo, additional, and Zegans, Michael E., additional
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- 2023
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15. Early Addition of Topical Corticosteroids in the Treatment of Bacterial Keratitis
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Ray, Kathryn J, Srinivasan, Muthiah, Mascarenhas, Jeena, Rajaraman, Revathi, Ravindran, Meenakshi, Glidden, David V, Oldenburg, Catherine E, Sun, Catherine Q, Zegans, Michael E, McLeod, Stephen D, Acharya, Nisha R, and Lietman, Thomas M
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Clinical Research ,Eye Disease and Disorders of Vision ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Administration ,Topical ,Adult ,Aza Compounds ,Confidence Intervals ,Dose-Response Relationship ,Drug ,Double-Blind Method ,Drug Administration Schedule ,Drug Therapy ,Combination ,Eye Infections ,Bacterial ,Female ,Fluoroquinolones ,Follow-Up Studies ,Humans ,Keratitis ,Linear Models ,Male ,Middle Aged ,Moxifloxacin ,Multivariate Analysis ,Prednisolone ,Quinolines ,Severity of Illness Index ,Time Factors ,Treatment Outcome ,Ophthalmology and optometry - Abstract
ImportanceScarring from bacterial keratitis remains a leading cause of visual loss.ObjectiveTo determine whether topical corticosteroids are beneficial as an adjunctive therapy for bacterial keratitis if given early in the course of infection.Design, setting, and participantsThe Steroids for Corneal Ulcers Trial (SCUT) was a randomized, double-masked, placebo-controlled trial that overall found no effect of adding topical corticosteroids to topical moxifloxacin hydrochloride in bacterial keratitis. Here, we assess the timing of administration of corticosteroids in a subgroup analysis of the SCUT. We define earlier administration of corticosteroids (vs placebo) as addition after 2 to 3 days of topical antibiotics and later as addition after 4 or more days of topical antibiotics.Main outcomes and measuresWe assess the effect of topical corticosteroids (vs placebo) on 3-month best spectacle-corrected visual acuity in patients who received corticosteroids or placebo earlier vs later. Further analyses were performed for subgroups of patients with non-Nocardia keratitis and those with no topical antibiotic use before enrollment.ResultsPatients treated with topical corticosteroids as adjunctive therapy within 2 to 3 days of antibiotic therapy had approximately 1-line better visual acuity at 3 months than did those given placebo (-0.11 logMAR; 95% CI, -0.20 to -0.02 logMAR; P = .01). In patients who had 4 or more days of antibiotic therapy before corticosteroid treatment, the effect was not significant; patients given corticosteroids had 1-line worse visual acuity at 3 months compared with those in the placebo group (0.10 logMAR; 95% CI, -0.02 to 0.23 logMAR; P = .14). Patients with non-Nocardia keratitis and those having no topical antibiotic use before the SCUT enrollment showed significant improvement in best spectacle-corrected visual acuity at 3 months if corticosteroids were administered earlier rather than later.Conclusions and relevanceThere may be a benefit with adjunctive topical corticosteroids if application occurs earlier in the course of bacterial corneal ulcers.
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- 2014
16. Visual Recovery in Treated Bacterial Keratitis
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Srinivasan, Muthiah, Mascarenhas, Jeena, Rajaraman, Revathi, Ravindran, Meenakshi, Lalitha, Prajna, Ray, Kathryn J, Zegans, Michael E, Acharya, Nisha R, Lietman, Thomas M, Keenan, Jeremy D, and Group, Steroids for Corneal Ulcers Trial
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Adult ,Aged ,Anti-Bacterial Agents ,Aza Compounds ,Corneal Ulcer ,Eye Infections ,Bacterial ,Female ,Fluoroquinolones ,Glucocorticoids ,Humans ,Male ,Middle Aged ,Moxifloxacin ,Prednisolone ,Quinolines ,Recovery of Function ,Visual Acuity ,Steroids for Corneal Ulcers Trial Group ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
Bacterial keratitis is a leading cause of visual impairment worldwide. However, the natural history of treated bacterial keratitis has not been well characterized. We performed a secondary analysis of the Steroids for Corneal Ulcers Trial (SCUT; clinicaltrials.gov #NCT00324168) to better characterize the rate of visual acuity improvement after successful antimicrobial treatment.
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- 2014
17. The Steroids for Corneal Ulcers Trial (SCUT): Secondary 12-Month Clinical Outcomes of a Randomized Controlled Trial
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Srinivasan, Muthiah, Mascarenhas, Jeena, Rajaraman, Revathi, Ravindran, Meenakshi, Lalitha, Prajna, O'Brien, Kieran S, Glidden, David V, Ray, Kathryn J, Oldenburg, Catherine E, Zegans, Michael E, Whitcher, John P, McLeod, Stephen D, Porco, Travis C, Lietman, Thomas M, Acharya, Nisha R, and Group, Steroids for Corneal Ulcers Trial
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Clinical Trials and Supportive Activities ,Clinical Research ,Eye Disease and Disorders of Vision ,6.1 Pharmaceuticals ,5.1 Pharmaceuticals ,Administration ,Topical ,Adult ,Anti-Bacterial Agents ,Aza Compounds ,Bacteria ,Corneal Ulcer ,Double-Blind Method ,Eye Infections ,Bacterial ,Female ,Fluoroquinolones ,Glucocorticoids ,Humans ,Male ,Middle Aged ,Moxifloxacin ,Nocardia ,Nocardia Infections ,Ophthalmic Solutions ,Prednisolone ,Quinolines ,Treatment Outcome ,Visual Acuity ,Steroids for Corneal Ulcers Trial Group ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
PurposeTo determine whether topical corticosteroids as adjunctive therapy for bacterial keratitis improves long-term clinical outcomes.DesignRandomized, placebo-controlled, double-masked clinical trial.MethodsThis multicenter trial compared 1.0% prednisolone sodium phosphate to placebo in the treatment of bacterial keratitis among 500 patients with culture-positive ulcers receiving 48 hours of moxifloxacin before randomization. The primary endpoint was 3 months from enrollment, and 399 patients were evaluated at 12 months. The outcomes examined were best spectacle-corrected visual acuity (BSCVA) and scar size at 12 months. Based on previous results, regression models with adjustments for baseline status and/or causative organism were used for analysis.ResultsNo significant differences in clinical outcomes by treatment group were seen with the prespecified regression models (BSCVA: -0.04 logMAR, 95% CI, -0.12 to 0.05, P = .39; scar size: 0.03 mm, 95% CI, -0.12 to 0.18, P = .69). A regression model including a Nocardia-treatment arm interaction found corticosteroid use associated with a mean 1-line improvement in BSCVA at 12 months among patients with non-Nocardia ulcers (-0.10 logMAR, 95% CI, -0.19 to -0.02, P = .02). No significant difference was observed in 12-month BSCVA for Nocardia ulcers (0.18 logMAR, 95% CI, -0.04 to 0.41, P = .16). Corticosteroids were associated with larger mean scar size at 12 months among Nocardia ulcers (0.47 mm, 95% CI, 0.06-0.88, P = .02) and no significant difference was identified by treatment for scar size for non-Nocardia ulcers (-0.06 mm, 95% CI, -0.21 to 0.10, P = .46).ConclusionsAdjunctive topical corticosteroid therapy may be associated with improved long-term clinical outcomes in bacterial corneal ulcers not caused by Nocardia species.
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- 2014
18. Evaluation of fungal keratitis using a newly developed computer program, Optscore, for grading digital corneal photographs.
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Toutain-Kidd, Christine M, Porco, Travis C, Kidd, Eric M, Srinivasan, M, Prajna, Namperumalsamy V, Acharya, Nisha, Lietman, Thomas, and Zegans, Michael E
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Humans ,Corneal Ulcer ,Eye Infections ,Fungal ,Image Interpretation ,Computer-Assisted ,Observer Variation ,Photography ,Radiographic Image Enhancement ,Diagnostic Techniques ,Ophthalmological ,Regression Analysis ,Reproducibility of Results ,Software ,Eye Disease and Disorders of Vision ,Clinical Research ,Eye ,Corneal ulcer grading ,digital photography ,Mycotic Ulcer Treatment Trial ,Optscore ,Steroids for Corneal Ulcers Trial ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Epidemiology - Abstract
PurposeTo validate computer software developed to assess digital corneal photographs of fungal keratitis in clinical research.MethodsA cornea specialist and five medical students (after training) graded on two occasions 100 corneal photographs of patients with fungal keratitis using Optscore software. Variables assessed were lesion area, location, degree of opacity, percentage of the ulcer lying within a central 4 mm circle of the cornea. Intraclass correlation coefficients (ICCs) were used to assess intragrader reliability, agreement of the students with the corneal specialist, and the reliability of the group mean of the student raters. The area determined using Optscore was compared to the area estimated from slit lamp and to visual acuity.ResultsAs a group, medical students achieved an ICC greater than 0.9 for five out of the seven assessed variables. Similar levels of consistency were found after analyzing the graders' individual results compared to the specialist. The area estimated using slit lamp examination was highly correlated with the mean area determined by Optscore, as was the logarithm of the minimum angle of resolution visual acuity at enrollment.ConclusionsNon-expert graders using Optscore to assess digital photographs of fungal keratitis are self-consistent, agree with an expert grader both as a group and individually, and measurements of ulcer area obtained from Optscore are highly correlated with measurements of the same patients obtained on clinical examination. These observations support the validity of Optscore for assessing corneal pathology associated with fungal keratitis and make it a promising clinical research tool.
- Published
- 2014
19. A rise in the frequency of lasR mutant Pseudomonas aeruginosa among keratitis isolates between 1993 and 2021
- Author
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Shanks, Robert M. Q., primary, Atta, Sarah, additional, Stella, Nicholas A., additional, Sundar-Raj, Chollapadi V., additional, Romanowski, John E., additional, Grewal, Arman S., additional, Shanks, Hazel Q., additional, Mumper, Sonya M., additional, Dhaliwal, Deepinder K., additional, Mammen, Alex, additional, Callaghan, Jake D., additional, Calvario, Rachel C., additional, Romanowski, Eric G., additional, Kowalski, Regis P., additional, Zegans, Michael E., additional, and Jhanji, Vishal, additional
- Published
- 2023
- Full Text
- View/download PDF
20. Deficiency in the Midst of Abundance: Xerophthalmia Case Series and Vitamin A Levels in a New England Hospital
- Author
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Li, Xiao Y., primary, Maja, Ayodele K., additional, Sanchez, George, additional, Srinivas, Sowmya, additional, and Zegans, Michael E., additional
- Published
- 2023
- Full Text
- View/download PDF
21. Cefiderocol: A new and effective topical monotherapy treatment for experimental extensively-drug resistant Pseudomonas aeruginosa keratitis
- Author
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Romanowski, Eric G., primary, Mumpers, Sonya M, additional, Shanks, Hazel Q, additional, Yates, Kathleen A, additional, Mandell, Jonathan B, additional, Zegans, Michael E, additional, and Shanks, Robert M. Q., additional
- Published
- 2023
- Full Text
- View/download PDF
22. Rise in frequency of lasR mutant Pseudomonas aeruginosa among keratitis isolates between 1993 and 2021
- Author
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Shanks, Robert MQ, primary, Atta, Sarah, additional, Stella, Nicholas A, additional, Sundar-Raj, Chollapadi V, additional, Romanowski, John E, additional, Grewal, Arman S., additional, Shanks, Hazel Q, additional, Mumper, Sonya M, additional, Dhaliwal, Deepinder K, additional, Mammen, Alex, additional, Callaghan, Jake D, additional, Calvario, Rachel C, additional, Romanowski, Eric G., additional, Kowalski, Regis P, additional, Zegans, Michael E, additional, and Jhanji, Vishal, additional
- Published
- 2023
- Full Text
- View/download PDF
23. Emerging Moxifloxacin Resistance in Pseudomonas aeruginosa Keratitis Isolates in South India
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Oldenburg, Catherine E, Lalitha, Prajna, Srinivasan, Muthiah, Rajaraman, Revathi, Ravindran, Meenakshi, Mascarenhas, Jeena, Borkar, Durga S, Ray, Kathryn J, Zegans, Michael E, McLeod, Stephen D, Porco, Travis C, Lietman, Thomas M, and Acharya, Nisha R
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Ophthalmology and Optometry ,Clinical Trials and Supportive Activities ,Eye Disease and Disorders of Vision ,Clinical Research ,Rare Diseases ,Antimicrobial Resistance ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Anti-Bacterial Agents ,Aza Compounds ,Communicable Diseases ,Emerging ,Cornea ,Corneal Ulcer ,Double-Blind Method ,Drug Resistance ,Bacterial ,Drug Therapy ,Combination ,Eye Infections ,Bacterial ,Fluoroquinolones ,Glucocorticoids ,Humans ,India ,Microbial Sensitivity Tests ,Moxifloxacin ,Prednisolone ,Pseudomonas Infections ,Pseudomonas aeruginosa ,Quinolines ,Antibiotic resistance ,corneal ulcer ,fluoroquinolones ,infection ,Pseudomonas ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Epidemiology ,Ophthalmology and optometry ,Public health - Abstract
PurposeTo describe temporal trends in Pseudomonas aeruginosa resistance to moxifloxacin in keratitis isolates from South India.MethodsThe Steroids for Corneal Ulcers Trial (SCUT) was a randomized, double-masked, placebo-controlled trial assessing outcomes in patients with culture positive bacterial corneal ulcers randomized to receive prednisolone phosphate or placebo. All patients received moxifloxacin, and susceptibility to moxifloxacin was measured at baseline using Etest. We investigated trends in moxifloxacin susceptibility of P. aeruginosa during 2007, 2008, and 2009 isolated in SCUT in South India.ResultsThere were 89 P. aeruginosa isolates during 2007, 2008, and 2009 in SCUT that were eligible for this study. There was an increase in the proportion of resistant isolates from 19% in 2007 to 52% in 2009 (p = 0.02, χ(2) test for trend). Logistic regression showed that there was a 2-fold increase in odds of resistance per 1 year increase during the study period (odds ratio 2.16, 95% confidence interval 1.09-4.26, p = 0.027).ConclusionsWe found a sharp increase in the proportion of isolates that were resistant to moxifloxacin from 2007 to 2009. Further work needs to be done to characterize the nature of this increase.
- Published
- 2013
24. The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole.
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Prajna, N Venkatesh, Krishnan, Tiruvengada, Mascarenhas, Jeena, Rajaraman, Revathi, Prajna, Lalitha, Srinivasan, Muthiah, Raghavan, Anita, Oldenburg, Catherine E, Ray, Kathryn J, Zegans, Michael E, McLeod, Stephen D, Porco, Travis C, Acharya, Nisha R, Lietman, Thomas M, and Mycotic Ulcer Treatment Trial Group
- Subjects
Mycotic Ulcer Treatment Trial Group ,Humans ,Fungi ,Corneal Ulcer ,Eye Infections ,Fungal ,Mycoses ,Natamycin ,Triazoles ,Pyrimidines ,Ophthalmic Solutions ,Antifungal Agents ,Treatment Outcome ,Keratoplasty ,Penetrating ,Administration ,Topical ,Double-Blind Method ,Wound Healing ,Visual Acuity ,Adult ,Middle Aged ,Female ,Male ,Corneal Perforation ,Voriconazole ,Eye Disease and Disorders of Vision ,Clinical Research ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Opthalmology and Optometry ,Ophthalmology & Optometry - Abstract
ObjectiveTo compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis.MethodsThis phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400.Main outcome measuresThe primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty.ResultsA total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycintreated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient=0.18 logMAR; 95% CI, 0.30 to 0.05; P=.006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio=0.42; 95% CI, 0.22 to 0.80; P=.009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient=0.41 logMAR; 95% CI,0.61 to 0.20; P
- Published
- 2013
25. Association Between Cytotoxic and Invasive Pseudomonas aeruginosa and Clinical Outcomes in Bacterial Keratitis
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Borkar, Durga S, Fleiszig, Suzanne MJ, Leong, Chelsia, Lalitha, Prajna, Srinivasan, Muthiah, Ghanekar, Avanti A, Tam, Connie, Li, Y, Zegans, Michael E, McLeod, Stephen D, Lietman, Thomas M, and Acharya, Nisha R
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Infectious Diseases ,Eye Disease and Disorders of Vision ,Clinical Research ,Neurosciences ,Eye ,Anti-Infective Agents ,Aza Compounds ,Bacterial Toxins ,Bacterial Typing Techniques ,Corneal Ulcer ,DNA ,Bacterial ,Exotoxins ,Eye Infections ,Bacterial ,Fluoroquinolones ,Genotype ,Glucocorticoids ,Humans ,L-Lactate Dehydrogenase ,Middle Aged ,Moxifloxacin ,Polymerase Chain Reaction ,Pseudomonas Infections ,Pseudomonas aeruginosa ,Quinolines ,Virulence ,Visual Acuity ,Ophthalmology and optometry - Abstract
ObjectivesTo determine whether cytotoxic and invasive Pseudomonas aeruginosa strains differentially influence clinical presentation, outcomes, or therapeutic response in bacterial keratitis.MethodsPseudomonas aeruginosa isolates from the National Eye Institute-funded Steroids for Corneal Ulcers Trial were subtyped as cytotoxic or invasive strains. The main outcome measure compared between the 2 subtypes was change in visual acuity at 3 months using Huber robust regression, adjusting for topical corticosteroid treatment.ResultsOf 101 confirmed P aeruginosa isolates from the Steroids for Corneal Ulcers Trial, 74 had a classically cytotoxic or invasive genotype. While corneal ulcers caused by genotypically invasive P aeruginosa strains were associated at presentation with significantly better visual acuity than corneal ulcers caused by genotypically cytotoxic P aeruginosa strains when adjusting for the effect of ulcer location (P= .008), invasive ulcers had improved significantly less than cytotoxic ulcers at 3 months (0.35; 95% CI, 0.04-0.66 logMAR; P= .03 [3.5-line difference]). Compared with topical moxifloxacin alone, adjunctive treatment with topical corticosteroids was associated with significantly more improvement in visual acuity in the invasive subgroup (P= .04) but was associated with less improvement in visual acuity in the cytotoxic subgroup (P= .07).ConclusionsRational profiling of differentially expressed virulence determinants (eg, cytotoxicity and invasiveness for P aeruginosa) could be used as a tool for decision making in the management of infections to optimize outcomes.
- Published
- 2013
26. Prior Elicitation and Bayesian Analysis of the Steroids for Corneal Ulcers Trial
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See, Craig W, Srinivasan, Muthiah, Saravanan, Somu, Oldenburg, Catherine E, Esterberg, Elizabeth J, Ray, Kathryn J, Glaser, Tanya S, Tu, Elmer Y, Zegans, Michael E, McLeod, Stephen D, Acharya, Nisha R, and Lietman, Thomas M
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Clinical Research ,Clinical Trials and Supportive Activities ,Eye Disease and Disorders of Vision ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Administration ,Topical ,Anti-Infective Agents ,Aza Compounds ,Bayes Theorem ,Corneal Ulcer ,Double-Blind Method ,Eye Infections ,Bacterial ,Fluoroquinolones ,Glucocorticoids ,Humans ,Moxifloxacin ,Ophthalmic Solutions ,Prednisolone ,Quinolines ,Surveys and Questionnaires ,Treatment Outcome ,Visual Acuity ,Bacterial keratitis ,Corneal ulcer ,Clinical trial ,Statistics ,Prior distribution ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Epidemiology ,Ophthalmology and optometry ,Public health - Abstract
PurposeTo elicit expert opinion on the use of adjunctive corticosteroid therapy in bacterial corneal ulcers. To perform a Bayesian analysis of the Steroids for Corneal Ulcers Trial (SCUT), using expert opinion as a prior probability.MethodsThe SCUT was a placebo-controlled trial assessing visual outcomes in patients receiving topical corticosteroids or placebo as adjunctive therapy for bacterial keratitis. Questionnaires were conducted at scientific meetings in India and North America to gauge expert consensus on the perceived benefit of corticosteroids as adjunct treatment. Bayesian analysis, using the questionnaire data as a prior probability and the primary outcome of SCUT as a likelihood, was performed. For comparison, an additional Bayesian analysis was performed using the results of the SCUT pilot study as a prior distribution.ResultsIndian respondents believed there to be a 1.21 Snellen line improvement, and North American respondents believed there to be a 1.24 line improvement with corticosteroid therapy. The SCUT primary outcome found a non-significant 0.09 Snellen line benefit with corticosteroid treatment. The results of the Bayesian analysis estimated a slightly greater benefit than did the SCUT primary analysis (0.19 lines verses 0.09 lines).ConclusionIndian and North American experts had similar expectations on the effectiveness of corticosteroids in bacterial corneal ulcers; that corticosteroids would markedly improve visual outcomes. Bayesian analysis produced results very similar to those produced by the SCUT primary analysis. The similarity in result is likely due to the large sample size of SCUT and helps validate the results of SCUT.
- Published
- 2012
27. Nocardia Keratitis: Clinical Course and Effect of Corticosteroids
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Lalitha, Prajna, Srinivasan, Muthiah, Rajaraman, Revathi, Ravindran, Meenakshi, Mascarenhas, Jeena, Priya, Jeganathan Lakshmi, Sy, Aileen, Oldenburg, Catherine E, Ray, Kathryn J, Zegans, Michael E, McLeod, Stephen D, Lietman, Thomas M, and Acharya, Nisha R
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Eye Disease and Disorders of Vision ,Clinical Research ,Neurosciences ,Clinical Trials and Supportive Activities ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Eye ,Administration ,Topical ,Adult ,Anti-Infective Agents ,Aza Compounds ,Corneal Ulcer ,Double-Blind Method ,Eye Infections ,Bacterial ,Female ,Fluoroquinolones ,Glucocorticoids ,Humans ,Male ,Middle Aged ,Moxifloxacin ,Nocardia ,Nocardia Infections ,Polymerase Chain Reaction ,Prednisolone ,Quinolines ,Treatment Outcome ,Visual Acuity ,Clinical Sciences ,Opthalmology and Optometry ,Public Health and Health Services ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
PurposeTo compare the clinical course of Nocardia species keratitis with keratitis resulting from other bacterial organisms and to assess the effect of corticosteroids as adjunctive therapy using data collected from the Steroids for Corneal Ulcers Trial.DesignSubgroup analysis of a randomized controlled trial.Methodssetting: Multicenter randomized controlled trial. study population: Five hundred patients with bacterial keratitis randomized 1:1 to topical corticosteroid or placebo who had received at least 48 hours of topical moxifloxacin. intervention/observation procedure: Topical prednisolone phosphate 1% or placebo and clinical course of Nocardia keratitis. main outcome measures: Best spectacle-corrected visual acuity and infiltrate or scar size at 3 months from enrollment.ResultsOf 500 patients enrolled in the trial, 55 (11%) had a Nocardia corneal ulcer. Patients with Nocardia ulcers had better presentation visual acuity compared with non-Nocardia ulcers (median Snellen visual acuity, 20/45, compared with 20/145; P < .001) and comparable 3-month visual acuity (median, 20/25, vs 20/40; P = .25). Nocardia ulcers had approximately 2 lines less of improvement in visual acuity compared with non-Nocardia ulcers (0.21 logarithm of the minimal angle of resolution; 95% confidence interval, 0.09 to 0.33 logarithm of the minimal angle of resolution; P = .001). This difference may reflect the better starting visual acuity in patients with Nocardia ulcers. In Nocardia ulcers, corticosteroids were associated with an average 0.4-mm increase in 3-month infiltrate or scar size (95% confidence interval, 0.03 to 0.77 mm; P = .03).ConclusionsNocardia ulcers responded well to treatment. They showed less overall improvement in visual acuity than non-Nocardia ulcers, but had better presentation acuity. Corticosteroids may be associated with worse outcomes.
- Published
- 2012
28. Organism, Minimum Inhibitory Concentration, and Outcome in a Fungal Corneal Ulcer Clinical Trial
- Author
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Lalitha, Prajna, Prajna, N Venkatesh, Oldenburg, Catherine E, Srinivasan, Muthiah, Krishnan, Tiruvengada, Mascarenhas, Jeena, Vaitilingam, CM, McLeod, Stephen D, Zegans, Michael E, Porco, Travis C, Acharya, Nisha R, and Lietman, Thomas M
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Clinical Research ,Clinical Trials and Supportive Activities ,Eye Disease and Disorders of Vision ,Antifungal Agents ,Corneal Ulcer ,Double-Blind Method ,Eye Infections ,Fungal ,Fungi ,Humans ,Microbial Sensitivity Tests ,Mycoses ,Natamycin ,Prospective Studies ,Pyrimidines ,Treatment Outcome ,Triazoles ,Visual Acuity ,Voriconazole ,fungus ,keratitis ,susceptibility ,voriconazole ,natamycin ,Clinical Sciences ,Opthalmology and Optometry ,Ophthalmology & Optometry ,Ophthalmology and optometry - Abstract
PurposeTo analyze the minimum inhibitory concentration (MIC) of isolates from fungal keratitis to natamycin and voriconazole and to assess the relationship between organism, MIC, and clinical outcome.MethodsData were collected as part of a randomized, controlled, double-masked clinical trial. Main outcome measures included best spectacle-corrected visual acuity, infiltrate/scar size, time to reepithelialization, and perforation. Speciation and analysis of MIC to natamycin and voriconazole were done according to Clinical and Laboratory Standards Institute standards. The relationship between MIC and organism, organism and outcome measure, and each outcome measure and MIC were assessed.ResultsOf the 120 samples obtained in the trial, 84 isolates had an identifiable organism and were available for further analyses. Fusarium spp and Aspergillus spp were the most commonly isolated organisms. MIC was significantly different across the groups of organisms (P = 0.0001). A higher MIC was significantly associated with an increased likelihood of perforation [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.02-4.04; P = 0.04]. There was no significant association between MIC and 3-week visual acuity (OR, 0.058; 95% CI, -0.01 to 0.13; P = 0.11), 3-month visual acuity (OR, 0.01; 95% CI,-0.08 to 1.04; P = 0.79), 3-week infiltrate/scar size (OR, 0.12, 95% CI, -0.02 to 0.27; P = 0.10), 3-month infiltrate/scar size (OR, 0.12; 95% CI, -0.02 to 0.25; P = 0.09), or time to reepithelialization (hazards ratio, 1.19; 95% CI, 0.98-1.45; P = 0.08).ConclusionA higher MIC was associated with an increased odds of perforation. The results of this study suggest that resistance to antifungal medication may be associated with worse outcomes in fungal keratitis.
- Published
- 2012
29. Endogenous endophthalmitis and other ocular manifestations of injection drug use
- Author
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Luong, Preston M., Tsui, Edmund, Batra, Nikhil N., and Zegans, Michael E.
- Published
- 2019
- Full Text
- View/download PDF
30. Increased Intraocular Pressure During Hemodialysis: Ocular Dialysis Disequilibrium
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Maja, Ayodele K., primary, Lewis, Chad Y., additional, Steffen, Eric, additional, Zegans, Michael E., additional, and Graber, Martha L., additional
- Published
- 2022
- Full Text
- View/download PDF
31. Acute effects of postural changes and lower body positive and negative pressure on the eye
- Author
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Van Akin, M. P., primary, Lantz, O. M., additional, Fellows, A. M., additional, Toutain-Kidd, Christine, additional, Zegans, Michael, additional, Buckey, J. C., additional, and Anderson, A. P., additional
- Published
- 2022
- Full Text
- View/download PDF
32. Vision Loss Associated With the Opioid Epidemic
- Author
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Luong, Preston M., Tsui, Edmund, Batra, Nikhil, Chapman, Christopher B., and Zegans, Michael E.
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- 2017
- Full Text
- View/download PDF
33. Bacterial corneal ulcer associated with common variable immune deficiency
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Tsui, Edmund, Deng, Jie, Siedlecki, Andrew N, and Zegans, Michael E
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- 2016
- Full Text
- View/download PDF
34. The cif Virulence Factor Gene Is Present in Isolates From Patients With Pseudomonas aeruginosa Keratitis
- Author
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Bahl, Christopher D., St. Laurent, Jessica D., Karthikeyan, R. Siva Ganesa, Priya, J. Lakshmi, Prajna, Lalitha, Zegans, Michael E., and Madden, Dean R.
- Published
- 2017
- Full Text
- View/download PDF
35. Patterns of Antifungal Resistance in Adult Patients With Fungal Keratitis in South India
- Author
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Prajna, N. Venkatesh, primary, Lalitha, Prajna, additional, Krishnan, Tiruvengada, additional, Rajaraman, Revathi, additional, Radnakrishnan, Naveen, additional, Srinivasan, Muthiah, additional, Devi, Lumbini, additional, Das, Manoranjan, additional, Liu, Zijun, additional, Zegans, Michael E., additional, Acharya, Nisha R., additional, Porco, Travis C., additional, Lietman, Thomas M., additional, and Rose-Nussbaumer, Jennifer, additional
- Published
- 2022
- Full Text
- View/download PDF
36. Association of Biofilm Formation, Psl Exopolysaccharide Expression, and Clinical Outcomes in Pseudomonas aeruginosa Keratitis: Analysis of Isolates in the Steroids for Corneal Ulcers Trial
- Author
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Zegans, Michael E., DiGiandomenico, Antonio, Ray, Kathryn, Naimie, Amanda, Keller, Ashley E., Stover, C. Kendall, Lalitha, Prajna, Srinivasan, Muthiah, Acharya, Nisha R., and Lietman, Thomas M.
- Published
- 2016
- Full Text
- View/download PDF
37. Sequential endogenous endophthalmitis, fungal keratitis, bacteremia and vertebral osteomyelitis in a person who injects drugs
- Author
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Lewis, Chad Y., primary, Zegans, Michael E., additional, Batra, Nikhil N., additional, and Jordan, Kelsey L., additional
- Published
- 2021
- Full Text
- View/download PDF
38. Comparison of two azithromycin distribution strategies for controlling trachoma in Nepal
- Author
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Holm Susan Osaki, Jha Hem C., Bhatta Ramesh C., Chaudhary J.S.P., Thapa B.B., Davis Dale, Pokhrel Ram Prasad, Yinghui Miao, Zegans Michael, Schachter Julius, Frick Kevin D., Tapert Lisa, and Lietman Thomas M.
- Subjects
Azithromycin/supply and distribution ,Trachoma/drug therapy ,Comparative study ,Randomized controlled trials ,Nepal ,Public aspects of medicine ,RA1-1270 - Abstract
OBJECTIVE: The study compares the effectiveness of two strategies for distributing azithromycin in an area with mild-to-moderate active trachoma in Nepal. METHODS: The two strategies investigated were the use of azithromycin for 1) mass treatment of all children, or 2) targeted treatment of only those children who were found to be clinically active, as well as all members of their household. FINDINGS: Mass treatment of children was slightly more effective in terms of decreasing the prevalence of clinically active trachoma (estimated by clinical examination) and of chlamydial infection (estimated by DNA amplification tests), although neither result was statistically significant. CONCLUSION: Both strategies appeared to be effective in reducing the prevalence of clinically active trachoma and infection six months after the treatment. Antibiotic treatment reduced the prevalence of chlamydial infection more than it did the level of clinically active trachoma.
- Published
- 2001
39. PRAME immunohistochemistry is useful in the evaluation of conjunctival melanomas, nevi, and primary acquired melanosis
- Author
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LeBlanc, Robert E., primary, Miller, Donald M., additional, and Zegans, Michael E., additional
- Published
- 2021
- Full Text
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40. Interaction between Bacteriophage DMS3 and host CRISPR region inhibits group behaviors of Pseudomonas aeruginosa
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Zegans, Michael E., Wagner, Jeffrey C., Cady, Kyle C., Murphy, Daniel M., Hammond, John H., and O'Toole, George A.
- Subjects
Pseudomonas aeruginosa -- Physiological aspects ,Bacteriophages -- Physiological aspects ,Host-bacteria relationships -- Research ,Biological sciences - Abstract
Bacteriophage infection has profound effects on bacterial biology. Clustered regular interspaced short palindromic repeats (CRISPRs) and cas (CRISPR-associated) genes are found in most archaea and many bacteria and have been reported to play a role in resistance to bacteriophage infection. We observed that lysogenic infection of Pseudomonas aeruginosa PAl4 with bacteriophage DMS3 inhibits biofilm formation and swarming motility, both important bacterial group behaviors. This inhibition requires the CRISPR region in the host. Mutation or deletion of five of the six cas genes and one of the two CRISPRs in this region restored biofilm formation and swarming to DMS3 lysogenized strains. Our observations suggest a role for CRISPR regions in modifying the effects of lysogeny on P. aeruginosa.
- Published
- 2009
41. Oral Miltefosine as Salvage Therapy for Refractory Acanthamoeba Keratitis
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Thulasi, Praneetha, primary, Saeed, Hajirah N., additional, Rapuano, Christopher J., additional, Hou, Joshua H., additional, Appenheimer, Alpheus B., additional, Chodosh, James, additional, Kang, Joann J., additional, Morrill, Amber M., additional, Vyas, Neil, additional, Zegans, Michael E., additional, Zuckerman, Richard, additional, and Tu, Elmer Y., additional
- Published
- 2021
- Full Text
- View/download PDF
42. Clinical characteristics of Mooren's ulcer in South India
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Srinivasan, Muthaiah, Zegans, Michael E., Zelefsky, Joseph R., Kundu, Arunava, Lietman, Thomas, Whitcher, John P., and Cunningham, Emmett T., Jr.
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Ulcers -- Development and progression ,Ulcers -- Care and treatment ,Ulcers -- Research ,Eye diseases -- Development and progression ,Eye diseases -- Care and treatment ,Eye diseases -- Research ,Health - Published
- 2007
43. Roles for flagellar stators in biofilm formation by Pseudomonas aeruginosa
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Toutain, Christine M., Caizza, Nicky C., Zegans, Michael E., and O'Toole, George A.
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- 2007
- Full Text
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44. Antifungal activity of Propranolol against Fusarium keratitis isolates from the Mycotic Ulcer Treatment Trial (MUTT) and the United States
- Author
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Bao, Ruina, primary, Ross, Brandon S., additional, Perez, Cecilia G., additional, Poimenidou, Galini, additional, Prajna, N. Venkatesh, additional, Cramer, Robert A., additional, and Zegans, Michael E., additional
- Published
- 2021
- Full Text
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45. Multifunctional Monoclonal Antibody Targeting Pseudomonas aeruginosa Keratitis in Mice
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Hebert, Wesley, primary, DiGiandomenico, Antonio, additional, and Zegans, Michael, additional
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- 2020
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46. Evidence for two flagellar stators and their role in the motility of Pseudomonas aeruginosa
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Toutain, Christine M., Zegans, Michael E., and O'Toole, George A.
- Subjects
Bacteriology -- Research ,Biological sciences - Abstract
Pseudomonas aeruginosa is a ubiquitous bacterium capable of twitching, swimming, and swarming motility. In this study, we present evidence that P. aeruginosa has two flagellar stators, conserved in all pseudomonads as well as some other gram-negative bacteria. Either stator is sufficient for swimming, but both are necessary for swarming motility under most of the conditions tested, suggesting that these two stators may have different roles in these two types of motility.
- Published
- 2005
47. An outbreak of conjunctivitis due to atypical Streptococcus pneumoniae
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Martin, Michael, Turco, John H., Zegans, Michael E., Facklam, Richard R., Sodha, Samir, Elliott, John A., Pryor, John H., Beall, Bernard, Erdman, Dean D., Baumgartner, Yolanda Y., Sanchez, Paul A., Schwartzman, Joseph D., Montero, Jose, Schuchat, Anne, and Whitney, Cynthia G.
- Subjects
Dartmouth College ,College students -- Diseases ,Pneumococcal infections -- Demographic aspects ,Conjunctivitis -- Demographic aspects - Abstract
A total of 698 students at Dartmouth College in New Hampshire developed an eye infection called conjunctivitis between January and April, 2002. The infection was caused by a bacterium called Streptococcus pneumoniae. The specific strain was found to be the same one that caused outbreaks of conjunctivitis in the US in 1980. Risk factors included contact lens use, contact with an infected student, being on a sports team, and living in a fraternity or sorority house or attending parties at one.
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- 2003
48. Disappearance of trachoma from Western Nepal. (Brief Report)
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Jha, Hem, Chaudary, J.S.P., Bhatta, Ramesh, Miao, Yinghui, Osaki-Holm, Susan, Gaynor, Bruce, Zegans, Michael, Bird, Mariko, Yi, Elizabeth, Holbrook, Karen, Whitcher, John P., and Lietman, Thomas
- Subjects
Trachoma -- Demographic aspects ,Trachoma -- Prevention ,Prevalence studies (Epidemiology) ,Health ,Health care industry ,World Health Organization - Published
- 2002
49. Subgroup Analysis in the Steroids for Corneal Ulcers Trial—Reply
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Srinivasan, Muthiah, Mascarenhas, Jeena, Rajaraman, Revathi, Ravindran, Meenakshi, Glidden, David, Oldenburg, Catherine E., Whitcher, John P., Zegans, Michael E., McLeod, Stephen D., Lietman, Thomas M., and Acharya, Nisha R.
- Published
- 2012
- Full Text
- View/download PDF
50. The Steroids for Corneal Ulcers Trial: Study Design and Baseline Characteristics
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Srinivasan, Muthiah, Mascarenhas, Jeena, Rajaraman, Revathi, Ravindran, Meenakshi, Lalitha, Prajna, Glidden, David V., Ray, Kathryn J., Hong, Kevin C., Oldenburg, Catherine E., Lee, Salena M., Zegans, Michael E., McLeod, Stephen D., Lietman, Thomas M., and Acharya, Nisha R.
- Published
- 2012
- Full Text
- View/download PDF
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