Jennifer Rose-Nussbaumer

All Publications

• Association between in vitro susceptibility and clinical outcomes in fungal keratitis. Journal of ophthalmic inflammation and infection Lu, L., Prajna, N. V., Lalitha, P., Rajaraman, R., Srinivasan, M., Arnold, B. F., Acharya, N., Lietman, T., Rose-Nussbaumer, J. 2024; 14 (1): 42

  Abstract

  The purpose of this study was to assess the association between antifungal susceptibility as measured by minimum inhibitory concentration (MIC) and clinical outcomes in fungal keratitis.This pre-specified secondary analysis of the Mycotic Ulcer Treatment Trial II (MUTT II) involved patients with filamentous fungal keratitis presenting to Aravind Eye Hospitals in South India. Antifungal susceptibility testing for natamycin and voriconazole was performed on all samples with positive fungal culture results according to Clinical and Laboratory Standards Institute Guidelines. The relationship between MIC and clinical outcomes of best-corrected visual acuity, infiltrate or scar size, corneal perforation, need for therapeutic penetrating keratoplasty, and time to re-epithelialization were assessed.We obtained MIC values from 141 patients with fungal keratitis. The most commonly cultured organisms were Aspergillus (46.81%, n = 66) and Fusarium (44.68%, n = 63) species. Overall, there was no association between antifungal MICs and clinical outcomes. Subgroup analysis revealed that among Fusarium-positive cases, higher voriconazole MIC was correlated with worse three-month best-corrected visual acuity (p = 0.03), increased need for therapeutic penetrating keratoplasty (p = 0.04), and time to re-epithelialization (p = 0.03). No significant correlations were found among Aspergillus-positive cases. There were no significant correlations found between natamycin MIC and clinical outcomes among organism subgroups.Decreased susceptibility to voriconazole was associated with increased odds of requiring a therapeutic penetrating keratoplasty in Fusarium-positive cases. Susceptibility to natamycin was not associated with any of the measured outcomes.

  View details for DOI 10.1186/s12348-024-00418-w

  View details for PubMedID 39222170

  View details for PubMedCentralID PMC11368879

• Steroids and Cross-Linking for Ulcer Treatment Trial II: Baseline Characteristics. Cornea Prajna, V. N., Radhakrishnan, N., Lalitha, P. S., Rajaraman, R., Christy, J., Venugopal, A., Abdelrahman, S., Srinivasan, A., Varnado, N., Arnold, B., Amescua, G., Lietman, T. M., Rose-Nussbaumer, J. R. 2024

  Abstract

  The Steroids and Cross-linking for Ulcer Treatment Trial is an NIH-funded international, randomized, double-masked, sham and placebo-controlled clinical trial to determine the benefit of adjunctive corneal cross-linking with riboflavin and/or topical difluprednate in addition to topical antibiotic drops for treatment of smear-positive bacterial ulcers. The purpose of this study was to explore the baseline characteristics for infection of patients enrolled, and the ocular comorbidities of patients screened for inclusion.Of the 2005 patients with smear-positive bacterial ulcers screened, 280 patients were enrolled. Descriptive statistics were used to summarize and characterize the data.Eligible patients in India had baseline factors associated with agricultural work (N = 132; 47%) and manual labor (N = 54; 19%), whereas patients in the United States were associated with contact lens wear (N = 11; 69%) (P <0.001). Nearly, 10% of patients with unilateral infectious keratitis are at risk of bilateral blindness because of preexisting visual disability in their other eye and thus ineligible for inclusion. India had higher rates of exclusionary factors for blindness in the other eye such as cataract (N = 48; 27%) and glaucoma (N = 24; 13) compared with the United States (N = 0; 0%) (P <0.001).While corneal ulceration is an important cause of disability in technologically advanced countries, it occurs more frequently in low and middle-income countries, and the implications on these populations should be considered. These baseline factors can be evaluated to address such health care disparities.

  View details for DOI 10.1097/ICO.0000000000003678

  View details for PubMedID 39208371

• A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthameoba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) Study. Research square Prajna, V., Prajna, L., Sharma, S., de Freitas, D., Höfling-Lima, A. L., Varnado, N., Abdelrahman, S., Cavallino, V., Arnold, B., Lietman, T., Rose-Nussbaumer, J. 2024

  Abstract

  Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro Rose Bengal Photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates.22,23 In one published series RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthameoba keratitis not responsive to medical therapy.This international, randomized, sham and placebo controlled 2-arm clinical trial, randomizes patients with smear positive fungal and acanthameoba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) Topical antimicrobial plus sham RB-PDT or 2) Topical antimicrobial plus RB-PDT.We anticipate that RB-PDT will improve best spectacle corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via clinicaltrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request.NCT, NCT05110001, Registered November 5, 2021. https://www.clinicaltrials.gov/study/NCT05110001.

  View details for DOI 10.21203/rs.3.rs-4165312/v1

  View details for PubMedID 39011096

  View details for PubMedCentralID PMC11247944

• Tissue Loss During Eye Bank Processing. JAMA ophthalmology Naranjo, A., Clover, J., Chamberlain, W., Stoeger, C. G., Lin, C. C., Rose-Nussbaumer, J. 2024

  View details for DOI 10.1001/jamaophthalmol.2024.1336

  View details for PubMedID 38753323

• Locality is the strongest predictor of expert performance in image-based differentiation of bacterial and fungal corneal ulcers from India. Indian journal of ophthalmology Rosenberg, C. R., Prajna, V., Srinivasan, M. K., Lalitha, P. C., Krishnan, T., Rajaraman, R., Venugopal, A., Acharya, N., Seitzman, G. D., Rose-Nussbaumer, J., Woodward, M. A., Lietman, T. M., Campbell, J. P., Keenan, J. D., Redd, T. K. 2024

  Abstract

  This study sought to identify the sources of differential performance and misclassification error among local (Indian) and external (non-Indian) corneal specialists in identifying bacterial and fungal keratitis based on corneal photography.This study is a secondary analysis of survey data assessing the ability of corneal specialists to identify acute bacterial versus fungal keratitis by using corneal photography. One-hundred images of 100 eyes from 100 patients with acute bacterial or fungal keratitis in South India were previously presented to an international cohort of cornea specialists for interpretation over the span of April to July 2021. Each expert provided a predicted probability that the ulcer was either bacterial or fungal. Using these data, we performed multivariable linear regression to identify factors predictive of expert performance, accounting for primary practice location and surrogate measures to infer local fungal ulcer prevalence, including locality, latitude, and dew point. In addition, Brier score decomposition was used to determine experts' reliability ("calibration") and resolution ("boldness") and were compared between local (Indian) and external (non-Indian) experts.Sixty-six experts from 16 countries participated. Indian practice location was the only independently significant predictor of performance in multivariable linear regression. Resolution among Indian experts was significantly better (0.08) than among non-Indian experts (0.01; P < 0.001), indicating greater confidence in their predictions. There was no significant difference in reliability between the two groups (P = 0.40).Local cornea experts outperformed their international counterparts independent of regional variability in tropical risk factors for fungal keratitis. This may be explained by regional characteristics of infectious ulcers with which local corneal specialists are familiar.

  View details for DOI 10.4103/IJO.IJO_3396_22

  View details for PubMedID 38454845

• Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1): outcome masked, placebo-controlled trial comparing two types of corneal transplant surgeries and effect of rho kinase inhibitors on endothelial cell loss protocol. BMJ open ophthalmology Chamberlain, W., Lin, C. C., Li, J. Y., Gensheimer, W., Clover, J., Jeng, B. H., Varnado, N., Abdelrahman, S., Arnold, B. F., Lietman, T. M., Rose-Nussbaumer, J. 2024; 9 (1)

  Abstract

  It remains uncertain which endothelial keratoplasty (EK) technique yields the best outcomes while maintaining safety, particularly in eyes with coexisting ocular conditions. Moreover, the impact of endothelial cell loss (ECL) on long-term graft survival requires further investigation. Adjuvant ripasudil, a rho kinase inhibitor, may address the challenge of ECL in corneal transplantation. This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1), a multicentre, outcome-masked, randomised, placebo-controlled, four-arm clinical trial.A total of 160 eligible patients with endothelial dysfunction will be enrolled from five participating sites in the USA. The patients will be randomly assigned in a 2×2 factorial design to one of the following treatment groups: group 1-ultrathin Descemet stripping endothelial keratoplasty (UT-DSAEK) plus topical ripasudil 0.4%; group 2-UT-DSAEK plus topical placebo; group 3-Descemet membrane endothelial keratoplasty (DMEK) plus topical ripasudil 0.4% and group 4-DMEK plus topical placebo. Primary outcomes include the best spectacle-corrected visual acuity at 12 months and ECL at 12 months. Secondary outcomes include visual acuity at different time points, vision-related quality of life, endothelial cell morphology and cost-effectiveness.The study outcomes will be analysed using mixed effects linear regression models, taking into account the treatment arms and relevant covariates. Adverse events, including rebubble procedures, graft failure and graft rejection, will be documented and analysed using appropriate statistical methods.DETECT I aims to provide evidence on the comparative effectiveness of UT-DSAEK and DMEK, as well as the potential benefits of adjuvant topical ripasudil in reducing ECL. The results of this trial will contribute to optimising corneal transplantation techniques and improving long-term graft survival, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation.A data and safety monitoring committee (DSMC) has been empaneled by the NEI.All study protocols will be subject to review and approval by WCG IRB as the single IRB of record.This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.

  View details for DOI 10.1136/bmjophth-2023-001454

  View details for PubMedID 38286566

• Toric Monofocal Intraocular Lenses for the Correction of Astigmatism during Cataract Surgery: A Report by the American Academy of Ophthalmology. Ophthalmology Al-Mohtaseb, Z., Steigleman, W. A., Pantanelli, S. M., Lin, C. C., Hatch, K. M., Rose-Nussbaumer, J. R., Santhiago, M., Olsen, T. W., Kim, S. J., Schallhorn, J. M. 2023

  Abstract

  To review the published literature evaluating the visual and refractive outcomes and rotational stability of eyes implanted with toric monofocal intraocular lenses (IOLs) for the correction of keratometric astigmatism during cataract surgery and to compare those outcomes with outcomes of eyes implanted with nontoric monofocal IOLs and other astigmatism management methods performed during cataract surgery. This assessment was restricted to the toric IOLs available in the United States.A literature search of English-language publications in the PubMed database was last conducted in July 2022. The search identified 906 potentially relevant citations, and after review of the abstracts, 63 were selected for full-text review. Twenty-one studies ultimately were determined to be relevant to the assessment criteria and were selected for inclusion. The panel methodologist assigned each a level of evidence rating; 12 studies were rated level I and 9 studies were rated level II.Eyes implanted with toric IOLs showed excellent postoperative uncorrected distance visual acuity (UCDVA), reduction of postoperative refractive astigmatism, and good rotational stability. Uncorrected distance visual acuity was better and postoperative cylinder was lower with toric IOLs, regardless of manufacturer, when compared with nontoric monofocal IOLs. Correcting pre-existing astigmatism with toric IOLs was more effective and predictable than using corneal relaxing incisions (CRIs), especially in the presence of higher magnitudes of astigmatism.Toric monofocal IOLs are effective in neutralizing pre-existing corneal astigmatism at the time of cataract surgery and result in better UCDVA and significant reductions in postoperative refractive astigmatism compared with nontoric monofocal IOLs. Toric IOLs result in better astigmatic correction than CRIs, particularly at high magnitudes of astigmatism.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

  View details for DOI 10.1016/j.ophtha.2023.10.010

  View details for PubMedID 38149945

• Mediators of Visual Acuity in Descemet Membrane Endothelial Keratoplasty and Ultrathin Descemet Stripping Automated Endothelial Keratoplasty. Cornea Lin, C. C., Chamberlain, W. D., Kakigi, C., Arnold, B. F., Rose-Nussbaumer, J. 2023

  Abstract

  The aim of this study was to investigate mediators of visual acuity in ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) compared with Descemet membrane endothelial keratoplasty (DMEK).This was a prespecified secondary analysis of the Descemet Endothelial Thickness Comparison Trial, a prospective, randomized controlled trial comparing UT-DSAEK with DMEK. Subjects with Fuchs endothelial dystrophy or pseudophakic bullous keratopathy presenting to 2 academic centers were enrolled and randomized to either UT-DSAEK (n = 25 eyes) or DMEK (n = 25 eyes). Higher order aberrations (HOAs) and corneal densitometry were measured with Pentacam Scheimpflug imaging at 3, 6, 12, and 24 months.The posterior corneal surface at the 6.0-mm optical zone had significantly less total HOAs (P <0.001) in the DMEK group compared with UT-DSAEK at 24 months. Anterior and posterior corneal densitometry improved from baseline to 24 months for both UT-DSAEK and DMEK, but there was no significant difference between the 2 groups. Corneal densitometry and posterior HOAs were both associated with best-corrected visual acuity (P <0.05). DMEK had 1.3 logarithm of the minimum angle of resolution better visual acuity compared with UT-DSAEK at 24 months. Approximately 64% of this effect was mediated through posterior HOAs, whereas none was mediated through anterior HOAs or densitometry.Decreased posterior HOAs mediate better visual acuity and account for improved vision after DMEK compared with UT-DSAEK. Corneal light scatter as measured by densitometry is similar between UT-DSAEK and DMEK, indicating that the increased thickness and stromal-stromal interface in UT-DSAEK do not significantly affect visual acuity.

  View details for DOI 10.1097/ICO.0000000000003434

  View details for PubMedID 37986182

• Validation of the C-DU(KE) Calculator as a Predictor of Outcomes in Patients Enrolled in Steroids for Corneal Ulcer and Mycotic Ulcer Treatment Trials. Cornea Arboleda, A., Prajna, N. V., Lalitha, P., Srinivasan, M., Rajaraman, R., Krishnan, T., Mousa, H. M., Feghali, J., Acharya, N. R., Lietman, T. M., Perez, V. L., Rose-Nussbaumer, J. 2023

  Abstract

  The aim of this study was to validate the C-DU(KE) calculator as a predictor of treatment outcomes on a data set derived from patients with culture-positive ulcers.C-DU(KE) criteria were compiled from a data set consisting of 1063 cases of infectious keratitis from the Steroids for Corneal Ulcer Trial (SCUT) and Mycotic Ulcer Treatment Trial (MUTT) studies. These criteria include corticosteroid use after symptoms, visual acuity, ulcer area, fungal etiology, and elapsed time to organism-sensitive therapy. Univariate analysis was performed followed by multivariable logistic regressions on culture-exclusive and culture-inclusive models to assess for associations between the variables and outcome. The predictive probability of treatment failure, defined as the need for surgical intervention, was calculated for each study participant. Discrimination was assessed using the area under the curve for each model.Overall, 17.9% of SCUT/MUTT participants required surgical intervention. Univariate analysis showed that decreased visual acuity, larger ulcer area, and fungal etiology had a significant association with failed medical management. The other 2 criteria did not. In the culture-exclusive model, 2 of 3 criteria, decreased vision [odds ratio (OR) = 3.13, P < 0.001] and increased ulcer area (OR = 1.03, P < 0.001), affected outcomes. In the culture-inclusive model, 3 of 5 criteria, decreased vision (OR = 4.9, P < 0.001), ulcer area (OR = 1.02, P < 0.001), and fungal etiology (OR = 9.8, P < 0.001), affected results. The area under the curves were 0.784 for the culture-exclusive model and 0.846 for the culture-inclusive model which were comparable to the original study.The C-DU(KE) calculator is generalizable to a study population from large international studies primarily taking place in India. These results support its use as a risk stratification tool assisting ophthalmologists in patient management.

  View details for DOI 10.1097/ICO.0000000000003313

  View details for PubMedID 37335849

• Optimizing Office-Based Pterygium Surgery Collis, S., Sun, C., Parikh, N., Padmanabhan, S., Schallhorn, J., Rose-Nussbaumer, J., Yang, D., Bloomer, M., Pasricha, N., Chan, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795605311

• Effect of Simultaneous Endothelial Keratoplasty and Cataract Surgery: A Secondary Analysis of the Descemet Endothelial Thickness Comparison Trial. Cornea Chamberlain, W., Lin, C. C., Yue, J., Cavallino, V., Benetz, B. A., Lass, J. H., Arnold, B., Lietman, T. M., Rose-Nussbaumer, J. 2023

  Abstract

  Combining cataract surgery with endothelial keratoplasty (triple EK) is a common practice and may be safer because it commits the patient to only one surgery. This study aimed to determine whether outcomes of pseudophakic endothelial keratoplasty and triple EK have similar outcomes.This was a non-prespecified secondary analysis of a multicenter, double-masked, randomized, controlled clinical trial. Enrollment centers included the Casey Eye Institute at Oregon Health and Sciences University and the Byers Eye Institute at Stanford University. Patients with damaged or diseased endothelium and were considered good candidates for either Descemet membrane endothelial keratoplasty or ultrathin Descemet stripping automated endothelial keratoplasty were randomized to one of the two surgeries 1-2 days prior to surgery. If the patient had a cataract, they underwent simultaneous cataract surgery. The primary outcome was visual acuity at 6 months. Visual acuity at 3, 12, and 24 months, 3, 6, 12, and 24 month endothelial cell density and intraoperative and postoperative complications were also recorded.Those who had pseudophakic EK generally were older, more likely to be male, and more likely to have worse baseline vision with higher corneal densitometry values. After controlling for baseline visual acuity and type of keratoplasty, those that underwent Triple-EK had 0.09 better LogMAR lines better visual acuity at 6 (95% CI -0.17 to -0.10; P = 0.02) and 12 months (95% CI -0.21 to -0.07; P = 0.03). Although those receiving Triple- EK had nearly one-half LogMAR line better visual acuity at 24 months, it was no longer statistically significant (95% CI -0.20 to -0.05; P = 0.36). There was no statistically significant difference in ECD between groups at any timepoint. Those undergoing triple EK were more likely to have at least one adverse event (P = 0.02).Earlier intervention with Triple-EK may improve visual acuity outcomes after endothelial keratoplasty compared with staged procedures, but may also increase the risks of adverse events including the need for re-bubble.NCT02373137.

  View details for DOI 10.1097/ICO.0000000000003306

  View details for PubMedID 37167477

• Comparison of Water-Free Commercially Available Cyclosporine Ophthalmic Preparations-Different, but the Same. JAMA ophthalmology Lozano, A. N., Shen, A., Rose-Nussbaumer, J. 2023

  View details for DOI 10.1001/jamaophthalmol.2023.0850

  View details for PubMedID 37022711

• How Are Sicca Signs and Symptoms Associated With Depression Among Men Classified With and Without Sjogren Disease? AMERICAN JOURNAL OF OPHTHALMOLOGY Nortey, J., Shiboski, C., Rose-Nussbaumer, J., Bunya, V. Y., Lietman, T., Gonzales, J. A. 2023; 247: 96-102

  Abstract

  Sjögren disease (SjD) cohorts represent rich resources to study associations between dry eye/mouth (sicca) signs/symptoms and depression. Because SjD affects mainly women, little is known about men with sicca signs/symptoms and associations with depression. The Sjögren's International Collaborative Clinical Alliance contained many men allowing for studying associations between sicca signs/symptoms and depression. We hypothesized that sicca symptoms would be positively associated with depression in males.Cross-sectional study.At baseline, participants completed questionnaires and underwent ocular and oral examinations. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression models were used to identify associations between depression and SjD diagnostic criteria and sicca symptoms.Of 309 males, 98 were classified as SjD, whereas 198 were classified as non-SjD. We found that having a labial salivary gland biopsy with focus score ≥1 foci/mm2 was associated with a lower odds of being classified as depressed (odds ratio [OR]: 0.36, 95% CI: 0.18-0.73, P = .01). Having positive anti-Sjögren syndrome antigen A antibody was associated with lower odds of being classified as depressed (OR: 0.44, 95% CI: 0.23-0.88, P = .02). Higher odds of depression were found with ocular burning (OR: 3.16, 95% CI: 1.74-5.73, P < .001), light sensitivity (OR: 2.59, 95% CI: 1.48-4.55, P = .001), and complaints of dry mouth (OR: 4.58, 95% CI: 1.54-13.63, P = .006).Ophthalmologists should be specific when inquiring about ocular discomfort (focusing on burning and light sensitivity) and consider querying about depression and/or providing mental health resources to those who endorse such qualities.

  View details for DOI 10.1016/j.ajo.2022.09.016

  View details for Web of Science ID 000912601300001

  View details for PubMedID 36220352

• Risk factors for corneal ulcers: a population-based matched case-control study in Nepal BRITISH JOURNAL OF OPHTHALMOLOGY Byanju, R., Kandel, R., Poudyal, B., Bhandari, S., Ligal, A., Pradhan, S., Gautam, M., Shrestha, P., Sah, R., Gonzales, J. A., Porco, T. C., Whitcher, J. P., Srinivasan, M., Upadhyay, M., Lietman, T. M., Keenan, J., O'Brien, K. S., Village-Integrated Eye Worker Tria 2023; 107 (12): 1771-1775

  Abstract

  We aimed to examine risk factors for corneal ulcer in a rural and peri-urban setting in Nepal.This population-based matched case-control study was nested in a cluster randomised trial in 24 village development committees in Nepal. Incidence density sampling was used to match incident corneal opacity cases to controls, matching on time of opacity, age, sex and location. Cases and controls were invited to participate in a survey of risk factors for corneal ulcer. Risk factors were evaluated using conditional logistic regression to account for matching.Of the 540 participants with incident opacities identified in the trial, 433 were willing to participate in this substudy and matched to a control. Compared with controls, cases had lower odds of having any education vs no education (adjusted OR, aOR 0.60, 95% CI 0.39 to 0.94), working in non-manual labour occupations vs manual labour occupations (aOR 0.64, 95% CI 0.42 to 0.95) and preferring medical shops for ocular trauma versus eye care system centres (aOR 0.58, 95% CI 0.37 to 0.92). Cases had higher odds of protective goggle use versus no protection (aOR 3.8, 95% CI 1.3 to 11.0) and having an ocular injury vs none (aOR 7.7, 95% CI 4.3 to 13.6) compared with controls.We found ocular injury, manual labour and lower education to be strongly associated with the development of corneal ulcer. Given the persistent burden of corneal blindness in this area, prevention efforts could target efforts to increase access to care in areas where these factors are common.

  View details for DOI 10.1136/bjo-2022-322141

  View details for Web of Science ID 000865498900001

  View details for PubMedID 36202599

  View details for PubMedCentralID PMC10076439

• Management of Pain after Photorefractive Keratectomy: A Report by the American Academy of Ophthalmology. Ophthalmology Steigleman, W. A., Rose-Nussbaumer, J., Al-Mohtaseb, Z., Santhiago, M. R., Lin, C. C., Pantanelli, S. M., Kim, S. J., Schallhorn, J. M. 2022

  Abstract

  OBJECTIVE: To evaluate current best practices for postoperative photorefractive keratectomy (PRK) pain control.METHODS: Literature searches in the PubMed database were last conducted in October 2021 and were restricted to publications in English. This search identified 219 citations, of which 84 were reviewed in full text for their relevance to the scope of this assessment. Fifty-one articles met the criteria for inclusion; 16 studies were rated level I, 33 studies were rated level II, and 2 studies were rated level III.RESULTS: Systemic opioid and nonsteroidal anti-inflammatory drugs (NSAIDs); topical NSAIDs; postoperative cold patches; bandage soft contact lenses (BCLs), notably senofilcon A contact lenses; and topical anesthetics were demonstrated to offer significantly better pain control than comparison treatments. Some other commonly reported pain mitigation interventions such as systemic gabapentinoids, chilled intraoperative balanced salt solution (BSS) irrigation, cycloplegia, and specific surface ablation technique strategies offered limited improvement in pain control over control treatments.CONCLUSIONS: Systemic NSAIDs and opioid medications, topical NSAIDs, cold patches, BCLs, and topical anesthetics have been shown to provide improved pain control over alternative strategies and allow PRK-associated pain to be more tolerable for patients.

  View details for DOI 10.1016/j.ophtha.2022.07.028

  View details for PubMedID 36207168

• Mediators of the Effect of Corneal Cross-Linking on Visual Acuity for Fungal Ulcers: A Prespecified Secondary Analysis From the Cross-Linking-Assisted Infection Reduction Trial CORNEA Prajna, N., Radhakrishnan, N., Lalitha, P., Liu, Z., Keenan, J. D., Arnold, B. F., Rose-Nussbaumer, J. 2022; 41 (10): 1217-1221

  Abstract

  The purpose of this study was to determine whether astigmatism or corneal scarring is mediating the reduced visual acuity among patients with fungal keratitis randomized to corneal cross-linking (CXL).This was a prespecified exploratory outcome from an outcome-masked, 2 × 2 factorial design, randomized controlled clinical trial.Consecutive patients presented with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India.Study eyes were randomized to one of 4 treatment combinations using an adaptive randomization protocol. The treatment arms included (1) topical natamycin 5% alone, (2) topical natamycin 5% plus CXL, (3) topical amphotericin B 0.15% alone, and (4) topical amphotericin 0.15% plus CXL. Best spectacle-corrected visual acuity (BSCVA), contact lens over-refraction, and scar size and depth as measured by a masked study ophthalmologist using a standardized protocol were recorded at 3 months. Pentacam Scheimpflug imaging was also obtained at 3 months.BSCVA and contact lens over-refraction, infiltrate and/or scar size and depth, total astigmatism of the front and back of the cornea, total lower-order and higher-order aberrations of the anterior and posterior cornea, and total densitometry of the anterior, central, and posterior stroma were recorded. We performed a mediation analysis looking at the proportion of the effect of CXL on BSCVA that was mediated through scar size, scar depth, astigmatism and density.BSCVA at 3 months was available for 99 of 111 patients (89%) who had a mean of 0.82-LogMAR (SD 0.68). Three-month infiltrate and/or scar size ( P < 0.001), depth ( P < 0.001), and densitometry ( P = 0.001) were statistically significant predictors of 3-month BSCVA. Astigmatism seemed to mediate 23% of the effect of CXL on BSCVA, whereas scar size mediated 23%, scar depth 17%, and densitometry 7%.Corneal scarring and astigmatism are mediators of worse visual acuity after cross-linking in fungal keratitis. Corneal densitometry may be a helpful cornea-specific variable for clinicians and researchers in determining the effect of corneal scarring on visual acuity in specific patients and as an objective study outcome.NCT02570321.

  View details for Web of Science ID 000853939800006

  View details for PubMedID 35044972

• Role of Ophthalmology in Emerging Infectious Diseases. JAMA ophthalmology Rose-Nussbaumer, J., Doan, T. 2022

  View details for DOI 10.1001/jamaophthalmol.2022.4017

  View details for PubMedID 36069833

• Changes in Corneal Power up to Two Years after Endothelial Keratoplasty: Results from the Randomized Controlled DETECT Trial. American journal of ophthalmology Chamberlain, W., Shen, E., Werner, S., Lin, C., Rose-Nussbaumer, J. 2022

  Abstract

  PURPOSE: To compare changes in corneal power measurements after Descemet membrane endothelial keratoplasty (DMEK) vs. ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK).SETTING: Hospital centers DESIGN: : Post-hoc sub-analysis of the randomized controlled DETECT Trial METHODS: : 50 eyes (38 patients) with endothelial dysfunction from Fuchs' endothelial dystrophy or pseudophakic bullous keratopathy were randomized to DMEK or UT-DSAEK 1 to 2 days prior to surgery. Total Corneal Refractive Power (TCRP) and anterior/posterior simulated keratometry were obtained using Scheimpflug imaging preoperatively (baseline) and postoperatively at 3, 6, 12, and 24 months. Spectacle refractions were performed at 6, 12, and 24 months after surgery.RESULTS: Mean hyperopic shift of TCRP from baseline to 12 months was 0.80±1.1 (p=0.002) in the DMEK group and 0.69±0.84 (p<0.001) in the UT-DSAEK group. Posterior corneal curvature (Km) steepened (more negative dioptric power) by 0.42±0.10 (p<0.001) in DMEK and 0.54±0.09 (p<0.001) in UT-DSAEK. Mean change in TCRP and posterior corneal curvature did not differ between DMEK and UT-DSAEK (TCRP, p=0.71; posterior Km, p=0.36).CONCLUSIONS: Sustained steepening in posterior corneal curvature with loss in total corneal power contributes to hyperopic shifts after endothelial keratoplasty. Changes in corneal measurements do not differ between DMEK and UT-DSAEK.

  View details for DOI 10.1016/j.ajo.2022.07.009

  View details for PubMedID 35870491

• Femtosecond Laser-Assisted Cataract Surgery: A Report by the American Academy of Ophthalmology. Ophthalmology Lin, C. C., Rose-Nussbaumer, J. R., Al-Mohtaseb, Z. N., Pantanelli, S. M., Steigleman, W. A., Hatch, K. M., Santhiago, M. R., Kim, S. J., Schallhorn, J. M. 2022

  Abstract

  PURPOSE: To evaluate refractive outcomes, safety, and cost-effectiveness of femtosecond laser-assisted cataract surgery (FLACS) compared with phacoemulsification cataract surgery (PCS).METHODS: A PubMed search of FLACS was conducted in August 2020. A total of 727 abstracts were reviewed and 33 were selected for full-text review. Twelve articles met inclusion criteria and were included in this assessment. The panel methodologist assigned a level of evidence rating of I to all 12 studies.RESULTS: No significant differences were found in mean uncorrected distance visual acuity, best-corrected distance visual acuity, or the percentage of eyes within ± 0.5 and ± 1 diopter of intended refractive target between FLACS and PCS. Intraoperative and postoperative complication rates were similar between the 2 groups, and most studies showed no difference in endothelial cell loss between FLACS and PCS at various time points between 1 and 6 months. In large randomized controlled studies in the United Kingdom and France, FLACS was less cost-effective than PCS.CONCLUSIONS: Both FLACS and PCS have similar excellent safety and refractive outcomes. At this time, one technique is not superior to the other, but economic analyses performed in some populations have shown that FLACS is less cost-effective.

  View details for DOI 10.1016/j.ophtha.2022.04.003

  View details for PubMedID 35570159

• Village-integrated eye workers for prevention of corneal ulcers in Nepal (VIEW study): a cluster-randomised controlled trial LANCET GLOBAL HEALTH O'Brien, K. S., Byanju, R., Kandel, R. P., Poudyal, B., Gonzales, J. A., Porco, T. C., Whitcher, J. P., Srinivasan, M., Upadhyay, M., Lietman, T. M., Keenan, J. D., Village-Integrated Eye Worker Tria 2022; 10 (4): E501-E509

  Abstract

  Corneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.A cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.We assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control group (incidence 1·18 cases [0·82-1·70] per 1000 person-years; incidence rate ratio 1·03 [95% CI 0·63-1·67]; p=0·93). Medication allergy was self-reported in 0·2% of participants.We did not detect a reduction in the incidence of corneal ulceration during the first 3 years of a community-based corneal ulcer prevention programme. Further study might be warranted in more rural areas where basic eye care facilities are not available.National Eye Institute.

  View details for Web of Science ID 000861072000003

  View details for PubMedID 35303460

  View details for PubMedCentralID PMC9814976

• Clinical Trial Design-The Best Approach Is Often the Simple One. JAMA ophthalmology Ma, K. K., Rose-Nussbaumer, J. 2022

  View details for DOI 10.1001/jamaophthalmol.2022.0054

  View details for PubMedID 35238898

• Expert Performance in Visual Differentiation of Bacterial and Fungal Keratitis OPHTHALMOLOGY Redd, T. K., Prajna, N., Srinivasan, M., Lalitha, P., Krishnan, T., Rajaraman, R., Venugopal, A., Lujan, B., Acharya, N., Seitzman, G. D., Rose-Nussbaumer, J., Lietman, T. M., Campbell, J., Keenan, J. D., Corneal Ulcer Image Interpretation 2022; 129 (2): 227-230

  Abstract

  This study quantifies the performance of an international cohort of cornea specialists in image-based differentiation of bacterial and fungal keratitis, identifying significant regional variation and establishing a reference standard for comparison against machine learning models.

  View details for Web of Science ID 000747770500016

  View details for PubMedID 34624299

  View details for PubMedCentralID PMC8792176

• Patterns of Antifungal Resistance in Adult Patients With Fungal Keratitis in South India: A Post Hoc Analysis of 3 Randomized Clinical Trials. JAMA ophthalmology Prajna, N. V., Lalitha, P., Krishnan, T., Rajaraman, R., Radnakrishnan, N., Srinivasan, M., Devi, L., Das, M., Liu, Z., Zegans, M. E., Acharya, N. R., Porco, T. C., Lietman, T. M., Rose-Nussbaumer, J. 1800

  Abstract

  Importance: Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce.Objective: To evaluate changes in antifungal resistance over time.Design, Setting, and Participants: Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021.Interventions: Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute.Main Outcomes and Measures: The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole.Results: A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients. Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P=.06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P=.01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P<.001). Fusarium species had a 1.06-fold increase in natamycin resistance (95% CI, 1.05-1.08; P<.001), Aspergillus had a 1.09-fold increase in resistance (95% CI, 1.05-1.15; P<.001), and other filamentous fungi had a 1.07-fold increase in resistance to natamycin per year (95% CI, 1.04-1.10; P<.001).Conclusions and Relevance: This post hoc analysis suggests that susceptibility to both natamycin and voriconazole may be decreasing over the last decade in South India. While a trend of increasing resistance could impact treatment of mycoses in general and infectious fungal keratitis in particular, further study is needed to confirm these findings and determine their generalizability to other regions of the world.Trial Registration: ClinicalTrials.gov Identifiers: NCT00996736 and NCT02570321.

  View details for DOI 10.1001/jamaophthalmol.2021.5765

  View details for PubMedID 35024776

• Survey of the American Glaucoma Society Membership on Current Glaucoma Drainage Device Placement and Postoperative Corticosteroid Use. Clinical ophthalmology (Auckland, N.Z.) Yonamine, S., Ton, L., Rose-Nussbaumer, J., Ying, G., Ahmed, I. I., Chen, T. C., Weiner, A., Gedde, S. J., Han, Y. 2022; 16: 2305-2310

  Abstract

  Purpose: To assess practice patterns and opinions of glaucoma specialists regarding glaucoma drainage device tube shunt placement and post-operative anti-inflammatory medication use. We also assess the perceived need for a randomized control trial to compare them.Patients and Methods: An online survey was distributed to a group of glaucoma specialists from the American Glaucoma Society via the American Glaucoma Society forum from April to August 2021.Results: One hundred and twenty-eight responses were included. Ninety percent placed tubes in the anterior chamber. Sixty-one percent reported that evidence suggested the superiority of sulcus tube placement over the anterior chamber, whereas 34% reported there was not enough evidence to suggest superiority of either in preventing endothelial cell loss. Comparing these techniques for intraocular pressure control, 49% reported evidence suggested sulcus tube placement superiority whereas 46% reported there was not enough evidence. Over 40% of respondents reported that they were either unfamiliar with literature or that there was not enough evidence to support the superiority of difluprednate 0.05% over prednisolone 1% for post-operative use in preventing endothelial cell loss and for intraocular pressure control. Ninety percent and 81% of respondents respectively would benefit from randomized control trials comparing outcomes of anterior chamber vs sulcus tube placement and post-operative corticosteroid usage.Conclusion: Most glaucoma specialists surveyed place glaucoma drainage device tube in the anterior chamber over the sulcus. A randomized control trial to determine optimal tube placement and post-operative anti-inflammatory medication use for preventing endothelial cell loss would change current glaucoma drainage device practice patterns.

  View details for DOI 10.2147/OPTH.S369673

  View details for PubMedID 35903751

• Associations Between Smoking and Primary Sjogren Syndrome Classification Using the Sjogren's International Collaborative Clinical Alliance Cohort ACR OPEN RHEUMATOLOGY Gebreegziabher, E. A., Oldenburg, C. E., Shiboski, S. C., Baer, A. N., Jordan, R. C., Rose-Nussbaumer, J. R., Bunya, V. Y., Akpek, E. K., Criswell, L. A., Shiboski, C. H., Lietman, T. M., Gonzales, J. A. 2022; 4 (3): 231-237

  Abstract

  The objective of this study was to examine the association of smoking with Primary Sjögren syndrome (pSS) classification and pSS diagnostic test results. We hypothesized that past and current smokers would have lower odds of being classified as having Sjögren syndrome (SS) and lower odds of having abnormal individual SS diagnostic test results compared with nonsmokers.Participants with suspected or established pSS were enrolled into the Sjögren's International Collaborative Clinical Alliance (SICCA) registry and had oral, ocular, and rheumatologic examinations performed; blood and saliva samples collected; and labial salivary gland biopsy examinations performed; they also completed questionnaires at baseline. Logistic regression was used to determine whether smoking status was associated with pSS classification and individual pSS diagnostic test results.A total of 3514 participants were enrolled in SICCA. A total of 1541 (52.9%) met classification criteria for pSS. Compared with never smokers, current smokers had reduced odds of being classified as having pSS, reduced odds of having a focus score ≥ 1 and serologic positivity for anti-SSA/anti-SSB antibodies, and lower odds of having abnormal signs or test results of dry eye disease. Compared with never smokers, past smokers did not have a statistically significant reduction in odds of being classified as having pSS and of having abnormal individual pSS diagnostic test results.Compared with never smokers, current smokers in the SICCA cohort had lower odds of being classified as having pSS, lower odds of exhibiting abnormal signs and test results for dry eye disease, and lower odds of having a labial salivary gland biopsy supportive of pSS classification. Such negative associations, however, do not suggest that current smoking is of any benefit with respect to pSS.

  View details for DOI 10.1002/acr2.11362

  View details for Web of Science ID 000728512200001

  View details for PubMedID 34889071

  View details for PubMedCentralID PMC8916552

• Double-masked, sham and placebo-controlled trial of corneal cross-linking and topical difluprednate in the treatment of bacterial keratitis: Steroids and Cross-linking for Ulcer Treatment Trial (SCUT II) study protocol. BMJ open ophthalmology Radhakrishnan, N., Prajna, V. N., Prajna, L. S., Venugopal, A., Narayana, S., Rajaraman, R., Amescua, G., Porco, T. C., Lietman, T. M., Rose-Nussbaumer, J. 2021; 6 (1): e000811

  Abstract

  Although antibiotics are successful at achieving microbiological cure in infectious keratitis, outcomes are often poor due to corneal scarring. Ideal treatment of corneal ulcers would address both the infection and the inflammation. Adjunctive topical steroid treatment may improve outcomes by reducing inflammation. Corneal cross-linking (CXL) is a novel prospective therapy that may simultaneously reduce both inflammatory cells and bacterial pathogens. The purpose of this study is to determine differences in 6-month visual acuity between standard medical therapy with antibiotics versus antibiotics with adjunctive early topical steroid therapy versus antibiotic treatment plus CXL and early topical steroids.This international, randomised, sham and placebo-controlled, three-arm clinical trial randomises patients with smear positive bacterial ulcers in a 1:1:1 fashion to one of three treatment arms: (1) topical 0.5% moxifloxacin plus topical placebo plus sham CXL; (2) topical 0.5% moxifloxacin plus difluprednate 0.05% plus sham CXL; or (3) the CXL group: topical 0.5% moxifloxacin plus difluprednate 0.05% plus CXL.We anticipate that both adjunctive topical steroids and CXL will improved best spectacle corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings and journal publications. Our data will also be available on reasonable request.NCT04097730.

  View details for DOI 10.1136/bmjophth-2021-000811

  View details for PubMedID 34901464

  View details for PubMedCentralID PMC8634009

• Double-masked, sham and placebo-controlled trial of corneal cross-linking and topical difluprednate in the treatment of bacterial keratitis: Steroids and Cross-linking for Ulcer Treatment Trial (SCUT II) study protocol BMJ OPEN OPHTHALMOLOGY Radhakrishnan, N., Prajna, V. N., Prajna, L. S., Venugopal, A., Narayana, S., Rajaraman, R., Amescua, G., Porco, T. C., Lietman, T. M., Rose-Nussbaumer, J. 2021; 6 (1)

  View details for DOI 10.1136/bmjophth-2021-000811

  View details for Web of Science ID 000724321400003

• Statistical Significance vs Clinical Significance-That Is the Question JAMA OPHTHALMOLOGY Rose-Nussbaumer, J. 2021; 139 (11): 1235

  View details for DOI 10.1001/jamaophthalmol.2021.4139

  View details for Web of Science ID 000707428100001

  View details for PubMedID 34648026

• Descemet Endothelial Thickness Comparison Trial: Two-Year Results from a Randomized Trial Comparing Ultrathin Descemet Stripping Automated Endothelial Keratoplasty with Descemet Membrane Endothelial Keratoplasty OPHTHALMOLOGY Rose-Nussbaumer, J., Lin, C. C., Austin, A., Liu, Z., Clover, J., McLeod, S. D., Porco, T. C., Lietman, T. M., Dresner, S. M., Benetz, B., Lass, J. H., Chamberlain, W. D. 2021; 128 (8): 1238-1240

  View details for Web of Science ID 000677479200023

• Masking Is Not Just for COVID-19 JAMA OPHTHALMOLOGY Schallhorn, J. M., Rose-Nussbaumer, J. 2021; 139 (9): 1013-1014

  View details for DOI 10.1001/jamaophthalmol.2021.2706

  View details for Web of Science ID 000679477900001

  View details for PubMedID 34323933

• Cross-Linking Assisted Infection Reduction (CLAIR): A Randomized Clinical Trial Evaluating the Effect of Adjuvant Cross-Linking on Bacterial Keratitis CORNEA Prajna, N., Radhakrishnan, N., Lalitha, P., Rajaraman, R., Narayana, S., Austin, A. F., Liu, Z., Keenan, J. D., Porco, T. C., Lietman, T. M., Rose-Nussbaumer, J. 2021; 40 (7): 837-841

  Abstract

  To determine whether there is a benefit to adjuvant corneal cross-linking (CXL) for bacterial keratitis.This is an outcome-masked, randomized controlled clinical trial. Consecutive patients presenting with a smear-positive bacterial ulcer at Aravind Eye Hospitals at Madurai, Pondicherry, and Coimbatore in India were enrolled. Study eyes were randomized to topical moxifloxacin 0.5% or topical moxifloxacin 0.5% plus CXL. The primary outcome of the trial was microbiological cure at 24 hours on repeat culture. Secondary outcomes included best spectacle corrected visual acuity at 3 weeks and 3 months, percentage of study participants with epithelial healing at 3 weeks and 3 months, infiltrate and/or scar size at 3 weeks and 3 months, 3-day smear and culture, and adverse events.Those randomized to CXL had 0.60 decreased odds of culture positivity at 24 hours (95% confidence interval [CI]: 0.10-3.50; P = 0.65), 0.9 logarithm of the minimum angle of resolution lines worse visual acuity (95% CI: -2.8 to 4.6; P = 0.63), and 0.41-mm larger scar size (95% CI: -0.48 to 1.30; P = 0.38) at 3 months. We note fewer corneal perforations or need for therapeutic penetrating keratoplasty in the CXL group.We were unable to confirm a benefit to adjuvant CXL in the primary treatment of moderate bacterial keratitis. However, CXL may reduce culture positivity and complication rates; therefore, a larger trial to fully evaluate this is warranted.NCT02570321.

  View details for DOI 10.1097/ICO.0000000000002510

  View details for Web of Science ID 000711687900009

  View details for PubMedID 33079921

• Cross-Linking Assisted Infection Reduction: One-year Follow-up of a Randomized Clinical Trial Evaluating Cross-Linking for Fungal Keratitis OPHTHALMOLOGY Prajna, N., Radhakrishnan, N., Lalitha, P., Austin, A., Liu, Z., Keenan, J. D., Porco, T. C., Lietman, T. M., Rose-Nussbaumer, J. 2021; 128 (6): 950-952

  View details for Web of Science ID 000687323600029

  View details for PubMedID 33031809

• Keratoplasty Outcomes in Patients With Uveitis CORNEA Hennein, L., Lambert, N. G., Chamberlain, W., Hirabayashi, K., Rose-Nussbaumer, J., Schallhorn, J. M. 2021; 40 (5): 590-595

  Abstract

  To examine the corneal transplant failure rates and associations with uveitic eye disease.The retrospective chart review identified 70 eyes from 42 patients with uveitis that underwent 40 primary transplants and 30 repeat transplants at 2 major academic centers over a 9-year period. The graft failure rate was calculated. Variables hypothesized to be associated with graft failure were analyzed as covariates using a Cox proportional hazards analysis clustered by the patients to determine their association with failure rates.Of the 70 grafts, the mean duration of follow-up for patients was 40.6 months (range 4-90 months) and the median survival time was 24.1 months (interquartile range of 9-290 months). Twenty-two patients (52%) had graft failure. There was a higher rate of graft failure in patients with infectious uveitis as compared to those with noninfectious uveitis (hazard ratio 2.46, P = 0.031). Patients with successful grafts had their inflammation controlled for a longer period of time before transplantation as compared to those with failed grafts (38.6 vs. 13.6 months, P = 0.004). Worse preoperative visual acuities were significantly associated with graft failure (P < 0.001).There is limited knowledge of corneal transplant outcomes in uveitic patients in the current literature. In our study, over half of the grafts failed. Infectious uveitis (especially viral) was a strong predictor of graft failure. A shorter period of inflammation control before transplantation, previously failed grafts, and worse preoperative visual acuity were also associated with graft failure.

  View details for DOI 10.1097/ICO.0000000000002527

  View details for Web of Science ID 000656630100009

  View details for PubMedID 33038154

• Predictors of Vision-Related Quality of Life After Endothelial Keratoplasty in the Descemet Endothelial Thickness Comparison Trials. Cornea Pickel, J., Chamberlain, W. D., Lin, C. C., Austin, A., Clover, J., Lietman, T. M., Rose-Nussbaumer, J. 2021; 40 (4): 449–52

  Abstract

  PURPOSE: To determine which baseline characteristics are associated with vision-related quality of life (QOL) after endothelial keratoplasty.METHODS: A patient- and outcome-masked randomized clinical trial. Consecutive patients presenting with isolated endothelial disease requiring endothelial keratoplasty at Oregon Health Sciences University and Stanford University. Study eyes randomized to one of the 2 types of endothelial keratoplasty were given the national eye institute vision function questionnaire 25 at baseline and 12 months. In this prespecified secondary outcome, we assessed the role of recipient and donor characteristics as predictors of the 12-month national eye institute vision function questionnaire 25 change score.RESULTS: The mean vision function questionnaire (VFQ) score was 74 (SD 14) at baseline and increased to 82 (SD 12) at 3 months and 87 (SD 10) at 12 months. We were unable to find a difference in vision-related QOL in study participants who underwent Descemet membrane endothelial keratoplasty compared with ultrathin Descemet stripping endothelial keratoplasty [coef -0.98, 95% confidence interval (CI) -9.27 to 7.31; P = 0.82]. In multivariable analysis, patients who underwent endothelial keratoplasty in 2 eyes had approximately 8 points higher VFQ at 12 months after the second eye than those who had only one eye enrolled (95% CI 0.10-15.72; P = 0.047). Posterior densitometry produced an approximately 1-point increase each in the VFQ change score for each 1 grayscale unit increase at baseline (95% CI 0.26-1.81; P = 0.009). Although the sample size was small, a diagnosis of pseudophakic bullous keratopathy had approximately 19-points more improvement on average compared with Fuchs (95% CI 7.68-30.00; P = 0.001).CONCLUSIONS: Bilateral endothelial keratoplasty resulted in higher vision-related QOL compared with unilateral. Baseline densitometry, objective measure of corneal haze that predicts vision-related QOL, may play a role in monitoring disease progression.

  View details for DOI 10.1097/ICO.0000000000002431

  View details for PubMedID 33881810

• Overview of Neurotrophic Keratopathy and a Stage-Based Approach to Its Management EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE Safi, M., Rose-Nussbaumer, J. 2021; 47 (3): 140-143

  Abstract

  Neurotrophic keratopathy (NK) occurs because of disruption of corneal sensory innervation. There are many etiologies that can lead to NK, such as infection, trauma, topical medication use, cornea surgery, and intracranial tumors among others. We review the current available treatment options and provide a stage-based approach to its management.

  View details for DOI 10.1097/ICL.0000000000000760

  View details for Web of Science ID 000656626600003

  View details for PubMedID 33208601

• Neuropathic Pain in the Eyes, Body, and Mouth: Insights from the Sjogren's International Collaborative Clinical Alliance PAIN PRACTICE Gebreegziabher, E. A., Bunya, V. Y., Baer, A. N., Jordan, R. C., Akpek, E. K., Rose-Nussbaumer, J., Criswell, L. A., Shiboski, C. H., Lietman, T. M., Gonzales, J. A. 2021; 21 (6): 630-637

  Abstract

  To evaluate how ocular, oral, and bodily neuropathic pain symptoms, which characterize small fiber neuropathies, are associated with Sjögren's syndrome (SS) classification based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria.Participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) registry had ocular, rheumatologic, oral, and labial salivary gland (LSG) biopsy examinations, blood and saliva samples collected, and completed questionnaires at baseline. We used mixed effects modeling with age, country, gender, and depression being fixed effects and study site, a random effect, to determine if neuropathic pain indicators (assessed via questionnaires) were associated with being classified as SS.A total of 3,514 participants were enrolled into SICCA, with 1,541 (52.9%) meeting the 2016 ACR/EULAR classification criteria for SS. There was a negative association between being classified as SS and experiencing bodily neuropathic pain features of needle-like pain, prickling/tingling sensation, ocular neuropathic pain of constant burning, and constant light sensitivity, and having a presumptive diagnosis of neuropathic oral pain.We found that those classified as SS had lower scores/reports of painful neuropathies compared with those classified as non-SS. Non-SS patients with dry eye disease or symptoms could benefit from pain assessment as they may experience painful small-fiber neuropathies (SFNs). Pain questionnaires may help identify pain associated with SFNs in patients with SS and non-SS dry eye. Future studies would be helpful to correlate self-reports of pain to objective measures of SFNs in those with SS, non-SS dry eye, and healthy controls.

  View details for DOI 10.1111/papr.13000

  View details for Web of Science ID 000618891200001

  View details for PubMedID 33527744

  View details for PubMedCentralID PMC10911963

• Intraocular Lens Power Calculation in Eyes with Previous Excimer Laser Surgery for Myopia: A Report by the American Academy of Ophthalmology. Ophthalmology Pantanelli, S. M., Lin, C. C., Al-Mohtaseb, Z. n., Rose-Nussbaumer, J. R., Santhiago, M. R., Steigleman, W. A., Schallhorn, J. M. 2021

  Abstract

  To review the literature to evaluate the outcomes of intraocular lens (IOL) power calculation in eyes with a history of myopic LASIK or photorefractive keratectomy (PRK).Literature searches were conducted in the PubMed database in January 2020. Separate searches relevant to cataract surgery outcomes and corneal refractive surgery returned 1169 and 162 relevant citations, respectively, and the full text of 24 was reviewed. Eleven studies met the inclusion criteria for this assessment; all were assigned a level III rating of evidence by the panel methodologist.When automated keratometry was used with a theoretical formula designed for eyes without previous laser vision correction, the mean prediction error (MPE) was universally positive (hyperopic), the mean absolute errors (MAEs) and median absolute errors (MedAEs) were relatively high (0.72-1.9 diopters [D] and 0.65-1.73 D, respectively), and a low (8%-40%) proportion of eyes were within 0.5 D of target spherical equivalent (SE). Formulas developed specifically for this population requiring both prerefractive surgery keratometry and manifest refraction (i.e., clinical history, corneal bypass, and Feiz-Mannis) produced a proportion of eyes within 0.5 D of target SE between 26% and 44%. Formulas requiring only preoperative keratometry or no history at all had lower MAEs (0.42-0.94 D) and MedAEs (0.30-0.81 D) and higher (30%-68%) proportions within 0.5 D of target SE. Strategies that averaged several methods yielded the lowest reported MedAEs (0.31-0.35 D) and highest (66%-68%) proportions within 0.5 D of target SE. Even after using the best-known methods, refractive outcomes were less accurate in eyes that had previous excimer laser surgery for myopia compared with those that did not have it.Calculation methods requiring both prerefractive surgery keratometry and manifest refraction are no longer considered the gold standard. Refractive outcomes of cataract surgery in eyes that had previous excimer laser surgery are less accurate than in eyes that did not. Patients should be advised of this refractive limitation when considering cataract surgery in the setting of previous corneal refractive surgery. Conclusions are limited by the small sample sizes and retrospective nature of nearly all existing literature in this domain.

  View details for DOI 10.1016/j.ophtha.2020.10.031

  View details for PubMedID 33500124

• Re: Prajna et al.: Cross-Linking Assisted Infection Reduction: a randomized clinical trial evaluating the effect of adjuvant cross-linking on outcomes in fungal keratitis (<i>Ophthalmology</i>. 2020;127:159-166) REPLY OPHTHALMOLOGY Prajna, N., Radhakrishnan, N., Lalitha, P., Keenan, J. D., Porco, T. C., Lietman, T. M., Rose-Nussbaumer, J. 2021; 128 (1): E5

  View details for Web of Science ID 000600748500002

  View details for PubMedID 32896388

• Re: Prajna et al.: Cross-Linking Assisted Infection Reduction: a randomized clinical trial evaluating the effect of adjuvant cross-linking on outcomes in fungal keratitis (<i>Ophthalmology</i>. 2020;127:159-166) <i>REPLY</i> OPHTHALMOLOGY Prajna, N., Radhakrishnan, N., Lalitha, P., Keenan, J. D., Porco, T. C., Lietman, T. M., Rose-Nussbaumer, J. 2021; 128 (1): E6-E7

  View details for Web of Science ID 000600748500004

  View details for PubMedID 32828552

• Multifocal and Accommodating Intraocular Lenses for the Treatment of Presbyopia: A Report by the American Academy of Ophthalmology. Ophthalmology Schallhorn, J. M., Pantanelli, S. M., Lin, C. C., Al-Mohtaseb, Z. N., Steigleman, W. A., Santhiago, M. R., Olsen, T. W., Kim, S. J., Waite, A. M., Rose-Nussbaumer, J. R. 2021

  Abstract

  To review the published literature assessing the efficacy and safety of presbyopia-correcting intraocular lenses (IOLs) for the treatment of presbyopia after cataract removal.Literature searches were undertaken in January 2018 and September 2020 in the PubMed, Medline, and Cochrane Library databases. This yielded 761 articles, of which 34 met the criteria for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. Thirteen studies were rated level I and 21 studies were rated level II.Presbyopia-correcting lenses were effective at improving distance and near visual acuity after cataract surgery. Near acuity at different focal lengths was related directly to the effective add power of multifocal and extended depth-of-focus (EDOF) IOLs. Most multifocal and EDOF lenses that were compared with a control monofocal lens demonstrated that patient-reported spectacle independence was superior to the monofocal lens. All patients who had multifocal and EDOF lenses implanted showed decreased contrast sensitivity and reported more visual phenomena as compared with control participants who received monofocal lenses.Presbyopia-correcting lenses improve uncorrected near and distance visual acuity and decrease spectacle dependence after cataract surgery. Mesopic contrast sensitivity is decreased compared with monofocal lenses, and patient-reported visual phenomena are more likely in patients receiving multifocal or EDOF lenses.

  View details for DOI 10.1016/j.ophtha.2021.03.013

  View details for PubMedID 33741376

• Descemet Endothelial Thickness Comparison Trial: Two-year Results from a Randomized Trial Comparing Ultrathin Descemet Stripping Automated Endothelial Keratoplasty to Descemet Membrane Endothelial Keratoplasty. Ophthalmology Rose-Nussbaumer, J., Lin, C. C., Austin, A., Liu, Z., Clover, J., McLeod, S. D., Porco, T. C., Lietman, T. M., Dresner, S. M., Benetz, B. A., Lass, J. H., Chamberlain, W. 2020

  View details for DOI 10.1016/j.ophtha.2020.12.021

  View details for PubMedID 33359556

• Metagenomic Deep Sequencing to Investigate for an Infectious Etiology of Iridocorneal Endothelial Syndrome CORNEA Sutra, P., Rose-Nussbaumer, J., Gonzales, J. A., Wang, K., Hinterwirth, A., Seitzman, G., Bloomer, M., Acharya, N., Doan, T. 2020; 39 (10): 1307-1310

  Abstract

  Iridocorneal endothelial (ICE) syndrome is a group of rare ocular conditions that result from abnormal corneal endothelial cells, leading to secondary glaucoma, iris distortions, and corneal edema. The etiology of ICE is unknown, although it has been associated with viral infections, such as herpes simplex virus. In this study, we sought to identify an infectious etiology for ICE using advanced molecular techniques.Metagenomic RNA sequencing (MDS) is a high-throughput sequencing approach that can identify all pathogens in any clinical sample, including RNA viruses. Descemet membrane and aqueous fluid from patients with ICE syndrome were subjected to MDS testing.Samples from 3 patients with ICE were analyzed. MDS was performed on the aqueous fluid of 3 patients and Descemet membrane and endothelial cell tissue from 1 patient. Viral pathogens were not identified in any of the samples.We were unable to identify a viral etiology in the tissues of patients with the Chandler variant of ICE syndrome, although this study was limited by sample size.

  View details for DOI 10.1097/ICO.0000000000002368

  View details for Web of Science ID 000575998500018

  View details for PubMedID 32398422

  View details for PubMedCentralID PMC7483698

• Ocular Clinical Signs and Diagnostic Tests Most Compatible With Keratoconjunctivitis Sicca: A Latent Class Approach CORNEA Gonzales, J. A., Shiboski, S. C., Bunya, V. Y., Akpek, E. K., Rose-Nussbaumer, J., Seitzman, G. D., Criswell, L. A., Shiboski, C. H., Lietman, T. M. 2020; 39 (8): 1013-1016

  Abstract

  To evaluate the ocular signs and tests for keratoconjunctivitis sicca (KCS) in the absence of a gold standard.Cross-sectional study of participants from the Sjögren's International Collaborative Clinical Alliance (SICCA) registry. Participants had oral/ocular/rheumatologic examinations, blood/saliva samples collected, and salivary gland biopsy. Latent class analysis (LCA) identified clusters of patients based on 3 to 4 predictor variables relating to signs or tests of KCS. The resulting model-based "gold standard" classification formed the basis for estimated sensitivity and specificity associated with these predictors.A total of 3514 participants were enrolled into SICCA, with 52.9% classified as SS. LCA revealed a best-fit model with 2 groups. For the gold standard-positive group, an abnormal tear breakup time, ocular staining score (OSS), and Schirmer I had a sensitivity of 99.5%, 91.0%, and 47.4%, respectively. For the gold standard-negative group, an abnormal tear breakup time, OSS, and Schirmer I had a specificity of 32.0%, 84.0%, and 88.5%, respectively. OSS components (fluorescein and lissamine staining), exhibited a sensitivity of 82.6% and 90.5%, respectively, in the gold standard-positive group, whereas these signs in the gold standard-negative group had a specificity of 88.8% and 73.0%, respectively.OSS and its components (fluorescein and lissamine staining) differentiated 2 groups from each other better than other KCS parameters and had relatively high sensitivity and specificity.

  View details for DOI 10.1097/ICO.0000000000002311

  View details for Web of Science ID 000559736500018

  View details for PubMedID 32251167

  View details for PubMedCentralID PMC7410365

• Reply. Ophthalmology Venkatesh Prajna, N., Radhakrishnan, N., Lalitha, P., Porco, T., Lietman, T. M., Rose-Nussbaumer, J. 2020; 127 (8): e56-e57

  View details for DOI 10.1016/j.ophtha.2020.02.031

  View details for PubMedID 32703393

• Clinical Outcomes of Micropulse Transscleral Cyclophotocoagulation in Patients with a History of Keratoplasty JOURNAL OF OPHTHALMOLOGY Lee, J., Vu, V., Lazcano-Gomez, G., Han, K., Suvannachart, P., Rose-Nussbaumer, J., Schallhorn, J., Hwang, D., Han, Y. 2020; 2020: 6147248

  Abstract

  To examine the surgical outcomes and graft conditions in patients receiving micropulse transscleral cyclophotocoagulation (MP-TSCPC) to treat post-keratoplasty ocular hypertension.This retrospective observational study included 30 eyes of 28 consecutive glaucoma patients with a history of penetrating keratoplasty (PKP) or Descemet's stripping automated endothelial keratoplasty (DSAEK) who underwent MP-TSCPC at the University of California, San Francisco from 09/2015 to 08/2018. Using the Wilcoxon signed-rank test, we compared preoperative and postoperative intraocular pressure (IOP), number of glaucoma medications, visual acuity, and central corneal thickness at 1, 3, 6, and 12 months. Postoperative complications, additional surgeries, and graft failures were also recorded at these follow-up times. Linear regression model was used to study whether PKP vs. DSAEK affects the effectiveness of MP-TSCPC.Thirty eyes from 28 patients were followed for 12 months. IOP was significantly decreased from preop at all follow-up points (P < 0.001). There was no significant change in the number of glaucoma drops, visual acuity, or CCT. At 12 months, 21 of the 30 eyes met the definition of success, and only one underwent repeat PKP due to graft rejection. The type of corneal transplant was not a significant factor for IOP reduction at the last follow-up.MP-TSCPC achieved desirable IOP control and success rates for postkeratoplasty patients while resulting in minimal complications and graft failure. It appears to be a safe and effective procedure in patients who received corneal transplant with one-year follow-up.

  View details for DOI 10.1155/2020/6147248

  View details for Web of Science ID 000552370500001

  View details for PubMedID 32695499

  View details for PubMedCentralID PMC7368213

• The Prognostic Value of Persistent Culture Positivity in Fungal Keratitis in the Mycotic Antimicrobial Localized Injection Trial AMERICAN JOURNAL OF OPHTHALMOLOGY Pickel, J., Narayana, S., Krishnan, T., Ramakrishnan, S., Samantaray, P., Porco, T. C., Redd, T., Lietman, T. M., Rose-Nussbaumer, J. 2020; 215: 1-7

  Abstract

  To evaluate the utility of repeat cultures at days 3 and 7 after starting antifungal medications for predicting outcomes in fungal keratitis.Prespecified secondary analysis of the randomized clinical Mycotic Antimicrobial Localized Injection trial.Patients presenting to Aravind Eye Hospital, Pondicherry, India, with fungal keratitis and visual acuity worse than 20/70 received topical natamycin and were randomized to either receive intrastromal injection of voriconazole or topical therapy alone. All subjects received corneal cultures at date of presentation, day 3, and day 7. Outcome measures included 3-week and 3-month visual acuity and scar size, corneal perforation, and/or the need for therapeutic penetrating keratoplasty (TPK). Visual acuity and scar size were analyzed with multiple linear regression controlling for baseline measures. Survival analysis was used to analyze the risk of corneal perforation and/or need for TPK.Of the 70 study subjects with fungal keratitis, 25 of 69 (36%) remained culture positive at day 3, and 20 of 62 (32%) were culture positive at day 7. Culture positivity at day 3 conferred a hazard ratio of 2.8 for requiring TPK (P = .03) but was not a statistically significant predictor of perforation, scar size, or final visual acuity. Culture positivity at day 7 had a hazard ratio of 3.5 for requiring TPK (P = .003). Those with positive cultures at day 7 had on average 3 logMAR lines worse visual acuity at 3 months (95% confidence interval 0.9 to 5.2 logMAR lines, P = .006) and 1.1 mm larger scar size at 3 months after controlling for baseline measures (95% confidence interval 0.1 to 2.2 mm; P = .03).While not as predictive as day 7 cultures, culture positivity at day 3 after starting treatment is a significant predictor of the need for TPK in patients with moderate-to-severe filamentous fungal keratitis. This has applications for risk stratification, and may facilitate earlier consideration of TPK in high-risk patients.

  View details for DOI 10.1016/j.ajo.2020.02.021

  View details for Web of Science ID 000542119700001

  View details for PubMedID 32171765

• Change in Central and Peripheral Corneal Thickness in UT-DSAEK and DMEK in the Descemet Endothelial Thickness Comparison Trial Gutowski, M., Rose-Nussbaumer, J., Lin, C., Austin, A., Labadzinzki, P., Clover, J., Chamberlain, W. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554528301272

• Corneal Collagen Cross-Linking Under General Anesthesia for Pediatric Patients With Keratoconus and Developmental Delay CORNEA Ahmad, T. R., Pasricha, N. D., Rose-Nussbaumer, J., T. Oatts, J., M. Schallhorn, J., Indaram, M. 2020; 39 (5): 546-551

  Abstract

  To report the clinical characteristics and outcomes of pediatric patients with keratoconus (KCN) who underwent corneal collagen cross-linking (CXL) under general anesthesia for developmental delay or inability to cooperate with topical anesthesia.In this retrospective case series, we reviewed the medical charts of pediatric patients with KCN who had CXL under general anesthesia from January 2018 to April 2019. Baseline disease characteristics of patients with and without developmental delay were compared using the Pearson χ test and the t test. Main outcomes were anesthesia or surgical complications and postoperative best corrected visual acuity (BCVA), keratometry (K) values, and caregiver report of eye-rubbing behavior.Fourteen eyes of 9 patients were reviewed. All were habitual eye rubbers at baseline. Six (66.7%) were developmentally delayed. Compared with patients without developmental delay, developmentally delayed patients were diagnosed and treated at older ages (16.0 vs. 13.9 years), experienced longer delays from diagnosis to surgery (20.7 vs. 8.8 weeks), and had lower BCVA (20/70 vs. 20/40), higher steep K values (54.0 vs. 50.9), and a higher incidence of corneal scarring (75.0% vs. 33.3%) and monocular vision loss (50.0% vs. 0.0%) at baseline, although these differences were not statistically significant. No anesthesia or surgical complications occurred. BCVA and K values were stable at postoperative month 6, with no clinically or statistically significant change observed for either measure. Eight patients decreased or stopped eye rubbing.We demonstrate the efficacy and safety of CXL under general anesthesia in halting the progression of KCN for pediatric patients with developmental delay or an inability to cooperate with the procedure until topical anesthesia.

  View details for DOI 10.1097/ICO.0000000000002197

  View details for Web of Science ID 000536162900003

  View details for PubMedID 31725701

• Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy (vol 9, 16385, 2019) SCIENTIFIC REPORTS Pan, P., Weisenberger, D. J., Zheng, S., Wolf, M., Hwang, D. G., Rose-Nussbaumer, J. R., Jurkunas, U. V., Chan, M. F. 2020; 10 (1): 2395

  Abstract

  An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  View details for DOI 10.1038/s41598-020-59304-9

  View details for Web of Science ID 000513497100015

  View details for PubMedID 32024933

  View details for PubMedCentralID PMC7002491

• Cross-Linking-Assisted Infection Reduction <i>A Randomized Clinical Trial Evaluating the Effect of Adjuvant Cross</i>-<i>Linking on Outcomes in Fungal Keratitis</i> OPHTHALMOLOGY Prajna, N., Radhakrishnan, N., Lalitha, P., Austin, A., Ray, K. J., Keenan, J. D., Porco, T. C., Lietman, T. M., Rose-Nussbaumer, J. 2020; 127 (2): 159-166

  Abstract

  To determine if there is a benefit to adjuvant corneal crosslinking (CXL) and to compare natamycin versus amphotericin B for filamentous fungal keratitis.Outcome-masked, 2×2 factorial design, randomized controlled clinical trial.Consecutive patients presenting with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India.Study eyes were randomized to 1 of 4 treatment combinations using an adaptive randomization protocol. The treatment arms included (1) topical natamycin 5% alone, (2) topical natamycin 5% plus CXL, (3) topical amphotericin B 0.15% alone, and (4) topical amphotericin 0.15% plus CXL.The primary outcome of the trial was microbiological cure at 24 hours on repeat culture. Secondary outcomes included best spectacle-corrected visual acuity (BSCVA) at 3 weeks and 3 months, percentage of study participants with epithelial healing at 3 days, 3 weeks, and 3 months, infiltrate or scar size at 3 weeks and 3 months, 3-day smear and culture, and adverse events.Those randomized to CXL regardless of medication (topical natamycin or amphotericin) had 1.32-fold increased odds of 24-hour culture positivity, although this was not statistically significant (95% confidence interval [CI], 0.57-3.06; P = 0.51). We were also unable to find a difference in 24-hour culture positivity between those randomized to amphotericin and those randomized to natamycin when evaluating as a group regardless of whether or not they received CXL (coefficient 1.10; 95% CI, 0.47-2.54; P = 0.84). The BSCVA was approximately 0.22 logarithm of the minimum angle of resolution (logMAR) (2.2 Snellen lines) worse on average at 3 weeks among those receiving CXL regardless of medication (95% CI, -0.04 to 0.40; P = 0.04) and 0.32 logMAR (3.2 Snellen lines) worse visual acuity at 3 months after controlling for baseline visual acuity (95% CI, 0.03-0.54; P = 0.02). There was no difference in infiltrate or scar size, percentage of epithelialized or adverse events when comparing CXL with no CXL or the 2 topical medications.There appears to be no benefit of adjuvant CXL in the primary treatment of moderate filamentous fungal ulcers, and it may result in decreased visual acuity.

  View details for DOI 10.1016/j.ophtha.2019.08.029

  View details for Web of Science ID 000508226400009

  View details for PubMedID 31619359

  View details for PubMedCentralID PMC6982573

• Corneal Light Scatter After Ultrathin Descemet Stripping Automated Endothelial Keratoplasty Versus Descemet Membrane Endothelial Keratoplasty in Descemet Endothelial Thickness Comparison Trial: A Randomized Controlled Trial. Cornea Hirabayashi, K. E., Chamberlain, W., Rose-Nussbaumer, J., Austin, A., Stell, L., Lin, C. C. 2020

  Abstract

  PURPOSE: To compare the degree of corneal light scatter as measured by densitometry in ultrathin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK) in the Descemet endothelial thickness comparison trial.METHODS: This was a prespecified secondary analysis of the Descemet endothelial thickness comparison trial, which was a prospective, randomized controlled trial. Subjects with isolated endothelial dysfunction were enrolled and were randomized to either UT-DSAEK or DMEK. Corneal opacity was quantitatively measured by Pentacam densitometry (OCULUS) at 3, 6, and 12 months.RESULTS: Fifty eyes of 38 patients were enrolled at the Casey Eye Institute at Oregon Health & Science University and the Byers Eye Institute at Stanford University. Corneal densitometry for the anterior and posterior layers improved in both UT-DSAEK and DMEK after surgery. The decrease was more pronounced in the posterior layer for both groups. However, there was no difference in the degree of corneal light scatter between UT-DSAEK and DMEK at postoperative month 12, and no difference in change in densitometry was observed between the 2 arms from baseline to month 12.CONCLUSIONS: Both UT-DSAEK and DMEK experience an improvement in the degree of corneal light scatter after surgery. However, there was no difference in densitometry between the 2 groups at month 12. Therefore, other factors such as higher order aberrations in the posterior cornea rather than stromal-stromal interface haze mediate the superior visual outcomes in DMEK compared with UT-DSAEK.

  View details for DOI 10.1097/ICO.0000000000002256

  View details for PubMedID 31939923

• A double masked randomised 4-week, placebo-controlled study in the USA, Thailand and Taiwan to compare the efficacy of oral valganciclovir and topical 2% ganciclovir in the treatment of cytomegalovirus anterior uveitis: study protocol BMJ OPEN Takhar, J. S., Joye, A. S., Somkijrungroj, T., Laovirojjanakul, W., Lin, C., Lietman, T. M., Porco, T. C., Keenan, J. D., Gebreegziabher, E. A., Seitzman, G. D., Rose-Nussbaumer, J., Doan, T. A., Acharya, N. R., Gonzales, J. A. 2019; 9 (12): e033175

  Abstract

  Cytomegalovirus (CMV) anterior uveitis is a recognised cause of anterior uveitis in immunocompetent patients and is preventable cause of vision loss. Ocular sequelae include corneal endothelial damage which can cause corneal oedema and failure, as well as glaucoma. Recurrences of inflammation are common and therefore patients are often exposed to long-term therapy. Oral therapy is available in the form of valganciclovir, although with the caveat of systemic side effects such as bone marrow suppression and renal failure necessitating regular interval laboratory monitoring. Recent reports have demonstrated that topical 2% ganciclovir solution may offer promising treatment outcomes in patients with CMV anterior uveitis with superior safety, cost-effectiveness and convenience profiles. An investigation into the relative equipoise of these therapies is warranted for these reasons.The Systemic and Topical Control of Cytomegalovirus Anterior uveitis: Treatment Outcomes (STACCATO) trial is designed as a multicentre, block randomised by site, double-masked, placebo-controlled trial comparing the efficacy of oral valganciclovir, 2% topical ganciclovir and placebo in treating PCR-proven CMV anterior uveitis. Participant clinical evaluation will occur at three study time points by a masked study ophthalmologist over a 28-day period to assess resolution of ocular inflammation (secondary outcome). A control group will provide additional information about the possible impact that the infected host's immune response may play in controlling local viral replication. The primary analysis is an analysis of covariance (three arms) correcting for baseline to compare quantitative CMV viral load in the anterior chamber (AC) aqueous fluid before and 7 days after treatment.The University of California San Francisco Committee on Human Research and the Khon Kaen University Institutional Review Board have given ethical approval. The results of this trial will be presented at local and international meetings and submitted for peer-reviewed journals for publication.NCT03576898.

  View details for DOI 10.1136/bmjopen-2019-033175

  View details for Web of Science ID 000512773400231

  View details for PubMedID 31862739

  View details for PubMedCentralID PMC6937053

• Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy SCIENTIFIC REPORTS Pan, P., Weisenberger, D. J., Zheng, S., Wolf, M., Hwang, D. G., Rose-Nussbaumer, J. R., Jurkunas, U. V., Chan, M. F. 2019; 9: 16385

  Abstract

  Homeostatic maintenance of corneal endothelial cells is essential for maintenance of corneal deturgescence and transparency. In Fuchs endothelial corneal dystrophy (FECD), an accelerated loss and dysfunction of endothelial cells leads to progressively severe visual impairment. An abnormal accumulation of extracellular matrix (ECM) is a distinctive hallmark of the disease, however the molecular pathogenic mechanisms underlying this phenomenon are not fully understood. Here, we investigate genome-wide and sequence-specific DNA methylation changes of miRNA genes in corneal endothelial samples from FECD patients. We discover that miRNA gene promoters are frequent targets of aberrant DNA methylation in FECD. More specifically, miR-199B is extensively hypermethylated and its mature transcript miR-199b-5p was previously found to be almost completely silenced in FECD. Furthermore, we find that miR-199b-5p directly and negatively regulates Snai1 and ZEB1, two zinc finger transcription factors that lead to increased ECM deposition in FECD. Taken together, these findings suggest a novel epigenetic regulatory mechanism of matrix protein production by corneal endothelial cells in which miR-199B hypermethylation leads to miR-199b-5p downregulation and thereby the increased expression of its target genes, including Snai1 and ZEB1. Our results support miR-199b-5p as a potential therapeutic target to prevent or slow down the progression of FECD disease.

  View details for DOI 10.1038/s41598-019-52727-z

  View details for Web of Science ID 000495373400003

  View details for PubMedID 31705138

  View details for PubMedCentralID PMC6841734

• Re: Narayana et al.: Mycotic antimicrobial localized injection: a randomized clinical trial evaluating intrastromal injection of voriconazole (<i>Ophthalmology</i>. 2019;126:1084-1089) REPLY OPHTHALMOLOGY Narayana, S., Krishnan, T., Ramakrishnan, S., Austin, A., Lietman, T., Rose-Nussbaumer, J. 2019; 126 (11): E86-E87

  View details for DOI 10.1016/j.ophtha.2019.07.003

  View details for Web of Science ID 000490992500006

  View details for PubMedID 31635709

• Demographic and socioeconomic barriers and treatment seeking behaviors of patients with infectious keratitis requiring therapeutic penetrating keratoplasty INDIAN JOURNAL OF OPHTHALMOLOGY Shah, H., Radhakrishnan, N., Ramsewak, S., Chiu, S., Joseph, S., Rose-Nussbaumer, J., Prajna, N. 2019; 67 (10): 1593-1598

  Abstract

  To understand demographic and socioeconomic barriers and treatment-seeking behaviors of patients with infectious keratitis requiring therapeutic penetrating keratoplasty (TPK) in a developing country.This prospective non-comparative questionnaire- based study included all patients presenting to Aravind Eye Hospital, Madurai with infectious keratitis that eventuated to TPK between November 2015 and October 2016. A structured questionnaire was administered on post-operative day 3 to collect data on the demographic details, predisposing factors, prior treatment received, and treatment expenditures.In total, 227 patients underwent TPK between November 2015 and October 2016 for infectious keratitis. The majority of patients were males (n = 132, 58.1%), illiterate (n = 129, 56.8%), and had a family monthly income of less than INR 6000 (n = 142, 62.5%). Most of the patients (n = 163, 71.8%) had prior treatment with an ophthalmologist before presenting to our hospital. The mean distance travelled to reach our centre was 269.2 ± 298.5 km. The mean duration of disease before the presentation was 20.3 ± 21.1 days. Corneal smear was positive for fungus in 163 (88.1%) and Aspergillus was the most commonly isolated fungi in 55 (41.3%) cultures. The mean total cost of treatment was INR 8752.87 ± 7615.39 per patient. There was a positive correlation between the duration of the disease (rho 0.19, P = 0.0034) and the costs of treatment (rho 0.2, P = 0.0024) with the distance travelled by the patient.Patients who travelled a farther distance had a delayed onset of presentation and spent significantly more than their respective counterparts.

  View details for DOI 10.4103/ijo.IJO_1821_18

  View details for Web of Science ID 000488008300020

  View details for PubMedID 31546487

  View details for PubMedCentralID PMC6786147

• Neurotrophic keratitis after micropulse transscleral diode laser cyclophotocoagulation. American journal of ophthalmology case reports Perez, C. I., Han, Y., Rose-Nussbaumer, J., Ou, Y., Hsia, Y. C. 2019; 15: 100469

  Abstract

  PURPOSE: To report two cases of neurotrophic keratitis (NK) after micropulse transscleral cyclophotocoagulation (MP-TCP).OBSERVATIONS: Two patients with predisposing factors for decreased corneal sensation developed NK 1 month after MP-TCP. Both patients did not heal with initial treatment with topical antibiotic and preservative free artificial tears. One patient required use of a bandage contact lens and the other patient required tarsorrhaphy. Both eyes experienced recurrence of NK.CONCLUSIONS AND IMPORTANCE: NK can be triggered after MP-TCP in patients with underlying predisposing factors for decreased corneal sensation. This uncommon but vision-threatening complication should be discussed preoperatively with high-risk patients as a possible adverse event after MP-TCP and followed closely postoperatively.

  View details for DOI 10.1016/j.ajoc.2019.100469

  View details for PubMedID 31193794

• Mycotic Antimicrobial Localized Injection <i>A Randomized Clinical Trial Evaluating Intrastromal Injection of Voriconazole</i> OPHTHALMOLOGY Narayana, S., Krishnan, T., Ramakrishnan, S., Samantaray, P., Austin, A., Pickel, J., Porco, T., Lietman, T., Rose-Nussbaumer, J. 2019; 126 (8): 1084-1089

  Abstract

  To determine if there is a benefit to adjuvant intrastromal voriconazole (ISV) injections for primary treatment of filamentous fungal keratitis.Outcome-masked, randomized controlled clinical trial.Patients with moderate vision loss resulting from a smear-positive fungal ulcer.Study eyes were randomized to topical natamycin plus ISV injection versus topical natamycin alone.The primary outcome of the trial was microbiological cure on 3-day repeat culture analysis. Secondary outcomes included microbiological cure on 7-day repeat culture analysis; 3-week and 3-month best spectacle-corrected visual acuity; infiltrate or scar size or both; rate of perforation; therapeutic penetrating keratoplasty (TPK); and other adverse events.A total of 151 patients with smear-positive ulcers were screened and 70 were enrolled at Aravind Eye Hospital, Pondicherry, India. Baseline cultures grew Fusarium in 19 samples (27%), Aspergillus in 17 samples (24%), and other filamentous fungi in 19 samples (27%) and showed negative results in 13 samples (19%). Those randomized to ISV injection had 1.82 times the odds of 3-day culture positivity after controlling for baseline culture status (95% confidence interval [CI], 0.65-5.23; P = 0.26, bias-corrected logistic regression) and 1.98 times the odds of positive 7-day culture results, after controlling for baseline culture status (95% CI, 0.69-5.91; P = 0.20, bias-corrected logistic regression). Those randomized to ISV injection showed 0.5 logMAR lines (approximately 0.5 Snellen lines) of decreased visual acuity (95% CI, -2.6 to 3.6 lines; P = 0.75) and 0.55 mm worse infiltrate or scar size or both at 3 months after controlling for baseline values (95% CI, -0.13 to 1.25; P = 0.11). Intrastromal voriconazole injections showed a 2.85-fold increased hazard of perforation after controlling for baseline infiltrate depth (95% CI, 0.76-10.75; P = 0.12) but no difference in the rate of TPK (hazard ratio, 0.95; 95% CI, 0.44-2.04; P = 0.90).There seems to be no benefit to adding ISV injections to topical natamycin in the primary treatment of moderate to severe filamentous fungal ulcers. Studies consistently suggest that voriconazole has a limited role in the treatment of filamentous fungal ulcers.

  View details for DOI 10.1016/j.ophtha.2019.03.020

  View details for Web of Science ID 000475845500012

  View details for PubMedID 30904540

  View details for PubMedCentralID PMC6646068

• Repeatability and Reproducibility of Slit Lamp, Optical Coherence Tomography, and Scheimpflug Measurements of Corneal Scars OPHTHALMIC EPIDEMIOLOGY Das, M., Menda, S. A., Panigrahi, A. K., Prajna, N., Yen, M., Tsang, B., Kumar, A., Rose-Nussbaumer, J., Acharya, N. R., McCulloch, C. E., Lietman, T. M., McLeod, S. D., Keenan, J. D. 2019; 26 (4): 251-256

  Abstract

  Purpose: To determine the repeatability and reproducibility of anterior segment optical coherence tomography (AS-OCT) and Scheimpflug photography for several measurements of corneal scars, including scar size, scar depth, and corneal thickness. Methods: A series of patients treated for fungal keratitis at a tertiary eye care center in South India were recalled two years after successful treatment. Eyes with corneal scars had a slit lamp examination performed by two ophthalmologists masked to the other's examination. For AS-OCT and Scheimpflug photography, each eye had two scans taken by one technician and a third scan taken by a separate technician. Scar measurements were subsequently assessed from AS-OCT images by three graders masked to each other's results. Repeatability and reproducibility were assessed by calculating the intra-class correlation coefficient (ICC) from mixed effects linear regression models. Results: Fifty eyes had all measurements taken. The corneal scar size, measured as the geometric mean of the two longest perpendicular meridians, ranged from 0.8 to 5.4 (mean 2.8 mm, 95%CI 2.6 to 3.1). Scar size measurements taken by two separate individuals were most reproducible when the border of the scar was traced from the OCT (ICC 0.90, 95%CI 0.86 to 0.94), and least repeatable when assessed from slit lamp examination (ICC 0.80, 95%CI 0.70 to 0.90). Conclusions: AS-OCT and Scheimpflug imaging of corneal scars produced measurements with acceptable reproducibility that could be useful as cornea-specific outcomes for clinical trials.

  View details for DOI 10.1080/09286586.2019.1600199

  View details for Web of Science ID 000482344000005

  View details for PubMedID 31018742

• Corneal Higher-Order Aberrations in Descemet Membrane Endothelial Keratoplasty versus Ultrathin DSAEK in the Descemet Endothelial Thickness Comparison Trial A Randomized Clinical Trial OPHTHALMOLOGY Duggan, M. J., Rose-Nussbaumer, J., Lin, C. C., Austin, A., Labadzinzki, P. C., Chamberlain, W. D. 2019; 126 (7): 946–57

  View details for DOI 10.1016/j.ophtha.2019.02.007

  View details for Web of Science ID 000472015700015

• Changes in Anterior and Posterior Corneal Astigmatism after Descemet Membrane Endothelial Keratoplasty versus Ultrathin Descemet Stripping Automated Endothelial Keratoplasty: Results from the Randomized Controlled DETECT Trial Werner, S., Rose-Nussbaumer, J., Lin, C., Austin, A., Chamberlain, W. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800707027

• Effect of Unilateral Endothelial Keratoplasty on Vision-Related Quality-of-Life Outcomes in the Descemet Endothelial Thickness Comparison Trial (DETECT): A Secondary Analysis of a Randomized Clinical Trial JAMA OPHTHALMOLOGY Ang, M. J., Chamberlain, W., Lin, C. C., Pickel, J., Austin, A., Rose-Nussbaumer, J. 2019; 137 (7): 747–54

  View details for DOI 10.1001/jamaophthalmol.2019.0877

  View details for Web of Science ID 000481513900005

• Overexpression of MMPs in Corneas Requiring Penetrating and Deep Anterior Lamellar Keratoplasty INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Wolf, M., Clay, S. M., Oldenburg, C. E., Rose-Nussbaumer, J., Hwang, D. G., Chan, M. F. 2019; 60 (5): 1734-1747

  Abstract

  Matrix metalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases involved in wound healing processes, including neovascularization and fibrosis. We assessed MMP protein expression levels in diseased corneas of patients requiring penetrating and deep anterior lamellar keratoplasty. The purpose of this study was to test the hypothesis that upregulation of MMPs in diseased corneas is positively associated with clinical levels of corneal neovascularization and fibrosis.Protein expression levels of nine individual MMPs were quantified simultaneously in human corneal lysates by using the Bio-Plex Pro Human MMP 9-Plex Panel and the MAGPIX technology. Measurements of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, and MMP13 were performed on diseased specimens from 21 patients undergoing corneal transplantation (17 for penetrating keratoplasty and 4 for deep anterior lamellar keratoplasty) and 6 normal control corneas.Luminex-based expression analysis revealed a significant overexpression of four of the nine MMPs tested (MMP2, MMP8, MMP12, and MMP13) in patient samples compared to control. Significant overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 was observed in diseased corneas with neovascularization compared with diseased corneas without neovascularization. Overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 also corresponded with the levels of corneal fibrosis. Finally, reduced expression of MMP3 was detected in keratoconus patients.Multiple MMPs are expressed in the corneas of patients with chronic disease requiring keratoplasty even when the pathologic process appears to be clinically inactive. In particular, the expression of several MMPs (MMP2, MMP8, MMP12, and MMP13) is positively associated with increased levels corneal fibrosis and neovascularization.

  View details for DOI 10.1167/iovs.18-25961

  View details for Web of Science ID 000466757300049

  View details for PubMedID 31022731

  View details for PubMedCentralID PMC6485316

• Corneal Higher-Order Aberrations in DMEK versus UT-DSAEK in DETECT: A Randomized Clinical Trial. Ophthalmology Duggan, M. J., Rose-Nussbaumer, J., Lin, C. C., Austin, A., Labadzinzki, P. C., Chamberlain, W. D. 2019

  Abstract

  PURPOSE: To compare corneal higher-order aberrations (HOA) following ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK).DESIGN: Patient and outcome-masked, randomized controlled clinical trial.PARTICIPANTS: Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or pseudophakic bullous keratopathy who were considered good candidates for DMEK or UT-DSAEK.METHODS: Corneal anterior and posterior surface HOA were measured with Scheimpflug imaging before surgery and at 3, 6, and 12 months post-operatively. Zernike orders 3-8 were calculated at 4.0- and 6.0-mm-diameter optical zones (OZ). HOA after UT-DSAEK and DMEK were compared and correlation was performed between best spectacle-corrected visual acuity (BSCVA) and HOA at each time point.MAIN OUTCOME MEASURES: Higher-order aberrations of the anterior and posterior cornea, expressed as the root mean square deviation from a best fit sphere reference surface.RESULTS: At 3, 6, and 12 months after surgery, the posterior corneal surface had significantly less coma (P≤0.003) and total HOA (P≤0.001) in DMEK compared to UT-DSAEK (4.0- and 6.0-mm OZ). Posterior trefoil (P≤0.034), secondary astigmatism (P≤0.042), and tetrafoil (P≤0.045) were lower in DMEK than UT-DSAEK at 3, 6, or 12 months (either 4.0- or 6.0-mm OZ). There were no significant differences in anterior surface HOA between DMEK and UT-DSAEK at any time point. Compared to baseline, total posterior HOA was significantly increased (P≤0.036) in UT-DSAEK at 3, 6, and 12 months, in contrast to DMEK where it was significantly decreased (P≤0.044) at 6 and 12 months (4.0- and/or 6.0-mm OZ). At 6 and 12 months, posterior corneal total HOA correlated moderately with BSCVA (rho≤0.635, P≤0.001) (4.0- and 6.0-mm OZ). There were no moderate or strong correlations between anterior or combined corneal surface HOA at any time point after surgery.CONCLUSIONS: DMEK results in less posterior corneal HOA compared to UT-DSAEK. DMEK decreases and UT-DSAEK increases posterior corneal HOA compared to pre-surgical values. Total posterior corneal HOA correlates moderately with 6- and 12-month post-operative visual acuity and may partially account for the better visual acuity observed after DMEK.

  View details for PubMedID 30776384

• Donor, Recipient, and Operative Factors Associated With Increased Endothelial Cell Loss in the Cornea Preservation Time Study Lass, J. H., Benetz, B., Patel, S. V., Szczotka-Flynn, L. B., O'Brien, R., Ayala, A. R., Maguire, M. G., Daoud, Y. J., Greiner, M. A., Hannush, S. B., Lee, W., Mauger, T. F., Menegay, H. J., Mifflin, M. D., Raizman, M. B., Rose-Nussbaumer, J., Schultze, R. L., Schmidt, G. A., Sugar, A., Terry, M. A., Verdier, D. D., Beck, R., Gal, R., Redford, M., Aldave, A. J., Dunn, S. P., McCall, T. L., Navarro, L., Pramanik, S., Ross, K. W., Rosenwasser, G. O., Terry, M. A., Verdier, D. T., Ross, K. W., Dahl, P., Drury, D. C., Farazdaghi, S. M., Hoover, C. K., Penta, J. G., Soper, M. C., Stoeger, C. G., Williams, D. V., Musch, D. C., Bourne, W., Colby, K. A., Fisher, M., Fishman, R., Redford, M., Aldave, A., Berdy, G., Bokosky, J., Croasdale, C., Daoud, Y., Dunn, S., Gillette, T., Goins, K., Gupta, P., Hammersmith, K., Hannush, S., Hardten, D., Jeng, B., Jones, M., Lahners, W., Lee, W., Macsai, M., Mauger, T., Maverick, K., McCall, T., Van Meter, W., Mian, S., Mifflin, M., Nirankari, V., Nordlund, M., Oliva, M., Patel, S., Pramanik, S., Raber, I., Raizman, M., Rose-Nussbaumer, J., Rosenwasser, G., Schultze, R., Seedor, J., Shamie, N., Song, J., Stark, W., Stulting, R., Sugar, A., Tauber, S., Terry, M., Thomas, K., Tu, E., Verdier, D., Yoo, S., Adler, V., Caraballo, W., Dahl, P., Dorn, G., Drury, D., Farazdaghi, S., Fout-Caraza, E., Gore, P., Grimes, V., Hoover, C., Van Klinken, D., Liang, N., Mays, T., McCoy, K., McEntire, W., Meinecke, E., Penta, J., Ross, K., Schipper, M., Schmidt, G., Stoeger, C., Tramber, M., Cornea Preservation Time Study Grp AMER MEDICAL ASSOC. 2019: 185-193

  Abstract

  Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival.To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study.This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included.The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days.Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images.The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm2), lower screening ECD (-234 [-331 to -137] per 500 cells/mm2), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm2), and operative complications (-324 [-516 to -133] in cells/mm2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD.Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

  View details for DOI 10.1001/jamaophthalmol.2018.5669

  View details for Web of Science ID 000458631500016

  View details for PubMedID 30422157

  View details for PubMedCentralID PMC6439830

• Descemet Endothelial Thickness Comparison Trial A Randomized Trial Comparing Ultrathin Descemet Stripping Automated Endothelial Keratoplasty with Descemet Membrane Endothelial Keratoplasty OPHTHALMOLOGY Chamberlain, W., Lin, C. C., Austin, A., Schubach, N., Clover, J., McLeod, S. D., Porco, T. C., Lietman, T. M., Rose-Nussbaumer, J. 2019; 126 (1): 19–26

  Abstract

  To compare clinical outcomes of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) in the treatment of corneal endothelial dysfunction.Patient and outcome-masked, randomized controlled clinical trial.Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or pseudophakic bullous keratopathy who were considered good candidates for DMEK or UT-DSAEK.Study eyes were randomized by the eye bank to UT-DSAEK or DMEK 1 to 2 days before surgery.The primary outcome of the trial was best spectacle-corrected visual acuity (BSCVA) at 6 months. Secondary outcomes included 3- and 12-month BSCVA; 3-, 6-, and 12-month endothelial cell counts; intraoperative and postoperative complications; and change in pachymetry.A total of 216 patients with endothelial dysfunction were screened, and 50 eyes of 38 patients were enrolled by 2 surgeons at Casey Eye Institute at Oregon Health & Science University in Portland, Oregon, and at Byers Eye Institute at Stanford University in Palo Alto, California. Overall, we found DMEK to have better visual acuity outcomes compared with UT-DSAEK after correcting for baseline visual acuity: compared with UT-DSAEK, those randomized to DMEK had 1.5 lines better BSCVA at 3 months (95% confidence interval [CI], 2.5-0.6 lines better; P = 0.002), 1.8 lines better BSCVA at 6 months (95% CI, 2.8-1.0 lines better; P < 0.001), and 1.4 lines better BSCVA at 12 months (95% CI, 2.2-0.7 lines better; P < 0.001). Average endothelial cell counts were 1963 cells/mm2 in DMEK and 2113 cells/mm2 in UT-DSAEK at 6 months (P = 0.17) and 1855 cells/mm2 in DMEK and 2070 cells/mm2 in UT-DSAEK at 12 months (P = 0.051). Intraoperative and postoperative complication rates were similar between groups.Descemet membrane endothelial keratoplasty had superior visual acuity results compared with UT-DSAEK at 3, 6, and 12 months in patients with isolated endothelial dysfunction with similar complication rates.

  View details for PubMedID 29945801

• Effect of Unilateral Endothelial Keratoplasty on Vision-Related Quality-of-Life Outcomes in the Descemet Endothelial Thickness Comparison Trial (DETECT): A Secondary Analysis of a Randomized Clinical Trial. JAMA ophthalmology Ang, M. J., Chamberlain, W. n., Lin, C. C., Pickel, J. n., Austin, A. n., Rose-Nussbaumer, J. n. 2019

  Abstract

  Vision-related quality of life can be a valuable outcome for some interventions in ophthalmology. In the primary Descemet Endothelial Thickness Comparison Trial (DETECT), Descemet membrane endothelial keratoplasty (DMEK) had superior postoperative visual acuity compared with ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK). It is of interest to determine whether this trend extends to quality of life.To determine the effect of UT-DSAEK and DMEK on vision-related quality of life.A prespecified secondary analysis of a 2-surgeon patient- and outcome-masked randomized clinical trial was conducted at the Casey Eye Institute in Portland, Oregon, and Byers Eye Institute in Palo Alto, California. The study was conducted between January 20, 2015, and April 26, 2017. DETECT enrolled 38 individuals and included 50 eyes with isolated endothelial dysfunction; for this analysis, the second eye from a single participant was excluded along with any questionnaires in the first eye after second eye surgery for evaluation of 38 eyes at baseline and 3 months and 26 eyes at 12 months. Mean (SD) baseline visual acuity was 0.35 (0.31) logMAR in the DMEK arm and 0.28 (0.22) logMAR in the UT-DSAEK arm. Each arm consisted of 19 participants: 18 individuals with Fuchs dystrophy and 1 participant with pseudophakic bullous keratopathy.Study eyes were randomized to receive either UT-DSAEK or DMEK.Responses to the National Eye Institute (NEI) Visual Function Questionnaire-39 (VFQ-39) administered at baseline and 3 and 12 months postoperatively were analyzed using the NEI-defined traditional subscales and composite score on a 100-point scale and with a Rasch-refined analysis.There were more women in both arms of the study (UT-DSAEK, 12 [63%]; DMEK, 11 [58%]); mean (SD) age was 68 (11) years in the UT-DSAEK arm and 68 (4) years in the DMEK arm. Overall, study participants experienced a 9.1-point improvement in NEI VFQ-39 composite score at 3 months compared with baseline (N = 38; 95% CI, 4.9-13.3; P < .001), and an 11.6-point improvement at 12 months compared with baseline (n = 26; 95% CI, 6.8-16.4; P < .001). Eyes randomized to DMEK had 0.9 points more improvement in NEI VFQ-39 composite score at 3 months compared with UT-DSAEK after controlling for baseline NEI VFQ-39 (95% CI, -6.2 to 8.0; P = .80).Improvement in vision-related quality of life was not shown to be greater with DMEK compared with UT-DSAEK.ClinicalTrials.gov identifier: NCT02373137.

  View details for PubMedID 31046075

• Factors Associated With Graft Rejection in the Cornea Preservation Time Study AMERICAN JOURNAL OF OPHTHALMOLOGY Stulting, R., Lass, J. H., Terry, M. A., Benetz, B., Cohen, N. J., Ayala, A. R., Maguire, M. G., Croasdale, C., Daoud, Y. J., Dunn, S. P., Goins, K. M., Gupta, P. C., Macsai, M. S., Mian, S. I., Pramanik, S., Rose-Nussbaumer, J., Song, J. C., Stark, W. J., Sugar, A., Verdier, D. D., Szczotka-Flynn, L. B., Cornea Preservation Time Study Grp 2018; 196: 197-207

  Abstract

  To identify factors related to graft rejection following Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS).Cohort study within a multicenter randomized clinical trial.A total of 1330 eyes of 1090 subjects undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0-7 days (n = 675) or 8-14 days (n = 655) and followed for 3 years. Central endothelial cell density (ECD) was determined by a central image analysis reading center. Multivariable Cox models adjusted for PT, recipient diagnosis, and surgeon effect were used to identify factors associated with rejection.Cumulative probability of definite graft rejection was 3.6% (99% confidence interval 2.5%-5.3%). Younger recipient age was associated with graft rejection (P < .001; hazard ratio: 0.53 [0.33, 0.83] per decade). PT, donor-recipient sex mismatch, recipient diagnosis, recipient race, graft size, discontinuation of topical corticosteroids and immune-modulators, prior immunizations within 3 months, and prior glaucoma surgery were not associated with rejection (P > .01). Among clear grafts with an ECD measurement at baseline and 3 years (n = 913), endothelial cell loss (ECL) was greater in eyes that experienced a rejection episode (n = 27) than in those that did not (n = 886) (48% vs 38%, P = .03). Twelve of 44 eyes (27%) with definite graft rejection subsequently failed, comprising 15% of the 79 failures in the CPTS.Graft rejection is uncommon after DSAEK and more likely with younger age, in a study cohort mostly > 50 years old. Rejection increases ECL, but it is not a leading cause of DSAEK failure.

  View details for DOI 10.1016/j.ajo.2018.10.005

  View details for Web of Science ID 000452812500029

  View details for PubMedID 30308200

  View details for PubMedCentralID PMC6258266

• Donor, Recipient, and Operative Factors Associated with Graft Success in the Cornea Preservation Time Study OPHTHALMOLOGY Terry, M. A., Aldave, A. J., Szczotka-Flynn, L. B., Liang, W., Ayala, A. R., Maguire, M. G., Croasdale, C., Daoud, Y. J., Dunn, S. P., Hoover, C. K., Macsai, M. S., Mauger, T. F., Pramanik, S., Rosenwasser, G. D., Rose-Nussbaumer, J., Stulting, R., Sugar, A., Tu, E. Y., Verdier, D. D., Yoo, S. H., Lass, J. H., Cornea Preservation Time Study Grp 2018; 125 (11): 1700-1709

  Abstract

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

  View details for DOI 10.1016/j.ophtha.2018.08.002

  View details for Web of Science ID 000446986000012

  View details for PubMedID 30098353

  View details for PubMedCentralID PMC6196643

• Therapeutic Penetrating Keratoplasty Button Cultures in The Mycotic Ulcer Treatment Trial II: A Randomized Trial Comparing Oral Voriconazole Versus Placebo AMERICAN JOURNAL OF OPHTHALMOLOGY Cho, J., Prajna, N., Lalitha, P., Rajaraman, R., Krishnan, T., Lin, Y., Ray, K. J., Lietman, T. M., Rose-Nussbaumer, J., Mycotic Ulcer Treatment Trial Grp 2018; 192: 142-145

  Abstract

  To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis.Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial.Study Participants: Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK).Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops.TPK button culture positivity.A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90-0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32-4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16-51.70; P = .003).There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.

  View details for DOI 10.1016/j.ajo.2018.05.007

  View details for Web of Science ID 000441226900021

  View details for PubMedID 29758184

  View details for PubMedCentralID PMC6584760

• Village-Integrated Eye Worker trial (VIEW): rationale and design of a cluster-randomised trial to prevent corneal ulcers in resource-limited settings BMJ OPEN O'Brien, K. S., Byanju, R., Kandel, R., Poudyal, B., Gautam, M., Gonzales, J. A., Porco, T. C., Whitcher, J. P., Srinivasan, M., Upadhyay, M., Lietman, T. M., Keenan, J. D., Village-Integrated Eye Worker 2018; 8 (8): e021556

  Abstract

  Corneal opacity is a leading cause of blindness worldwide. In resource-limited settings, untreated traumatic corneal abrasions may result in infection and ultimately, opacity. Although antimicrobial treatment of corneal ulcers may successfully cure infections, the scarring that accompanies the resolution of infection can still result in visual impairment. Prevention may be the optimal approach for reducing corneal blindness. Studies have employed community health workers to provide prompt administration of antimicrobials after corneal abrasions to prevent infections, but these studies were not designed to determine the effectiveness of such a programme.The Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed to assess the effectiveness of a community health worker intervention to prevent corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were randomised to receive a corneal ulcer prevention programme or to no intervention. Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to diagnose corneal abrasions, provide antimicrobials and to refer participants when needed. An annual census is conducted over 3 years in all study VDCs to assess the incidence of corneal ulceration via corneal photography (primary outcome). Masked outcome assessors grade corneal photographs to determine the presence or absence of incident corneal opacities. The primary analysis is negative binomial regression to compare the incidence of corneal ulceration by study arm.The University of California San Francisco Committee on Human Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have given ethical approval for the trial. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication.NCT01969786; Pre-results.

  View details for DOI 10.1136/bmjopen-2018-021556

  View details for Web of Science ID 000446470200090

  View details for PubMedID 30099393

  View details for PubMedCentralID PMC6089291

• DMEK results in significantly less higher-order aberration than UT-DSAEK: Results from the DETECT trial. Duggan, M., Rose-Nussbaumer, J., Lin, C. C., Austin, A., Chamberlain, W. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912504200

• How Are Ocular Signs and Symptoms of Dry Eye Associated With Depression in Women With and Without Sjogren Syndrome? AMERICAN JOURNAL OF OPHTHALMOLOGY Gonzales, J. A., Chou, A., Rose-Nussbaumer, J. R., Bunya, V. Y., Criswell, L. A., Shiboski, C. H., Lietman, T. M. 2018; 191: 42-48

  Abstract

  To determine whether ocular phenotypic features of keratoconjunctivitis sicca (KCS) and/or participant-reported symptoms of dry eye disease are associated with depression in women participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA).Cross-sectional study.Women enrolled in the SICCA registry from 9 international research sites. Participants met at least 1 of 5 inclusion criteria for registry enrollment (including complaints of dry eyes or dry mouth, a previous diagnosis of Sjögren syndrome (SS), abnormal serology (positive anti-Sjögren syndrome antigen A and/or B [anti-SSA and/or anti-SSB]), or elevated antinuclear antibody and rheumatoid factor), bilateral parotid gland enlargement, or multiple dental caries). At baseline, participants had oral, ocular, and rheumatologic examination; blood and saliva collection; and a labial salivary gland biopsy (LSGB). They also completed an interview and questionnaires including assessment of depression with the Patient Health Questionnaire 9 (PHQ-9). Univariate logistic regression was used to assess the association between depression and demographic characteristics, participant-reported health, phenotypic features of Sjögren syndrome, and participant-reported symptoms. Mixed-effects modeling was performed to determine if phenotypic features of KCS and/or participant-reported symptoms of dry eye disease were associated with depression, controlling for health, age, country or residence, and sex and allowing for nonindependence within geographic site.Dry eye complaints produced a 1.82-fold (95% confidence interval [CI] 1.38-2.40) higher odds of having depression compared to being symptom-free (P < .001). Additionally, complaints of specific ocular sensations were associated with a higher odds of depression including burning sensation (odds ratio 2.25, 95% CI 1.87-2.72, P < .001) compared to those without complaints. In both women with and without SS, the presence of symptoms of dry eyes and/or dry mouth rather than SS itself resulted in higher odds of depression. One particular ocular phenotypic feature of SS, a positive ocular staining score, was inversely correlated with depression.Participant-reported eye symptoms, particularly specific ocular sensations such as burning, were found to be positively associated with individual American College of Rheumatology/EUropean League Against Rheumatism (ACR/EULAR) SS criteria items.

  View details for DOI 10.1016/j.ajo.2018.04.004

  View details for Web of Science ID 000437387100011

  View details for PubMedID 29655640

  View details for PubMedCentralID PMC6040656

• Effect of Donor Characteristics on Visual Outcomes and Endothelial Cell Count in the Descemet Endothelial Thickness Comparison Trial Lin, Y., Chamberlain, W., Lin, C. C., Austin, A., Shubach, N., Clover, J., Mcleod, S., Porco, T., Lietman, T., Rose-Nussbaumer, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912508207

• The Significance of Repeat Cultures in the Treatment of Severe Fungal Keratitis AMERICAN JOURNAL OF OPHTHALMOLOGY Ray, K. J., Prajna, N., Lalitha, P., Rajaraman, R., Krishnan, T., Patel, S., Das, M., Shah, R., Dhakhwa, K., McLeod, S. D., Zegans, M. E., Acharya, N. R., Lietman, T. M., Rose-Nussbaumer, J., Mycotic Ulcer Treatment Trial Grp 2018; 189: 41-46

  Abstract

  To identify fungal keratitis patients who are at risk of a poor outcome and may benefit from closer follow-up or more aggressive treatment.Secondary analysis of randomized clinical trial data.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.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).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.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).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.

  View details for DOI 10.1016/j.ajo.2018.02.003

  View details for Web of Science ID 000431473300008

  View details for PubMedID 29438654

  View details for PubMedCentralID PMC6034515

• Expert practice patterns and opinions on corneal cross-linking for infectious keratitis BMJ OPEN OPHTHALMOLOGY Hsia, Y. C., Moe, C. A., Lietman, T. M., Keenan, J. D., Rose-Nussbaumer, J. 2018; 3 (1): e000112

  Abstract

  To assess the current opinion and practice patterns from cornea experts regarding the benefit of corneal cross-linking (CXL) for infectious keratitis (IK).An international survey was distributed to corneal specialists via an internet survey. The survey data collected were analysed with descriptive statistics.A survey was sent to 190 recipients, and 29 (15%) respondents completed the survey with an average of 7 years' experience using CXL. A majority of respondents (66%) used CXL to treat IK due to bacterial, fungal, protozoan or unknown aetiology. Main indications to use CXL as adjuvant therapy were worsening infiltrate diameter or depth despite therapy (74%), followed by antibiotic resistance (68%), corneal thinning (53%), poor compliance with medication (26%) and other reasons (21%). Most respondents felt CXL would be at least moderately helpful as an adjuvant therapy for bacterial (96%) or fungal (75%) keratitis; about half (46%) thought it would be helpful for acanthamoeba keratitis. As sole therapy, fewer respondents believed CXL would be at least moderately helpful to treat bacterial (75%), fungal (58%) and acanthamoeba (43%) keratitis.The survey offered insights into current expert practices and opinions of using CXL as therapy for IK. The results of this survey serve to guide in the design of future clinical studies.

  View details for DOI 10.1136/bmjophth-2017-000112

  View details for Web of Science ID 000435917500005

  View details for PubMedID 29657977

  View details for PubMedCentralID PMC5895970

• Regression Discontinuity and Randomized Controlled Trial Estimates: An Application to The Mycotic Ulcer Treatment Trials OPHTHALMIC EPIDEMIOLOGY Oldenburg, C. E., Prajna, N., Krishnan, T., Rajaraman, R., Srinivasan, M., Ray, K. J., O'Brien, K. S., Glymour, M., Porco, T. C., Acharya, N. R., Rose-Nussbaumer, J., Lietman, T. M. 2018; 25 (4): 315-322

  Abstract

  We compare results from regression discontinuity (RD) analysis to primary results of a randomized controlled trial (RCT) utilizing data from two contemporaneous RCTs for treatment of fungal corneal ulcers.Patients were enrolled in the Mycotic Ulcer Treatment Trials I and II (MUTT I & MUTT II) based on baseline visual acuity: patients with acuity ≤ 20/400 (logMAR 1.3) enrolled in MUTT I, and >20/400 in MUTT II. MUTT I investigated the effect of topical natamycin versus voriconazole on best spectacle-corrected visual acuity. MUTT II investigated the effect of topical voriconazole plus placebo versus topical voriconazole plus oral voriconazole. We compared the RD estimate (natamycin arm of MUTT I [N = 162] versus placebo arm of MUTT II [N = 54]) to the RCT estimate from MUTT I (topical natamycin [N = 162] versus topical voriconazole [N = 161]).In the RD, patients receiving natamycin had mean improvement of 4-lines of visual acuity at 3 months (logMAR -0.39, 95% CI: -0.61, -0.17) compared to topical voriconazole plus placebo, and 2-lines in the RCT (logMAR -0.18, 95% CI: -0.30, -0.05) compared to topical voriconazole.The RD and RCT estimates were similar, although the RD design overestimated effects compared to the RCT.

  View details for DOI 10.1080/09286586.2018.1469156

  View details for Web of Science ID 000433991400006

  View details for PubMedID 29718751

  View details for PubMedCentralID PMC5980795

• Bacterial Keratitis: Isolated Organisms and Antibiotic Resistance Patterns in San Francisco CORNEA Peng, M. Y., Cevallos, V., McLeod, S. D., Lietman, T. M., Rose-Nussbaumer, J. 2018; 37 (1): 84-87

  Abstract

  Understanding the spectrum of pathogens in a given geographic region is important when deciding on empiric antibiotic therapy. In this study, we evaluate the spectrum of bacterial organisms cultured from corneal samples and their antibiotic sensitivities to guide initial treatment of keratitis.We performed a retrospective case review of cultures from suspected infectious keratitis cases at the Francis I. Proctor Foundation, University of California, San Francisco, from 1996 through 2015. Logistic regression models were used to assess the risk of culturing methicillin-resistant Staphylococcus aureus (MRSA) from ulcers over time and the association between the year cultured and moxifloxacin resistance.A total of 522 of 2203 (23.7%) cultures grew bacterial organisms believed to be the etiology of infection, with available antibiotic sensitivity data. Of these, 338 (65.3%) grew gram-positive organisms with the most common being methicillin-sensitive Staphylococcus aureus (20.1%, N = 105). One hundred eighty (34.7%) grew gram-negative species with Pseudomonas aeruginosa as the most prevalent organism (10.9%, N = 57). There was 1.13 increased odds of culturing MRSA for each 1-year increase in the culture date (P = 0.01) and 1.26 increased odds of culturing an organism resistant to moxifloxacin with each 1-year increase in the culture date after controlling for the infectious organism (P < 0.001).Gram-positive organisms are the most commonly identified etiology of microbial keratitis in this series. Approximately 35% of cultured organisms had variable susceptibility to moxifloxacin, and resistance seems to be increasing over time. The risk of culturing MRSA increased over time.

  View details for DOI 10.1097/ICO.0000000000001417

  View details for Web of Science ID 000429224800022

  View details for PubMedID 29053557

  View details for PubMedCentralID PMC5716884

• Update on the Management of Infectious Keratitis OPHTHALMOLOGY Austin, A., Lietman, T., Rose-Nussbaumer, J. 2017; 124 (11): 1678-1689

  Abstract

  Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and although culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungus and Acanthamoeba. Next-generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However, outcomes remain poor secondary to corneal melting, scarring, and perforation. Adjuvant therapies aimed at reducing the immune response associated with keratitis include topical corticosteroids. The large, randomized, controlled Steroids for Corneal Ulcers Trial found that although steroids provided no significant improvement overall, they did seem beneficial for ulcers that were central, deep or large, non-Nocardia, or classically invasive Pseudomonas aeruginosa; for patients with low baseline vision; and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial (MUTT) I showed a benefit of topical natamycin over topical voriconazole for fungal ulcers, particularly among those caused by Fusarium. MUTT II showed that oral voriconazole did not improve outcomes overall, although there may have been some effect among Fusarium ulcers. Given an increase in nonserious adverse events, the authors concluded that they could not recommend oral voriconazole. Viral keratitis differs from bacterial and fungal cases in that it is often recurrent and is common in developed countries. The Herpetic Eye Disease Study (HEDS) I showed a significant benefit of topical corticosteroids and oral acyclovir for stromal keratitis. HEDS II showed that oral acyclovir decreased the recurrence of any type of herpes simplex virus keratitis by approximately half. Future strategies to reduce the morbidity associated with infectious keratitis are likely to be multidimensional, with adjuvant therapies aimed at modifying the immune response to infection holding the greatest potential to improve clinical outcomes.

  View details for DOI 10.1016/j.ophtha.2017.05.012

  View details for Web of Science ID 000413236000029

  View details for PubMedID 28942073

  View details for PubMedCentralID PMC5710829

• Predictors of Corneal Perforation or Need for Therapeutic Keratoplasty in Severe Fungal Keratitis A Secondary Analysis of the Mycotic Ulcer Treatment Trial II JAMA OPHTHALMOLOGY Prajna, N., Krishnan, T., Rajaraman, R., Patel, S., Shah, R., Srinivasan, M., Das, M., Ray, K. J., Oldenburg, C. E., McLeod, S. D., Zegans, M. E., Acharya, N. R., Lietman, T. M., Rose-Nussbaumer, J., Mycotic Ulcer Treatment Trial Grp 2017; 135 (9): 987-991

  Abstract

  Identifying 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.To 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).This 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.The primary outcome of this secondary analysis was the rate of corneal perforation or the need to undergo TPK.The 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.These results suggest that risk stratification from baseline ulcer characteristics can identify those at highest risk for developing corneal perforation and/or needing TPK.clinicaltrials.gov Identifier: NCT00996736.

  View details for DOI 10.1001/jamaophthalmol.2017.2914

  View details for Web of Science ID 000410669300023

  View details for PubMedID 28817744

  View details for PubMedCentralID PMC6038821

• Empirical treatment of bacterial keratitis: an international survey of corneal specialists BMJ OPEN OPHTHALMOLOGY Austin, A., Schallhorn, J., Geske, M., Mannis, M., Lietman, T., Rose-Nussbaumer, J. 2017; 2 (1)

  Abstract

  New antibiotic agents and changing susceptibility patterns may have changed the empirical treatment of bacterial keratitis. Our objective in this study was to survey cornea specialists' practice patterns in the initial treatment of bacterial ulcers.This study consisted of a short online survey emailed to members of the Cornea Society listserv for an international sample of cornea specialists. Data collection began July 2014 and ended October 2014.A total of 1009 surveys were emailed, and we received 140 (14%) responses. The majority of US clinicians surveyed (n=83, 80%) chose fortified antibiotics empirically, with 55% (n=57) selecting fortified vancomycin and 16% (n=17) using fluoroquinolone alone. International respondents were twice as likely to use fluoroquinolone monotherapy (31%, n=11, p=0.07) and less likely to use fortified vancomycin (33%, n=12, p=0.03). Forty-five per cent (n=46) of US respondents reported that their initial antibiotic choice covered methicillin-resistant Staphylococcus aureus, compared with 22% (n=8) of international respondents (p<0.01). Overall, respondents who were concerned about availability of antibiotics and toxicity were 20.86 (p<0.001) and 7.48 (p<0.001) times more likely to choose fluoroquinolone monotherapy, respectively. If respondents' primary considerations were broad spectrum coverage or antibiotic resistance they had 7.10 (p<0.001) and 12.51 (p<0.001) times the odds of using fortified vancomycin, respectively.Practice patterns for the initial treatment of bacterial keratitis vary with clinicians in the USA being more likely to use fortified antibiotics versus fluoroquinolone monotherapy and more concerned with resistant organisms than their international peers.

  View details for DOI 10.1136/bmjophth-2016-000047

  View details for Web of Science ID 000441775400011

  View details for PubMedID 29226254

  View details for PubMedCentralID PMC5718621

• Adjunctive Oral Voriconazole Treatment of <i>Fusarium</i> Keratitis A Secondary Analysis From the Mycotic Ulcer Treatment Trial II JAMA OPHTHALMOLOGY Prajna, N., Krishnan, T., Rajaraman, R., Patel, S., Shah, R., Srinivasan, M., Devi, L., Das, M., Ray, K. J., O'Brien, K. S., Oldenburg, C. E., McLeod, S. D., Zegans, M. E., Acharya, N. R., Lietman, T. M., Rose-Nussbaumer, J., Mycotic Ulcer Treatment Trial Grp 2017; 135 (6): 520-525

  Abstract

  Fusarium keratitis is common and often results in poor outcomes. No new treatments since natamycin have become available.To explore the role of adjuvant oral voriconazole on clinical outcomes in Fusarium keratitis.In this prespecified subgroup analysis of a multicenter, double-masked, placebo-controlled randomized clinical trial, 240 patients from the Aravind Eye Care System in India, the Lumbini Eye Hospital and Bharatpur Eye Hospital in Nepal, and the University of California, San Francisco, who had culture-positive fungal ulcer and baseline visual acuity of 20/400 or worse were randomized to receive oral voriconazole vs placebo. Enrollment started May 24, 2010, and the last patient study visit was November 23, 2015. All patients received topical voriconazole, 1%, and after the results of the Mycotic Ulcer Treatment Trial (MUTT) II became available, topical natamycin, 5%, was added for all patients. Data analysis was performed from September 2 to October 28, 2016.The primary outcome of the trial was the rate of corneal perforation or the need for therapeutic penetrating keratoplasty. Secondary outcomes included rate of reepithelialization, best spectacle-corrected visual acuity, and infiltrate or scar size at 3 months.Of the 240 study participants, 72 (30.4%) were culture positive for Fusarium species (41 [56.9%] male and 31 [43.1%] female; median [interquartile range] age, 50 [45-57] years). Of these, 33 (45.8%) were randomized to oral voriconazole and 39 (54.2%) to placebo. Fusarium ulcers randomized to oral voriconazole had a 0.43-fold decreased hazard of perforation or therapeutic penetrating keratoplasty compared with placebo after controlling for baseline infiltrate depth (95% CI, 0.22-fold to 0.84-fold; P = .01). Multiple linear regression revealed a 1.89-mm decreased infiltrate and/or scar size at 3 weeks (95% CI, -2.69 to -1.09 mm; P < .001) and a 0.83-mm decreased infiltrate and/or scar size at 3 months after correcting for baseline values (95% CI, -1.33 to -0.32 mm; P = .001) in eyes randomized to oral voriconazole vs placebo. Eyes treated with oral voriconazole also had a mean 0.29 decreased logMAR (improved) (Snellen equivalent 20/40) visual acuity at 3 months after controlling for baseline visual acuity, although this finding was not statistically significant (95% CI, -0.57 to 0.002; P = .052).Although MUTT II could not find a benefit for all corneal ulcers, Fusarium keratitis may benefit from the addition of oral voriconazole to topical natamycin, and physicians should consider prescribing oral voriconazole in these cases.clinicaltrials.gov Identifier: NCT00996736.

  View details for DOI 10.1001/jamaophthalmol.2017.0616

  View details for Web of Science ID 000403471700007

  View details for PubMedID 28426856

  View details for PubMedCentralID PMC5847083

• The Utility of Repeat Culture in Fungal Corneal Ulcer Management: A Secondary Analysis of the MUTT-I Randomized Clinical Trial AMERICAN JOURNAL OF OPHTHALMOLOGY Ray, K. J., Lalitha, P., Prajna, N., Rajaraman, R., Krishnan, T., Srinivasan, M., Ryg, P., Mcleod, S., Acharya, N. R., Lietman, T. M., Rose-Nussbaumer, J., Mycotic Ulcer Treatment Trial Grp 2017; 178: 157-162

  Abstract

  To determine whether patients who had a positive repeated culture was predictive of worse clinical outcome than those who achieved microbiological cure at 6 days in the Mycotic Ulcer Treatment Trial I (MUTT-I).Secondary analysis from a multicenter, double-masked, randomized clinical trial.setting: Multiple hospital sites of the Aravind Eye Care System, India.Patients with culture-positive filamentous fungal ulcers and visual acuity of 20/40 to 20/400 reexamined 6 days after initiation of treatment.Corneal scraping and cultures were obtained from study participants at day 6 after enrollment.We assessed 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate/scar size, corneal perforation, and re-epithelialization rates stratified by culture positivity at day 6.Of the 323 patients with smear-positive ulcers enrolled in MUTT-I, 299 (92.6%) were scraped and cultured 6 days after enrollment. Repeat culture positivity was 31% (92/299). Among patients who tested positive at enrollment, those with positive 6-day cultures had significantly worse 3-month BSCVA (0.39 logMAR; 95% confidence interval [CI]: 0.24-0.44; P < .001), had larger 3-month scar size (0.39 mm; 95% CI: 0.06-0.73; P = .02), were more likely to perforate or require therapeutic penetrating keratoplasty (odds ratio: 6.27; 95% CI: 2.73-14.40; P < .001), and were slower to re-epithelialize (hazard ratio: 0.33; 95% CI: 0.21-0.50; P < .001) than those with a negative 6-day culture result.Early microbiological cure on culture is a predictor of clinical response to treatment.

  View details for DOI 10.1016/j.ajo.2017.03.032

  View details for Web of Science ID 000402591700018

  View details for PubMedID 28385473

  View details for PubMedCentralID PMC5493314

• Penetrating Keratoplasty at a Tertiary Referral Center in Ethiopia: Indications and Outcomes CORNEA Ayalew, M., Tilahun, Y., Holsclaw, D., Indaram, M., Stoller, N. E., Keenan, J. D., Rose-Nussbaumer, J. 2017; 36 (6): 665-668

  Abstract

  To describe the indications, visual acuity outcomes, and graft survival after penetrating keratoplasty (PKP) in Addis Ababa, Ethiopia.The medical records of patients who underwent PKP at Menelik II Hospital between September 2000 and September 2013 were retrospectively reviewed. The prespecified outcomes were graft survival, visual acuity, and complication rates.A total of 321 patients underwent PKP during the study period and were included in the analysis. Indications for surgery were trachoma or leukoma in 141 (44%), keratoconus in 45 (14%), corneal dystrophy in 46 (14%), pseudophakic or aphakic bullous keratopathy in 28 (9%), trauma in 27 (8%), previous graft failure in 18 (6%), active ulcer, burn, or perforation in 9 (3%), and others in 7 (2%). The graft survival rate was 80% overall at 2 years but varied considerably depending on the indication for surgery. Uncorrected visual acuity improved from baseline mean logarithm of the minimum angle of resolution 2.09 (SD 0.67) to mean logarithm of the minimum angle of resolution of 1.53 (SD 1.03) at 2 years. A number of factors affected the visual acuity outcomes. Patients were not routinely refracted, and only 18% (N = 60) of patients had access to corrective spectacles or contact lenses postoperatively. Complication rates were high with infectious keratitis being the most common.PKP is becoming a viable treatment for corneal opacity in developing countries. However, the high burden of disease and lack of corrective lenses remain significant obstacles to overcome.

  View details for DOI 10.1097/ICO.0000000000001190

  View details for Web of Science ID 000403262500007

  View details for PubMedID 28368993

  View details for PubMedCentralID PMC5419864

• Multimodal Assessment of Corneal Thinning Using Optical Coherence Tomography, Scheimpflug Imaging, Pachymetry, and Slit-Lamp Examination CORNEA Oatts, J. T., Keenan, J. D., Mannis, T., Lietman, T. M., Rose-Nussbaumer, J. 2017; 36 (4): 425-430

  Abstract

  To assess the relationship between corneal thinning measured by clinician-graded slit-lamp examination compared with ultrasound pachymetry (USP), anterior segment optical coherence tomography (AS-OCT), and the Pentacam.Patients with corneal thinning underwent USP, AS-OCT, Pentacam measurements and standardized clinical grading by 2 cornea specialists estimating thinning on slit-lamp examination. Reproducibility of each testing modality was assessed using the intraclass correlation coefficient. Bland-Altman plots were used to determine precision and limits of agreement (LOA) between imaging modalities and clinical grading.We included 22 patients with corneal thinning secondary to infectious or inflammatory keratitis. Mean percent stromal thinning estimated by grader 1 was 51% (SD 31) and grader 2 was 49% (SD 33). The intraclass correlation coefficient between the masked examiners was 0.95 (95% confidence interval, 0.88-0.98). Graders were more similar to each other than to any other modality with 2% difference and 4.6% of measurements outside the LOA. When measuring the area of maximum thinning, AS-OCT measured approximately 10% thicker than human graders while the Pentacam measured approximately 10% thinner than human graders with 16.7% outside the LOA. USP measured approximately 20% thinner than human graders with 5.6% outside the LOA.Trained corneal specialists have a high degree of agreement in location and degree of corneal thinning when measured in a standardized fashion on the same day. Other testing modalities had acceptable reproducibility and agreement with clinical examination and each other, although Scheimpflug imaging fared worse for corneal thinning, particularly in the periphery, than the other modalities.

  View details for Web of Science ID 000395788000006

  View details for PubMedID 28129300

  View details for PubMedCentralID PMC5493313

• Effect of mitomycin c and 5-flurouracil adjuvant therapy on the outcomes of Ahmed glaucoma valve implantation CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Cui, Q. N., Hsia, Y. C., Lin, S. C., Stamper, R. L., Rose-Nussbaumer, J., Mehta, N., Porco, T. C., Naseri, A., Han, Y. 2017; 45 (2): 128-134

  Abstract

  To examine the effect of mitomycin c and 5-flurouracil on treatment outcomes following Ahmed glaucoma valve implantation.Retrospective consecutive case series.Fifty patients who received Ahmed glaucoma valve implantation from 1999 to 2013 in the San Francisco Veterans Administration Hospital.The +INJECTION group received intraoperative mitomycin c followed by postoperative mitomycin c and/or 5-flurouracil, whereas the -INJECTION group did not.Primary outcome was treatment success at 1 year post-implantation. Intraocular pressure, hypertensive phase, and the number of glaucoma medications were also examined.Twenty-six patients/eyes in the +INJECTION group and 24 patients/eyes in the -INJECTION group were included. Treatment success was higher in the +INJECTION compared with the -INJECTION group (86 vs. 58%; P = 0.04). Intraocular pressure was lower in the +INJECTION compared with the -INJECTION group at 1, 3, 6 and 12 months (P ≪ 0.00001, P = 0.00003, 0.0008 and 0.024). Hypertensive phase occurred less often in the +INJECTION compared with the -INJECTION group (3.8 vs. 54%; P = 0.021). The +INJECTION group required fewer medications compared with the -INJECTION group (P = 0.02, 0.002, 0.003 and 0.008 at 1, 3, 6 and 12 months). Complication rates were comparable between groups (46.2 and 54.2%; P = 0.63).Adjuvant treatment with antifibrotics following Ahmed glaucoma valve implantation decreased the hypertensive phase and improved surgical outcomes without impacting complication rates at 1 year. This study postulates a role for antifibrotics in the postoperative management of Ahmed glaucoma valves.

  View details for DOI 10.1111/ceo.12811

  View details for Web of Science ID 000398058700006

  View details for PubMedID 27490793

• A nxiety in patients undergoing cataract surgery: a pre- and postoperative comparison CLINICAL OPHTHALMOLOGY Ramirez, D. A., Brodie, F. L., Rose-Nussbaumer, J., Ramanathan, A. 2017; 11: 1979-1986

  Abstract

  Reducing surgery-related patient anxiety without under-emphasizing surgical risk is challenging for even the most experienced surgeon. The purpose of this study is to identify specific anxieties faced by patients in hopes of better informing the preoperative surgeon-patient dialogue.Comprehensive and specialty ophthalmology clinics at the University of California, San Francisco.A prospective, survey-based study in which a pre- and postoperative questionnaire was administered to patients undergoing routine phacoemulsification. The surgeon was masked to patient enrollment and questionnaire responses.A 36-item questionnaire on patient anxiety was developed from existing literature, building on the validated Surgical Fear Questionnaire. Patients were eligible if they were aged >18 years and willing to participate. Patients were excluded if having more than phacoemulsification alone or if unable to respond in English, and were retroactively excluded if there were complications during surgery. The primary outcome was self-reported anxiety on an 11-point Likert scale.Sixty-one patients were included for analysis. Preoperatively, patients reported greatest anxiety around the operation itself and becoming blind. Reflecting postoperatively, patients reported the greatest anxiety for the operation itself. Statistically significant decreases were greatest for anxiety about the operation failing (p<0.001) and becoming blind (p<0.001). No decrease was observed for the operation itself (p=0.1).More effort must be made to specifically discuss the steps of the operation itself and the expected visual outcomes to alleviate patient anxiety. The authors hope these data can provide insight for surgeons into patient anxiety surrounding cataract surgery and help strengthen the patient-physician relationship.

  View details for DOI 10.2147/OPTH.S146135

  View details for Web of Science ID 000415187700001

  View details for PubMedID 29184388

  View details for PubMedCentralID PMC5689065

• Effect of pretreatment with antifungal agents on clinical outcomes in fungal keratitis CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Sun, C. Q., Prajna, N., Krishnan, T., Rajaraman, R., Srinivasan, M., Raghavan, A., O'Brien, K. S., McLeod, S. D., Acharya, N. R., Rose-Nussbaumer, J., Mycotic Ulcer Treatment Trial Grp 2016; 44 (9): 763-767

  Abstract

  To determine if pretreatment with antifungal agents is predictive of worse clinical outcome in a fungal keratitis clinical trial.Non-pre-specified subgroup analysis of a randomized controlled trial in a tertiary hospital.Three hundred twenty-three fungal ulcer cases with an enrolment visual acuity of 20/40 to 20/400.The Mycotic Ulcer Treatment Trial I was a randomized, double-masked trial to determine the optimal treatment for filamentous fungal keratitis at the Aravind Eye Care System, India. Enrolled cases were randomized to receive topical natamycin or voriconazole. Prior antifungal medication use, dose and duration were collected at enrolment. A subgroup analysis was performed to determine if patients using natamycin or azoles at presentation have worse clinical outcomes compared with those who were not pretreated.Three-month visual acuity (primary), 3-month infiltrate or scar size, corneal perforation and/or transplant and re-epithelialization time.Of the 323 patients enrolled, 44% presented on an antifungal agent. Pretreated patients had larger mean baseline infiltrate size (P < 0.001) and epithelial defect size (P = 0.02). Multivariate regression analysis demonstrated that pretreatment was associated with significantly worse 3-month visual acuity (P = 0.006), larger 3-month scar size (P < 0.001) and increased odds of corneal perforation and/or transplant (P = 0.001).Fungal keratitis that is smear-positive despite being pretreated with appropriate antifungal agents appears to be a risk factor for worse outcomes, likely a result of initial ulcer severity and treatment failure. These patients may benefit from more aggressive multimodal therapy at a tertiary centre.

  View details for DOI 10.1111/ceo.12794

  View details for Web of Science ID 000392711900004

  View details for PubMedID 27329780

  View details for PubMedCentralID PMC5177485

• Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II) A Randomized Clinical Trial JAMA OPHTHALMOLOGY Prajna, N., Krishnan, T., Rajaraman, R., Patel, S., Srinivasan, M., Das, M., Ray, K. J., O'Brien, K. S., Oldenburg, C. E., McLeod, S. D., Zegans, M. E., Porco, T. C., Acharya, N. R., Lietman, T. M., Rose-Nussbaumer, J., Mycotic Ulcer Treatment Trial II 2016; 134 (12): 1365-1372

  Abstract

  To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis.The 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.Study 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%.The 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.A 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 < .001 after Holms-Šidák correction for multiple comparisons).There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. All patients in this study were enrolled in India and Nepal; therefore, it is possible that organisms in this region may exhibit characteristics different from those in other regions of the world.clinicaltrials.gov Identifier: NCT00996736.

  View details for DOI 10.1001/jamaophthalmol.2016.4096

  View details for Web of Science ID 000390600300010

  View details for PubMedID 27787540

  View details for PubMedCentralID PMC6044431

• Clinical Outcomes of Descemet Membrane Endothelial Keratoplasty During the Surgeon Learning Curve Versus Descemet Stripping Endothelial Keratoplasty Performed at the Same Time. Journal of clinical & experimental ophthalmology Rose-Nussbaumer, J., Alloju, S., Chamberlain, W. 2016; 7 (5)

  Abstract

  PURPOSE: To compare outcomes after Descemet Membrane Endothelial Keratoplasty (DMEK) and traditional Descemet Stripping Endothelial Keratoplasty (DSEK) during the surgeon's DMEK learning curve in a prospective, non-randomized, consecutive, interventional case series.METHODS: Consecutive patients presenting to the university eye clinics and undergoing endothelial keratoplasty were included. Data including patient demographics, visual acuity, endothelial cell counts and complications were recorded at baseline, as well as 3 and 6 months post-operatively. The primary outcome for this study was BSCVA at 6 months. Pre-specified secondary outcomes included endothelial cell counts and complication rates.RESULTS: A total of 60 eyes of 42 consecutive patients met inclusion criteria, underwent endothelial keratoplasty, and were included in this analysis. Of these, 18 eyes of 14 patients had DSEK while 42 eyes of 28 patients had DMEK. After controlling for baseline visual acuity, study participants undergoing DMEK had a statistically significant approximately half-line improvement in visual acuity compared with DSEK at 3 months (P=0.05) but not at 6 months (P=0.22). DMEK patients experienced an average of 43% endothelial cell loss compared with 25% in DSEK. There were 5 primary graft failures after DMEK compared with 0 after DSEK and but this was not a statistically significant difference (P=0.09).CONCLUSION: During the surgeon's DMEK learning curve there was some evidence of improved visual acuity outcomes in DMEK. We observed worse 6-month endothelial cell loss among DMEK patients; however this may improve with surgeon experience.

  View details for DOI 10.4172/2155-9570.1000599

  View details for PubMedID 28018708

• Survey of Experts on Current Endothelial Keratoplasty Techniques. Journal of clinical & experimental ophthalmology Chamberlain, W., Austin, A., Terry, M., Jeng, B. H., Rose-Nussbaumer, J. 2016; 7 (5)

  Abstract

  OBJECTIVE: To survey cornea specialists' opinions on different endothelial keratoplasty techniques and to gauge the perceived need for and utility of a randomized controlled trial (RCT) comparing them.METHODS: A short survey was distributed to a group of cornea specialists at the Endothelial Keratoplasty Group meeting at the American Academy of Ophthalmology meeting in November 2015.RESULTS: Thirty-three of 80 practicing surgeons present at the EKG meeting participated in the survey, yielding a response rate of 41%. Ninety-seven percent (n=32) of our respondents reported performing Descemet's Stripping Endothelial Keratoplasty (DSEK) regularly, and 70% reported having performed Descemet's Membrane Endothelial Keratoplasty (DMEK) at least once (n=23). While most respondents (n=26, 79%) thought there was at least some evidence that DMEK is superior to DSEK in terms of visual acuity, there was less certainty about comparing ultrathin-DSEK (UT-DSEK) to DMEK with 48% (n=16) thinking there was at least some evidence of DMEK's superiority, 6% (n=2) thinking there was at least some evidence of UT-DSEK's superiority, and 30% (n=10) unsure. Seventy-two percent (n=23) of respondents thought an RCT comparing visual acuity outcomes in UT-DSEK versus DMEK would be at least moderately beneficial, and 82% (n=27) reported they were at least moderately likely to change their EK technique based on the results of said RCT.CONCLUSION: There is substantial interest in an RCT comparing visual acuity outcomes in UT-DSEK versus DMEK.

  View details for DOI 10.4172/2155-9570.1000608

  View details for PubMedID 28149669

• Paraproteinemic keratopathy as the presenting sign of hematologic malignancy AMERICAN JOURNAL OF HEMATOLOGY Mannis, T. E., Mannis, G. N., Waterhouse, E. G., Aldave, A. J., Rose-Nussbaumer, J. 2016; 91 (9): 961–62

  View details for DOI 10.1002/ajh.24327

  View details for Web of Science ID 000385237100167

  View details for PubMedID 26872417

  View details for PubMedCentralID PMC6038815

• Risk factors for low vision related functioning in the Mycotic Ulcer Treatment Trial: a randomised trial comparing natamycin with voriconazole BRITISH JOURNAL OF OPHTHALMOLOGY Rose-Nussbaumer, J., Prajna, N., Krishnan, T., Mascarenhas, J., Rajaraman, R., Srinivasan, M., Raghavan, A., Oldenburg, C. E., O'Brien, K. S., Ray, K. J., Porco, T. C., McLeod, S. D., Acharya, N. R., Keenan, J. D., Lietman, T. M., Mycotic Ulcer Treatment Trial Grp 2016; 100 (7): 929-932

  Abstract

  The Mycotic Ulcer Treatment Trial I (MUTT I) was a double-masked, multicentre, randomised controlled trial, which found that topical natamycin is superior to voriconazole for the treatment of filamentous fungal corneal ulcers. In this study, we determine risk factors for low vision-related quality of life in patients with fungal keratitis.The Indian visual function questionnaire (IND-VFQ) was administered to MUTT I study participants at 3 months. Associations between patient and ulcer characteristics and IND-VFQ subscale score were assessed using generalised estimating equations.323 patients were enrolled in the trial, and 292 (90.4%) completed the IND-VFQ at 3 months. Out of a total possible score of 100, the average VFQ score for all participants was 81.3 (range 0-100, SD 23.6). After correcting for treatment arm, each logMAR line of worse baseline visual acuity in the affected eye resulted in an average 1.2 points decrease on VFQ at 3 months (95% CI -1.8 to 0.6, p<0.001). Those who required therapeutic penetrating keratoplasty had an average of 25.2 points decrease on VFQ after correcting for treatment arm (95% CI -31.8 to -18.5, p<0.001). Study participants who were unemployed had on average 28.5 points decrease on VFQ (95% CI -46.9 to -10.2, p=0.002) after correcting for treatment arm.Monocular vision loss from corneal opacity due to fungal keratitis reduced vision-related quality of life. Given the relatively high worldwide burden of corneal opacity, improving treatment outcomes of corneal infections should be a public health priority.Clinicaltrials.gov Identifier: NCT00996736.

  View details for DOI 10.1136/bjophthalmol-2015-306828

  View details for Web of Science ID 000380747000011

  View details for PubMedID 26531051

  View details for PubMedCentralID PMC4965324

• Use of adjunctive topical corticosteroids in bacterial keratitis CURRENT OPINION IN OPHTHALMOLOGY Ni, N., Srinivasan, M., McLeod, S. D., Acharya, N. R., Lietman, T. M., Rose-Nussbaumer, J. 2016; 27 (4): 353-357

  Abstract

  Topical corticosteroid use in the setting of infectious keratitis has been a controversial issue. The aim of this review is to provide an update on the evidence for use of topical corticosteroids in addition to antibiotics in bacterial keratitis.Judicious use of steroids is postulated to limit the inflammatory component of bacterial keratitis, but can theoretically retard healing. Three small randomized controlled trials and one large-scale trial, the Steroids for Corneal Ulcers Trial, have provided the most recent evidence to address this debate. Adjunctive topical corticosteroids initiated after at least 48 h of antibiotic usage in cases of culture-proven bacterial keratitis appear generally safe in the treatment of bacterial keratitis. They may be beneficial in cases of severe ulcers especially when initiated early in the course of the infection, in non-Nocardia ulcers, and in certain Pseudomonas ulcers.Several randomized controlled trials have greatly contributed to our understanding of the controversy over steroid use in the management of bacterial keratitis. Future studies are needed to confirm subgroup analysis findings and define optimal timing, dosage, and the most appropriate treatment populations.

  View details for DOI 10.1097/ICU.0000000000000273

  View details for Web of Science ID 000378417800014

  View details for PubMedID 27096374

  View details for PubMedCentralID PMC6038813

• Changing Azole Resistance A Secondary Analysis of the MUTT I Randomized Clinical Trial JAMA OPHTHALMOLOGY Prajna, N., Lalitha, P., Rajaraman, R., Krishnan, T., Raghavan, A., Srinivasan, M., O'Brien, K. S., Zegans, M., McLeod, S. D., Acharya, N. R., Keenan, J. D., Lietman, T. M., Rose-Nussbaumer, J., Mycotic Ulcer Treatment Trial Grp 2016; 134 (6): 693-696

  Abstract

  The 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.To determine whether antifungal resistance increased during the Mycotic Ulcer Treatment Trial I (MUTT I), as measured by minimum inhibitory concentrations (MICs) in baseline cultures.This 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.Corneal smears and cultures were obtained from all study participants at baseline. Susceptibility testing was performed for each culture-positive specimen.Minimum inhibitory concentration of voriconazole and natamycin in baseline cultures.Of 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).Susceptibility 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.clinicaltrials.gov Identifier: NCT00996736.

  View details for DOI 10.1001/jamaophthalmol.2016.0530

  View details for Web of Science ID 000379596300016

  View details for PubMedID 27054515

  View details for PubMedCentralID PMC4962688

• Inter-grader Agreement of the Ocular Staining Score in the Sjogren's. International Clinical Collaborative Alliance (SICCA) Registry AMERICAN JOURNAL OF OPHTHALMOLOGY Rose-Nussbaumer, J., Lietman, T. M., Shiboski, C. H., Shiboski, S. C., Bunya, V. Y., Akpek, E. K., Srinivasan, M., Mascarenhas, J., Massaro-Giordano, G., Mcnamara, N. A., Whitcher, J. P., Gaynor, B. D., Sjogren's Int Collaborative Clinic 2015; 160 (6): 1150-1153

  Abstract

  To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists.Reliability analysis within a prospective, observational, multicenter cohort study.Those enrolled in the National Institutes of Health-funded Sjögren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining.Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85-0.96) and 0.90 for the left eye (95% CI 0.83-0.97). Corneal staining (right eye 0.86, 95% CI 0.76-0.93, left eye 0.90, 95% CI 0.81-0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80-0.93, left eye 0.85, 95% CI 0.75-0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64-0.89; left eye 0.81, 95% CI 0.68-0.90).Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjögren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test.

  View details for DOI 10.1016/j.ajo.2015.08.021

  View details for Web of Science ID 000365243400009

  View details for PubMedID 26302236

  View details for PubMedCentralID PMC4651820

• Expert opinion in the management of aqueous Deficient Dry Eye Disease (DED) BMC OPHTHALMOLOGY Sy, A., O'Brien, K. S., Liu, M. P., Cuddapah, P. A., Acharya, N. R., Lietman, T. M., Rose-Nussbaumer, J. 2015; 15: 133

  Abstract

  Dry eye disease (DED) affects millions of people worldwide. There are a variety of new treatments beyond traditional therapies such as preservative free artificial tears. Here, we conduct a survey to identify the most common treatments used among specialists and assess their interest in newer therapies.An international survey was distributed to dry eye researchers and expert practitioners via an internet survey. The survey data collected were analyzed with descriptive statistics.One hundred and fifteen respondents completed the survey; of these, 66 % were cornea specialists. The most commonly prescribed topical treatments included cyclosporine A (CSA) 0.05 % (71/104, 68 %), fluorometholone (FML) 0.1 % (59/99, 60 %), loteprednol etabonate 0.5 % (50/99, 51 %), and autologous serum eye drops (ASD; 48/97, 49 %). The most commonly prescribed non-topical medications included essential fatty acid supplements (72/104, 69 %), low-dose doxycycline (oral; 61/100, 61 %), and flaxseed supplements (32/96, 33 %) as well as punctal plugs (76/102, 75 %). Respondents reported treatment with topical corticosteroids for 2 to 8 weeks (46/86, 53 %), followed by less than 2 weeks (24/86, 28 %) and with topical CSA between 2 to 8 weeks (45/85, 53 %) followed by 2 to 6 months (24/85, 28 %). The top three signs and symptoms reported to indicate treatment response were, in order, fluorescein staining of the cornea, reduction in foreign body sensation, and reduction in burning sensation.This survey offers insight into current expert opinion in the treatment of DED. The results of this survey are hypothesis generating and will aid in the design of future clinical studies.

  View details for DOI 10.1186/s12886-015-0122-z

  View details for Web of Science ID 000362808500001

  View details for PubMedID 26462481

  View details for PubMedCentralID PMC4604775

• Association of Pretreatment With Antifungal Medication and Fungal Resistance in the Mycotic Ulcer Treatment Trial I JAMA OPHTHALMOLOGY Prajna, N., Prajna, L., O'Brien, K. S., Sun, C. Q., Acharya, N., Lietman, T. M., Rose-Nussbaumer, J., Mycotic Ulcer Treatment Trial Grp 2015; 133 (10): 1210-1211

  View details for DOI 10.1001/jamaophthalmol.2015.2040

  View details for Web of Science ID 000362965300025

  View details for PubMedID 26110254

  View details for PubMedCentralID PMC4962690

• Current Concepts in the Management of Unique Post-keratoplasty Infections. Current ophthalmology reports Schallhorn, J. M., Rose-Nussbaumer, J. 2015; 3 (3): 184-191

  Abstract

  As corneal transplantation has evolved, the spectrum of post-surgical infection has changed and often presents a diagnostic and therapeutic challenge. Lamellar techniques hold the potential of improved outcomes and decreased post-operative complications, however, they create a lamellar interface, which is a potential space for sequestration of infectious organisms. In addition, while keratoprosthesis offers vision to patients who are poor candidates for traditional keratoplasty, infectious complications can be severe and sight threatening. Although antimicrobials remain the mainstay of treatment, definitive management often requires surgical intervention.

  View details for PubMedID 26618075

• Vision-Related Quality-of-Life Outcomes in the Mycotic Ulcer Treatment Trial I A Randomized Clinical Trial JAMA OPHTHALMOLOGY Rose-Nussbaumer, J., Prajna, N., Krishnan, K., Mascarenhas, J., Rajaraman, R., Srinivasan, M., Raghavan, A., Oldenburg, C. E., O'Brien, K. S., Ray, K. J., McLeod, S. D., Porco, T. C., Lietman, T. M., Acharya, N. R., Keenan, J. D., Mycotic Ulcer Treatment Trial I Gr 2015; 133 (6): 642-646

  Abstract

  Given the limitations in health care resources, quality-of-life measures for interventions have gained importance.To determine whether vision-related quality-of-life outcomes were different between the natamycin and voriconazole treatment arms in the Mycotic Ulcer Treatment Trial I, as measured by an Indian Vision Function Questionnaire.Secondary analysis (performed October 11-25, 2014) of a double-masked, multicenter, randomized, active comparator-controlled, clinical trial at multiple locations of the Aravind Eye Care System in South India that enrolled patients with culture- or smear-positive filamentous fungal corneal ulcers who had a baseline visual acuity of 20/40 to 20/400 (logMAR of 0.3-1.3).Study participants were randomly assigned to topical voriconazole, 1%, or topical natamycin, 5%.Subscale score on the Indian Vision Function Questionnaire from each of the 4 subscales (mobility, activity limitation, psychosocial impact, and visual function) at 3 months.A total of 323 patients were enrolled in the trial, and 292 (90.4%) completed the Indian Vision Function Questionnaire at 3 months. The majority of study participants had subscale scores consistent with excellent function. After adjusting for baseline visual acuity and organism, we found that study participants in the natamycin-treated group scored, on average, 4.3 points (95% CI, 0.1-8.5) higher than study participants in the voriconazole-treated group (P = .046). In subgroup analyses looking at ulcers caused by Fusarium species and adjusting for baseline best spectacle-corrected visual acuity, the natamycin-treated group scored 8.4 points (95% CI, 1.9-14.9) higher than the voriconazole-treated group (P = .01). Differences in quality of life were not detected for patients with Aspergillus or other non-Fusarium species as the causative organism (1.5 points [95% CI, -3.9 to 6.9]; P = .52).We found evidence of improvement in vision-related quality of life among patients with fungal ulcers who were randomly assigned to natamycin compared with those randomly assigned to voriconazole, and especially among patients with Fusarium species as the causative organism. Incorporation of quality-of-life measures in clinical trials is important to fully evaluate the effect of the studied interventions.clinicaltrials.gov Identifier:NCT00996736.

  View details for DOI 10.1001/jamaophthalmol.2015.0319

  View details for Web of Science ID 000356044400013

  View details for PubMedID 25764482

  View details for PubMedCentralID PMC4962866

• Training clinicians treating HIV to diagnose cytomegalovirus retinitis BULLETIN OF THE WORLD HEALTH ORGANIZATION Heiden, D., Tun, N., Maningding, E., Heiden, M., Rose-Nussbaumer, J., Chan, K., Khizniak, T., Yakubenko, A., Lewallen, S., Keenan, J. D., Saranchuk, P. 2014; 92 (12): 903-908

  Abstract

  Acquired immunodeficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis continues to be a neglected source of blindness in resource-poor settings. The main issue is lack of capacity to diagnose CMV retinitis in the clinical setting where patients receive care and all other opportunistic infections are diagnosed.We developed and implemented a four-day workshop to train clinicians working in human immunodeficiency virus (HIV) clinics how to perform binocular indirect ophthalmoscopy and diagnose CMV retinitis. Workshops comprised both classroom didactic instruction and direct clinical eye examinations in patients with advanced AIDS. Between 2007 and 2013, 14 workshops were conducted in China, Myanmar and the Russian Federation.Workshops were held with local clinicians at HIV clinics supported by nongovernmental organizations, public-sector municipal hospitals and provincial infectious disease referral hospitals. Each setting had limited or no access to locally- trained ophthalmologists, and an HIV-infected population with advanced disease.Clinicians learnt how to do binocular indirect ophthalmoscopy and to diagnose CMV retinitis. One year after the workshop, 32/38 trainees in Myanmar did systematic eye examination for early diagnosis of CMV retinitis as standard care for at-risk patients. In China and the Russian Federation, the success rates were lower, with 10/15 and 3/5 trainees, respectively, providing follow-up data.Skills necessary for screening and diagnosis of CMV retinitis can be taught in a four-day task-oriented training workshop. Successful implementation depends on institutional support, ongoing training and technical support. The next challenge is to scale up this approach in other countries.

  View details for DOI 10.2471/BLT.14.142372

  View details for Web of Science ID 000346957700015

  View details for PubMedID 25552774

  View details for PubMedCentralID PMC4264397

• Clinically Symptomatic Vasitis: Clinical Correlations in a Rare Condition SYSTEMS BIOLOGY IN REPRODUCTIVE MEDICINE Clavijo, R. I., Rose-Nussbaumer, J., Turek, P. J. 2010; 56 (6): 445-449

  Abstract

  Vasitis, or inflammation of the vas deferens, is a rare condition. When diagnosed pathologically, it has been linked to vasectomy, prostatectomy, and herniorrhaphy. When diagnosed clinically, relationships with potential causative factors are unclear. We investigated the clinical factors associated with clinically symptomatic vasitis in a retrospective series of patients. From the history, physical examination, and clinical course, we analyzed associated risk factors. Clinical care patterns were also examined to assess the effectiveness of different treatments. Among 11 patients, the mean patient age at presentation was 47 years (range 29-60 years). The mean diameter of the affected vas deferens was 0.97 cm. Associated procedures included ipsilateral herniorrhaphy (4 patients), radical prostatectomy (2 patients), perianal fistulectomy (1 patient), and bilateral testicular biopsy (1 patient). Furthermore, epididymitis was reported in one patient after testicular trauma, and another patient had congenital unilateral absence of the vas deferens. No patient had a history of vasectomy. Three patients were HIV positive and 6 were active smokers. Six of the 11 patients improved with medical management that included nonsteroidal and steroidal anti-inflammatories and antibiotics. One patient was lost to follow-up. Similar to studies of pathologically detected vasitis, this unique study of clinical vasitis suggests that prior herniorrhaphy, prostatectomy, and possibly HIV infection may be risk factors for its development. In addition, the use of anti-inflammatories and antibiotics warrants further investigation as potentially effective treatments.

  View details for DOI 10.3109/19396368.2010.519814

  View details for Web of Science ID 000284219300005

  View details for PubMedID 20964559