Successful treatment of an extensively drug-resistant pseudomonal ulcer associated with contaminated artificial tears.

Purpose: To report a case of bacterial keratitis caused by an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain linked to contaminated artificial tears in the United States. The ulcer was successfully treated without perforation or extracorneal spread. Observations: An 81-year-old patient presented with a corneal ulcer of the right eye. The patient had a notable complex ocular history including glaucoma and corneal edema from corneal decompensation after prolonged retained lens fragment. Despite starting hourly fortified tobramycin and vancomycin eye drops, the infiltrate grew significantly by the next day. Bacterial culture grew Pseudomonas aeruginosa that was resistant to all tested antibiotics except for intermediate susceptibility to colistin and susceptibility to cefiderocol. Tobramycin-soaked collagen shields were applied daily for three days, and the patient was started on fortified colistin eye drops. The ulcer improved and, after seven weeks of therapy, the infiltrate resolved and resulted in a large central corneal scar. Conclusions and Importance: A combination of fortified colistin and tobramycin (administered via a combination of fortified eye drops and tobramycin-soaked collagen shields) appears to be an effective treatment option for extensively drug-resistant Pseudomonas aeruginosa corneal ulcers.

How to assess pharmacogenomic tests for implementation in the NHS in England.

AIMS: Pharmacogenomic testing has the potential to target medicines more effectively towards those who will benefit and avoid use in individuals at risk of harm. Health economies are actively considering how pharmacogenomic tests can be integrated into health care systems to improve use of medicines. However, one of the barriers to effective implementation is evaluation of the evidence including clinical usefulness, cost-effectiveness, and operational requirements. We sought to develop a framework that could aid the implementation of pharmacogenomic testing. We take the view from the National Health Service (NHS) in England. METHODS: We used a literature review using EMBASE and Medline databases to identify prospective studies of pharmacogenomic testing, focusing on clinical outcomes and implementation of pharmacogenomics. Using this search, we identified key themes relating to the implementation of pharmacogenomic tests. We used a clinical advisory group with expertise in pharmacology, pharmacogenomics, formulary evaluation, and policy implementation to review data from our literature review and the interpretation of these data. With the clinical advisory group, we prioritized themes and developed a framework to evaluate proposals to implement pharmacogenomics tests. RESULTS: Themes that emerged from review of the literature and subsequent discussion were distilled into a 10-point checklist that is proposed as a tool to aid evidence-based implementation of pharmacogenomic testing into routine clinical care within the NHS. CONCLUSION: Our 10-point checklist outlines a standardized approach that could be used to evaluate proposals to implement pharmacogenomic tests. We propose a national approach, taking the view of the NHS in England. Using this approach could centralize commissioning of appropriate pharmacogenomic tests, reduce inequity and duplication using regional approaches, and provide a robust and evidence-based framework for adoption. Such an approach could also be applied to other health systems.

Development and Validation of a Natural Language Processing Algorithm to Extract Descriptors of Microbial Keratitis From the Electronic Health Record.

PURPOSE: The purpose of this article was to develop and validate a natural language processing (NLP) algorithm to extract qualitative descriptors of microbial keratitis (MK) from electronic health records. METHODS: In this retrospective cohort study, patients with MK diagnoses from 2 academic centers were identified using electronic health records. An NLP algorithm was created to extract MK centrality, depth, and thinning. A random sample of patient with MK encounters were used to train the algorithm (400 encounters of 100 patients) and compared with expert chart review. The algorithm was evaluated in internal (n = 100) and external validation data sets (n = 59) in comparison with masked chart review. Outcomes were sensitivity and specificity of the NLP algorithm to extract qualitative MK features as compared with masked chart review performed by an ophthalmologist. RESULTS: Across data sets, gold-standard chart review found centrality was documented in 64.0% to 79.3% of charts, depth in 15.0% to 20.3%, and thinning in 25.4% to 31.3%. Compared with chart review, the NLP algorithm had a sensitivity of 80.3%, 50.0%, and 66.7% for identifying central MK, 85.4%, 66.7%, and 100% for deep MK, and 100.0%, 95.2%, and 100% for thin MK, in the training, internal, and external validation samples, respectively. Specificity was 41.1%, 38.6%, and 46.2% for centrality, 100%, 83.3%, and 71.4% for depth, and 93.3%, 100%, and was not applicable (n = 0) to the external data for thinning, in the samples, respectively. CONCLUSIONS: MK features are not documented consistently showing a lack of standardization in recording MK examination elements. NLP shows promise but will be limited if the available clinical data are missing from the chart.

Ultrasound Biomicroscopy in Pseudophakic Patients with Unexplained Recurrent Hyphema or Vitreous Hemorrhage.

PURPOSE: To describe IOL haptic with iris or ciliary body touch on ultrasound biomicroscopy (UBM) in pseudophakic patients with unexplained recurrent hyphema or vitreous hemorrhage. METHODS: Retrospective chart review of 10 patients who presented with unexplained recurrent hyphema and or vitreous hemorrhage. RESULTS: There were eight posterior chamber intraocular lenses (PCIOL) and two sulcus lenses. Four cases had a history of glaucoma; two cases which had a history of trabeculectomy were found to have some bridging vessels along the sclerostomy requiring argon laser gonioplasty. No preceding trauma or retinal pathology was found. UBM revealed haptic-ciliary body or haptic-iris touch in cases with a PCIOL and haptic-iris touch in both sulcus lens cases. One case with a PCIOL did not reveal any haptic-iris or ciliary body touch and instead displacement of the optic temporally, though haptics remained intracapsular. CONCLUSIONS: UBM is a useful tool to evaluate haptic position in pseudophakic patients with unexplained recurrent hyphema and/or vitreous hemorrhage. This is the largest existing series of patients with this clinical entity reported from a single institution.

Macular edema is a rare finding in untreated vitreoretinal lymphoma: small case series and review of the literature.

BACKGROUND: To determine the occurrence of macular edema (ME) in vitreoretinal lymphoma (VRL). METHODS: Retrospective analysis of 17 patients (31 eyes) with VRL. A review of the literature was done as well. RESULTS: Nine patients (15 eyes) had fluorescein angiography and/or optical coherence tomography at presentation. In the ME group (six eyes of four patients), three patients (five eyes) had prior chemotherapy and radiation. Excluding eyes with radiation retinopathy (three eyes), rate of ME was 25% (3/12). When two unirradiated fellow eyes of eyes with radiation retinopathy were also excluded, ME rate was 10% (1/10). Excluding the eyes with intraocular surgery, the rate of ME was 0%. In the group without ME (nine eyes of six patients), one patient (one eye) was treated with chemotherapy and radiation and three patients (five eyes) with chemotherapy. Review of the literature showed that the ME was found between 2 and 60% of cases, but most of the cases with ME had prior interventions. CONCLUSIONS: Macular edema in VRL is not uncommon but usually related to prior interventions. Macular edema as an initial presentation of VRL is rare.

Telemedicine for ophthalmic consultation services: use of a portable device and layering information for graders.

Introduction We compared remote, image-based patient consultations to in-person consultations at emergency department and inpatient hospital settings. Methods Patients evaluated by the ophthalmic consultation services (gold standard) were imaged over a two-week period. A trained study coordinator took anterior segment photographs (AS) and posterior segment photographs (PS) with a portable camera (PictorPlus, Volk Optical, Cleveland, OH). Ophthalmologists (graders) determined photograph quality, presence of pathology, and their confidence in disease detection. At a separate session, graders reassessed photographs accompanied by a one-sentence summary of demographics and chief complaint (CHx). We computed accuracy and reliability statistics. Results We took AS photographs of 24 eyes of 15 patients and PS photographs of 39 eyes of 20 patients. The majority of images were rated as acceptable or excellent in quality (AS: 89-96%; PS: 70-75%). Graders detected AS pathology with 62-81% sensitivity based on photographs, increasing to 87-88% sensitivity with photographs plus CHx. Graders detected PS pathology with 79-86% sensitivity based on a photograph only, increasing to 100% sensitivity with photographs plus CHx. Discussion In this pilot study, there is evidence that portable ophthalmic imaging technologies could enable ophthalmologists to remotely evaluate anterior and posterior segment eye diseases with good sensitivity. The ophthalmologist could detect ocular pathology on photographs more accurately if they were provided brief clinical information.

Fungal Endophthalmitis Associated With DSAEK and Thermal Sclerostomy.

An 85-year-old man with remote thermal sclerostomy and Descemet's stripping automated endothelial keratoplasty (DSAEK) in the right eye presented urgently for pain and blurred vision in that eye. Examination revealed bleb purulence and vitreous cellular aggregates concerning for endophthalmitis. Microscopy of a vitreous sample revealed yeast and pseudohyphae. He developed corneal infiltrates consistent with fungal infection. Therapy included topical, intravitreal, and systemic antifungals voriconazole and amphotericin. Fungal pathogens have very rarely been reported to cause bleb-associated endophthalmitis and should be considered in addition to bacterial pathogens. Vitreous aspiration should be performed in all cases of bleb-related endophthalmitis and include fungal studies. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:691-693.].

Corneal High-Order Aberrations and Backscatter in Fuchs' Endothelial Corneal Dystrophy.

PURPOSE: Suboptimal visual acuity after endothelial keratoplasty has been attributed to increased anterior corneal high-order aberrations (HOAs). In this study, we determined anterior and posterior corneal HOAs over a range of severity of Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 108 eyes (62 subjects) with a range of severity of FECD and 71 normal eyes (38 subjects). METHODS: All corneas were examined by using slit-lamp biomicroscopy to determine the severity of FECD versus normality. Fuchs' endothelial corneal dystrophy corneas were categorized as mild, moderate, or advanced according to the area and confluence of guttae and the presence of clinically visible edema. Normal corneas were devoid of any guttae. Wavefront errors from the anterior and posterior corneal surfaces were derived from Scheimpflug images and expressed as Zernike polynomials through the sixth order over a 6-mm diameter optical zone. Backscatter from the anterior 120 µm and posterior 60 µm of the cornea also was measured from Scheimpflug images and was standardized to a fixed scatter source. Variables were compared between FECD and control eyes by using generalized estimating equation models to adjust for age and correlation between fellow eyes. MAIN OUTCOME MEASURES: High-order aberrations, expressed as root mean square of wavefront errors, and backscatter of the anterior and posterior cornea. RESULTS: Total anterior corneal HOAs were increased in moderate (0.61±0.27 µm, mean ± standard deviation; P = 0.01) and advanced (0.66±0.28 µm; P = 0.01) FECD compared with controls (0.47±0.16 µm). Total posterior corneal HOAs were increased in mild (0.22±0.09 µm; P = 0.017), moderate (0.22±0.08 µm; P < 0.001), and advanced (0.23±0.09 µm; P < 0.001) FECD compared with controls (0.16±0.03 µm). Anterior and posterior corneal backscatter were higher for all severities of FECD compared with controls (P ≤ 0.02, anterior; P ≤ 0.001, posterior). CONCLUSIONS: Anterior and posterior corneal HOAs and backscatter are higher than normal even in early stages of FECD. The early onset of HOAs in FECD might contribute to the persistence of HOAs and incomplete visual rehabilitation after endothelial keratoplasty.

Corneal abnormalities early in the course of Fuchs' endothelial dystrophy.

PURPOSE: Corneas with advanced Fuchs' endothelial dystrophy that require endothelial keratoplasty manifest anterior corneal structural and cellular abnormalities that have been associated with visual deficits before and after endothelial keratoplasty. In this study, we determined the onset of these abnormalities in the course of the disease. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty-three eyes (39 subjects) with a range of severity of Fuchs' dystrophy and 25 eyes (13 subjects) with normal corneas. METHODS: All corneas were examined using slit-lamp biomicroscopy, ultrasonic pachymetry, and confocal microscopy. The clinical grade of Fuchs' dystrophy was assessed according to the presence and extent of guttae and clinically evident edema and was categorized as mild (grades 1 and 2), moderate (grades 3 and 4), or advanced (grades 5 and 6). Normal corneas were devoid of any central guttae (grade 0). Corneal backscatter (haze) was measured from the confocal image light intensity profile. Stromal cell density and number and the presence of abnormal subepithelial cells were determined from confocal images. Comparisons between groups were made by using generalized estimating equation models. MAIN OUTCOME MEASURES: Anterior corneal backscatter, stromal cell density and number, presence of subepithelial cells, and central corneal thickness. RESULTS: Anterior corneal backscatter was 18% to 67% higher in eyes with moderate and advanced Fuchs' dystrophy compared with normal eyes (P ≤ 0.003); a similar trend was noted in mild Fuchs' dystrophy eyes compared with normal eyes (P = 0.08). Stromal cell density and the absolute number of stromal cells in the anterior 10% of the stroma were approximately 20% and 27% lower, respectively, in Fuchs' dystrophy (regardless of severity) compared with normal (P < 0.001). Abnormal subepithelial cells were visible in 9%, 19%, and 30% of corneas with mild, moderate, and advanced Fuchs' dystrophy, respectively. Only corneas with advanced Fuchs' dystrophy were thicker than normal (P < 0.001). CONCLUSIONS: Anterior corneal cellular and structural abnormalities begin early in the course of Fuchs' dystrophy, before the onset of clinically evident edema. The chronicity of these changes can explain their incomplete resolution after endothelial keratoplasty, and understanding the onset of these may help to determine the optimal time to intervene to achieve best outcomes.

Assessing the effectiveness of surface cleaning methods in intravitreal injection procedure rooms.

PURPOSE: To assess cleaning effectiveness of room surfaces in an office-based intravitreal injection practice by using adenosine triphosphate (ATP) luminometry. DESIGN: Prospective, comparative case series. PARTICIPANTS: A total of 792 intravitreal injection room surfaces were sampled (396 before cleaning, 396 after cleaning) using 3 cleaning methods. METHODS: Three cleaning methods were evaluated: baseline terminal cleaning, directed terminal cleaning, and enhanced terminal cleaning. For each method, residual ATP bioburden (relative light units [RLUs]/sample) was sampled from 9 high-touch injection room surfaces before and after terminal cleaning using the 3M Clean-Trace ATP System (3M Inc, St. Paul, MN). Surface ATP RLUs were used to compare cleaning methods and against an ATP benchmark of fewer than 250 RLU. Differences between cleaning methods were compared by using paired t tests with Bonferroni correction for 3 comparisons. MAIN OUTCOME MEASURES: Surface ATP RLU levels. RESULTS: In baseline terminal cleaning and directed terminal cleaning, the median ATP level of all surfaces exceeded threshold when sampled after terminal cleaning (391 RLU and 264 RLU, respectively), and levels were increased significantly at the completion of the injection clinic and before terminal cleaning (780 RLU and 626 RLU, respectively; P < 0.003). In enhanced terminal cleaning, the median ATP level was below threshold after terminal cleaning (71 RLU), was unchanged at the completion of injection clinic and before terminal cleaning (63 RLU; P = 0.27), and was significantly lower than after the baseline terminal and directed terminal cleaning methods (P < 0.003). CONCLUSIONS: An easily adopted enhanced terminal cleaning program reduced surface ATP bioburden in intravitreal injection rooms to less than clean benchmarks used in nonophthalmologic healthcare settings.

An evidence-based clinical protocol for diagnosis of acute appendicitis decreased the use of computed tomography in children.

PURPOSE: The increased use of computed tomography (CT) to diagnose appendicitis in children has led to a concern for the possibility of increased CT-related cancer morbidity. We designed a clinical protocol for the diagnosis and treatment of appendicitis in children in an attempt to decrease the use of CT scans at our institution. METHODS: Patients who had surgical consultation for suspected appendicitis were placed on the clinical protocol. Data concerning diagnosis and treatment were collected prospectively. Retrospective data from patients admitted to our institution with acute appendicitis before the clinical protocol were collected as historical controls. RESULTS: One hundred twelve patients were diagnosed and treated by our protocol between June and November 2009. Of these, 100 patients underwent an appendectomy for acute appendicitis. They were compared with 146 patients from 2007. In-house CT use decreased from 71.2% to 51.7% (P = .01). Preoperative ultrasound use increased from 2.7% to 21% (P < .001). The negative appendectomy rate increased (6.8% vs 11%, P = .25). CONCLUSIONS: Our findings suggest that the implementation of an evidence-based clinical protocol for the diagnosis and treatment of acute appendicitis in children may safely decrease the use of CT scans and increase the use of ultrasound.

Hepatic epithelioid hemangioendothelioma: MR imaging findings.

We report the MRI findings in three patients with pathologically proven hepatic epithelioid hemangioendothelioma, a rare tumor of the liver that is not well described in the MR imaging literature. The recognition of the imaging features of this rare malignancy may help further early detection and surgical treatment of this potentially curable disease.

Appendectomy using single-incision pediatric endosurgery for acute and perforated appendicitis.

BACKGROUND: Single-incision pediatric endosurgical (SIPES) appendectomy has been reported in few pediatric surgical centers. We have adopted the technique recently and have offered it to all patients in whom appendectomy was indicated. The purpose of this study was to report our experience with SIPES appendectomy for acute appendicitis, perforated appendicitis, and interval appendectomy, and to compare the results with those from patients who underwent conventional laparoscopic appendectomy 1 year previously. METHODS: After IRB approval, data on all SIPES appendectomies performed in our hospital were prospectively collected, including operative time, intra- and postoperative complications, conversion rate, blood loss, and hospital length of stay. Cases were stratified into three categories: acute appendicitis, perforated appendicitis, and interval appendectomy. They were compared to patients operated on in 2007 using conventional laparoscopic (three-trocar) appendectomy. RESULTS: During the study period, 75 SIPES appendectomies were undertaken. Mean age was 11 years (range = 2-19 years) and mean weight was 45 kg (range = 12-132 kg). All SIPES appendectomies were completed laparoscopically, and additional trocars were placed in 20% of cases. SIPES interval appendectomies took the longest and had the highest conversion rate (33%). Follow-up data was available in 63 patients (82%) at a median of 3 weeks. There were three wound infections in the SIPES group (4%) and one in the 151 control patients. Compared to historic controls, operative time was shorter with SIPES compared to conventional laparoscopy for acute appendicitis (37 ± 12.3 vs. 44.1 ± 20.3 min, p = 0.01, 95% CI = 32-42 min). CONCLUSION: SIPES appendectomy is a very good alternative to the conventional laparoscopic approach, especially for acute appendicitis. It is technically more challenging for perforated appendicitis and interval appendectomy. Yet, with appropriate consideration and skill, scarless appendectomy is achievable.

Synthesis of Chiral Aziridines through Decarboxylative Generation of Sulfur Ylides and their Reaction with Chiral Sulfinyl Imines.

Reaction of sulfur ylide with a series of aryl substituted chiral non-racemic sulfinyl imines afforded the corresponding aziridines in high yield and good stereoselection. The sulfur ylides were generated by the thermally induced decarboxylation of carboxymethylsulfonium betaines. A drop in the diastereomeric ratio was observed when going from electron deficient to electron releasing aryl substituted imines. Sulfonium methylidene aziridinations involving the decarboxylation of carboxymethylsulfonium betaine functionality compliments existing technologies with the advantages of the reaction protocol, levels of conversion and scope.

Aryl-substituted sulfonium betaines: preparation and use in the epoxidation of aldehydes.

Thermally induced decarboxylation of carboxymethylsulfonium betaines results in formation of the corresponding sulfur ylides in situ. Decarboxylation rates for a range of arylcarboxymethylsulfonium betaine salts have been determined using NMR spectroscopy, and the efficiency of ylide generation and trapping has been evaluated via methylidene transfer to a range of aldehydes to form epoxides.