Ipsilateral Lesion Detection Refinement for Tomosynthesis.

Computer-aided detection (CAD) frameworks for breast cancer screening have been researched for several decades. Early adoption of deep-learning models in CAD frameworks has shown greatly improved detection performance compared to traditional CAD on single-view images. Recently, studies have improved performance by merging information from multiple views within each screening exam. Clinically, the integration of lesion correspondence during screening is a complicated decision process that depends on the correct execution of several referencing steps. However, most multi-view CAD frameworks are deep-learning-based black-box techniques. Fully end-to-end designs make it very difficult to analyze model behaviors and fine-tune performance. More importantly, the black-box nature of the techniques discourages clinical adoption due to the lack of explicit reasoning for each multi-view referencing step. Therefore, there is a need for a multi-view detection framework that can not only detect cancers accurately but also provide step-by-step, multi-view reasoning. In this work, we present Ipsilateral-Matching-Refinement Networks (IMR-Net) for digital breast tomosynthesis (DBT) lesion detection across multiple views. Our proposed framework adaptively refines the single-view detection scores based on explicit ipsilateral lesion matching. IMR-Net is built on a robust, single-view detection CAD pipeline with a commercial development DBT dataset of 24675 DBT volumetric views from 8034 exams. Performance is measured using location-based, case-level receiver operating characteristic (ROC) and case-level free-response ROC (FROC) analysis.

Systemic and Ocular Comorbidities of Black, Hispanic, and White Women with Cataracts.

Background: Cataracts are one of the leading causes of blindness in the world and disproportionately affect the elderly people and women. Sex- and race-related differences in cataract formation are not well understood. Furthermore, race and socioeconomic factors can play a role in developing systemic diseases. Earlier studies have supported a link between certain systemic diseases and cataract formation. Our study examined race-related differences in ocular and systemic comorbidities and analyzed differences among races and insurance types for cataract surgery visual outcomes among female patients with cataracts. Materials and Methods: Data were collected retrospectively and patients were grouped by race and insurance classifications. Female patients at a large tertiary center with an International Classification of Disease, 9th Edition (ICD-9) or ICD-10 cataract diagnosis or cataract extraction procedure code between January 2013 and June 2018 were included. A total of 909 female patients were included in the study. Frequency of systemic and ocular comorbidities was analyzed. Demographic factors were also compared among races. Finally, characteristics of cataract surgery patients, such as age at surgery, preoperative best-corrected visual acuity (BCVA), and visual outcomes among races and insurance types were analyzed. Results: There are differences among races for frequency of smoking, hemoglobin A1c, hypertension, and diabetes mellitus in female patients with cataracts and differences among races and insurance types for preoperative BCVA for patients who underwent cataract surgery (p < 0.001 for all). Conclusions: Female minority and non-minority patients with cataracts have a high frequency of systemic and ocular comorbidities at our county hospital. Patients with no insurance and white and Hispanic patients had worse preoperative BCVA.

Cataract Surgery Considerations for Diabetic Patients.

PURPOSE OF REVIEW: Given the epidemiology and demographic trends of diabetes mellitus and cataracts, ophthalmologists are likely to encounter patients with both comorbidities at an increasing frequency. Patients with diabetes represent a higher risk population than healthy patients for cataract surgery. In this review, we discuss key risks and risk-mitigation practices when performing cataract surgery on these patients. RECENT FINDINGS: Patients with diabetes continue to represent a high-risk surgical population: Nagar et al. suggest a dose-dependent relationship may exist between number of intravitreal injections and likelihood of posterior capsular rupture. However, novel treatments are improving outcomes for patients with diabetes. Several studies have reported intracameral phenylephrine/ketorolac may reduce the incidence of post-operative cystoid macular edema while others have discussed the efficacy of pre-treatment and post-treatment with intravitreal bevacizumab on improving cataract surgery outcomes in patients with diabetic retinopathy. Pre-operatively, ophthalmologists should perform an enhanced evaluation, consider timing and lens selection decisions, and complete any appropriate pre-operative treatment. Peri-operatively, surgeons should be aware of pupillary dilation adjustments, combination surgery options, and potential complications. Post-operatively, clinicians should address pseudophakic cystoid macular edema, diabetic macular edema, diabetic retinopathy, and posterior capsular opacification.

Orbital Varix Masquerading as an Intraorbital Lymphoma.

Clinical context was paramount to the diagnosis and management of a patient with periorbital pain and a history of systemic lymphoma.

Eyes of a Hurricane: The Effect of Hurricane Harvey on Ophthalmology Consultations at Houston's County Hospital.

OBJECTIVE: This study aimed to characterize ophthalmology consultations ordered after Hurricane Harvey compared to consultations ordered during the same time period of the prior year. METHODS: A retrospective chart review was performed at an urban, level 1 trauma center of a county hospital. All patients were included who received an electronic health record, documented ophthalmology consultation order between September 2017 and October 2017 (the time period immediately following Hurricane Harvey) or September 2016 and October 2016. Patient demographic risk factors were collected. Patient ICD10 clinical diagnoses were categorized as extraocular, intraocular, infectious, physiological, or other, and then subcategorized as trauma or non-trauma-related. A geographical heat map was generated to compare the changes in diagnosis volume by zip code to the magnitude of rainfall in the county. RESULTS: Following Hurricane Harvey, ophthalmology consultation volume decreased, number of infectious ophthalmology diagnoses increased (P < 0.001), percentage of patients on immunosuppression increased (P < 0.001), and the number of private insurance payers increased while the number of county-funded insurance payers decreased (P = 0.003). CONCLUSIONS: The risk of infectious eye diagnosis was double the risk of traumatic eye diagnosis from Hurricane Harvey flooding. During public disaster planning, different ophthalmological medical resources and responses should be considered for flooding versus high-wind events.

Process Mapping and Activity-Based Costing of the Intravitreal Injection Procedure.

PURPOSE/AIM OF THE STUDY: To quantify the cost of performing an intravitreal injection (IVI) utilizing activity-based costing (ABC), which allocates a cost to each resource involved in a manufacturing process. MATERIALS AND METHODS: A prospective, observational cohort study was performed at an urban, multi-specialty ophthalmology practice affiliated with an academic institution. Fourteen patients scheduled for an IVI-only visit with a retina ophthalmologist were observed from clinic entry to exit to create a process map of time and resource utilization. Indirect costs were allocated with ABC and direct costs were estimated based on process map observations, internal accounting records, employee interviews, and nationally-reported metrics. The primary outcome measure was the cost of an IVI procedure in United States dollars. Secondary outcomes included operating income (cost subtracted from revenue) of an IVI and patient-centric time utilization for an IVI. RESULTS: The total cost of performing an IVI was $128.28; average direct material, direct labor, and overhead costs were $2.14, $97.88, and $28.26, respectively. Compared to the $104.40 reimbursement set by the Centers for Medicare and Medicaid Services for Current Procedural Terminology code 67028, this results in a negative operating income of -$23.88 (-22.87%). The median clinic resource-utilizing time to complete an IVI was 32:58 minutes (range [19:24-1:28:37]); the greatest bottleneck was physician-driven electronic health record documentation. CONCLUSIONS: Our study provides an objective and accurate cost estimate of the IVI procedure and illustrates how ABC may be applied in a clinical context. Our findings suggest that IVIs may currently be undervalued by payors.

A virtual COVID-19 ophthalmology rotation.

The coronavirus (COVID-19) pandemic temporarily suspended medical student involvement in clinical rotations, resulting in the need to develop virtual clinical experiences. The cancellation of clinical ophthalmology electives and away rotations reduces opportunities for exposure to the field, to network with faculty, conduct research, and prepare for residency applications. We review the literature and discuss the impact and consequences of COVID-19 on undergraduate medical education with an emphasis on ophthalmic undergraduate medical education. We also discuss innovative learning modalities used from medical schools around the world during the COVID-19 pandemic such as virtual didactics, online cases, and telehealth. Finally, we describe a novel, virtual neuro-ophthalmology elective created to educate medical students on neuro-ophthalmology foundational principles, provide research and presentation opportunities, and build relationships with faculty members. These innovative approaches represent a step forward in further improving medical education in ophthalmology during COVID-19 pandemic and beyond.

Efficacy of quality improvement and patient safety workshops for students: a pilot study.

BACKGROUND: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes. METHODS: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause Analysis (RCA), Plan-Do-Study-Act (PDSA) Cycles, Evidence Based Medicine (EBM), and Patient Handoffs. Each workshop included a hands-on component to engage learners in practical applications of QI/PS skills in their careers. Change in knowledge, attitudes, and behaviors was assessed via pre- and post-surveys using 5-point Likert scales, and analyzed using either the McNemar test or non-parametric Wilcoxon signed-rank test. Surveys also gathered qualitative feedback regarding strengths, future areas for improvement, and reasons for attending the workshops. RESULTS: Data was collected from 88.5% of learners (n = 185/209); 19.5% of learners reported prior formal instruction in these topics. Statistically significant improvements in learners' confidence were observed for each workshop. Additionally, after attending workshops, learners felt comfortable teaching the learned QI/PS skill to colleagues (mean pre/post difference 1.96, p < 0.0001, n = 139) and were more likely to pursue QI/PS projects in their careers (mean pre/post difference 0.45, p < 0.0001, n = 139). Lastly, learners demonstrated a statistically significant increase in knowledge in four out of five skills workshop topics. CONCLUSION: Few medical students have formal instruction in QI/PS tools. This pilot study highlights advantages of incorporating an innovative, student-directed modified 'flipped classroom' methodology, with a focus on active experiential learning and minimal didactic instruction.

Regional Comparison of Goblet Cell Number and Area in Exposed and Covered Dry Eyes and Their Correlation with Tear MUC5AC.

To compare goblet cell (GC) number and area in the covered superior (SB) versus exposed temporal (TB) bulbar conjunctiva in control versus aqueous tear deficient eyes (ATD) and evaluate correlation with tear MUC5AC protein. SB and TB impression cytology performed on control eyes, Sjögren syndrome (SS) ATD, and non-SS ATD was stained with period acid Schiff. GC number and area were measured with image analysis software. Protein-normalized MUC5AC level was measured in Schirmer strip-collected tears. Compared to control conjunctiva, GC number and area were significantly lower in SS, non-SS, and combined ATD groups in exposed TB, and were also significantly lower in SS and combined ATD groups in covered SB. In all ATD, GC number and area were significantly correlated, but differences between SB and TB were non-significant. Normalized tear MUC5AC protein was lower in all ATD groups versus control eyes, and correlated only with GC area. GCs are significantly decreased in the covered and exposed conjunctiva in SS. GC area may be a better disease measure than number for ATD. Correlation between tear MUC5AC concentration and GC area suggests tear MUC5AC mucin can be used as a disease-relevant biomarker for conjunctiva GC health.

Postoperative Horner Syndrome After Lung Transplantation.

BACKGROUND: Horner syndrome arises from a disruption along the oculosympathetic efferent chain and can be caused by a variety of pathological and iatrogenic etiologies. We present 3 cases of postoperative Horner syndrome after bilateral lung transplantation. METHODS: The electronic health records of 3 patients with iatrogenic Horner syndrome after lung transplantation were examined, including notes from each patient's medical history, operative and postoperative records, and ophthalmology consultation results. A literature review was performed. RESULTS: All 3 of our patients displayed anisocoria and ptosis, symptoms consistent with Horner syndrome, and the patients from Cases 1 and 2 showed reversal of anisocoria after an application of topical apraclonidine. CONCLUSIONS: Ophthalmologists should be aware of the risk of Horner syndrome after lung transplantation.

Vertebrobasilar ischemia (VBI) related neuro-ophthalmic syndromes after routine activities involving hyperextension or rotation of the neck (hairdresser syndrome).

BACKGROUND: Vertebrobasilar insufficiency (VBI) after rotation or hyperextension of the neck during otherwise routine activities is uncommon "hairdresser syndrome" (HDS). We report three such cases presenting with neuro-ophthalmic complaints (Horner syndrome, ophthalmoplegia, and transient vision loss). METHODS: A retrospective review was performed of the electronic health records of three patients seen in the neuro-ophthalmology clinic of Houston Methodist Hospital with acute neuro-ophthalmological signs after neck hyperextension. A literature review was also performed. RESULTS: While various ischemic signs of VBI have been previously documented, to our knowledge, these are the first cases in the English ophthalmic literature to describe the presenting neuro-ophthalmologic signs of HDS. CONCLUSION: Clinicians should consider the possibility of neck hyperextension as a potential mechanism and precipitating event for acute neuro-ophthalmic presentations of VBI. Patients with a history of occupational (e.g., carpenter), recreational (e.g., bow hunter), or cosmetic (hairdresser) neck hyperextension (i.e., possible HDS) should undergo structural and vascular neuroimaging of both the head and neck (e.g., CT/CTA or MRI/MRA) to look for evidence of posterior fossa ischemia and/or vertebrobasilar lesion (e.g., occlusion, dissection, FMD, and pseudoaneurysm).

Bilateral central retinal/ophthalmic artery occlusion and near-complete ophthalmoplegia after bilateral lung transplant.

PURPOSE: Recognize a rare yet existing risk of severe visual loss as a postoperative complication of bilateral lung transplant. OBSERVATIONS: A 62-year-old male had undergone bilateral lung transplant for end-stage idiopathic pulmonary fibrosis and emphysema overlap syndrome. The operation was initially off-pump; however, during the left lung transplantation, cardiopulmonary bypass conversion was necessary to maintain intraoperative hemodynamic stability. On post-operative day 4, shortly after extubation and full recovery from sedation, the patient reported bilateral no light perception vision. There were no other associated neurologic symptoms. A computed tomographic (CT) of the head, cranial magnetic resonance (MR) scan of the head, MR angiogram of the circle of Willis and neck were negative. Neuro-ophthalmologic examination revealed no light perception vision in both eyes(OU). The pupils were non-reactive to light (amaurotic pupils). The intraocular pressure measured 18 mm Hg OU, and complete bilateral ophthalmoplegia was present. The fundus exam showed bilateral pallid optic disc edema, cherry red spots, with arteriolar attenuation, and mildly dilated and tortuous veins. Stroke work up was negative. CONCLUSIONS AND IMPORTANCE: A case of post-operative visual loss and ophthalmoplegia carrying significant and permanent quality of life implications. It questions the role disruption of homeostasis during cardiopulmonary bypass contributes for this outcome.

Improving Accuracy and Efficiency with Concurrent Use of Artificial Intelligence for Digital Breast Tomosynthesis.

PURPOSE: To evaluate the use of artificial intelligence (AI) to shorten digital breast tomosynthesis (DBT) reading time while maintaining or improving accuracy. MATERIALS AND METHODS: A deep learning AI system was developed to identify suspicious soft-tissue and calcified lesions in DBT images. A reader study compared the performance of 24 radiologists (13 of whom were breast subspecialists) reading 260 DBT examinations (including 65 cancer cases) both with and without AI. Readings occurred in two sessions separated by at least 4 weeks. Area under the receiver operating characteristic curve (AUC), reading time, sensitivity, specificity, and recall rate were evaluated with statistical methods for multireader, multicase studies. RESULTS: Radiologist performance for the detection of malignant lesions, measured by mean AUC, increased 0.057 with the use of AI (95% confidence interval [CI]: 0.028, 0.087; P < .01), from 0.795 without AI to 0.852 with AI. Reading time decreased 52.7% (95% CI: 41.8%, 61.5%; P < .01), from 64.1 seconds without to 30.4 seconds with AI. Sensitivity increased from 77.0% without AI to 85.0% with AI (8.0%; 95% CI: 2.6%, 13.4%; P < .01), specificity increased from 62.7% without to 69.6% with AI (6.9%; 95% CI: 3.0%, 10.8%; noninferiority P < .01), and recall rate for noncancers decreased from 38.0% without to 30.9% with AI (7.2%; 95% CI: 3.1%, 11.2%; noninferiority P < .01). CONCLUSION: The concurrent use of an accurate DBT AI system was found to improve cancer detection efficacy in a reader study that demonstrated increases in AUC, sensitivity, and specificity and a reduction in recall rate and reading time.© RSNA, 2019See also the commentary by Hsu and Hoyt in this issue.

PAX3-FOXO1 drives miR-486-5p and represses miR-221 contributing to pathogenesis of alveolar rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft-tissue sarcoma in childhood and histologically resembles developing skeletal muscle. Alveolar rhabdomyosarcoma (ARMS) is an aggressive subtype with a higher rate of metastasis and poorer prognosis. The majority of ARMS tumors (80%) harbor a PAX3-FOXO1 or less commonly a PAX7-FOXO1 fusion gene. The presence of either the PAX3-FOXO1 or PAX7-FOXO1 fusion gene foretells a poorer prognosis resulting in clinical re-classification as either fusion-positive (FP-RMS) or fusion-negative RMS (FN-RMS). The PAX3/7-FOXO1 fusion genes result in the production of a rogue transcription factors that drive FP-RMS pathogenesis and block myogenic differentiation. Despite knowing the molecular driver of FP-RMS, targeted therapies have yet to make an impact for patients, highlighting the need for a greater understanding of the molecular consequences of PAX3-FOXO1 and its target genes including microRNAs. Here we show FP-RMS patient-derived xenografts and cell lines display a distinct microRNA expression pattern. We utilized both loss- and gain-of function approaches in human cell lines with knockdown of PAX3-FOXO1 in FP-RMS cell lines and expression of PAX3-FOXO1 in human myoblasts and identified microRNAs both positively and negatively regulated by the PAX3-FOXO1 fusion protein. We demonstrate PAX3-FOXO1 represses miR-221/222 that functions as a tumor suppressing microRNA through the negative regulation of CCND2, CDK6, and ERBB3. In contrast, miR-486-5p is transcriptionally activated by PAX3-FOXO1 and promotes FP-RMS proliferation, invasion, and clonogenic growth. Inhibition of miR-486-5p in FP-RMS xenografts decreased tumor growth, illustrating a proof of principle for future therapeutic intervention. Therefore, PAX3-FOXO1 regulates key microRNAs that may represent novel therapeutic vulnerabilities in FP-RMS.

Biallelic Dicer1 Loss Mediated by aP2-Cre Drives Angiosarcoma.

Angiosarcoma is an aggressive vascular sarcoma with an extremely poor prognosis. Because of the relative rarity of this disease, its molecular drivers and optimal treatment strategies are obscure. DICER1 is an RNase III endoribonuclease central to miRNA biogenesis, and germline DICER1 mutations result in a cancer predisposition syndrome, associated with an increased risk of many tumor types. Here, we show that biallelic Dicer1 deletion with aP2-Cre drives aggressive and metastatic angiosarcoma independent of other genetically engineered oncogenes or tumor suppressor loss. Angiosarcomas in aP2-Cre;Dicer1Flox/- mice histologically and genetically resemble human angiosarcoma. miR-23 target genes, including the oncogenes Ccnd1 as well as Adam19, Plau, and Wsb1 that promote invasiveness and metastasis, were enriched in mouse and human angiosarcoma. These studies illustrate that Dicer1 can function as a traditional loss-of-function tumor suppressor gene, and they provide a fully penetrant animal model for the study of angiosarcoma development and metastasis. Cancer Res; 77(22); 6109-18. ©2017 AACR.