Clinical Implications of Alternating Hypointense Bands on OCT Angiography in Retinal Vascular Occlusive Disease.

PURPOSE: To demonstrate the relationship between alternating hypointense signal bands on OCT angiography (OCTA), real-time fluorescein angiography (FA), and structural OCT findings in patients with retinal vascular occlusive disease (RVOD). DESIGN: Retrospective, consecutive case series. SUBJECTS: Consecutive patients with a clinical diagnosis of acute RVOD and alternating bands of hypointense OCTA flow signal on en face projections. METHODS: Complete ophthalmic examination and multimodal imaging, including color fundus photography, real-time FA, spectral-domain OCT, and OCTA performed with different instruments having different scan speeds and acquisition protocols. MAIN OUTCOME MEASURES: The primary outcomes were: hypointense OCTA band characteristics (number, width, orientation, and location), OCTA acquisition characteristics (speed and scan direction), and FA findings including delayed arteriovenous (AV) transit and pulsatile flow. Secondary outcomes were: structural OCT changes including retinal fluid, paracentral acute middle maculopathy (PAMM) lesion, and a prominent middle limiting membrane (p-MLM) sign. RESULTS: OCT angiography hypointense bands were detected in the superficial and deep vascular plexuses in 9 eyes of 9 patients with either partial central retinal vein occlusion (RVO) or nonischemic RVO. When obtained on the same device, hypointense bands were thinner and more numerous at lower (100 kHz) scan speeds compared with higher (200 kHz) scan speeds. Band orientation was parallel to the OCTA scan direction, and their extent correlated with the area of delayed AV transit on FA. Structural OCT showed multiple PAMM lesions in 78% of cases and a p-MLM sign centered in the fovea in 44% of cases. CONCLUSIONS: OCT hypointense bands are a novel biomarker in RVOD indicating delayed AV transit and pulsatile filling without the need for dye angiography. Structural OCT often shows PAMM in these eyes and, less commonly, a p-MLM sign. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Anomaly-guided weakly supervised lesion segmentation on retinal OCT images.

The availability of big data can transform the studies in biomedical research to generate greater scientific insights if expert labeling is available to facilitate supervised learning. However, data annotation can be labor-intensive and cost-prohibitive if pixel-level precision is required. Weakly supervised semantic segmentation (WSSS) with image-level labeling has emerged as a promising solution in medical imaging. However, most existing WSSS methods in the medical domain are designed for single-class segmentation per image, overlooking the complexities arising from the co-existence of multiple classes in a single image. Additionally, the multi-class WSSS methods from the natural image domain cannot produce comparable accuracy for medical images, given the challenge of substantial variation in lesion scales and occurrences. To address this issue, we propose a novel anomaly-guided mechanism (AGM) for multi-class segmentation in a single image on retinal optical coherence tomography (OCT) using only image-level labels. AGM leverages the anomaly detection and self-attention approach to integrate weak abnormal signals with global contextual information into the training process. Furthermore, we include an iterative refinement stage to guide the model to focus more on the potential lesions while suppressing less relevant regions. We validate the performance of our model with two public datasets and one challenging private dataset. Experimental results show that our approach achieves a new state-of-the-art performance in WSSS for lesion segmentation on OCT images.

The impact of the COVID-19 lockdown on retinopathy of prematurity screening and management in the United States: a multicenter study.

PURPOSE: To study the effect of the pandemic-related lockdown (physical distance measures and movement restrictions) on the characteristics and management of retinopathy of prematurity (ROP). METHODS: In this controlled, multicenter cohort study, the medical records of patients born prematurely and screened for ROP in the neonatal intensive care unit during four time periods were reviewed retrospectively: (1) November 1, 2018, to March 15, 2019; (2) March 16, 2019, to August 2, 2019 (lockdown control period); (3) November 1, 2019, to March 15, 2020; and (4) March 16, 2020-August 2, 2020. RESULTS: A total of 1,645 patients met inclusion criteria. Among the 1,633 patients with complete data, mean gestational age (GA) at birth was 28.2, 28.4, 28.0, and 28.3 weeks across time periods 1 to 4, respectively (P = 0.16). The mean birth weight of all patients was 1079.1 ± 378.60 g, with no significant variation across time periods (P = 0.08). There were fewer patients screened during the lockdown period (n = 411) compared with the period immediately before (n = 491) and the same period in the prior year (n = 533). Significantly more patients were screened using indirect ophthalmoscopy, compared to digital imaging (telemedicine), during the lockdown (P < 0.01). There were 11.7%, 7.7%, 9.0%, and 8.8% of patients requiring treatment in each time period, respectively (P = 0.42), with a median postmenstrual age at initial treatment of 37.2, 36.45, 37.1, and 36.3 weeks, respectively (P = 0.32). CONCLUSIONS: We recorded a decrease in the number of infants meeting criteria for ROP screening during the lockdown. The GA at birth and birth weight did not differ. Significantly more infants were screened with indirect ophthalmoscopy, compared to digital imaging, during the lockdown.

Evolution of the 'omega sign' on optical coherence tomography.

PURPOSE: To present the early post-operative evolution of retained subretinal perfluoro-n-octane (PFO) as captured on OCT. METHODS: Case report of a patient. RESULTS: A 58-year-old woman was noted to have subretinal PFO after undergoing autologous retinal graft for macular hole closure under PFO tamponade. Serial OCT identified the subretinal PFO as early as the first postoperative day and demonstrates progressive consolidation and encapsulation of the PFO bubble by the surrounding outer retina. CONCLUSION: Subretinal PFO is usually seen several weeks in the postoperative course once the gas endotamponade has resorbed sufficiently for OCT imaging. In this case, PFO tamponade enabled its imaging early. Its subsequent evolution into the classic "omega sign" may suggest a granulomatous encapsulation of the PFO bubble.

The prognostic value of emergency department measured hypertension: A systematic review and meta-analysis.

OBJECTIVES: The objective was to assess the prognostic value of hypertension detected in the emergency department (ED). METHODS: The ED presents a unique opportunity to predict long-term cardiovascular disease (CVD) outcomes with its potential for high-footfall, and large-scale routine data collection applied to underserved patient populations. A systematic review and meta-analyses were conducted to assess the prognostic performance and feasibility of ED-measured hypertension as a risk factor for long-term CVD outcomes. We searched MEDLINE and Embase databases and gray literature sources. The target populations were undifferentiated ED patients. The prognostic factor of interest was hypertension. Feasibility outcomes included prevalence, reliability, and follow-up attendance. Meta-analyses were performed for feasibility using a random effect and exact likelihood. RESULTS: The searches identified 1072 studies after title and abstract review, 53 studies had their full text assessed for eligibility, and 26 studies were included. Significant heterogeneity was identified, likely due to the international populations and differing study design. The meta-analyses estimate of prevalence for ED-measured hypertension was 0.31 (95% confidence interval  0.25-0.37). ED hypertension was persistent outside the ED (FE estimate of 0.50). The proportion of patients attending follow-up was low with an exact likelihood estimate of 0.41. Three studies examined the prognostic performance of hypertension and demonstrated an increased risk of long-term CVD outcomes. CONCLUSION: Hypertension can be measured feasibly in the ED and consequently used in a long-term cardiovascular risk prediction model. There is an opportunity to intervene in targeted individuals, using routinely collected data.

ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTIONS DURING THE COVID-19 PANDEMIC WITH IMPLEMENTATION OF UNIVERSAL MASKING.

PURPOSE: To evaluate the rates of postintravitreal injection-related endophthalmitis during the COVID-19 pandemic with institution of both physician and patient face masking. METHODS: All eyes receiving intravitreal injections of any kind from a single large tertiary retina practice in Houston, TX before (August 2017-March 22, 2020) and after (March 23, 2020-September 2020) COVID-19 pandemic universal masking protocols. The total number of injections and cases of acute injection-related endophthalmitis were determined from billing records and subsequent retrospective chart review. The primary outcome was the rate of endophthalmitis after intravitreal injection. Secondary outcomes included visual acuity, time until initial presentation, patient age, and differences in the overall number of injections performed monthly pre-COVID-19 and post-COVID-19. RESULTS: A total of 134, 097 intravitreal injections were performed during the study period (111,679 pre-COVID-19 and 22,418 post-COVID-19 masking protocols). A total of 41 cases of acute endophthalmitis occurred in the pre-COVID group (0.04%, one in 2,500) and 7 cases in the post-COVID group (0.03%, one in 3,333) P = 0.85. CONCLUSION: In this single center, retrospective study, the implementation of universal patient and physician masking as practiced during the COVID-19 pandemic did not significantly affect the rate of postintravitreal injection endophthalmitis.

Locally Invasive Diffuse Iris Ring Melanoma Presenting as Unilateral Severe Glaucoma: Case Report and Review of Molecular Genetics.

We report the clinical history and histopathological findings in a case of diffuse iris ring melanoma (DIM) and review the most recent literature and modern molecular genetics of this entity. An 85-year-old Hispanic man presented with severe unilateral glaucoma, managed at an outside institution for 2 years prior to presentation. Diffuse pigmentation was noted in the angle, on the intraocular lens implant, and in the vitreous without clear demonstration of a mass on ultrasound biomicroscopy. Workup for metastatic cutaneous melanoma was negative. Histopathological examination of the enucleated eye revealed a mixed cell type iris ring melanoma with diffuse intraocular involvement. Gene expression profiling (GEP) revealed a class 2 molecular signature indicating a very high risk for metastases. Unilateral glaucoma presenting with marked pigmentation in the anterior chamber angle should be managed as melanoma until proven otherwise. Iris ring melanomas are known to have an aggressive clinical course, and recent molecular analyses indicate that they are likely primarily GEP class 2 with a very poor prognosis, similar to the majority of ciliary body melanomas.

Characteristic Visual Field Defect From Lateral Geniculate Body Stroke.

ABSTRACT: A 58-year-old man presented with a complaint of subjective visual field loss on the right side and hypertensive emergency. Examination revealed a right homonymous hemianopia. Computed tomography imaging revealed an acute stroke of the left lateral geniculate body. A few months later, automated perimetry revealed characteristic visual field changes associated with this lesion. In this report, the anatomy, pathophysiology, clinical findings, and previously reported etiologies of lateral geniculate body lesions are reviewed.

Systematic literature search, review and dissemination methodology for the COVID-19 pandemic.

Purpose of the study: SARS-CoV-2 has caused healthcare systems globally to reorganise. A pandemic paradox emerged; while clinicians were desperate for information on a new disease, they had less time to find and evaluate the vast volume of publications at times of significant strain on healthcare systems.A multidisciplinary team undertook a weekly literature search capturing all COVID-19 publications. We also monitored free open access medical education (FOAMed) sources for emerging themes. Title and abstract screening pooled the most relevant papers for emergency medicine. Three summary types were created, a 'Top 5 Flash Update', a journal club and a rapid response to emerging FOAMed themes. From these summaries, three modes of dissemination were used: short written summaries, blogs and podcasts. These were amplified through social media. Study design: A retrospective review was conducted assessing the impact of this knowledge dissemination strategy for the period of March to September 2020. Results: In total, 64 687 papers were identified and screened. Of the papers included in the 'Top 5', 28.3% were on epidemiology, 23.6% treatment, 16.7% diagnostics, 12% prognosis, 8.7% pathophysiology with the remaining 10.7% consisting of PPE, public health, well-being and 'other'. We published 37 blogs, 17 podcasts and 18 Top 5 Flash Updates. The blogs were read 138 343 times, the Top 5 Flash Updates 68 610 times and the podcasts had 72 501 listens. Conclusion: A combination of traditional academic and novel social media approaches can address the pandemic paradox clinicians are facing.

Regionally Specific Economic Impact of Screening and Treating Retinopathy of Prematurity in Middle-Income Societies in the Philippines.

PURPOSE: To estimate the economic effects of implementing a universal screening and treatment program for retinopathy of prematurity (ROP) in the Philippines with the Economic Model for Retinopathy of Prematurity (EcROP). METHODS: The EcROP is a cost-effectiveness, cost-benefit, and cost-utility analysis. Fifty parents of legally blind individuals (aged 3 to 28 years) from three schools for the blind in the Philippines were interviewed to estimate the societal burden of raising a blind child. A decision tree analytic model, with deterministic and probabilistic sensitivity analysis, was used to calculate the incremental cost-effectiveness ratio (primary outcome) and the incremental monetary benefit (secondary outcome) for implementing an optimal national ROP program, compared to estimates of the current policy. Findings were extrapolated to estimate the national economic benefit of an ideal screening and treatment program. RESULTS: The incremental cost-effectiveness ratio for a national program over the current policy was strongly favorable to the ideal program for the Philippines and represents an opportunity for substantial societal cost savings. The per-child incremental, annual monetary benefit of a national program over the current policy was $2,627. Extrapolating to the population of children at risk in 1 year showed that the national annual net benefit estimate would be $64,320,692, which is favorable to the current policy. CONCLUSIONS: The EcROP demonstrates that implementing a national ROP screening and treatment program is cost-saving and cost-effective, and would substantially decrease childhood blindness in the Philippines. [J Pediatr Ophthalmol Strabismus. 2019;56(6):388-396.].

Atypical pituitary adenoma with orbital invasion: Case report and review of the literature.

Pituitary adenoma invasion into the orbit is a rare phenomenon with only 22 cases, including the present case, in the literature. Our case is a 31-year-old man who presented with biopsy-proven atypical pituitary adenoma invading the right orbit after a prior resection. We compare his clinical course with previous cases and discuss clinical features, radiological features, management considerations, histologic features, and prognosis. Cases are organized by specific pituitary tumor type to aid in determining appropriate management. Early surgical intervention is the key, especially in the setting of pathologic features indicating aggressive tumor behavior or worsening visual function but is generally not indicated in prolactin-secreting adenomas that may respond to medical therapy. The role of radiation therapy is not fully established; however, it should be strongly considered in conjunction with or after surgery, especially in cases where complete resection is not achieved or histological and molecular analyses indicate a high likelihood of recurrence. More uniform and comprehensive data about management and outcomes are needed to determine the optimal treatment approach for this rare entity.

Neurothekeoma of the Cornea.

Neurothekeomas (NTKs) are benign cutaneous neoplasms of fibrohistiocytic origin and most commonly occur in the head, neck, and upper extremities. Traditionally, NTK and nerve sheath myxoma (NSM) were classified as subtypes of a single neoplasm with a common histogenesis, but recently immunostaining has demonstrated that the lesions are most likely of distinct cellular origin. Rarely, NTKs have been reported to occur in the ocular adnexa, and the present case of a 39-year-old female is the first to describe a cellular NTK originating in the cornea and mimicking a Salzmann's nodular degeneration. This report describes the clinical and pathological findings of the patient, discusses the changes in the classification of these rare neoplasms in light of advances in immunohistochemistry, and reviews all cases of ocular NTK found in the literature.

Modified Rapid AChE Method (MRAM) for Hirschsprung Disease Diagnosis: A Journey from Meier-Ruge Until Now.

Hirschsprung disease (HSCR) can be diagnosed using a variety of histological and immunohistochemical methods and stains. Because of the nature of the condition and the need for a rapid diagnostic confirmation, those methods with high accuracy and fast turnaround times are preferred. The authors of this paper have used rapid acetylcholinesterase (AChE) immunohistochemistry in conjunction with standard H&E in order to optimize diagnostic accuracy, and present a modified rapid AChE method (MRAM) that has been successfully utilized for over 20 years. The authors also present a list of over 30 different methods and stains that have been proposed for Hirschsprung disease diagnosis.

Does MAP2 have a role in predicting the development of anti-NMDAR encephalitis associated with benign ovarian teratoma? A report of six new pediatric cases.

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is a potentially fatal neurologic syndrome in which patients present with a spectrum of central nervous system deficits. Sixty percent of the cases can be attributed to the presence of tumors, most often ovarian teratomas. This report examines 6 pediatric patients who presented with neurologic deficits associated with the presence of such tumors. These cases illustrate a perplexing phenomenon, where benign teratomas could have a possible association with anti-NMDAR encephalitis. The purpose of this study was to compare the histology and immunohistochemistry of tumors associated with this syndrome to ovarian teratomas found in patients presenting with no neurologic symptoms. After obtaining institutional review board approval, 57 cases of ovarian teratomas were identified at our institution over 12 years. Six patients were identified with anti-NMDAR encephalitis. A panel of immunostains, including S100, GFAP, MAP2, and NeuN was applied to patients' tumor sections as well as the 6 controls from age-matched patients. No qualitative histologic or immunohistochemical differences were seen between the study cases and control group. Because no qualitative differences were identified between the study cases and the control group, testing of paired serum and cerebrospinal fluid remains the best method for diagnosis of anti-NMDAR encephalitis. Tumor banking with molecular analysis of ovarian teratomas, including whole-genome sequencing and comparative genomic hybridization between ovarian tissue saved from patients with and without anti-NMDAR encephalitis, is necessary to fully understand the etiopathogenesis of anti-NMDAR encephalitis.

Xeroderma pigmentosa: three new cases with an in depth review of the genetic and clinical characteristics of the disease.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by hypersensitivity of the skin and eyes to UV-radiation as a result of a defect in one of eight genes. Seven genes (XPA-XPG) have a defect in Nucletoide Excision Repair (NER), while the eighth gene XPV has a defect in polymerase η, which is responsible for replication of UV-damaged DNA to produce corrected daughter strands. We present the varied clinical courses of three African-American female patients with XP. Additionally, we present a review of the literature that focuses on the various clinical manifestations as well as the genetic and molecular mechanisms underlying this disease.

The spectrum of pulmonary malformation in trisomy-21 patient. A review with emphasis on the molecular-genetic basis.

Gene overexpression has been identified as a primary determining factor for the distinct Down syndrome (DS) phenotypes. Previous genetic research has identified a spectrum of gene expressions responsible for many of the observed traits in DS patients including cardiovascular, brain, and GI anomalies. However, the molecular/genetic basis underlying pulmonary anomalies are yet to be identified, even though respiratory complications represent the leading cause of morbidity and mortality in DS patients. In this article, we will discuss the Etiopathogenesis and spectrum of pulmonary anomalies in DS patients.

Spinal cysticercosis mimicking a tumor in a pediatric patient.

Parasitic infections of the central nervous system (CNS) occur mostly in underdeveloped regions of the world. Neurocysticercosis (NC) occurs when the larval form of the T. solium tapeworm invades the CNS. Spinal cysticercosis is an extremely rare type of NC and occurs when the cyst occupies the subarachnoid space of the spinal column. Previous cases have been successfully treated through both surgical and medical means. The current case describes the symptoms, diagnosis, and treatment of a patient with this extremely uncommon manifestation of neurocysticercosis.