Circular statistics for analyzing changes in retinal nerve fiber layer.

OBJECTIVE: To evaluate the use of circular statistics to analyze retinal nerve fibre layer (RNFL) thickness in eyes with and without a prior history of optic neuritis (ON). DESIGN: Single-centre consecutive study. PARTICIPANTS: Twenty-two multiple sclerosis patients and 20 healthy control subjects. METHODS: Data on 28 eyes with a history of ON of 22 multiple sclerosis patients and 40 eyes of 20 healthy control subjects collected in 2010 and 2015. RNFL thickness was measured separately in 12 sectors around the optic nerve head. We used circular statistics to calculate the mean weighted vector of RNFL thickness for each sector and eye in 2 measurements made 5 years apart (2010 and 2015). Comparisons of weighted mean vectors between groups were made using a paired Mardia-Watson-Wheeler test. RESULTS: The directions of the mean weighted vectors for ON eyes were 45.8º in 2010 and 56.0º in 2015, whereas in control eyes the directions were 319.4º in 2010 and 188.9º in 2015. No significant differences were found between 2010 and 2015 in any of the 2 groups. However, significant differences were found between ON and control eyes in 2010 and 2015. CONCLUSIONS: This paper provides an example of how to use circular statistics in cases of directional data in ophthalmology and demonstrates that circular statistics are a suitable tool for this purpose.

Computer aided volumetric assessment of orbital structures in patients with Graves' orbitopathy: correlation with serum thyroid antiperoxidase antibodies and disease activity.

INTRODUCTION: Graves' disease is an autoimmune disorder. Goiter and Graves' orbitopathy are frequently seen clinically. It would be helpful for the diagnosis, grading, prognosis, and treatment of this condition if it was possible to find serum biomarkers to establish a connection between the plasma levels of these compounds and orbital changes. METHODS: A retrospective study was performed by revising the medical records of 44 patients with Graves' orbitopathy and 15 controls. The Osirix software (Pixmeo, Geneva, Switzerland) was used for manual orbital measurements. Plasma levels of Graves' orbitopathy substances were obtained in the analytical review of the patients. RESULTS: A greater muscle volume was observed in patients with Graves' orbitopathy in relation to the control group (p < 0.001). The clinical activity score (CAS) was associated to total muscle mass (p = 0.013) and retrorbital fat (p = 0.048). Our results indicated a direct relationship between serum concentrations of anti-thyroid peroxidase antibodies and inferior rectus thickening (p = 0.036); however, we did not observe a positive correlation between other muscle volumes and serum concentrations of various thyroid-related substances. CONCLUSIONS: This study is the first that uses Osirix measurement software to manually assess orbital features in patients with Graves' orbitopathy. These measurements were compared to the outcomes of tests performed in a laboratory. Among several serum biomarkers, anti-thyroid peroxidase appears to be a reliable biomarker that correlates positively with inferior rectus muscle thickness in patients with thyroid eye disease. This may help to improve the management of this disease.

Improvement of Prostaglandin-Associated Periorbitopathy after Discontinuing Treatment.

Objectives: To report that the periorbital changes induced by prostaglandin analogue (PGA) eye drops are partially reversible after discontinuing treatment. Materials and Methods: Nine patients with prostaglandin-associated periorbitopathy seen in a referral oculoplastic practice were included in this study, eight with unilateral glaucoma and one with bilateral open-angle glaucoma. All of them had been treated with topical PGA for at least one year, before the treatment was discontinued for cosmetic reasons. Results: In all cases, there were evident periocular differences between the treated eye and the fellow eye, consisting mainly of deepening of the upper eyelid sulcus and eyelid fat pad reduction. One year after discontinuing the PGA eye drops, improvement of these features was observed. Conclusion: Clinicians and patients should be aware of the side effects of topical PGA therapy on periorbital tissues, and that these side effects can partially regress after discontinuation of the medication.

Association of Influenza Activity and Environmental Conditions With the Risk of Invasive Pneumococcal Disease.

Importance: Streptococcus pneumoniae is the most commonly identified cause of bacterial pneumonia, and invasive pneumococcal disease (IPD) has a high case fatality rate. The wintertime coseasonality of influenza and IPD in temperate countries has suggested that pathogen-pathogen interaction or environmental conditions may contribute to IPD risk. Objectives: To evaluate the short-term associations of influenza activity and environmental exposures with IPD risk in temperate countries and to examine the generalizability of such associations across multiple jurisdictions. Design, Setting, and Participants: This case-crossover analysis of 19 566 individuals with IPD from 1998 to 2011 combined individual-level outcomes of IPD and population-level exposures. Participants lived in 12 jurisdictions in Canada (the province of Alberta and cities of Toronto, Vancouver, and Halifax), Australia (Perth, Sydney, Adelaide, Brisbane, and Melbourne), and the United States (Baltimore, Providence, and Philadelphia). Data were analyzed in 2019. Exposures: Influenza activity, mean temperature, absolute humidity, and UV radiation at delays of 1 to 3 weeks before case occurrence in each jurisdiction. Main Outcomes and Measures: Matched odds ratios (ORs) for IPD associated with changes in exposure variables, estimated using multivariable conditional logistic regression models. Heterogeneity in effects across jurisdictions were evaluated using random-effects meta-analytic models. Results: This study included 19 566 patients: 9629 from Australia (mean [SD] age, 42.8 [30.8] years; 5280 [54.8%] men), 8522 from Canada (only case date reported), and 1415 from the United States (only case date reported). In adjusted models, increased influenza activity was associated with increases in IPD risk 2 weeks later (adjusted OR [aOR] per SD increase, 1.07; 95% CI, 1.01-1.13). Increased humidity was associated with decreased IPD risk 1 week later (aOR per 1 g/m3, 0.98; 95% CI, 0.96-1.00). Other associations were heterogeneous; metaregression suggested that combinations of environmental factors might represent unique local risk signatures. For example, the heterogeneity in effects of UV radiation and humidity at a 2-week lag was partially explained by variation in temperature (UV index: coefficient, 0.0261; 95% CI, 0.0078 to 0.0444; absolute humidity: coefficient, -0.0077; 95% CI, -0.0125 to -0.0030). Conclusions and Relevance: In this study, influenza was associated with increased IPD risk in temperate countries. This association was not explained by coseasonality or case characteristics and appears generalizable. Absolute humidity was associated with decreased IPD risk in the same jurisdictions. The generalizable nature of these associations has important implications for influenza control and advances the understanding of the seasonality of this important disease.

Heavy precipitation, drinking water source, and acute gastrointestinal illness in Philadelphia, 2015-2017.

Runoff from heavy precipitation events can lead to microbiological contamination of source waters for public drinking water supplies. Philadelphia is a city of interest for a study of waterborne acute gastrointestinal illness (AGI) because of frequent heavy precipitation, extensive impervious landcover, and combined sewer systems that lead to overflows. We conducted a time-series analysis of the association between heavy precipitation and AGI incidence in Philadelphia, served by drinking water from Delaware River and Schuylkill River source waters. AGI cases on each day during the study period (2015-2017) were captured through syndromic surveillance of patients' chief complaint upon presentation at local emergency departments. Daily precipitation was represented by measurements at the Philadelphia International Airport and by modeled precipitation within the watershed boundaries, and we also evaluated stream flowrate as a proxy of precipitation. We estimated the association using distributed lag nonlinear models, assuming a quasi-Poisson distribution of the outcome variable and with adjustment for potential confounding by seasonal and long-term time trends, ambient temperature, day-of-week, and major holidays. We observed an association between heavy precipitation and AGI incidence in Philadelphia that was primarily limited to the spring season, with significant increases in AGI that peaked from 8 to 16 days following a heavy precipitation event. For example, the increase in AGI incidence related to airport precipitation above the 95th percentile (vs no precipitation) during spring reached statistical significance on lag day 7, peaked on day 16 (102% increase, 95% confidence interval: 16%, 252%), and declined while remaining significantly elevated through day 28. Similar associations were observed in analyses of watershed-specific precipitation in relation to AGI cases within the populations served by drinking water from each river. Our results suggest that heavy precipitation events in Philadelphia result in detectable local increases in waterborne AGI.

Thyroid eye disease: current and potential medical management.

INTRODUCTION: Thyroid eye disease (TED) is the most frequent extra-thyroid manifestation of Graves' disease and it is more frequent in middle age and in female gender. Nowadays, the causal mechanisms of this disease are not completely understood, but the current available studies suggest that the main causative factor is the thyroid stimulating hormone receptor. MATERIALS AND METHODS: To collect reports on TED medical management, a thorough literature search was performed in PubMed database. An additional search was made in Google Scholar to complete the collected items. RESULTS: Among the indentified risk factors, tobacco habit is the most relevant. The main criteria to choose a suitable treatment are the activity and severity of the disease. Support measures can be used to improve the patient's symptoms in any phase of the disease. There is a large number of drugs proposed to manage TED, although with different reported rates of success. CONCLUSIONS: Currently, the drugs of choice are corticosteroids in moderate-to-severe and in sight-threatening forms. The main problem of corticosteroids is their spectrum of side effects. Therefore, other alternatives are being suggested for medical management of this disease. The efficacy of these alternatives remains unclear.

Age and gender influence on foveal avascular zone in healthy eyes.

The foveal avascular zone (FAZ) is the capillary-free area in the central macula with high photoreceptor density and metabolic activity. In the present study we measured the superficial and deep macular foveal avascular zone (sFAZ, dFAZ) in the eyes of healthy adults of both sexes of various ages ranging from 10 to 69 years using optical coherence tomography angiography (OCT-A) in order to evaluate the influence of gender and age on FAZ size. A cross-sectional study was carried out in 240 eyes of 120 healthy subjects, OCT-A was performed by means of a Topcon swept source OCT. sFAZ and dFAZ areas were measured using the IMAGEnet6 software package. Subjects were grouped by age (six groups) and gender. The mean ±â€¯sd age of the subjects was 39.2 ±â€¯17.4 years (50% women, 50% men), ranging from 10 to 69 years. The overall mean sFAZ size in women (0.297 ±â€¯0.110 mm2) was significantly larger (p = 0.002) than in men (0.254 ±â€¯0.098 mm2). Similarly, the overall mean dFAZ in women (0.322 ±â€¯0.111 mm2) was significantly larger (p < 0.001) than in men (0.273 ±â€¯0.099). However, when analyzed by age group, these gender differences appeared only in groups younger than 20 years old and older than 50 years old. Men did not show differences among the six age groups. In women, for both sFAZ and dFAZ, the 20-29 year old group had a smaller FAZ size than the 50-59 year old group. In conclusion for both sFAZ and dFAZ, women have larger areas than men, but this occurs only in the young and old age groups. In men, age does not seem to influence the size of the FAZ, but in women, both sFAZ and dFAZ were significantly smaller in younger than in older ages. These results suggest that retinal changes in retinal structure caused by aging may be different in woman than in men, probably reflecting the more hormonal variations known to exist with age in women.

Systemic Diffuse Large B-Cell Lymphoma Presenting as Bilateral Orbital Vasculopathy.

The authors report a case of a 58-year-old man with bilateral proptosis and signs of orbital inflammation without any associated systemic findings. MRI showed diffuse orbital infiltration. An intraconal orbital biopsy revealed polyclonal lymphoplasmacytic infiltration and non-necrotizing lymphoid small-vessel vasculopathy. The orbital symptoms resolved following a 2-week course of oral prednisone. Three months later, the patient experienced abdominal pain and weight loss. Ultrasonographic investigation showed hepatosplenomegaly, a retroperitoneal mass, and inguinal lymphadenopathy. A lymph node biopsy revealed a diffuse large B-cell lymphoma. The patient underwent chemotherapy but died 6 months later with metastatic disease. This case suggests that diffuse orbital inflammation with nonspecific vasculitis may be an early paraneoplastic finding associated with diffuse large B-cell lymphoma.

Eyelid Kaposi Sarcoma in an HIV-negative Patient.

Kaposi sarcoma (KS) is a low-grade, multicentric vascular neoplasm. Most commonly, it involves the skin, but it can occur at any site on the body. The cutaneous lesions are often located on the lower legs, genitalia, oral mucosa, and face. KS is categorized in four different types: classic, endemic, epidemic or AIDS associated, and transplantation associated. We report a case of HIV-negative, classic KS located on the eyelid. The eyelid lesion was completely excised, and after a 1-year follow-up, no recurrences were observed. Ocular involvement by KS in a patient who is serologically negative for HIV is extremely rare.

Cortical blindness secondary to posterior reversible encephalopathy syndrome, recovered by successful blood pressure management.

We report a case of cortical blindness secondary to posterior leukoencephalopathy syndrome, which was successfully treated by blood pressure management. A 66-year-old white man presented at the emergency room complaining of severe frontal headache, disorientation, and progressive blurred vision. The initial physical examination disclosed a blood pressure of 200/176 mmHg. One hour later the patient exhibited mental confusion and bilateral blindness. Computed tomography and magnetic resonance imaging were performed, and a systemic workup was conducted, resulting in a diagnosis of posterior leukoencephalopathy syndrome. This syndrome is a rare manifestation of systemic hypertension that requires proper diagnosis and management to avoid irreversible brain damage. Early recognition of this condition and prompt control of the patient's blood pressure are essential because they may bring about a reversal of the syndrome, which may otherwise result in permanent brain damage.

Cortical blindness secondary to posterior reversible encephalopathy syndrome, recovered by successful blood pressure management / Cegueira cortical secundária à síndrome de encefalopatia reversível posterior recuperada pelo controle bem sucedido da pressão arterial

ABSTRACT We report a case of cortical blindness secondary to posterior leukoencephalopathy syndrome, which was successfully treated by blood pressure management. A 66-year-old white man presented at the emergency room complaining of severe frontal headache, disorientation, and progressive blurred vision. The initial physical examination disclosed a blood pressure of 200/176 mmHg. One hour later the patient exhibited mental confusion and bilateral blindness. Computed tomography and magnetic resonance imaging were performed, and a systemic workup was conducted, resulting in a diagnosis of posterior leukoencephalopathy syndrome. This syndrome is a rare manifestation of systemic hypertension that requires proper diagnosis and management to avoid irreversible brain damage. Early recognition of this condition and prompt control of the patient's blood pressure are essential because they may bring about a reversal of the syndrome, which may otherwise result in permanent brain damage.

RESUMO Relatamos um caso de cegueira cortical secundário à síndrome de leucoencefalopatia posterior recuperado pelo controle bem sucedido da pressão arterial. Um homem branco de 66 anos de idade compareceu à emergência com queixa de dor de cabeça frontal severa, desorientação e embaçamento progressivo da visão. O exame físico inicial revelou uma pressão arterial de 200/176 mmHg. Uma hora depois, o paciente apresentou confusão mental e cegueira bilateral. Após a tomografia e a ressonância nuclear magnética, o tratamento sistêmico foram realizados e o diagnóstico de síndrome da leucoencefalopatia posterior foi realizado. A síndrome de leucoencefalopatia posterior é uma manifestação rara de hipertensão sistêmica que requer um diagnóstico e gerenciamento adequados para evitar danos cerebrais irreversíveis. O reconhecimento precoce desta condição e o controle imediato da pressão arterial são essenciais porque podem levar à reversão da síndrome, o que, de outra forma, pode resultar em dano cerebral permanente.

Risk of Fall-Related Injury due to Adverse Weather Events, Philadelphia, Pennsylvania, 2006-2011.

OBJECTIVES: Following a surge in fall-related visits to local hospital emergency departments (EDs) after a severe ice storm, the Philadelphia Department of Public Health examined the association between inclement winter weather events and fall-related ED visits during a 5-year period. METHODS: Using a standardized set of keywords, we identified fall-related injuries in ED chief complaint logs submitted as part of Philadelphia Department of Public Health's syndromic surveillance from December 2006 through March 2011. We compared days when falls exceeded the winter fall threshold (ie, "high-fall days") with control days within the same winter season. We then conducted matched case-control analysis to identify weather and patient characteristics related to increased fall-related ED visits. RESULTS: Fifteen high-fall days occurred during winter months in the 5-year period. In multivariable analysis, 18- to 64-year-olds were twice as likely to receive ED care for fall-related injuries on high-fall days than on control days. The crude odds of ED visits occurring from 7:00 am to 10:59 am were 70% higher on high-fall days vs control days. Snow was a predictor of a high-fall day: the adjusted odds of snow before a high-fall day as compared with snow before a control day was 13.4. CONCLUSIONS: The association between the number of fall-related ED visits and weather-related fall injuries, age, and timing suggests that many events occurred en route to work in the morning. Promoting work closures or delaying openings after severe winter weather would allow time for better snow or ice removal, and including "fall risk" in winter weather advisories might effectively warn morning commuters. Both strategies could help reduce the number of weather-related fall injuries.

Genetic factors influencing frontostriatal dysfunction and the development of dementia in Parkinson's disease.

The dual syndrome hypothesis for cognitive impairment in Parkinson's disease (PD) establishes a dichotomy between a frontrostriatal dopamine-mediated syndrome, which leads to executive deficits, and a posterior cortical syndrome, which leads to dementia. Certain genes have been linked to these syndromes although the exact contribution is still controversial. The study's objective was to investigate the role of APOE, MAPT, COMT, SNCA and GBA genes in the dual syndromes. We genotyped APOE (rs429358 and rs7412), MAPT (rs9468), COMT (rs4680) and SNCA (rs356219) risk polymorphisms and sequenced GBA in a cohort of 298 PD patients. The degree of dopaminergic depletion was investigated with [123I]FP-CIT SPECTs and the presence of dementia was ascertained with a long-term review based on established criteria. The association between genetic and imaging parameters was studied with linear regression, and the relationship with dementia onset with Cox regression. We found that APOE2 allele (Pput = 0.002; Pcau = 0.01), the minor allele 'G' in SNCA polymorphism (Pput = 0.02; Pcau = 0.006) and GBA deleterious variants in (Pput = 0.01; Pcau = 0.001) had a detrimental effect on striatal [123I]FP-CIT uptake in PD. Conversely, Met/Met carriers in COMT polymorphism had increased caudate uptake (Pcau = 0.03). The development of dementia was influenced by APOE4 allele (HR = 1.90; P = 0.03) and GBA deleterious variants (HR = 2.44; P = 0.01). Finally, we observed no role of MAPT locus in any of the syndromes. As a conclusion, APOE2, SNCA, COMT and GBA influence frontostriatal dysfunction whereas APOE4 and GBA influence the development of dementia, suggesting a double-edged role of GBA. The dichotomy of the dual syndromes may be driven by a broad dichotomy in these genetic factors.

Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.

Parkinson's disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

Novel variant in the TP63 gene associated to ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome.

BACKGROUND: Ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome is a disorder resulting from anomalous embryonic development of ectodermal tissues. There is evidence that AEC syndrome is caused by mutations in the TP63 gene, which encodes the p63 protein. This is an important regulatory protein involved in epidermal proliferation and differentiation. MATERIALS AND METHODS: Genome sequencing was performed in DNA from peripheral blood leukocytes of a newborn with AEC syndrome and her parents. Variants were searched in all coding exons and intron-exon boundaries of the TP63 gene. RESULTS: A heterozygous missense variant (NM_003722.4:c.1063G>C (p.Asp355His) was found in the newborn patient. No variants were found in either of the parents. CONCLUSIONS: We identified a previously unreported variant in TP63 gene which seems to be involved in the somatic malformations found in the AEC syndrome. The absence of this variant in both parents suggests that the variant appeared de novo.

Incidence of medically attended influenza during pandemic and post-pandemic seasons through the Influenza Incidence Surveillance Project, 2009-13.

BACKGROUND: Since the introduction of pandemic influenza A (H1N1) to the USA in 2009, the Influenza Incidence Surveillance Project has monitored the burden of influenza in the outpatient setting through population-based surveillance. METHODS: From Oct 1, 2009, to July 31, 2013, outpatient clinics representing 13 health jurisdictions in the USA reported counts of influenza-like illness (fever including cough or sore throat) and all patient visits by age. During four years, staff at 104 unique clinics (range 35-64 per year) with a combined median population of 368,559 (IQR 352,595-428,286) attended 35,663 patients with influenza-like illness and collected 13,925 respiratory specimens. Clinical data and a respiratory specimen for influenza testing by RT-PCR were collected from the first ten patients presenting with influenza-like illness each week. We calculated the incidence of visits for influenza-like illness using the size of the patient population, and the incidence attributable to influenza was extrapolated from the proportion of patients with positive tests each week. FINDINGS: The site-median peak percentage of specimens positive for influenza ranged from 58.3% to 77.8%. Children aged 2 to 17 years had the highest incidence of influenza-associated visits (range 4.2-28.0 per 1000 people by year), and adults older than 65 years had the lowest (range 0.5-3.5 per 1000 population). Influenza A H3N2, pandemic H1N1, and influenza B equally co-circulated in the first post-pandemic season, whereas H3N2 predominated for the next two seasons. Of patients for whom data was available, influenza vaccination was reported in 3289 (28.7%) of 11,459 patients with influenza-like illness, and antivirals were prescribed to 1644 (13.8%) of 11,953 patients. INTERPRETATION: Influenza incidence varied with age groups and by season after the pandemic of 2009 influenza A H1N1. High levels of influenza virus circulation, especially in young children, emphasise the need for additional efforts to increase the uptake of influenza vaccines and antivirals. FUNDING: US Centers for Disease Control and Prevention.

Eyelid metastasis as the initial presentation of a renal cell carcinoma.

Renal cell carcinoma (RCC) often metastasizes to the lungs, liver, brain, and bones. Eyelid metastasis of a distant RCC is an infrequent condition. Breast carcinoma and lung malignancies are responsible of most eyelid metastases, although other malignancies may also metastasize to the eyelid. We report a case with eyelid metastasis as a first presentation of a distant RCC.

Viruses associated with acute respiratory infections and influenza-like illness among outpatients from the Influenza Incidence Surveillance Project, 2010-2011.

BACKGROUND: The Influenza Incidence Surveillance Project (IISP) monitored outpatient acute respiratory infection (ARI; defined as the presence of ≥ 2 respiratory symptoms not meeting ILI criteria) and influenza-like illness (ILI) to determine the incidence and contribution of associated viral etiologies. METHODS: From August 2010 through July 2011, 57 outpatient healthcare providers in 12 US sites reported weekly the number of visits for ILI and ARI and collected respiratory specimens on a subset for viral testing. The incidence was estimated using the number of patients in the practice as the denominator, and the virus-specific incidence of clinic visits was extrapolated from the proportion of patients testing positive. RESULTS: The age-adjusted cumulative incidence of outpatient visits for ARI and ILI combined was 95/1000 persons, with a viral etiology identified in 58% of specimens. Most frequently detected were rhinoviruses/enteroviruses (RV/EV) (21%) and influenza viruses (21%); the resulting extrapolated incidence of outpatient visits was 20 and 19/1000 persons respectively. The incidence of influenza virus-associated clinic visits was highest among patients aged 2-17 years, whereas other viruses had varied patterns among age groups. CONCLUSIONS: The IISP provides a unique opportunity to estimate the outpatient respiratory illness burden by etiology. Influenza virus infection and RV/EV infection(s) represent a substantial burden of respiratory disease in the US outpatient setting, particularly among children.