Foveal avascular zone size and mfERG metrics in diabetes and prediabetes: a pilot study of the relationship between structure and function.

PURPOSE: Previous studies have demonstrated functional and structural retinal changes in type 2 diabetes (T2DM). However, less is understood in prediabetes, which is an important precursor to T2DM. Here, we evaluate the microvasculature structure of the foveal avascular zone (FAZ) and how it is correlated with retinal function as measured by the multifocal electroretinogram (mfERG) across levels of glucose dysfunction to uncover how T2DM and prediabetes alter this structure-function relationship. METHODS: 33 subjects were included: 9 controls, 12 prediabetes, 12 T2DM with no retinopathy or edema. Subjects were aged 30-70 years, had BCVA of 20/25 or better, and had no confounding ocular conditions. Blood was collected via fingerstick to determine Hemoglobin A1c (HbA1c), which was used along with previous diagnosis, to determine study grouping. Optical coherence tomography angiography (OCTA) was used to analyze the FAZ area and was corrected for refractive error. FAZ area was measured by hand using the Heidelberg Spectralis software. mfERG (VERIS 6.3) metrics implicit time (IT) and amplitude were evaluated in the foveal region, macular region, and averaged over the posterior pole of the right eye. Regression analysis was performed between each study group parameter to determine relationships, and t tests with corrections were used to compare groups. RESULTS: FAZ area (superficial plexus) was negatively correlated with mfERG posterior pole amplitude (p < 0.01, R2 = 0.30), foveal amp (p = 0.02 R2 = 0.17) and macular amplitude (p = 0.02 R2 = 0.18) across all 33 study subjects. FAZ and mfERG metrics were not significantly different between study groups in this cohort except for IT, which was more delayed in the diabetes group compared to other groups. CONCLUSION: FAZ area is correlated with mfERG amplitudes but not IT. This suggests a link between the structural metrics and retinal function. Longitudinal follow-up work would be helpful to determine the timing of these changes in prediabetes.

Characteristics of people with epilepsy in three Eastern African countries - a pooled analysis.

BACKGROUND: Epilepsy is one of the most common neurological disorders worldwide. Yet, its treatment gap is large in some areas and especially in sub-Saharan Africa data on clinical, radiological and semiological characteristics, as well as on treatment of persons with epilepsy (PWE) are still scarce. METHODS: We pooled data from four cross-sectional studies on epilepsy in eastern Africa. Two studies from Malawi and Uganda were community-based; two studies in Tanzania (urban Dar es Salaam and rural Haydom) were hospital-based. Clinical characteristics of PWE were assessed by the same questionnaire. Additionally, data on treatment were collected and computed tomography (CT) scans were performed. RESULTS: Overall, 1179 PWE were included in our analysis (581 (49.3%) female, median age 22 years (IQR 15-32 years)). Up to 25% of the patients had focal onset seizures. Those showed a higher rate of remarkable CT scan findings, with especially post-ischaemic and neurocysticercosis-associated lesions, compared to PWE with generalized onset seizures (35.1% vs. 20%). The majority of the patients experienced tonic-clonic seizures (70-85%). Only 67-78% of PWE received anti-seizure medication (ASM) treatment in the community-based studies, mostly monotherapy with phenobarbital, phenytoin or carbamazepine. Yet, underdosage was frequent and a large proportion of PWE received alternative non-ASM treatment consisting of herbal treatment (up to 83%) and/or scarification (up to 20%). CONCLUSIONS: Epilepsy is common in sub-Saharan Africa, often caused by neurocysticercosis or ischaemic strokes. PWE suffer from high seizure rates and subsequent injuries, as well as from socio-economic consequences due to insufficient ASM treatment. This pooled analysis illustrates the need for structural programmes for adequate identification, education, assessment and treatment of PWE in sub-Saharan Africa.

Comparative incidence of early and late bloodstream and respiratory tract co-infection in patients admitted to ICU with COVID-19 pneumonia versus Influenza A or B pneumonia versus no viral pneumonia: wales multicentre ICU cohort study.

OBJECTIVE: The aim is to characterise early and late respiratory and bloodstream co-infection in patients admitted to intensive care units (ICUs) with SARS-CoV-2-related acute hypoxemic respiratory failure (AHRF) needing respiratory support in seven ICUs within Wales, during the first wave of the COVID-19 pandemic. We compare the rate of positivity of different secondary pathogens and their antimicrobial sensitivity in three different patient groups: patients admitted to ICU with COVID-19 pneumonia, Influenza A or B pneumonia, and patients without viral pneumonia. DESIGN: Multicentre, retrospective, observational cohort study with rapid microbiology data from Public Health Wales, sharing of clinical and demographic data from seven participating ICUs. SETTING: Seven Welsh ICUs participated between 10 March and 31 July 2020. Clinical and demographic data for COVID-19 disease were shared by each participating centres, and microbiology data were extracted from a data repository within Public Health Wales. Comparative data were taken from a cohort of patients without viral pneumonia admitted to ICU during the same period as the COVID-19 cohort (referred to as no viral pneumonia or 'no viral' group), and to a retrospective non-matched cohort of consecutive patients with Influenza A or B admitted to ICUs from 20 November 2017. The comparative data for Influenza pneumonia and no viral pneumonia were taken from one of the seven participating ICUs. PARTICIPANTS: A total of 299 consecutive patients admitted to ICUs with COVID-19 pneumonia were compared with 173 and 48 patients admitted with no viral pneumonia or Influenza A or B pneumonia, respectively. MAIN OUTCOME MEASURES: Primary outcome was to calculate comparative incidence of early and late co-infection in patients admitted to ICU with COVID-19, Influenza A or B pneumonia and no viral pneumonia. Secondary outcome was to calculate the individual group of early and late co-infection rate on a per-patient and per-sample basis, with their antimicrobial susceptibility and thirdly to ascertain any statistical correlation between clinical and demographic variables with rate of acquiring co-infection following ICU admission. RESULTS: A total of 299 adults (median age 57, M/F 2:1) were included in the COVID-19 ICU cohort. The incidence of respiratory and bloodstream co-infection was 40.5% and 15.1%, respectively. Staphylococcus aureus was the predominant bacterial pathogen within the first 48 h. Gram-negative organisms from Enterobacterales group were predominantly seen after 48 h in COVID-19 cohort. Comparative no viral pneumonia cohort had lower rates of respiratory tract infection and bloodstream infection. The influenza cohort had similar rates respiratory tract infection and bloodstream infection. Mortality in all three groups was similar, and no clinical or demographic variables were found to increase the rate of co-infection and ICU mortality. CONCLUSIONS: Higher incidence of bacterial co-infection was found in COVID-19 cohort as compared to the no viral pneumonia cohort admitted to ICUs for respiratory support.

Diagnosis of colorectal and emergency surgical site infections in the era of enhanced recovery: an all-Wales prospective study.

AIM: Surgical site infections (SSIs) are associated with increased morbidity, hospital stay and cost. The literature reports that 25% of patients who undergo colorectal surgical procedures develop a SSI. Due to the enhanced recovery programme, patients are being discharged earlier with some SSIs presenting in primary care, making accurate recording of SSIs difficult. The aim of this study was to accurately record the 30-day SSI rate after surgery performed by colorectal surgeons nationally within Wales. METHOD: During March 2019, a national prospective snapshot study of all patients undergoing elective or emergency colorectal and general surgical procedures under the care of a colorectal consultant at 12 Welsh hospitals was completed. There was a multimodal 30-day follow-up using electronic records, clinic visits and/or telephone calls. Diagnosis of SSI was based on Centers for Disease Control and Prevention diagnostic criteria. RESULTS: Within Wales, of the 545 patients included, 13% developed a SSI within 30 days, with SSI rates of 14.3% for elective surgery and 11.7% for emergency surgery. Of these SSIs, 49.3% were diagnosed in primary care, with 28.2% of patients being managed exclusively in the community. There were two peaks of diagnosis at days 5-7 and days 22-28. SSI rates between laparoscopic (8.6%) and open (16.2%) surgeries were significantly different (p = 0.028), and there was also a significantly different rate of SSI between procedure groups (p = 0.001), with high SSI rates for colon (22%) and rectal (18.9%) surgery compared with general surgical procedures. CONCLUSION: This first all-Wales prospective study demonstrated an overall SSI rate of 13%. By incorporating accurate primary care follow-up it was found that 49.3% of these SSIs were diagnosed in primary care.

Fundus motion during mfERG testing.

PURPOSE: The purpose of this study was to assess eye movements during a multifocal ERG (mfERG) recording. This study evaluated the relationship between bivariate contour ellipse areas (BCEAs), mfERG amplitudes (Amps) and mfERG implicit times (ITs) with repeat testing and experienced subjects. METHODS: Thirty subjects were selected (15 experienced to ocular procedures and 15 novices). All were confirmed to have healthy retinas and at least 20/25 vision. MfERGs with a stimulus near 100% contrast and 4-min m-sequence were recorded on two different days using our common clinical technique, which did not constrain the head. VERIS with fundus monitoring system was used for recording with a Burian-Allen electrode. An external camera captured the fundus during each mfERG recording. The optic nerve head position was tracked in each video using a custom algorithm in order to determine BCEAs. Each subject performed one mfERG on two different days. MfERGs were analyzed for Amps and ITs for the fovea and whole eye. RESULTS: There was no correlation between the mfERG metrics and BCEAs with repeat testing. There were also no differences between the experienced and novice subjects for mfERG Amps, ITs or BCEAs. Eye movements between visits were highly correlated (multiple r = 0.67). BCEAs were larger during mfERGs (1.04 ± 0.8 deg2) than those observed in previous literature using brief viewing tasks (< 0.3 deg2). The proportion of time spent fixating within 1.0 and 2.0 degrees of the central hexagon was 68 and 93%, respectively. CONCLUSIONS: This study is the first to evaluate the stability of the retina while recording a mfERG in healthy subjects and indicates that the center of fixation during a mfERG stays within the central hexagon. Eye stability during an initial recording is the best indicator of stability on the second recording. The amount of movement during these recordings did not seem to affect the mfERG Amps or ITs. These data suggest clinical confidence with mfERGs when recording novice patients.

Integration of prevention and control measures for female genital schistosomiasis, HIV and cervical cancer.

Female genital schistosomiasis as a result of chronic infection with Schistosoma haematobium (commonly known as bilharzia) continues to be largely ignored by national and global health policy-makers. International attention for large-scale action against the disease focuses on whether it is a risk factor for the transmission of human immunodeficiency virus (HIV). Yet female genital schistosomiasis itself is linked to pain, bleeding and sub- or infertility, leading to social stigma, and is a common issue for women in schistosomiasis-endemic areas in sub-Saharan Africa. The disease should therefore be recognized as another component of a comprehensive health and human rights agenda for women and girls in Africa, alongside HIV and cervical cancer. Each of these three diseases has a targeted and proven preventive intervention: antiretroviral therapy and pre-exposure prophylaxis for HIV; human papilloma virus vaccine for cervical cancer; and praziquantel treatment for female genital schistosomiasis. We discuss how female genital schistosomiasis control can be integrated with HIV and cervical cancer care. Such a programme will be part of a broader framework of sexual and reproductive health and rights, women's empowerment and social justice in Africa. Integrated approaches that join up multiple public health programmes have the potential to expand or create opportunities to reach more girls and women throughout their life course. We outline a pragmatic operational research agenda that has the potential to optimize joint implementation of a package of measures responding to the specific needs of girls and women.

La schistosomiase génitale féminine, résultant d'une infection chronique à Schistosoma haematobium (également connue sous le nom de bilharziose), continue d'être largement ignorée par les responsables des politiques de santé nationales et internationales. Si le monde lui accorde son attention en vue de mener une action à grande échelle contre la maladie, c'est surtout pour déterminer s'il s'agit d'un facteur de risque pour la transmission du virus de l'immunodéficience humaine (VIH). Pourtant, la schistosomiase génitale féminine est associée à des douleurs, des saignements et peut engendrer l'hypofertilité, voire la stérilité. Par conséquent, celles qui en souffrent sont souvent stigmatisées, et le problème est courant dans les régions endémiques d'Afrique subsaharienne. Cette maladie doit donc être considérée comme composante à part entière d'une approche globale de la santé et des droits humains pour les femmes et filles africaines, à l'instar du VIH et du cancer du col de l'utérus. Chacune de ces trois maladies fait l'objet d'une intervention préventive ciblée qui a déjà fait ses preuves: le traitement antirétroviral et la prophylaxie pré-exposition pour le VIH; le vaccin contre le papillomavirus humain pour le cancer du col de l'utérus; et l'administration de praziquantel pour la schistosomiase génitale féminine. Le présent document se penche sur la manière d'intégrer la schistosomiase génitale féminine dans la prise en charge du VIH et du cancer du col de l'utérus. Un tel programme fera partie d'un cadre plus vaste consacré aux droits et à la santé sexuelle et reproductive, à l'émancipation des femmes et à la justice sociale en Afrique. Les approches intégrées qui regroupent plusieurs programmes de santé publique permettent d'élargir des perspectives ou de créer des opportunités visant à atteindre un plus grand nombre de filles et de femmes tout au long de leur vie. Nous exposons les grandes lignes d'un programme de recherches pragmatiques et opérationnelles capable d'optimiser la mise en œuvre conjointe d'une série de mesures qui répondent aux besoins spécifiques des filles et des femmes.

Los responsables de formular las políticas sanitarias nacionales y globales siguen ignorando en gran medida la esquistosomiasis genital femenina como consecuencia de la infección crónica por Schistosoma haematobium (conocida comúnmente como bilharziasis). La atención internacional para adoptar medidas de gran alcance contra la enfermedad se centra en determinar si es un factor de riesgo para la transmisión del virus de la inmunodeficiencia humana (VIH). Sin embargo, la propia esquistosomiasis genital femenina está vinculada al dolor, las hemorragias y la infertilidad o subfertilidad, lo que conduce al estigma social, además de ser un problema común para las mujeres de las áreas en donde la esquistosomiasis es endémica en el África subsahariana. Por consiguiente, la enfermedad debe ser reconocida como otro componente de un programa integral de salud y de derechos humanos para las mujeres y las niñas de África, junto con el VIH y el cáncer de cuello uterino. Cada una de estas tres enfermedades tiene una intervención preventiva específica y comprobada: la terapia antirretroviral y la profilaxis previa a la exposición para el VIH; la vacuna contra el virus del papiloma humano para el cáncer de cuello uterino; y el tratamiento con praziquantel para la esquistosomiasis genital femenina. Se analiza cómo el control de la esquistosomiasis genital femenina se puede integrar con la atención del VIH y el cáncer de cuello uterino. Ese programa formará parte de un marco más amplio de salud y de derechos sexuales y reproductivos, de empoderamiento de la mujer y de justicia social en África. Los enfoques integrados que unen múltiples programas de salud pública tienen el potencial de ampliar o crear oportunidades para llegar a más niñas y mujeres a lo largo de sus vidas. Se describe a grandes rasgos un programa de investigación operacional pragmático que tiene el potencial de optimizar la implementación conjunta de una serie de medidas que respondan a las necesidades específicas de las niñas y de las mujeres.

Modelling for Taenia solium control strategies beyond 2020.

The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis. The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available. In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases. In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets. The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches. In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium. We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. solium transmission, including model comparison, refinement, calibration and validation. Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies.

Taenia solium est un cestode qui entraîne une charge intersectorielle économique et sanitaire considérable en provoquant une neurocysticercose humaine et une cysticercose porcine. La feuille de route sur les maladies tropicales négligées, publiée en 2012 par l'Organisation mondiale de la Santé (OMS), appelait à développer une stratégie de contrôle validée pour T. solium ; cependant, cette stratégie n'est pas encore disponible à l'heure actuelle. En 2019, l'OMS a lancé une procédure de consultation mondiale visant à préciser les objectifs de contrôle de T. solium après 2020, afin de rédiger une nouvelle feuille de route sur les maladies tropicales négligées. Deux groupes qui travaillent sur des modèles mathématiques de taeniasis et cysticercose (modèles cystiSim et EPICYST) ainsi qu'une série d'autres intervenants ont donc organisé un atelier pour fournir une contribution technique à cette consultation et développer un programme de recherche destiné à soutenir les efforts de réalisation des objectifs ultérieurs à 2020. L'atelier a donné naissance à une collaboration, CystiTeam, qui s'intéresse à la biologie des populations, à la dynamique de transmission, à l'épidémiologie et au contrôle de T. solium en employant des méthodes de modélisation mathématique. Le présent document retrace l'évolution du contrôle de T. solium, en particulier l'usage de la modélisation pour contribuer à atteindre les objectifs d'après 2020 en la matière. Nous abordons les diverses étapes de renforcement de la confiance accordée aux capacités prédictives des modèles mathématiques et informatiques existants sur la transmission de T. solium, notamment la comparaison, l'optimisation, le calibrage et la validation des modèles. Élargir le partenariat CystiTeam en intégrant d'autres groupes de recherche et intervenants, surtout ceux opérant dans différentes zones géographiques et endémiques, accroîtra les chances d'amélioration de l'applicabilité pour les modèles de transmission de T. solium, et permettra ainsi d'établir des stratégies de lutte contre la taeniasis et la cysticercose.

El cestodo Taenia solium es responsable de una importante carga sanitaria y económica transversal debido a la neurocisticercosis humana y la cisticercosis porcina. En la hoja de ruta de la Organización Mundial de la Salud (OMS) de 2012 sobre las enfermedades tropicales desatendidas se solicitaba la elaboración de una estrategia validada para el control de T. solium; sin embargo, dicha estrategia aún no está disponible. En 2019, la OMS inició una consulta mundial destinada a perfeccionar los objetivos de control de T. solium aplicables a partir de 2020 con miras a elaborar una hoja de ruta nueva sobre las enfermedades tropicales desatendidas. Consecuentemente, dos grupos que trabajan en modelos matemáticos de teniasis y cisticercosis (modelos cystiSim y EPICYST), junto con un grupo de otros interesados, organizaron un seminario para contribuir técnicamente a la consulta de la OMS y elaborar un plan de investigación a fin de apoyar los esfuerzos para lograr los objetivos a partir de 2020. El seminario impulsó la formación de un equipo de colaboración, CystiTeam, para abordar la biología de la población, la dinámica de la transmisión, la epidemiología y el control de T. solium mediante enfoques de modelos matemáticos. En el presente documento se describen las novedades en el control de T. solium y, en particular, la aplicación de modelos para ayudar a lograr los objetivos a partir de 2020 sobre el control de T. solium. Se analizan las etapas necesarias para mejorar la confianza en las capacidades de predicción de los modelos matemáticos y computacionales existentes sobre la transmisión de T. solium, incluyendo la comparación, el perfeccionamiento, el ajuste y la validación de los modelos. La ampliación de la asociación CystiTeam a otros grupos de investigación e interesados, en particular los que operan en diferentes zonas geográficas y endémicas, reforzará las perspectivas de mejorar la aplicabilidad de los modelos sobre las transmisión de T. solium para fundamentar las estrategias de control de la teniasis y la cisticercosis.

Case Report: Long-term Structural and Functional Effects of Ethambutol Optic Neuropathy.

SIGNIFICANCE: This case report demonstrates reduction in the retinal nerve fiber layer (RNFL) thickness and an abnormal electroretinogram after toxic optic neuropathy from ethambutol, more than 1 year after improvements in visual acuity (VA) and visual fields (VFs) were seen. Although many studies have described complications of ethambutol, continuing reduction in RNFL thickness 2 years after discontinuation has not been described elsewhere. PURPOSE: It is well known that ethambutol can cause optic nerve toxicity, visual impairment, and VF loss. Visual acuity can be regained after stopping the drug; however, the amount and time frame are variable. There are few data on long-term follow-up of these cases to direct clinicians how to proceed once VA has stabilized. Here we present a case with 2 years of follow-up for a patient with ethambutol toxicity, showing the condition change even after VA becomes normal. CASE REPORT: A 61-year-old man presented shortly after discontinuing ethambutol for Mycobacterium avium complex. Visual acuity values were 20/70 in the right eye and 20/125 in the left eye with cecocentral VF scotomas. Optical coherence tomography showed normal RNFL. Visual-evoked potentials were significantly reduced and delayed. Over the course of 2 years, the patient became asymptomatic as VA and VF returned to normal and visual-evoked potential improved. However, the optical coherence tomography RNFL was reduced from each visit to the next, and the electroretinogram showed decreased scotopic and photopic amplitudes. CONCLUSIONS: Signs of ethambutol toxicity may remain or worsen years after discontinuation, even in the absence of patient symptoms and with normal VA and VF.

Functional retinal outcomes in patients with prediabetes and type 2 diabetes.

PURPOSE: Type 2 diabetes (T2DM) is a leading cause of visual impairment. Its precursor, prediabetes (preDM), is growing in numbers every year. While it is well known that T2DM causes changes in retinal function early in the disease process, it is likely that some of these changes emerge during the preDM stage. This study evaluates retinal function measures in patients with preDM to determine if there are differences in colour vision, contrast sensitivity (CS), and multifocal electroretinogram (mfERG) measures present before T2DM is diagnosed. METHODS: The L'Anthony desaturated D-15 test, Mars Chart CS test, and mfERG were administered on the right eye of 43 participants; 15 controls (HbA1c ≤ 5.6%), 17 with preDM (HbA1c 5.7%-6.4%), and 11 with T2DM (either physician diagnosed or with untreated HbA1c ≥ 6.5%). HbA1c values were measured at the time of the other tests. Colour vision confusion scores (CVCS) were calculated from the D-15 using the method developed by Torok. Multivariate regression (which controlled for age differences) was used to evaluate the relationship of HbA1c and functional measures. Kruskal-Wallis tests were also used to evaluate differences between groups with post-hoc analysis. RESULTS: CVCSs were significantly different between the three groups (p = 0.009). There was an association between higher CVCS and higher HbA1c values across all groups as well as specifically within the preDM group when controlling for age (R2  = 0.29, p = 0.01 and R2  = 0.39, p = 0.02 respectively). Multivariate regression of all of the functional tests together and HbA1c found only colour vision remained significant, indicating that the functional examination metrics may provide redundant data, with similar changes in prediabetes where colour vision may be the strongest indicator early in the process. CONCLUSIONS: Patients with prediabetes have functional changes that can be measured in the retina before the diagnosis of diabetes, with the L'Anthony D-15 colour vision test providing the strongest association with glucose dysregulation in this population. This has important implications for follow up and screening for diabetes within optometric practices. Further studies are needed to follow these patients over time to see how and when these metrics change.

Duct Stenting Versus Modified Blalock-Taussig Shunt in Neonates With Duct-Dependent Pulmonary Blood Flow: Associations With Clinical Outcomes in a Multicenter National Study.

BACKGROUND: Infants born with cardiac abnormalities causing dependence on the arterial duct for pulmonary blood flow are often palliated with a shunt usually between the subclavian artery and either pulmonary artery. A so-called modified Blalock-Taussig shunt allows progress through early life to an age and weight at which repair or further more stable palliation can be safely achieved. Modified Blalock-Taussig shunts continue to present concern for postprocedural instability and early mortality such that other alternatives continue to be explored. Duct stenting (DS) is emerging as one such alternative with potential for greater early stability and improved survival. METHODS: The purpose of this study was to compare postprocedural outcomes and survival to next-stage palliative or reparative surgery between patients undergoing a modified Blalock-Taussig shunt or a DS in infants with duct-dependent pulmonary blood flow. All patients undergoing cardiac surgery and congenital interventions in the United Kingdom are prospectively recruited to an externally validated national outcome audit. From this audit, participating UK centers identified infants <30 days of age undergoing either a Blalock-Taussig shunt or a DS for cardiac conditions with duct-dependent pulmonary blood flow between January 2012 and December 31, 2015. One hundred seventy-one patients underwent a modified Blalock-Taussig shunt, and in 83 patients, DS was attempted. Primary and secondary outcomes of survival and need for extracorporeal support were analyzed with multivariable logistic regression. Longer-term mortality before repair and reintervention were analyzed with Cox proportional hazards regression. All multivariable analyses accommodated a propensity score to balance patient characteristics between the groups. RESULTS: There was an early (to discharge) survival advantage for infants before next-stage surgery in the DS group (odds ratio, 4.24; 95% confidence interval, 1.37-13.14; P=0.012). There was also a difference in the need for postprocedural extracorporeal support in favor of the DS group (odds ratio, 0.22; 95% confidence interval, 0.05-1.05; P=0.058). Longer-term survival outcomes showed a reduced risk of death before repair in the DS group (hazard ratio, 0.25; 95% confidence interval, 0.07-0.85; P=0.026) but a slightly increased risk of reintervention (hazard ratio, 1.50; 95% confidence interval, 0.85-2.64; P=0.165). CONCLUSIONS: DS is emerging as a preferred alternative to a surgical shunt for neonatal palliation with evidence for greater postprocedural stability and improved patient survival to destination surgical treatment.

Foveal amplitudes of multifocal electroretinograms are larger following full-field electroretinograms.

PURPOSE: The clinical standards for multifocal electroretinograms (mfERG) call for adaption to normal room lighting before the mfERG begins. They specify that any assessments where bright lights are used, should be done after the mfERG to prevent excess stimulation of retinal cells. However, full-field electroretinograms (FFERG) are performed prior to mfERGs in some clinical settings. It is unclear from the literature whether the FFERG has an impact on the mfERG. This study seeks to examine the effect of the FFERG on the mfERG when performed sequentially. METHODS: Thirty young healthy subjects (age 27.1 ± 3.5 years) were included. Patients reported for two visits and were fully dilated at both visits. At visit one, a FFERG was recorded (VERIS 6.2) using our clinical protocol which includes an ISCEV standard flash sequence; each flash condition was repeated 4-6 times. Following the FFERG, an mfERG was recorded using a 4-min m-sequence at near 100% contrast. At visit two, only the mfERG was recorded. A Burian-Allen contact lens electrode filled with celluvisc was used for all recordings. The two mfERGs were compared for foveal, peripheral, and overall implicit time (IT) and amplitudes (amp). Paired t tests were used to evaluate the data. Coefficient of variation and Bland-Altman analysis was also reported for this patient group. RESULTS: There was a small but statistically significant difference in foveal amplitudes (amp) (p = 0.004) wherein the amp was larger following the FFERG stimuli. The mean difference was 11.1 nV/deg2 (100.9 nV vs 89.8 nV). There was no difference in foveal IT (p = 0.66). There was no difference in overall IT or amp when averaging the entire eye (p = 0.44 amp and p = 0.54 IT) or just evaluating the periphery (p = 0.87 amp and p = 0.051 IT). Bland-Altman analysis found a coefficient of repeatability overall was 1.57 ms (IT) and 10.7 nV/deg2 (amp). CONCLUSIONS: The difference in foveal amplitude is likely the result of a small long-term cone adaptation, but further studies are needed. While it is statistically significant, the small difference is unlikely to be clinically important. These results should help increase clinical confidence in mfERG results when recorded following a FFERG.

The corneal nerve density in the sub-basal plexus decreases with increasing myopia: a pilot study.

PURPOSE: Myopia can cause many changes in the health of the eye. As it becomes more prevalent worldwide, more patients seek correction in the form of glasses, contact lenses and refractive surgery. In this study we explore the impact that high myopia has on central corneal nerve density by comparing sub basal nerve plexus density measured by confocal microscopy in a variety of refractive errors. METHODS: Seventy healthy adult subjects between the ages of 21-50 years participated in this study. The study took place in two phases with no overlapping subjects (n = 30 phase 1 and n = 40 phase 2). In both phases an autorefraction, keratometry reading, corneal thickness measure and confocal corneal scan of the sub basal nerve plexus were performed for both eyes. There were 11 hyperopes (+0.50 to +3.50DS), six emmetropes (-0.25 to +0.50DS), 30 low myopes (-5.50 to -0.50DS), and 23 high myopes (-5.50DS and above). In the second phase of the study additional tests were performed including an axial length, additional corneal scans, and a questionnaire that asked about age of first refractive correction and contact lens wear. Corneal nerves were imaged over the central cornea with a Nidek CS4 confocal microscope (460 × 345 µm field). Nerves were evaluated using the NeuronJ program for density calculation. One eye was selected for inclusion based on image quality and higher refractive error (more myopic or hyperopic). RESULTS: As myopia increased, nerve density decreased (t1  = 3.86, p < 0.001). We also note a decrease in data scatter above -7 D. The relationship between axial length values and nerve density was also significant and the slope was not as robust as refractive error (t1  = 2.4, p < 0.04). As expected there was a significant difference between the four groups in axial length (F3  = 19.9, p < 0.001) and age of first refractive correction of the myopic groups (14.9 vs 11.5 years; t46  = 2.99 p < 0.01). There was no difference in keratometry readings or corneal thickness between the groups (F3  = 0.6, p = 0.66 and F3  = 1.2, p = 0.33 respectively). CONCLUSION: Corneal nerve density in the sub-basal plexus decreased with increasing myopia. This could have implications for corneal surgery and contact lens wear in this patient population.

Arteriole tortuosity associated with diabetic retinopathy and cholesterol.

PURPOSE: Earlier identification of diabetic eye disease is an important research effort. Retinopathy is widely acknowledged but retinal vessel changes are not evaluated as stringently. Here, we create a multivariate model for the association between retinal vessel tortuosity (RVT) and other health factors in patients with diabetes. METHODS: Three hundred eyes of 150 patients with diabetes were included. Three investigators independently reviewed telemedicine fundus photographs and scored the level of diabetic retinopathy (DR) and RVT. These scores were evaluated for agreement and averaged. Also collected were age, duration of diabetes, presence or absence of diabetic nephropathy or neuropathy, blood pressure, total cholesterol, and hemoglobin A1c. A regression model evaluating the association of tortuosity with other factors was created. RESULTS: There was very high agreement between the three graders for level of DR (κ = 0.84). Agreement between the three graders for RVT varied substantially: poor for venous tortuosity (κ = 0.23) and fair for arteriole tortuosity (κ = 0.44) and overall gut tortuosity (κ = 0.42). The overall gut tortuosity was the most reproducible for the graders with a correlation coefficient of 0.923. There were univariate associations between arteriole tortuosity and venous tortuosity, DR level, and cholesterol. The selected best multivariate model found arteriole tortuosity to be associated with DR and cholesterol levels. CONCLUSIONS: First, RVT, particularly for venules, is difficult to grade consistently; therefore, future studies examining tortuosity should focus on arterioles. Second, the model indicates that there is an association between vessel changes, DR, and systemic cholesterol levels. Although DR and RVT are readily available to assess concurrently on a photograph, the addition of cholesterol to this model indicates that patients with RVT may warrant further follow-up on health factors, such as cholesterol levels.

Correlation of tear osmolarity and dry eye symptoms in convention attendees.

PURPOSE: To assess the correlation between tear osmolarity readings and symptoms of dry eye in a nonclinical convenience sample and to determine how well symptoms and osmolarity correlate with the self-assessment of dry eye. METHODS: Two hundred forty-nine attendees in the exhibit hall at an optometric educational meeting agreed to participate in a dry eye study. Contact lens wearers were excluded. Volunteers supplied demographic information and completed a 5-item Dry Eye Questionnaire (DEQ-5) and answered the question "Do you think you have dry eye" with a yes or no response. Osmolarity testing was done using the TearLab instrument on the right eye, then on the left eye. Pearson correlation analyses were performed to determine the relationship between variables. RESULTS: There was no correlation between DEQ-5 scores and average tear osmolarity (correlation coefficient, 0.02) and highest osmolarity (correlation coefficient, 0.03). The mean DEQ-5 score was significantly higher among subjects who self-reported dry eye (mean, 11.3; p < 0.0001) compared with those who did not (mean, 5.4; p < 0.0001). No differences were observed between the yes and no self-reported dry eye groups and average osmolarity (p = 0.23) and highest osmolarity (p = 0.14). CONCLUSIONS: In this nonclinical population, there was no significant correlation between tear osmolarity and ocular symptoms as reported or between tear osmolarity and the self-assessment of dry eye.

Differences in neuroretinal function between adult males and females.

PURPOSE: To determine whether neuroretinal function differs in healthy adult males and females younger and older than 50 years. METHODS: This study included one eye from each of 50 normal subjects (29 females and 21 males). Neuroretinal function was assessed using first-order P1 implicit times (ITs) and N1-P1 amplitudes (AMPs) obtained from photopic multifocal electroretinograms. To assess local differences, retinal maps of local IT and (separately) AMP averages were constructed for each subject group. To examine global differences, each subject's 103 ITs and (separately) AMPs were also averaged to create whole-eye averages. Subsequently, retinal maps and whole-eye averages of one subject group were compared with those of another. RESULTS: In subjects younger than 50 years, neuroretinal function differed significantly between the males and females: local ITs were significantly shorter at 83 of 103 tested retinal locations, and whole-eye IT averages were shorter (p = 0.015) in the males compared with the females. In contrast, no analysis indicated that the males and females older than 50 years were significantly different. A subanalysis showed that the females who reported a hysterectomy (n = 5) had the longest whole-eye ITs of all subject groups (p ≤ 0.0013). In the females who did not report a hysterectomy, neuroretinal function was worse in the females older than 50 years compared with the females younger than 50 years: local ITs were significantly longer at 62 of 103 retinal locations tested, and whole-eye IT averages tended to be greater (p = 0.04). Conversely, ITs were not statistically different between the younger and older males. N1-P1 amplitudes did not differ between the sexes. CONCLUSIONS: Multifocal electroretinogram IT differs between males and females, depending on the age group and hysterectomy status.

Variations in Retinal Oxygen Saturation in a Diverse Healthy Population.

Purpose: Local retinal oxygen saturation is a research technique, which has the potential as a biomarker for diabetes. However, normative data has not been established. This study examined differences in oxygen saturation around the macula and characterizes the relationship between age, race, refractive error (RE), sex, blood pressure (BP), prediabetic status and oxygen saturation. Methods: Fifty-nine subjects aged 22-69 (38.8 ± 14.7 years) were included who were racially diverse and with equal gender distribution. None had eye disease. Oxygen saturation was taken with the Zilia Ocular in 4 locations around the macula 3.1 degrees from the fovea and they were also averaged. BP, RE, and HbA1c were noted. Regression analyses for oximetry and other factors were completed as were t-tests with multiple comparison corrections. Results: There were significant variations in oximetry measures by race, with higher pigmentation levels associated with lower oximetry values (p < 0.01). There was no relationship between oximetry and sex (p = 0.34), RE (p = 0.67), BP (systolic p = 0.61, diastolic p = 0.71) nor prediabetic status (p = 0.87). Oximetry was associated with age when controlling for race (P < 0.002). Nasal-temporal variations showed nasal oximetry to higher than temporal measures (P < 0.01). Conclusion: This study revealed race/pigmentation is an important influence on oximetry measures. Retinal location also caused variations, likely due to proximity to larger vessels nasally. No differences in sex, RE nor BP were observed to alter local oxygen saturation. However, age was correlated when considered with race. This study will inform our future work in different disease states and is an important first step in evaluating this technology.

This study evaluates a new research instrument (Zilia Ocular) which measures how much oxygen is in the very small blood vessels of the retina. Our group wanted to evaluate healthy people to find out if the measurements the instrument takes are different in different sexes, ages, races, glasses prescriptions and blood pressures. We also looked at if they were changed in people with prediabetes and if it is different in different locations on the retina. We found that the measures are different in different races and ages. The measures also change with location in the eye. The other factors did not change the measurements of oxygen saturation on this instrument. We need to know this information because we want to detect changes in the retina in diabetes in diverse patient groups; however, we need to know about normal variations to better understand and collect that data.

Evaluation of retinal structure and function in prediabetes.

Purpose: Alterations in retinal structure and function have been well documented in type 2 diabetes (T2DM). However, few studies have evaluated the eye in prediabetes (preDM), a precursor to T2DM. It is unknown which retinal deficits, if any, occur before T2DM diagnosis. This study evaluates retinal structure via optical coherence tomography (OCT) and retinal function via multifocal electroretinogram (mfERG) N1 and P1 in those with PreDM. The goal is to evaluate associations between structure and function across glucose dysfunction. Methods: 85 subjects (aged 28-69yrs) were tested with VERIS mfERG and Heidelberg Spectralis OCT. Demographic and health information was collected. Subjects were grouped by HbA1c: 33 controls (HbA1c <5.7%), 31 with preDM (HbA1c 5.7-6.4%), and 21 with T2DM (HbA1c >6.4% at the time of testing or diagnosed by physician) and mild or no retinopathy. mfERG N1 and P1 latency and amplitude were measured for the right eye in the foveal hexagon (central 2.4°). Average macular thickness was also measured over the central 3.3°. Groups were compared with ANOVA and corrected t-tests. Models of these associations with diabetes diagnosis (in groups above) were created with backward multivariate regression. Results: The T2DM group was exceptionally well-controlled with an HbA1c of 7.0% ± 0.68 but also had elevated systolic blood pressure compared to other groups (P<0.01). The age of the control group was younger (P<0.01), so other testing was age controlled. There was a borderline but statistically significant difference in P1 between the control group and both the preDM and T2DM groups after Bonferroni corrections (P<0.03). There was also a difference in N1 latency between the control and other groups (P<0.001). A multivariate model demonstrated a significant relationship between T2DM/PreDM diagnosis and delayed N1 latency, reduced foveal thickness, and age. Conclusions: Structure and function together can provide an associative model of preDM or T2DM changes for patients. Based on this multivariate model, N1 is strongly associated with preDM and T2DM. N1 findings and decreasing foveal thickness are additive and can together inform ocular health related to preDM. Future longitudinal studies are needed to understand changes in function and structure in preDM and T2DM.

Test-retest repeatability in macular retinal oximetry.

CLINICAL RELEVANCE: Evaluation of retinal macular oxygen saturation in healthy controls can aid in understanding the pathological changes seen in similar locations of those with vascular diseases like diabetes. BACKGROUND: The aim of this study was to determine the test-retest repeatability of localised retinal oximetry measurements in the macula on the Zilia Oximeter within healthy subjects of different races, 18-40 years old. Oxygen saturation was measured between three time points within the same locations of the right eye. METHODS: Twenty seven subjects were included (aged 26.3 ± 3.6 years). All were confirmed to have healthy retinas and at least 6/9 vision. Oximetry measurements were taken using the Zilia to acquire local oxygen saturation measurements (300 µm diameter) at four points 3.1 degrees from the fovea in the superior/temporal, superior/nasal, inferior/temporal, and inferior/nasal locations. Oximetry measurements were taken twice on the same day 20 minutes apart and then again 1-2 weeks later. Oximetry data was analysed with intraclass correlation between visits. To assess intrasubject repeatability, the Bland-Altman repeatability coefficient and coefficient of variation were calculated. RESULTS: Average Intraclass correlation for the three acquisition times of the right eye was 0.78. The averaged intrasubject repeatability coefficient for the three acquisition times was 8.4. The averaged coefficient of variation was 5.4%. CONCLUSION: The Zilia oximeter has good macular test-retest repeatability; however, multiple measurements may be needed to ensure accuracy.