Review of En-Face Choroidal Imaging Using Spectral-Domain Optical Coherence Tomography

Investigations of choroidal vasculature have been of particular interest given choroidal vascular dysfunction are thought to be related with a number pathologic conditions such as central serous chorioretinopathy and various forms of AMD, including polypoidal choroidal vasculopathy. On the other hand, en face imaging of the choroid allows an exceptional alternative to histopathologic evaluation of the choroid, and can be used to quantify choroidal vascular structures. Our former study verified differences in the macular choroid in AMD and control patients previously noted on histopathologic studies. The use of phase-resolved approaches in larger population longitudinal studies reveal the sequence of RPE and choroidal changes in the pathogenesis of various AMD subtypes, which cannot be done using histopathology. Issues with lateral resolution of the OCT system in measuring choriocapillaris size could be solved by incorporating the axial dimension of the choriocapillaris into choriocapilaris diameter assessment (assuming the choriocapillaris are round in vivo), and by correcting for anisometric pixel resolution. Forthcoming studies are required to determine whether areas of choriocapillaris correlate with areas of RPD lesions

Review of En-Face Choroidal Imaging Using Spectral-Domain Optical Coherence Tomography

Investigations of choroidal vasculature have been of particular interest given choroidal vascular dysfunction are thought to be related with a number pathologic conditions such as central serous chorioretinopathy and various forms of AMD, including polypoidal choroidal vasculopathy. On the other hand, en face imaging of the choroid allows an exceptional alternative to histopathologic evaluation of the choroid, and can be used to quantify choroidal vascular structures. Our former study verified differences in the macular choroid in AMD and control patients previously noted on histopathologic studies. The use of phase-resolved approaches in larger population longitudinal studies reveal the sequence of RPE and choroidal changes in the pathogenesis of various AMD subtypes, which cannot be done using histopathology. Issues with lateral resolution of the OCT system in measuring choriocapillaris size could be solved by incorporating the axial dimension of the choriocapillaris into choriocapilaris diameter assessment (assuming the choriocapillaris are round in vivo), and by correcting for anisometric pixel resolution. Forthcoming studies are required to determine whether areas of choriocapillaris correlate with areas of RPD lesions

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Much-Ado About Acute Vision Loss

A previously healthy myopic 35-year-old Caucasian man without any significant medical or surgical history developed acute bilateral vision loss.Progressive fatigue and right face, arm, and leg pain.Magnetic Resonance Imagin

Much-Ado About Acute Vision Loss

A previously healthy myopic 35-year-old Caucasian man without any significant medical or surgical history developed acute bilateral vision loss.Progressive fatigue and right face, arm, and leg pain.Magnetic Resonance ImagingAttache

Much-Ado About Acute Vision Loss

A previously healthy myopic 35-year-old Caucasian man without any significant medical or surgical history developed acute bilateral vision loss.Progressive fatigue and right face, arm, and leg pain.Magnetic Resonance ImagingAttache

A Pilot Study of Morphometric Analysis of Choroidal Vasculature <em>In Vivo</em>, Using En Face Optical Coherence Tomography

<div><h3>Purpose</h3><p>To study the ability of volumetric spectral domain optical coherence tomography (SD-OCT) to perform quantitative measurement of the choroidal vasculature <em>in vivo</em>.</p> <h3>Methods</h3><p>Choroidal vascular density and vessel size were quantified using en face choroidal scans from various depths below the retinal pigment epithelium (RPE) in 58 eyes of 58 patients with either epiretinal membranes (ERM), early age-related macular degeneration (AMD), or reticular pseudo-drusen (RPD). For each patient, we used the macular volume scan (6×6 mm cube) for vessel quantification, while high-definition (HD) cross-section raster scans were used to qualitatively assess vascularity of the choroidal sub-layers, and measure choroidal thickness.</p> <h3>Results</h3><p>Of the 58 patients, more were female (66% versus 34% male), of whom 14 (24%) had ERM, 11 (19%) early AMD, and 33 (57%) RPD. Compared to intact choriocapillaris in all ERM (100%), none of the RPD and only 5/11 (45%) early AMD eyes had visible choriocapillaris on either cross section or C-scans (p-value<0.001). When comparing select regions from the most superficial C-scans, early AMD group had lowest vascular density and RPD had highest (p-value 0.04). Qualitative evaluation of C-scans from all three groups revealed a more granular appearance of the choriocapillaris in ERM versus increased stroma and larger vessels in the RPD eyes.</p> <h3>Conclusions</h3><p>SD-OCT can be used to qualitatively and quantitatively assess choroidal vascularity <em>in vivo</em>. Our findings correlate to previously reported histopathologic studies. Lack of choriocapillaris on HD cross-sections or C-scans in all RPD and about half of early AMD eyes suggests earlier choroidal involvement in AMD and specifically, RPD.</p> </div

Choroidal Thickness.

<p>AMD = age-related macular degeneration; crude versus adjusted for age and gender; Control = epiretinal membranes; early AMD patients = drusen, advanced reticular patients = reticular pseudodrusen with advanced atrophic or neovascular lesions.</p>*<p>Analysis of variance (ANOVA) p-values. Pairwise comparisons were statistically significant between Drusen and early reticulars (p = 0.04), but not significant when comparing other subtypes of AMD (p>0.05).</p>Ac<p>: Analysis of covariance (ANCOVA) p-value, adjusting for age and gender. When the ANOVA or ANCOVA were statistically significant (p<0.05), Bonferroni adjusted p-values were calculated for the pairwise comparisons.</p

Qualitative Choriocapillaris Assessment Comparing C-Scans and B-Scans (Example 2).

<p>Comparing another example of control (top panel), early age-related macular degeneration (AMD, middle panel) and reticular (bottom panel) patients, reveals qualitatively different appearance of representative C-scans obtained just below the retinal pigment epithelium in reticular groups (bottom right) than in the control and AMD groups (top right and center right, respectively). Red boxes on the B-Scans (left) show magnified and colorized selected areas of choroidal vasculature from the regions contained by the smaller red boxes on the C-Scans (right) for each group. Blue boxes on the B-Scans (left) show magnified areas of selected stroma from the regions contained by the smaller blue boxes on the C-Scans (right). Stromal sections demonstrate more patchy whitish regions in the RPD group (bottom panel) as compared to the control and AMD groups (top and middle panels) but similar vessel density due to the presence of larger vessels.</p