Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut.

Purpose: Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases. We investigated the microbial composition in patients with glaucoma and healthy controls. Moreover, we analyzed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup-to-disc ratio (VCDR; quantifying glaucoma severity). Methods: The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 patients with glaucoma and 1247 age- and sex-matched participants without glaucoma were included in our analyses. Stool samples were used to generate 16S rRNA gene profiles. We assessed associations with 233 genera and species. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings. Results: Several butyrate-producing taxa (e.g. Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, and Shuttleworthia) were less abundant in people with glaucoma compared to healthy controls. The same taxa were also associated with lower IOP and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses. Conclusions: Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results suggest that microbial dysbiosis plays a role in the pathophysiology of glaucoma.

Temporal-to-Nasal Macular Ganglion Cell and Inner Plexiform Layer Ratios in a Large Adult Twin Cohort: Correlations With Age and Heritability.

Purpose: Temporal-to-nasal macular ganglion cell layer thickness ratios are reduced in albinism. We explored similar ratios in a large twin cohort to investigate ranges in healthy adults, correlations with age, and heritability. Methods: More than 1000 twin pairs from TwinsUK underwent macular optical coherence tomography (OCT) scans. Automated segmentation yielded thicknesses for the combined ganglion cell and inner plexiform layer (GCIPL) in Early Treatment of Diabetic Retinopathy Study subfields. Participants with diseases likely to affect these layers or segmentation accuracy were excluded. Inner and outer ratios were defined as the ratio of temporal-to-nasal GCIPL thickness for inner and outer subfields respectively. Corresponding ratios were obtained from a smaller cohort undergoing OCTs with a different device (three-dimensional (3D)-OCT, Topcon, Japan). Results: Scans from 2300 twins (1150 pairs) were included (mean [SD] age, 53.9 (16.5) years). Mean (SD) inner and outer ratios were 0.89 (0.09) and 0.84 (0.11), correlating negatively with age (coefficients, -0.17 and -0.21, respectively). In males (150 pairs) ratios were higher and did not correlate significantly with age. Intrapair correlation coefficients were higher in monozygotic than dizygotic pairs; age-adjusted heritability estimates were 0.20 and 0.23 for inner and outer ratios, respectively. For the second cohort (n = 166), mean (SD) ratios were 0.93 (0.08) and 0.91 (0.09), significantly greater than for the larger cohort. Conclusions: Our study gives reference values for temporal-to-nasal macular GCIPL subfield ratios. Weak negative correlations with age emerged. Genetic factors may contribute to ∼20% to 23% of the variance in healthy individuals. The ratios differ according to the OCT platform used.

Prevalence, Concordance, and Heritability of Vitreomacular Interface Abnormalities in a Twin Study.

Purpose: The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the prevalence case wise concordance between monozygotic and dizygotic twin pairs, and heritability of common VMI abnormalities, including epiretinal membrane (ERM), posterior vitreous detachment (PVD), vitreomacular adhesion (VMA), vitreomacular traction (VMT), lamellar macular holes (LMHs), and full-thickness macular holes (FTMHs). Methods: This is a single-center, cross-sectional classical twin study of 3406 TwinsUK participants over the age of 40 years who underwent spectral domain macular optical coherence tomography (SD-OCT) scans which were graded for signs of VMI abnormalities. Case wise concordance was calculated and the heritability of each VMI abnormality was estimated using OpenMx structural equation modeling. Results: In this population (mean age = 62.0 years [SD = 10.4 years], range = 40-89 years) the overall prevalence of ERM was 15.6% (95% confidence interval [CI] = 14.4-16.9) and increased with age, posterior vitreous detachment affected 21.3% (20.0-22.7), and VMA was diagnosed in 11.8% (10.8-13.0). Monozygotic twins were more concordant for all traits than dizygotic twins, and age, spherical equivalent refraction (SER), and lens status-adjusted heritability was estimated at 38.9% (95% CI = 33.6-52.8) for ERM, 53.2% (95% CI = 41.8-63.2) for PVD, and 48.1% (95% CI = 33.6-58) for VMA. Conclusions: Common VMI abnormalities are heritable and therefore have an underlying genetic component. Given the sight-threatening potential of VMI abnormalities, further genetic studies, such as genomewide association studies, would be useful to identify genes and pathways implicated in their pathogenesis.

Building the barricade-DIY slit lamp breath shield.

Ophthalmologists were concerned about the risk of SARS-COV-2 transmission via droplets given the close proximity to the patient during slit lamp examination. There is a need to design a simple, low-cost, waterproof breath shield to minimise risk of infection.Dimensions of the Haag-Streit slit lamp (model BM 900) were recorded to guide accurate design of the breath shield. A questionnaire was circulated among slit lamp users on their perceived risk and concern about SARS-CoV-2 transmission and their perception of how effective different designs of breath shields would be at protecting them from an infection. A number of breath shield prototypes were designed and trialled. Plan, Do, Study, Act (PDSA) cycles were used to improve the design. Materials used to create the breath shields included transparent A3 laminating pouches and laminator, two sheets of A4 paper, scissors, hole punch and a ruler. The breath shield was designed to fit over the objective lens on the slit lamp after temporarily removing the standard, manufacturer-provided breath shield, before replacing it. The breath shields were cleaned after every patient with alcohol wipes and removed for deep cleaning with hand soap and water after each session. We used a proof of concept experiment using fluorescein instilled spray to test the effectiveness of each breath shield at preventing droplet transmission to the slit lamp user.Following four PDSA cycles, a breath shield that is user-friendly, easy to clean was produced. The percentage of confidence that the final design would be effective at preventing droplet transmission increased from 5.6% to 80%.Implementation of a low cost, simple to make, transparent, waterproof breath shield together with other forms of person protective equipment (PPE) creates a safe working environment for clinicians and patients. This intervention can be readily replicated and modified for other slit lamp models.

Segmented Macular Layer Volumes from Spectral Domain Optical Coherence Tomography in 184 Adult Twins: Associations With Age and Heritability.

Purpose: To investigate segmented macular layer volumes from a healthy adult twin cohort (TwinsUK), exploring changes with age and heritability. Methods: Macular spectral domain optical coherence tomography images were acquired from monozygotic (MZ) and dizygotic (DZ) twins in a cross-sectional study. The following layer volumes were derived for circles of 3 and 6 mm diameter around the foveal center, using automated segmentation software: retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptors (PR), retinal pigment epithelium (RPE), and total retinal volume (TRV). Correlation coefficients (intereye; age; intrapair for MZ and DZ pairs) were quantified; heritability was estimated using structural equation modeling. Results: Scans from 184 participants were included. Intereye correlation was highest for TRV and GCIPL. Negative correlations with age (for 3- or 6-mm areas, or both) were observed for TRV, RNFL, GCIPL, and INL. Positive correlations were observed for PR, RPE, and OPL. For all layers, intrapair correlation was greater for MZ than DZ pairs. Heritability estimates were highest (>80%) for TRV and GCIPL volume, and lowest for RPE volume. Conclusions: Although TRV was negatively correlated with age, all layers did not show negative correlation. Some inner layers thinned with age, whereas some outer volumes increased (not the ONL). Reduced RPE phagocytic function with age and remodeling in the OPL could be contributing factors. Heritability estimates were highest for inner retinal layers (particularly GCIPL), and lowest for RPE volume.

Definitive Zygosity Scores in the Peas in the Pod Questionnaire is a Sensitive and Accurate Assessment of the Zygosity of Adult Twins.

Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the 'peas in the pod' questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.

Incidence of Late-Stage Age-Related Macular Degeneration in American Whites: Systematic Review and Meta-analysis.

PURPOSE: To estimate incidence of age-related macular degeneration (AMD) by subtype in American whites aged ≥50 years. DESIGN: Systematic review and meta-analysis. SETTING: Prospective cohort studies of AMD incidence in populations of white European ancestry published in MEDLINE, EMBASE, and Web of Science. STUDY POPULATION: Fourteen publications in 10 populations that examined AMD incident cases were identified. OBSERVATION PROCEDURE: Data on age-sex-specific incidence of late AMD, geographic atrophy (GA) and neovascular AMD (NVAMD), year of recruitment, AMD grading method, and continent were extracted. MAIN OUTCOME MEASURE(S): Annual incidence of late AMD, GA, and NVAMD by age-sex in American whites aged ≥50 years from a Bayesian meta-analysis of incidence studies was compared with incidence extrapolated from published prevalence estimates. RESULTS: Incidence rates from the review agreed with those derived from prevalence, but the latter were based on more data, especially at older ages and by AMD subtypes. Annual incidence (estimated from prevalence) of late AMD in American whites was 3.5 per 1000 aged ≥50 years (95% credible interval 2.5, 4.7 per 1000), equivalent to 293 000 new cases in American whites per year (95% credible interval 207 000, 400 000). Incidence rates approximately quadrupled per decade in age. Annual incidence GA rates were 1.9 per 1000 aged ≥50 years, NVAMD rates were 1.8 per 1000. Late AMD incidence was 38% higher in women vs men (95% credible interval 6%, 82%). CONCLUSIONS: Estimating AMD incidence from prevalence allows better characterization at older ages and by AMD subtype where longitudinal data from incidence studies are limited.

Improving phlebotomy handover to doctors: a quality improvement project.

AIM: To design a hospital-standardised phlebotomy handover method to improve the communication between phlebotomists and doctors. To reduce delays in patient management and discharges which occur due to poor handover. METHOD: Qualitative data was collected to gauge junior doctors' experiences of the current handover process. Quantitative data was collected over a two-week period across two medical wards to measure the proportion of requested bloods that could not be taken by phlebotomists that were successfully handed over to doctors. Brainstorming sessions were held with junior doctors, phlebotomists and ward staff in order to design a, cheap, effective, sustainable, hospital-wide method of handover. The chosen intervention was a red ward-based phlebotomy handover folder for phlebotomists to place stickers of unbled patients in. The folder was trialled on two medical wards. Feedback obtained helped improve the intervention before implementing it hospital-wide. RESULTS: Seventeen of 23 junior doctors (74%) felt that a formalised handover process would be very useful. Baseline measurement over two weeks revealed that 24/129 blood tests ordered for phlebotomists to take were not taken. Only three (13%) of these were handed over to doctors. Post-intervention, 18/106 blood tests requested were not taken. All 18 (100%) were successfully handed over to doctors. CONCLUSIONS: Implementation of a hospital-standardised phlebotomy handover folder dramatically improved the communication and handover between phlebotomists and doctors allowing for medical teams to take prompt action on unbled patients. This intervention will help improve patient safety, reduce delays in management/discharge and reduce the number of jobs handed over to evening on-call teams.

Khat: social habit or cultural burden? A survey and review.

The aim of this article was to investigate the psychological and socioeconomic ramifications of Khat on its users and their communities. A thorough literature review was undertaken and a questionnaire was distributed among a Somali community in South London. From the 62 individuals surveyed, 79% were born in Somalia and 15% in the United Kingdom. Participants were asked to answer specific questions about their Khat use, their attitudes toward Khat use, and its perceived effect on their communities. The harms of Khat use are numerous, although they are not well recognized by its users. Khat's legal status means that it is widely available. Measures to reconsider its legality should be considered given the harm on its users.

The estimated prevalence and incidence of late stage age related macular degeneration in the UK.

BACKGROUND: UK estimates of age related macular degeneration (AMD) occurrence vary. AIMS: To estimate prevalence, number and incidence of AMD by type in the UK population aged ≥50 years. METHODS: Age-specific prevalence rates of AMD obtained from a Bayesian meta-analysis of AMD prevalence were applied to UK 2007-2009 population data. Incidence was estimated from modelled age-specific prevalence. RESULTS: Overall prevalence of late AMD was 2.4% (95% credible interval (CrI) 1.7% to 3.3%), equivalent to 513 000 cases (95% CrI 363 000 to 699 000); estimated to increase to 679 000 cases by 2020. Prevalences were 4.8% aged ≥65 years, 12.2% aged ≥80 years. Geographical atrophy (GA) prevalence rates were 1.3% (95% CrI 0.9% to 1.9%), 2.6% (95% CrI 1.8% to 3.7%) and 6.7% (95% CrI 4.6% to 9.6%); neovascular AMD (NVAMD) 1.2% (95% CrI 0.9% to 1.7%), 2.5% (95% CrI 1.8% to 3.4%) and 6.3% (95% CrI 4.5% to 8.6%), respectively. The estimated number of prevalent cases of late AMD were 60% higher in women versus men (314 000 cases in women, 192 000 men). Annual incidence of late AMD, GA and NVAMD per 1000 women was 4.1 (95% CrI 2.4% to 6.8%), 2.4 (95% CrI 1.5% to 3.9%) and 2.3 (95% CrI 1.4% to 4.0%); in men 2.6 (95% CrI 1.5% to 4.4%), 1.7 (95% CrI 1.0% to 2.8%) and 1.4 (95% CrI 0.8% to 2.4%), respectively. 71 000 new cases of late AMD were estimated per year. CONCLUSIONS: These estimates will guide health and social service provision for those with late AMD and enable estimation of the cost of introducing new treatments.

Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis.

OBJECTIVE: To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study design and time trends. DESIGN: Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases. PARTICIPANTS: Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD). METHODS: Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI). MAIN OUTCOME MEASURES: Log odds and prevalence of AMD. RESULTS: There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI, 3.8-4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0-1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1-2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3-7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%-2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%-7.7%) at age 80 and 20% (95% CrI, 14%-27%) at age 90. CONCLUSIONS: Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry.