Detection of Early Loss of Color Vision in Age-Related Macular Degeneration - With Emphasis on Drusen and Reticular Pseudodrusen

Purpose: To evaluate chromatic sensitivity in patients with age-related macular degeneration (AMD) characterized by drusen and reticular pseudodrusen. To investigate whether the severity of color vision loss can distinguish between various stages of AMD and hence be used as an index of progression toward advanced AMD. Methods: Chromatic sensitivity was measured by using the Color Assessment and Diagnosis (CAD) test in asymptomatic individuals with early and intermediate AMD and compared to normative data. All study participants had logMAR visual acuity of 0.3 or better. The CAD thresholds measured in eyes with and without reticular pseudodrusen were also compared and related to central macular thickness (CMT). Student's t-test P values < 0.05 were considered significant. Results: All early- and intermediate-AMD eyes (n = 90) had chromatic sensitivity loss in either RG (red/green) or YB (yellow/blue), or both (P < 0.0001) as compared to age-matched normal subjects. The eyes exhibited a range of CAD thresholds affecting both color mechanisms, but YB color thresholds were in general higher than RG thresholds (P < 0.001). Intermediate-AMD patients exhibited large intersubject variability. In general, eyes with reticular pseudodrusen and eyes with CMT < 200 μm had significantly higher CAD thresholds. Conclusions: The anatomic integrity of cone photoreceptors remains relatively unaffected in early and intermediate stages of AMD. The processing of cone signals in the retina can, however, be heavily disrupted with subsequent loss of both YB and RG chromatic sensitivity. The greatest losses were observed in eyes with reticular pseudodrusen

Loss of chromatic sensitivity in patients with age-related maculopathy - correlation with structural changes in the retina

Purpose: To assess colour vision in Age-related macular degeneration (AMD) while relating chromatic sensitivity to the severity of AMD and AMD morphologies such as drusen and reticular pseudodrusen. To evaluate if chromatic functional loss precedes structural changes in initial stages of AMD, and if it can be a valuable risk stratification tool for advanced AMD. Methods: Chromatic sensitivity was tested using the Colour Assessment and Diagnosis (CAD) test developed by City, University of London and correlated to the structural changes from fundus photography and spectral domain OCT. All patients were asymptomatic with a visual acuity of 6/12 or better. CAD thresholds were compared to clinical classification in all AMD eyes (Ferris et al., 2013); Soft drusen and Reticular drusen (RPD); Central macular thickness (CMT); Fundus autofluorescence (FAF) pattern (Einbock et al., 2005; Wong et al., 2014) and Soft drusen characteristics (Bird et al., 1995). Cases of conversion to ‘Wet’ AMD were identified through a repeat clinical assessment after the first 12 months. Chromatic sensitivity in early onset drusen (EOD) included comparing their colour thresholds to AMD eyes. Student t-test were used for correlation and P200 μm was statistically significant with P<0.01 for RG and <0.002 for YB. Review of baseline CAD thresholds in cases converted to wet AMD at the end of 12 months, revealed six eyes had converted to wet AMD. The baseline CAD thresholds of these eyes were not conclusive of being predictive of the impending change to wet AMD. Conclusions: The visual acuity and hence the integrity of cone photoreceptors remains relatively unaffected in early and intermediate stages of AMD. The processing of cone signals in the retina can however be heavily disrupted with subsequent loss of both YB and RG chromatic sensitivity in the eyes. The greatest losses relate to eyes with reticular pseudodrusen. Chromatic sensitivity change was indicative in early macular thinning but failed to herald the onset of wet AMD in our study sample

Femicide Rates in Mexican Cities along the US-Mexico Border

Mexican cities along the US-Mexico border, especially Cd. Juarez, became notorious due to high femicide rates supposedly associated with maquiladora industries and the NAFTA. Nonetheless, statistical evaluation of data from 1990 to 2012 shows that their rates are consistent with other Mexican cities' rates and tend to fall with increased employment opportunities in maquiladoras. Femicide rates in Cd. Juarez are in most years like rates in Cd. Chihuahua and Ensenada and, as a share of overall homicide rates, are lower than in most cities evaluated. These results challenge conventional wisdom and most of the literature on the subject

Qualitative and quantitative OCT response of diffuse diabetic macular oedema to macular laser photocoagulation

PURPOSE: To assess the quantitative and morphological changes of the macula in response to macular grid laser for diabetic macular oedema (DMO) using optical coherence tomography (OCT). PATIENTS AND METHODS: Cirrus OCT macular cube scans of 30 eyes of 25 patients were retrospectively analysed before and 4 months after macular grid laser for diffuse DMO. The oedema was quantified and response evaluated in the nine early-treatment diabetic retinopathy study (ETDRS) zones of the macula. Post-laser OCT changes were compared with the baseline features, including morphology patterns, changes in both logarithmic transformed (logOCT) and standardised average macular thickness (AMT), total macular volume, number of parafoveal quadrants involved, and the presence of intact 3rd hyper-reflective band (HRB). RESULTS: The rate of change of retinal thickness in response to laser was maximum in the central (8.17%) and perifoveal inferior quadrants (0.04%). Diffuse retinal thickening on OCT responded best to treatment. The AMT of 300-350 μm had the worst response (+0.94%). Eyes with less than four quadrants of oedema showed good response. Disrupted HRB was associated with poor visual gain (-0.33 ETDRS letters). CONCLUSION: The topographic location of oedema on the retinal map and the morphological patterns of the oedema on OCT are useful predictors of treatment response in diffuse DMO

Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581] (Journal of Hepatology (2021) 75(3) (572–581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled ‘Jinyoung Byan’; the correct spelling is ‘Jinyoung Byun’ as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused

Corrigendum to \u2018An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs\u2019 [J Hepatol 2021;75(3):572\u2013581] (Journal of Hepatology (2021) 75(3) (572\u2013581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled \u2018Jinyoung Byan\u2019; the correct spelling is \u2018Jinyoung Byun\u2019 as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

BACKGROUNDS & AIMS Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. METHODS We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts. RESULTS We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57 genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (T)1 and T17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders. CONCLUSIONS This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. LAY SUMMARY Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC