New forays into measurement of ocular biomechanics.

PURPOSE OF REVIEW: The field of corneal biomechanics has rapidly progressed in recent years, reflecting technological advances and an increased understanding of the clinical significance of measuring these properties. This review will evaluate in-vivo biomechanical properties obtained by current technologies and compare them regarding their relevance to established biomechanical properties obtained by gold-standard ex-vivo techniques normally conducted on elastic materials. RECENT FINDINGS: Several new technologies have appeared in recent years, including vibrational optical coherence tomography (VOCT) and the corneal indentation device (CID). These techniques provide promising new opportunities for minimally invasive and accurate measurements of corneal viscoelastic properties. SUMMARY: Alterations in corneal biomechanics are known to occur in several corneal degenerative diseases and after refractive surgical procedures. The measurement of corneal biomechanical properties has the capability to diagnose early disease and monitor corneal disease progression. Several new technologies have emerged in recent years, allowing for more accurate and less invasive measurements of corneal biomechanical properties, most notably the elastic modulus.

Update of penetrance estimates in Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare genetic syndrome caused by pathogenic or likely pathogenic germline variants in the FLCN gene. Patients with BHD syndrome have an increased risk of fibrofolliculomas, pulmonary cysts, pneumothorax and renal cell carcinoma. There is debate regarding whether colonic polyps should be added to the criteria. Previous risk estimates have mostly been based on small clinical case series. METHODS: A comprehensive review was conducted to identify studies that had recruited families carrying pathogenic or likely pathogenic variants in FLCN. Pedigree data were requested from these studies and pooled. Segregation analysis was used to estimate the cumulative risk of each manifestation for carriers of FLCN pathogenic variants. RESULTS: Our final dataset contained 204 families that were informative for at least one manifestation of BHD (67 families informative for skin manifestations, 63 for lung, 88 for renal carcinoma and 29 for polyps). By age 70 years, male carriers of the FLCN variant have an estimated 19% (95% CI 12% to 31%) risk of renal tumours, 87% (95% CI 80% to 92%) of lung involvement and 87% (95% CI 78% to 93%) of skin lesions, while female carriers had an estimated 21% (95% CI 13% to 32%) risk of renal tumours, 82% (95% CI 73% to 88%) of lung involvement and 78% (95% CI 67% to 85%) of skin lesions. The cumulative risk of colonic polyps by age 70 years old was 21% (95% CI 8% to 45%) for male carriers and 32% (95% CI 16% to 53%) for female carriers. CONCLUSIONS: These updated penetrance estimates, based on a large number of families, are important for the genetic counselling and clinical management of BHD syndrome.

Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

Heavy Drinking by Occupation in Spain: Differences Between Weekdays and the Weekend.

Estimating occupational disparity in heavy drinking jointly for weekdays and the weekend may be misleading for prevention purposes, because reasons for disparity in both periods may differ. The main objective was to assess occupational disparity in heavy average drinking (HAD) by week period and sex. 42,108 employees aged 16-64 were recruited from national surveys in Spain between 2011 and 2020. The outcome was HAD, defined as daily alcohol intake over 20 g (men) or 10 g (women). Occupation was classified in 15 categories. HAD adjusted prevalence ratios (HAD-aPRs) taking all occupations as reference, and relative adjusted excess prevalences (HAD-aEPs) comparing the weekend to weekdays in each occupation, were estimated using Poisson regression models with robust variance adjusted for sociodemographic and health covariates. The HAD-aPRs comparing each occupation with all occupations ranged 0.63-1.92 on weekdays and 0.65-1.45 on the weekend, with the highest aPRs on weekdays in construction, hospitality and primary-sector workers (1.92-1.62). The weekend-weekdays HAD-aEPs by occupation ranged 2.60-8.33, with the highest values in technicians/administrators, other professionals, teachers and health professionals (8.33-6.44). The global aEP was higher in women (6.04) than in men (3.92), especially in occupations just mentioned (8.70-11.73 in women vs. 3.64-6.32 in men). There was a considerable relative disparity in HAD risk between occupations on weekdays, with the highest risks in certain low-skilled occupations. Such disparity decreased on the weekend. The relative weekend increase in HAD risk was greater in women and in certain high-skilled occupations. This should be considered when designing prevention interventions on harmful drinking.

Exploring the Associated Genetic Causes of Diabetic Retinopathy as a Model of Inflammation in Retinal Diseases.

To investigate potential biomarkers and biological processes associated with diabetic retinopathy (DR) using transcriptomic and proteomic data. The OmicsPred PheWAS application was interrogated to identify genes and proteins associated with DR and diabetes mellitus (DM) at a false discovery rate (FDR)-adjusted p-value of <0.05 and also <0.005. Gene Ontology PANTHER analysis and STRING database analysis were conducted to explore the biological processes and protein interactions related to the identified biomarkers. The interrogation identified 49 genes and 22 proteins associated with DR and/or DM; these were divided into those uniquely associated with diabetic retinopathy, uniquely associated with diabetes mellitus, and the ones seen in both conditions. The Gene Ontology PANTHER and STRING database analyses highlighted associations of several genes and proteins associated with diabetic retinopathy with adaptive immune response, valyl-TRNA aminoacylation, complement activation, and immune system processes. Our analyses highlight potential transcriptomic and proteomic biomarkers for DR and emphasize the association of known aspects of immune response, the complement system, advanced glycosylation end-product formation, and specific receptor and mitochondrial function with DR pathophysiology. These findings may suggest pathways for future research into novel diagnostic and therapeutic strategies for DR.

Free Access to Direct-Acting Antivirals in Spain: More Favorable Impact on Hepatitis C Mortality Among Highly Educated People.

BACKGROUND: In 2015, hepatitis C treatment with direct-acting antivirals (DAAs) became free and widespread in Spain, significantly reducing hepatitis C-related mortality. However, health interventions can sometimes widen health inequalities. The objective of this study is to assess the impact of DAA treatment on hepatitis C-related mortality by educational level. METHODS: We analyzed deaths from hepatitis C, unspecified liver cirrhosis, hepatocellular carcinoma, alcohol-related liver diseases, other liver diseases, and human immunodeficiency virus (HIV) disease among individuals living in Spain during 2012-2019 and aged ≥25 years. We calculated age-standardized mortality rates per million person-years by period, sex, and education. Using quasi-Poisson segmented regression models, we estimated the annual percent change in rates in pre- and postintervention periods by education level and the relative inequality index (RII). RESULTS: Hepatitis C mortality rates among low, middle, and highly educated people decreased from 25.2, 23.2, and 20.3/million person-years in the preintervention period to 15.8, 13.7, and 10.4 in the postintervention period. Mortality rates from other analyzed causes also decreased. Following the intervention, downward trends in hepatitis C mortality accelerated at all education levels, although more in highly educated people, and the RII increased from 2.1 to 2.7. For other analyzed causes of death, no favorable changes were observed in mortality trends, except for liver cirrhosis, hepatocellular carcinoma, HIV disease, and alcohol-related liver disease among higher educated people. CONCLUSIONS: Results suggest that DAA treatments had a very favorable impact on hepatitis C mortality at all education levels. However, even in a universal and free healthcare system, highly educated people seem to benefit more from DAA treatment than less educated people.

Random Allelic Expression in Inherited Retinal Disease Genes.

Inherited retinal diseases (IRDs) are a significant contributor to visual loss in children and young adults, falling second only to diabetic retinopathy. Understanding the pathogenic mechanisms of IRDs remains paramount. Some autosomal genes exhibit random allelic expression (RAE), similar to X-chromosome inactivation. This study identifies RAE genes in IRDs. Genes in the Retinal Information Network were cross-referenced with the recent literature to identify expression profiles, RAE, or biallelic expression (BAE). Loss-of-function intolerance (LOFI) was determined by cross-referencing the existing literature. Molecular and biological pathways that are significantly enriched were evaluated using gene ontology. A total of 184 IRD-causing genes were evaluated. Of these, 31 (16.8%) genes exhibited RAE. LOFI was exhibited in 6/31 (19.4%) of the RAE genes and 18/153 (11.8%) of the BAE genes. Brain tissue exhibited BAE in 107/128 (83.6%) genes for both sexes. The molecular pathways significantly enriched among BAE genes were photoreceptor activity, tubulin binding, and nucleotide/ribonucleotide binding. The biologic pathways significantly enriched for RAE genes were equilibrioception, parallel actin filament bundle assembly, photoreceptor cell outer segment organization, and protein depalmitoylation. Allele-specific expression may be a mechanism underlying IRD phenotypic variability, with clonal populations of embryologic precursor cells exhibiting RAE. Brain tissue preferentially exhibited BAE, possibly due to selective pressures against RAE. Pathways critical for cellular and visual function were enriched in BAE, which may offer a survival benefit.

Effect of tramadol and DOACs with special attention to dabigatran on concomitant use, on the risk of mayor bleeding using BIFAP database in Spain.

BACKGROUND: Tramadol, a weak opioid, inhibits the reuptake of serotonin, a key feature on vascular homeostasis. A suspected interaction exists between dabigatran and tramadol, which might trigger an excess on risk of bleeding however, there is a gap in knowledge on this topic. PURPOSE: To estimate the effects of tramadol, dabigatran and concomitant use on the risk of hospitalized major bleeds (Gastrointestinal bleeding and intra-extracranial bleeds). METHODS: Among a validated established cohort of new users of oral anticoagulants for non-valvular atrial fibrillation (NVAF) aged 18 years or older, we identified all hospitalized bleed episodes (GIB and extra/intracranial bleeds) within 2008-2015. A nested case-control analysis was conducted using conditional logistic regression. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated for dabigatran, tramadol, and concomitant use. Several sensitivity analyses were carried out. RESULTS: aORs (95%CIs) for current use of only dabigatran, only tramadol and concomitant users were 1.73 (1.37-2.18) and 1.38 (1.13-1.67) and 2.04 (0.74-5.67) compared with non-users of both drugs (>365 days). aORs for current continuers and non-continuer users of dabigatran were 1.36 (1.00-1.86) and 2.19 (1.61-2.98), respectively. For the latter, non-continuer users with a short duration of dabigatran cumulated the highest risk (3.36 [1.88-5.99]). There also was an increased risk with concomitant use of tramadol and rivaroxaban (2.24 [1.19-4.21]), or antagonist of vitamin K (1.30 [1.00-1.69]). CONCLUSION: There was a trend towards and increased risk of excess bleeds when using concomitantly with dabigatran. The effect decreases with a narrower definition of current use.

HISTOPATHOLOGIC CONFIRMATION OF LYMPHOCYTIC INFILTRATION OF THE OPTIC NERVE AND INNER RETINA IN BIRDSHOT CHORIORETINOPATHY.

PURPOSE: To describe new histological findings involving the inner retina in birdshot chorioretinopathy. METHODS: Evaluation of the inner retinal pathology of the eye of a patient with bilateral birdshot chorioretinopathy who underwent enucleation for a unilateral ciliochoroidal melanoma. RESULTS: Histopathological sections showed focal perivascular lymphocytic infiltration at the optic nerve head that extended into the adjacent inner retina, mainly involving the ganglion and nerve fiber layers. CONCLUSION: We have previously shown that birdshot chorioretinopathy has multiple foci of lymphocytes in the choroid. This is the first report that demonstrates lymphocytic infiltration of the inner retinal layers. This may lead to the bipolar and Müller cell dysfunction that ultimately results in an electronegative electroretinogram.

Initial Investigations of Intrinsically Disordered Regions in Inherited Retinal Diseases.

Intrinsically disordered regions (IDRs) are protein regions that are unable to fold into stable tertiary structures, enabling their involvement in key signaling and regulatory functions via dynamic interactions with diverse binding partners. An understanding of IDRs and their association with biological function may help elucidate the pathogenesis of inherited retinal diseases (IRDs). The main focus of this work was to investigate the degree of disorder in 14 proteins implicated in IRDs and their relationship with the number of pathogenic missense variants. Metapredict, an accurate, high-performance predictor that reproduces consensus disorder scores, was used to probe the degree of disorder as a function of the amino acid sequence. Publicly available data on gnomAD and ClinVar was used to analyze the number of pathogenic missense variants. We show that proteins with an over-representation of missense variation exhibit a high degree of disorder, and proteins with a high amount of disorder tolerate a higher degree of missense variation. These proteins also exhibit a lower amount of pathogenic missense variants with respect to total missense variants. These data suggest that protein function may be related to the overall level of disorder and could be used to refine variant interpretation in IRDs.

Methodology used to estimate alcohol-attributable mortality in Spain, 2001-2017. / Metodología utilizada para estimar la mortalidad atribuible a alcohol en España, 2001-2017.

The objective is to describe and discuss methods and assumptions to estimate the mortality attributable to alcohol in Spain in 2001-2017. The annual mean number of deaths attributable to alcohol (DAAs) was estimated based on 19 groups of alcohol-related causes of death (18 partially attributable and one directly attributable), and 20 alcohol population-attributable fractions (PAFs), resulting from combining sex, 5 age groups, and the periods 2001-2009 and 2010-2017, for each cause group. Deaths from causes were obtained from the Spanish National Institute of Statistics. For partially attributable causes, Spain-specific PAFs were calculated using the Levin formula with alcohol exposure data from health surveys and sales statistics, and relative risks from international meta-analyses. Annual prevalences of ex-drinkers and seven levels of daily alcohol consumption were considered. The underestimation of self-reported daily average consumption with respect to the sales statistics was corrected by multiplying by a factor of 1.58-3.18, depending on the calendar year. DAA rates standardized by age and standardized proportions of general mortality attributable to alcohol, according to sex, age group, calendar period, type of drinker and autonomous community were calculated. Sensitivity analyses were performed to assess how the DAA estimates changed when changing some methodological options, such as the ex-drinker criterion or the introduction of a latency period.

El objetivo es describir y discutir los métodos y asunciones para estimar la mortalidad atribuible a alcohol en España en 2001-2017. Se estimó el nº medio anual de muertes atribuibles a alcohol (MAAs) basándose en 19 grupos de causas de muerte relacionadas con alcohol (18 parcialmente atribuibles y uno directamente atribuible), y 20 fracciones atribuibles poblacionales al alcohol (FAPs) para cada grupo de causas, resultantes de combinar sexo, 5 grupos de edad, y los períodos 2001-2009 y 2010-2017. Las muertes por causa se obtuvieron del Instituto Nacional de Estadística. Para las causas parcialmente atribuibles se calcularon FAPs específicas para España, usando la fórmula de Levin con datos de exposición al alcohol procedentes de encuestas de salud y estadísticas de ventas, y riesgos relativos procedentes de metanálisis internacionales. Se consideraron las prevalencias anuales de exbebedores y de siete niveles de consumo diario de alcohol. Se corrigió la subestimación del consumo medio diario autoinformado con respecto a las estadísticas de venta, multiplicando por un factor de 1,58-3,18, dependiendo del año-calendario. Se calcularon tasas de MAA y porcentajes de la mortalidad general atribuibles a alcohol estandarizados por edad, según sexo, grupo de edad, periodo-calendario, tipo de bebedor y comunidad autónoma. Se realizaron análisis de sensibilidad observando cómo cambiaban las estimaciones de MAA al hacerlo algunas opciones metodológicas, como el criterio de exbebedor o la introducción de un período de latencia.

Stroke Risk before and after Central Retinal Artery Occlusion: A Population-based Analysis.

PURPOSE: To determine the risk of stroke, transient ischemic attack (TIA), and transient monocular vision loss (TMVL) before and after a central retinal artery occlusion (CRAO). DESIGN: Population-based, retrospective case series. PARTICIPANTS: Patients diagnosed with a CRAO in Olmsted County, Minnesota, from 1976 to 2016. METHODS: Patients living in Olmsted County with a diagnosis code of CRAO from 1976 to 2016 were reviewed. New CRAOs were confirmed, and stroke, TIA, and TMVL events in the 15 days before and after CRAO were recorded. MAIN OUTCOME MEASURES: Incidence of stroke, TIA, and TMVL events in the 15 days before and after CRAO. RESULTS: Eighty-nine patients with a CRAO were identified, providing an annual incidence of 2.58/100 000 (95% confidence interval [CI], 2.04-3.11). Median age at the time of CRAO was 76 years (range, 46-100 years); 56.2% were male, and 89.9% of the cohort was White. In the 15 days before and after CRAO, there were 2 ischemic strokes (2.2%), 1 hemorrhagic stroke (1.1%), 2 TIAs (2.2%), and 9 TMVL events (10.1%). Starting in 1999, 15 of 45 patients underwent magnetic resonance imaging within 2 months of CRAO. One patient (6.7%) had evidence of asymptomatic diffusion restriction, and 9 patients (60%) had a remote infarct. CONCLUSIONS: This population-based study demonstrated that the risk of symptomatic ischemic stroke is 2.2% in the 15 days before and after a CRAO, which is slightly lower than most studies from tertiary centers. These data should be considered as practice recommendations are developed regarding the urgency of neurovascular workup in patients with acute CRAO.

Mediterranean diet and diabetes risk in a cohort study of individuals with prediabetes: propensity score analyses.

AIMS: Randomized controlled trials have demonstrated the efficacy of several dietary patterns plus physical activity to reduce diabetes onset in people with prediabetes. However, there is no evidence on the effect from the Mediterranean diet on the progression from prediabetes to diabetes. We aimed to evaluate the effect from high adherence to Mediterranean diet on the risk of diabetes in individuals with prediabetes. METHODS: Prospective cohort study in Spanish Primary Care setting. A total of 1184 participants with prediabetes based on levels of fasting plasma glucose and/or glycated hemoglobin were followed up for a mean of 4.2 years. A total of 210 participants developed diabetes type 2 during the follow up. Hazard ratios of diabetes onset were estimated by Cox proportional regression models associated to high versus low/medium adherence to Mediterranean diet. Different propensity score methods were used to control for potential confounders. RESULTS: Incidence rate of diabetes in participants with high versus low/medium adherence to Mediterranean diet was 2.9 versus 4.8 per 100 persons-years. The hazard ratios adjusted for propensity score and by inverse probability weighting (IPW) had identical magnitude: 0.63 (95% confidence interval, 0.43-0.93). The hazard ratio in the adjusted model using propensity score matching 1:2 was 0.56 (95% confidence interval, 0.37-0.84). CONCLUSIONS: These propensity score analyses suggest that high adherence to Mediterranean diet reduces diabetes risk in people with prediabetes.

SURGICAL OUTCOMES OF VASOPROLIFERATIVE RETINAL TUMORS' REFRACTORY TO NONINVASIVE THERAPIES.

PURPOSE: To evaluate the outcomes of surgical treatment of refractory vasoproliferative retinal tumors (VPTs) and its complications. METHODS: Clinical charts of all patients diagnosed with VPTs who underwent surgical treatment from 2005 to 2020 were reviewed. Clinical features, surgical techniques, and outcomes were evaluated. RESULTS: From 25 eyes of 23 patients with VPTs, 17 (68%) eyes underwent surgical intervention to treat tumor activity and associated complications including epiretinal membrane (n = 10, 59%), retinal detachment (n = 8, 47%), and vitreous hemorrhage (n = 3, 18%). All eyes underwent pars plana vitrectomy with endolaser/cryotherapy to control tumor activity and to treat associated complications. Three cases required tumor resection. At the end of follow-up (mean 55.4 months, range 2-305 months), no eye presented tumor activity or retinal detachment after one or two surgeries. There was no epiretinal membrane recurrence. The mean baseline best-corrected visual acuity was 1.2 ± 0.7 logMAR, and the mean final best-corrected visual acuity was 0.7 ± 0.6 logMAR ( P < 0.05). The best-corrected visual acuity improved two or more lines in 12 (70.5%) eyes at the end of follow-up. CONCLUSION: In this series of patients with large active VPTs, surgical intervention allowed control of the tumor activity in all patients and provided overall satisfactory anatomic and functional outcomes.

BILATERAL SERPIGINOUS-LIKE CHORIORETINITIS ASSOCIATED WITH CILIOCHOROIDAL MELANOMA: A Clinicopathologic Correlation.

PURPOSE: To report the clinicopathologic correlation of a case of bilateral serpiginous-like chorioretinitis (SLC) associated with unilateral ciliochoroidal melanoma. METHODS: A 71-year-old white woman was diagnosed with progressive SLC in both eyes associated with ciliochoroidal melanoma in the right eye. Clinical findings and imaging before and after enucleation in the right eye were correlated to histologic and immunohistochemistry sections. RESULTS: Examination and imaging identified a peripheral bilobed amelanotic lesion with low reflectivity on B-scan ultrasound with an associated exudative detachment in the right eye. Additionally, multiple areas of new SLC lesions in the macula and peripapillary region in the right eye and along the inferior arcade in the left eye were observed. Oncologic evaluation confirmed a Class 2, ciliochoroidal melanoma, and the eye was enucleated. Autoimmune and infectious laboratory evaluations for the etiology of the SLC lesions were negative. Histopathology of the enucleated eye confirmed the diagnosis of uveal melanoma with lymphocytic inflammation at the edges of the tumor itself and in the areas of discrete SLC lesions. Immunohistochemistry identified similar predominantly CD3 and CD8 T cells and fewer CD20 B cells in both regions. CONCLUSION: Serpiginous-like chorioretinitis may present as a paraneoplastic, predominantly T-lymphocyte inflammation associated with intraocular tumor such as uveal melanoma.

CHOROIDAL AMYLOID DEPOSITION: A Multicenter Study of Amyloid Lesions Identified in Late Indocyanine Green Angiography.

PURPOSE: To characterize choroidal amyloid angiopathy (CAA) using late-phase indocyanine green angiography (ICGA). METHODS: This was a multicenter retrospective observational case series on patients with transthyretin (ATTR) and AL amyloidosis who underwent ICGA. The timing of hyperfluorescence and longitudinal changes were analyzed. RESULTS: Thirty-two patients (27 with ATTR and 5 with AL) with mean age of 58.9 ± 17.4 years were included. Hyperfluorescent spots in the very late phases of ICGA, corresponding to CAA, were observed in 49 of 55 eyes (89%). The median time to maximal staining was 672 (95% confidence interval, 644-752) seconds, which was significantly later than the initial staining (503 [95% confidence interval, 447-521], P < 0.0001; Wilcoxon signed rank test). In seven patients with ATTR amyloidosis who underwent follow-up of ICGA, the CAA was stable in two patients and improved in five patients during treatment. However, 3 patients (43%) had worsening vitreous opacities in both eyes, and 4 patients (57%) developed secondary open-angle glaucoma. CONCLUSION: Most patients with amyloidosis were found to have CAA on ICGA. Up to 12.5 minutes is required for maximal ICG staining. Choroidal amyloid angiopathy improved in most patients with systemic treatment and may serve as a marker of systemic disease status.

Signal Peptide Variants in Inherited Retinal Diseases: A Multi-Institutional Case Series.

Signal peptide (SP) mutations are an infrequent cause of inherited retinal diseases (IRDs). We report the genes currently associated with an IRD that possess an SP sequence and assess the prevalence of these variants in a multi-institutional retrospective review of clinical genetic testing records. The online databases, RetNet and UniProt, were used to determine which IRD genes possess a SP. A multicenter retrospective review was performed to retrieve cases of patients with a confirmed diagnosis of an IRD and a concurrent SP variant. In silico evaluations were performed with MutPred, MutationTaster, and the signal peptide prediction tool, SignalP 6.0. SignalP 6.0 was further used to determine the locations of the three SP regions in each gene: the N-terminal region, hydrophobic core, and C-terminal region. Fifty-six (56) genes currently associated with an IRD possess a SP sequence. Based on the records review, a total of 505 variants were present in the 56 SP-possessing genes. Six (1.18%) of these variants were within the SP sequence and likely associated with the patients' disease based on in silico predictions and clinical correlation. These six SP variants were in the CRB1 (early-onset retinal dystrophy), NDP (familial exudative vitreoretinopathy) (FEVR), FZD4 (FEVR), EYS (retinitis pigmentosa), and RS1 (X-linked juvenile retinoschisis) genes. It is important to be aware of SP mutations as an exceedingly rare cause of IRDs. Future studies will help refine our understanding of their role in each disease process and assess therapeutic approaches.

Effects of the COVID-19 pandemic on the Colombian labour market: Disentangling the effect of sector-specific mobility restrictions.

We assess the effect of the COVID-19 pandemic and particularly the sector-specific mobility restrictions on the Colombian labour market. We exploit the sectoral and temporal variation of the restriction policies to identify their effect. Mobility restrictions significantly reduced employment, accounting for approximately a quarter of the total job loss between February and April of 2020. The remaining three quarters of the job losses could be attributed to the disease's regional patterns and other epidemiological and economic factors affecting the whole country. Therefore, we should expect important employment losses even in the absence of such restrictions. We also assess the effect of restrictions on the intensive margin, finding negative, although smaller effects on the number of hours worked and wages. Most of the employment effect is driven by salaried workers, while self-employment was more responsive to the disease spread. Finally, we find that women are disproportionally affected: mobility restrictions account for a third of the recent increase of the gender gap in salaried employment.

Effets de la pandémie de COVID­19 sur le marché du travail colombien : analyse des répercussions liées aux restrictions de mobilité par secteur. Dans cet article, nous évaluons les répercussions de la pandémie de COVID­19, et notamment des restrictions en matière de mobilité propres à chaque secteur, sur le marché du travail colombien. Nous nous appuyons sur les variations temporelles et sectorielles des politiques de restriction pour déterminer leurs effets. Les restrictions de mobilité ont sensiblement détérioré l'emploi en détruisant environ un quart du nombre total d'emplois supprimés entre février et avril 2020, les trois­quarts restants pouvant être imputés aux caractéristiques régionales de la pandémie ainsi qu'à d'autres facteurs épidémiologiques et économiques touchant l'ensemble du pays. Nous pourrions donc nous attendre à d'importantes destructions d'emplois, même en l'absence de telles restrictions. Nous évaluons également les effets des restrictions à la marge intensive, et nous constatons des effets négatifs mais plus faibles sur le nombre d'heures travaillées ainsi que sur les salaires. Les effets de ces restrictions sur l'emploi sont motivés en grande partie par les travailleurs salariés, les travailleurs indépendants se montrant plus réactifs face à la propagation de la maladie. Enfin, nous constatons que les femmes sont touchées de façon disproportionnée, les restrictions de mobilité comptant pour un tiers de l'accentuation récente de l'écart hommes­femmes en matière d'emploi salarié.

Substance use in sexual context among Spanish resident men who have sex with men. / Consumo sexualizado de drogas entre hombres que tienen sexo con hombres residentes en España.

We analysed patterns of sexualized drug use (SDU) and pinpointed the one with the highest risk for the acquisition/transmission of HIV/Sexually Transmitted Infections (STIs) in a sample of men who have sex with men (MSM) residing in Spain. Additionally, we also identified the most affected subpopulations by highest risk SDU pattern. In 2016, we promoted an online survey in gay dating apps. We estimated the prevalence of several HIV/STI risk indicators for each identified SDU pattern. We built two different Poisson regression models identifying factors associated to the pattern associated with the highest risk. All analyses were carried out by HIV status. Of 2,883 MSM, 21.9% self-reported SDU in the last 12 months. All patterns of SDU were more frequent in HIV+ MSM. Of the four SDU patterns identified (chemsex, recreational drugs, sexual performance enhancing drugs, and cannabinoids), the most frequent was chemsex (21.9% in HIV+ vs 6.6% in HIV-). It also comprised the highest risk profile for HIV/STI. Among HIV-, chemsex was associated with living in a city of > 1,000,000 inhabitants, living sexuality in an open way and having been paid for sex, having had unprotected anal intercourse (UAI) in the last 12 months and having ever received an STI diagnosis. Among HIV+, it was associated with being 30-49 years old, having paid for sex, having had UAI and having been diagnosed with an STI in the last 12 months. Given its high prevalence, especially among HIV positive individuals, and its association with subpopulations with high-risk behaviour, chemsex could be playing a relevant role in the acquisition/transmission of HIV and other STIs.

Analizar los patrones de consumo sexualizado de drogas (CSD) e identificar cual es el de mayor riesgo para la adquisición/transmisión del VIH y de otras infecciones de transmisión sexual (ITS) en una muestra de hombres que tienen sexo con hombres (HSH) residentes en España. Adicionalmente, también se identifican las subpoblaciones más afectadas por el patrón de CSD de mayor riesgo. En 2016, se realizó una encuesta online en app de contacto gay. Se identificaron los patrones de CSD y se estimaron las prevalencias de varios indicadores de riesgo para el VIH/ITS para cada uno.  Se construyeron dos modelos multivariantes de Poisson identificando factores asociados al patrón de mayor riesgo. Todos los análisis se realizaron en función del estado serológico frente al VIH. De 2883 HSH, el 21,9% refirió CSD en los últimos 12 meses. Todos los patrones de CSD fueron más frecuentes en los VIH+. De los cuatro patrones identificados (chemsex, drogas recreacionales, drogas para mejorar el rendimiento sexual y cannabinoides) el más prevalente y de mayor riesgo, fue el chemsex (21,9% en VIH+ vs. 6,6% en VIH-). En los VIH- el chemsex se asoció con: ciudad de residencia > 1 000 000 habitantes, vivir la sexualidad abiertamente, haber cobrado por tener sexo, haber mantenido relaciones anales desprotegidas (RAD) en el último año y haber sido diagnosticado de una ITS. En los VIH+ se asoció con: tener 30-49 años, haber pagado por tener relaciones sexuales, haber tenido RAD y haber sido diagnosticado de ITS en el último año. Dada su elevada prevalencia especialmente en VIH+ y a que se observa fundamentalmente en poblaciones con perfiles de alto riesgo, el chemsex podría estar jugando un papel relevante en la adquisición y/o transmisión del VIH y otras ITS.

Trends and equity in the use of health services in Spain and Germany around austerity in Europe.

BACKGROUND: Following the 2008 economic crisis many countries implemented austerity policies, including reducing public spending on health services. This paper evaluates the trends and equity in the use of health services during and after that period in Spain - a country with austerity policies - and in Germany - a country without restriction on healthcare spending. METHODS: Data from several National Surveys in Spain and several waves of the Socio-Economic Panel in Germany, carried out between 2009 and 2017, were used. The dependent variables were number of doctor's consultations and whether or not a hospital admission occurred. The measure of socioeconomic position was education. In each year, the estimates were made for people with and without pre-existing health problems. First, the average number of doctor's consultations and the percentage of respondents who had had been hospitalized were calculated. Second, the relationship between education and use of those health services was estimated by calculating the difference in consultations using covariance analysis - in the case of number of consultations - and by calculating the percentage ratio using binomial regression - in the case of hospitalization. RESULTS: The annual mean number of consultations went down in both countries. In Spain the average was 14.2 in 2009 and 10.4 in 2017 for patients with chronic conditions; 16.6 and 13.5 for those with a mental illness; and 6.4 and 5.9 for those without a defined illness. In Germany, the averages were 13.8 (2009) and 12.9 (2017) for the chronic group; 21.1 and 17.0 for mental illness; and 8.7 and 7.5 with no defined illness. The hospitalization frequency also decreased in both countries. The majority of the analyses presented no significant differences in relation to education. CONCLUSION: In both Spain and Germany, service use decreased between 2009 and 2017. In the first few years, this reduction coincided with a period of austerity in Spain. In general, we did not find socioeconomic differences in health service use.