Population-Based Utility of van Herick Grading for Angle-Closure Detection

Primary angle-closure glaucoma accounts for half of glaucoma-related blindness worldwide with a disproportionate burden of disease found in Asian populations. The clinical reference standard for diagnosis of angle closure is gonioscopy, but van Herick (VH) grading of limbal anterior chamber depth (LACD) has been used as a screening tool, with varying sensitivities and specificities on classifying gonioscopically occludable angles reported in Chinese and other East Asian populations. A cutoff of VH grade ≤1 (modified grade ≤15%) has been found to have sensitivities ranging from 19% to 84% and specificities from 86% to 100%, whereas a higher cutoff VH grade ≤2 (modified grade ≤25%) has had sensitivities ranging from 54% to 99% and specificities from 65% to 96%. However, the efficacy of using the VH test as a screening tool in community-based screening programs to identify gonioscopically occludable angle has not been investigated. The purpose of this study was to determine the sensitivity and specificity of modified VH grading of LACD in detecting gonioscopically defined primary angle-closure suspects (PACS) among subjects screened for participation in the Zhongshan Angle Closure Prevention (ZAP) Trial in southern China

TIE1 and TEK signalling, intraocular pressure, and primary open-angle glaucoma: a Mendelian randomization study

Background: In primary open-angle glaucoma (POAG), lowering intraocular pressure (IOP) is the only proven way of slowing vision loss. Schlemm’s canal (SC) is a hybrid vascular and lymphatic vessel that mediates aqueous humour drainage from the anterior ocular chamber. Animal studies support the importance of SC endothelial angiopoietin-TEK signalling, and more recently TIE1 signalling, in maintaining normal IOP. However, human genetic support for a causal role of TIE1 and TEK signalling in lowering IOP is currently lacking. Methods: GWAS summary statistics were obtained for plasma soluble TIE1 (sTIE1) protein levels (N = 35,559), soluble TEK (sTEK) protein levels (N = 35,559), IOP (N = 139,555) and POAG (Ncases = 16,677, Ncontrols = 199,580). Mendelian randomization (MR) was performed to estimate the association of genetically proxied TIE1 and TEK protein levels with IOP and POAG liability. Where significant MR estimates were obtained, genetic colocalization was performed to assess the probability of a shared causal variant (PPshared) versus distinct (PPdistinct) causal variants underlying TIE1/TEK signalling and the outcome. Publicly available single-nucleus RNA-sequencing data were leveraged to investigate differential expression of TIE1 and TEK in the human ocular anterior segment. Results: Increased genetically proxied TIE1 signalling and TEK signalling associated with a reduction in IOP (− 0.21 mmHg per SD increase in sTIE1, 95% CI = − 0.09 to − 0.33 mmHg, P = 6.57 × 10–4, and − 0.14 mmHg per SD decrease in sTEK, 95% CI = − 0.03 to − 0.25 mmHg, P = 0.011), but not with POAG liability. Colocalization analysis found that the probability of a shared causal variant was greater for TIE1 and IOP than for TEK and IOP (PPshared/(PPdistinct + PPshared) = 0.98 for TIE1 and 0.30 for TEK). In the anterior segment, TIE1 and TEK were preferentially expressed in SC, lymphatic, and vascular endothelium. Conclusions: This study provides novel human genetic support for a causal role of both TIE1 and TEK signalling in regulating IOP. Here, combined evidence from cis-MR and colocalization analyses provide stronger support for TIE1 than TEK as a potential IOP-lowering therapeutic target

TIE1 and TEK signalling, intraocular pressure, and primary open-angle glaucoma: a Mendelian randomization study

BACKGROUND: In primary open-angle glaucoma (POAG), lowering intraocular pressure (IOP) is the only proven way of slowing vision loss. Schlemm's canal (SC) is a hybrid vascular and lymphatic vessel that mediates aqueous humour drainage from the anterior ocular chamber. Animal studies support the importance of SC endothelial angiopoietin-TEK signalling, and more recently TIE1 signalling, in maintaining normal IOP. However, human genetic support for a causal role of TIE1 and TEK signalling in lowering IOP is currently lacking. METHODS: GWAS summary statistics were obtained for plasma soluble TIE1 (sTIE1) protein levels (N = 35,559), soluble TEK (sTEK) protein levels (N = 35,559), IOP (N = 139,555) and POAG (Ncases = 16,677, Ncontrols = 199,580). Mendelian randomization (MR) was performed to estimate the association of genetically proxied TIE1 and TEK protein levels with IOP and POAG liability. Where significant MR estimates were obtained, genetic colocalization was performed to assess the probability of a shared causal variant (PPshared) versus distinct (PPdistinct) causal variants underlying TIE1/TEK signalling and the outcome. Publicly available single-nucleus RNA-sequencing data were leveraged to investigate differential expression of TIE1 and TEK in the human ocular anterior segment. RESULTS: Increased genetically proxied TIE1 signalling and TEK signalling associated with a reduction in IOP (- 0.21 mmHg per SD increase in sTIE1, 95% CI = - 0.09 to - 0.33 mmHg, P = 6.57 × 10-4, and - 0.14 mmHg per SD decrease in sTEK, 95% CI = - 0.03 to - 0.25 mmHg, P = 0.011), but not with POAG liability. Colocalization analysis found that the probability of a shared causal variant was greater for TIE1 and IOP than for TEK and IOP (PPshared/(PPdistinct + PPshared) = 0.98 for TIE1 and 0.30 for TEK). In the anterior segment, TIE1 and TEK were preferentially expressed in SC, lymphatic, and vascular endothelium. CONCLUSIONS: This study provides novel human genetic support for a causal role of both TIE1 and TEK signalling in regulating IOP. Here, combined evidence from cis-MR and colocalization analyses provide stronger support for TIE1 than TEK as a potential IOP-lowering therapeutic target

Deep learning of the retina enables phenome- and genome-wide analyses of the microvasculature.

Background: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health as well as tumorigenesis. The retinal fundus is a window for human in vivo non-invasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. Methods: We utilized 97,895 retinal fundus images from 54,813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated fractal dimension (FD) as a measure of vascular branching complexity, and vascular density. We associated these indices with 1,866 incident ICD-based conditions (median 10y follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. Results: Low retinal vascular FD and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular FD and density identified 7 and 13 novel loci respectively, which were enriched for pathways linked to angiogenesis (e.g., VEGF, PDGFR, angiopoietin, and WNT signaling pathways) and inflammation (e.g., interleukin, cytokine signaling). Conclusions: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights on genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health records, biomarker, and genetic data to inform risk prediction and risk modification

Presbyopia:Effectiveness of correction strategies

Presbyopia is a global problem affecting over a billion people worldwide. The prevalence of unmanaged presbyopia is as high as 50% of those over 50 years of age in developing world populations due to a lack of awareness and accessibility to affordable treatment, and is even as high as 34% in developed countries. Definitions of presbyopia are inconsistent and varied, so we propose a redefinition that states “presbyopia occurs when the physiologically normal age-related reduction in the eye's focusing range reaches a point, when optimally corrected for distance vision, that the clarity of vision at near is insufficient to satisfy an individual's requirements”. Presbyopia is inevitable if one lives long enough, but intrinsic and extrinsic risk factors including cigarette smoking, pregnancy history, hyperopic or astigmatic refractive error, ultraviolet radiation, female sex (although accommodation is similar to males), hotter climates and some medical conditions such as diabetes can accelerate the onset of presbyopic symptoms. Whilst clinicians can ameliorate the symptoms of presbyopia with near vision spectacle correction, bifocal and progressive spectacle lenses, monovision, translating or multifocal contact lenses, monovision, extended depth of focus, multifocal (refractive, diffractive and asymmetric designs) or ‘accommodating’ intraocular lenses, corneal inlays, scleral expansion, laser refractive surgery (corneal monovision, corneal shrinkage, corneal multifocal profiles and lenticular softening), pharmacologic agents, and electro-stimulation of the ciliary muscle, none fully overcome presbyopia in all patients. While the restoration of natural accommodation or an equivalent remains elusive, guidance is gives on presbyopic correction evaluation techniques

Simultaneous detection and differentiation of Entamoeba histolytica, E. dispar, E. moshkovskii, Giardia lamblia and Cryptosporidium spp. in human fecal samples using multiplex PCR and qPCR-MCA

Entamoeba histolytica, Giardia lamblia and Cryptosporidium spp. are common causes of diarrheal and intestinal diseases all over the world. Microscopic methods are useful in the diagnosis of intestinal parasites (IPs), but their sensitivity was assessed approximately 60 percent. Recently, molecular techniques have been used increasingly for the identification and characterization of the parasites. Among those, in this study we have used multiplex PCR and Real-time PCR with melting curve analysis (qPCR-MCA) for simultaneous detection and differentiation of E. histolytica, E. dispar, E. moshkovskii, G. lamblia and Cryptosporidium spp. in human fecal samples. Twenty DNA samples from 12 E. histolytica and 8 E. dispar samples and twenty stool samples confirmed positive for G. lamblia and Cryptosporidium spp. were analyzed. After DNA extraction from the samples, multiplex PCR was done for detection and differentiation of above mentioned parasites. QPCR-MCA was also performed for the detection and differentiation of 11 isolates of above mentioned parasite in a cycle with a time and temperature. Multiplex PCR was able to simultaneous detect and differentiate of above mentioned parasite in a single reaction. QPCR-MCA was able to differentiate genus and species those five protozoa using melting temperature simultaneously at the same time and temperature programs. In total, qPCR-MCA diagnosed 7/11 isolation of E. histolytica, 6/8 isolation of E. dispar, 1/1 E. moshkovskii Laredo, 10/11�G. Lamblia and 6/11 Cryptosporidium spp. Application of multiplex PCR for detection of more than one species in a test in developing countries, at least in reference laboratories has accurate diagnosis and plays a critical role in differentiation of protozoan species. Multiplex PCR assay with a template and multi template had different results and it seems that using a set of primers with one template has higher diagnostic capability in compare with multi template. The results of this study showed that the use of the qPCR-MCA can be an effective method to simultaneous distinguish of the above mentioned parasites. © 2016 Elsevier B.V

Identification of Acanthamoeba spp. from water and soil of public parks in north of Iran

Acanthamoeba, a free-living and opportunistic protozoan parasite, is a causative agent of severe human infections of the cornea and brain. The present study evaluated the distribution and genotyping of Acanthamoeba spp. in water and soil of recreational places in various areas in Guilan province in northern Iran. Eighty water and 20 soil samples were collected from the study area. Water samples were vacuum filtered through a 0.45 mu m pore-size membrane filter. Soil samples were washed with sterile distilled water, and washings were similarly filtered, as mentioned for water samples. The filtered material was cultured on non-nutrient agar plates seeded with heat-killed Escherichia coli. Molecular analysis was performed by PCR and sequencing using specific primers for Acanthamoeba. Finally, 26 isolates were successfully sequenced. According to culture and PCR methods, 54% of water and 100% of soil samples were contaminated with Acanthamoeba. Based on the sequencing data, genotypes T4 (47%), T5 (35.29%) and, T3 (11.76%), T11 (5.88%) were identified in water samples. GenotypesT4 (66.6%), T5 (22.2%) and T15 (11.1%) identified in water samples. Most isolates might present a potential health hazard for humans in this region. To the best of our knowledge, this is the first comprehensive survey of water and soil of recreational areas in northern Iran and the first report on identifying genotype T15 from soil sources