Objectives: Previous studies have demonstrated that patients with diabetic retinopathy (DR) have a higher prevalence of risk factors known to be associated with cardiovascular disease (CVD). We hypothesized that patients with more severe DR could have a higher relative risk of CVD. Methods: To test this hypothesis, we used the National Health Insurance Research Database (NHIRD) to evaluate whether associations exist between DR and CVD. The data for this nationwide population-based retrospective cohort study were obtained from the NHIRD in Taiwan from 2001 to 2013. The assessed study outcome used was the incidence and other statistical analyses of CVD in patients with DR during a 13-year follow-up period. Results: Our findings obtained from 2001 to 2013 suggest that the incidence rates of CVD are 2.026 times that of diabetes mellitus (DM) without DR (95% C.I. = 1.876–2.187) and 2.75 times that of DM with DR (95% C.I. = 2.487–3.04) compared with the Non-DM group. Conclusion: The relative risk of CVD in DR was greater than that in the Non-DM group for both men and women. Targeted monitoring of DM, especially the co-existence of diabetic retinopathy, is of utmost importance in the clinical care of the DM population.
We commonly diagnose ocular diseases via both morphological changes and symptoms. It is necessary to develop biochemically based assays for early or follow-up diagnosis of these diseases with a focus on robustness and ease of handling. To lay out a prospective path toward this goal, we describe and propose the use of ultrahigh sensitive paper-based ELISA (p-ELISA), which uses a treated piece of filter paper to monitor the activity of ocular diseases (i.e., detecting the vascular endothelial growth factor (VEGF) concentration in aqueous humour for proliferative diabetic retinopathy or age-related macular degeneration diagnosis). The advantages of p-ELISA include the following: (1) the capacity to directly measure biomarker concentrations in aqueous humour using only a tiny sample volume (as little as 2 μL); (2) significantly increased sensitivity compared to conventional ELISA (fg/mL levels); and (3) inexpensive materials and a short operation duration. P-ELISA is a novel point-of-care diagnostic tool with the significant potential to advance ophthalmological treatment guidelines by facilitating early detection and routinely monitoring therapeutic response.
Exosomes are membranous structures measuring between 40–120 nm that are secreted by various cells of the human body into the body fluid system. Exosomes contain proteins, mRNA, miRNA, and signaling molecules, and physiologically they assist in the intercellular transport of proteins and RNA molecules. In this study, we used an immunoaffinity filter paper platform combined with scanning electron microscopy and microfluidic systems to detect the size of exosomes within the aqueous humor. Eight aqueous humor samples showed three distinct sizes of exosomes that were significantly different on scanning electron microscopy(P < 0.01). We further used nanoparticle tracking analysis to assess the size distribution of exosomes within the aqueous humor. We found significantly different distributions of exosomes between patients with three different ocular diseases and patients with normal cataracts as controls. An obvious peak of exomeres(size around 35 nm)was found in the patients with central retinal vein occlusion and vitreous hemorrhage. Flare-ups of large exosomes(size 90–120 nm)were found in the patients with the inflammatory ocular disease pars planitis. No obvious peaks in exomeres or large exosomes were found in the control group. There was a high association between the distribution of exosomes and the pathogenesis of ocular diseases. After intravitreal anti-vascular endothelial growth factor treatment, the aqueous humor from the patients with neovascular diseases showed a significant reduction in exosomes in nanoparticle tracking analysis. These findings suggest that at least three distinct sizes of exosomes exist in the aqueous humor:(1)exomeres:<35 nm;(2)small exosomes:60–80 nm; and (3)large exosomes:90–120 nm. Different sizes of exosomes may have different implications in normal or diseased eyes.
<b><i>Purpose:</i></b> In normal tension glaucoma (NTG), factors other than elevated intraocular pressure are likely to have a role in the pathogenesis of optic neuropathy. Recent studies of glaucoma or retinal ganglion cells (RGCs) reveal that the cytokine interleukin-6 (IL-6) is linked to the pathogenesis of glaucoma and may regulate RGC survival or death. The IL-6 (-174) G allele has also been shown to increase the IL-6 protein. We hypothesized that the IL-6 (-174) polymorphism may be a predisposing genetic factor affecting the severity of glaucoma. The aim of the present study was to evaluate the IL-6 polymorphism and serum IL-6 levels as a potential risk factor related to the severity of NTG. <b><i>Methods:</i></b> A total of 256 subjects with NTG in the Chinese population were enrolled. The patients were genotyped for the IL-6 (-174) C/G polymorphism. Genomic DNA was amplified by a polymerase chain reaction, followed by the enzymatic restriction fragment length polymorphism technique. Serum IL-6 levels were measured by ELISA. Patient age at diagnosis, cup/disc (C/D) ratio, rim area (RA), retinal nerve fiber layer (RNFL) thickness, and visual field (VF) were analyzed. The associations between genotypes of IL-6 (-174) C/G and the clinical parameters were calculated using a logistic regression. <b><i>Results:</i></b> The IL-6 (-174) GC genotype in NTG patients was significantly associated with a smaller C/D ratio (<i>p</i> = 0.04), larger RA (<i>p</i> = 0.04), and thicker RNFL (<i>p</i> = 0.05) compared with IL-6 (-174) GG patients. The allele frequency of IL-6 (-174) C was significantly higher in the NTG patients at an early-moderate stage than at an advanced stage according to the C/D ratio (OR 0.55; 95% CI 0.31-0.99). Pattern standard deviation of VF was borderline lower in IL-6 (-174) GC patients (<i>p</i> = 0.06), and serum IL-6 levels were borderline higher in advanced stages than in early-moderate stages (7.66 ± 3.22 vs. 4.46 ± 3.83 pg/mL; <i>p</i> = 0.06). <b><i>Conclusion:</i></b> The IL-6 (-174) GC genotype is associated with a smaller C/D ratio, larger RA, and thicker RNFL compared with IL-6 (-174) GG in NTG patients. We found that the IL-6 (-174) G/C polymorphism and serum IL-6 levels may be associated with the severity of NTG.
Here, we discuss the development of a paper-based diagnostic device that is inexpensive, portable, easy-to-use, robust, and capable of running simultaneous tests to monitor a relevant inflammatory protein for clinical diagnoses i.e. C-reactive protein (CRP). In this study, we first attempted to make a paper-based diagnostic device via the wax printing method, a process that was used in previous studies. This device has two distinct advantages: 1) reduced manufacturing and assay costs and operation duration via using wax printing method to define hydrophobic boundaries (for fluidic devices or general POC devices); and, 2) the hydrophilicity of filter paper, which is used to purify and chromatographically correct interference caused by whole blood components with a tiny amount of blood sample (only 5 μL). Diagnosis was based on serum stain length retained inside the paper channels of our device. This is a balanced function between surface tension and chromatographic force following immune reactions (CRP assays) with a paper-embedded biomarker.
Emerging roles of exosomes in the pathogenesis of major blindness-threatening diseases, such as age-related macular degeneration, glaucoma, and corneal dystrophy, were discovered by aqueous humor analysis. A new diagnostic method using cellulose-based devices and microfluidic chip techniques for the isolation of exosomes from aqueous humor is less cumbersome and saves time. This method will enable more investigations for aqueous humor analysis in the future.
Abstract Identification of an early biomarker and effective testing device to differentiate dry eye disease secondary to autoimmune disease (Sjögren’s syndrome dry eye disease) from non-Sjögren’s dry eye disease are prerequisites for appropriate treatment. We aimed to demonstrate the capacity of a new photo-detection device to evaluate tear lactoferrin levels as a tool for differentiating systemic conditions associated with dry eye disease. Patients with non-Sjögren’s and Sjögren’s syndrome dry eye disease (n = 54 and n = 52, respectively) and controls (n = 11) were enrolled. All participants completed the Ocular Surface Disease Index questionnaire. Tear collection was performed with Schirmer test, and tear break-up time was examined using a slit lamp. Tear lactoferrin was evaluated using our newly developed photo-detection device. The average lactoferrin concentration was significantly lower in samples from patients with non-Sjögren’s dry eye disease (0.337 ± 0.227 mg/mL, n = 54) and Sjögren’s syndrome dry eye disease (0.087 ± 0.010 mg/mL, n = 52) than in control samples (1.272 ± 0.54 mg/mL, n = 11) (p < 0.0001). Further, lactoferrin levels were lower in patients with Sjögren’s syndrome dry eye disease than in those with non-Sjögren’s dry eye disease (p < 0.001). Our cost-effective, antibody-free, highly sensitive photo-detection device for evaluating tear lactoferrin levels can assist ophthalmologists in differentiating different types of dry eye diseases.
Abstract Real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) using specimens collected from nasopharyngeal and/or oropharyngeal swabs is the standard screening approach for coronavirus disease 2019 (COVID‐19). While PCR is rapid and highly accurate, it requires costly laboratory equipment and healthcare professionals that limit its use for large‐scale screening of mild or asymptomatic patients. Self‐collection kits for use in the home could remedy this and have consequently received great attention. In April, 2020, a self‐collection kit from LapCorp was the first such kit to be approved by the FDA. In the following month, May 2020, another kit developed by Everlywell received FDA approval, and more kits are evidently on their way to the market in the United Kingdom and elsewhere. Because these home‐based, self‐collection kits are easy to use and may be more acceptable for patients, they provide a superior screening option for mild or asymptomatic patients under self‐quarantine. These kits conserve personal protective equipment and healthcare manpower already in short supply. The primary issues affecting the efficacy of this approach are the potential for inappropriate sampling and insufficient clinical examination. A detailed review of the commercially available kits currently available is provided and their prospective impact is noted during the current pandemic.
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