The molecular basis of retinal ganglion cell death in glaucoma.

Screening for breast cancer.

Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). Choice of treatment should be based on the assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves' hyperthyroidism. In moderate-to-severe and active GO i.v. glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive counseling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) teprotumumab; (e) rituximab and (f) tocilizumab. Sight-threatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations.

/pdf/the-2021-european-group-on-graves-orbitopathy-eugogo-752f9uyirr.pdf

The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy

Retinal microglia: Just bystander or target for therapy?

Contact lenses as a minimally invasive platform for diagnostics and drug delivery have emerged in recent years. Contact lens sensors have been developed for analyzing the glucose composition of tears as a surrogate for blood glucose monitoring and for the diagnosis of glaucoma by measuring intraocular pressure. However, the eye offers a wider diagnostic potential as a sensing site and therefore contact lens sensors have the potential to improve the diagnosis and treatment of many diseases and conditions. With advances in polymer synthesis, electronics and micro/nanofabrication, contact lens sensors can be produced to quantify the concentrations of many biomolecules in ocular fluids. Non- or minimally invasive contact lens sensors can be used directly in a clinical or point-of-care setting to monitor a disease state continuously. This article reviews the state-of-the-art in contact lens sensor fabrication, their detection, wireless powering, and readout mechanisms, and integration with mobile devices and smartphones. High-volume manufacturing considerations of contact lenses are also covered and a case study of an intraocular pressure contact lens sensor is provided as an example of a successful product. This Review further analyzes the contact lens market and the FDA regulatory requirements for commercialization of contact lens sensors.

/pdf/contact-lens-sensors-in-ocular-diagnostics-3cjapb8hja.pdf

Contact Lens Sensors in Ocular Diagnostics

Noninvasive biomarkers are urgently needed for early detection of breast cancer since the risk of recurrence, morbidity and mortality are closely related to disease stage at the time of primary surgery. In the past decade, many proteomics-based approaches were developed that utilize the protein profiling of human body fluids or identification of putative biomarkers to obtain more knowledge on the effects of cancer emergence and progression. Herein, we report on an analysis of proteins in the tear fluid from breast carcinoma patients and healthy women using a de novo proteomic approach and 25 mixed samples from each group. This study included 25 patients with primary invasive breast carcinoma and 25 age-matched healthy controls. We performed a MALDI-TOF-TOF-driven semi-quantitative comparison of tear protein levels in cancer (CA) and control (CTRL) using a de novo approach in pooled samples. Over 150 proteins in the tear fluid of CTRL and CA were identified. Using an in-house-developed algorithm we found more than 20 proteins distinctly upregulated or downregulated in the CTRL and CA groups. We identified several proteins that had modified expression in breast cancer patients. These proteins are involved in host immune system pathways (e.g., C1Q1 or S100A8) and different metabolic cascades (ALDH3A or TPI). Further validation of the results in an independent population combined with individual protein profiling of participants is needed to confirm the specificity of our findings and may lead to a better understanding of the pathological mechanism of breast cancer.

/pdf/comparison-of-tear-protein-levels-in-breast-cancer-patients-32xvejna4x.pdf

Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach

Purpose
To analyze protein patterns in the aqueous humor of glaucoma patients in comparison to control subject using two different methods.

Transthyretin and complex protein pattern in aqueous humor of patients with primary open-angle glaucoma.

Ocular and systemic autoimmune diseases impair the proteome patterns of tear fluid. To learn more about the complex pathological processes in autoimmune thyroid eye disease (TED) it is essential to get detailed information on these proteins. Therefore, the purpose of this prospective and controlled study was to detect and evaluate possible changes in the proteomic patterns in tear fluid of patients with TED. Tear samples from TED patients with various disease severity and activity, and healthy controls were analyzed with the SELDI-TOF-MS-technology using arrays with different chromatographic surfaces (CM10 cation exchange, H50 reversed-phase). Data were analyzed by multivariate statistical techniques and artificial neural networks. The discriminate analysis revealed significant changes (p<0.05) in the protein profiles of TED patients compared to controls. We obtained a set of protein biomarkers that allowed us to clearly discriminate between patients and controls with a very high sensitivity and specificity (ROC curve, r=0.99). All possible biomarkers found in this study had a molecular weight between 3000 and 20,000 Da. The majority of the proteins was downregulated in the patient group, with only few proteins overexpressed in comparison to healthy controls. The SELDI-TOF-MS is an accurate method for proteome analysis in tear fluid of TED patients. These proteins may serve as biomarkers for diagnosis and follow-up during treatment.

Proteomics in autoimmune thyroid eye disease.

Purpose: Antibodies against heat shock proteins have been identified in sera of human glaucoma patients in several studies and immunization with heat shock protein 60 (HSP 60) causes retinal ganglion cell (RGC) loss in an animal model of experimental autoimmune glaucoma The aim of this study was to observe the time course of increased anti-retina antibody appearance in the serum and characterize the identification of prominent autoantibodies that accompany HSP 60 immunization in a rat model of experimental autoimmune glaucomaMethods: Eight weeks after immunization with HSP 60 retinal flatmounts were prepared and RGCs were counted in eight predefined areas and compared to controls Serum collected before, as well as four and eight weeks after, immunization was used to detect antibody patterns against bovine retinal antigens using Western blotting techniques These patterns were analyzed by multivariate statistical methods Autoantibodies that were prominently increased were further identified through mas

Enhanced characterization of serum autoantibody reactivity following HSP 60 immunization in a rat model of experimental autoimmune glaucoma.

Non-invasive biomarkers for early breast cancer detection are urgently needed, as the risk of recurrent morbidity and mortality is closely related to the stage of the disease at the time of primary surgery. Currently, there are no established clinical biomarkers for breast cancer. Evaluation of protein expression patterns in body fluids using proteomic technologies can be used to discover new biomarkers for the detection of breast cancer. The aim of this study was to identify a biomarker signature identifying primary non-metastatic breast cancer and healthy controls. We screened 91 serum samples including 45 breast cancer patients and 46 healthy women using a proteomic approach. We found 14 biomarkers whose combination detects breast cancer patients from non-cancer controls with a sensitivity of 89% and specificity of 67%. Five biomarkers were comparable with previously identified proteins from published data using similar approaches. This biomarker panel allows accurate discrimination between breast cancer and healthy individuals. In addition, it could distinguish subgroups of breast cancer based on patterns of several specific biomarkers. Further validation of biomarkers could potentially facilitate the early diagnosis of breast cancer as an aid to imaging diagnostics.

/pdf/serum-proteome-profiling-of-primary-breast-cancer-indicates-q6czsowcj0.pdf

Serum proteome profiling of primary breast cancer indicates a specific biomarker profile.

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