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Purpose: To compare Behçet uveitis patients who presented in the 1990s and 2000s.Methods: Records of 170 patients seen in 1990-1994 and 258 patients seen in 2000-2004 were reviewed. Presenting features were analyzed in the whole cohort. Uveitis attacks, vision, complications, and immunomodulatory treatment (IMT) were compared in patients with 3-year follow-up.Results: Posterior segment involvement was less common, visual acuity was better, and more patients received IMT before referral in the 2000s. Follow-up revealed no significant difference in number of uveitis attacks in the first 3 years. Less eyes lost useful vision, no patient became legally blind, and fewer severe ocular complications occurred in the 2000s. IMT was started within 3 months in more patients and interferon alfa-2a was used only in the latter study period.Conclusions: The findings suggest a milder disease at referral, lower rate of severe complications, and a better 3-year visual outcome in patients who presented in the early 2000s. [ABSTRACT FROM AUTHOR]

AimsTo study spatial–contrast function and short-wavelength sensitivity deficits in a migraine population with a disease duration of 30 years or less.Materials and methodsIn this prospective, cross-sectional study, we evaluated 28 subjects with migraine headache and 15 nonheadache healthy controls. Visual fields were evaluated using the Humphrey Field Analyzer 750i and the 30-2, blue and yellow threshold programme. Contrast sensitivity (CS) was measured at 1.5, 3, 6, 12, and 18 cpd spatial frequencies, using the Functional Acuity Contrast Test (F.A.C.T.™). The results of the visual field parameters (mean defect (MD) and pattern standard defect (PSD)) and CS were compared with 15 age-equivalent normal subjects.ResultsShort-wavelength amplitude perimetry (SWAP) parameters and CS scores at all spatial frequencies were significantly altered in the migraine patients when compared with the control subjects. Visual field parameters correlated significantly with contrast sensitivity scores: positively for MD (r=0.39, P=0.01; r=0.43, P=0.005; r=0.56, P=0.0001; r=0.45, P=0.003; r=0.48, P=0.0001) and negatively for PSD (r=−0.45, P=0.003; r=−0.45, P=0.003; r=−0.51, P=0.001; r=−0.53, P=0.0001; and r=−0.67, P=0.0001) at all (1.5, 3, 6,12, and 18 cpd) spatial frequencies, respectively. Migraine duration correlated negatively with MD (r=−0.42, P=0.04) and positively with PSD (r=0.42, P=0.03).ConclusionMigraineurs had significantly altered visual field and contrast function at all spatial frequencies to the normal population. These defects share some features with early stages of glaucoma and may relate a possibility for a common vascular disease pathogenesis in these two conditions.Eye (2007) 21, 218–223. doi:10.1038/sj.eye.6702251; published online 3 February 2006 [ABSTRACT FROM AUTHOR]

Purpose: Familial occurrence has been reported in approximately 8% of Turkish patients with Behçet's disease. Our aim was to compare the clinical course of ocular Behçet's disease among siblings.Methods: We retrospectively studied five pairs of siblings with ocular involvement of Behçet's disease. No other family member of these siblings had any symptom of Behçet's disease.Results: The siblings comprised three sister-brother pairs, one sister-sister pair, and one brother-brother pair. There was a 5-10-year difference between the age at onset of ocular disease among siblings. Three of the five pairs (two sister-brother, one brother-brother) had a dissimilar course of disease activity. Female siblings had an earlier age at onset and tended to have a worse prognosis than their brothers.Conclusions: It is generally acknowledged that male sex is associated with a worse prognosis. In this study, however, we observed that, among siblings with a dissimilar course, female patients were more severely affected than male patients. Poor ocular prognosis in a patient does not indicate aggressive treatment in his/her sibling. We believe that each sibling should be managed on an individual basis. [ABSTRACT FROM AUTHOR]

Mechanical forces shape physiological structure and function within cell and tissue microenvironments, during which cells strive to restore their shape or develop an adaptive mechanism to maintain cell integrity depending on strength and type of the mechanical loading. While some cells are shown to experience permanent plastic deformation after a repetitive mechanical tensile loading and unloading, the impact of such repetitive compression on deformation of cells is yet to be understood. As such, the ability to apply cyclic compression is crucial for any experimental setup aimed at the study of mechanical compression taking place in cell and tissue microenvironments. Here, we demonstrate such cyclic compression using a microfluidic compression platform on live cell actin in SKOV-3 ovarian cancer cells. Live imaging of the actin cytoskeleton dynamics of the compressed cells was performed for varying pressures applied sequentially in ascending order during cell compression. Additionally, recovery of the compressed cells was investigated by capturing actin cytoskeleton and nuclei profiles of the cells at zero time and 24 h-recovery after compression in end point assays. This was performed for a range of mild pressures within the physiological range. Results showed that the phenotypical response of compressed cells during recovery after compression with 20.8 kPa differed observably from that for 15.6 kPa. This demonstrated the ability of the platform to aid in the capture of differences in cell behaviour as a result of being compressed at various pressures in physiologically relevant manner. Differences observed between compressed cells fixed at zero time or after 24 h-recovery suggest that SKOV-3 cells exhibit deformations at the time of the compression, a proposed mechanism cells use to prevent mechanical damage. Thus, biomechanical responses of SKOV-3 ovarian cancer cells to sequential cyclic compression and during recovery after compression could be revealed in a flexible microdevice. As demonstrated in this work, the observation of morphological, cytoskeletal and nuclear differences in compressed and non-compressed cells, with controlled micro-scale mechanical cell compression and recovery and using live-cell imaging, fluorescent tagging and end point assays, can give insights into the mechanics of cancer cells., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Onal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Compressive stress enables the investigation of a range of cellular processes in which forces play an important role, such as cell growth, differentiation, migration, and invasion. Such solid stress can be introduced externally to study cell response and to mechanically induce changes in cell morphology and behavior by static or dynamic compression. Microfluidics is a useful tool for this, allowing one to mimic in vivo microenvironments in on-chip culture systems where force application can be controlled spatially and temporally. Here, we review the mechanical compression applications on cells with a broad focus on studies using microtechnologies and microdevices to apply cell compression, in comparison to off-chip bulk systems. Due to their unique features, microfluidic systems developed to apply compressive forces on single cells, in 2D and 3D culture models, and compression in cancer microenvironments are emphasized. Research efforts in this field can help the development of mechanoceuticals in the future., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Purpose : To develop an algorithm for the diagnosis of Behçet's disease (BD) uveitis based on ocular findings. Methods : Following an initial survey among uveitis experts, we collected multi-center retrospective data on 211 patients with BD uveitis and 207 patients with other uveitides, and identified ocular findings with a high diagnostic odds ratio (DOR). Subsequently, we collected multi-center prospective data on 127 patients with BD uveitis and 322 controls and developed a diagnostic algorithm using Classification and Regression Tree (CART) analysis and expert opinion. Results : We identified 10 items with DOR >5. The items that provided the highest accuracy in CART analysis included superficial retinal infiltrate, signs of occlusive retinal vasculitis, and diffuse retinal capillary leakage as well as the absence of granulomatous anterior uveitis or choroiditis in patients with vitritis. Conclusion : This study provides a diagnostic tree for BD uveitis that needs to be validated in future studies.

Objectives: Cone-beam computed tomography (CBCT) scans enable quantification of interproximal bone loss after implant procedures in dental patients. In order for this quantification to be accurate, software is typically used to manipulate image sets captured before and after implantation to obtain their exact registration (i.e., alignment). However, no affordable CBCT image registration software is currently available for dental applications. Thus, the aim of the present study was to develop a freely available graphical user interface, called DentIR, that automates 2-dimensional (2-D) or 3-D image registration for use in planning dental treatment., Methods: The DentIR app was designed using the MATLAB environment, downloaded to a desktop personal computer (PC and Mac), and tested for its ease of use and alignment accuracy in the absence of the MATLAB environment., Results: The DentIR app enabled previewing of the CBCT images in 3-D to allow for filtering of each frame to reduce noise and blurring before registration. The 2-D or 3-D registration was tested with four transformation methods. The accuracy of each method was assessed by comparing the mean squared error and the peak signal-to-noise ratio values that were provided by the DentIR app. The registered images could be saved as Portable Network Graphics (PNG) images., Conclusions: The free, user-friendly DentIR app was easily downloadable to Mac or PC platforms. It provided accurate image registration to aid in the planning of dental treatment. Future updates of the DentIR app include adding the ability to register more than two images at once, enhancing image editing options and enabling registration of a cropped portion of the image for more in-depth analyses.

Breast cancer cells (BCC) and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by BCC. Despite contradictory findings, this interaction is perceived as a paracrine loop. Further, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of BCC with macrophages in 2D and 3D. While both BCC and macrophages showed invasion/chemotaxis to fetal bovine serum, only macrophages showed chemotaxis to BCC in custom designed 3D cell-on-a-chip devices. These results were in agreement with gradient simulation results and ELISA results showing that macrophage-derived-EGF was not secreted into macrophage-conditioned-medium. Live cell imaging of BCC in the presence and absence of iressa showed that macrophages but not macrophage-derived-matrix modulated adhesion and motility of BCC in 2D. 3D co-culture experiments in collagen and matrigel showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages promoted and reduced migration of BCC in collagen and matrigel, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC whereas BCC required direct contact to interact with macrophage-derived-EGF. Therefore, we propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

"After a certain high level of technical skill is achieved, science and art tend to coalesce in aesthetics, plasticity, and form. The greatest scientists are always artists as well." said Albert Einstein. Currently, photographic images bridge the gap between microfluidic/lab-on-a-chip devices and art. However, the microfluidic chip itself should be a form of art. Here, novel vibrant epoxy dyes are presented in combination with a simple process to fill and preserve microfluidic chips, to produce microfluidic art or art-on-a-chip. In addition, this process can be used to produce epoxy dye patterned substrates that preserve the geometry of the microfluidic channels-height within 10% of the mold master. This simple approach for preserving microfluidic chips with vibrant, colorful, and long-lasting epoxy dyes creates microfluidic chips that can easily be visualized and photographed repeatedly, for at least 11 years, and hence enabling researchers to showcase their microfluidic chips to potential graduate students, investors, and collaborators., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: To investigate the effect of interferon alfa-2a on T regulatory (Treg) cells, T helper 17 (Th17) cells, and expression of Toll-like receptors (TLRs) in Behçet disease (BD) patients with uveitis., Methods: Twenty-seven patients who received interferon alfa-2a for active BD uveitis despite conventional immunomodulatory therapies and healthy controls were enrolled. Peripheral blood Treg and Th17 cell frequencies were determined by flow cytometry as gated cells for CD3+CD4+Foxp3+ and CD3+CD4+IL17A+, respectively. Th17 RAR-related orphan receptor (ROR)γt mRNA expression was verified by real-time PCR (RT-PCR). Treg and Th17 cell cytokines were detected by ELISA in the supernatant of short-term cell cultures. RT-PCR was used to assess expression of TLR-2, TLR-3, TLR-4, TLR-8, and TLR-9 using cDNA prepared from CD4+ T cells and monocytes., Results: Treg and Th17 cell frequencies and Th17 RORγt expression were significantly elevated, and IL-10 concentration in Treg cell supernatants was significantly lower in BD patients than in controls. Th17 IL-17, IL-6, IL-21, IL-22, IL-23, IFN-γ, and TNF-α concentrations were significantly higher and all TLR expressions were significantly elevated in patients. Interferon alfa-2a led to a significant reversal in Treg and Th17 cell frequencies, Th17 RORγt expression, Treg and Th17 cell cytokine production, and TLR expression by CD4+ T cells and monocytes., Conclusions: Despite a relative increase in Treg cells, impaired IL-10 production suggests that Treg dysfunction may play a role in induction of BD uveitis. Favorable effects of interferon alfa-2a may be associated with recovery of Treg cell function, suppression of Th17 cells, and reduced expression of TLRs on CD4+ T cells and monocytes.

Purpose: To quantitatively analyze in vivo morphology of subfoveal choroid during an acute attack of Behçet uveitis., Methods: In this prospective study, 28 patients with Behçet uveitis of ≤4-year duration, and 28 control subjects underwent enhanced depth imaging optical coherence tomography. A novel custom software was used to calculate choroidal stroma-to-choroidal vessel lumen ratio. Subfoveal choroidal thickness was measured at fovea and 750 μm nasal, temporal, superior, and inferior to fovea. Patients underwent fluorescein angiography and indocyanine green angiography. Receiver operating characteristic curve and area under the curve were computed for central foveal thickness. The eye with a higher Behçet disease ocular attack score 24 was studied. The main outcome measures were choroidal stroma-to-choroidal vessel lumen ratio and choroidal thickness., Results: The mean total Behçet disease ocular attack score 24, fluorescein angiography, and indocyanine green angiography scores were 7.42 ± 4.10, 17.42 ± 6.03, and 0.66 ± 0.73, respectively. Choroidal stroma-to-choroidal vessel lumen ratio was significantly higher in patients (0.413 ± 0.056 vs. 0.351 ± 0.063, P = 0.003). There were no significant differences in subfoveal choroidal thickness between patients and control subjects. Choroidal stroma-to-choroidal vessel lumen ratio correlated with retinal vascular staining and leakage score of fluorescein angiography (r = 0.300, P = 0.036). Central foveal thickness was significantly increased in patients (352.750 ± 107.134 μm vs. 263.500 ± 20.819 μm, P < 0.001). Central foveal thickness showed significant correlations with logarithm of minimum angle of resolution vision, Behçet disease ocular attack score 24, total fluorescein angiography score, retinal vascular staining and/or leakage and capillary leakage scores of fluorescein angiography, and total indocyanine green angiography score. At 275 μm cutoff, diagnostic sensitivity and specificity of central foveal thickness for acute Behçet uveitis were 89% and 72%, respectively (area under the curve = 0.902; 95% CI = 0.826-0.978, P < 0.001)., Conclusion: There was choroidal stromal expansion which was not associated with thickening of the choroid. Central foveal thickness may be used as a noninvasive measure to assess inflammatory activity in early Behçet uveitis.

Purpose: To screen for psychological disorders in patients with active uveitis., Methods: Patients were screened for depression (BDI-II), state anxiety (STAI-I), VR-QOL (NEI-VFQ-25), and HR-QOL (SF-36). Association of depression and anxiety with sociodemographic and clinical parameters and with VR-QOL and HR-QOL were analyzed. Multivariate linear regression models were constructed for NEI-VFQ-25 and SF-36 subscales., Results: Of 99 patients, 37.3% screened positive for depression and 52.5% for anxiety. Depressed patients had lower visual acuity in the better seeing eye (p = 0.013) and more frequently panuveitis (p = 0.018). Anxious patients were younger (p = 0.009), had earlier onset of uveitis (p = 0.015), and had more frequently panuveitis (p = 0.016). Bivariate comparisons showed significant associations between psychological disorders and VR-QOL and HR-QOL. Significant bivariate associations were mostly lost in multivariate analyses for anxiety, but were preserved for depression., Conclusions: A positive screening test for depression and anxiety is common in patients with uveitis. Low vision and panuveitis are associated with depression. Depression is associated with impairment of VR-QOL and HR-QOL.

Purpose: To report the efficacy and safety of interferon (IFN) α-2a in patients with cystoid macular edema (CME) associated with presumed ocular tuberculosis (TB)., Methods: We reviewed the clinical records of 5 patients with presumed ocular TB who had been treated with IFN α-2a for recurrent CME during or after completion of anti-tubercular therapy. IFN α-2a was administered at an initial dose of 3 million IU per day and then tapered after the initial response. Treatment efficacy was assessed by central macular thickness (CMT) measurement using spectral-domain optical coherence tomography and visual acuity., Results: Three patients were men, and 2 were women. Patients were aged between 38 and 66 years. Mean CMT was 483 ± 178.6 μm at baseline, 302.3 ± 56 μm at 1 week, 312.3 ± 49.5 μm at 1 month, and 286.2 ± 31.9 μm at 3 months. Mean LogMAR visual acuity was 0.6 ± 0.4 at baseline, 0.4 ± 0.3 μm at 1 week, 0.3 ± 0.3 at 1 month, and 0.3 ± 0.3 at 3 months. The treatment was interrupted for 10 days because of neutropenia after 2 weeks in 1 patient and discontinued in another after 10 days because of intolerance. Total treatment duration was 3-24 months in the remaining 4 patients., Conclusion: The present small case series suggests that IFN α-2a may be an effective and safe therapeutic option for CME that is associated with presumed ocular TB.

Uveitis is one of the fields in ophthalmology where a tremendous evolution took place in the past 25 years. Not only did we gain access to more efficient, more targeted, and better tolerated therapies, but also in parallel precise and quantitative measurement methods developed allowing the clinician to evaluate these therapies and adjust therapeutic intervention with a high degree of precision. Objective and quantitative measurement of the global level of intraocular inflammation became possible for most inflammatory diseases with direct or spill-over anterior chamber inflammation, thanks to laser flare photometry. The amount of retinal inflammation could be quantified by using fluorescein angiography to score retinal angiographic signs. Indocyanine green angiography gave imaging insight into the hitherto inaccessible choroidal compartment, rendering possible the quantification of choroiditis by scoring indocyanine green angiographic signs. Optical coherence tomography has enabled measurement and objective monitoring of retinal and choroidal thickness. This multimodal quantitative appraisal of intraocular inflammation represents an exquisite security in monitoring uveitis. What is enigmatic, however, is the slow pace with which these improvements are integrated in some areas. What is even more difficult to understand is the fact that clinical trials to assess new therapeutic agents still mostly rely on subjective parameters such as clinical evaluation of vitreous haze as a main endpoint; whereas a whole array of precise, quantitative, and objective modalities are available for the design of clinical studies. The scope of this work was to review the quantitative investigations that improved the management of uveitis in the past 2-3 decades.