A portable widefield fundus camera with high dynamic range imaging capability

Fundus photography is indispensable for clinical detection and management of eye diseases. Limited image contrast and field of view (FOV) are common limitations of conventional fundus cameras, making it difficult to detect subtle abnormalities at the early stages of eye diseases. Further improvements of image contrast and FOV coverage are important to improve early disease detection and reliable treatment assessment. We report here a portable fundus camera, with a wide FOV and high dynamic range (HDR) imaging capabilities. Miniaturized indirect ophthalmoscopy illumination was employed to achieve the portable design for nonmydriatic, widefield fundus photography. Orthogonal polarization control was used to eliminate illumination reflectance artifact. With independent power controls, three fundus images were sequentially acquired and fused to achieve HDR function for local image contrast enhancement. A 101{\deg} eye-angle (67{\deg} visual-angle) snapshot FOV was achieved for nonmydriatic fundus photography. The effective FOV can be readily expanded up to 190{\deg} eye-angle (134{\deg} visual-angle) with the aid of a fixation target, without the need of pharmacologic pupillary dilation. The effectiveness of HDR imaging was validated with both normal healthy and pathologic eyes, compared to a conventional fundus camera.Comment: 12 pages, 8 figure

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy : a systematic review and meta-analysis of observational data

Background Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin ScalePeer reviewe

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: A systematic review and meta-analysis of observational data

Background: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods: We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days). Results: The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics. Conclusion: The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty

Update in Molecular Testing for Intraocular Lymphoma

The diagnosis of primary vitreoretinal lymphoma and central nervous system lymphoma is challenging. In cases with intraocular involvement, vitreous biopsy plays a pivotal role. Several diagnostic tests are employed to confirm a diagnosis and include cytologic evaluation, immunohistochemistry, flow cytometry, and cytokine analysis. The limitations of these conventional diagnostic tests stem from the often paucicellular nature of vitreous biopsy specimens and the fragility of malignant cells ex vivo. Several emerging molecular techniques show promise in improving the diagnostic yield of intraocular biopsy, possibly enabling more accurate and timely diagnoses. This article will review existing diagnostic modalities for intraocular lymphoma, with an emphasis on currently available molecular tests

Zileuton, 5-Lipoxygenase Inhibitor, Acts as a Chemopreventive Agent in Intestinal Polyposis, by Modulating Polyp and Systemic Inflammation

<div><p>Purpose</p><p>Leukotrienes and prostaglandins, products of arachidonic acid metabolism, sustain both systemic and lesion-localized inflammation. Tumor-associated Inflammation can also contribute to the pathogenesis of colon cancer. Patients with inflammatory bowel disease (IBD) have increased risk of developing colon cancer. The levels of 5-lipoxygenase (5-LO), the key enzyme for leukotrienes production, are increased in colon cancer specimens and colonic dysplastic lesions. Here we report that Zileuton, a specific 5-LO inhibitor, can prevent polyp formation by efficiently reducing the tumor-associated and systemic inflammation in APC^Δ468 mice.</p><p>Experimental Design</p><p>In the current study, we inhibited 5-LO by dietary administration of Zileuton in the APC^Δ468 mouse model of polyposis and analyzed the effect of <i>in vivo</i> 5-LO inhibition on tumor-associated and systemic inflammation.</p><p>Results</p><p>Zileuton-fed mice developed fewer polyps and displayed marked reduction in systemic and polyp-associated inflammation. Pro-inflammatory cytokines and pro-inflammatory innate and adaptive immunity cells were reduced both in the lesions and systemically. As part of tumor-associated inflammation Leukotriene B4 (LTB4), product of 5-LO activity, is increased focally in human dysplastic lesions. The 5-LO enzymatic activity was reduced in the serum of Zileuton treated polyposis mice.</p><p>Conclusions</p><p>This study demonstrates that dietary administration of 5-LO specific inhibitor in the polyposis mouse model decreases polyp burden, and suggests that Zileuton may be a potential chemo-preventive agent in patients that are high-risk of developing colon cancer.</p></div

Zileuton is inhibiting the polyp formation in APCΔ468 colon and small intestine.

<p>A) Representative H&E stained 5μm Swiss rolls sections of small untreated intestine and colon of Zileuton treated and control APC^Δ468 mice, blue arrows indicate polyps appearing in this sections. B) Cumulative bar graphs of the polyp number appearing in APC^Δ468 mice small intestine (31.67±7.7 polyps in Zileuton group, n = 6, vs 83.88±6.5 polyps, n = 8, in the control group, p = 0.0002, closed bars) and colon (4.5±1.3 polyps in Zileuton group vs 8.9±0.8 polyps in control group, P = 0.0107, open bars, N = 6). C) Reflectance fluorescence of flayed opened colon, probe ProSense 680, representative whole mount of APC^Δ468 colon of APC^Δ468 Zileuton fed colon; red arrows polyps D) dot plot of the number of polyps; (3 closed dots) APC^Δ468 untreated colon polyps, (3 open dots) APC^Δ468 treated colon polyps. Statistics: unpaired one tailed t test.</p

Frequency of lymphoid and myeloid cells isolated from APCΔ468Zileuton treated and APCΔ468 spleen and mesenteric lymph nodes (MLN).

<p>A) representative dot plots and the gating procedure of single cells suspencions isolated from APC^Δ468 and APC^Δ468Zileuton treated spleens. B) cummulative results of flow cytomentry of both spleen and MNL single cell suspencions. Black bars APC^Δ468, and open bars APC^Δ468Zileuton treated cellls. Flow cytometry analyzed with flow jo software, <i>One tailed unpaired</i> t test.</p

Zileuton treatment reduces the tumor infiltrating inflammatory cells in polyps.

<p>A) 1, 3, 5, 7: representative APC^Δ468/+ polyps; 2, 4, 6, 8: representative Zileuton treated APC^Δ468/+ polyps. B) calculation of positive cells as % frequency to the total cells; Black bars APC^Δ468/+, and open bars APC^Δ468/+ Zileuton treated. C) LTB4 ELISA of B6 (gray bars), APC^Δ468/+ (black bars), and APC^Δ468/+ Zileuton treated (open bars). D) ELISA human biopsy extracts. C) LTB4 ELISA of B6 (gray bars), APC^Δ468/+ (black bars), and APC^Δ468/+ Zileuton treated (open bars). D) ELISA human biopsy extracts. Black bars healthy tissue, Open bars tumor extracts. one tailed unpaired t test with Welch’s correction, * P<0.05, **P<0.005, one tail unpaired t test.</p

Zileuton treatment inhibits the proliferation rates of non epithelial cells in polyps, and increases the apoptosis rates in polyps.

<p>A) Polyp BrdU⁺ cells in small intestine and colon of Zileuton treated and control APC^Δ468 mice. Black bars total BrdU⁺ in APC^Δ468 polyps, open bars total BrdU⁺ in Zileuton APC^Δ468 polyps (17.4±0.91 BrdU⁺ cells per high power field in the control group vs 11.13±0.87 BrdU⁺ cells in Zileuton fed group; P = 0.0001). B) Polyp apoptotic cells in small intestine and colon of Zileuton treated APC^Δ468 polyps (open bars) and APC^Δ468 polyps (black bars).One tailed unpaired t test.</p