Ectopic Cilia: A Histopathological Study

Cilia are normally found at the eyelid margin, while ectopic cilia are one or more lash follicles appearing in an abnormal position within the eyelid. We herein report two cases of cilia located in the palpebral conjunctiva. A 31-year-old female and a 46-year-old male presented with ectopic cilia in the superior palpebral conjunctiva. Histopathological study of the excised ectopic cilia and related lesions showed the cilia-related lesion to be located in the epithelial pit that contains goblet cells, which is consistent with the crypts of Henle. The hair follicle was surrounded by granulation tissue, while a dermal papilla and a hair matrix, which are known to produce hair follicles, did not exist in the excised tissue. While anterior ectopic cilia are congenital, ectopic cilia in the palpebral conjunctiva may be acquired, and these aberrant cilia are associated with crypts of Henle and chronic inflammation

Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: A multicenter retrospective study

PurposeTo evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol.DesignRetrospective longitudinal cohort study.Participants140 BD uveitis patients treated with IFX enrolled in our previous study.MethodsMedical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs).Main outcome measures10-year IFX continuation rate and change in LogMAR VA.ResultsOf 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years.ConclusionsAmong BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence

Expression of Vascular Endothelial Growth Factor-C in the Trabecular Meshwork of Patients with Neovascular Glaucoma and Primary Open-Angle Glaucoma

The Abstract: Purpose To investigate the expression of vascular endothelial growth factor (VEGF)-C and vascular endothelial growth factor receptor (VEGFR)3 in the trabecular meshwork (TM) of patients with glaucoma and cultured TM cells. Methods: The expressions of VEGF-C in angle tissues collected by trabeculectomy from patients with glaucoma and non-glaucomatous choroidal malignant melanoma were analyzed by immunohistochemistry. Additionally, VEGF-C concentrations were determined in the aqueous humor of patients with glaucoma by ELISA. The expressions of VEGFR3, which is a receptor of VEGF-C in cultured TM cells, were analyzed by Western blot analysis and immunocytochemistry. Cultured TM cells were stimulated by oxidative stress, hypoxia, or high glucose conditions, and VEGF-C concentrations in supernatants and cell lysates were determined by ELISA. Results: VEGF-C immunoreactivity was positive in TM tissues of glaucoma patients, but not in those of non-glaucomatous controls. VEGF-C concentrations in the aqueous humor of patients with neovascular glaucoma and primary open-angle glaucoma were lower than those with non-glaucoma patients. VEGFR3 was expressed in cultured TM cells. VEGF-C concentrations in supernatants or cell lysates of TM cells cultured under oxidative stress and hypoxia were significantly elevated compared with those under steady conditions (p < 0.05). VEGF-C concentrations in supernatants and cell lysates of TM cells cultured in high glucose were significantly higher than those in low glucose (p < 0.01). Conclusions: VEGF-C was expressed in TM tissues of patients with glaucoma, which was secreted from cultured TM cells under various pathological conditions. These results suggest that VEGF-C may be involved in the pathology of glaucoma

Placental growth factor stabilizes VEGF receptor-2 protein in retinal pigment epithelial cells by downregulating glycogen synthase kinase 3 activity

Placental growth factor (PlGF) belongs to the vascular endothelial growth factor (VEGF) family of proteins that participate in angiogenesis and vasculogenesis. Anti-VEGF therapy has become the standard treatment for ocular angiogenic disorders in ophthalmological practice. However, there is emerging evidence that anti-VEGF treatment may increase the risk of atrophy of the retinal pigment epithelium (RPE), which is important for the homeostasis of retinal tissue. Whereas the cytoprotective role of VEGF family molecules, particularly that of VEGF A (VEGFA) through its receptor VEGF receptor-2 (VEGFR-2), has been recognized, the physiological role of PlGF in the retina is still unknown. In this study, we explored the role of PlGF in the RPE using PlGF-knockdown RPE cells generated by retrovirus-based PlGF-shRNA transduction. We show that VEGFA reduced apoptosis induced by serum starvation in RPE cells, whereas the antiapoptotic effect of VEGFA was abrogated by VEGFR-2 knockdown. Furthermore, PlGF knockdown increased serum starvation-induced cell apoptosis and unexpectedly reduced the protein level of VEGFR-2 in the RPE. The antiapoptotic effect of VEGFA was also diminished in PlGF-knockdown RPE cells. In addition, we found that degradation of VEGFR-2 in RPE cells and inactivated by PlGF via AKT phosphorylation. Overall, the present data inactivation

Systemic factors related to soluble (pro)renin receptor in plasma of patients with proliferative diabetic retinopathy

<div><p>(Pro)renin receptor [(P)RR], a new component of the tissue renin-angiotensin system (RAS), plays a crucial role in inflammation and angiogenesis in the eye, thus contributing to the development of proliferative diabetic retinopathy (PDR). In this study, we investigated systemic factors related to plasma levels of soluble form of (P)RR [s(P)RR] in patients with PDR. Twenty type II diabetic patients with PDR and 20 age-matched, non-diabetic patients with idiopathic macular diseases were enrolled, and plasma levels of various molecules were measured by enzyme-linked immunosorbent assays. Human retinal microvascular endothelial cells were stimulated with several diabetes-related conditions to evaluate changes in gene expression using real-time quantitative PCR. Of various systemic parameters examined, the PDR patients had significantly higher blood sugar and serum creatinine levels than non-diabetic controls. Protein levels of s(P)RR, prorenin, tumor necrosis factor (TNF)-α, complement factor D (CFD), and leucine-rich α-2-glycoprotein 1 (LRG1) significantly increased in the plasma of PDR subjects as compared to non-diabetes, with positive correlations detected between s(P)RR and these inflammatory molecules but not prorenin. Estimated glomerular filtration rate and serum creatinine were also correlated with plasma s(P)RR, but not prorenin, levels. Among the inflammatory molecules correlated with s(P)RR in the plasma, TNF-α, but not CFD or LRG1, application to retinal endothelial cells upregulated the mRNA expression of (P)RR but not prorenin, while stimulation with high glucose enhanced both (P)RR and prorenin expression. These findings suggested close relationships between plasma s(P)RR and diabetes-induced factors including chronic inflammation, renal dysfunction, and hyperglycemia in patients with PDR.</p></div

Effect of bixalomer on coronary artery calcification in hemodialysis patients with hyperphosphatemia: a multi-center, randomized controlled trial

Abstract Background Calcium carbonate is a first-line therapy for hyperphosphatemia in hemodialysis patients but is associated with progressive coronary and aortic calcification. Sevelamer compounds are alternatives to calcium-containing phosphate binders as they contain lower calcium levels. The sevelamer compound, bixalomer, is a calcium-free insoluble polymer that has been shown to be effective and safe in comparison with calcium carbonate. We therefore compared the effect of bixalomer vs calcium carbonate on coronary artery calcification in hemodialysis patients with hyperphosphatemia. Methods In this open-label, randomized phase IV trial across 23 sites throughout Japan, 85 patients with chronic kidney disease were randomized to bixalomer (n = 44) or calcium carbonate (n = 41) therapy and monitored for 12 months. Bixalomer was administered at a dosage of 1500 mg/day (500 mg three times a day) and calcium carbonate was administered at a dosage of 3000 mg/day (1000 mg three times a day). The primary outcome was the change in coronary artery calcium over time measured using computed tomography. Levels of serum phosphorus, calcium, intact parathyroid hormone, and the occurrence of adverse events were also reported over the course of the study. Results The mean (± standard deviation) changes in coronary artery calcium scores from baseline to 12 months were significantly higher in the calcium carbonate vs bixalomer group (268.6 ± 320.1 vs 126.7 ± 154.8, respectively; between-group difference p = 0.029). At 12 months in the bixalomer group, serum phosphorus and intact parathyroid hormone levels were significantly higher; serum calcium was significantly lower (p <  0.05). The most frequent adverse events were shunt stenosis in the bixalomer group, and shunt stenosis and common cold in the calcium carbonate group. There were no significant between-group differences in adverse drug reaction incidences. Conclusions The safety profile of bixalomer was comparable to that of calcium carbonate. Bixalomer further reduced coronary artery calcification, compared with calcium carbonate, in hemodialysis patients with hyperphosphatemia. Trial registration UMIN/R000015330 Registered 13 February 201

Plasma concentrations of inflammatory and angiogenic molecules.

<p>Plasma concentrations of inflammatory and angiogenic molecules.</p

Upregulation of s(P)RR, prorenin and activated prorenin protein levels in the plasma of PDR patients.

<p>Protein levels of s(P)RR (A), prorenin (B), and activated prorenin (C) in the plasma of the non-DM and PDR subjects. Black symbols indicate individual samples. n = 20 in each group, **<i>p</i> < 0.01, Student’s t test. (D) Correlation between s(P)RR and prorenin was not detected in the plasma of patients with PDR (n = 20, Spearman rank correlation).</p