Intense Pulsed Light Combined With Meibomian Gland Massage for Recurrent Corneal Erosion: a Review of Clinical Effectiveness

Purpose: To observe the therapeutic effect on recurrent corneal erosion syndrome (RCES) by intense pulsed light (IPL) combined with meibomian gland massage. Methods: We recruited 30 patients (30 eyes) with RCES as the RCES group and 31 patients (31 eyes) as the control group. Both the groups received eyelash sampling, Demodex count, meibomian gland infrared photography, and the blepharolipin score. The RCES group was divided into the treatment group and the observation group again. Results: Parameters in the RCES group were higher than those in the control group. The parameters of the treatment group were decreased compared with the observation group. During the follow-up period, one patient in the treatment group relapsed. Conclusion: Meibomian gland dysfunction and Demodex infection may be associated with RCES. IPL combined with meibomian gland massage can significantly improve meibomian gland function, reduce the number of Demodex, and effectively control the relapse of RCES.

FOXO transcription factors are required for normal somatotrope function and growth

Understanding the molecular mechanisms underlying pituitary organogenesis and function is essential for improving therapeutics and molecular diagnoses for hypopituitarism. We previously found that deletion of the forkhead factor, Foxo1, in the pituitary gland early in development delays somatotrope differentiation. While these mice grow normally, they have reduced growth hormone expression and free serum IGF1 levels, suggesting a defect in somatotrope function. FOXO factors show functional redundancy in other tissues, so we deleted both Foxo1 and its closely related family member, Foxo3, from the primordial pituitary. We find that this results in a significant reduction in growth. Consistent with this, male and female mice in which both genes have been deleted in the pituitary gland (dKO) exhibit reduced pituitary growth hormone expression and serum IGF1 levels. Expression of the somatotrope differentiation factor, Neurod4, is reduced in these mice. This suggests a mechanism underlying proper somatotrope function is the regulation of Neurod4 expression by FOXO factors. Additionally, dKO mice have reduced Lhb expression and females also have reduced Fshb and Prl expression. These studies reveal FOXO transcription factors as important regulators of pituitary gland function.

Mathematical evaluation of post-radiotherapy salivary gland function using salivary gland scintigraphy

Objective: Xerostomia is the most common treatment-related toxicity after radiotherapy (RT) for head and neck carcinoma, reducing the quality of life of patients due to a decrease in salivary gland function. Methods: Salivary gland scintigraphy was performed to quantitatively evaluate the salivary gland functions in patients undergoing RT. It was done chronologically for 62 salivary glands of 31 patients before RT and retested 12 months later. Results: The salivary gland functions of most patients deteriorated post-RT and recovered when the radiation dose to the salivary gland was not high. The mean dose to the salivary gland was found to be the most reliable factor in deteriorating salivary gland function, and the tolerance dose was determined to be 46 Gy. The recovery rate of salivary gland function after 1 year of RT was 72% in the RT alone group (n = 10), 56% in the conformal radiotherapy group (n = 15), and 44% in the bioradiotherapy group (n = 6). Conclusion: Scintigraphy revealed that the salivary glands recovered from post-RT hypofunction when decreased doses were administered. The determined tolerance dose of 46 Gy may guide the approach to minimizing associated xerostomia in RT. Advances in knowledge: In this study, the average tolerated dose to the salivary glands was 46 Gy.

Transient Activation of Hedgehog Signaling Inhibits Cellular Senescence and Inflammation in Radiated Swine Salivary Glands through Preserving Resident Macrophages

Salivary gland function is commonly and irreversibly damaged by radiation therapy for head and neck cancer. This damage greatly decreases the patient’s quality of life and is difficult to remedy. Previously, we found that the transient activation of Hedgehog signaling alleviated salivary hypofunction after radiation in both mouse and pig models through the inhibition of radiation-induced cellular senescence that is mediated by resident macrophages in mouse submandibular glands. Here we report that in swine parotid glands sharing many features with humans, the Hedgehog receptor PTCH1 is mainly expressed in macrophages, and levels of PTCH1 and multiple macrophage markers are significantly decreased by radiation but recovered by transient Hedgehog activation. These parotid macrophages mainly express the M2 macrophage marker ARG1, while radiation promotes expression of pro-inflammatory cytokine that is reversed by transient Hedgehog activation. Hedgehog activation likely preserves parotid macrophages after radiation through inhibition of P53 signaling and consequent cellular senescence. Consistently, VEGF, an essential anti-senescence cytokine downstream of Hedgehog signaling, is significantly decreased by radiation but recovered by transient Hedgehog activation. These findings indicate that in the clinically-relevant swine model, transient Hedgehog activation restores the function of irradiated salivary glands through the recovery of resident macrophages and the consequent inhibition of cellular senescence and inflammation.

The Schistosoma mansoni nuclear receptor FTZ-F1 maintains esophageal gland function via transcriptional regulation of meg-8.3

Schistosomes infect over 200 million of the world’s poorest people, but unfortunately treatment relies on a single drug. Nuclear hormone receptors are ligand-activated transcription factors that regulate diverse processes in metazoans, yet few have been functionally characterized in schistosomes. During a systematic analysis of nuclear receptor function, we found that an FTZ-F1-like receptor was essential for parasite survival. Using a combination of transcriptional profiling and chromatin immunoprecipitation (ChIP), we discovered that the micro-exon gene meg-8.3 is a transcriptional target of SmFTZ-F1. We found that both Smftz-f1 and meg-8.3 are required for esophageal gland maintenance as well as integrity of the worm’s head. Together, these studies define a new role for micro-exon gene function in the parasite and suggest that factors associated with the esophageal gland could represent viable therapeutic targets.

Mean Tear-Film Lipid Layer Thickness and Video Display Terminal Time as Risk Factors for Abnormal Blinking in Children

Objective: To explore the risk factors for abnormal blinking in children and the role of the tear-film lipid layer thickness (LLT) as a function of duration of video display terminal (VDT) use in children.Methods: Children attending the Optometry Clinic of Xinhua Hospital affiliated with Shanghai Jiao Tong University were recruited for the study between June 2019 and June 2020. Time spent viewing a VDT (VDTt) over the previous 6 months was recorded. Incomplete blinking (IB) and blinking rate were measured over a 10 s period using the Lipiview® interferometer (Tear Science, Morrisville, NC, USA), and participants were allocated into groups with normal blinking (NBG, blink rate < 20 blinks/min) and abnormal blinking (ABG, blink rate ≥ 20 blinks/min). T-test, chi-square test and Mann-Whitney U-test were used to compare the differences in tear film (TF) stability indexes and meibomian gland function indexes between the two groups. Binary logistic analysis was used to analyze the risk factors for abnormal blinking and protective factors related to children's use of VDT, and receiver operating characteristic (ROC) curve analysis was also conducted.Results: A total of 167 children were included, with no statistically significant differences in age or sex between the two groups. According to the t-test, VDTt was significantly higher in ABG than NBG, while TF stability indices including tear break up time, LLT and the height of the tear meniscus, were significantly higher in NBG than ABG (P < 0.001). The results also showed better meibomian gland function in NBG than ABG (P < 0.05). Binary logistic analysis showed that VDTt is an important risk factor for abnormal blinking, and the average of LLT (AVG) was found to be an important protective factor for children using a VDT for long periods, with a cut-off value of 1.5 h and 57.5 nm, respectively. ROC curve analysis showed that the area under the curve value of VDTt and AVG was 0.833 and 0.969, respectively (P < 0.001).Conclusion: In children, VDTt is an important risk factor for abnormal blinking, and the AVG is an important protective factor for children using VDT for long periods.

Meibomian gland dysfunction is highly prevalent among first-time visitors at a Norwegian dry eye specialist clinic

To investigate the prevalence of meibomian gland dysfunction (MGD) in patients presenting with subjective dry eye-related symptoms at their first-time consultation in a Norwegian specialized ocular surface clinic. Additionally, to explore the accuracy of the ocular surface disease index score (OSDI) as an extensively applied tool to assess the severity of dry eye symptoms and MGD diagnosis. Patients with subjective dry eye-related complaints (n = 900) attending the clinic for the first time, from 2012 to 2016, were included in the study. At the baseline, patients completed the OSDI questionnaire. Subsequently, objective clinical tests, including fluorescein break-up time (FBUT), Schirmer-I test, ocular surface staining (OSS), and meibomian gland function assessment using gland expressibility and meibum quality were performed. The association between MGD and its severity in relation to symptom severity defined by OSDI-score was examined. MGD was found in 93.8% of the study group. MGD prevalence was not significantly different between groups based on age (p = 0.302) or sex (p = 0.079). There was a significant association between severity of MGD and dry eye-related symptoms (p = 0.014). OSS was significantly higher in patients with severe symptoms (p = 0.031). Sensitivity and specificity of positive symptom-score (OSDI ≥ 13) for disclosing MGD were 85.5% and 30.4%, respectively. MGD was highly prevalent, not associated with age and sex. OSDI ≥ 13 had high sensitivity and high positive predictive value (PPV), but low specificity and negative predictive value (NPV) for disclosing MGD. This underscores the importance of meibomian gland assessment in patients with dry eye-related symptoms.

Hypercortisolism in patients with cholestasis is associated with disease severity

Background Cholestasis might lead to an impairment of adrenal function as suggested by in vitro and in vivo data as well as by clinical findings. Bile acid and adrenal steroid metabolism not only share the receptors farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (TGR5), but supraphysiological bile acid levels were found to stimulate steroidogenesis independent of FXR and TGR5. Our previous experimental findings revealed that mice fed bile acids or subjected to common bile duct ligation develop hypercortisolemia. We thus aimed to assess adrenal gland function in patients with cholestasis. Methods Adrenal gland function was assessed in 36 patients with cholestasis and in 32 patients without cholestasis by measuring total serum cortisol, adrenocorticotropic hormone (ACTH), as well as the increase of cortisol 20 and 30 min after administration of 1 µg of ACTH. Bile acid levels and bile acid pool composition were determined by high-resolution mass spectrometry. Results Patients with cholestasis per definition had markedly elevated levels of alkaline phosphatase (AP), bilirubin and serum bile acids. Baseline cortisol and maximum cortisol after ACTH stimulation were significantly higher in patients with cholestasis compared to controls. Increase of cortisol after ACTH stimulation and ACTH did not differ. In the cholestasis group, baseline cortisol correlated with bilirubin but not with AP, total serum bile acids and levels of conjugated and unconjugated bile acid species. Patients with duration of cholestasis < 6 months (n = 30) had significantly higher baseline cortisol levels than those with long standing cholestasis (> 6 months), together with higher bilirubin levels. Conclusions We find no evidence of adrenal insufficiency in non-cirrhotic patients with cholestasis. In contrast, patients with cholestasis show hypercortisolism associated with disease severity as mirrored by levels of bilirubin. Lack of ACTH increase in cholestasis suggests a direct effect of cholestasis on adrenals and not on the pituitary gland. Further studies are needed to elucidate the mechanism of cortisol elevation in patients with cholestasis and its clinical significance.