Complement decay-accelerating factor inhibits inflammation-induced myopia development.

Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-ß, IL-6, TNF-α, and IL-1ß may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-ß) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.

Propofol-based total intravenous anesthesia is associated with less postoperative recurrence than desflurane anesthesia in thyroid cancer surgery.

BACKGROUND: The effects of anesthesia in patients undergoing thyroid cancer surgery are still not known. We investigated the relationship between the type of anesthesia and patient outcomes following elective thyroid cancer surgery. METHODS: This was a retrospective cohort study of patients who underwent elective surgical resection for papillary thyroid carcinoma between January 2009 and December 2019. Patients were grouped according to the type of anesthesia they received, desflurane or propofol. A Kaplan-Meier analysis was conducted, and survival/recurrence curves were presented from the date of surgery to death/recurrence. Univariable and multivariable Cox regression models were used to compare hazard ratios for recurrence after propensity matching. RESULTS: A total of 621 patients (22 deaths, 3.5%) under desflurane anesthesia and 588 patients (32 deaths, 5.4%) under propofol anesthesia were included. Five hundred and eighty-eight patients remained in each group after propensity matching. Propofol anesthesia was not associated with better survival compared to desflurane anesthesia in the matched analysis (P = 0.086). However, propofol anesthesia was associated with less recurrence (hazard ratio, 0.38; 95% confidence interval, 0.25-0.56; P < 0.001) in the matched analysis. CONCLUSIONS: Propofol anesthesia was associated with less recurrence, but not mortality, following surgery for papillary thyroid carcinoma than desflurane anesthesia. Further prospective investigation is needed to examine the influence of propofol anesthesia on patient outcomes following thyroid cancer surgery.

Incidence, Risk Factors and Management of Postoperative Complications in Horizontal Strabismus Surgery.

OBJECTIVE: To report the incidence, risk factors and management of postoperative complications after horizontal strabismus surgery. DESIGN: Retrospective Cohort study. PARTICIPANTS: The study assessed 1,273 patients with 1,035 cases of exotropia and 238 cases of esotropia, with a minimum 18-month follow-up. METHODS: Retrospective review of strabismus operation patients' medical records included baseline demographics, age at surgery, pre/postoperative visual acuity, and deviation. Complications were categorized as surgical site (infection, scarring, cyst, granuloma, ischemia) and strabismus-related (recurrence, diplopia), with analysis of incidence, risk factors, and management. RESULTS: Among surgical site complications, the incidence of infection, pyogenic granuloma, and anterior segment ischemia were similar between the exotropia (0.3%, 0.3%, 0.2%) and esotropia (0.8%, 0%, 0.4%) groups (p = .221, 0.406, 0.515). In contrast, the esotropia group presented a higher risk of conjunctival inclusion cyst and conjunctival scar than the exotropia group, with incidences of 5.0% vs 2.2% and 6.3% vs 1.3%, respectively (p = .004, <0.001). Regarding strabismus complications, the incidence of early recurrence was not significant between the two groups, with 10.0% in the exotropia group and 10.5% in the esotropia group (p = .553). Older age and poor initial visual acuity were associated with early recurrence (p < .001). The esotropia group had a higher risk of persistent diplopia than the exotropia group, with incidences of 4.2% vs 2.0%, respectively (p = .003). CONCLUSION: Esotropia carries a higher risk of conjunctival inclusion cysts, conjunctival scarring, and persistent diplopia compared to the exotropia group, while both groups exhibit similar rates of early recurrence and other surgical site complications.

Fallopia Japonica and Prunella vulgaris inhibit myopia progression by suppressing AKT and NFκB mediated inflammatory reactions.

BACKGROUND: The increased global incidence of myopia requires the establishment of therapeutic approaches. This study aimed to investigate the effect of Fallopia Japonica (FJ) and Prunella vulgaris (PV) extract on myopia caused by monocular form deprivation (MFD). METHODS: We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJ extract (FJE) and PV extract (PVE) lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. RESULTS: FJE + PVE reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-ß1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type I collagen expression. CONCLUSIONS: Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.

Myopia Development in Tree Shrew Is Associated with Chronic Inflammatory Reactions.

In this study, we aimed to investigate whether chronic retinal inflammation is involved in the pathogenesis of form-deprivation myopia (FDM) using tree shrews as an animal model. Twenty-one tree shrews were randomly divided into 7-day/14-day FDM (FDM7/FDM14) groups and their corresponding 7-day/14-day control groups. Refraction and axial length were measured. To determine the effects of form deprivation on inflammation, we used real-time polymerase chain reaction (PCR) and immunohistochemistry to assess the expression levels of several proinflammatory cytokines. At day 0, the eyes in the FDM and control groups were hyperopic. However, after 7 and 14 days of form deprivation, the refractive error of the eyes in the FDM7 and FDM14 groups shifted from +6.6 ± 0.3 diopters (D) to +4.0 ± 0.5 D and from +6.4 ± 0.3 D to +5.0 ± 0.3 D, respectively. The levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and nuclear factor κB were increased in the FDM eyes, compared with those in the control eyes. The increase in matrix metalloproteinase-2 expression was greater in the FDM eyes than in the contralateral and control eyes, whereas collagen type I expression was downregulated. In conclusion, chronic inflammation may play a crucial pathogenic role in form-deprivation myopia in tree shrews.

Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: Non-antiviral therapeutic options are required for the treatment of hospitalised patients with COVID-19. CD24Fc is an immunomodulator with potential to reduce the exaggerated inflammatory response to tissue injuries. We aimed to evaluate the safety and efficacy of CD24Fc in hospitalised adults with COVID-19 receiving oxygen support. METHODS: We conducted a randomised, double-blind, placebo-controlled, phase 3 study at nine medical centres in the USA. Hospitalised patients (age ≥18 years) with confirmed SARS-CoV-2 infection who were receiving oxygen support and standard of care were randomly assigned (1:1) by site-stratified block randomisation to receive a single intravenous infusion of CD24Fc 480 mg or placebo. The study funder, investigators, and patients were masked to treatment group assignment. The primary endpoint was time to clinical improvement over 28 days, defined as time that elapsed between a baseline National Institute of Allergy and Infectious Diseases ordinal scale score of 2-4 and reaching a score of 5 or higher or hospital discharge. The prespecified primary interim analysis was done when 146 participants reached the time to clinical improvement endpoint. Efficacy was assessed in the intention-to-treat population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT04317040. FINDINGS: Between April 24 and Sept 22, 2020, 243 hospitalised patients were assessed for eligibility and 234 were enrolled and randomly assigned to receive CD24Fc (n=116) or placebo (n=118). The prespecified interim analysis was done when 146 participants reached the time to clinical improvement endpoint among 197 randomised participants. In the interim analysis, the 28-day clinical improvement rate was 82% (81 of 99) for CD24Fc versus 66% (65 of 98) for placebo; median time to clinical improvement was 6·0 days (95% CI 5·0-8·0) in the CD24Fc group versus 10·0 days (7·0-15·0) in the placebo group (hazard ratio [HR] 1·61, 95% CI 1·16-2·23; log-rank p=0·0028, which crossed the prespecified efficacy boundary [α=0·0147]). 37 participants were randomly assigned after the interim analysis data cutoff date; among the 234 randomised participants, median time to clinical improvement was 6·0 days (95% CI 5·0-9·0) in the CD24Fc group versus 10·5 days (7·0-15·0) in the placebo group (HR 1·40, 95% CI 1·02-1·92; log-rank p=0·037). The proportion of participants with disease progression within 28 days was 19% (22 of 116) in the CD24Fc group versus 31% (36 of 118) in the placebo group (HR 0·56, 95% CI 0·33-0·95; unadjusted p=0·031). The incidences of adverse events and serious adverse events were similar in both groups. No treatment-related adverse events were observed. INTERPRETATION: CD24Fc is generally well tolerated and accelerates clinical improvement of hospitalised patients with COVID-19 who are receiving oxygen support. These data suggest that targeting inflammation in response to tissue injuries might provide a therapeutic option for patients hospitalised with COVID-19. FUNDING: Merck & Co, National Cancer Institute, OncoImmune.

The Effects of Modified Graded Recession, Anteriorization and Myectomy of Inferior Oblique Muscles on Superior Oblique Muscle Palsy.

BACKGROUND: The aim was to investigate the effect of inferior oblique (IO) operation (IO myectomy or graded recession and anteriorization) for unilateral and bilateral superior oblique muscle palsy (SOP); Methods: A total of 167 eyes undergoing IO surgery by a single surgeon between 2008 and 2015 were retrospectively reviewed. The method for treating symmetric bilateral SOP was bilateral IO myectomy (n = 102) and the method for treating unilateral SOP or non-symmetric bilateral SOP was IO-graded recession and anteriorization (n = 65). Associated clinical results and other factors were analyzed; Results: Head tilt, vertical deviation, IO overaction, SO underaction degree and ocular torsion angle were all clearly changed, but there was no statistically significance between these two procedures. Mean preoperative torsional angle was 15.3 ± 6.4 degree, which decreased to 5.3 ± 2.7 degree after surgery. Preoperative torsional angle, IOOA and SOUA degree were all significantly affected in postoperative torsional angle (p = 0.025, 0.003 and 0.038). Horizontal rectus muscle and IO muscle operation did not interfere with each other's results (p = 0.98); Conclusions: Symmetric bilateral SOP could be treated with bilateral IO myectomy and IO-graded recession and anteriorization should be reserved for unilateral SOP or non-symmetric bilateral SOP.

Anti-Inflammatory Effects of Resveratrol on Human Retinal Pigment Cells and a Myopia Animal Model.

Resveratrol is a key component of red wine and other grape products. Recent studies have characterized resveratrol as a polyphenol, and shown its beneficial effects on cancer, metabolism, and infection. This study aimed to obtain insights into the biological effects of resveratrol on myopia. To this end, we examined its anti-inflammatory influence on human retinal pigment epithelium cells and in a monocular form deprivation (MFD)-induced animal model of myopia. In MFD-induced myopia, resveratrol increased collagen I level and reduced the expression levels of matrix metalloproteinase (MMP)2, transforming growth factor (TGF)-ß, and nuclear factor (NF)-κB expression levels. It also suppressed the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. Resveratrol exhibited no significant cytotoxicity in ARPE-19 cells. Downregulation of inflammatory cytokine production, and inhibition of AKT, c-Raf, Stat3, and NFκB phosphorylation were observed in ARPE-19 cells that were treated with resveratrol. In conclusion, the findings suggest that resveratrol inhibits inflammatory effects by blocking the relevant signaling pathways, to ameliorate myopia development. This may make it a natural candidate for drug development for myopia.

Diacerein Inhibits Myopia Progression through Lowering Inflammation in Retinal Pigment Epithelial Cell.

Myopia is a highly prevalent refractive disorder. We investigated the effect of diacerein on monocular form deprivation (MFD) in hamsters as a possible therapeutic intervention. Diacerein is an anthraquinone derivative drug whose active metabolite is rhein. Diacerein or atropine was applied to the MFD hamsters, and their refractive error and axial length were measured after 21 days. The refractive error (control: -0.91 ± 0.023, atropine: -0.3 ± 0.08, and diacerein: -0.27 ± 0.07 D) and axial length (control: 0.401 ± 0.017, atropine: 0.326 ± 0.017, and diacerein: 0.334 ± 0.016 mm) showed statistically significant differences between control, atropine-treated, and diacerein-treated MFD eyes. Furthermore, we determined the level of transforming growth factor-beta- (TGF-) ß1, matrix metalloproteinase- (MMP-) 2, type I collagen, interleukin- (IL-) 6, IL-8, and monocyte chemoattractant protein- (MCP-) 1 in the retina. Atropine and diacerein suppressed levels of the myopia-related TGF-ß1 and MMP-2 while increasing type I collagen expression. They also inhibited the interleukin IL-6, IL-8, and MCP-1 levels. Diacerein reduced the IL-6, IL-8, and MCP-1 expression in ARPE-19 cells. Furthermore, diacerein inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. This suggests that diacerein has a therapeutic effect on myopia and is a potential treatment option.

Perfluorooctanoic acid in indoor particulate matter triggers oxidative stress and inflammation in corneal and retinal cells.

To investigate the particle size distribution of particulate matter and the concentration of specific perfluorinated compounds in indoor dust samples from several locations. Then, we used cell-based assays to investigate the effect of perfluorinated compounds on human corneal epithelial (HCEpiC), endothelial cells (HCEC) and retinal pigment epithelial cells (RPE). Indoor dust samples were collected at five different locations and PM50-10, PM10-2.5, and PM2.5-1 were fractionized. The presence and levels of 8:2 fluorotelomer alcohol, 10:2 fluorotelomer alcohol, and perfluorooctanoic acid were detected by gas chromatography-mass spectrometry. The effect of perfluorooctanoic acid on the activation of reactive oxygen species, transepithelial resistance as well as the expression of interleukin (IL)-6 and IL-8 were determined. The basolateral media of human corneal epithelial or human corneal endothelial cells were used to treat human corneal endothelial or retinal pigment epithelial cells, respectively to indicate the potential of ocular surface inflammation may result in retinal inflammation. Among perfluorinated compounds, only perfluorooctanoic acid was detected in all indoor dust samples. Perfluorooctanoic acid had the highest concentration among all perfluorinated compounds in the samples. Exposure to perfluorooctanoic acid impaired tight junction sealing and increased the levels of reactive oxygen species in human corneal epithelial cells. In human corneal epithelial cells, secretion of IL-6 and IL-8 in both apical and basolateral media was promoted significantly by perfluorooctanoic acid treatment. Stimulation with the basolateral media from perfluorooctanoic acid-treated human corneal epithelial cells induced inflammation in human corneal endothelial cells. The treatment of retinal pigment epithelial cells with the basolateral media from stimulated human corneal endothelial cells also elicited the secretion of proinflammatory cytokines. The results indicate that perfluorooctanoic acid exposure impaired the tight junction of corneal cells and caused inflammatory reactions in the retina. Exposure of the cornea to perfluorooctanoic acid contained in particulate matter might induce oxidative stress and inflammation in the retina and represent a risk factor for age-related macular degeneration.