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.

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.

Increased risk of glaucoma development in patients with central serous chorioretinopathy: results of a 11-year population-based cohort study.

PURPOSE: To investigate whether patients with central serous chorioretinopathy (CSC) have increased risk of developing glaucoma. METHODS: Patients diagnosed with CSC between 1 January 2008 and 31 December 2018 were included in this study using data from the Taiwanese National Health Insurance Research Database (NHIRD). The CSC cohort was matched with a non-CSC cohort using the propensity score matching method, based on sex, age (in 10-year intervals), index date year, comorbidities, and steroid use, resulting in equal numbers of patients in both cohorts. Patients were followed up until 31 December 2019 or until they were withdrawn from the NHIRD. The incidence of glaucoma was compared between the two cohorts using the Cox regression model, and the risk of developing glaucoma was estimated using the Kaplan-Meier method. RESULTS: After adjusting for sex, age, comorbidities, and steroid use, the CSC cohort showed a significantly higher risk of developing glaucoma compared to those without CSC (adjusted HR = 3.99; 95% CI = 3.44-4.62). The cumulative incidence of glaucoma in the CSC cohort was also significantly higher than in the non-CSC cohort (log-rank test, p < 0.001). Among the glaucoma subtypes, normal tension glaucoma had the highest risk (adjusted HR = 5.79; 95% CI = 3.41-9.85), followed by primary open-angle glaucoma (adjusted HR = 2.77; 95% CI = 2.12-3.62). CONCLUSIONS: In conclusion, our study shows that CSC patients are at a higher risk of developing glaucoma, especially NTG. Awareness and regular glaucoma screenings are essential for patients with CSC.

Acupuncture modulates development of myopia by reducing NLRP3 inflammasome activation via the dopamine-D1R signaling pathway.

BACKGROUND: Dopamine has been suggested to be a stop signal for eye growth and affects the development of myopia. Acupuncture is known to increase dopamine secretion and is widely used to treat myopia clinically. OBJECTIVE: The aim of this study was to determine if acupuncture inhibits myopia progression in form deprived Syrian hamsters by inducing rises in dopamine content that in turn suppress inflammasome activation. METHODS: Acupuncture was applied at LI4 and Taiyang every other day for 21 days. The levels of molecules associated with the dopamine signaling pathway, inflammatory signaling pathway and inflammasome activation were determined. A dopamine agonist (apomorphine) was used to evaluate if activation of the dopaminergic signaling pathway suppresses myopia progression by inhibiting inflammasome activation in primary retinal pigment epithelial (RPE) cells. A dopamine receptor 1 (D1R) inhibitor (SCH39166) was also administered to the hamsters. RESULTS: Acupuncture inhibited myopia development by increasing dopamine levels and activating the D1R signaling pathway. Furthermore, we also demonstrated that nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome activation was inhibited by activation of the D1R signaling pathway. CONCLUSION: Our findings suggest that acupuncture inhibits myopia development by suppressing inflammation, which is initiated by activation of the dopamine-D1R signaling pathway.

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.

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.

Increased risk of Alzheimer's disease among patients with age-related macular degeneration: A nationwide population-based study.

OBJECTIVE: This study aimed to investigate the risk of Alzheimer's disease among patients with age-related macular degeneration and its association with confounding comorbidities. METHOD: This was a population-based, retrospective cohort study. By accessing data from the National Health Insurance Research Database of Taiwan, we identified 10,578 patients aged 50-100 years who were newly diagnosed with age-related macular degeneration between 2000 and 2012 and 10,578 non- age-related macular degeneration individuals. The comorbidities assessed were osteoporosis, diabetes, cirrhosis, cerebrovascular disease, chronic kidney disease, hypertension, hyperlipidemia, coronary artery disease, and chronic obstructive pulmonary disease. RESULTS: Patients with age-related macular degeneration had a 1.23-fold increased risk of their condition advancing to Alzheimer's disease (aHR = 1.23, 95% CI = 1.04-1.46). The younger patients were diagnosed with age-related macular degeneration, the more likely patients got Alzheimer's disease (50-64 age group: aHR = 1.97, 95% CI = 1.04-3.73; 65-79 age group: aHR = 1.27, 95% CI = 1.02-1.58; 80-100 age group: aHR = 1.06, 95% CI = 0.78-1.45). In addition, there were significantly higher risks of Alzheimer's disease for patients with cirrhosis (aHR = 1.50, 95% CI = 1.09-2.06) in the age-related macular degeneration cohort than in the non-age-related macular degeneration cohort. CONCLUSION: Patients with age-related macular degeneration may exhibit a higher risk of Alzheimer's disease than people without age-related macular degeneration.

Resveratrol Attenuates Staphylococcus Aureus-Induced Monocyte Adhesion through Downregulating PDGFR/AP-1 Activation in Human Lung Epithelial Cells.

Staphylococcus aureus (S. aureus) is a very common Gram-positive bacterium. It is widely distributed in air, soil, and water. S. aureus often causes septicemia and pneumonia in patients. In addition, it is considered to play a key role in mediating cell adhesion molecules upregulation. Resveratrol is a natural antioxidant with diverse biological effects, including the modulation of immune function, anti-inflammation, and cancer chemoprevention. In this study, we proved that S. aureus-upregulated vascular cell adhesion molecule-1 (VCAM-1) expression in human lung epithelial cells (HPAEpiCs) was inhibited by resveratrol. We also observed that resveratrol downregulated S. aureus-enhanced leukocyte count in bronchoalveolar lavage (BAL) fluid in mice. In HPAEpiCs, S. aureus stimulated c-Src, PDGFR, p38 MAPK, or JNK1/2 phosphorylation, which was inhibited by resveratrol. S. aureus induced the adhesion of THP-1 cells (a human monocytic cell line) to HPAEpiCs, which was also reduced by resveratrol. Finally, we found that S. aureus induced c-Src/PDGFR/p38 MAPK and JNK1/2-dependent c-Jun and ATF2 activation and in vivo binding of c-Jun and ATF2 to the VCAM-1 promoter, which were inhibited by resveratrol. Thus, resveratrol functions as a suppressor of S. aureus-induced inflammatory signaling, not only by inhibiting VCAM-1 expression but also by diminishing c-Src, PDGFR, JNK1/2, p38 MAPK, and AP-1 activation in HPAEpiCs.

Resveratrol inhibits Staphylococcus aureus-induced TLR2/MyD88/NF-κB-dependent VCAM-1 expression in human lung epithelial cells.

Staphylococcus aureus is the most commonly found Gram-positive bacterium in patients admitted to intensive-care units, causing septicaemia or pneumonia. S. aureus is considered to play an important role in the induction of cell adhesion molecules. Resveratrol, a compound found in the skins of red fruits, may inhibit the inflammatory signalling pathways involved in lung diseases. In the present paper, we have shown that resveratrol reduced S. aureus-mediated VCAM-1 (vascular cell adhesion molecule-1) expression in HPAEpiCs (human lung epithelial cells) and lungs of mice. In an in vivo study, we have shown that resveratrol inhibited S. aureus-induced pulmonary haematoma and leucocyte count in BAL (bronchoalveolar lavage) fluid in mice. In an in vitro study, we observed that resveratrol attenuated S. aureus-induced TLR2 (Toll-like receptor 2), MyD88 (myeloid differentiation factor 88) and PI3K (phosphoinositide 3-kinase) complex formation. S. aureus stimulated Akt, JNK1/2 (c-Jun N-terminal kinase 1/2) and p42/p44 MAPK (mitogen-activated protein kinase) phosphorylation, which were inhibited by resveratrol. In addition, S. aureus induced IκB (inhibitor of nuclear factor κB) α and NF-κB (nuclear factor κB) p65 phosphorylation and NF-κB p65 translocation, which were reduced by resveratrol. Finally, we found that S. aureus induced NF-κB and p300 complex formation and p300 phosphorylation, which were inhibited by resveratrol. Thus resveratrol functions as a suppressor of S. aureus-induced inflammatory signalling not only by inhibiting VCAM-1 expression, but also by reducing TLR2-MyD88-PI3K complex formation and Akt, JNK1/2, p42/p44 MAPK, p300 and NF-κB activation in HPAEpiCs.

Evaluating the reliability, validity and minimally important difference of the Taiwanese version of the diabetes quality of life (DQOL) measurement.

BACKGROUND: Few diabetes HRQOL instruments are available in Chinese language. We tested psychometric properties of a Diabetes Quality of Life (DQOL) in Chinese language for diabetes patients in Taiwan and estimated its minimally important differences (MIDs). METHODS: Data were collected from 337 patients treated in diabetes clinics of a Taiwan teaching hospital. Pearson's correlations among domain scores of the DQOL (satisfaction, impact, and worry), the D-39S (a diabetes-specific instrument, including domains of diabetes control, energy and mobility, social burden and anxiety and worry, and sexual functioning) and the RAND-12 (a generic instrument, including physical health composite (PHC) and mental health composite (MHC)) were estimated to determine convergent/discriminant validity. Known-groups validity was examined using 2-hour postprandial plasma glucose (2 h PPG), hemoglobin A1c (HbA1c)) and presence of complications (retinopathy, neuropathy, and diabetic foot complications rather than the known groups of cardiovascular and cerebrovascular complications). We used a combined anchor- and distribution-based approach to establish MIDs. RESULTS: The DQOL scores were more strongly correlated with the physical domains of the D-39S (diabetes control and energy and mobility) and RAND-12 PHC than psychological domains of the D-39S (social burden, anxiety and worry, and sexual functioning) and RAND-12 MHC. The DQOL showed satisfactory discriminative ability for the known groups of 2 h PPG and HbA1c (effect size (ES) > or = 0.2) and retinopathy, neuropathy, and diabetic foot complications (ES > or = 0.3), but less satisfactory for the known groups of cardiovascular and cerebrovascular complications. MIDs for the DQOL domains were 3-5 points for satisfaction, 4-5 points for impact, 6-8 points for worry, and 3-4 points for overall HRQOL. CONCLUSION: We validated a DQOL in Chinese language for diabetes patients in Taiwan and provided MIDs to facilitate the measure of diabetes HRQOL.

Diabetes-specific or generic measures for health-related quality of life? Evidence from psychometric validation of the D-39 and SF-36.

OBJECTIVE: There is a debate regarding the use of disease-specific versus generic instruments for health-related quality of life (HRQOL) measures. We tested the psychometric properties of HRQOL measures using the Diabetes-39 (D-39) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). METHODS: This was a cross-sectional study collecting data from 280 patients in Taiwan. Exploratory factor analysis was conducted to evaluate construct validity of the two instruments. Known-groups validity was examined using laboratory indicators (fasting, 2-hour postprandial plasma glucose, and hemoglobin A1c), presence of diabetic complications (retinopathy, nephropathy, neuropathy, diabetic foot disorder, cardiovascular and cerebrovascular disorders), and psychosocial variables (sense of well-being and self-reported diabetes severity). Overall discriminative power of the two instruments was evaluated using the C-statistic. RESULTS: Three distinct factors were extracted through factor analysis. These factors tapped all subscales of the D-39, fourphysical subscales of the SF-36, and four mental subscales of the SF-36, respectively. Compared with the SF-36, the D-39 demonstrated superior known-groups validity for 2-hour postprandial plasma glucose groups but was inferior for complication groups. Compared with the SF-36, the D-39 discriminated better between self-reported severity known groups, but was inferior between well-being groups. In overall discriminative power, the D-39 discriminated better between laboratory known groups. The SF-36, however, was superior in discriminating between complication known groups. CONCLUSIONS: For psychometric properties, the D-39 and the SF-36 were superior to each other in different regards. The combined use of a disease-specific instrument and a generic instrument may be a useful strategy for diabetes HRQOL assessment.