Characteristics of Optic Disc and Visual Field Changes in Patients with Thyroid-Associated Orbitopathy and Open-Angle Glaucoma.

This study aimed to characterize the changes in the visual field (VF) patterns and disc morphology of patients with thyroid-associated orbitopathy (TAO) and open-angle glaucoma (OAG). A retrospective review of the medical records at the Tri-Service General Hospital in Taiwan identified 396 eyes of 198 patients with thyroid-associated glaucoma. A final follow-up of VF examination in 140 eyes revealed 114 eyes with VF defects, indicating disease progression. The characteristics of and changes in disc morphology, optical coherence tomography findings, and VF defects were statistically analyzed. The most common VF defects at the initial diagnosis and the end of the follow-up period were inferior partial arcuate (17%) and paracentral (15%) defects, respectively. The most common VF defect in patients with unspecific disc signs was an unspecific scotoma (13%). The most common optic disc feature was disc cupping (51%), followed by parapapillary atrophy (48%). The most frequent location of nerve fiber layer thinning was the inferotemporal region (48%). VF defects showed a significantly more pronounced progression in the non-nerve fiber bundle group than in the nerve fiber bundle group (p < 0.001). This study details the characteristics and progression of disc morphology and VF defects in patients with TAO and OAG.

The Role of Ophiopogonin D in Atherosclerosis: Impact on Lipid Metabolism and Gut Microbiota.

Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in Ophiopogon japonicus, is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE[Formula: see text] mice on the development of atherosclerosis and gut microbiota. To investigate the potential ability of OPD to alleviate atherosclerosis, 24 eight-week-old male ApoE[Formula: see text] mice (C57BL/6 background) were fed a high-fat diet (HFD) for 12 weeks, and 8 male C57BL/6 mice were fed a normal diet, serving as the control group. ApoE[Formula: see text] mice were randomly divided into the model group, OPD group, and simvastatin group ([Formula: see text]= 8). After treatment for 12 consecutive weeks, the results showed that OPD treatment significantly decreased the plaque formation and levels of serum lipid compared with those in the model group. In addition, OPD improved oral glucose tolerance and insulin resistance as well as reducing hepatocyte steatosis. Further analysis revealed that OPD might attenuate atherosclerosis through inhibiting mTOR phosphorylation and the consequent lipid metabolism signaling pathways mediated by SREBP1 and SCD1 in vivo and in vitro. Furthermore, OPD treatment led to significant structural changes in gut microbiota and fecal metabolites in HFD-fed mice and reduced the relative abundance of Erysipelotrichaceae genera associated with cholesterol metabolism. Collectively, these findings illustrate that OPD could significantly protect against atherosclerosis, which might be associated with the moderation of lipid metabolism and alterations in gut microbiota composition and fecal metabolites.

The impact of glucosamine on age-related macular degeneration in patients: A nationwide, population-based cohort study.

PURPOSE: To analyze the association between glucosamine (GlcN) use and the risk of age-related macular degeneration (AMD) using claims data from the National Health Insurance Research Database (NHIRD). METHODS: A retrospective, population-based study was conducted with NHIRD data from a 14-year period (2000-2013). Chi-squared and Student's t-tests were used to evaluate differences between the study and comparison cohorts for categorical and continuous variables, respectively. Risk factors for disease development were examined by the adjusted hazard ratio (aHR) with 95% confidence interval. Kaplan-Meier analysis was performed to compare the cumulative risk of AMD between the two cohorts. RESULTS: In total, 1,344 patients with GlcN treatment were enrolled in the study cohort and 5,376 patients without GlcN use were enrolled in the comparison cohort. The incidence rate of AMD was lower with GlcN use (3.65%) than without GlcN use (5.26%) (P = 0.014). GlcN use was associated with a lower risk of developing AMD among patients with hyperlipidemia, coronary artery disease, chronic obstructive pulmonary disease, stroke, other neurological disorders, or degenerative arthritis. Although the incidence of wet type AMD did not significantly differ (P = 0.91), the incidence of dry type AMD was lower in patients with GlcN use (2.9%) than those without GlcN use (4.84%) (P = 0.003). Kaplan-Meier analysis similarly revealed a lower rate of dry type AMD in patients with GlcN use compared to those without GlcN use (log-rank P = 0.004). CONCLUSIONS: GlcN treatment can decrease the risk of developing dry type AMD. Further prospective controlled studies are needed to determine the effectiveness of GlcN treatment in patients with AMD and the associated mechanism.

Evaluation of the relationship between central serous chorioretinopathy and liver cirrhosis: A nationwide, population-based study.

BACKGROUND: Central serous chorioretinopathy (CSCR) and liver cirrhosis share numerous risk factors and may have possible connections. We aimed to investigate whether patients with liver cirrhosis and the severity of cirrhosis have an increased incidence of CSCR. METHODS: This population-based retrospective cohort study was conducted by collecting data from the Taiwan National Health Insurance Research Database from January 1, 2000, to December 31, 2015. We included patients who were newly diagnosed with cirrhosis and selected an equal number of sex- and age-matched control subjects. The effect of cirrhosis on the risk of CSCR was examined via a Cox proportional hazard regression analysis. The cumulative incidence of CSCR was assessed with the Kaplan-Meier method and the log-rank test. RESULTS: Both groups in this study comprised a total of 25 925 individuals. The cirrhotic patients had a significantly higher cumulative risk of developing CSCR in following years than patients without cirrhosis (log-rank test < 0.001). Furthermore, compared with noncirrhotic patients, the risk of CSCR was increased 3.59-fold (95% confidence interval [CI], 2.31-5.28) in cirrhotic patients with complications, and 2.34-fold (95% CI, 1.27-3.24) in cirrhotic patients without complications. Additionally, male sex, springtime, diabetes mellitus, hepatitis B virus, and hepatitis C virus statistical significantly increased the incidence of CSCR. CONCLUSION: Cirrhosis is an independent indicator of CSCR. Among the cirrhotic population, patients with ascites and other complications have a higher incidence of CSCR than those with uncomplicated cirrhosis. Physicians should be observant when managing cirrhotic patients with visual disturbances.

Glucosamine-Induced Autophagy through AMPK⁻mTOR Pathway Attenuates Lipofuscin-Like Autofluorescence in Human Retinal Pigment Epithelial Cells In Vitro.

Age-related macular degeneration (AMD) is a vision-threatening age-associated disease. The retinal pigment epithelial (RPE) cells phagocytose and digest photoreceptor outer segment (POS). Incomplete digestion of POS leads to lipofuscin accumulation, which contributes to the pathology of the AMD. Autophagy could help reduce the amount of lipofuscin accumulation. In the present study, we evaluated the effects of glucosamine (GlcN), a natural supplement, on the induction of autophagy and POS-derived lipofuscin-like autofluorescence (LLAF) in ARPE-19 cells in vitro, and investigated the potential molecular pathway involved. Our results revealed that GlcN had no effect on phagocytosis of POS at the lower doses. GlcN treatment induced autophagy in cells. GlcN decreased the LLAF in native POS-treated cells, whereas malondialdehyde or 4-hydroxynonenal-modified POS attenuated this effect. 3-Methyladenine inhibited GlcN-induced autophagy and attenuated the effect of GlcN on the decrease of the native POS-derived LLAF. Furthermore, GlcN induced the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR), whereas Compound C inhibited these effects of GlcN. Altogether, these results suggest that GlcN decreased the native POS-derived LLAF through induction of autophagy, at least in part, by the AMPK⁻mTOR pathway. This mechanism has potential for the preventive treatment of lipofuscin-related retinal degeneration such as AMD.

Combined trabeculotomy-trabeculectomy using the modified Safer Surgery System augmented with MMC: its long-term outcomes of glaucoma treatment in Asian children.

BACKGROUND: This study aimed to study the long-term surgical outcomes of combined trabeculotomy-trabeculectomy (CTT) using the modified Safer Surgery System in treating childhood glaucoma at a tertiary medical center in Taiwan. METHODS: Retrospective, consecutive, noncomparative case series. We retrospectively reviewed medical records of 42 pediatric patients (age 0-18 years) who had CTT performed on their 65 eyes using the modified Safer Surgery System. The study period spanned 18 years (from January 1, 1997, to December 31, 2014). We evaluated the outcome in terms of postoperative intraocular pressure (IOP), axial length growth, disc cupping reversal, and use of antiglaucoma medications. The surgical success was rated using the Kaplan-Meier survival analysis and based on the incidence of complications. RESULTS: The mean follow-up period was 85.05 ± 32.17 months (range 14-200). After operation, IOP dropped significantly from 35.76 ± 9.44 mmHg (mean ± SD) to 16.18 ± 7.20 mmHg together with a significant reversal of optic disc cupping. Similarly, the use of antiglaucoma medications was also significantly reduced in number from 1.26 ± 0.50 to 0.43 ± 0.70. Most of the axial lengths of the eyes measured at the last follow-up visit showed growths within the average ± 2 SDs in comparison with the healthy, age-matched population. After surgery, the qualified success rate was 90.77% at the end of the first year, 90.77% at the second year, 87.64% at the fifth year, 84.51% at the 10th year, and 81.38% at the 15th year. No serious intraoperative or postoperative complications were found. CONCLUSIONS: For Taiwanese children, the combined trabeculotomy-trabeculectomy using the modified Safer Surgery System offered an efficient and safe surgical option for treating glaucoma with long-term satisfactory control of IOP.

Silibinin treatment prevents endotoxin-induced uveitis in rats in vivo and in vitro.

Uveitis, an intraocular inflammatory disease, occurs mostly in young people and can result in the loss of socioeconomic capabilities. Silibinin has been shown to exert anti-inflammatory effects in human retinal pigment epithelial (RPE) cells. The present study investigated the anti-inflammatory effect of silibinin pretreatment on endotoxin-induced uveitis (EIU) in rats and the mechanisms by which it exerts these effects. Uveitis was induced via injection of lipopolysaccharides (LPS) into Lewis rats. Twenty-four hours after the LPS injection, histological examination showed that silibinin decreased inflammatory cell infiltration in the anterior segment of the eyes of LPS-treated rats. Analyses of the aqueous humor showed that silibinin decreased cell infiltration, protein concentration, nitric oxide (NO), and prostaglandin (PG)-E2 production. Western blot analysis indicated that silibinin decreased the expression of inducible NO synthase (iNOS), cyclooxygenase (COX-2), and phosphorylated IkB in the iris-ciliary body (ICB). Immunohistochemistry showed that silibinin decreased intercellular adhesion molecule (ICAM-1) expression in the ICB. In addition, western blot analysis showed that silibinin attenuated the expression of iNOS, COX-2, ICAM-1, and nuclear p65 in LPS-treated RAW cells. In conclusion, silibinin pretreatment prevents EIU and the subsequent production of proinflammatory mediators and ICAM-1, at least in part, by blocking the NF-κB-dependent signaling pathway both in vivo and in vitro. These effects may contribute to the silibinin-mediated preventive effects on intraocular inflammatory diseases such as acute uveitis.

Subthreshold transpupillary thermotherapy in Chinese patients with myopic choroidal neovascularization: one- and two-year follow up.

BACKGROUND: To perform a safety and efficacy study of subthreshold transpupillary thermotherapy (TTT) in Chinese patients with choroidal neovascularization (CNV) secondary to pathologic myopia. METHODS: In a prospective study, patients with subfoveal or juxtafoveal CNV secondary to high myopia underwent subthreholdTTT with fixed treatment and follow-up protocols. From October 2002 to July 2005, 12 and 24 months of follow up were completed for 21 eyes and 13 eyes respectively. RESULTS: The mean best-corrected visual acuities (BCVA) were maintained at the baseline level at 1 and 2 years. Seventy-two per cent of eyes and 63% of eyes had stable or improved BCVA at 12 and 24 months.Thirty-four per cent and 39% of eyes had a moderate gain in vision (improved by three or more lines) at 12 and 24 months respectively.The average number of subthreshold TTT treatments was 1.7. The major complication of subthresholdTTT included laserrelated low-grade retinal pigment epithelium atrophy in two eyes of young patients with clear lenses. The final VA was significantly associated with pretreated VA (r = 0.614, P = 0.003).The final VA improvement was significantly associated with pretreatment VA in negative correlation (r=-0.731, P = 0.0002, Person correlation test). CONCLUSIONS: Subthreshold TTT in Chinese patients with pathologic myopia and subfoveal or juxtafoveal CNV generally maintained vision at 1- and 2-year follow up. Using decreased power of subthreshold TTT, especially in the younger patients with a clear lens, is suggested.

Inhibitory effects of glucosamine on endotoxin-induced uveitis in Lewis rats.

PURPOSE: Glucosamine sulfate (GS) is a naturally occurring sugar that exerts immunosuppressive effects in vitro and in vivo. The authors investigated whether GS modulates the inflammatory reaction in endotoxin-induced uveitis (EIU) of rats and the mechanisms by which it exerts its effects. METHODS: Two-hundred micrograms of lipopolysaccharide (LPS) was injected subcutaneously into Lewis rats to induce EIU. Doses of GS (10, 100, or 1000 mg/kg) were divided into three aliquots and administered intraperitoneally 30 minutes before LPS injection, concurrently with LPS injection, and 30 minutes after LPS injection. Twenty-four hours after LPS injection, aqueous humor was collected for cell counting and measurement of protein concentration. Immunohistochemical staining of the iris-ciliary body was performed to evaluate the effects of GS on intercellular adhesion molecule (ICAM)-1 and nuclear factor (NF)-kappaB activation and to demonstrate macrophage infiltration. The effects of various doses of GS pretreatment were also examined using a mouse macrophage cell line (RAW264.7 cells) and LPS stimulation. Levels of prostaglandin (PG)-E2 and nitric oxide (NO) were determined. Expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were measured using Western blot analysis. The effect of GS on LPS-induced NF-kappaB activation in RAW cells was also examined. RESULTS: Cell counting and analysis of protein concentration in aqueous humor revealed that GS suppressed EIU in rats treated with a high dose of GS (1000 mg/kg). Immunohistochemistry showed that treatment with GS reduced ICAM-1 expression and suppressed activation of NF-kappaB in the iris-ciliary body. The main inflammatory cells in the iris-ciliary body during EIU were macrophages. In LPS-stimulated macrophage RAW cell culture, GS inhibited the production of NO and PG-E2, the expression of iNOS and COX-2, and the activation of NF-kappaB. CONCLUSIONS: GS suppresses EIU in rats by blockading the NF-kappaB-dependent signaling pathway and the subsequent production of ICAM-1 and proinflammatory mediators. This study has extended the authors' previous observation that GS is a potentially important compound for reducing ICAM-1-mediated inflammatory effects in the eye.