We aim to investigate the role of medication adherence history in treatment needed diabetic retinopathy (TNDR). We conducted a retrospective nested case-control study using 3 population-based ...databases in Taiwan. The major one was the 2-million-sample longitudinal health and welfare population-based database from 1997 to 2017, a nationally representative random sample of National Health Insurance Administration enrolled beneficiaries in 2010 (LHID2010). The national death registry and national cancer registry were also checked to verify the information. The outcome was defined as the TNDR. The Medication possession ratio (MPR) was defined as the ratio of total days of diabetes mellitus (DM) medication supply divided by total observation days. MPR ≥ 80% was proposed as good medication adherence. The association of MPR and the TNDR was analyzed. Other potential confounders and MPR ratio were also evaluated. A total of (n = 44,628) patients were enrolled. Younger aged, male sex and patients with less chronic illness complexity or less diabetes complication severity tend to have poorer medication adherence. Those with severe comorbidity or participating pay-for-performance program (P4P) revealed better adherence. No matter what the characteristics are, patients with good MPR showed a significantly lower likelihood of leading to TNDR after adjustment with other factors. The protection effect was consistent for up to 5 years. Good medication adherence significantly prevents treatment needed diabetic retinopathy. Hence, it is important to promote DM medication adherence to prevent risks of diabetic retinopathy progression, especially those who opt to have low medication adherence.
In recent years, optical coherence tomography (OCT) biomarkers for specific retinal diseases have been found to be associated with treatment outcome and disease recurrence. The main purposes of this ...study were to identify OCT biomarkers for myopic choroidal neovascularization (mCNV) treated with intravitreal injection of anti‐vascular endothelial growth factor (anti‐VEGF). OCT features in 43 eyes of 39 patients with mCNV treated with anti‐VEGF with at least 1 year of follow‐up were retrospectively analyzed. Eyes with subretinal hyperreflective material (SHM) in baseline spectral‐domain OCT (SD‐OCT) had significantly more visual improvement than eyes without SHM at month 6 (p = 0.007) and had a trend of more visual improvement than eyes without SHM (p = 0.058) at month 12. Eyes with subretinal fluid (SRF) at baseline had significantly more central retinal thickness (CRT) decrease than patients without SRF at month 6 and 12 (p = 0.012 and 0.006 respectively). In univariate regression analysis, dome‐shaped macula (DSM), SRF in baseline OCT image and fuzzy border of mCNV when entering pro re nata (PRN) injection protocol tended to have higher risk of disease recurrence in 1 year (odds ratio: 14.86 (p = 0.003), 3.75 (p = 0.049) and 22.92 (p < 0.001) respectively). However, they were not significant in multivariate regression analysis. OCT biomarkers at baseline could provide prognostic information for mCNV management.
We investigated the independent impact of potential risk factors on myopia in young adults.
A survey study was conducted with male military conscripts aged 18 to 24 years between February 2010 and ...March 2011 in Taiwan. The participants were examined using non-cycloplegic autorefraction and biometry. The participants provided data about potential risk factors, including age, parental myopia, education, near work, outdoor activity, and urbanization. Myopia was defined as the mean spherical equivalent of the right eye of ≤ 0.5 diopters (D).
Among 5145 eligible participants, 5048 (98.11%) had refraction and questionnaire data available; 2316 (45.88%) of these received axial length examination. The prevalence of myopia was 86.1% with a mean refractive error of -3.66 D (SD = 2.73) and an axial length of 25.40 mm (SD = 1.38). Older age, having myopic parents, higher education level, more time spent reading, nearer reading distance, less outdoor activity, and higher urbanization level were associated with myopia and longer axial length. More computer use was related to longer axial length. All risk factors associated with myopia also were predictors of high myopia (≤ -6.0 D), with the exception of outdoor activity. Finally, an interaction analysis showed shorter axial length was associated with more time spent outdoors only at high urbanization level.
Older age, parental myopia, higher education level, more near work, less outdoor activity, and higher urbanization level were independent predictors of myopia. These data provided evidence to the multifactorial nature of myopia in young men in Taiwan.
Chronic hyperglycemia involves persistent high-glucose exposure and correlates with retinal degeneration. It causes various diseases, including diabetic retinopathy (DR), a major cause of adult ...vision loss. Most in vitro studies have investigated the damaging short-term effects of high glucose exposure on retinal pigment epithelial (RPE) cells. DR is also a severe complication of diabetes. In this study, we established a model with prolonged high-glucose exposure (15 and 75 mM exogenous glucose for two months) to mimic RPE tissue pathophysiology in patients with hyperglycemia. Prolonged high-glucose exposure attenuated glucose uptake and clonogenicity in ARPE-19 cells. It also significantly increased reactive oxygen species levels and decreased antioxidant protein (superoxide dismutase 2) levels in RPE cells, possibly causing oxidative stress and DNA damage and impairing proliferation. Western blotting showed that autophagic stress, endoplasmic reticulum stress, and genotoxic stress were induced by prolonged high-glucose exposure in RPE cells. Despite a moderate apoptotic cell population detected using the Annexin V-staining assay, the increases in the senescence-associated proteins p53 and p21 and SA-β-gal-positive cells suggest that prolonged high-glucose exposure dominantly sensitized RPE cells to premature senescence. Comprehensive next-generation sequencing suggested that upregulation of oxidative stress and DNA damage-associated pathways contributed to stress-induced premature senescence of ARPE-19 cells. Our findings elucidate the pathophysiology of hyperglycemia-associated retinal diseases and should benefit the future development of preventive drugs.
Graphical Abstract
Prolonged high-glucose exposure downregulates glucose uptake and oxidative stress by increasing reactive oxygen species (ROS) production through regulation of superoxide dismutase 2 (SOD2) expression. Autophagic stress, ER stress, and DNA damage stress (genotoxic stress) are also induced by prolonged high-glucose exposure in RPE cells. Consequently, multiple stresses induce the upregulation of the senescence-associated proteins p53 and p21. Although both apoptosis and premature senescence contribute to high glucose exposure-induced anti-proliferation of RPE cells, the present work shows that premature senescence rather than apoptosis is the dominant cause of RPE degeneration, eventually leading to the pathogenesis of DR.
To investigate a possible association between retinal vein occlusion (RVO) and an increased risk of developing acute myocardial infarction (AMI).
A population-based retrospective cohort study using ...the entire population of the Taiwan National Health Insurance Research Database (NHIRD) from 1st January, 2001 to 31st December, 2013.
A total of 37921 subjects with RVO were enrolled in the RVO group, and 113763 subjects without RVO were enrolled in the comparison group. The comparison group consisted of randomly selected individuals who were propensity score (PS)-matched with the RVO group at a ratio of 1:3, based on age, gender, obesity, stroke, hyperviscosity syndrome, glaucoma, and the use of antithrombotic drugs. A log-rank test was used to compare the cumulative hazard of AMI between the two groups. A multivariate Cox regression analysis was used to estimate the adjusted hazard ratios (HRs) of AMI, adjusted for PS, diabetes, hypertension, hyperlipidemia, congestive heart failure, and chronic renal failure.
The mean age of the cohort was 62.4±13.2 years. RVO patients had significantly higher proportions of diabetes, hypertension, hyperlipidemia, congestive heart failure, and chronic renal failure than the comparisons. The mean follow-up period was 5.52 years in the RVO group and 5.55 years in the comparison group (p = 0.16). A log-rank test comparing the cumulative hazard curves of AMI for the two groups revealed a significant difference (p<0.0001). In the multivariate Cox regression after adjustment for PS and confounders, the RVO group had a significantly higher risk of AMI (adjusted HR = 1.21; 95% CI: 1.13 to 1.30). When the RVO group was divided into central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) and analyzed separately, both groups had significantly higher adjusted HRs for developing AMI than the comparison group. Moreover, the CRVO group had a significantly higher risk of AMI than the BRVO group.
People with RVO are at significantly greater risk of developing AMI than individuals without RVO.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Under metabolic stress conditions such as hypoxia and glucose deprivation, an increase in the AMP:ATP ratio activates the AMP-activated protein kinase (AMPK) pathway, resulting in the modulation of ...cellular metabolism. Metformin, which is widely prescribed for type 2 diabetes mellitus (T2DM) patients, regulates blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells. At the molecular level, the most well-known mechanism of metformin-mediated cytoprotection is AMPK pathway activation, which modulates metabolism and protects cells from degradation or pathogenic changes, such as those related to aging and diabetic retinopathy (DR). Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR. This review focuses on new insights into the anticancer effects of metformin and its potential modulation of several novel types of nonapoptotic cell death, including ferroptosis, pyroptosis, and necroptosis. In addition, the antimetastatic and immunosuppressive effects of metformin and its hypothesized mechanism are also discussed, highlighting promising cancer prevention strategies for the future.
PURPOSE OF REVIEWOcular sarcoidosis is one of the most common causes of uveitis worldwide. The diagnosis and treatment of patients with ocular sarcoidosis remains challenging in some cases. It is ...important for clinicians to keep up to date with new diagnostic and treatment tools for this disease.
RECENT FINDINGSThe International Workshop on Ocular Sarcoidosis diagnostic criteria were first proposed in 2009 and revised in 2017. The new criteria contained two partsocular presentation and systemic investigation. The diagnostic value of liver enzymes was reduced in the new criteria, whereas the value placed of lymphopenia and the CD4/CD8 ratio in bronchoalveolar lavage fluid were increased. Despite not being included in the criteria, recent studies have also highlighted the diagnostic value of serum soluble interleukin-2 receptors. Recent ophthalmologic imaging also provides useful insights for the differential diagnosis.Many new treatments for ocular sarcoidosis have been developed in recent years. The introduction of biological immunomodulatory agents for uveitis treatment represents a big improvement. Antitumor necrosis factor-alpha antibodies, including adalimumab, have been proven to be effective for treating ocular sarcoidosis. Many studies have also suggested that other biological agents could be effective and well tolerated. Newer intravitreal dexamethasone and fluocinolone implants have been developed. Patients treated with these implants have experienced good and sustained control of their intraocular inflammation.
SUMMARYDiagnosis and treatment options for ocular sarcoidosis have changed over time. However, challenges still exist in some difficult patients. Future studies should focus on finding more sensitive biomarkers and developing more effective immunomodulatory treatments with longer efficacy and less side effects.
The definite diagnosis of Coats disease can be challenging especially in its advanced stage, as it could mimic other severe ophthalmic conditions, such as retinoblastoma. 1 The natural history of ...Coats disease can progress to blindness and even bulbi atrophy if not treated properly. 2 Thus, early diagnosis and appropriate treatment are important. ...retinitis persisted with newly developed exudative retinal detachment even after 3 months of antiviral treatment. ...the treatment was switched to oral valganciclovir under the impression of suspected CMV infection, which turned out to be no help. Fundus exam revealed profuse lipid exudates along vessels with groups of telangiectatic vessels (Figure 1C). ...fundus angiography showed typical light bulb dilations of the leaking telangiectatic vessels along with nonperfusion area at temporal and inferior periphery (Figure 1D).
Age-related macular degeneration (AMD) is the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris among elderly individuals and is the leading cause of ...blindness worldwide. Thus, a better understanding of the underlying mechanisms in retinal tissue activated by blue light exposure is important for developing novel treatment and intervention strategies. In this study, blue-light-emitting diodes with a wavelength of 440 nm were applied to RPE cells at a dose of 3.7 ± 0.75 mW/cm
for 24 h. ARPE-19 cells were used to investigate the underlying mechanism induced by blue light exposure. A trypan blue exclusion assay was used for the cell viability determination. Flow cytometry was used for apoptosis rate detection and autophagy analysis. An immunofluorescence microscopy analysis was used to investigate cellular oxidative stress and DNA damage using DCFDA fluorescence staining and an anti-γH2AX antibody. Blue light exposure of zebrafish larvae was established to investigate the effect on retinal tissue development in vivo. To further demonstrate the comprehensive effect of blue light on ARPE-19 cells, next-generation sequencing (NGS) was performed for an ingenuity pathway analysis (IPA) to reveal additional related mechanisms. The results showed that blue light exposure caused a decrease in cell proliferation and an increase in apoptosis in ARPE-19 cells in a time-dependent manner. Oxidative stress increased during the early stage of 2 h of exposure and activated DNA damage in ARPE-19 cells after 8 h. Furthermore, autophagy was activated in response to blue light exposure at 24-48 h. The zebrafish larvae model showed the unfavorable effect of blue light in prohibiting retinal tissue development. The RNA-Seq results confirmed that blue light induced cell death and participated in tissue growth inhibition and maturation. The current study reveals the mechanisms by which blue light induces cell death in a time-dependent manner. Moreover, both the in vivo and NGS data uncovered blue light's effect on retinal tissue development, suggesting that exposing children to blue light could be relatively dangerous. These results could benefit the development of preventive strategies utilizing herbal medicine-based treatments for eye diseases or degeneration in the future.
To offer consensus on the utilization of corticosteroids (CS) for treating non-infectious uveitis in the context of clinical practice in Taiwan. This entails examining the different administration ...methods, their advantages and disadvantages, and considering alternative treatments according to the prevailing evidence and health policies.
Ten ophthalmologists and one rheumatologist convened on December 11, 2022, to review and discuss literature on the topic. The databases explored were the Central Cochrane library, EMBASE, Medline, PUBMED, and Web of Science using relevant keywords. The search spanned from January 1996 to June 2023. After the initial results of the literature review were presented, open voting determined the final statements, with a statement being accepted if it secured more than 70% agreement. This consensus was then presented at significant meetings for further discussions before the final version was established.
A flow chart and nine statements emerged from the deliberations. They address the importance of CS in uveitis management, guidelines for using topical CS, indications for both periocular or intravitreal and systemic therapies, and tapering and discontinuation methods for both topical and systemic CS.
While CS are a cornerstone for non-infectious uveitis treatment, their administration requires careful consideration, depending on the clinical situation and the specific type of uveitis. The consensus generated from this article provides a guideline for practitioners in Taiwan, taking into account local health policies and the latest research on the subject. It emphasizes the significance of strategic tapering, the potential for alternative therapies, and the importance of patient-centric care.