Bridging the gap in managing dry eye disease: a consensus report by the Taiwan society of cataract and refractive surgeons.

BACKGROUND: An impaired ocular surface presents substantial challenges in terms of planning for cataract surgery. As a multifactorial ocular disorder, dry eye disease (DED) is common in the general population and prevalent in patients scheduled for lens replacement surgery. Cataract surgery can exacerbate DED and worsen several ocular parameters. Timely diagnosis and appropriate treatment of DED are vital to ensuring positive ophthalmic surgical outcomes. This consensus report of the Taiwan Society of Cataract and Refractive Surgeons (TSCRS) regarding the management of DED before, during, and after cataract surgery highlights the gaps between clinical guidelines and several aspects of DED, including diagnostic testing, diagnostic criteria, and clinical practice treatment. METHODS: An expert panel of five specialists in the field of ophthalmology was recruited to develop consensus statements regarding the management of DED in both the general population and in patients undergoing cataract surgery in Taiwan. Two separate meetings of the five specialists, who were endorsed by the TSCRS, were convened for this purpose. A survey questionnaire consisting of binary or multiple-choice questions was developed through a consensus-driven formulation process. A percentage value was calculated for each statement, and a minimum of 60% agreement (equivalent to three out of five members) was required to achieve consensus. The second discussion meeting involved the presentation of the finalized consensus statements and concluded the consensus development process. Lastly, the finalized consensus statements were approved by all the experts, and the formulated recommendations for DED in the general population and prospective cataract surgery patients were accordingly presented. RESULTS: The optimal algorithm for managing DED in the general population and in patients scheduled for cataract surgery was developed to address the unmet needs of this cohort in Taiwan. CONCLUSION: This report provides recommendations for managing dry eye disease. It is essential to screen and confirm DED through endorsed questionnaires and tests and then diagnose it. Treatment and management of DED should follow a stepwise approach. Screening and diagnosing DED is also recommended before cataract surgery. After cataract surgery, relatively aggressive treatment strategies are recommended to manage DED effectively.

General deep learning model for detecting diabetic retinopathy.

BACKGROUND: Doctors can detect symptoms of diabetic retinopathy (DR) early by using retinal ophthalmoscopy, and they can improve diagnostic efficiency with the assistance of deep learning to select treatments and support personnel workflow. Conventionally, most deep learning methods for DR diagnosis categorize retinal ophthalmoscopy images into training and validation data sets according to the 80/20 rule, and they use the synthetic minority oversampling technique (SMOTE) in data processing (e.g., rotating, scaling, and translating training images) to increase the number of training samples. Oversampling training may lead to overfitting of the training model. Therefore, untrained or unverified images can yield erroneous predictions. Although the accuracy of prediction results is 90%-99%, this overfitting of training data may distort training module variables. RESULTS: This study uses a 2-stage training method to solve the overfitting problem. In the training phase, to build the model, the Learning module 1 used to identify the DR and no-DR. The Learning module 2 on SMOTE synthetic datasets to identify the mild-NPDR, moderate NPDR, severe NPDR and proliferative DR classification. These two modules also used early stopping and data dividing methods to reduce overfitting by oversampling. In the test phase, we use the DIARETDB0, DIARETDB1, eOphtha, MESSIDOR, and DRIVE datasets to evaluate the performance of the training network. The prediction accuracy achieved to 85.38%, 84.27%, 85.75%, 86.73%, and 92.5%. CONCLUSIONS: Based on the experiment, a general deep learning model for detecting DR was developed, and it could be used with all DR databases. We provided a simple method of addressing the imbalance of DR databases, and this method can be used with other medical images.

A Novel Procedure for the Management of Severe Hyphema after Glaucoma Filtering Surgery: Air-Blood Exchange under a Slit-Lamp Biomicroscopy.

Background and Objectives: This study introduces a novel office-based procedure involving air-blood exchange under a slit-lamp microscope for treatment of severe hyphema after filtering surgery. Materials and Methods: This retrospective study enrolled 17 patients (17 eyes) with a diagnosis of primary open-angle glaucoma with severe hyphema (≥4-mm height) after filtering surgery. All patients were treated with air-blood exchange under a slit-lamp using room air (12 patients) or 12% perfluoropropane (C3F8; five patients). Results: The procedures were successful in all 17 patients; they exhibited clear visual axes without complications during follow-up. In the room air group, the mean visual acuity (VA) and hyphema height significantly improved from 1.70 ± 1.07 LogMAR and 5.75 ± 1.14 mm before the procedure to 0.67 ± 0.18 LogMAR and 2.83 ± 0.54 mm after the procedure (p = 0.004; p < 0.001). In the C3F8 group, the mean VA showed a trend, though not significant, for improvement from 1.70 ± 1.10 LogMAR to 0.70 ± 0.19 LogMAR (p = 0.08); the mean hyphema height showed a trend for improvement from 5.40 ± 0.96 mm to 3.30 ± 0.45 mm. Compared with the C3F8 group, the room air group showed the same efficacy with a shorter VA recovery time. Conclusions: "Air-blood exchange under a slit-lamp using room air" is a convenient, rapid, inexpensive, and effective treatment option for severe hyphema after filtering surgery, and may reduce the risk of failure of filtering surgery.

Glucosamine impedes transforming growth factor ß1-mediated corneal fibroblast differentiation by targeting Krüppel-like factor 4.

BACKGROUND: Transforming growth factor (TGF) family members play important roles in the regulation of corneal integrity, and the pathogenesis of corneal fibrosis. Currently, there are no effective agents targeting TGF-ß signaling to diminish corneal fibrosis. Glucosamine (GlcN), which is widely used in the treatment of osteoarthritis, abrogates the morphologic effects of TGF-ß2 on retinal pigmented epithelial cells in a mouse disease model. Here, we sought to determine whether GlcN would exert beneficial effects against TGF-ß1-induced corneal fibrosis. METHODS: In human corneal fibroblasts (HCFs) treated with GlcN, the expression of Krüppel-like factor 4 (KLF4) and its downstream signaling effects were determined in the presence and absence of TGF-ß1 using immunoblot analysis. We further explored GlcN inhibition of fibroblast-to-myofibroblast differentiation via KLF4 siRNA. The effect of cycloheximide on KLF4 protein levels with or without GlcN administration was assessed to determine whether GlcN affects the stability of the KLF4 protein. RESULTS: In HCFs, GlcN induced the expression of KLF4, which regulated the maturation and maintenance of the ocular surface. GlcN partially suppressed the TGF-ß1-induced expression of alpha-smooth muscle actin (α-SMA) and reduced the collagen contraction capacity in HCFs, suggesting a decrease in fibroblast-to-myofibroblast differentiation. This effect appeared to be mediated through suppression of Smad2 phosphorylation and ERK-dependent signaling. The levels of KLF4 mRNA were increased by GlcN and decreased by TGF-ß1 and the TGF-ß1-induced α-SMA mRNA expression was upregulated when the KLF4 gene was silenced. GlcN also appeared to stabilize the KLF4 protein, reducing its turnover in corneal fibroblasts. CONCLUSION: These findings shed light on a novel mechanism by which GlcN suppresses TGF-ß1-induced fibroblast-to-myofibroblast differentiation through the upregulation of KLF4 expression. Current strategies for treating corneal fibrosis were not effective. Elevating KLF4 levels through the use of GlcN might provide an effective alternative to alleviate the development and progression of corneal fibrosis.

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.

Benefit of hyperbaric oxygen therapy treatment in direct traumatic optic neuropathy: case report.

Direct traumatic optic neuropathy (TON) is a devastating condition and clinical challenge. Its adequate treatment remains controversial. Hyperbaric oxygen (HBO2) therapy has been proposed as an adjunctive treatment for eye disease but has rarely been used in optic neuropathy. The patient was a 57-year-old woman who had direct TON and brain injury after contusion injury. After receiving delayed HBO2 therapy her visual acuity got better - from hand motion to 6/60 - along with improvement of visual field and color vision. She was treated at 2.5 atmospheres absolute for 100 minutes, five times a week, for a total of 61 sessions. Our case highlights that HBO2 may be beneficial as an alternative treatment for direct TON, particularly when combined with brain injury. Although this entity is promising, further randomized controlled trials will be needed to clarify the efficacy of HBO2 in the treatment of direct TON.

Hypoxia and hyperoxia differentially control proliferation of rat neural crest stem cells via distinct regulatory pathways of the HIF1α-CXCR4 and TP53-TPM1 proteins.

BACKGROUND: Neural crest stem cells (NCSCs) are a population of adult multipotent stem cells. We are interested in studying whether oxygen tensions affect the capability of NCSCs to self-renew and repair damaged tissues. NCSCs extracted from the hair follicle bulge region of the rat whisker pad were cultured in vitro under different oxygen tensions. RESULTS: We found significantly increased and decreased rates of cell proliferation in rat NCSCs (rNCSCs) cultured, respectively, at 0.5% and 80% oxygen levels. At 0.5% oxygen, the expression of both hypoxia-inducible factor (HIF) 1α and CXCR4 was greatly enhanced in the rNCSC nuclei and was suppressed by incubation with the CXCR4-specific antagonist AMD3100. In addition, the rate of cell apoptosis in the rNCSCs cultured at 80% oxygen was dramatically increased, associated with increased nuclear expression of TP53, decreased cytoplasmic expression of TPM1 (tropomyosin-1), and increased nuclear-to-cytoplasmic translocation of S100A2. Incubation of rNCSCs with the antioxidant N-acetylcysteine (NAC) overcame the inhibitory effect of 80% oxygen on proliferation and survival of rNCSCs. CONCLUSIONS: Our results show for the first time that extreme oxygen tensions directly control NCSC proliferation differentially via distinct regulatory pathways of proteins, with hypoxia via the HIF1α-CXCR4 pathway and hyperoxia via the TP53-TPM1 pathway. Developmental Dynamics 246:162-185, 2017. © 2016 Wiley Periodicals, Inc.

Neurotrophic and neuroprotective potential of human limbus-derived mesenchymal stromal cells.

BACKGROUND AIMS: The purpose of this study was to examine neurotrophic and neuroprotective effects of limbus stroma-derived mesenchymal stromal cells (L-MSCs) on cortical neurons in vitro and in vivo. METHODS: Cultured L-MSCs were characterized by flow cytometry and immunofluorescence through the use of specific MSC marker antibodies. Conditioned media were collected from normoxia- and hypoxia-treated L-MSCs to assess neurotrophic effects. Neuroprotective potentials were evaluated through the use of in vitro hypoxic cortical neuron culture and in vivo rat focal cerebral ischemia models. Neuronal morphology was confirmed by immunofluorescence with the use of anti-MAP2 antibody. Post-ischemic infarct volume and motor behavior were assayed by means of triphenyltetrazolium chloride staining and open-field testing, respectively. Human growth antibody arrays and enzyme-linked immunoassays were used to analyze trophic/growth factors contained in conditioned media. RESULTS: Isolated human L-MSCs highly expressed CD29, CD90 and CD105 but not CD34 and CD45. Mesenchymal lineage cell surface expression pattern and differentiation capacity were identical to MSCs derived form human bone marrow and adipose tissue. The L-MSC normoxic and hypoxic conditioned media both promoted neurite outgrowth in cultured cortical neurons. Hypoxic conditioned medium showed superior neurotrophic function and neuroprotective potential with reduced ischemic brain injury and improved functional recovery in rat focal cerebral ischemia models. Human growth factor arrays and enzyme-linked immunoassays measurements showed neuroprotective and growth-associated cytokines (vascular endothelial growth factor [VEGF], VEGFR3, brain-derived neurotrophic factor, insulin-like growth factor -2 and hepatocyte growth factor) contained in conditioned media. Hypoxic exposure caused VEGF and brain-derived neurotrophic factor upregulation, possibly contributing to neurotrophic and neuroprotective effects. CONCLUSIONS: L-MSCs can secrete various neurotrophic factors stimulating neurite outgrowth and protecting neurons against brain ischemic injury through paracrine mechanism.

Investigation of corneal epithelial thickness and irregularity by optical coherence tomography after transepithelial photorefractive keratectomy.

CLINICAL RELEVANCE: Corneal epithelial healing after refractive surgery is a clinically significant issue, especially for surface ablation procedures, and this can be monitored using optical coherence tomography (OCT). BACKGROUND: The aim of this work is to investigate the corneal epithelial thickness and irregularity by OCT after transepithelial photorefractive keratectomy (t-PRK) and analyse its correlation with visual and refractive outcomes. METHODS: Patients aged ≥18 years with myopia, with or without astigmatism, who underwent t-PRK between May 2020 and August 2021 were included. All participants were subjected to complete ophthalmic examinations and OCT pachymetry at every follow-up visit. Patients were followed up at 1 week and 1, 3, and 6 months postoperatively. RESULTS: A total of 67 patients (126 eyes) were enrolled in this study. One month postoperatively, spherical equivalent refraction and visual acuity achieved preliminary stability. However, central corneal epithelial thickness (CCET) and standard deviation of the corneal epithelial thickness (SDcet) took 3-6 months to progressive recovery. Patients with higher baseline spherical equivalent refraction were associated with slower epithelial recovery. At every follow-up time point, a significant superior-inferior difference in the minimum corneal epithelial thickness area was observed. Higher stromal haze was correlated with higher spherical equivalent refraction (both baseline and residual) but had no relation with visual outcomes. There was a significant correlation between higher CCET with a better uncorrected distance visual acuity and lower corneal epithelial thickness irregularity. CONCLUSIONS: CCET and SDcet measured by OCT seem to be a good auxiliary indicator for reflecting the status of corneal wound recovery after t-PRK surgery. However, a well-designed randomised control study is needed to confirm the study results.

Anterior chamber paracentesis and pH values in patients with acute primary angle closure.

BACKGROUND: To assess the efficacy and safety of anterior chamber paracentesis (ACP) and the changes in pH values in eyes with acute primary angle closure (APAC). METHODS: This retrospective case-control study involved 22 patients with APAC who underwent ACP (study group) and 21 patients with APAC who did not undergo ACP (control group). Intraocular pressure (IOP) and visual acuity were measured before treatment and 15 min and 24 h after treatment in both groups. The pH of aqueous humor was measured immediately after ACP in the study group. RESULTS: A total of 43 eyes in 43 patients were reviewed. The IOP 15 min after ACP (23.3 ± 9.6 mmHg) and 24 h after ACP (21.6 ± 12.0 mmHg) were significantly lower than that before ACP (58.6 ± 12.9 mmHg). The IOP 15 min after ACP was significantly lower than the IOP 15 min after conventional treatment (55.4 ± 10.3 mmHg). Visual acuity recovery was achieved earlier after ACP than after conventional treatment. Hyphema after ACP was noted in one eye. The mean pH of the aqueous humor in APAC was 6.99 ± 0.35. The pH of the aqueous humor significantly correlated with the duration of acute IOP elevation and the IOP before ACP. CONCLUSIONS: ACP is an effective and safe procedure. The pH of aqueous humor is lower in eyes with APAC of longer duration and in eyes with higher IOP at presentation.

Correlation of microRNA-145 levels and clinical severity of pterygia.

PURPOSE: MicroRNA-145 (miR-145) has known anti-tumor properties and has been reported to be involved in regulating corneal epithelium differentiation. The exact role of miR-145 in ocular tissue remains unclear. In this study, we evaluate the effect of miR-145 expression levels on pterygium properties. SETTING: Ophthalmology department of a tertiary medical center. DESIGN: : Case series study. METHODS: Information regarding patient age, pterygium recurrence and pterygium severity (extension [E], vascularity [V] and thickness [T]) were gathered from records. Expression levels of miR-145 were obtained through examination of excised pterygium tissue. Correlations between age, pterygium classification, and miR-145 levels were evaluated. RESULTS: This study evaluated 253 patients (mean age 54.1±10.8 years). As pterygium severity increased, miR-145 levels decreased. Negative correlations were also found between miR-145 expression levels and pterygium extension (E) and vascularity (V). Thickness (T) had a weak negative correlation. There was only a mild negative correlation between patient age and miR-145 levels, which was only seen in patients with primary pterygium (not recurrent ones). Additionally, miR-145 expression was significantly higher in primary samples than in recurrent ones. CONCLUSIONS: We demonstrated an association between miR-145 and pterygium characteristics, consistent with its known tumor suppression effect. Because the management of pterygium is often difficult, we suggest that miR-145 should be further studied as a potential treatment.

Prevalence of meibomian gland dysfunction at a tertiary centre in Taiwan.

CLINICAL RELEVANCE: Meibomian gland dysfunction and dry eye disease are closely related conditions that often coexist and can contribute to the development of each other. Understanding the similarities and differences between these diseases can assist clinicians in implementing effective treatments for both conditions in a clinical setting. BACKGROUND: Dry eye disease is a multifactorial disease of the tears and ocular surface. This study aimed to evaluate the demographic characteristics of patients with meibomian gland dysfunction in Taiwan, investigate the association between meibomian gland dysfunction and dry eye parameters, and estimate the prevalence of meibomian gland dysfunction among patients with dry eye symptoms at a tertiary referral centre. METHODS: This cross-sectional study enrolled patients aged ≥20 years who complained of dry eye symptoms and visited a tertiary centre between September 2019 and March 2020. The patients completed the Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires before undergoing ocular examination. The lipid layer thickness and meiboscale scores were recorded. In addition, the study measured tear film break-up time, examined corneal staining, and evaluated the number of meibomian glands yielding liquid secretions using a slit lamp. RESULTS: The study evaluated 202 eyes of 202 patients with a mean age of 58.05 ± 13.34 years. The prevalence of meibomian gland dysfunction was 93%. Mean meiboscale score and age were negatively associated, and tear film break-up time was positively associated with the mean number of meibomian glands yielding liquid secretions. Hyperlipidaemia and smoking were the main risk factors for Meibomian gland dysfunction. CONCLUSIONS: The prevalence of meibomian gland dysfunction among patients with dry eye symptoms was extremely high at the tertiary centre, highlighting the strong relationship between Meibomian gland dysfunction and dry eye disease. Clinicians should consider meibomian gland dysfunction as a possible cause of dry eye.

Anterior capsular contraction syndrome with hyperopic shift.

PURPOSE: To present a case of anterior capsular contraction syndrome with hyperopic shift two weeks after an uncomplicated combined cataract surgery and pars plana vitrectomy. OBSERVATIONS: A 55-year-old man, with no known risk factors, who developed anterior capsular contraction syndrome with hyperopic shift two weeks after an uncomplicated combined cataract surgery and pars plana vitrectomy. Hyperopic shift was caused by posterior displacement of the intraocular lens with anterior flexion of the haptics. Manual peeling of the anterior capsule using the can-opener approach and microscissors successfully restored vision and corrected refractive errors. CONCLUSIONS AND IMPORTANCE: Anterior capsular contraction syndrome is a complication of cataract surgery and is known to be affected by zonular weakness, pre-existing systemic and ocular conditions, intraocular lens materials, and intraoperative complications. Careful maneuver with surgery or laser can effectively restore vision and correct refraction.

Acellular Porcine Cornea Produced by Supercritical Carbon Dioxide Extraction: A Potential Substitute for Human Corneal Regeneration.

PURPOSE: The aim of this study was to develop a non-cytotoxic, biocompatible innovative acellular porcine cornea (APC) for corneal wound healing and corneal blindness treatment. METHODS: APC was produced by using supercritical carbon dioxide (SCCO2) to decellularize the porcine cornea. Decellularization of the porcine cornea was examined by hematoxylin and eosin staining and 4,6-diamidino-2-phenylindole, dihydrochloride staining. The residual DNA content of APC was analyzed in comparison with the native porcine cornea. Virus inactivation up to at least 6 log10 was confirmed for the stepwise process of APC for 4 different model viruses. In addition, a series of in vitro and in vivo tests in accordance with ISO-10993 biocompatibility assay and animal performance tests were performed. RESULTS: APC produced by the SCCO2 process revealed complete decellularization, without any residual non-collagenous proteins. The scanning electron microscopy structural features of the decellularized cornea were similar to those of human. APC was found to be nontoxic and exhibited excellent biocompatibility in both in vitro and in vivo studies. The animal performance test proved that APC exerted excellent adaptability on the cornea and no sign of irritation and good compatibility in lamellar corneal transplantation. CONCLUSIONS: APC manufactured by SCCO2 technology revealed complete cells and non-collagenous protein removal compared with the Triton-sodium dodecyl sulfate decellularization process. APC showed excellent biocompatibility in rabbit lamellar corneal transplantation with a follow-up to 1 year. APC can be a potential substitute for human-donated cornea for corneal transplantation in the near future.

Mitomycin C for the prevention of corneal haze in photorefractive keratectomy: a meta-analysis and trial sequential analysis.

PURPOSE: To evaluate the anti-haze effect and visual outcome after intraoperative mitomycin C (MMC) use during photorefractive keratectomy (PRK) in myopia or myopic astigmatism patients. METHODS: We searched in PubMed, EMBASE, Cochrane Library and Google Scholar comprehensively to obtain studies comparing the clinical effects after PRK with and without MMC published until February 2020. Meta-analysis of primary outcome (corneal haze rate) and secondary outcomes [predictability, efficacy, safety and corneal endothelial cell density (ECD)] were conducted. We used trial sequential analysis (TSA) in an effort to collect firm evidence supporting our conclusion. RESULTS: Of the included 11 randomized controlled trials, five cohort and one case-control studies, 3536 eyes (2232 and 1304 in the MMC and control groups, respectively) were enrolled for meta-analysis. The TSA disclosed strong evidence of decline in corneal haze rate in the MMC group compared with that of the control group. In the subgroup analysis of duration, MMC seemed to reduce corneal haze rate in early-onset and late-onset haze. Predictability of refraction and visual acuity were greater in the MMC groups, not significantly though. The proportion of patients losing at least two lines of best corrected visual acuity postoperatively in the MMC groups was lower than that in the control groups. The corneal postoperative ECD showed no significant difference between the MMC and control groups. CONCLUSION: Our meta-analysis revealed that MMC is an important anti-haze agent in PRK for reducing both early- and late-onset haze and can also help improving predictability of refraction and subjective postoperative visual acuity.

Beneficial Effects of Hypercapnic Acidosis on the Inhibition of Transforming Growth Factor ß-1-induced Corneal Fibrosis in Vitro.

PURPOSE: Corneal scarring is a common poor outcome of corneal trauma. Transforming growth factor ß-1 plays a vital role in corneal fibrosis, inducing keratocyte transformation to myofibroblasts. Other than corneal transplantation, no other curative treatment methods for corneal scarring are currently available. Hypercapnic acidosis exerts anti-inflammatory and anti-migratory effects on numerous organs; however, its effect on corneal fibroblasts remains unknown. Hence, this study aimed to evaluate the effect of hypercapnic acidosis on transforming growth factor ß-1-induced fibrosis in corneal fibroblasts and to elucidate the underlying mechanisms. MATERIALS AND METHODS: Corneal fibroblasts were obtained from human limbal tissue and cultured with or without transforming growth factor ß-1 under hypercapnic acidosis or no-hypercapnic acidosis conditions, and subjected to scratch wound, cell migration, and collagen matrix contraction assays. Furthermore, immunocytochemistry was performed to evaluate the alpha-smooth muscle actin stress fiber. Finally, western blotting was performed to assess the expression of proteins in the NF-κB and Smad pathways. RESULTS: Hypercapnic acidosis suppressed collagen gel contraction capacity in transforming growth factor ß-1-treated corneal fibroblasts and inhibited transforming growth factor ß-1-induced cell migration. Moreover, hypercapnic acidosis downregulated corneal fibrosis marker alpha-smooth muscle actin in transforming growth factor ß-1-treated corneal fibroblasts. Furthermore, hypercapnic acidosis suppressed transforming growth factor ß-1-induced fibrosis, at least partly, by inhibiting Smad2/3 phosphorylation and down-regulating p-IκB-dependent and RelB signaling transduction. CONCLUSIONS: Hypercapnic acidosis inhibits transforming growth factor ß-1-induced corneal fibroblast migration, collagen gel contraction capacity, and alpha smooth muscle actin expression, potentially through the Smad and NF-κB pathways. Therefore, hypercapnic acidosis may be a potentially useful anti-fibrotic therapy for corneal scarring.

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.

Association between Optic Neuritis and Inflammatory Bowel Disease: A Population-Based Study.

Extraintestinal manifestations are common in patients with inflammatory bowel disease (IBD), and optic neuritis (ON) is a rare but severe one. This study aimed to evaluate possible factors associated with ON in patients with IBD. Adult patients with IBD who were not with concomitant ON on the index date identified from the Taiwan National Health Insurance Research Database (NHIRD) from the years 2000 to 2013 were included. A four-fold matched group was selected using age, sex and year of index date for comparison. All the patients were followed up until the development of ON or the end of the study period. Data of included patients were extracted and analyzed statistically. The mean follow-up time for all patients was 7.13 ± 5.21 years. At the study period conclusion, eight (0.18%) and five (0.003%) patients with and without IBD, respectively, had developed ON (p = 0.001). Adjusted HRs showed that patients with IBD aged between 30 and 39 years, with comorbidities including neuromyelitis optica (NMO), acute disseminated encephalomyelitis (ADEM), systemic lupus erythematosus (SLE) and with a higher Charlson Comorbidity Index, had a significantly higher risk of developing ON (all p < 0.005). Among the eight IBD patients who developed ON, only one patient was diagnosed with Crohn's disease, the male gender was slightly dominant, and two (25%) patients received antitumor necrosis factor α (anti-TNF α) treatment for IBD. Patients with IBD have a higher risk of developing ON compared to patients without IBD. ON occurs more frequently in IBD patients aged between 30 and 39 years, with comorbidities including NMO, ADEM and SLE. Other factors besides anti-TNF α treatment for IBD are more likely associated with the development of ON.

Prevalence and risk factors for myopia in Taiwanese diabetes mellitus patients: a multicenter case-control study in Taiwan.

This population-based retrospective cohort study investigated the prevalence of myopia among patients with Type 1 and Type 2 diabetes mellitus (DM) and evaluate risk factors for myopia in these groups. Records from 2000 to 2012 with at least one year of follow-up from the Taiwan National Health Insurance Research Database were included. This study included 35,538 patients with DM and 71,076 patients without DM. Patients with DM had a significantly higher adjusted hazard ratio for myopia in all age groups and both sexes compared with patients without DM. The subgroup analysis results revealed that the rates of myopia and astigmatism were significantly higher among patients with DM compared with patients without DM aged < 60 years. However, the rates of high myopia or myopia progression to high myopia did not differ significantly between the two groups. These findings indicate that DM is a critical risk factor for myopia and astigmatism among patients aged < 60 years. Therefore, active surveillance and earlier treatment of myopia are critical for patients with DM.

Glucosamine inhibits epidermal growth factor-induced proliferation and cell-cycle progression in retinal pigment epithelial cells.

PURPOSE: To investigate the effects and mechanisms of glucosamine (GlcN) on the proliferation of retinal pigment epithelial cells in response to epidermal growth factor (EGF). METHODS: Cell proliferation was measured in the human retinal pigment epithelial cell line (ARPE-19) cells with the 4-[3-(4iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay and cell counting. The results were confirmed in human donor cells with the carboxyfluorescein diacetate succinimidyl ester cell proliferation assay (CFSE) cell proliferation assay. In ARPE-19 cells, cell-cycle progression was determined by flow cytometry; the protein levels of cell cycle regulators and heat shock protein 90 (Hsp90) were measured by western blotting; the levels and branching of N-glycans were assessed using the L-Phaseolus vulgaris agglutinin lectin-binding assay; and the modulation of N-glycans on EGF receptor (EGFR) was examined by western blotting. RESULTS: GlcN inhibited retinal pigment epithelium (RPE) proliferation in a dose-dependent manner. During cell-cycle progression induced by EGF, GlcN caused delays at the G(1)-S and G(2)-M transitions without affecting cell viability. GlcN modulated the level and branching of N-glycans on EGFR, suppressed phosphorylation of EGFR, and reduced phosphorylation of extracellular signal-regulated kinases, erine/threonine protein kinase, and the signal transducer and activator of transcription 3 (STAT3). GlcN had only minor effects on the expression of Hsp90, Grp78, and transcription factor CHOP/GADD 153 markers of nonspecific stress in the endoplasmic reticulum. CONCLUSIONS: GlcN effectively suppressed proliferation of RPE cells in vitro. This effect appeared to be achieved through modification of N-glycans on EGFR. Further research into the role of GlcN as a potential agent for the prevention and treatment of RPE-mediated ocular proliferative disorders, such as proliferative vitreoretinopathy, and other EGF-dependent proliferative cell-growth disorders, is warranted.