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AbstractPurpose 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.Methods 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.Results 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.Conclusion 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.

Objectives: This study aimed to use deep learning to identify glaucoma and normal eyes in groups with high myopia using fundus photographs. Methods: Patients who visited Tri-Services General Hospital from 1 November 2018 to 31 October 2022 were retrospectively reviewed. Patients with high myopia (spherical equivalent refraction of ≤−6.0 D) were included in the current analysis. Meanwhile, patients with pathological myopia were excluded. The participants were then divided into the high myopia group and high myopia glaucoma group. We used two classification models with the convolutional block attention module (CBAM), an attention mechanism module that enhances the performance of convolutional neural networks (CNNs), to investigate glaucoma cases. The learning data of this experiment were evaluated through fivefold cross-validation. The images were categorized into training, validation, and test sets in a ratio of 6:2:2. Grad-CAM visual visualization improved the interpretability of the CNN results. The performance indicators for evaluating the model include the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results: A total of 3088 fundus photographs were used for the deep-learning model, including 1540 and 1548 fundus photographs for the high myopia glaucoma and high myopia groups, respectively. The average refractive power of the high myopia glaucoma group and the high myopia group were −8.83 ± 2.9 D and −8.73 ± 2.6 D, respectively (p = 0.30). Based on a fivefold cross-validation assessment, the ConvNeXt_Base+CBAM architecture had the best performance, with an AUC of 0.894, accuracy of 82.16%, sensitivity of 81.04%, specificity of 83.27%, and F1 score of 81.92%. Conclusions: Glaucoma in individuals with high myopia was identified from their fundus photographs.

Objective: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. Methods: A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000–2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan–Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. Results: Kaplan–Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10–3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04–3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08–4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51–6.14). Conclusion: DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients.

Uveitis is a sight-threatening disease that can be associated with many different etiologies. Successful treatment of uveitis relies on accurate diagnosis and prompt efficient therapy. History taking, physical and ocular examinations, systemic evaluations, and response to treatment provide crucial information to differentiate possible etiologies involved in the pathophysiology of intraocular inflammation. This article provides recommendations for a step-wise approach to patients with uveitis in Taiwan based on an expert meeting and consensus. Systemic evaluations for uveitis should be performed step-by-step and include investigation of patients’ general systemic conditions, ruling out infectious etiologies, and obtaining evidential biomarkers to diagnose a specific disease entity.

Ankylosing spondylitis (AS) is known to increase the risk of stroke. Among patients with AS, uveitis is the most common extra-articular manifestation. However, no previous investigations have discussed the association between uveitis and the risk for developing stroke in patients with AS. This retrospective cohort study aimed to explore the relationship between uveitis and the incidence of stroke in patients with AS by obtaining medical records from January 1, 2000, to December 31, 2015, from the National Health Insurance Research Database, according to the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. The primary outcome was the incidence of stroke. Pearson’s chi-square test and Fisher’s exact test were used to analyze variables. Kaplan–Meier survival curves and univariate and multivariate Cox proportional hazard regression models with and without Fine and Gray’s competing risk model were used to analyze data. Total 828 AS patients with uveitis and 3,312 AS patients without uveitis were identified. During the follow-up period, 137 patients in the uveitis group and 344 in the non-uveitis group developed stroke. Uveitis is a significant risk factor for stroke development in patients with AS (adjusted hazard ratio = 1.846, p < 0.001). Age, diabetes mellitus, hyperlipidemia, hypertension, congestive heart failure, chronic obstructive pulmonary disease, asthma, coronary artery disease, and atrial fibrillation were associated with a higher risk of stroke. After subgroup analysis, both anterior uveitis and posterior segment involvement were found to increase the risk of stroke in patients with AS. Uveitis is associated with an increased risk in both ischemic and hemorrhagic strokes in patients with AS. Therefore, when uveitis is identified, clinicians should pay more attention to the cerebrovascular risk in patients with AS, especially in those with underlying comorbidities.

BackgroundUveitis, a sight-threatening ocular inflammatory state, is associated with autoimmune diseases and systemic inflammation. This prolonged systemic inflammation may cause plaque formation in coronary arteries, subsequently resulting in acute coronary syndrome (ACS).MethodsThis retrospective, population-based study (15-year period) used the Longitudinal Health Insurance Database based on the National Health Insurance Research Database in Taiwan. Chi-square and Student’s t-tests were used to examine differences between the study and comparison cohorts for categorical and continuous variables, respectively. Fine and Gray’s competing risk model was used to determine the hazard ratio of the risk of ACS. Furthermore, the cumulative risk of ACS was determined using Kaplan-Meier analysis.ResultsA total of 1,111 patients with AS and uveitis were enrolled in this study cohort, and 4,444 patients with AS without uveitis were enrolled in the comparison cohort. After adjustment for age, sex, and comorbidities, patients with AS and uveitis demonstrated an increased risk of ACS compared to those without uveitis (adjusted hazard ratio: 1.675, p

PurposeDiabetic macular edema (DME) is a common cause of vision impairment and blindness in patients with diabetes. However, vision loss can be prevented by regular eye examinations during primary care. This study aimed to design an artificial intelligence (AI) system to facilitate ophthalmology referrals by physicians.MethodsWe developed an end-to-end deep fusion model for DME classification and hard exudate (HE) detection. Based on the architecture of fusion model, we also applied a dual model which included an independent classifier and object detector to perform these two tasks separately. We used 35,001 annotated fundus images from three hospitals between 2007 and 2018 in Taiwan to create a private dataset. The Private dataset, Messidor-1 and Messidor-2 were used to assess the performance of the fusion model for DME classification and HE detection. A second object detector was trained to identify anatomical landmarks (optic disc and macula). We integrated the fusion model and the anatomical landmark detector, and evaluated their performance on an edge device, a device with limited compute resources.ResultsFor DME classification of our private testing dataset, Messidor-1 and Messidor-2, the area under the receiver operating characteristic curve (AUC) for the fusion model had values of 98.1, 95.2, and 95.8%, the sensitivities were 96.4, 88.7, and 87.4%, the specificities were 90.1, 90.2, and 90.2%, and the accuracies were 90.8, 90.0, and 89.9%, respectively. In addition, the AUC was not significantly different for the fusion and dual models for the three datasets (p = 0.743, 0.942, and 0.114, respectively). For HE detection, the fusion model achieved a sensitivity of 79.5%, a specificity of 87.7%, and an accuracy of 86.3% using our private testing dataset. The sensitivity of the fusion model was higher than that of the dual model (p = 0.048). For optic disc and macula detection, the second object detector achieved accuracies of 98.4% (optic disc) and 99.3% (macula). The fusion model and the anatomical landmark detector can be deployed on a portable edge device.ConclusionThis portable AI system exhibited excellent performance for the classification of DME, and the visualization of HE and anatomical locations. It facilitates interpretability and can serve as a clinical reference for physicians. Clinically, this system could be applied to diabetic eye screening to improve the interpretation of fundus imaging in patients with DME.

PurposeAnkylosing spondylitis (AS) is a risk factor for acute coronary syndrome (ACS). However, the influence of infectious insults, such as endophthalmitis, on the risk of ACS among AS patients has not been studied yet. In this study, we aimed to investigate the relationship between endophthalmitis in patients with AS and the incidence of ACS.MethodsThis retrospective cohort study extracted medical records from the Taiwan Longitudinal Health Insurance Database (LHID) from January 1, 2000, to December 31, 2015. The primary outcome was the incidence of ACS. Univariate and multivariate Cox regression analyses with and without Fine and Gray’s competing risk model and Kaplan–Meier survival curve were used for the analyses. Spearman’s rank correlation coefficient was performed for sensitivity analysis.ResultsWe identified 530 AS patients with endophthalmitis and 2,120 AS patients without endophthalmitis for comparison. The incidence rate of endophthalmitis in our study population was 2.66%. The overall incidence rate of ACS was 1,595.96 per 100,000 person-years in AS patients with endophthalmitis and 953.96 per 100,000 person-years in AS patients without endophthalmitis (adjusted HR = 1.787; 95% CI: 1.594–2.104, p < 0.001). In comparison to those without comorbidities, higher adjusted HRs were found in AS patients with endophthalmitis and comorbidities such as diabetes mellitus, hyperlipidemia, hypertension, cerebrovascular accident, congestive heart failure, chronic obstructive pulmonary disease, asthma, and coronary artery disease. Besides, the age ≥ 60 years revealed a high risk for ACS in AS patients with endophthalmitis.ConclusionEndophthalmitis was found to be an independent risk factor for ACS in patients with AS. Further clinical studies are required to elucidate the underlying mechanisms and status of systemic inflammation during endophthalmitis.

Proliferative vitreoretinopathy (PVR) progression is associated with TGF-β2-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells. In cancer cells, miR-4516 downregulates orthodenticle homeobox 1 (OTX1)-mediated cell invasion. Moreover, OTX1 is shown to be involved in invasion and EMT. The purpose of this study was to assess whether microRNA (miR-4516) suppresses EMT in RPE cells. EMT features were assessed using Western blotting, immunocytochemical staining, scratch-wound healing, modified Boyden chamber assay, and collagen gel contraction assay. For in vivo testing, a rabbit model was used, which involved induction of PVR by injection of transfected spontaneously arising RPE (ARPE) cells into the vitreous chamber. The putative target of miR-4516 was identified by luciferase reporter assay. Results showed that TGF-β2-induced transdifferentiation and migration of RPE cells was inhibited by miR-4516 delivery. Overexpression of miR-4516 led to upregulation of zonula occludens-1, downregulation of α-smooth muscle actin and vimentin, and cell contractility-all EMT features-in the TGF-β2-treated ARPE-19 cells. MiR-4516 regulated OTX1 expression negatively by binding to its 3'-UTR. TGF-β2-induced phosphorylated ERK was inhibited in miR-4516-overexpressing ARPE-19 cells. MiR-4516 suppressed experimental PVR in vitro and in vivo. In conclusion, the overexpression of miR-4516 suppresses TGF-β2-induced EMT in a PVR model, and its role in PVR depends on OTX1/ERK. Further research is needed to develop a feasible treatment method to prevent and treat PVR.

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory disease. Excess cardiovascular risks were well recognized in patients with AS and were attributed to prolonged systemic inflammation. Uveitis is one of the most common extra-articular symptoms of AS and is also considered an indicator of systemic inflammation. This study aimed to investigate whether uveitis was a risk factor for developing acute myocardial infarction (AMI) in patients with AS using the National Health Insurance Research Database (NHIRD).MethodsData were collected from the NHIRD over a fifteen-year period. Variables were analyzed using the Pearson chi-square test and Fisher’s exact test. Risk factors for the occurrence of AMI were examined by calculating hazard ratio. Kaplan-Meier analysis was performed to compare the cumulative incidence of AMI in the uveitis and non-uveitis cohorts.ResultsA total of 5905 patients with AS were enrolled, including 1181 patients with uveitis (20%) and 4724 patients without uveitis (80%). The Kaplan–Meier method with the log-rank test showed that the uveitis group had a significantly higher cumulative hazard for patients with AMI than the non-uveitis group (p < 0.001). The adjusted hazard ratio (aHR) of AMI was higher in the uveitis group than in the non-uveitis group (aHR = 1.653, p < 0.001). Stratified analysis revealed that patients with uveitis had an increased risk of developing AMI regardless of their sex (male/female aHR = 1.688/1.608, p < 0.001). Patients with uveitis in all age groups were independently associated with an increased risk of developing AMI compared to those without uveitis (20–39 years/40–59 years/≥ 60 years, aHR = 1.550, 1.579, 3.240, p < 0.001). Patients with uveitis had a higher probability of developing AMI regardless of comorbidities. Uveitis patients with comorbidities had a higher risk of developing AMI compared to uveitis patients without comorbidities.ConclusionUveitis is a significant risk factor for developing AMI in patients with AS. Physicians should be aware of the potential cardiovascular risk in AS patients with uveitis, especially simultaneously with other traditional risk factors of AMI. Further prospective studies are needed to elucidate the underlying mechanism between uveitis and AMI in patients with AS.

Background: Ischemic optic neuropathy (ION) is a possible extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD). We investigate the relation between IBD and ION and possible risk factors associated with their incidence.Methods: Medical records were extracted from the National Health Insurance Research Database (NHIRD) from January 1, 2000, to December 31, 2013. The main outcome was ION development. Univariate and multivariate Cox regression analyses were performed.Results: We enrolled 22,540 individuals (4,508 with IBD, 18,032 without). The cumulative risk of developing ION was significantly greater for patients with IBD vs. patients without (Kaplan–Meier survival curve, p = 0.009; log-rank test). Seven (5%) and five (0.03%) patients developed ION in the IBD and control groups, respectively. Patients with IBD were significantly more likely to develop ION than those without IBD [adjusted hazard ratio (HR) = 4.135; 95% confidence interval: 1.312–11.246, p = 0.01]. Possible risk factors of ION development were age 30–39 years, diabetes mellitus (DM), hypertension, ischemic heart disease (IHD), atherosclerosis, and higher Charlson comorbidity index revised (CCI_R) value.Conclusion: Patients with IBD are at increased risk of subsequent ION development. Moreover, for patients with comorbidities, the risk of ION development is significantly higher in those with IBD than in those without.

The purpose of this study was to assess whether microRNA (miR)-1285 can suppress the epithelial-mesenchymal transition (EMT) in retinal pigment epithelial cells. Expression of miR-1285 was evaluated using quantitative real-time polymerase chain reaction (RT-qPCR). The features of EMT were assessed using Western blotting, immunocytochemical staining, scratch wound healing tests, modified Boyden chamber assay, and collagen gel contraction assay. A rabbit model of proliferative vitreoretinopathy (PVR) was used for in vivo testing, which involved the induction of PVR by injection of transfected ARPE cells into the vitreous chamber. Luciferase reporter assay was performed to identify the putative target of miR-1285. The expression of miR-1285 was downregulated in ARPE-19 cells treated with transforming growth factor (TGF)-β. Overexpression of miR-1285 led to upregulation of zonula occludens-1, downregulation of α-smooth muscle actin and vimentin, cell migration and cell contractility-all EMT features-in the TGF-β2-treated ARPE-19 cells. The reporter assay indicated that the 3' untranslated region of Smad4 was the direct target of miR1285. PVR progression was alleviated in the miR-1285 transfected rabbits. In conclusion, overexpression of miR-1285 attenuates TGF-β2-induced EMT in a rabbit model of PVR, and the effect of miR-1285 in PVR is dependent on Smad4. Further research is warranted to develop a feasible therapeutic approach for the prevention and treatment of PVR.

PurposeTo 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).MethodsA 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.ResultsIn 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).ConclusionsGlcN 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.

We evaluated the clinical utility of ultra-widefield imaging as an adjunctive tool for training resident ophthalmologists in the detection of retinal breaks. This was a prospective study conducted at a secondary health care center (Tri-Service General Hospital) in Taiwan. Participants were 44 patients (53 eyes) who were referred to our hospital after being diagnosed with retinal breaks. Patients first underwent an indirect ophthalmoscopy examination of the total fundus without scleral depression by our junior (first and second year) or senior (third and fourth year) resident ophthalmologist and then underwent an ultra-widefield imaging examination with a central image and four gaze-steered (up, down, nasal, and temporal) images to determine the number of retinal breaks in the total fundus and the four quadrants. Of the total 53 eyes, 31 were examined by junior residents and 22 were examined by senior residents. In the group of junior residents, ultra-widefield imaging was significantly better at detecting retinal breaks of the total fundus (49 vs. 33 retinal breaks, p < 0.001) and the temporal quadrant (17 vs. 10 retinal breaks, p = 0.018) than indirect ophthalmoscopy. In the group of senior residents, there was no significant difference in the ability to detect retinal breaks in the total fundus or each of the four quadrants with ultra-widefield imaging or indirect ophthalmoscopy. Our results indicate that, compared to indirect ophthalmoscopy, ultra-widefield imaging with a central image and four gaze-steered images has a better performance and is a useful adjunct tool for the detection of retinal breaks in junior resident training. Additionally, it could be a useful method for teaching indirect ophthalmoscopy examination to junior residents.

Aims: The purpose of this study was to investigate the effects of glucosamine (GlcN) on hydrogen peroxide (H2O2)-induced premature senescence in human retinal pigment epithelial (RPE) cells in vitro. Materials and Methods: We analyzed the cell viability of H2O2-treated human RPE cells by the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate assay. The effect of GlcN on the intracellular levels of reactive oxygen species (ROS) in H2O2-treated human RPE cells was examined by the fluorescent dye 2′, 7′-dichlorodihydrofluorescein diacetate. The effect of GlcN on the stress-induced premature senescence (SIPS) in H2O2-treated human RPE cells was evaluated by senescence-associated β-galactosidase (SA-β-Gal) staining. We quantified the effect of GlcN on the protein levels of p21 in H2O2-treated human RPE cells by western blotting. Results: H2O2reduced the cell viability of human RPE cells. H2O2induced the increase of intracellular ROS, whereas GlcN reduced the increase of intracellular ROS due to H2O2treatment in human RPE cells. GlcN reduced the SIPS in H2O2-treated human RPE cells and reduced the increase of the p21 protein level in H2O2-treated human RPE cells. Conclusions: GlcN attenuates the oxidative stress caused by H2O2on the increase of ROS and the induction of SIPS in human RPE cells, at least in part, by suppressing the p21 pathway. These effects may contribute to the GlcN-mediated antioxidative effects in the eye in age-related macular degeneration.

PurposeWe assessed whether mitomycin-C (MMC) has different antifibrotic mechanisms in trabeculectomy wound healing.MethodsWe identified 2 concentrations of MMC as "low-dose" by using WST-1 assay, Lactic dehydrogenase assay, and fluorescence-activated cell sorting flow cytometry. Senescence-associated β-galactosidase (SA-β-gal) and fibrotic gene expression was examined through immunocytochemistry, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, Western blotting, zymography, and modified scratch assay in vitro. In vivo, 0.1 mL of MMC or normal saline was injected to Tenon's capsule before trabeculectomy in a rabbit model. SA-β-gal expression, apoptotic cell death, and collagen deposition in sites treated and not treated with MMC were evaluated using terminal dUTP nick end labeling assay and histochemical staining. Bleb function and intraocular pressure (IOP) levels were examined 3, 7, 14, 21, 28, and 35 days after trabeculectomy.ResultsIn vitro, human Tenon's fibroblast (HTF) senescence was confirmed by observing cell morphologic change, SA-β-gal accumulation, formation of senescence-associated heterochromatin, increased p16INK4a and p21CIP1/WAF1 expression, lower percentage of Ki-67-positive cells, and decreased COL1A1 release. Increased expression of α-SMA, COL1A1, and Smad2 signaling in TGF-β1-induced stress fibers were passivated in senescent HTFs. In addition, cellular migration enhanced by TGF-β1was inactivated. In vivo, histological examination indicated increased SA-β-gal accumulation, lower apoptosis ratios, and looser collagen deposition in sites treated with 0.2 μM MMC. Low-dose MMC-induced cellular senescence prolonged trabeculectomy bleb survival and reduced IOP levels in a rabbit model.ConclusionLow-dose MMC-induced cellular senescence is involved in the antifibrotic mechanism of trabeculectomy wound healing.

Background and Objectives: This case report discusses possible causes of chorioretinal fold (CRF) formation. Materials and Methods: A case report. Results: A 48-year-old man presented with a history of high myopia and primary open-angle glaucoma in both eyes. He underwent a trabeculectomy followed by phacoemulsification in both eyes. Two months later, he complained of blurred vision in the right eye. The intraocular pressure (IOP) was 17 mmHg in the left eye and 9 mmHg in the right eye. Refraction showed a hyperopic shift in both eyes. Slit-lamp examination showed a deep anterior chamber without cells and a well-functional bleb without leakage. Fundus examination revealed CRFs in the macula of the right eye. No papilledema, choroidal lesions, or other retinal lesions were found. Wrinkling of CRFs at the macula, an increase in central foveal thickness, and a fluid cleft were demonstrated by spectral-domain optical coherence tomography. After using steroid eye drops, the IOP in the right eye and refraction in both eyes recovered to the baseline level. Visual acuity improved in both eyes. Conclusions: CRFs in trabeculectomized eyes with normal IOP after phacoemulsification have not been reported. This case demonstrated that the trabeculectomized eye remains at risk of CRF formation, even if the IOP is normal without hypotony. The importance of a detailed fundus examination in patients with unexplained blurred vision may be necessary after having undergone these procedures. The early recognition of the cause of visual loss may facilitate immediate treatment and may avoid irreversible changes with permanent visual loss.

Choroid metastasis is the initial presentation of pleomorphic carcinoma (PC) of the lung. PC is classified as poorly differentiated non-small cell lung carcinoma. It has a tendency to metastasize early and has a poor response to chemotherapy, which often results in poor prognosis. We report the case of a 63-year-old woman with a one-month history of deteriorating vision in the left eye. Fundus examination, fluorescein angiography, indocyanine green angiography, and B-scan sonography demonstrated choroidal metastasis of the left eye. Positron emission tomography/computed tomography (PET/CT) revealed a tumor with increased uptake in the left upper lung. Subsequent bronchoscopic biopsy confirmed a pleomorphic carcinoma of the lungs. Choroid metastasis as an initial presentation of PC in the lung is rare. Usually, it represents the late course of disseminated disease with hematogenous spread. Prompt diagnosis is imperative for patients to immediately initiate treatment.

Scar formation can cause the failure of glaucoma filtration surgery. We investigated the effect of AR12286, a selective Rho-associated kinase inhibitor, on myofibroblast transdifferentiation and intraocular pressure assessment in rabbit glaucoma filtration surgery models. Cell migration and collagen contraction were used to demonstrate the functionality of AR12286-modulated human conjunctival fibroblasts (HConFs). Polymerase chain reaction quantitative analysis was used to determine the effect of AR12286 on the production of collagen Type 1A1 and fibronectin 1. Cell migration and collagen contraction in HConFs were activated by TGF-β1. However, compared with the control group, rabbit models treated with AR12286 exhibited higher reduction in intraocular pressure after filtration surgery, and decreased collagen levels at the wound site in vivo. Therefore, increased α-SMA expression in HConFs induced by TGF-β1 could be inhibited by AR12286, and the production of Type 1A1 collagen and fibronectin 1 in TGF-β1-treated HConFs was inhibited by AR12286. Overall, the stimulation of HConFs by TGF-β1 was alleviated by AR12286, and this effect was mediated by the downregulation of TGF-β receptor-related SMAD signaling pathways. In vivo results indicated that AR12286 thus improves the outcome of filtration surgery as a result of its antifibrotic action in the bleb tissue because AR12286 inhibited the TGF-β receptor-related signaling pathway, suppressing several downstream reactions in myofibroblast transdifferentiation.

Ischemia-reperfusion (I/R) injury is associated with numerous retinal diseases, such as diabetic retinopathy, acute glaucoma, and other vascular retinopathies. Hypercapnic acidosis (HCA) has a protective effect on lung, myocardial, and central nervous system ischemic injury models. However, no study has evaluated its protective effects in an experimental retinal I/R injury model. In this study, retinal I/R injury was induced in Sprague Dawley rats by elevating the intraocular pressure to 110 mmHg for 60 minutes. HCA was induced before and after the injury. After 24 hours, the terminal dUTP nick end labeling assay was performed. Moreover, the ratios of cleaved caspase-3/total caspase-3, phosphorylated IκB/IκB, and phosphorylated p38 were measured through Western blotting. After 7 days, the rats' aqueous humor was analyzed. In addition, electroretinography and retinal thickness measurement were performed in the rats. Moreover, the retinal neural cell line RGC-5 was exposed to 500 μM H2O2 for 24 hours to induce a sustained oxidative stress in vitro. The effects of HCA were evaluated by comparing oxidative stress, MAPK signals, NF-κB signals, survival rates, and apoptosis rates in the RGC-5 cells before and after H2O2 exposure. We further investigated whether the potent I/R-protective heat shock protein (HSP) 32 contribute to protective effects of HCA. Our results indicated that HCA has protective effects against retinal I/R injury both in vivo and in vitro, at multiple levels, including antiapoptotic, anti-inflammatory, antioxidative, and functional retinal cell protection. Further research clarifying the role of HCA in retinal I/R injury prevention and treatment is warranted.

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.

The objective of this study was to evaluate the effects of silibinin on cell proliferation in platelet-derived growth factor (PDGF)-treated human Tenon's fibroblasts (HTFs). The effect of silibinin on cell proliferation in PDGF-treated HTFs was determined by examining the expression of proliferating cell nuclear antigen (PCNA) and performing WST-1 assays. Cell cycle progression was evaluated using flow cytometry. The related cyclins and cyclin-dependent kinases (CDKs) were also analyzed using western blot. A modified rat trabeculectomy model was established to evaluate the effect of silibinin on cell proliferation in vivo. Western blot analysis was carried out to determine the effect of silibinin on the expression of PDGF receptor and on the downstream signaling pathways regulated by PDGF receptor. PDGF elevated the expression of PCNA in HTFs, and this elevation was inhibited by silibinin. The inhibitory effect of silibinin on cell proliferation was also confirmed via WST-1 assay. PDGF-stimulated cell cycle in HTFs was delayed by silibinin, and the related cyclin D1 and CDK4 were also suppressed by silibinin. In the rat model of trabeculectomy, silibinin reduced the expression of PCNA at the site of blebs in vivo. The effects of silibinin on PDGF-stimulated HTFs were mediated via the downregulation of PDGF receptor-regulated signaling pathways, such as ERKs and STATs, which may be partially caused by the downregulation of N-glycosylation of PDGF receptor beta (PDGFRβ). The effect of silibinin on modulation of N-glycosylation of PDGFRβ was mediated in a proteasome-dependent manner. Silibinin inhibited cell proliferation and delayed cell cycle progression in PDGF-treated HTFs in vitro. PDGF also modulated the process of N-glycosylation of the PDGFRβ in a proteasome-dependent manner. Our findings suggest that silibinin has potential therapeutic applications in glaucoma filtering surgery.

BACKGROUND: To evaluate the efficacy of Ahmed Glaucoma Valve (AGV) surgery and the optimal interval between penetrating keratoplasty (PKP) and AGV implantation in a population of Asian patients with preexisting glaucoma who underwent PKP. METHODOLOGY/PRINCIPAL FINDINGS: In total, 45 eyes of 45 patients were included in this retrospective chart review. The final intraocular pressures (IOPs), graft survival rate, and changes in visual acuity were assessed to evaluate the outcomes of AGV implantations in eyes in which AGV implantation occurred within 1 month of post-PKP IOP elevation (Group 1) and in eyes in which AGV implantation took place more than 1 month after the post-PKP IOP evaluation (Group 2). Factors that were associated with graft failure were analyzed, and the overall patterns of complications were reviewed. By their final follow-up visits, 58% of the patients had been successfully treated for glaucoma. After the operation, there were no statistically significant differences between the groups with respect to graft survival (p = 0.98), but significant differences for IOP control (p = 0.049) and the maintenance of visual acuity (VA) (p21 mm Hg. The most common surgical complication, aside from graft failure, was hyphema. CONCLUSIONS/SIGNIFICANCE: Early AGV implantation results in a higher probability of AGV survival and a better VA outcome without increasing the risk of corneal graft failure as a result of post-PKP glaucoma drainage tube implantation.

Background: We evaluated the association between glaucoma and fracture risk in a retrospective cohort of individuals with (n = 3,810) and without (n = 3,810) glaucoma, matched 1:1 for age, sex, and index year obtained using Taiwan's National Health Insurance Research Database. Methods: Patients with glaucoma were categorized into three groups reflecting the glaucoma severity: no more than two types of medical treatment, more than two types of medical treatment, and surgery. Data were analyzed using Cox proportional hazard regression models. Results: During a mean follow-up period of 11.6 years, 750 participants with and 711 without glaucoma developed fractures. Glaucoma was significantly associated with increased fracture risk (adjusted HR [aHR] = 1.18, p = 0.005), particularly in the foot (aHR = 1.25, p < 0.001), femur (aHR = 1.24, p = 0.021), and hip (aHR = 1.30, p = 0.001), but not in the upper limbs and axial skeleton. Those who received more than two types of medical treatment showed a significant association with a higher fracture risk than did those who received no more than two types of medical treatment (aHR = 1.231, p = 0.026). However, patients with surgery showed a significant association with lower fracture risk than those who received medical treatment, with almost the same risk as that of patients without glaucoma. Conclusion: Glaucoma seems independently associated with increased fracture risk, especially lowerlimb fractures. In patients receiving medical treatment for glaucoma, a higher degree of severity of glaucoma was significantly associated with higher fracture risk. The fracture risk was decreased in those with severe glaucoma warranting surgery. This is the first nationwide study concerning the epidemiological correlation between two diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]