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We present an unusual case of uveitis secondary to avelumab and pembrolizumab in a 39-year-old Taiwanese male with stage IV clear cell renal cell carcinoma (ccRCC) and lung metastasis, who initially received pembrolizumab as his primary treatment. However, the patient experienced skin and liver immune-related adverse events (irAEs) after the seventh dose of pembrolizumab, which prompted a switch to avelumab. The patient began to experience gradual blurring of vision after completing the fifth cycle of avelumab immunotherapy. Ophthalmic examinations revealed findings consistent with bilateral anterior uveitis. Despite an initial lack of significant improvement with steroid treatment, the patient's vision and inflammation improved upon discontinuation of avelumab. Due to the occurrence of uveitis, avelumab was switched back to pembrolizumab. However, three months after initiating pembrolizumab, the patient developed foggy vision and bilateral anterior uveitis with cystoid macular edema (CME). The administration of topical, oral, and subconjunctival steroids resulted in an improvement in vision and the resolution of CME, without the need to discontinue pembrolizumab. Over the subsequent eighteen months, there has been no recurrence of uveitis, and there is no evidence of relapse or further metastasis in his ccRCC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate whether intravitreal aflibercept was safe and effective in patients with acute nonarteritic anterior ischemic optic neuropathy (NAION). Methods: This was a chart study of 25 individuals with acute NAION (25 eyes). An intravitreal injection of 2 mg/0.05 mL of aflibercept was administered to fifteen participants. The remaining ten patients in the control group were given standard care. The researchers measured the initial visual acuity, retinal nerve fiber layer thickness (RNFLT), and automated perimetry. During the follow-up period, the researchers measured the final visual acuity, RNFLT, automated perimetry, and side effects. Results: Visual acuity and visual field assessment were significantly improved in the study group, and optical coherence tomography testing demonstrated significant disc edema resolution. The therapy results differed significantly between the two groups regarding visual outcomes (F = 0.027, p = 0.039) and RNFLT decrease (F = 5.507, p = 0.003). However, the difference in visual field alterations was not significant (F = 0.724, p = 0.387). Conclusions: Intravitreal injection of aflibercept can significantly improve visual acuity and resolve disc edema in patients with acute NAION. Intravitreal aflibercept may be an alternative treatment for acute NAION. However, a large series investigation is needed to assess the long-term therapeutic benefit and safety of intravitreal aflibercept in patients with acute NAION. [ABSTRACT FROM AUTHOR]

This retrospective case-control study aimed to investigate associations between disease severity of Alzheimer's dementia (AD) and macular thickness. Data of patients with AD who were under medication (n = 192) between 2013 and 2020, as well as an age- and sex-matched control group (n = 200) with normal cognitive function, were included. AD patients were divided into subgroups according to scores of the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Macular thickness was analyzed via the Early Treatment Diabetic Retinopathy Study (ETDRS) grid map. AD patients had significant reductions in full macula layers, including inner circle, outer inferior area, and outer nasal area of the macula. Similar retinal thinning was noted in ganglion cells and inner plexiform layers. Advanced AD patients (MMSE score < 18 or CDR ≥ 1) showed more advanced reduction of macular thickness than the AD group (CDR = 0.5 or MMSE ≥ 18), indicating that severe cognitive impairment was associated with thinner macular thickness. Advanced AD is associated with significant macula thinning in full retina and inner plexiform layers, especially at the inner circle of the macula. Macular thickness may be a useful biomarker of AD disease severity. Retinal imaging may be a non-invasive, low-cost surrogate for AD. [ABSTRACT FROM AUTHOR]

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1β production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression. [ABSTRACT FROM AUTHOR]

A 25-year-old female with diabetes and hypertension presented with progressive painless blurred vision in her left eye ten days after she received her third dose of the SARS-CoV-2 mRNA vaccine BNT162b2 (Pfizer-BioNTech). The clinical examination confirmed the diagnosis of Central Retinal Vein Occlusion (CRVO) complicated with macular edema. Three doses of anti-vascular endothelial growth factor (VEGF) were injected intravitreally. Visual acuity was improved from 20/100 to 20/30, but recurrence was noted at 6 months. Several cases of retinal vein occlusion (RVO) after COVID-19 vaccination have been reported. However, the present case is the youngest female individual documented to have CRVO after SARS-CoV-2 vaccination. This case demonstrates that the macular edema might be recurrent in patients with risk factors for CRVO who receive SARS-CoV-2 vaccination, suggesting the need for careful consideration of the treatment strategy and close follow-up. Although the definite pathogenesis still needs to be carefully determined, this report highlights the possible association between RVO and mRNA-based COVID-19 vaccination, even in young individuals. [ABSTRACT FROM AUTHOR]

Purpose: Neurodegenerative diseases are associated with neuroinflammation along with activation of microglia and oxidative stress, but currently lack effective treatments. Punicalagin is a natural bio-sourced product that exhibits anti-inflammatory effects on several chronic diseases; however, the anti-inflammatory and anti-oxidative effects on microglia have not been well examined. This study aimed to investigate the effects of punicalagin on LPS-induced inflammatory responses, NLRP3 inflammasome activation, and the production of ROS using murine microglia BV2 cells. Methods: BV2 cells were pre-treated with punicalagin following LPS treatment to induce inflammation. The secretion of NO and PGE2 was analyzed by Griess reagent and ELISA respectively, while the expressions of iNOS, COX-2, STAT3, ERK, JNK, and p38 were analyzed using Western blotting, the production of IL-6 was measured by ELISA, and the activity of NF-κB was detected using promoter reporter assay. To examine whether punicalagin affects NLRP3 inflammasome activation, BV2 cells were stimulated with LPS and then treated with ATP or nigericin. The secretion of IL-1β was measured by ELISA. The expressions of NLRP3 inflammasome-related proteins and phospho IκBα/IκBα were analyzed using Western blotting. The production of intracellular and mitochondrial ROS was analyzed by flow cytometry. Results: Our results showed that punicalagin attenuated inflammation with reduction of pro-inflammatory mediators and cytokines including iNOS, COX-2, IL-1β, and reduction of IL-6 led to inhibition of STAT3 phosphorylation by LPS-induced BV2 cells. Punicalagin also suppressed the ERK, JNK, and p38 phosphorylation, attenuated NF-κB activity, inhibited the activation of the NLRP3 inflammasome, and reduced the production of intracellular and mitochondrial ROS by LPS-induced BV2 cells. Conclusion: Our results demonstrated that punicalagin attenuated LPS-induced inflammation through suppressing the expression of iNOS and COX-2, inhibited the activation of MAPK/NF-κB signaling pathway and NLRP3 inflammasome, and reduced the production of ROS in microglia, suggesting that punicalagin might have the potential in treating neurodegenerative diseases. Graphical [ABSTRACT FROM AUTHOR]

This article analyzes the macular choroidal thickness in normal Taiwanese eyes using enhanced depth imaging optical coherence tomography (EDI OCT). The study includes 295 eyes of 295 normal Taiwanese subjects and examines the relationships between choroidal thickness and various clinical parameters. The results show that age and spherical equivalent refractive error (SERE) have a significant correlation with macular choroidal thickness, while gender and axial length (AL) do not. The study also finds that choroidal thickness decreases with age and is thinner in individuals with myopia. These findings highlight the importance of identifying clinical risk factors for macular choroidal thinning in order to preserve eye vision effectively. [Extracted from the article]

Purpose. To evaluate the long-term anatomic and functional outcomes of autologous neurosensory retinal free flap transplantation (ART) for patients with refractory large macular hole (MH). Design. Retrospective interventional case series. Methods. We reviewed 9 patients who underwent ART for their refractory large MH. In this extended follow-up study, postoperative assessment including spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) were recorded at 12, 15, 18, 21, and 24 months after surgery. Results. The macular hole of all patients appeared successfully closed during the whole follow-up period. The mean logMAR BCVA improved from 1.61 ± 0.44 (preoperative) to 0.72 ± 0.30 (12 months after surgery) (p < 0.001). Thereafter, the mean BCVA remained stable at each follow-up. At the mean 16.0 ± 0.8 months postoperatively, inner retinal cystic changes were observed in 4 eyes (44.4%), but these did not significantly affect vision. Conclusion. ART is a good alternative technique for closing large refractory macular holes. Although inner retinal cystic changes were observed in 4 eyes (44.4%), this phenomenon did not significantly affect visual acuity. It provides long-term good anatomical and functional results, especially in cases where insufficient ILM or lens capsule are left. [ABSTRACT FROM AUTHOR]

Background andObjectives: This 10-year multicenter retrospective study reviewed the clinical manifestations, diagnostic tests, and treatment modalities of tubercular uveitis (TBU), including direct infection and indirect immune-mediated hypersensitivity to mycobacterial antigens in Taiwan. Materials and Methods: This retrospective chart review of patients with TBU was conducted at 11 centers from 1 January 2008 to 31 December 2017. We used a multiple regression model to analyze which factors influenced best-corrected visual acuity (BCVA) improvement. Results: A total of 79 eyes from 51 patients were included in the study. The mean age was 48.9 ± 16.4 years. The mean change of LogMAR BCVA at last visit was −0.21 ± 0.45. Diagnostic tools used include chest X-ray, chest computed tomography, Mantoux test, interferon gamma release test (QuantiFERON-TB Gold test), intraocular fluid tuberculosis polymerase chain reaction, and bronchial alveolar lavage. The clinical manifestations included 48% posterior uveitis and 37% panuveitis. In the sample, 55% of the cases were bilateral and 45% unilateral. There was 60.76% retinal vasculitis, 35.44% choroiditis, 21.52% serpiginous-like choroiditis, 17.72% vitreous hemorrhage, 12.66% posterior synechiae, 6.33% retinal detachment, and 3.80% choroidal granuloma. Treatment modalities included rifampicin, isoniazid, pyrazinamide, ethambutol, oral steroid, posterior triamcinolone, non-steroidal anti-inflammatory drugs, vitrectomy, and immunosuppressants. BCVA improved in 53.2% of eyes and remained stable in 32.9% of eyes. In the final model of multiple regression, worse initial BCVA, pyrazinamide, and receiving vitrectomy predicted better BCVA improvement. Ethambutol was associated with worse visual outcomes. Seven eyes experienced recurrence. Conclusions: This is the largest 10-year multicenter retrospective study of TBU in Taiwan to date, demonstrating the distribution of clinical manifestations and clinical associations with better treatment outcomes. The study provides a comprehensive description of TBU phenotypes in Taiwan and highlights considerations for the design of further prospective studies to reliably assess the role of ATT and vitrectomy in patients with TBU. [ABSTRACT FROM AUTHOR]

Amantadine hydrochloride (HCl) is commonly prescribed for treating influenza A virus infection and Parkinson's disease. Recently, several studies have indicated that the use of amantadine HCl is associated with corneal edema; however, the cytotoxic effect of amantadine HCl has not been investigated. In the present study, the effects of amantadine HCl on cell growth, proliferation, and apoptosis in bovine cornea endothelial cells, and in vitro endothelial permeability were examined. Results showed that lower doses of amantadine HCl do not affect cell growth (≤ 20 μΜ), whereas higher doses of amantadine HCl inhibits cell growth (≥ 50 μΜ), induces apoptosis (2000 μΜ), increases sub-G1 phase growth arrest (2000 μΜ), causes DNA damage (≥ 1000 μΜ), and induces endothelial hyperpermeability (≥ 1000 μΜ) in bovine cornea endothelial cells; additionally, we also found that amantadine HCl attenuates the proliferation (≥ 200 μΜ) and arrests cell cycle at G1 phase (≥ 200 μΜ) in bovine cornea endothelial cells. In the present study, we measured the cytotoxic doses of amantadine HCl on cornea endothelial cells, which might be applied in evaluating the association of corneal edema. [ABSTRACT FROM AUTHOR]

Fluorescein angiography showed disc edema with dye leakage (OD; Figure 1C) and a single point of hyperfluorescence with focal area of retinal pigment epithelium (RPE) decompensation over the temporal superior vessel arcade (OS; Figure 1D). At the visit of six-week follow-up, the disc edema (OD) and the serous detachment (OS) were both reduced (Figure 1E,F) with best corrected visual acuity (BCVA) restored to 20/20 (OD) and 20/25 (OS). (A) Initial fundus photography of the right eye shows optic disc edema. [Extracted from the article]

Acute retinal pigment epitheliitis (ARPE) is a rare, transient macular disorder affecting healthy young adults. We describe the morphologic appearance of the retina by spectral-domain optical coherence tomography (SD-OCT) and to evaluate both the anatomic changes and the functional visual acuity changes over time in the course of disease. A 35-year-old healthy male presented with 1-week history of sudden-onset bilateral central scotoma with blurry vision. He denied trauma, excessive sun exposure, or drug abuse history or alkyl nitrites before. The medical and ocular examinations were unremarkable. The best-corrected visual acuity (BCVA) was 20/200 (OU) at the initial visit. Slit-lamp examination result was normal. Fundus examination revealed subfoveal yellowish lesions with a halo-like pigment in both eyes. The SD-OCT imaging showed subtle disruption of the retinal pigment epithelium (RPE) and abnormal hyperreflectivity throughout the full thickness of the foveola in both eyes. Six weeks later, the BCVA improved to 20/30 (OU) without any treatment. Six months later, the BCVA observed deteriorated to 20/50 (OU). SD-OCT demonstrated ellipsoid zone and cone outer segment tips line defects at the fovea with sharply defined borders. One year later from the initial visit, the BCVA improved to 20/20 (OU), but persisted macular microhole presents on the SD-OCT. The patient was followed for 1 year without any treatment. Thereafter, we noted that in the case of poor initial visual acuity, external limiting membrane, or outer nuclear layer involvement, as determined by SD-OCT, at the baseline might need longer time for visual acuity. The natural course of ARPE may involve the demonstration of a minor outer retinal defect that is similar to a macular microhole. In ARPE, like SD-OCT findings, the location of the initial lesion is the photoreceptor outer segments. It is not just limited to the RPE. [ABSTRACT FROM AUTHOR]

Purpose: To describe a case of Cytomegalovirus (CMV) retinitis in both eyes complicated with unilateral corneal endotheliitis in an iatrogenic immunocompromised patient.Methods: A retrospective case report.Result: A 58-year-old male, on long-term immunosuppressive treatment for chronic glomerulonephritis and nephrotic syndrome. Ocular examination revealed bilateral vitritis and necrotizing retinitis and concurrent corneal endotheliitis with ocular hypertension in his left eye. The PCR result showed positivity for CMV infection by diagnostic aqueous aspiration. Vitritis/retinitis in both eyes resolved gradually after systemic valganciclovir use, and the endotheliitis in the left eye regressed after topical antiviral treatment. There was no recurrence of retinitis/endotheliitis with a maintenance dose of oral valganciclovir. Unfortunately, tractional macular hole developed in the left eye and complicated the visual outcome.Conclusion: CMV retinitis may occur in HIV-negative immunocompromised individuals, but CMV endotheliitis generally appears in the immunocompetent. It is a rare combination of CMV retinitis and endotheliitis in this patient. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the functional and anatomical outcome of the 0.7 mg dexamethasone (Ozurdex) intravitreal implant (IVD) in eyes with long-term macular edema after macular epiretinal membrane removal. Methods. We enrolled 40 eyes with persistent macular edema at least 12 months after epiretinal membrane removal. Twenty eyes in the IVD group received IVD and the other 20 eyes were in the control group. The main outcome measures were change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT). Results. For eyes in the IVD group, the mean BCVA improved by 3.45 lines to 0.47 logMAR one month after IVD. However, the mean BCVA improved by only 0.14 lines to 0.74 logMAR at the same time in eyes in the control group. Six months later, the mean BCVA improved to 0.31 and 0.74 logMAR in the IVD and control groups, respectively. In the IVD group, the mean CFT decreased rapidly by 116.8 μm to 333.9 μm one month after IVD. Thereafter the CFT decreased at a slower pace. In the control group, the CFT remained static during the follow-up period. However, in the IVD group, 6 months after IVD, the CFT seemed to have a tendency to increase. Conclusions. Single IVD could significantly decrease macular edema and improve visual outcome for eyes with persistent long-term macular edema after macular ERM removal and the effect can be sustained as long as 6 months after the initial injection. However, in order to maintain the visual and anatomical outcome, repeat IVD might be considered if macular edema recurs. [ABSTRACT FROM AUTHOR]

Abstract: Noninfectious uveitis is a sight-threatening disease with an autoimmune or autoinflammatory basis. Systemic treatment is required if intraocular inflammation threatens a patient's vision or cannot be controlled locally and when it is associated with systemic rheumatic diseases. Corticosteroids and immunomodulatory chemotherapy are the conventional initial treatments. However, the various side effects of these therapies increase the burden on patients, not only physically but also mentally. Moreover, uncontrolled inflammation and poor visual outcomes have sometimes been recorded despite the combination of these medications or their high dosage. Antitumor necrosis factor-alpha (anti-TNF-α) and other biologic agents have been widely used to treat rheumatic diseases for >15 years. Randomized controlled clinical trials have demonstrated that anti-TNF-α can reduce and delay episodes of intraocular inflammation not only in patients with active uveitis but also in corticosteroid-dependent patients with inactive uveitis. The Taiwan Food and Drug Administration approved the use of adalimumab, an anti-TNF-α agent, for treating nonanterior noninfectious uveitis (NANIU) in 2017. This report provides a recommendation and a proposed stepladder approach for using anti-TNF-α agents to treat NANIU in Taiwan. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the morphological and functional outcomes of idiopathic epiretinal membrane (ERM) surgery between three different surgical techniques: ERM peeling only, whole-piece ILM peeling, and maculorrhexis ILM peeling. Patients and Methods. This is a retrospective, consecutive, and comparative study enrolling 60 patients from Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Surgery performed between July 2011 and June 2012 was done with ERM peeling only (group I). ERM peeling and ILM peeling as a whole piece (group II) were performed between July 2012 and July 2013. Surgery performed between August 2013 and December 2014 was done with maculorrhexis ILM peeling (group III). Main outcome measures include visual acuity change (BCVA) and central foveal thickness (CFT). Results. At 12 months postoperation, the mean BCVA in group III was significantly better than in group I and group II. Comparison of CFT reduction between the three groups revealed significantly more reduction in group III than in group II at all postoperative follow-up periods. Eyes with restoration of foveal depression were observed in 52.6% in group I, 52.4% in group III, but only 20% of eyes in group II. None of the eyes in both ILM peeling groups encountered recurrence of macular pucker formation. Conclusion. All three techniques can achieve visual acuity improvement and macular thickness reduction. Maculorrhexis ILM peeling achieves more rapid improvement of visual function, better final visual outcome, and a higher rate of normal foveal contour than whole-piece ILM peeling. [ABSTRACT FROM AUTHOR]

Hypoxia-induced retinal neovascularization plays a central role in the pathogenesis of diabetic retinopathy. This study aimed to investigate whether hypoxia leads to the release of nuclear high mobility group box 1 (HMGB1) peptides from cultured retinal pigment epithelial ARPE-19 cells, to determine the effect of HMGB1 on angiogenic cytokine production and elucidate the involved signaling pathways. A chemical hypoxia mimetic agent, cobalt chloride, induced SIRT1 downregulation, HMGB1 nucleocytoplasmic relocation and extracellular release from ARPE-19 cells, implicating its autocrine function. Resveratrol treatment significantly reduced secretion of HMGB1 from ARPE-19 cells exposed to hypoxia. Cell proliferation and cell cycle analyses demonstrated that exogenous HMGB1 caused significant growth suppression and G1 cell cycle arrest in ARPE-19 cells. Morphological observations showed that HMGB1 enhanced adhesion, but suppressed migration of ARPE-19 cells. More intriguingly, HMGB1 up-regulated expression of angiofibrogenic factors in ARPE-19 cells, including VEGF, bFGF, TGF-β2, and CTGF. Signal profiling characterization indicated that HMGB1 triggered hyperphosphorylation of Akt, p38 MAPK, and NF-κB, but not that of ERK, JNK, and Smad2, whereas inhibition of PI3K, MAPK, or NF-κB significantly attenuated the HMGB1-driven cytokine overproduction in ARPE-19 cells. Functional neutralization with anti-TLR4 and -RAGE antibodies confirmed that both receptors were involved in the cytokine overproduction. In conclusion, chemically-mimicked hypoxia induced nucleocytoplasmic relocation and release of HMGB1 peptides, which in turn up-regulated the production of angiofibrogenic factors in RPE cells, thereby contributing to the pathogenesis of hypoxia-associated diabetic retinopathies. Conversely, blockades of intraocular HMGB1 bioavailability or signal activation may prevent angiofibrogenesis in development of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

• Magnolol extracted from Magnolia Officinalis has anti-tumor properties • Magnolol promotes miR-200c-3p expression in retinoblastoma • miRNA-200c-3p inhibits EMT progression through Wnt16/β-catenin/ZEB1/E-cadherin axis • Magnolol could be used as adjuvant drug in chemotherapy to treat retinoblastoma Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3–4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear. The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, β-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo. Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/β-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma. Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effect of three consecutive intravitreal bevacizumab injections (IVB) on long-term outcome for patients with macular edema after epiretinal membrane (ERM) removal. Methods: All patients in both the treatment and control groups had persistent macular edema 3 months after ERM removal. The patients in the treatment group received three consecutive IVB in an interval of approximately 4 weeks. The main outcome measures included logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) and central foveal thickness (CFT) determined by optical coherence tomography. Results: Two weeks after the first IVB, CFT decreased significantly by 24.1 ± 4.2 μm in the treatment group versus 4.2 ± 2.1 μm in the control group (p < 0.001). However, the mean reduction in CFT after 12 months did not differ significantly between the two groups (35.2 ± 4.9 vs. 33.7 ± 4.6 μm, p = 0.824). No significant differences were found for logMAR BCVA between the two groups at each follow-up. Conclusion: IVB could significantly decrease macular edema 2 months after the initial injection but failed to make significant differences in final CFT and logMAR BCVA. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β2 (TGF-β2) has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), due to its ability to stimulate the overproduction of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), and remodeling of the extracellular matrix (ECM). Although intravitreal triamcinolone acetonide (TA) is clinically useful in the treatment of PVR and PDR, its molecular mechanism has yet to be fully elucidated. The present study investigated whether TA treatment altered TGF-β2-driven biological effects on the behavior of cultured human retinal pigment epithelial (RPE) cells, in order to determine which signaling pathway may be essential for the pharmacological action of TA. The R-50 human RPE cell line was treated with TA in the presence of TGF-β2, followed by analyses of cell viability and contraction using cell viability and collagen gel contraction assays. VEGF mRNA expression and protein production were measured using reverse transcription-quantitative PCR and ELISA, respectively. The phosphorylation status of signaling mediators and the protein expression of type I collagen (COL1A1), α-smooth muscle actin (α-SMA), and ECM-remodeling enzymes, including MMP-2 and MMP-9, were analyzed using western blotting. The gelatinolytic activity of MMPs was detected using gelatin zymography. TA treatment exhibited no prominent cytotoxicity but markedly antagonized TGF-β2-induced cytostatic effects on RPE cell viability and TGF-β2-enhanced contractility in collagen gels. In the context of TGF-β2-related signaling, TA significantly attenuated TGF-β2-elicited Smad2, extracellular-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Moreover, TA markedly mitigated TGF-β2-induced VEGF upregulation through ablation of p38 signaling activity. TA also partially attenuated TGF-β2-elicted expression of COL1A1, α-SMA, MMP-2, and MMP-9, but only suppressed TGF-β2-induced MMP-9 gelatinolytic activity. Mechanistically, the MEK/ERK signaling pathway may have a critical role in the TGF-β2-induced upregulation of COL1A1, α-SMA and MMP-9. In conclusion, TA may be considered a useful therapeutic agent for treating TGF-β2-associated intraocular angiogenesis and tissue remodeling, the underlying mechanism of which may involve the ERK and p38 MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Background/purpose: To evaluate the clinical manifestations, prognosis, recurrence rate and development of multiple sclerosis between papillitis group and retrobulbar group in Taiwanese patients with isolated acute optic neuritis (AON) after treatment with intravenous methylprednisolone pulse therapy.Methods: We retrospectively reviewed patients with AON who had received intravenous methylprednisolone pulse therapy. These patients were classified into retrobulbar or papillitis groups. Demographic characteristics, responsiveness to pulse therapy, recurrence rate and incidence of multiple sclerosis were compared between these two groups.Results: Of the 43 patients enrolled in this study, 19 patients (44%) were in the retrobulbar group and 24 patients (56%) were in the papillitis group. Seven cases (16%) showed periventricular plaque on magnetic resonance imaging (MRI). Among these seven patients, five developed definite or probable multiple sclerosis. The incidence of multiple sclerosis in patients with positive brain MRI findings was significantly higher than in patients with negative MRI findings (p = 0.002). There was no statistical difference in final visual acuity between the two group (p = 0.353). Sixteen patients suffered from recurrence of AON (21% in the papillitis group and 58% in the retrobulbar group, p = 0.029). Two patients (8%) in the papillitis group and six patients (32%) in the retrobulbar group developed multiple sclerosis (p = 0.061) with a mean interval of 21.6 +/- 11.2 months.Conclusion: AON in Taiwan has a relatively lower percentage of development of multiple sclerosis than in Western countries. The presence of periventricular plaque on MRI is significantly associated with the later development of multiple sclerosis. The retrobulbar group had a stronger association with recurrence and development of multiple sclerosis. [ABSTRACT FROM AUTHOR]

It has been reported that retinoic acid (RA) may inhibit the growth of RPE and be used in the treatment of proliferative vitreoretinopathy (PVR). However, previous reports in this field have been conflicting. The main reason for these contradictory findings is that different methods for evaluating the effects of RA on RPE from different species have been used. In human specimens, only RPE from the donor eye (stationary) but not RPE from the PVR membrane (already at active proliferation status) have been tested. This study tested the effects of RA on the growth of RPE using a novel in vitro model: RPE from the PVR membranes, which simulates the in vivo situation of PVR patients better than RPE from the donor eyes. This study also used various methods to solve the conflicting results reported previously. We found that both all transretinoic acid (all-RA) and 13-cis-retinoic acid (cis-RA) can promptly (though not completely) inhibit proliferation of RPE (inhibition rate of 89%-90%) over a very wide range of concentrations (10-9-10-5 M) and various lengths of periods (2-12 days) in a dosedependent and time-dependent manner and without evident cytotoxic effects. Previously reported disadvantages discovered from the study of RPE from donor eyes, e.g., the absence of inhibitory effects on the early passages of cultured cells and inhibition occurring only after long-term treatment, do not present in RPE cells from the PVR membrane. The proliferation of RPE recovered from the inhibition by RA rapidly after the discontinuation of treatment, indicating that a continuous supply of the drug over a long period, i.e., until the breakdown of the blood-retinal barrier has been repaired, is essential for the success of drug treatment of PVR. [ABSTRACT FROM AUTHOR]

This study investigated the regulatory role of microRNA 100 (miR-100) in hydrogen peroxide (H2O2)-induced apoptosis of human retinal pigment epithelial ARPE-19 cells. H2O2 induced oxidative cell death of cultured ARPE-19 cells was measured by cytotoxicity assay. qRT-PCR was used to quantify cytosolic and extracellular contents of miR-100. Kinase and miR-100 inhibition treatments were applied to determine the regulatory signaling pathways involved in cell death regulation. H2O2 dose-dependently reduced viability of ARPE-19 cells and simultaneously upregulated miR-100 levels in both cytosolic and extracellular compartments. Western blotting detection indicated that H2O2 elicited hyperphosphorylation of PI3K/Akt, ERK1/2, JNK, p38 MAPK, and p65 NF-κB. Further kinase inhibition experiments demonstrated that PI3K, p38 MAPK, and NF-κB activities were involved in oxidative-stress-induced miR-100 upregulation in ARPE-19 cells, while blockade of PI3K, JNK, and NF-κB signaling significantly attenuated the oxidative cell death. Intriguingly, MiR-100 antagomir treatment exerted a cytoprotective effect against the H2O2-induced oxidative cell death through attenuating the oxidation-induced AMPK hyperphosphorylation, restoring cellular mTOR and p62/SQSTM1 levels and upregulating heme oxygenase-1 expression. These findings support that miR-100 at least in part mediates H2O2-induced cell death of ARPE-19 cells and can be regarded as a preventive and therapeutic target for retinal degenerative disease. [ABSTRACT FROM AUTHOR]

There is currently a lack of guidelines with regard to tubercular uveitis (TBU) management in Taiwan. We therefore propose an evidence-based consensus on the management for TBU. The Taiwan Ocular Inflammation Society conducted a meeting that included nine ophthalmologist and one infection disease expert that focused on three broad areas of (1) nomenclature for TBU, (2) assessment and diagnosis for TBU, and (3) treatment of TBU. Brief literature review on TBU diagnosis and management was conducted that informed this panel meeting in order to make decisions on each consensus statements. In terms of our results, a consensus statements and recommendations for the diagnosis and management of TBU were developed. This consensus statement provides an algorithmic approach toward diagnosing and managing TBU. These statements are meant to enhance but not replace individual clinician–patient interactions and to facilitate real-world clinical practice improvement in terms of TBU patients care. [ABSTRACT FROM AUTHOR]