Erythropoietin in Optic Neuropathies: Current Future Strategies for Optic Nerve Protection and Repair.

Erythropoietin (EPO) is known as a hormone for erythropoiesis in response to anemia and hypoxia. However, the effect of EPO is not only limited to hematopoietic tissue. Several studies have highlighted the neuroprotective function of EPO in extra-hematopoietic tissues, especially the retina. EPO could interact with its heterodimer receptor (EPOR/ßcR) to exert its anti-apoptosis, anti-inflammation and anti-oxidation effects in preventing retinal ganglion cells death through different intracellular signaling pathways. In this review, we summarized the available pre-clinical studies of EPO in treating glaucomatous optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy and traumatic optic neuropathy. In addition, we explore the future strategies of EPO for optic nerve protection and repair, including advances in EPO derivates, and EPO deliveries. These strategies will lead to a new chapter in the treatment of optic neuropathy.

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.

AR12286 Alleviates TGF-ß-Related Myofibroblast Transdifferentiation and Reduces Fibrosis after Glaucoma Filtration Surgery.

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-ß1. 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-ß1 could be inhibited by AR12286, and the production of Type 1A1 collagen and fibronectin 1 in TGF-ß1-treated HConFs was inhibited by AR12286. Overall, the stimulation of HConFs by TGF-ß1 was alleviated by AR12286, and this effect was mediated by the downregulation of TGF-ß 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-ß receptor-related signaling pathway, suppressing several downstream reactions in myofibroblast transdifferentiation.

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.

Positron emission tomography/computed tomography scan of Vogt-Koyanagi-Harada syndrome with associated autoimmune thyroid disease: A case report and literature review.

RATIONALE: Vogt-Koyanagi-Harada (VKH) syndrome is a rare disease and could be associated with autoimmune thyroid disease (AITD). This report was aimed to investigate the utility of F-fludeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) for the diagnosis of VKH syndrome with AITD and to perform a literature review on the association between the 2 diseases. PATIENT CONCERNS: A 55-year-old woman without the history of ocular trauma suffered from chronic headache. She was presented with painful blurred vision of both eyes with headache for 2 weeks. Ophthalmic evaluations revealed panuveitis, exudative retinal detachment, and papilloedema in both eyes. The clinical symptoms and presentations are compatible with the diagnosis of VKH syndrome. Other examinations for intraocular infection, malignancy, and lupus choroidopathy were of negative results. The result of contrast-enhanced computed tomography (CT) of the brain was normal. Due to the history of cancer in the patient's families, a F-FDG PET/CT whole-body scan was performed. The result indicated a focal of 2-fluoro-2-deoxy-D-glucose (FDG) uptake at the right upper lobe of the thyroid. Therefore, the patient's thyroid function was examined and the result indicated euthyroidism with detectable thyroid peroxidase/thyroglobulin antibodies. DIAGNOSES: VKH syndrome with associated AITD. INTERVENTIONS: Treatment with intravenous pulse systemic methylprednisolone (1000 mg daily) was prescribed for 3 days and then shifted gradually to tapered oral steroid medication. OUTCOMES: Symptoms of papillitis and serous retinal detachment of VKH syndrome was relieved after steroid treatment LESSONS:: F-fludeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) can be used for the effective diagnosis of VKH syndrome with AITD.

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

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

Sumatriptan-induced angle-closure glaucoma: A case report.

RATIONALE: Drug-induced bilateral angle-closure glaucoma is a rare event and should be treated correctly and promptly to prevent visual loss. PATIENT CONCERNS: We report a rare case of sumatriptan-induced bilateral angle-closure glaucoma in a young woman with migraine, and explore the possible mechanism. DIAGNOSES: We describe the clinical outcome of a patient with sumatriptan-induced bilateral angle-closure glaucoma. The patient presented with bilateral acute elevation of intraocular pressure (IOP) and myopic shift. INTERVENTIONS: The clinical symptoms and signs resolved rapidly after treatment with a topical cycloplegic agent, topical steroid, and aqueous suppressant. OUTCOMES: Based on the suspicious of malignant glaucoma, we prescribed topical phenylephrine, whose application immediately lowered the IOP. All symptoms resolved after treatment with a long-acting cycloplegic agent, topical steroid, and aqueous suppressant for 3 days. LESSONS: We presume that the mechanism underlying sumatriptan-induced bilateral angle-closure glaucoma may be correlated to the malignant glaucoma. Timely diagnosis and appropriate treatment are essential for resolving this ophthalmic emergency.

Resveratrol inhibits transforming growth factor-ß2-induced epithelial-to-mesenchymal transition in human retinal pigment epithelial cells by suppressing the Smad pathway.

Proliferative vitreoretinopathy (PVR) is the main cause of failure following retinal detachment surgery. Transforming growth factor (TGF)-ß2-induced epithelial-to-mesenchymal transition (EMT) plays an important role in the development of PVR, and EMT inhibition decreases collagen gel contraction and fibrotic membrane formation, resulting in prevention of PVR. Resveratrol is naturally found in red wine and has inhibitory effects on EMT. Resveratrol is widely used in cardioprotection, neuroprotection, chemotherapy, and antiaging therapy. The purpose of this study was to investigate the effects of resveratrol on TGF-ß2-induced EMT in ARPE-19 cells in vitro. We found that resveratrol suppressed the decrease of zona occludens-1 (ZO-1) and caused an increase of alpha-smooth muscle actin expression in TGF-ß2-treated ARPE-19 cells, assessed using Western blots; moreover, it also suppressed the decrease in ZO-1 and the increase of vimentin expression, observed using immunocytochemistry. Resveratrol attenuated TGF-ß2-induced wound closure and cell migration in ARPE-19 cells in a scratch wound test and modified Boyden chamber assay, respectively. We also found that resveratrol reduced collagen gel contraction - assessed by collagen matrix contraction assay - and suppressed the phosphorylation of Smad2 and Smad3 in TGF-ß2-treated ARPE-19 cells. These results suggest that resveratrol mediates anti-EMT effects, which could be used in the prevention of PVR.

Silibinin Inhibits Platelet-Derived Growth Factor-Driven Cell Proliferation via Downregulation of N-Glycosylation in Human Tenon's Fibroblasts in a Proteasome-Dependent Manner.

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 (PDGFRß). The effect of silibinin on modulation of N-glycosylation of PDGFRß 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 PDGFRß in a proteasome-dependent manner. Our findings suggest that silibinin has potential therapeutic applications in glaucoma filtering surgery.

A rare manifestation of neuro-ophthalmic sarcoidosis: A case report.

PURPOSE: Anterior uveitis is the most common ocular manifestation of sarcoidosis. Ocular involvement affects approximately 30-60% of patients with systemic sarcoidosis; however, optic disc edema is a rare event. We report a patient who presented with a rare case of sarcoidosis with neuro-ophthalmic manifestations. CASE REPORT: A 22-year-old man was referred to our clinic with the primary complaint of a visual field defect over the temporal side of his right eye of 2 months duration. He did not have a history of systemic disease. At the first ophthalmic examination, the visual acuity, intraocular pressure, and slit lamp examination were normal. The fundus examination revealed bilateral optic disc edema. He was initially suspected of having a choroidal lesion between the disc and fovea of the right eye. To evaluate the possible lesion, the patient underwent brain magnetic resonance imaging (MRI), chest radiography, and chest computed tomography (CT). There were no abnormalities on the brain MRI, but the chest radiographs and CT images revealed bilateral mediastinal and hilar lymphadenomegaly. Histopathologic evaluation of an ultrasound-guided lymph node biopsy confirmed the diagnosis of sarcoidosis. CONCLUSION: Neuro-ophthalmic manifestations of sarcoidosis are rare but may be the only presenting sign of an otherwise occult disease. A high clinical suspicion for sarcoidosis and its inclusion as a differential diagnosis are key to establishing the diagnosis and proper treatment.

Silibinin inhibits ICAM-1 expression via regulation of N-linked and O-linked glycosylation in ARPE-19 cells.

To evaluate the effects of silibinin on intercellular adhesion molecule-1 (ICAM-1) expression, we used ARPE-19 cells as a model in which tumor necrosis factor (TNF-α) and interferon (IFN-γ) enhanced ICAM-1 expression. This upregulation was inhibited by silibinin. In an adherence assay using ARPE-19 and THP-1 cells, silibinin inhibited the cell adhesion function of ICAM-1. The inhibitory effects of silibinin on ICAM-1 expression were mediated via the blockage of nuclear translocation of p65 proteins in TNF-α and phosphorylation of STAT1 in IFN-γ-stimulated cells. In addition, silibinin altered the degree of N-linked glycosylation posttranslationally in ARPE-19 cells by significantly enhancing MGAT3 gene expression. Silibinin can increase the O-GlcNAc levels of glycoproteins in ARPE-19 cells. In a reporter gene assay, PUGNAc, which can also increase O-GlcNAc levels, inhibited NF-κB reporter activity in TNF-α-induced ARPE-19 cells and this process was augmented by silibinin treatment. Overexpression of OGT gene was associated with reduced TNF-α-induced ICAM-1 levels, which is consistent with that induced by silibinin treatment. Taken together, silibinin inhibits ICAM-1 expression and its function through altered O-linked glycosylation in NF-κB and STAT1 signaling pathways and decreases the N-linked glycosylation of ICAM-1 transmembrane protein in proinflammatory cytokine-stimulated ARPE-19 cells.

Efficient downregulation of VEGF in retinal pigment epithelial cells by integrin ligand-labeled liposome-mediated siRNA delivery.

BACKGROUND: The purpose of this study was to demonstrate the effectiveness of an integrin peptide ligand-labeled liposomal delivery system loaded with vascular endothelial growth factor (VEGF)-siRNA in a model study of gene therapy for retinopathy using human retinal pigment epithelial cells. METHODS: Arg(R)-Gly(G)-Asp(D) motif peptide conjugating polyethylene glycol modified (RGD-PEGylated) liposomes were prepared using a thin-film hydration method and optimized for surface charge, particle size, small interfering RNA (siRNA) load, and entrapment efficiency. Reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays were used to determine VEGF levels in retinal pigment epithelial cells. Cytotoxicity was determined using the 3-[4, 5-dimethylthiazol-2-yl]-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and flow cytometry. RESULTS: Physicochemical properties, including particle size, zeta potential, and siRNA load, of the prepared RGD-PEGylated liposomes and their entrapment efficiency were determined to be within the following ranges: 123.8-234.1 nm, 17.31-40.09 m V, 5.27%-6.33%, and >97%, respectively. RGD-PEGylated liposome-mediated fluorescent-labeled siRNA delivery demonstrated significantly enhanced cellular uptake, and 3 mol% RGD-PEGylated liposomes (having 3ß-[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol (DC-cholesterol) DSPE and DSPE-PEG(2000)-RGD with molar ratio of 50/47/3) were shown to have better efficacy with regard to specificity for retinal pigment epithelial cells, reduced cytotoxicity, and knockdown of the target molecule. CONCLUSION: By integrin receptor-mediated endocytosis, 3 mol% RGD-PEGylated liposomes were shown to be a suitable vector when loaded with VEGF-siRNA for efficient downregulation of VEGF in retinal pigment epithelial cells at both the protein and gene levels. This integrin ligand-modified liposomal delivery system has therapeutic potential for ocular gene therapy.

Erythropoietin protects adult retinal ganglion cells against NMDA-, trophic factor withdrawal-, and TNF-α-induced damage.

PURPOSE: This study aimed to evaluate the neuroprotective effect of EPO in the presence of N-methyl-d-aspartate (NMDA)-, trophic factor withdrawal (TFW)-, and tumor necrosis factor-alpha (TNF-α)-induced toxicity on total, small, and large retinal ganglion cells (RGCs). METHODS: Retinal cells from adult rats were cultured in a medium containing brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF), and forskolin. Expression of RGC markers and EPOR was examined using immunocytochemistry. RGCs were classified according to their morphological properties. Cytotoxicity was induced by NMDA, TFW, or TNF-α. RGC survival was assessed by counting thy-1 and neurofilament-l double-positive cells. RESULTS: EPO offered dose-dependent (EC50 = 5.7 ng/mL) protection against NMDA toxicity for small RGCs; protection was not significant for large RGCs. Time-course analysis showed that the presence of EPO either before or after NMDA exposure gave effective protection. For both small and large RGCs undergoing trophic factor withdrawal, EPO at concentrations of 1, 10, or 100 ng/mL improved survival. However, EPO had to be administered soon after the onset of injury to provide effective protection. For TNF-α-induced toxicity, survival of small RGCs was seen only for the highest examined concentration (100 ng/mL) of EPO, whereas large RGCs were protected at concentrations of 1, 10, or 100 ng/mL of EPO. Time-course analysis showed that pretreatment with EPO provided protection only for large RGCs; early post-treatment with EPO protected both small and large RGCs. Inhibitors of signal transduction and activators of transcription such as (STAT)-5, mitogen-activated protein kinases (MAPK)/extracellular-regulated kinase (ERK), and phosphatidyl inositol-3 kinase (PI3K)/Akt impaired the protective effect of EPO on RGCs exposed to different insults. CONCLUSION: EPO provided neuroprotection to cultured adult rat RGCs; however, the degree of protection varied with the type of toxic insult, RGC subtype, and timing of EPO treatment.

The longitudinal changes of the visual field in an Asian population with primary angle-closure glaucoma with and without an acute attack.

PURPOSE: To investigate the longitudinal changes of visual field (VF) in Asian patients with primary angle-closure glaucoma (PACG) occurring with and without an acute attack. METHODS: In this retrospective case series, 87 consecutive patients diagnosed with bilateral PACG during the period from 2000 to 2010 were included. The eyes of the enrolled patients were categorized into 2 groups: PACG with 1 documented episode of an acute episode in the affected eye (APACG); PACG without a previous documented acute episode in the fellow eye (CPACG). The historical change in the VF in both groups was assessed every 3 months for >2 years. RESULTS: Of the 174 eyes included in the study, 87 eyes belonged to the APACG group, and 87 eyes belonged to the CPACG group. The mean deviation (MD) in the APACG group decreased significantly from -6.22 to -6.73 dB between the 6- and 9-month follow-up periods (P=0.03). There were significant differences between the 2 groups in the MD index from the 9- to 24-month follow-up. The corrected pattern standard deviation (CPSD) in the APACG group increased significantly from 3.61 to 3.71 dB between the 6- and 9-month follow-up periods (P=0.04). The CPSD index was higher in the APACG group than in the CPACG group from the 9- to 24-month follow-up, which was a statistically significant difference. CONCLUSIONS: Glaucomatous VF damage in Asian patients with APACG was detected after a 6-month follow-up period, despite the presence of laser peripheral iridotomy in this population. In the patients with CPACG, there was no significant difference in the MD and CPSD during the follow-up period. Patients with APACG would benefit from regular monitoring of the decline in the VF.

Bevacizumab modulates epithelial-to-mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up-regulation.

PURPOSE: To investigate the effect of bevacizumab treatment on connective tissue growth factor (CTGF) expression and the induction of epithelial-to-mesenchymal transition in ARPE-19 cells and human donor retinal pigment epithelium (HRPE) cells in vitro. METHODS: We quantitated the protein and gene expression level of CTGF by ELISA. The effect of Fc-Fc receptor (Fc-FcR) interaction on CTGF expression was evaluated by CD64 siRNA silencing. Expression of epithelial-to-mesenchymal transition markers, alpha-smooth muscle actin (α-SMA) and zona occludens protein (ZO-1) was evaluated by Western blot. Cell migration and collagen gel contraction assay were examined by light microscopy, and collagen production was measured by ELISA. RESULTS: Bevacizumab stimulation increased CTGF expression in ARPE-19 and HRPE cells in a dose-dependent manner. CD64 gene silencing inhibited the effect of bevacizumab-induced CTGF up-regulation. Bevacizumab increased the expression of α-SMA and decreased the expression of ZO-1 in ARPE-19 cells. Bevacizumab also caused the release of type-1 collagen and increased cell migration and contraction of collagen. CONCLUSIONS: Bevacizumab exerts pro-fibrotic effects on human RPE cells at clinical doses by up-regulation of CTGF expression via an Fc-FcR interaction. This effect of bevacizumab may be one of the underlying mechanisms involved in age-related macular degeneration therapy or intravitreal bevacizumab-associated complications.

Early Ahmed glaucoma valve implantation after penetrating keratoplasty leads to better outcomes in an Asian population with preexisting glaucoma.

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) (p<0.05) were observed. One year after surgery, the success rates of IOP control in Group 1 and Group 2 were 80% and 46.7%, respectively, and these rates fell to 70% and 37.3%, respectively, by 2 years. Factors that were associated with a high risk of AGV failure were a diagnosis of preexisting angle-closure glaucoma, a history of previous PKP, and a preoperative IOP that was >21 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.

Laser confocal microscopy is a valuable, non-invasive tool for early diagnosis and characterisation of epithelial nests.

A 22-year-old woman presented with blurred vision and glare in the right eye, which had been present for three months. The patient had undergone laser-assisted in situ keratomileusis nine months previously and enhancement three months thereafter. On ophthalmological examination, visual acuity was 6/8.6 in the right eye and 6/6 in the left eye. An opaque epithelial nest below the flap with a visible demarcation line was detected along the pupil margin in the right eye. Subsequent laser confocal microscopy revealed the presence of epithelial cells in a whorled pattern with irregular astigmatism on corneal topography. Three months later, the clinical symptoms had worsened and a denser and larger wedge-shaped epithelial nest was observed. The nest was scraped. Six months later, the patient exhibited restored visual acuity (6/6) without glare. Laser confocal microscopy is a valuable, non-invasive tool and provides in vivo pathological images for early diagnosis and localisation of lesion depth in epithelial nests to guide appropriate surgical management.

Glucosamine modulates TNF-α-induced ICAM-1 expression and function through O-linked and N-linked glycosylation in human retinal pigment epithelial cells.

PURPOSE: The purpose of this article was to investigate the effects of glucosamine (GlcN) on the TNF-α-induced expression of intercellular adhesion molecule 1 (ICAM-1) and the function of ICAM-1 in ARPE-19 cells in vitro. METHODS: We quantified protein levels of TNF-α-induced ICAM-1 in ARPE-19 cells with Western blotting. The effects of GlcN on O-linked glycosylation, and therefore on ICAM-1 expression, were compared after the addition of alloxan, an inhibitor of O-linked N-acetylglucosamine transferase (OGT), or O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase (O-GlcNAcase [OGA]), or after OGT gene overexpression. The effect of GlcN on the N-linked glycosylation of ICAM-1 was evaluated by the change in its molecular mass on Western blotting. The effect of O-linked glycosylation on the nuclear factor κB (NF-κB) signaling pathway was examined using an NF-κB reporter gene assay. The effect of GlcN on ICAM-1 adhesion activity was examined using an ICAM-1 adhesion assay. RESULTS: GlcN, PUGNAc, and OGT overexpression inhibited TNF-α-induced ICAM-1 expression and NF-κB activity in ARPE-19 cells. Alloxan increased ICAM-1 expression and NF-κB activity in TNF-α-induced ARPE-19 cells. GlcN and tunicamycin reduced the molecular mass of TNF-α-induced ICAM-1 in ARPE-19 cells. The proteasome inhibitor MG-132 suppressed the GlcN-induced reduction in the molecular mass of TNF-α-induced ICAM-1. GlcN also attenuated the adhesion activity of TNF-α-induced ICAM-1. CONCLUSIONS: GlcN inhibits ICAM-1 expression and functions by modulating the O-linked glycosylation of factors involved in NF-κB signaling and by reducing the N-linked glycosylation of TNF-α-induced ICAM-1 in ARPE-19 cells. These effects may contribute to the GlcN-mediated anti-inflammatory effects in the eye.