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1.
Mediators Inflamm ; 2013: 863036, 2013.
Article in English | MEDLINE | ID: mdl-23766563

ABSTRACT

To test the hypothesis that brain-derived neurotrophic factor-(BDNF-) mediated neuroprotection is reduced by high-mobility group box-1 (HMGB1) in diabetic retina, paired vitreous and serum samples from 46 proliferative diabetic retinopathy and 34 nondiabetic patients were assayed for BDNF, HMGB1, soluble receptor for advanced glycation end products (sRAGE), soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and TBARS. We also examined retinas of diabetic and HMGB1 intravitreally injected rats. The effect of the HMGB1 inhibitor glycyrrhizin on diabetes-induced changes in retinal BDNF expressions was studied. Western blot, ELISA, and TBARS assays were used. BDNF was not detected in vitreous samples. BDNF levels were significantly lower in serum samples from diabetic patients compared with nondiabetics, whereas HMGB1, sRAGE, sICAM-1, and TBARS levels were significantly higher in diabetic serum samples. MCP-1 levels did not differ significantly. There was significant inverse correlation between serum levels of BDNF and HMGB1. Diabetes and intravitreal administration of HMGB1 induced significant upregulation of the expression of HMGB1, TBARS, and cleaved caspase-3, whereas the expression of BDNF and synaptophysin was significantly downregulated in rat retinas. Glycyrrhizin significantly attenuated diabetes-induced downregulation of BDNF. Our results suggest that HMGB1-induced downregulation of BDNF might be involved in pathogenesis of diabetic retinal neurodegeneration.


Subject(s)
Brain-Derived Neurotrophic Factor/blood , Diabetic Retinopathy/blood , HMGB1 Protein/pharmacology , Adult , Aged , Aged, 80 and over , Animals , Blotting, Western , Chemokine CCL2/metabolism , Diabetic Retinopathy/drug therapy , Enzyme-Linked Immunosorbent Assay , Female , Glycyrrhizic Acid/therapeutic use , Humans , Intercellular Adhesion Molecule-1/metabolism , Male , Middle Aged , Oxidative Stress/drug effects , Rats, Sprague-Dawley , Young Adult
2.
Ocul Immunol Inflamm ; 21(6): 468-74, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23734940

ABSTRACT

PURPOSE: To assess long-term efficacy and safety of infliximab for refractory Behçet disease (BD) uveitis and to evaluate the effect of withdrawal of infliximab after achieving long-term remission. METHODS: Retrospective study of 19 patients. RESULTS: Mean follow-up was 44.1 ± 36.5 months and mean number of infliximab infusions was 21.6 ± 14.6. At end of follow-up, there was significant improvement of visual acuity and reduction of central macular thickness. All patients achieved remission, 14 of whom were able to discontinue corticosteroids. Ten patients developed autoantibodies and 1 patient developed infusion reactions. Eight eyes underwent intraocular surgery without exacerbation of quiescent uveitis. After achieving complete remission, 5 patients discontinued infliximab and maintained remission during a mean of 24.6 ± 5.5 months. CONCLUSIONS: Infliximab is effective and safe for long-term treatment for refractory BD uveitis. Repeated infusions are required to maintain long-term remission, which may be sustained despite withdrawal of infliximab. Induction of autoantibodies is common.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Behcet Syndrome/complications , Uveitis, Posterior/drug therapy , Adolescent , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , Child , Female , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Humans , Infliximab , Infusions, Intravenous , Male , Remission Induction , Retrospective Studies , Time Factors , Tomography, Optical Coherence , Treatment Outcome , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Uveitis, Posterior/diagnosis , Uveitis, Posterior/etiology , Visual Acuity , Young Adult
3.
J Diabetes Res ; 2013: 539658, 2013.
Article in English | MEDLINE | ID: mdl-23671874

ABSTRACT

This study was conducted to determine levels of angiogenic and endothelial progenitor cell mobilizing (vasculogenic) factors in vitreous fluid from proliferative diabetic retinopathy (PDR) patients and correlate their levels with clinical disease activity. Vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), stem cell factor (SCF), soluble c-kit (s-kit), endothelial nitric oxide synthase (eNOS), and prostaglandin E2 (PGE2) levels were measured by ELISA in vitreous samples from 34 PDR and 15 nondiabetic patients. eNOS was not detected. VEGF, sVEGFR-2, SCF, and s-kit levels were significantly higher in PDR with active neovascularization compared with quiescent PDR and nondiabetic patients (P < 0.001; 0.007; 0.001; <0.001, resp.). In contrast, PGE2 levels were significantly higher in nondiabetic patients compared with PDR patients (P < 0.001). There were significant correlations between levels of sVEGFR-2 versus SCF (r = 0.950, P < 0.001), sVEGFR-2 versus s-kit (r = 0.941, P < 0.001), and SCF versus s-kit (r = 0.970, P < 0.001). Our findings suggest that upregulation of VEGF, sVEGFR-2, SCF, and s-kit supports the contributions of angiogenesis and vasculogenesis in pathogenesis of PDR.

4.
Acta Ophthalmol ; 91(6): e486-93, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23575246

ABSTRACT

PURPOSE: To determine prognostic factors in patients with Vogt-Koyanagi-Harada (VKH) disease who were treated with high-dose corticosteroids. METHODS: Retrospective analysis of 87 patients (174 eyes). RESULTS: At presentation, there were 53 patients with initial-onset acute VKH disease and 34 patients with chronic recurrent VKH disease. Chronic recurrent presentation was significantly associated with more severe anterior segment inflammation at presentation as indicated by presence of mutton-fat keratic precipitates, anterior chamber reaction ≥2+, iris nodules and posterior synechiae (p < 0.001 for all comparisons), less exudative retinal detachment at presentation (p < 0.001), more complications during the follow-up period (p < 0.001) and a worse visual outcome (p < 0.001). The use of immunomodulatory therapy (cyclosporine and mycophenolate mofetil) as first-line therapy significantly reduced the development of complications in the whole study group (p = 0.006) and in initial-onset acute group (p = 0.024) and improved visual outcome in the whole study group (p = 0.004) and in chronic recurrent group (p = 0.024). In the whole study group, final visual acuity of 20/20 was significantly associated with good initial visual acuity of >20/200 [odds ratio = 4.25; 95% Confidence interval (CI) = 1.53-11.89] and age older than 16 years was significantly associated with the development of complications (odds ratio = 3.15; 95% CI = 1.04-9.48). CONCLUSIONS: Chronic recurrent VKH disease is significantly associated with more severe anterior segment inflammation and less exudative retinal detachment at presentation, more ocular complications and a worse visual outcome than initial-onset acute VKH disease. Use of immunomodulatory therapy significantly improved the clinical outcomes.


Subject(s)
Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/analogs & derivatives , Uveomeningoencephalitic Syndrome/drug therapy , Acute Disease , Adolescent , Adult , Child , Child, Preschool , Chronic Disease , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Drug Therapy, Combination , Female , Fluorescein Angiography , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Prognosis , Recurrence , Retrospective Studies , Treatment Outcome , Uveomeningoencephalitic Syndrome/diagnosis , Visual Acuity , Young Adult
5.
Acta Diabetol ; 50(3): 363-71, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22864860

ABSTRACT

The proinflammatory lysophosphatidic acid (LPA) is a potent activator of several transcriptional factors and signaling pathways and a potent modulator of genes involved in inflammation, angiogenesis and fibrosis. This study was conducted to measure the levels of LPA and LPA-producing enzymes, autotaxin (ATX) and acylglycerol kinase (AGK) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the level of vascular endothelial growth factor (VEGF). In addition, we examined the expression of ATX, AGK and VEGF receptor-2 (VEGFR-2) in the retinas of diabetic rats. Vitreous samples from 42 PDR and 35 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blot analysis. VEGF, LPA and AGK levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p < 0.001 for all comparisons). ATX levels in PDR with active neovascularization and inactive PDR were significantly lower than those in nondiabetic patients (p = 0.045). Mean VEGF and AGK levels in PDR with active neovascularization were significantly higher than those in inactive PDR and nondiabetic patients (p < 0.001 for both comparisons). A significant correlation was observed between levels of VEGF and levels of AGK in PDR patients (r = 0.954; p < 0.001). Western blot analysis revealed a significant increase in the expression of AGK and VEGFR-2 in vitreous samples and the retinas of diabetic rats compared to nondiabetic controls, whereas ATX was significantly downregulated. Our findings suggest that ATX-AGK-LPA signaling axis might be an important player in the development and progression of diabetic retinopathy.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/metabolism , Lysophospholipids/metabolism , Phosphoric Diester Hydrolases/metabolism , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Biomarkers/metabolism , Disease Models, Animal , Female , Humans , Male , Middle Aged , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Vitreous Body/metabolism , Young Adult
6.
Acta Diabetol ; 50(4): 545-51, 2013 Aug.
Article in English | MEDLINE | ID: mdl-21947384

ABSTRACT

We determined the levels of the endogenous angiogenesis inhibitors soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), thrombospondin (TSP)-1 and TSP-2 in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and correlated their levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF). Vitreous samples from 30 PDR and 25 nondiabetic patients were studied by enzyme-linked immunosorbent assay. TSP-1 was not detected. VEGF and TSP-2 levels were significantly higher in PDR with active neovascularization compared with inactive PDR and nondiabetic patients (P < 0.001 for both comparisons). VEGF, sVEGFR-1 and TSP-2 levels were significantly higher in PDR with hemorrhage compared with PDR without hemorrhage and nondiabetic patients (P = 0.0063; 0.0144; <0.001, respectively). VEGF and sVEGFR-1 levels were significantly higher in PDR without traction retinal detachment (TRD) compared with PDR with TRD and nondiabetic patients (P = 0.038; 0.022, respectively). TSP-2 levels were significantly higher in PDR with TRD compared with PDR without TRD and nondiabetic patients (P < 0.001). There was a significant correlation between levels of VEGF and sVEGFR-1 (r = 0.427, P = 0.038). Our findings suggest that upregulation of sVEGFR-1 and TSP-2 may be a protective mechanism against progression of angiogenesis associated with PDR. TSP-2 might be associated with TRD.


Subject(s)
Angiogenesis Inducing Agents/metabolism , Diabetic Retinopathy/metabolism , Vitreous Body/metabolism , Angiogenesis Inducing Agents/analysis , Diabetic Retinopathy/pathology , Humans , Neovascularization, Pathologic , Thrombospondin 1/analysis , Thrombospondin 1/metabolism , Thrombospondins/analysis , Thrombospondins/metabolism , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-1/analysis , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vitreous Body/blood supply , Vitreous Body/chemistry
7.
Mediators Inflamm ; 2012: 697489, 2012.
Article in English | MEDLINE | ID: mdl-23118492

ABSTRACT

The aim of this study was to measure the levels of high-mobility group box-1 (HMGB1) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate its levels with clinical disease activity and the levels of vascular endothelial growth factor (VEGF), the angiogenic cytokine granulocyte-colony-stimulating factor (G-CSF), the endothelial cell angiogenic markers soluble vascular endothelial-cadherin (sVE-cadherin), and soluble endoglin (sEng). Vitreous samples from 36 PDR and 21 nondiabetic patients were studied by enzyme-linked immunosorbent assay. HMGB1, VEGF, sVE-cadherin, and sEng levels were significantly higher in PDR patients than in nondiabetics (P = 0.008; <0.001; <0.001; 0.003, resp.). G-CSF was detected in only 3 PDR samples. In the whole study group, there was significant positive correlation between the levels of HMGB1, and sVE-cadherin (r = 0.378, P = 0.007). In PDR patients, there was significant negative correlation between the levels of sVE-cadherin and sEng (r = -0.517, P = 0.0005). Exploratory regression analysis identified significant associations between active PDR and high levels of VEGF (odds ratio = 76.4; 95% confidence interval = 6.32-923) and high levels of sEng (odds ratio = 6.01; 95% confidence interval = 1.25-29.0). Our findings suggest that HMGB1, VEGF, sVE-cadherin and sEng regulate the angiogenesis in PDR.


Subject(s)
Diabetic Retinopathy/metabolism , Endothelial Cells/metabolism , HMGB1 Protein/metabolism , Vitreous Body/metabolism , Antigens, CD/metabolism , Biomarkers , Cadherins/metabolism , Enzyme-Linked Immunosorbent Assay , Humans , Logistic Models , Neovascularization, Pathologic , Vascular Endothelial Growth Factor A/metabolism
8.
Mediators Inflamm ; 2012: 493043, 2012.
Article in English | MEDLINE | ID: mdl-23055574

ABSTRACT

The aim of this study was to determine the levels of the angiogenic and fibrogenic factors osteopontin (OPN), high-mobility group box-1 (HMGB1), and connective tissue growth factor (CTGF) and the antiangiogenic and antifibrogenic pigment epithelium-derived factor (PEDF) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and rhegmatogenous retinal detachment with no PVR (RD). Vitreous samples from 48 PDR, 17 PVR and 30 RD patients were studied by enzyme-linked immunosorbent assay. OPN, HMGB1, CTGF, and PEDF levels were significantly higher in PDR patients than in RD patients (P < 0.001; 0.002; <0.001; <0.001, resp.). CTGF and PEDF levels were significantly higher in PVR patients than in RD patients (P < 0.001; 0.004, resp.). Exploratory logistic regression analysis identified significant associations between PDR and high levels of HMGB1, CTGF and PEDF, between PDR with active neovascularization and high levels of CTGF and PEDF, and between PDR with traction retinal detachment and high levels of HMGB1. In patients with PDR, there were significant correlations between the levels of PEDF and the levels of OPN (r = 0.544, P = 0.001), HMGB1 (r = 0.719, P < 0.001), and CTGF (r = 0.715, P < 0.001). In patients with PVR, there were significant correlations between the levels of OPN and the levels of HMGB1 (r = 0.484, P = 0.049) and PEDF (r = 0.559, P = 0.02). Our findings suggest that OPN, HMGB1, and CTGF contribute to the pathogenesis of proliferative vitreoretinal disorders and that increased levels of PEDF may be a response to counterbalance the activity of angiogenic and fibrogenic factors in PDR and PVR.


Subject(s)
Neovascularization, Pathologic/metabolism , Osteopontin/metabolism , Vitreoretinopathy, Proliferative/metabolism , Connective Tissue Growth Factor/metabolism , Eye Proteins/metabolism , HMGB1 Protein/metabolism , Humans , Nerve Growth Factors/metabolism , Serpins/metabolism , Vitreous Body/metabolism
9.
Acta Ophthalmol ; 90(8): e603-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22971163

ABSTRACT

PURPOSE: To study the effectiveness of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. The outcomes in this group were compared with those of another group of patients with VKH disease who were treated with corticosteroid monotherapy or with delayed addition of immunomodulatory therapy. METHODS: This prospective study included 19 patients (38 eyes) diagnosed with acute uveitis associated with VKH disease. RESULTS: The mean follow-up period was 27.0 ± 11.1 months (range 16-54 months). Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering prednisone to 10 mg or less daily was 5.1 ± 1.2 months (range 3-7 months). Ten (53%) patients discontinued treatment without relapse of inflammation. The mean time observed of treatment was 17.3 ± 11.9 months (range 3-41.5 months). Visual acuity of 20/20 was achieved by 38% of the eyes in the corticosteroid group and by 74% in the corticosteroid + MMF group (p < 0.001). Recurrent inflammation of ≥3 times was reduced significantly (p = 0.0383) in the corticosteroid + MMF group (3%) as compared to corticosteroid group (18%). Development of all complications was significantly higher in the corticosteroid group (43%) compared with the corticosteroid + MMF group (8%) (p < 0.001). None of the eyes in the corticosteroid + MMF group developed 'sunset glow fundus'. CONCLUSIONS: Addition of MMF as first-line therapy to corticosteroids in patients with acute uveitis associated with VKH disease leads to significant reduction in recurrences of uveitis and development of late complications and significantly improves visual outcome.


Subject(s)
Glucocorticoids/therapeutic use , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/analogs & derivatives , Uveitis, Posterior/drug therapy , Uveomeningoencephalitic Syndrome/drug therapy , Acute Disease , Administration, Oral , Adolescent , Adult , Child , Coloring Agents , Drug Therapy, Combination , Female , Fluorescein Angiography , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Indocyanine Green , Infusions, Intravenous , Male , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Mycophenolic Acid/therapeutic use , Ophthalmoscopy , Prednisone/administration & dosage , Prednisone/therapeutic use , Prospective Studies , Secondary Prevention , Treatment Outcome , Uveitis, Posterior/diagnosis , Uveitis, Posterior/etiology , Uveomeningoencephalitic Syndrome/complications , Uveomeningoencephalitic Syndrome/diagnosis , Visual Acuity/physiology , Young Adult
10.
Cytokine ; 59(2): 377-81, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22583692

ABSTRACT

Aqueous humor (AH) samples from 14 patients with presumed tuberculous uveitis (PTU), and 30 control patients were assayed for the proinflammatory cytokines interleukin IL-4, IL-12, IL-15, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α, the immunosuppressive cytokine IL-10, and the chemokines GRO-α/CXCL1, IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10 and SDF-1/CXCL12 with the use of a multiplex assay. Among cytokines, IL-4 and IL-12 were not detected. IL-15, IL-17, IFN-γ, TNF-α and IL-10 levels in AH were significantly higher in patients than in controls (p<0.001; p=0.004; p<0.001; p<0.001; p<0.001, respectively). Among chemokines, SDF-1 levels did not differ significantly between patients and controls, whereas GRO-α, IL-8, MIG and IP-10 levels were significantly higher in patients than in controls (p=0.001; p<0.001; p<0.001; p<0.001, respectively). Mean GRO-α levels in AH of PTU patients were 6-fold higher than IL-8 levels and mean IP-10 levels were 15-fold higher than MIG levels. Clinical disease activity correlated significantly with the levels of IL-15, IFN-γ, TNF-α and IP-10. Logistic regression analysis demonstrated a significant positive association between PTU and high levels of IFN-γ, IL-8, MIG and IP-10. These data suggest that both T helper (Th) Th(1) and Th(17) cells are involved in PTU and that the cytokine profile is polarized toward a Th(1) response. GRO-α and IP-10 might be involved in neutrophil and activated T lymphocyte chemoattraction in PTU, respectively.


Subject(s)
Aqueous Humor/immunology , Chemokines, CXC/metabolism , Cytokines/metabolism , Tuberculosis/complications , Tuberculosis/immunology , Uveitis/complications , Uveitis/immunology , Adult , Case-Control Studies , Female , Humans , Logistic Models , Male , Middle Aged , Young Adult
11.
Eur J Ophthalmol ; 22(3): 368-75, 2012.
Article in English | MEDLINE | ID: mdl-21928252

ABSTRACT

PURPOSE: To evaluate the effect of immunosuppressive therapy on best-corrected visual acuity (BCVA), fixation stability, and central retinal sensitivity in patients with Vogt-Koyanagi-Harada (VKH) disease in the acute uveitic phase. Methods. In this prospective study, 14 patients (28 eyes) were evaluated. Best-corrected visual acuity and MP-1 microperimetric evaluation of retinal sensitivity in the central 12 degrees and fixation stability were assessed at baseline and at 1, 3, 6, 9, and 12 months after treatment. Results. At baseline, logarithm of the minimum angle of resolution (logMAR) BCVA, fixation stability, and mean retinal sensitivity levels were 0.685 ± 0.6 (Snellen equivalent, 20/100), 61.2% ± 29.0%, and 2.75 ± 3.8 dB, respectively. At 3 months, logMAR BCVA (0.11 ± 0.2, Snellen equivalent 20/25) and fixation stability (86.4% ± 13.4%) were almost maximum (p<0.001 for both comparisons), and thereafter remained almost unchanged. Mean retinal sensitivity continued to improve up to 12 months (12.0 ± 2.3 dB, p<0.001); however, it was still significantly decreased. There were significant correlations between logMAR BCVA and mean retinal sensitivity at all time points. The percentages of BCVA improvement were significantly higher than the percentages of mean retinal sensitivity improvement at all time points (p<0.001 for all comparisons). Conclusions. Compared with microperimetry, BCVA significantly underestimates macular dysfunction in VKH disease.


Subject(s)
Immunosuppressive Agents/therapeutic use , Retina/physiopathology , Uveomeningoencephalitic Syndrome/drug therapy , Uveomeningoencephalitic Syndrome/physiopathology , Visual Acuity/physiology , Visual Field Tests , Adolescent , Adult , Child , Drug Therapy, Combination , Female , Fixation, Ocular/physiology , Fluorescein Angiography , Humans , Indocyanine Green , Male , Methylprednisolone/therapeutic use , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Prednisone/therapeutic use , Prospective Studies , Tomography, Optical Coherence , Young Adult
12.
Mol Vis ; 17: 1829-38, 2011.
Article in English | MEDLINE | ID: mdl-21850157

ABSTRACT

PURPOSE: To measure levels of high-mobility group box -1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the levels of the inflammatory biomarkers monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-1ß (IL-1ß), and granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, we examined the expression of HMGB1 in the retinas of diabetic mice. METHODS: Vitreous samples from 29 PDR and 17 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Retinas of mice were examined by immunofluorescence analysis and western blotting. RESULTS: HMGB1 was detected in all vitreous samples and sRAGE was detected in 5 PDR samples. IL-1ß was detected in 3PDR samples and GM-CSF was not detected. Mean HMGB1 levels in PDR with active neovascularization were twofold and threefold higher than that in inactive PDR and nondiabetic patients, respectively. Mean HMGB1 levels in PDR patients with hemorrhage were significantly higher than those in PDR patients without hemorrhage and nondiabetic patients (p=0.0111). There were significant correlations between levels of HMGB1 and levels of MCP-1 (r=0.333, p=0.025) and sICAM-1 (r=0.548, p<0.001). HMGB1 expression was also upregulated in the retinas of diabetic mice. CONCLUSIONS: Subclinical chronic inflammation might contribute to the progression of PDR.


Subject(s)
Biomarkers/analysis , Diabetes Complications/metabolism , Diabetes Mellitus/metabolism , Diabetic Retinopathy/metabolism , Inflammation/metabolism , Retina/metabolism , Retinal Neovascularization/metabolism , Vitreoretinopathy, Proliferative/metabolism , Vitreous Body/metabolism , Adult , Aged , Animals , Blotting, Western , Chemokine CCL2/analysis , Chemokine CCL2/biosynthesis , Diabetes Complications/pathology , Diabetes Complications/surgery , Diabetes Mellitus/pathology , Diabetes Mellitus/surgery , Diabetic Retinopathy/etiology , Diabetic Retinopathy/pathology , Diabetic Retinopathy/surgery , Enzyme-Linked Immunosorbent Assay , Female , HMGB1 Protein/analysis , HMGB1 Protein/biosynthesis , Humans , Intercellular Adhesion Molecule-1/analysis , Intercellular Adhesion Molecule-1/biosynthesis , Interleukin-1beta/analysis , Interleukin-1beta/biosynthesis , Male , Mice , Mice, Inbred C57BL , Middle Aged , Receptor for Advanced Glycation End Products , Receptors, Immunologic/analysis , Receptors, Immunologic/biosynthesis , Retina/pathology , Retinal Neovascularization/etiology , Retinal Neovascularization/pathology , Retinal Neovascularization/surgery , Vitrectomy , Vitreoretinopathy, Proliferative/etiology , Vitreoretinopathy, Proliferative/pathology , Vitreoretinopathy, Proliferative/surgery , Vitreous Body/pathology , Vitreous Body/surgery
13.
Immunobiology ; 216(9): 1004-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21531038

ABSTRACT

Aqueous humor (AH) samples from patients with Behçet's disease (BD) (n=29), Vogt-Koyanagi-Harada (VKH) disease (n=21), and HLA-B27-associated uveitis (n=8), and 42 control patients were assayed for the neutrophil chemoattractants CXCL1/GRO-α and CXCL8/IL-8 and the lymphocyte chemoattractants CXCL9/MIG, CXCL10/IP-10 and CXCL12/SDF-1 with the use of a multiplex chemokine assay. Chemokine levels except SDF-1 were significantly higher in the 3 disease groups than in normal controls. Considering all patients, mean GRO-α levels were 15-fold higher than IL-8 levels and mean IP-10 levels were 22-fold higher than MIG levels. In patients with the same disease activity, AH levels of GRO-α and IP-10 were significantly higher in patients with BD than in patients with VKH disease and HLA-B27-associated uveitis (p=0.0474; p<0.001, respectively). These data suggest that GRO-α and IP-10 are the predominant CXC chemokines involved in neutrophil and activated T lymphocyte chemoattraction in endogenous uveitis, particularly in BD.


Subject(s)
Aqueous Humor/metabolism , Behcet Syndrome/metabolism , Chemokine CXCL10/biosynthesis , Chemokine CXCL1/biosynthesis , Chemokine CXCL9/biosynthesis , Uveitis/metabolism , Uveomeningoencephalitic Syndrome/metabolism , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adult , Aqueous Humor/immunology , Behcet Syndrome/drug therapy , Behcet Syndrome/immunology , Biomarkers/analysis , Case-Control Studies , Chemokine CXCL1/immunology , Chemokine CXCL10/immunology , Chemokine CXCL9/immunology , Female , Gene Expression , HLA-B27 Antigen/analysis , HLA-B27 Antigen/immunology , Humans , Immunoassay , Lymphocyte Activation/immunology , Lymphocytes/immunology , Lymphocytes/metabolism , Male , Middle Aged , Neutrophils/immunology , Neutrophils/metabolism , Uveitis/drug therapy , Uveitis/immunology , Uveomeningoencephalitic Syndrome/drug therapy , Uveomeningoencephalitic Syndrome/immunology
14.
Clin Immunol ; 139(2): 177-84, 2011 May.
Article in English | MEDLINE | ID: mdl-21334264

ABSTRACT

We assayed aqueous humor (AH) samples from patients with Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, and HLA-B27-associated uveitis and control patients for the proinflammatory cytokines IL-15, IL-17, interferon-γ and tumor necrosis factor-α and the immunosuppressive cytokine IL-10. Cytokine levels were significantly higher in the three disease groups than in controls. In patients with similar disease activity, levels of IL-15 and IFN-γ were significantly higher in BD patients than in VKH and HLA-B27-associated uveitis groups. Logistic regression identified a significant negative correlation between BD and high levels of IL-10 and a significant positive correlation between VKH disease and high levels of IL-10. The proinflammatory cytokines versus IL-10 ratios were significantly higher in BD compared with other groups. These data suggest that both T helper (Th) 1 and Th17 cells are involved in endogenous uveitis immunopathogenesis. BD is characterized by extensive Th1 polarization, severe proinflammatory conditions and a low immunosuppressive status.


Subject(s)
Aqueous Humor/metabolism , Cytokines/metabolism , Uveitis/metabolism , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Adult , Aqueous Humor/drug effects , Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , Behcet Syndrome/immunology , Behcet Syndrome/metabolism , Cyclosporine/administration & dosage , Cyclosporine/pharmacology , Cyclosporine/therapeutic use , Female , HLA-B27 Antigen/genetics , Humans , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-15/metabolism , Interleukin-17/metabolism , Logistic Models , Male , Middle Aged , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Treatment Outcome , Tumor Necrosis Factor-alpha/metabolism , Uveitis/diagnosis , Uveitis/drug therapy , Uveitis/genetics , Uveitis/immunology , Uveomeningoencephalitic Syndrome/diagnosis , Uveomeningoencephalitic Syndrome/immunology , Uveomeningoencephalitic Syndrome/metabolism , Young Adult
16.
Eur J Ophthalmol ; 20(5): 852-7, 2010.
Article in English | MEDLINE | ID: mdl-20815096

ABSTRACT

PURPOSE: To compare central corneal thickness (CCT) measurements obtained using the Pentacam Scheimpflug system with those obtained using DGH ultrasound pachymetry (UP) in post-laser in situ keratomileusis (LASIK) eyes for myopia. METHODS: In a prospective study, measurement agreement was assessed in 143 eyes of 72 post-LASIK patients using both the Pentacam and UP at the Eye Consultants Center in Riyadh, Saudi Arabia. RESULTS: The mean CCT was 522 +/- 42.2 microm with the Oculus Pentacam and 516.2 +/- 40.6 microm with UP. The Bland-Altman plot showed that the mean +/- SD for the differences between the 2 devices was 5.8 +/- 13.6 microm, with 95% confidence interval limits ranging from -20.9 microm to 32.6 microm. A test of statistical significance indicated that the mean differences of 5.8 +/- 13.6 microm differed significantly from zero (p<0.001; Wilcoxon signed-rank test), thus indicating that the Pentacam measurements tended to overestimate CCT compared with UP. Analysis of regression showed a high correlation between the values obtained with both devices (r=0.947, p<0.001). CONCLUSIONS: In post-LASIK myopic eyes, although a high correlation has been shown between Pentacam and UP measurements, Pentacam tends to overestimate CCT compared to UP. Pentacam probably cannot be used interchangeably with UP in post-LASIK eyes for myopia.


Subject(s)
Cornea/pathology , Diagnostic Techniques, Ophthalmological/instrumentation , Keratomileusis, Laser In Situ , Myopia/surgery , Body Weights and Measures , Humans , Microscopy, Acoustic/methods , Photography/methods , Postoperative Period , Prospective Studies
17.
Ocul Immunol Inflamm ; 18(6): 424-31, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20735294

ABSTRACT

PURPOSE: To analyze clinical patterns, causes, and systemic disease associations among patients with uveitis admitted to King Abdulaziz University Hospital. METHODS: The authors retrospectively reviewed the medical records of 351 patients (600 eyes). RESULTS: The study subjects consisted of 183 (52.1%) males and 168 (47.9%) females, with a mean age of 39.9 ± 14.2 years at presentation. The most common anatomic diagnosis was panuveitis (68.6%), followed by posterior uveitis (12.7%), anterior uveitis (12.7%), and intermediate uveitis (6.0%). The most common identifiable specific diagnoses were presumed tuberculous uveitis (PTU) (28.2%), Vogt-Koyanagi-Harada (VKH) disease (19.4%), Behçet disease (BD) (12.5%), and toxoplasmosis (8.2%). After a mean follow-up period of 29.5 ± 22.1 months, 63.5% of the eyes achieved visual acuity of 20/40 or better. Eyes from patients with PTU had the worst final visual outcome. CONCLUSIONS: The most common anatomic diagnosis was panuveitis. PTU, VKH disease, BD, and toxoplasmosis were the most frequent specific diagnoses.


Subject(s)
Hospitalization , Hospitals, University , Uveitis/epidemiology , Uveitis/etiology , Adolescent , Adult , Age Distribution , Aged , Behcet Syndrome/complications , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Panuveitis/epidemiology , Panuveitis/etiology , Prevalence , Retrospective Studies , Saudi Arabia/epidemiology , Sex Distribution , Toxoplasmosis, Ocular , Tuberculosis, Ocular , Uveitis/microbiology , Uveitis/parasitology , Uveitis, Anterior/epidemiology , Uveitis, Anterior/etiology , Uveitis, Intermediate/epidemiology , Uveitis, Intermediate/etiology , Uveitis, Posterior/epidemiology , Uveitis, Posterior/etiology , Uveomeningoencephalitic Syndrome/complications , Young Adult
18.
Ocul Immunol Inflamm ; 18(2): 121-6, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20370342

ABSTRACT

PURPOSE: To identify the microbiological spectrum and visual outcome of bleb-associated endophthalmitis. METHODS: The medical records of patients treated for bleb-associated endophthalmitis were reviewed. RESULTS: Seventy-five patients were identified. Vitreous cultures were positive in 48 (64%) patients. The most common isolates were Streptococcus species in 24 (50%) eyes, gram-negative bacteria in 10 (20.8%) eyes, and Staphylococcus epidermidis in 7 (14.6%) eyes. Good visual outcome was achieved in 33 (44%) patients. On univariate analysis, shorter interval from onset of symptoms and treatment (p = .005), better initial visual acuity (p = .004), clear cornea at presentation (p = .048), isolation of less virulent organisms (p < .001), and absence of diabetes mellitus (p = .048) were significant positive predictors for good visual outcome. CONCLUSIONS: Bleb-associated endophthalmitis is associated with severe visual impairment. Clinical features associated with better visual outcome include early presentation, better presenting visual acuity, clear cornea at presentation, culture of a less virulent organism, and absence of diabetes mellitus.


Subject(s)
Bacteria/classification , Blister/microbiology , Endophthalmitis/microbiology , Eye Infections, Bacterial/microbiology , Visual Acuity , Adolescent , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Bacteria/isolation & purification , Blister/drug therapy , Blister/physiopathology , Child , Child, Preschool , Endophthalmitis/drug therapy , Endophthalmitis/physiopathology , Eye Infections, Bacterial/drug therapy , Eye Infections, Bacterial/physiopathology , Female , Glaucoma/surgery , Humans , Infant , Male , Middle Aged , Retrospective Studies , Saudi Arabia , Treatment Outcome , Young Adult
19.
Eur J Ophthalmol ; 20(1): 201-8, 2010.
Article in English | MEDLINE | ID: mdl-19882538

ABSTRACT

PURPOSE: To identify risk factors for the development of culture-positive endophthalmitis after repair of open globe injuries. METHODS: We retrospectively reviewed the medical records of 629 consecutive patients with open globe injuries admitted to King Abdulaziz University Hospital between May 1996 and January 2008. RESULTS: Endophthalmitis developed in 12 (1.9%) patients. The following factors were significantly associated with endophthalmitis by univariate analysis: delayed presentation (>24 hours) (p=0.008), rural address (p=0.013), and dirty wound (p=0.012). Logistic regression analysis identified dirty wound to be associated with the development of endophthalmitis (odds ratio = 11.6; 95% confidence interval [CI] = 2.67-50.6). On logistic regression analysis, presence of retained intraocular foreign body (IOFB) in association with rural address (odds ratio = 11.0; 95% CI = 1.44-83.3) or dirty wound (odds ratio = 9.2; 95% CI = 1.22-69.1) was associated with development of endophthalmitis. Endophthalmitis was a significant negative predictor for final good visual outcome (p=0.00261) and was significantly associated with hypotony (p=0.033). CONCLUSIONS: Delayed presentation, rural address, and dirty wound were associated with development of endophthalmitis. Retained IOFB in association with rural address or dirty wound was associated with a particularly high risk of endophthalmitis.


Subject(s)
Endophthalmitis/etiology , Eye Infections, Bacterial/etiology , Eye Injuries, Penetrating/surgery , Ophthalmologic Surgical Procedures/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Bacteria/isolation & purification , Child , Child, Preschool , Endophthalmitis/epidemiology , Eye Infections, Bacterial/epidemiology , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Risk Factors , Rural Population/statistics & numerical data , Saudi Arabia , Time Factors , Urban Population/statistics & numerical data
20.
J Cataract Refract Surg ; 35(4): 643-9, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19304084

ABSTRACT

PURPOSE: To estimate the incidence of acute-onset endophthalmitis after cataract surgery and to report its clinical features, microbiology, and final visual outcomes. SETTING: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. METHODS: This was a retrospective observational case series. RESULTS: The 10-year incidence of acute-onset endophthalmitis after cataract surgery was 0.068%: 0.049% for extracapsular cataract extraction (ECCE) and 0.085% for clear corneal phacoemulsification (P = .268). The incidence of endophthalmitis was 0.053% during the first 5 years of the study and 0.08% during the next 5 years. The most common presenting features were pain and poor red reflex. Of the 20 cases, 18 were culture positive. The culture isolates showed Staphylococcus species in 7 eyes (35%), Streptococcus species in 7 eyes (35%), polymicrobial or mixed infections in 3 eyes (15%), and Propionibacterium acnes in 1 eye (5%). Two patients (10%) achieved a final visual acuity of 20/40 or better, 5 (25%) had worse than 20/40 to better than 20/200, and 8 (40%) had worse than 20/200; 5 eyes (25%) were eviscerated. Visual outcomes were good in endophthalmitis cases after phacoemulsification and in cases caused by Staphylococcus epidermidis and worse in cases that had Streptococcus species endophthalmitis. CONCLUSIONS: Clear corneal phacoemulsification had a 1.73-fold higher risk for acute endophthalmitis than ECCE. Although the incidence of endophthalmitis after ECCE was lower than after phacoemulsification, the outcome was much worse in post-ECCE endophthalmitis cases. Poor visual outcomes were associated with more virulent organisms and delayed presentation.


Subject(s)
Bacteria/isolation & purification , Cataract Extraction , Cross Infection/microbiology , Endophthalmitis/microbiology , Eye Infections, Bacterial/microbiology , Visual Acuity/physiology , Acute Disease , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Cross Infection/diagnosis , Cross Infection/drug therapy , Endophthalmitis/diagnosis , Endophthalmitis/drug therapy , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/drug therapy , Female , Humans , Incidence , Lens Implantation, Intraocular , Male , Middle Aged , Postoperative Complications , Retrospective Studies
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