Lack of association between polymorphism rs540782 and primary open angle glaucoma in Saudi patients.

BACKGROUND: To investigate whether polymorphism rs540782 on chromsome 1, in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene, is a risk factor for primary open angle glaucoma (POAG). METHOD: The study genotyped 92 unrelated POAG cases and 95 control subjects from Saudi Arabia using Taq-Man® assay. RESULTS: The genotype frequency distribution did not deviate significantly from the Hardy-Weinberg equilibrium (p > 0.05). Overall, both the genotype and allele frequencies were not significantly different between cases and controls. The minor 'C' allele frequency was 49.4%, which was comparable to the Japanese population and higher than the Indian and Afro-Caribbean populations. Similarly, no significant association was found between genotypes and systemic diseases and health awareness/behavior domain variables. Importantly, glaucoma specific indices, such as intraocular pressure, cup/disc ratio and number of anti-glaucoma medication, also showed no statistically significant effect of genotypes within POAG cases. CONCLUSION: Polymorphism rs540782 is not a risk factor for POAG in the Saudi cohort.

Intraocular pressure trends after intravitreal injections of anti-vascular endothelial growth factor agents for diabetic macular edema.

PURPOSE: To study intraocular pressure (IOP) trends and risk factors of IOP elevation after intravitreal anti-vascular endothelial growth factor injections in diabetic macular edema. METHODS: A retrospective review of 760 eyes treated with intravitreal anti-vascular endothelial growth factor injections for diabetic macular edema was performed. The rate and risk factors of IOP elevation were assessed. Intraocular pressure elevation was defined as an increase above baseline IOP by ≥ 6 mmHg, increase above baseline by > 20%, or IOP elevation to > 24 mmHg on 2 or more consecutive visits after treatment. When more than one pretreatment IOP reading was available, baseline IOP was calculated as the mean of the available pretreatment IOP readings (up to a maximum of three last IOP readings). Intraocular pressure elevation was considered transient unless it was maintained throughout the follow-up or required treatment (persistent elevation). RESULTS: Over a mean follow-up of 18 months, persistent and transient IOP elevation occurred in 44 (5.8%) and 53 (7%) eyes, respectively. The majority of eyes with persistent IOP elevation (70.4%) showed IOP elevation of > 20% from baseline. Only 13 eyes (1.71%) met the more strict criteria (> 6 mmHg from baseline or an IOP elevation > 24 mmHg). Final IOP was higher in the persistent IOP elevation group than the rest of the eyes (P < 0.001). Only the number of injections was associated with IOP elevation (P < 0.001). CONCLUSION: Persistent IOP elevation after intravitreal anti-vascular endothelial growth factor injections for diabetic macular edema is uncommon but may be associated with a higher number of injections.

Comparisons of choroidal blood flow velocity between initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease and acute central serous chorioretinopathy.

OBJECTIVES: Acute central serous chorioretinopathy (CSC) and Vogt-Koyanagi-Harada (VKH) disease in the acute uveitic phase are characterized by serous retinal detachment caused by dysfunction of the choroid. The aim of this study is to compare blood flow velocity and pulse waveform parameters in the choroid between these two diseases. METHODS: In this study, 25 patients (50 eyes) with VKH disease, 21 patients (27 eyes) with CSC and 15 healthy controls (30 eyes) were studied. Laser speckle flowgraphy (LSFG) was performed at presentation. RESULTS: Choroidal mean blur rate (MBR), representing blood flow velocity in choroidal vessels, was significantly lower in the eyes affected by VKH disease compared with the healthy control and CSC eyes. CSC eyes had a significantly higher MBR compared with healthy controls. Among the analyzed pulse waveform parameters, blow-out time (BOT), falling rate (FR) and flow acceleration index (FAI) changed significantly. BOT value was significantly lower in CSC eyes than in healthy control and VKH eyes. FR and FAI values were significantly lower in VKH eyes than in healthy control and CSC eyes. There was a strong positive correlation between MBR and FAI. CONCLUSIONS: Our findings confirm different pathophysiology of these two diseases. Assessment of choroidal blood flow velocity and haemodynamics with LSFG provides useful information to differentiate acute CSC and initial-onset acute uveitis associated with VKH disease.

High-mobility group box-1 induces decreased brain-derived neurotrophic factor-mediated neuroprotection in the diabetic retina.

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.

Acute endophthalmitis caused by Staphylococcus lugdunesis after intravitreal bevacizumab (Avastin) injection.

PURPOSE: To report a case of culture-positive endophthalmitis after intravitreal injection of bevacizumab (Avastin) resulting in a devastating visual outcome. METHOD: A retrospective case report of a 51-year-old diabetic women who presented with further decrease in her vision, redness, and mild pain in her eye 3 days after intravitreal injection of Avastin for macular edema due to a branch retinal vein occlusion. RESULTS: Clinical diagnosis of endophthalmitis was made and, after obtaining a vitreous tap, intravitreal antibiotics were administered. Because of worsening of the endophthalmitis, pars plana vitrectomy was undertaken followed by repeat intravitreal antibiotics injection. The patient's ocular condition improved dramatically; however, her visual acuity did not improve. The cultures from vitreous taps revealed Staphylococcus lugdunesis. CONCLUSION: Intravitreal injection of Avastin may be associated with a risk of S. lugdunesis-caused endophthalmitis which can have a devastating effect on the final visual outcome.

Role of oxidative stress, inflammation, hypoxia and angiogenesis in the development of diabetic retinopathy.

Diabetic retinopathy (DR) is a retinal disease which is one of the most severe complications occuring due to diabetes mellitus and is a major cause of blindness. Patients who have diabetes mellitus for number of years develop characteristic group of lesions in the retina which leads to Diabetic retinopathy. It is a multifactorial condition occuring due to complex cellular interactions between biochemical and metabolic abnormalities taking place in all retinal cells. Considerable research efforts in the past 20 years have suggested that the microvasculature of the retina responds to hyperglycemia through a number of biochemical changes, which includes polyol pathway, protein kinase C activation, upregulation of advanced glycation end products formation and renin angiotensin system activation. Various previous studies had suggest that interaction of these biochemical changes may cause a cascade of events, such as apoptosis, oxidative stress, inflammation and angiogenesis which can lead to the damage of a diabetic retina, causing DR. This highlights that oxidative stress, inflammation, angiogenesis-related factors triggers the occurrence of retinal complication in diabetes are highlighted.

Endophthalmitis Due to Proteus vulgaris after Pars Plana Vitrectomy with Devastating Outcome.

Postoperative infectious endophthalmitis is rare, yet devastating loss of vision or loss of the eye can occur due to a highly purulent microorganism or uncontrolled endophthalmitis that may spread to all coats of the eye. We report, herewith, a case of rapidly progressive postoperative endophthalmitis after pars plana vitrectomy which ended up with enucleation. The isolated microorganism was Proteus vulgaris which has not been reported as causative bacteria of postoperative infections following pars plana vitrectomy.

ENDOGENOUS ENDOPHTHALMITIS CAUSED BY BRUCELLA MELITENSIS.

PURPOSE: Brucella is an intracellular gram-negative pathogen that acts as a facultative parasite. B. Melitensis endogenous endophthalmitis is quite rare. We herein report an unusual case of B. melitensis endophthalmitis with a good outcome after appropriate management. METHODS: A retrospective interventional case report of an 18-year-old boy who had unexplained interrupted fever and malaise for the past 4 months and was being treated as a case of fever of unknown origin. He presented with a 10-day history of pain and loss of vision in the left eye. Visual acuity in the left eye at time of presentation was counting fingers near face. Extensive anterior chamber reaction and flare, as well as, vitritis were found on examination. All blood and urine investigations and radiological imaging were negative. RESULTS: A diagnostic/therapeutic vitrectomy with antibiotic injection helped in identifying the offending organism and controlling the inflammation. Vitrectomy sample revealed B. melitensis with no sensitive result. Patient recovered vision in his eye to 20/150. Eye examination revealed a quiet eye, with flat retina and some retinal pigment epithelial changes at macula. CONCLUSION: B. melitensis endophthalmitis is a rarely encountered disease entity. High suspicion and prompt management with vitrectomy and appropriate antibiotic injection was successful in salvaging the patient's eye.

The angiogenic biomarker endocan is upregulated in proliferative diabetic retinopathy and correlates with vascular endothelial growth factor.

PURPOSE/AIM: Endocan is a proteoglycan specifically secreted by endothelial cells, is a marker of angiogenesis and endothelial cell activation in response to proangiogenic signals. The aim of this study was to measure the levels of endocan in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate its levels with clinical disease activity and the levels of the angiogenic biomarkers vascular endothelial growth factor (VEGF), soluble vascular endothelial-cadherin (sVE-cadherin) and soluble endoglin (sEng). In addition, we investigated the expression of endocan and correlated it with the level of vascularization in PDR epiretinal membranes. MATERIALS AND METHODS: Vitreous samples from 44 PDR and 29 non-diabetic patients were studied by enzyme-linked immunosorbent assay. Epiretinal membranes from 14 patients with PDR were studied by immunohistochemistry. RESULTS: Endocan, VEGF, sVE-cadherin and sEng levels were significantly higher in PDR patients than in non-diabetic patients (p < 0.001; p = 0.002; p < 0.001; p = 0.001, respectively). Endocan levels were significantly higher in patients with active PDR than in patients with inactive PDR and non-diabetic patients (p < 0.001). There were significant positive correlations between endocan levels and the levels of VEGF (r = 0.574, p < 0.001) and sVE-cadherin (r = 0.498, p < 0.001). In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed endocan. There was a significant positive correlation between the number of blood vessels expressing CD34 and the number of blood vessels expressing endocan (r = 0.933, p < 0.001). CONCLUSIONS: Our findings suggest that upregulation of endocan expression in PDR could be a reflection of endothelial cell activation associated with angiogenesis.

Prognostic factors in Vogt-Koyanagi-Harada disease.

PURPOSE: To identify prognostic factors for final visual outcome, development of complications, and recurrent inflammation in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: All patients diagnosed with acute uveitis associated with VKH disease at the King Khaled Eye Specialist Hospital and King Abdulaziz University Hospital between January 1999 and February 2004 were reviewed. Data collected included age, gender, initial and final visual acuities, clinical findings at presentation, interval between onset of disease and starting treatment, treatment received, complications, number of recurrences, extraocular manifestations, and duration of follow-up period. RESULTS: Sixty-eight patients were identified. There were 51 (75%) females and 17 (25%) males with a mean age of 25.04 +/- 10.28 years (range 7-55 years). The mean follow-up period was 34.4 +/- 20.1 months (range 8-62 months). The following factors were significantly associated with final visual acuity of 20/20 by univariate analysis: good initial visual acuity of better than 20/200 (p = 0.0415), absence of posterior synechiae of the iris at presentation (p = 0.0106), use of systemic corticosteroids for longer than nine months (p = 0.0479), slow tapering of systemic corticosteroids (p = 0.0024), absence of complications (p < 0.001), and absence of extraocular manifestations (p = 0.0124). Logistic regression analysis identified the use of systemic corticosteroids for longer than nine months to be associated with final visual acuity of 20/20 [odds ratio = 3.4; 95% confidence interval (CI) = 1.14-10.1]. The following factors were significantly associated with the development of complications by univariate analysis: age older than 18 years (p = 0.0161), initial visual acuity of 20/200 or worse (p = 0.0011), and presence of posterior synechiae of the iris at presentation (p = 0.0453). Factors identified after logistic regression analyses were age older than 18 years (odds ratio = 3.3; 95% CI = 1.33-8.17), and presence of posterior synechiae of the iris at presentation (odds ratio = 3.42; 9% CI = 1.38-8.47). Initial visual acuity of better than 20/200 was significantly associated with a lower risk of developing complications (odds ratio = 0.283; 95% CI = 0.129-0.629). The following factors were significantly associated with recurrent inflammation of three times or more by univariate analysis: initial visual acuity of 20/200 or worse (p = 0.0179), anterior chamber reaction of more than 2+ at presentation (p < 0.001), rapid tapering of systemic corticosteroids (p < 0.001), and development of extraocular manifestations (p = 0.0277). CONCLUSIONS: Clinical findings at presentation, duration and method of tapering of systemic corticosteroids, and development of extraocular manifestations are significantly associated with final visual acuity, development of ocular complications, and recurrent inflammation. The development of ocular complications was significantly associated with a worse final visual acuity.