Aleksandra Radosavljević

The role of CRP and inflammation in the pathogenesis of age-related macular degeneration.

Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving the multiple genetic and environmental factors that can result in severe visual loss. The etiology of AMD is not well understood. Many theories exist and feature mechanisms of oxidative stress, atherosclerotic-like changes, genetic predisposition and inflammation. The most recent clinical studies appointed to a great role of inflammation and C-reactive protein (CRP) in the pathogenesis of AMD. There is a large body of evidence indicating the association of CRP with endothelial dysfunction, oxidative stress and production of reactive oxygen species (ROS), as well as with lipid status disorder in AMD patients. According to recent studies, CRP is definitely not only the inflammatory marker but also a mediator of development of the vascular disorders in the retinal circulation. The results obtained from the present studies may help our understanding the pathogenesis of the retinal vascular disease associated with high levels of CRP.

The association of lipoprotein parameters and C-reactive protein in patients with age-related macular degeneration.

Background: Age-related macular degeneration (AMD) is the most common cause of visual impairment in individuals over 50 years of age, with the prevalence of 0.05% before the age of 50 rising to 30% after 74 years of age. An elevated concentration of plasma lipoproteins is considered to be one of the risk factors of AMD development. The aim of our study was to analyze the concentration of serum lipoproteins – total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-LDL cholesterol and triglycerides – as well as apolipoproteins – apoA1, apoB and Lp(a) – along with C-reactive protein (CRP) in patients with AMD in order to explore the possible association of lipid and inflammatory parameters with the pathogenesis of AMD. Material and Methods: In the cross-sectional study in the University clinical setting, 79 patients with AMD, aged 71.47 ± 7.02 years, and 84 aged-matched control subjects were included. The patients underwent complete ophthalmological examination including visual acuity assessment, color fundus photography and fluorescein angiography. Results: Statistical processing data revealed significantly higher total (p = 0.0002), LDL (p = 0.023), non-HDL cholesterol (p = 0.0014) and CRP (p = 0.049) values in AMD patients compared to control subjects. Conclusions: Based on the obtained results, it may be concluded that lipid status disorder and inflammation could play an important role in the development of AMD in elderly people.

Bioreactor validation and biocompatibility of Ag/poly(N-vinyl-2-pyrrolidone) hydrogel nanocomposites

Silver/poly(N-vinyl-2-pyrrolidone) (Ag/PVP) nanocomposites containing Ag nanoparticles at different concentrations were synthesized using γ-irradiation. Cytotoxicity of the obtained nanocomposites was determined by MTT assay in monolayer cultures of normal human immunocompetent peripheral blood mononuclear cells (PBMC) that were either non-stimulated or stimulated to proliferate by mitogen phytohemagglutinin (PHA), as well as in human cervix adenocarcinoma cell (HeLa) cultures. Silver release kinetics and mechanical properties of nanocomposites were investigated under bioreactor conditions in the simulated body fluid (SBF) at 37°C. The release of silver was monitored under static conditions, and in two types of bioreactors: perfusion bioreactors and a bioreactor with dynamic compression coupled with SBF perfusion simulating in vivo conditions in articular cartilage. Ag/PVP nanocomposites exhibited slight cytotoxic effects against PBMC at the estimated concentration of 0.4 μmol dm(-3), with negligible variations observed amongst different cell cultures investigated. Studies of the silver release kinetics indicated internal diffusion as the rate limiting step, determined by statistically comparable results obtained at all investigated conditions. However, silver release rate was slightly higher in the bioreactor with dynamic compression coupled with SBF perfusion as compared to the other two systems indicating the influence of dynamic compression. Modelling of silver release kinetics revealed potentials for optimization of Ag/PVP nanocomposites for particular applications as wound dressings or soft tissue implants.

The impact of inflammation to the antioxidant defense parameters in AMD patients

Background and aims: Oxidative stress and inflammation are postulated to be involved in the pathogenesis of the age-related macular degeneration (AMD) although the mechanism linking the oxidation and inflammation is still unknown. The aim of this study was the analysis of the antioxidant capacity measured by levels of the antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and total antioxidant status (TAS) along with the inflammatory markers such as Creactive protein (CRP), interleukin-6 (IL-6) and fibrinogen in AMD patients in order to analyze the relationship of the inflammatory markers with the antioxidant parameters and their association with AMD. Methods: The cross-sectional study, carried out in the University clinical setting, included 84 patients with the age-related macular degeneration, aged 71.25±7.14 years and 84 aged-matched control subjects (CG). Results: Statistical analysis revealed significantly lower GR (p=0.007) and TAS (p<0.000) values in the group of AMD patients compared to the controls. Logistic regression analysis showed that higher values of inflammatory markers (CRP>3 mg/L, IL>4.9 pg/mL, fibrinogen>3.8 g/L) and lower values of antioxidative parameters (SOD<900 U/gHb, GR<55 U/L and TAS<1.15 mmol/L) were significantly associated with AMD (ORCRP: 1.29, 95% CI 0.54-3.12, p<0.05; ORIL-6: 3.53, 95% CI 1.16–10.75, p=0.024; ORFIB: 3.06, 95% CI 1.78–7.92, p=0.019; ORSOD: 2.39, 95% CI 0.78–7.35, p<0.05; ORGR: 4.04, 95% CI 1.28–12.73, p=0.013; ORTAS: 2.9, 95% CI 1.4–6.3, p=0.032). Conclusions: Based on the results obtained, it may be concluded that the antioxidant defense system was significantly reduced in patients with AMD and the probability to develop AMD was higher in older individuals with lower values of antioxidant parameters and higher values of inflammatory markers.

Clinical Features of Ocular Sarcoidosis in Patients with Biopsy-proven Pulmonary Sarcoidosis in Serbia

ABSTRACT Purpose: To analyze clinical characteristics of ocular sarcoidosis in a group of biopsy-proven sarcoid patients treated at the single referral center for sarcoidosis in Serbia. Methods: A prospective study carried out on 88 biopsy-proven sarcoid patients between January 2012 and December 2014. All patients underwent complete ophthalmological examination. Results: Ocular sarcoidosis was present in 32 patients (36.4% of all) and included: eyelid skin lesions (2.3%); orbital inflammation (2.3%); conjunctival lesions (7.9%); anterior uveitis (2.3%); intermediate uveitis (1.1%); posterior uveitis (15.9%); panuveitis (5.7%), and neuro-ophthalmologic manifestations (9.1%). Complications included cataract (20.4%); glaucoma (5.7%); cystoid macular edema (3.4%); epiretinal membrane formation (4.5%); macular atrophy (2.3%); and choroidal neovascularization (1.1%). Binocular visual impairment was present in one patient (1.1%), due to complications of posterior uveitis (macular scars). Conclusions: Patients in Serbia demonstrated ocular sarcoidosis as the first most common site of extrapulmonary sarcoid manifestations, with more often neuro-ophthalmologic lesions than in other European populations.

The association of enzymatic and non-enzymatic antioxidant defense parameters with inflammatory markers in patients with exudative form of age-related macular degeneration

There are evidence that oxidative stress and inflammation are involved in the pathogenesis of the age-related macular degeneration (AMD). The aim of this study was to analyze the antioxidant defense parameters and inflammatory markers in patients with exudative form of AMD (eAMD), their mutual correlations and association with the specific forms of AMD. The cross-sectional study, included 75 patients with the eAMD, 31 patients with the early form, and 87 aged-matched control subjects. Significantly lower SOD, TAS and albumin values and higher GR, CRP and IL-6 were found in the eAMD compared to the early form (p<0.05). Significant negative correlations were found between GPx and fibrinogen (r = –0.254), TAS and IL-6 (r = –0.999) and positive correlations between uric acid and CRP (r = 0.292), IL-6 and uric acid (r = 0.398) in the eAMD. A significant association of CRP (OR: 1.16, 95% CI: 1.03–1.32, p = 0.018), fibrinogen (OR: 2.21, 95% CI: 1.14–4.85, p = 0.021), TAS (OR: 7.45, 95% CI: 3.97–14.35, p = 0.0001), albumin (OR: 1.25, 95% CI: 1.11–1.41, p = 0.0001) and uric acid (OR: 1.006, 95% CI: 1.00–1.02, p = 0.003) was found with the eAMD. In conclusion it may be suggested, there is a significant impairment of antioxidant and inflammatory parameter levels in eAMD patients. In addition, significant association exists between the tested inflammatory markers and antioxidant parameters with late-eAMD.

Oxidative stress in association with risk factors for the occurrence and development of age-related macular degeneration

Niz rezultata potvrđuje ulogu oksidativnog stresa u etiopatogenezi AMD i to bilo kao inicijalnog ili izolovanog uzrocnog faktora, ili kao dodatnog cinioca u sklopu drugih faktora rizika. Bolje poznavanje ove oblasti prosiruje mogucnosti prevencije ove, ali i drugih bolesti starijeg životnog doba.

Anterior ischemic optic neuropathy associated with metabolic syndrome

PURPOSE Metabolic syndrome denotes a common cluster of naturally connected risk factors including obesity, elevated blood pressure, insulin resistance, dyslipidemia, proinflammatory state and prothrombotic state. Anterior ischemic optic neuropathy is an acute ischaemic disorder of the optic nerve head and may lead to severe visual loss. METHODS We considered three patients with moderate degree of diabetic retinopathy and anterior ischemic optic neuropathy. They were submitted to endocrinological examination and the diagnosis of metabolic syndrome was established. RESULTS Cardiological examination revealed that blood pressure control was not optimal. The signs of left ventricular hypertrophy and diastolic dysfunction were confirmed by echocardiography. They are possible markers of preclinical cardiovascular disease. CONCLUSION We observed that a variety of well-known risk factors in metabolic syndrome may be involved in serious eye and cardiological complications. The early diagnosis and treatment of these patients can not only improve visual function but also prevent cardiovascular complications.

Vitreoretinal interface changes after uncomplicated phacoemulsification

Online first: January 30, 2018 SUMMARY Introduction/Objective The aim of this work was to examine the incidence of posterior vitreous detachment (PVD) after uncomplicated phacoemulsification, as well as the importance of optical coherence tomography (OCT) in detecting early changes on vitreoretinal interface. Methods PVD was evaluated in 120 eyes of 120 patients aged between 50 and 70 years by the combination of OCT and ultrasonography immediately prior and one, six, and 12 month after the phacoemulsification cataract surgery with intraocular lens implantation. Results The mean age was 57 ± 8.8 years in female and 58.6 ± 8.8 years in male subjects. The progress statuses were compared after cataract surgery at three time-points: after one, six, and 12 months. Significant progression of PVD in time was confirmed (χ2 = 78.32, p < 0.001). The Wilcoxon test determined that after six months (p < 0.001) and 12 months (p < 0.001) the disease progression was statistically significant in comparison to measurements after one month. In addition, after 12 months, in relation to progression status established after six months, there was significant progression of the disease (p < 0.001). Conclusion Vitreous body detachment after phacoemulsification surgery is common, and OCT plays a very important role in detecting initial changes on the vitreoretinal interface.

TNFRSF1A gene variant identified in a boy with recurrent episodes of fever

Online first: February 6, 2018 SUMMARY Introduction Fever of unknown origin is an important diagnostic challenge. Although rare, periodic fever syndromes may often present with a chronic or recurrent febrile condition with a variable temporal pattern of occurrence. Although clinical characteristics often indicate the syndrome in question, there are many atypical forms, and the genotype–phenotype relationship is highly complex, warranting in many cases the designation of a “syndrome spectrum” rather than a syndrome per se. The aim of this paper was to present a boy with recurrent fever of unknown origin. Case outline We hereby present a boy with recurrent fever of unknown origin who was by clinically guided partial exome sequencing found to have a heterozygous variant 434A>G in the TNFRSF1A gene, otherwise connected with tumor necrosis factor receptor-associated periodic fever syndrome. The patient responded well to short courses of glucocorticoids and is no longer subjected to unnecessary antibiotic treatment he had frequently received in the past. Conclusion Periodic fever syndromes should be kept in mind as a differential diagnostic possibility in children with fever of unknown origin.