Leber hereditary optic neuropathy in the population of Serbia.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. However, few countries have published their population-based findings related to this multisystemic disease. THE AIM: In order to get a better insight into the epidemiological and clinical picture of this maternally inherited disorder, we performed the first population-based clinical and molecular-genetic study of LHON in the Serbian population. METHODS: Prospective study included patients who were diagnosed with LHON after detailed medical examination and molecular-genetic confirmation. RESULTS: We identified 41 individuals from 12 genealogically unrelated families, carrying one of the three "primary" mitochondrial (mt) DNA point mutations associated with LHON. Fourteen of them were clinically affected, giving a minimum point prevalence of 1.9 per 1,000,000. The minimum point prevalence for mtDNA LHON mutations was 5.2 per 1,000,000. Male to female ratio was 6:1. Only one affected patient harboured mutant mtDNA in heteroplasmic condition. All patients were presented with common clinical findings. CONCLUSION: We observed significantly lower prevalence and higher gender ratio than expected. However, frequencies of primary mutations, incidence of heteroplasmy and clinical findings are in accordance with other studies in Caucasoid populations. Our results might be a consequence of poor recognition and misdiagnosis due to lack of diagnostic possibilities of the entity in different region of our country or less likely be in part due to specific haplotype background of Serbian population which should be further investigated.

Ocular complications after kidney transplantation: a case report and review of literature.

Membranoproliferative glomerulonephritis type II (MPGN II), also known as a dense deposit disease, is a chronic progressive kidney disease that often progresses to end-stage renal disease within 10 years. Most patients also have multiple subretinal white spots or drusen-like deposits that are histopathologically identical to the glomerular basement membrane deposits. The purpose is to determine ocular findings in a patient with MPGN II before and after renal transplantation and to correlate them with clinical characteristics related to transplantation and review of literature. We present a case of a 45-year-old female with MPGN II who developed bilateral serous retinal detachment and retinal hemorrhages in the left eye, which appeared 6 months after a renal transplant. Ocular complications in our case, with the exception on the retina, were present at the cornea and iris. Changes to the eyes were independent of the renal disease, because there was no recurrence of MPGN II on the renal graft.

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.

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.

Gender Associated Lipid and Apolipoprotein Profile in Patients with Age-Related Macular Degeneration.

The role of lipid parameters disorder in the development of age-related macular degeneration (AMD) is unclear. The aim of this study was to analyze lipid profile in these patients and to test the influence of gender on lipid profile of AMD patients, especially in the early and late form of the disease. 82 patients with AMD (mean age 70.3 yrs) and 80 age-matched control subjects were included in this study. Serum lipid and apolipoproteiin levels were determined using standardized methods. AMD patients had significantly higher values of total cholesterol (P=0.000), HDL-cholesterol (P=0.0003) and LDL-cholesterol (P=0.000) compared to control group. Significantly higher values of apo A1 (P=0.039), apo E (P=0.002), total-cholesterol (P=0.000), LDL-chol. (P=0.026), total HDL-chol (P=0.000), HDL3-chol. (P=0.005) and non-HDL-cholesterol (P=0.029) were found in female AMD patients compared to males with AMD. Females with the advanced form of the disease had significantly higher total cholesterol (P=0.006), HDL-C (P=0.004), non HDL-C (P=0.05) and apo E (P=0.014) compared to males with the same form of the disease. There is a significant disorder of lipid parameters in AMD patients especially in females. More severe forms of AMD are followed by the increase of atherogenic lipoproteins and apolipoproteins, and females have higher values of these parameters compared to males with the same form of AMD.

[Oxidation stress role in age-related cataractogenesis].

INTRODUCTION: Age-related cataract not only diminishes human life quality but it also represents a big impact on healthcare budget of almost every country as the population ages globally. Hence, cataract prevention is a big and true challenge, but a very difficult task to be accomplished. Nowadays cataract is more than a routinely recognized and almost always successfully operated ophthalmologic disease. The diagnosis of age-related cataract diagnosis might alert doctors to some systemic disorders on the whole body level. Increasing age is certainly the most essential age-related cataract risk factor. However, it seems that cataract could be a multifactor disease because of its individual, familiar, racial and gender expression differences. OXIDATION STRESS: Oxidation stress and its form caused by ultraviolet light- photo-oxidative stress--are considered to be crucial in the etiopathogenesis of cataract. All biomolecules suffer damages during cataract formation. On the other side, the lens possess a range of antioxidant elements and mechanisms of their action, which enable long lasting maintenance of lens transparency and functioning. Although they are primary characteristics of the lens, these antioxidant elements also depend on their systemic availability and consumption. This paper is a short literature review of the relation between oxidation stress and age-related cataract.

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.

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.

OBJETIVO: A síndrome metabólica indica um grupo comum dos seguintes achados clinicos: obesidade, hipertensão arterial, variações nos níveis de glicemia, dislipidemia, estado proinflamatório e o estado protrombótico. Neuropatia óptica isquêmica anterior é um distúrbio agudo isquêmico da cabeça do nervo óptico que pode levar à perda de visão. MÉTODOS: Consideramos três pacientes com retinopatia diabética não proliferativa moderada e neuropatia óptica isquêmica anterior. Os pacientes foram examinados por endocrinologistas e o diagnóstico de síndrome metabólica foi confirmado. RESULTADOS: O exame cardiológico revelou que o controle da pressão sangüínea não era adequado e tal anormalidade foi corrigida. A ecocardiografia confirmou os indícios de hipertrofia ventricular esquerda e disfunção diastólica. Estes são os marcadores possiveis da doença cardiovascular pré-clinica. CONCLUSÃO: Concluímos que os fatores de risco bem conhecidos, combinados na síndrome metabólica levaram às complicações oculares e às complicações cardiológicas. O diagnóstico anticipado e o tratamento destes pacientes pode não apenas melhorar a função visual mas também impedir as complicações cardiovasculares.

[Gigantic ovarian and suprarenal cysts ten years after enucleation of unilateral retinoblastoma].

INTRODUCTION: Retinoblastoma (RB) is the most common eye tumour in children and is curable. Patients with hereditary RB have increased risk of developing additional tumours, predominantly sarcomas. The published results on the treatment of bilateral RB have shown that 10-15% of patients develop second primary tumours (SPT). Average latent period, e.g. the period from the diagnosis of bilateral RB to the appearance of SPT is 10.4 years. In the literature, the appearance of second benign tumours in patients suffering from unilateral and bilateral RB has not been analyzed separately. However, the size and the location of benign tumours can cause serious complications. CASE OUTLINE: We present a 14-year-old female patient. At age 4 years, her left eye was enucleated owing to unilateral RB. In the postoperative period, she did not undergo irradiation, nor did she receive chemotherapy. On her regular ophthalmologic check-up, the patient informed us that her belly was "swelling" over the past four months. She had no pains or other complaints. The abdomen was significantly above the level of the chest, tense, painless on palpation, with obvious fluctuations. Abdominal echosonography confirmed the presence of a huge multilocular cystic formation, 19 x 18 cm in diameter, spreading from the pelvis to the epigastrium, and pressing the liver and spleen. A cyst of 4.7 cm in diameter was observed in the upper pole of the left kidney. Both the gigantic cyst of the left ovary (weighing 10300 g) and the left suprarenal cyst (weighing 30 g) were removed. CONCLUSION: We report a patient who developed second non-ocular tumours (ovarian and suprarenal cysts) after successful treatment of unilateral RB. Patients treated for RB (hereditary and non-hereditary) should be checked regularly and meticulously. Early recognition of tumours, treatment can prevent possible complications.

[Binocular vision and vertical strabismus].

BACKGROUND/AIM: Elevation in adduction is the most common pattern of vertical strabismus, and it is mostly treated with surgery. The results of weaking of inferior oblique muscle are very changeable. The aim of this study was to evaluate binocular vision using sensory tests before and one and six months after the surgery. METHODS: A total of 79 children were divided in two groups: the first, with inferior oblique muscle of overaction (n = 52), and the second with dissociated vertical deviation (DVD), and primary inferior oblique muscle overaction (n = 27). We tested them by polaroid mirror test (PMT), Worth test at distance and near, fusion amplitudes on sinoptofore, Lang I stereo test and Wirt-Titmus stereo test. We examined our patients before and two times after the surgery for vertical strabismus. RESULT: Foveal suppression in the group I was found in 60.5% of the patients before, and in 56.4% after the surgery. In group II Foveal suppression was detected in 64.7% of the patients before, but in 55.6% 6 months after the surgery with PMT. Worth test revealed suppression in 23.5% of the patients before, and in 40.7% after the vertical muscle surgery. Parafoveal fussion persisted in about 1/3 of the patients before the surgery, and their amplitudes were a little largen after the surgery in the group I patients. Lang I stereo test was negative in 53.9% before and 51.9% after the surgery in the group I, and in 48.2% of the patients before and after the surgery in the group II patients. Wirt-Titmus stereo test was negative in 74.5% of the patients before and in 72.9% after the surgery in the group I, but in the group II it was negative in 70.8% before and in 68.0% of the patients 6 months after the surgery. CONCLUSION: Binocular responses were found after surgury in 65.7% of the patients the group I and in 55.6% patients the group II. There was no significant difference between these two groups, but binocular responses were more often in the patients of the group I.

Metabolic syndrome and central retinal artery occlusion.

BACKGROUND: The accumulation of risk factors for central retinal artery occlusion can be seen in a single person and might be explained by the metabolic syndrome. CASE REPORT: We presented the case of a 52-year-old man with no light perception in his right eye. The visual loss was monocular and painless, fundoscopy showed central retinal artery occlusion and the laboratory investigation showed the raised erythrocyte sedimentation rate of 105 mm/h and the raised C-reactive protein of 22 mg/l. Specific laboratory investigations and fluorescein angiography excluded the presence of vasculitis, collagen vascular diseases, hypercoagulable state and antiphospholipid syndrome. CONCLUSION: The patient met all the five of the National Cholesterol Education Program (NCEP) criteria for the metabolic syndrome: hypertension, abnormal lipid profile, abnormal glucose metabolism, obesity and hyperuricemia. Measurement of C-reactive protein is useful for the assessment of therapeutic systemic effect on any abnormality in the metabolic syndrome. Individual therapy for all risk factors in the metabolic syndrome is necessary to prevent complications such as cardiovascular, retinal vascular diseases and stroke.

[Radiation retinopathy in patients treated for sinus and epipharingeal malignancies].

BACKGROUND: Radiation retinopathy is vasculopathy induced by ionising radiation delivered by either brachytherapy or teletherapy for ocular and nonocular malignancies. The first signs of radiation retinopathy typically occur a few months to a few years after the exposure to ionizing radiation. CASE REPORT: In the 3 of our patients, changes like capillary telangiectasia, microaneurysms, intraretinal hemorrhages, hard exudation, and capillary nonperfusion showed a clinical picture of macular edema. Two of the patients were suspected of diabetic retinopathy, and 1 patient had optic neuropathy. In our group of patients a latent period was between 3 and 8 years. The incidence of radiation retinopathy increases significantly with the total doses of radiation above 45 Gy, and, thus, it has not been found in the lower doses. CONCLUSION: Radiation retinopathy is a diagnostical and therapentical problem. Clinical picture can be identical to that of diabetic retinopathy suggesting a common pathophysiologic mechanism of the damage to capillary endothelial cells, and the importance of clinical examination, anamnesis and fluorescein angiography.