[ASSESSMENT OF QUALITY OF LIFE IN GLAUCOMA PATIENTS].

Glaucoma is a chronic, asymptomatic disorder which affects 2% of the population over 40 years of age. Glaucoma causes a significant vision impairment with the consequences on daily activities of patients which affect negatively their quality of life (QoL). The purpose of this paper is to give a review of instruments used in the QoL assessments of glaucoma patients and methods of performance based assessment of visual function in glaucoma in daily life. The PubMed was searched for the relevant literature. Thirteen quality of life scores used in glaucoma patients, method of performance-based assessments of the ability to carry out daily activities, and three utility measures were investigated. Despite the fact that there are no ideal instruments for the assessment of QoL of glaucoma patients, it should be incorporated in the plan of glaucoma patients treatment because of multiple benefits in optimizing the plan of treatment, education of the patients, the patients' self satisfaction, and in the reduction of financial burden of the health care system. The Glaucoma Quality of Life (GQL-15) score is acceptable in clinical practice due to its shortness and implementation.

Glaucoma, depression and quality of life: multiple comorbidities, multiple assessments and multidisciplinary plan treatment.

BACKGROUND: The present mini review evaluates assessment and comorbidity of glaucoma and depression with the possibilities of treatment options. SUBJECTS AND METHODS: Web of science was searched for relevant articles using search terms "glaucoma", "depression", "glaucoma and depression", "quality of life and glaucoma". The additional relevant papers were added from the bibliography of selected papers. All types of articles were included, no time period was defined. RESULTS: We have reviewed 11 studies regarding the comorbidities of glaucoma and depression. The number of participants in all studies ranged from 86 to 6760. Formats of scale in one study was clinician rated, others were self-reported scales. Two studies of the above mentioned studies explored specific types of glaucoma. In the three studies out of 11 there was no significant evidence of elevated depressive symptoms associated with glaucoma. In the six studies the prevalence of depression was significant among glaucoma patients. One study provided suboptimal assessments of depression in glaucoma patients. The other one showed the presence of glaucoma significantly associated with depression after adjustment for the demographic factor. Most of the studies used one scale, while two of them used two scales. The reviewed studies did not analyze the therapy options of included patients. CONCLUSION: The results presented in this review indicate that glaucoma is accompanied by depression in the majority of analyzed studies. The comorbidity of glaucoma and depression should be the subject of further research on both, self-reflecting and clinician-rated scales, taking into account subjective experience of patients and physicians. The therapy options should be taken into account in future researches focusing on the multidisciplinary approach including novel possibilities of treating both diseases respectively.

Temporal and regional changes of superoxide dismutase and glutathione peroxidase activities in rats exposed to focal cerebral ischemia.

Reactive oxygen species are important cause of tissue injury during cerebral ischemia and reperfusion (I/R). Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are intracellular enzymes responsible for endogenous antioxidant defense of tissues affected by I/R. The aim of this study was to examine temporal and regional changes of SOD and GSH-Px activities in animals exposed to transient focal cerebral ischemia. Male Wistar Hannover rats were subjected to the right middle cerebral artery occlusion for 2 h. The animals were sacrificed immediately, 0·5, 1, 2, 3, 6, 24, 48, 72 or 168 h after ischemic procedure. SOD and GSH-Px activities were determined spectrophotometrically in the hippocampus and parietal cortex, both unilaterally and contralaterally to the occlusion. Sham-operated animals were used as the control group. Our results indicated that transient focal cerebral ischemia causes significant changes in SOD activities in the hippocampus and parietal cortex such as in GSH-Px activities in the parietal cortex, unilaterally and contralaterally to the lesion in rats during different reperfusion periods. Statistically significant activation of GSH-Px was registered neither in the right nor in the left hippocampus of ischemic animals.

Croatian children's views towards importance of health care information.

The aim of research was to investigate: the need for health care information of Croatian adolescents aged from 13 to 18 years; the difference in evaluation of the frequency of receiving information between hospitalized and healthy children; if the hospitalized children expectations about the frequency of receiving health care information differed significantly from information they have actually received; whose information was most comprehensible to the hospitalized children (doctors, parents, other health care givers). The children were either hospitalized in the pediatrics departments or were high schools pupils (healthy children). The hospitalized children "Completely agreed" (92.7%) with the statement "When I am sick, I should receive information about my health" in comparison to the healthy children (85.1%). In comparison to healthy children, the hospitalized children assessed that doctors, other health care givers and parents should give them information more frequently. The experience of hospitalized children indicate that they received less information then they have actually excepted. The information received from doctors was mostly in correlation with the understanding of this information. We concluded that the children want to be informed about their health, especially hospitalized children. Health care professionals should offer understandable health care information according to the children's expectation.

Immunotherapy for Uveal Melanoma - Current Knowledge and Perspectives.

Uveal melanoma is the most prevalent primary intraocular tumour in adults with the incidence between five and six cases per million people in the United States and Europe. The prognosis of patients with uveal melanoma is unfavourable with a 5-year survival rate of 50-70% despite significant advances in local tumour treatment using radiotherapy or surgical resection. Approximately 50% of the patients develop metastases within 15 years from initial diagnosis, mostly in the liver. The median survival rate after the onset of metastases is 6 months. Potential treatment options for metastatic uveal melanoma are chemotherapy, targeted therapy, and immunotherapy but no method showed satisfactory results. Immunotherapy with checkpoint inhibition showed promising results in the treatment of cutaneous melanoma; however, it did not appear to be equally effective with uveal melanoma. This may be due to differences in mutational burden, expression of neoantigens between these two types of tumour, immunosuppressive tumour microenvironment, and low immunogenicity and immune privilege of uveal melanoma. Considering the disappointing results of treatment with anti-CTLA-4 and PD-1/PD-L1 blockade in patients with advanced uveal melanoma several new forms of therapies are being developed. This may include immunotherapy with IMCgp100, glembatumumab vedotin and the infusion of autologous TILs, targeted therapy with selective MEK inhibitors, epigenetic therapy, and nanotherapy. Better insight into the molecular and genetic profile of uveal melanoma will facilitate detection of new prognostic biomarkers and thus enable a better modification of the existing immunotherapy methods and development of new forms of treatment specifically designed for uveal melanoma patients.

The influence of medical and nonmedical factors to the progression of renal osteodystrophy.

We report a 13-year-old boy hospitalized for the first time at the age of 17 months with clinical and laboratory signs of chronic kidney disease (CKD) and renal osteodystrophy caused by severe obstructive uropathy of the single kidney. Prevention and treatment of renal osteodystrophy has been target for aggressive therapy and the great challenge for pediatric nephrologists. The outcome of the therapy of renal osteodystrophy is influenced by medical and non-medical factors. It was concluded that the place of living (in our example a small village distant from primary care physicians, far from the social care professionals and far from the hospital), inferior social and economical status with inadequate nutrition present negative factors that contributed to the outcome and development of CKD and its complications as is renal osteodystrohy. The coordination of medical and non-medical professionals is necessary on the primary and secondary level to achieve positive results of therapy in patients with CKD.

Activation of ERK and JNK MAP kinases in optic nerves of rats exposed to global cerebral ischemia.

OBJECTIVES: To determine the influence of global cerebral ischemia on the activation of extracellular-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK) in optic nerves of rats exposed to different reperfusion periods. MATERIALS AND METHODS: Transient global cerebral ischemia (20-min duration) was induced by the four-vessel occlusion method. After different reperfusion periods (5 and 10 min; 1; 6 and 12 h after ischemia), optic nerves were extracted and ERK and JNK activation signals were determined by Western immunoblot analyses. RESULTS: The activation signals of ERK and JNK were detected within first 10 min of reperfusion, but striking activation for both enzymes was found 1 h after ischemia. After a transient decrease, the activation of ERK returned to peak level after 12 h of reperfusion in the second wave of kinase activation. In that period, a slight increase of JNK activation was registered. CONCLUSION: Our results demonstrated for the first time that ERK and JNK were activated in rat optic nerves during early and later periods of reperfusion, suggesting their potential active role in the response of cerebral white matter tissue to ischemic injury.

Refractive Changes Associated with Diabetes Mellitus.

BACKGROUND AND METHODS: Diabetes mellitus is the most prevalent endocrinedisease in developed countries. In people with diabetes in addition to visionloss caused by diabetic retinopathy transient visual disturbances may occurfrequently caused by refractive changes. These changes in refraction are associated with variations in blood glucose levelsbut the underlying mechanism is still not fully understood. A systematic reviewwith a comprehensive literature search was performed in order to clarify the underlyingmechanisms regarding the connection of glycaemic control and refractive shift. RESULTS: Some studies have shown that increasedblood sugar leads to a myopic shift whilst others demonstrated that this changeis in a hyperopic direction. Changes in visual acuity in patients with diabetescould be an indicator of inadequate metabolic control or even the first sign ofdiabetes mellitus. CONCLUSION: This reviewgives a brief overview of current research regarding potential mechanisms ofglycemic control influence on refractive error. The aim isto emphasizethe importance ofunderstanding the relationship ofblood glucose concentration and refractive changes as one of thecommon but overlooked diabetic complications.

Flow Changes in Orbital Vessels Detected with Color Doppler Ultrasound in Patients with Early Dysthyroid Optic Neuropathy.

Thyroid-associated orbitopathy (TAO) is a common manifestation of Graves' disease. The aim of the study was to assess the six percent of patients with TAO that develop dysthyroid optic neuropathy (DON), which is the most serious complication of TAO. As DON can cause perma-nent damage, it is essential to detect DON early when visual loss is still reversible. Color Doppler ultrasound is a noninvasive diagnostic method, which may be useful in early detection of DON. Thirty-six patients with confirmed Graves' disease and active TAO were included, 21 (58%) of them with early DON (eDON) and 15 (42%) free from any signs of eDON. All study patients underwent Doppler ultrasound examination to determine the blood flow rates in the internal carotid artery, ophthalmic artery, and central retinal artery. Study results showed color Doppler ultrasound examination to have a potential to detect orbital blood flow changes in patients with eDON. Early detection of DON may result in earlier treatment and prevention of permanent optic nerve damage.

Prevalence of Open Angle Glaucoma in Risk Groups in Slavonia and Baranya Region.

The aim of this prospective study was to detect primary open angle glaucoma (POAG) in its early stage in patients at a higher risk of its development, and to identify the risk group with the highest prevalence of POAG. The study was conducted at Department of Ophthalmology, Osijek University Hospital Centre, and included 250 patients divided into five groups, as follows: group 1, patients with diabetes type 1 and type 2; group 2, patients with arterial hypertension (blood pressure >140/90 mm Hg); group 3, patients with positive family history of POAG; group 4, patients with myopia between -3.0 and -8.0 diopters; and group 5, control group including patients aged 40 with no risk factors for POAG development. Study results showed that distribution of glaucoma patients was not equal across the groups. The prevalence of POAG in all patients was 5.6%, whereas in patients with positive family history of POAG it was 14%, which was statistically significantly higher than in patients with diabetes and myopia (4% both), as well as in control group. The difference was greatest in comparison to control group. There was no statistically significant difference in glaucoma incidence between the group of patients with positive family history (14%) and patients with systemic hypertension (6%). The results obtained suggest that of all risk factors analyzed, positive family history of POAG is the most important risk factor for glaucoma development in all risk groups.

Decrease in Oxidative Stress Parameters after Post-Ischaemic Recombinant Human Erythropoietin Administration in the Hippocampus of Rats Exposed to Focal Cerebral Ischaemia.

Recombinant human erythropoietin (rhEpo) is a multi-functional drug with antioxidant potential. However, the underlying molecular mechanisms of its action are still unclear. The purpose of this study was to investigate the effects of rhEpo on the brain infarct volume as well as on the levels of the neuronal damage, oxidative stress parameters and active caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2) and haemeoxygenase-1 (HO-1) expressions in the hippocampi of rats exposed to the right middle cerebral artery occlusion (MCAO) for 1 hr. Ischaemic animals received either vehicle or rhEpo (5000 IU/kg, i.p.) immediately or 3 hr after the induction of ischaemia. Sham-operated, vehicle-treated animals served as the control group. Rats were killed 24 hr after the onset of the ischaemic or sham experimental procedure. MCAO caused ipsilateral brain infarction within the striatum and cortex. In the CA1 region of the hippocampi, we did not find significant neuronal loss, but a statistically significant rise in the active caspase-3 and Nrf2 protein expressions was registered. We detected also significant increases in the hippocampal levels of oxidative stress parameters (thiobarbituric acid-reactive substances, superoxide dismutase, glutathione peroxidase). Post-ischaemic administration of rhEpo significantly reduced the brain infarct volume, decreased levels of all tested oxidative stress parameters and increased the Nrf2 expression level. These findings suggest that decrease in oxidative stress parameters in the hippocampus could be an early indicator of post-ischaemic neuroprotective effect of rhEpo in rats exposed to focal cerebral ischaemia and that this effect could be attributable to additional post-ischaemic activation of Nrf2 endogenous antioxidant system.

Hyperbaric oxygen treatment: the influence on the hippocampal superoxide dismutase and Na+,K+-ATPase activities in global cerebral ischemia-exposed rats.

The influence of hyperbaric oxygen (HBO) treatment on the activities of superoxide dismutase (SOD) and Na(+),K(+)-ATPase was determined during different time periods of reperfusion in rats exposed to global cerebral ischemia. Ischemic animals were either sacrificed or exposed to the first HBO treatment 2, 24, 48 or 168 h after ischemic insult (for SOD activities measurement) or immediately, 0.5, 1, 2, 6, 24, 48, 72 or 168 h after ischemic procedure (for Na(+),K(+)-ATPase activities measurement). Hyperbaric oxygenation procedure was repeated for seven consecutive days. The results of presented experiments demonstrated the statistically significant increase in the hippocampal SOD activity 24 and 48 h after global cerebral ischemia followed by a decrease in the enzymatic activity 168 h after ischemic insult. In the ischemic rats treated with HBO the level of hippocampal SOD activity was significantly higher after 168 h of reperfusion in comparison to the ischemic, non HBO-treated animals. In addition, it was found that global cerebral ischemia induced a statistically significant decrease of the hippocampal Na(+),K(+)-ATPase activity starting from 1 to 168 h of reperfusion. Maximal enzymatic inhibition was obtained 24 h after the ischemic damage. Decline in Na(+),K(+)-ATPase activity was prevented in the animals exposed to HBO treatment within the first 24 h of reperfusion. Our results suggest that global cerebral ischemia induces significant alterations in the hippocampal SOD and Na(+),K(+)-ATPase activities during different periods of reperfusion. Enhanced SOD activity and preserved Na(+),K(+)-ATPase activity within particular periods of reperfusion, could be indicators of a possible beneficial role of HBO treatment in severe brain ischemia.

Effects of the hyperbaric oxygen treatment on the Na+,K+ -ATPase and superoxide dismutase activities in the optic nerves of global cerebral ischemia-exposed rats.

The effects of hyperbaric oxygen (HBO) treatment on the Na+,K+ -ATPase and superoxide dismutase (SOD) activities were examined in the optic nerves of the rats exposed to global cerebral ischemia. Animals were exposed to global cerebral ischemia of 20-min duration and were either sacrificed or exposed to the first HBO treatment immediately, 0.5, 1, 2, 6, 24, 48, 72 or 168 h after ischemic procedure (for Na+,K+ -ATPase activities measurement) or 2, 24, 48 or 168 h after ischemia (for SOD activities measurement). HBO procedure was repeated for 7 consecutive days. It was found that global cerebral ischemia induced a statistically significant decrease in the Na+,K+ -ATPase activity of the optic nerves, starting from 0.5 to 168 h of reperfusion. Maximal enzymatic inhibition was registered 24 h after the ischemic damage. The decline in the Na+,K+ -ATPase activity was prevented in the animals exposed to HBO treatment within the first 6 h of reperfusion. The results of the presented experiments demonstrated also a statistically significant increase in the SOD activity after 24, 48 and 168 h of reperfusion in the optic nerves of non-HBO-treated ischemic animals as well as in the ischemic animals treated with HBO. Our results indicate that global cerebral ischemia induced a significant alterations in the Na+,K+ -ATPase and SOD activities in the optic nerves during different periods of reperfusion. HBO treatment, started within the first 6 h of reperfusion, prevented ischemia-induced changes in the Na+,K+ -ATPase activity, while the level of the SOD activity in the ischemic animals was not changed after HBO administration.

The influence of MK-801 on the hippocampal free arachidonic acid level and Na+,K+-ATPase activity in global cerebral ischemia-exposed rats.

The influence of 20 min global cerebral ischemia on the free arachidonic acid (FAA) level and Na+,K+-ATPase activity in the rat hippocampus at different time points after ischemia was examined. In addition, the effect of MK-801 on mentioned parameters was studied. Animals were exposed to 20 min global cerebral ischemia and were sacrificed immediately, 0.5, 1, 2, 6, 24, 48, 72, and 168 h after ischemic procedure. The level of the FAA and the Na+,K+-ATPase activity was measured during all reperfusion periods examined. Various doses of MK-801 (0.3, 1.0, 3.0, and 5.0 mg/kg) had been injected 30 min before ischemic procedure started. It was found that 20 min global cerebral ischemia induces a statistically significant increase of the FAA level immediately after ischemia and during the first 0.5 h of reperfusion. After a transient decrease, the level of FAA level increased again after 24 and 168 h of recirculation. Treatment with 3.0 mg/kg of MK-801 significantly prevented the FAA accumulation immediately and 0.5 h after ischemic insult while application of 5.0 mg/kg of MK-801 exerted a protective effect during the first 24 h. Global cerebral ischemia induces the significant decline in the Na+,K+-ATPase activity in the hippocampus starting from 1 to 168 h of reperfusion. Maximal inhibition was obtained 24 h after the ischemic damage. Application of 3.0 mg/kg of MK-801 exerted statistically significant protection during the first 24 h while the treatment with 5.0 mg/kg of MK-801 prevented fall in enzymatic activity during all reperfusion periods examined. Our results suggest that, in spite of different and complex pathophysiological mechanisms involved in the increase of FAA level and the decrease of the Na+,K+-ATPase activity, blockade of NMDA receptor subtype provides a very important strategy for the treatment of the postischemic excitotoxicity.

Safety and efficacy of monotherapy change to fixed combination (travoprost 0.004%/timolol 0.5%) in 6 months follow up period.

PURPOSE: To assess the safety and efficacy of changing antiglaucoma therapy to the travoprost 0.004%/timolol 0.5% (TTFC) fixed combination from previous monotherapies. METHODS: Prospective, open-label, observational, multicenter cohort. A change was done from prior monotherapy at day 0 to TTFC dosed once a day, regardless in the evening or in the morning, without washout period. Active evaluation of systemic and local tolerability (adverse events), and efficacy. i.e., intraocular pressure (IOP) lowering was done at control 1 (day 30), control 2 (day 90) and control 3 (day 120). RESULTS: 40/155/170 patients (79/309/339 eyes) completed the study (120 days/ 90 days/baseline, respectfully). At control 1 excluded were patients with low tolerability (severe hyperemia (6 patients), discomfort (4), chest pain (1)) and non responders (IOP lowering less than 15% from baseline IOP or target IOP >18 mmHg (4 patients)). Mean IOP at control 1 was 15.92 +/- 1.85 mm Hg (21.66% reduction) for 155 patients (non responders excluded), at control 2 was for 155 patients 15.67 +/- 2.17 mm Hg (21.14% reduction), and at control 3 for 40 patients 16.28 +/- 1.59 mm Hg (19.86% reduction). At control 2 analysis of IOP reduction by 4 groups of previous monotherapy (timolol 0,5% (N = 33/66), latanoprost 0.005% (N = 49/98), betaxolol 0.5% (N = 30/60), and travoprost 0.004% (N = 43/85) was performed. 40 patients/79 eyes endured to control 3 (after day 90 free samples were not available for all patients). Analysis of IOP reduction by 4 groups of previous monotherapy medications was performed (timolol 0.5% (N = 7/14), latanoprost 0.005% (N = 14/28), betaxolol 0.5% (N = 7/14), travoprost 0.004% (N = 12/23)). CONCLUSIONS: Changing patients from prior monotherapy to TTFC can provide on average a further reduction in IOP, while demonstrating a favorable safety profile.