The Influence of Tear Film Quality on Visual Function.

BACKGROUND: The prevalence of dry eye disease (DED) is increasing globally, resulting in a variety of eye symptoms characterized by discomfort and visual disturbances. The accurate diagnosis of the disease is often challenging and complex, requiring specialized diagnostic tools. This study aimed to investigate the impact of tear film instability on visual function and to evaluate the value of post-blink blur time (PBBT) as an alternative method for assessing tear film stability. METHODS: The study included 62 subjects: 31 with subjective symptoms of DED (Group A) and a control group consisting of 31 healthy participants (Group B). Symptoms were assessed using the standard Schein questionnaire, supplemented with additional questions. PBBT was measured using standard Snellen charts to investigate a potential association between PBBT and tear film dysfunction. Additional clinical assessments included tear film break-up time (TBUT). RESULTS: Statistically significant differences were observed in the average values of PBBT and TBUT between the examined groups. The average PBBT was 8.95 ± 5.38 s in the group with DED and 14.66 ± 10.50 s in the control group, p < 0.001. Group A exhibited an average TBUT of 4.77 ± 2.37 s, while Group B had a TBUT of 7.63 ± 3.25 s, p < 0.001. Additionally, a strong positive correlation was identified between PBBT and TBUT values (r = 0.455; p < 0.001). CONCLUSIONS: The research confirms that tear film stability has an important role in the refraction of light and the maintenance of optical quality of vision. PBBT could potentially function as an objective and clinically significant screening test for DED.

Tear Biomarkers and Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative brain disorder that represents the most common type of dementia. It poses a significant diagnostic challenge that requires timely recognition and treatment. Currently, there is no effective therapy for AD; however, certain medications may slow down its progression. The discovery of AD biomarkers, namely, magnetic resonance imaging, positron emission tomography and cerebrospinal fluid molecules (amyloid-ß and tau) has advanced our understanding of this disease and has been crucial for identifying early neuropathologic changes prior to clinical changes and cognitive decline. The close interrelationship between the eye and the brain suggests that tears could be an interesting source of biomarkers for AD; however, studies in this area are limited. The identification of biomarkers in tears will enable the development of cost-effective, non-invasive methods of screening, diagnosis and disease monitoring. In order to use tears as a standard method for early and non-invasive diagnosis of AD, future studies need to be conducted on a larger scale.

Vitamin D and Diabetic Retinopathy.

Diabetic retinopathy (DR) is the most common eye disease complication of diabetes, and hypovitaminosis D is mentioned as one of the risk factors. Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are the best-known forms of vitamin D. Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D, with the sun being one of its main sources. Vitamin D is synthesized in the skin by exposure to sunlight without protective factors, but care must be taken to avoid the development of sunburn. It not only plays an important role in maintaining healthy bones and immune system but has also been highlighted in numerous studies to have an influence on various diseases, including diabetic retinopathy. A large number of people suffer from vitamin D hypovitaminosis worldwide, and diagnosis is made by measuring the concentration of 25-hydroxyvitamin D (25(OH)D) in serum. Its deficiency can cause numerous diseases and, as such, supplementation is necessary. Clinical studies have proven the effectiveness of vitamin D supplementation in the treatment of diabetic retinopathy, but with a doctor's recommendation and supervision due to possible negative side effects.

Liver metastasis in uveal melanoma - treatment options and clinical outcome.

Uveal melanoma (UM) is the most prevalent primary intraocular malignancy in adults with a stable incidence rate between five and seven cases per million in Europe and the United States. Although UM and melanoma from other sites have the same origin, UM has different epidemiological, biological, pathological and clinical features including characteristic metastatic hepatotropism. Despite improvements in the treatment of primary tumours, approximately 50% of patients with UM will develop metastases. In 90% of cases the liver is the first site of metastasis, however the mechanisms underlying this hepatic tropism have not been elucidated. Metastatic disease is associated with a very poor prognosis with a median overall survival of 6 to 12 months. Currently, there is no standard systemic treatment available for metastatic UM and once liver metastases have developed, prognosis is relatively poor. In order to prolong survival, close follow-up in all patients with UM is recommended for early detection and treatment. The treatment of metastatic UM includes systemic chemotherapy, immunotherapy and molecular targeted therapy. Liver-directed therapies, such as resection, radioembolization, chemoembolization, immunoembolization, isolated and percutaneous liver perfusion as well as thermal ablation represent available treatment options. However, to date a consensus regarding the optimal method of treatment is still lacking and the importance of setting guidelines in the treatment and management of metastatic UM is becoming a priority. Improvement in knowledge and a better insight into tumour biology, immunology and metastatic mechanism may improve current treatment methods and lead to the development of new strategies paving the way for a personalized approach.

Analysis of association of risk factors for age-related macular degeneration.

PURPOSE: To evaluate the significance of risk factors and analyze their interrelationship in developing age-related macular degeneration (AMD). MATERIALS AND DESIGN: This is a multicenter, cross-sectional study conducted in eight ophthalmology centers in Europe. The STARS (Simplified Thea AMD Risk-Assessment Scale) questionnaire was used to assess 12 risk factors grouped in four major categories. We used Welch's t-test/F ratios to determine statistically significant changes. The principal component analysis was done to investigate the association between risk factors. RESULTS: There were 3297 participants included in our data analysis. Nineteen percent of patients had a high risk of developing AMD, whilst 45.92% and 34.85% had moderate and small risk, respectively. Atherosclerosis appeared as the most relevant risk indicator for AMD development (Cohen's d = 0.861). Tukey's post hoc analysis of the smoking variable showed that ex-smokers (p < 0.001) have a significantly high risk of developing AMD. The Welch's t-test showed pseudophakic patients have a higher risk of developing AMD than phakic ones. Then, we conducted the principal component analysis, which revealed a significant connection between smoking and male gender and between smoking and atherosclerosis. Pseudophakic patients were generally older and had more often myocardial infarction as compared to phakic patients. We showed that higher BMI, history of arterial hypertension, hypercholesterolemia, and atherosclerosis tend to occur together as risk factors for AMD. CONCLUSION: Risk factors evaluated in our study should be considered for the development of AMD.

Psychiatric Disorders and Dry Eye Disease - A Transdisciplinary Approach.

Dry eye disease (DED) is a multifactorial disorder representing one of the most common ocular morbidities and a significant public health problem. It often results in eye discomfort, visual disturbances and potential damage to the corneal surface affecting quality of life (QOL). In recent years, the relationship between DED and psychiatric disorders has been gaining attention. A number of epidemiological studies have reported a possible association between dry eye and psychiatric disorders showing that the subjective symptoms of dry eye can be affected not only by changes of the tear film and ocular surface but also psychological factors such as anxiety, depression, schizophrenia, post-traumatic stress disorder (PTSP) and subjective happiness. Apart from psychiatric disorders, psychiatric medications are also considered as risk factors for DED due to their influence on the tear film status. The incidence of ocular side effects increases rapidly with the use of polypharmacy, a very common form of treatment used in psychiatry. There is often inconsistency between signs and symptoms of DED, where symptoms often are more related to non-ocular conditions including psychiatric disorders than to tear film parameters. Consequently, in many cases DED may be considered as a psychiatric as well as ophthalmological problem. Psychiatrists and ophthalmologists need to be aware of the potential influence of psychiatric disorders and medications on tear film stability. In treatment of psychiatric patients, an integrative and transdisciplinary approach will result in better functioning and higher QOL.

Inflammatory and angiogenic biomarkers in diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM) and a leading cause of blindness in working-age adults in developed countries. Numerous investigations have recognised inflammation and angiogenesis as important factors in the development of this complication of diabetes. Current methods of DR treatment are predominantly used at advanced stages of the disease and could be associated with serious side effects. Therefore, new diagnostic methods are needed in order to identify the initial stages of DR as well as monitoring the effects of applied therapy. Biochemical biomarkers are molecules found in blood or other biological fluid and tissue that indicate the existence of an abnormal condition or disease. They could be a valuable tool in detecting early stages of DR, identifying patients most susceptible to retinopathy progression and monitoring treatment outcomes. Biomarkers related to DR can be measured in the blood, retina, vitreous, aqueous humour and recently in tears. As the retina represents a small part of total body mass, a circulating biomarker for DR needs to be highly specific. Local biomarkers are more reliable as indicators of the retinal pathology; however, obtaining a sample of aqueous humour, vitreous or retina is an invasive procedure with potential serious complications. As a non-invasive novel method, tear analysis offers a promising direction in further research for DR biomarker detection. The aim of this paper is to review systemic and local inflammatory and angiogenic biomarkers relevant to this sight threatening diabetic complication.

Prevalence of diabetic retinopathy in the Dubrovnik-Neretva County.

OBJECTIVE: Diabetic retinopathy is one of the leading causes of blindness. We estimated the prevalence of diabetic retinopathy among a diabetic population in the Dubrovnik-Neretva County in the Republic of Croatia and searched for potential risk factors. METHODS: A prospective study was performed with 600 diabetic patients from different parts of the Dubrovnik-Neretva County who attended regular medical and ophthalmological check-ups at the General Hospital Dubrovnik from September 2014 to September 2015. Patients underwent a complete medical assessment by two ophthalmologists. Retinal examination included evaluation of the presence of diabetic retinopathy. Any retinopathy present was graded as mild non-proliferative retinopathy, moderate-severe non proliferative retinopathy or proliferative retinopathy. RESULTS: Retinopathy was present in 44.5% of the study sample. 20.7% had the mild form of diabetic retinopathy, 18.8% had the moderate-severe form, and 5.0% had proliferative diabetic retinopathy. The mean duration of diabetes was 12.94 years ± 6.85; 12.89 years ± 9.18 in men, 12.94 ± 6.54 in women. The mean BMI was 27.14 ± 2.98; for diabetics without diabetic retinopathy 26.19 ± 2.75; for those with the mild form 28.06 ± 3.01; for those with the moderate-severe form 28.49 ± 2.54; for those with proliferative diabetic retinopathy 28.79 ± 3.16. 168 (28%) patients were treated by laser and 22 (3.7%) by vitrectomy. CONCLUSION: The prevalence of diabetic retinopathy in the Dubrovnik-Neretva County is 44.5%. Regular screening to detect diabetic retinopathy is highly recommended as timely intervention can prevent most diabetic causes of blindness.

A Survey of Current Prophylactic Treatment for Ophthalmia Neonatorum in Croatia and a Review of International Preventive Practices.

BACKGROUND Ophthalmia neonatorum, or neonatal conjunctivitis, is an acute infection that occurs within the first 28 days of life. This aim of this survey was to evaluate the current methods of preventive treatment for ophthalmia neonatorum in maternity hospitals in Croatia. MATERIAL AND METHODS The annual hospital birth rate in Croatia is approximately 40,000. A clinical survey was undertaken with data collected using questionnaires sent to all 32 maternity hospitals in Croatia. There was a 100% response rate to the questionnaires. RESULTS Preventive treatment for ophthalmia neonatorum was administrated to all newborns in 75% (24/32) of Croatian maternity hospitals. In 45.8% of maternity hospitals, (11/32) these procedures were performed within the first hour after birth. In 54.2% of maternity hospitals (13/32), preventive treatment for ophthalmia neonatorum was administrated to all newborns from one to three hours after birth. The main treatment agent was tobramycin (83.3%). Other topical prophylactic treatments included povidone-iodine (8.3%), erythromycin (4.2%), and silver nitrate (4.2%). In 25% of obstetric units, prophylaxis for ophthalmia neonatorum was not used routinely, but in cases of diagnosed neonatal conjunctivitis, antibiotic treatment with tobramycin was mainly used. CONCLUSIONS A survey of all 32 maternity hospitals in Croatia showed variation in the prevalence of preventive treatment for ophthalmia neonatorum and the methods used. These findings support the need to implement standardized preventive measures that both conform to international clinical guidelines and recognize treatment availability in Croatia, where topical povidone-iodine is currently preferred for the prevention of ophthalmia neonatorum.

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.

Traumatic Optic Neuropathy - Case Report with Discussion on Diagnostic Procedures and Therapy.

Traumatic optic neuropathy (TON) is a serious vision threatening condition that can be caused by ocular or head trauma. Indirect damage to the optic nerve is the most common form of TON occurring in 0.5% to 5% of all closed head trauma cases. Although the degree of visual loss after indirect TON may vary, approximately 50% of all patients are left with 'light perception' or 'no light perception' vision, making TON a significant cause of permanent vision loss. We present a 47-year-old male patient with a history of right eye keratoconus following a motorcycle crash. Visual acuity was of 'counting fingers at 2 meters' on the right eye due to keratoconus and 'counting fingers at 1 meter' on the left eye as a consequence of trauma. The Octopus visual field showed diffuse re-duction in retinal sensitivity and the Ishihara color test indicated dysfunction of color perception on the left eye. Relative afferent pupillary defect was also present. Computed tomography revealed multifragmentary fracture of the frontal sinus and the roof of the left orbit without bone displacement. Based on the findings, conservative corticosteroid therapy without surgery was conducted. The patient responded well to treatment with complete ophthalmologic recovery.

Conjunctival Melanoma - Epidemiological Trends and Features.

Conjunctival melanoma is a rare but sight and life threatening malignancy. It accounts for 2%-5% of all ocular tumours and 5%-7% of all ocular melanomas with an incidence of 0.2-0.8 per million in the Caucasian population with rare cases reported in the non-Caucasians. In recent decades the incidence of uveal melanoma has been relatively stable whilst conjunctival and cutaneous melanoma have shown increasing incidence which may be connected to the result of environmental exposure to ultraviolet light. The dissimilarity in incidence between light and dark pigmented individuals observed in conjunctival melanomas compared to uveal and cutaneous melanomas may be related to differences in their histological structures and genetic profile. Recent molecular biological studies support the fact that each type of melanoma undergoes its own molecular changes and has characteristic biological behaviour. Further studies are required for each type of melanoma in order to ascertain their individual etiology and pathogenesis and based on this knowledge develop relevant preventative and treatment procedures.

Body mass index and retinopathy in type 1 diabetic patients.

Aim. To investigate whether body mass index (BMI) independently or in correlation with other risk factors is associated with diabetic retinopathy (DR) progression. Methods. The study included 176 patients with type 1 diabetes divided into three groups according to DR status: group 1 (no retinopathy; n = 86), group 2 (mild/moderate nonproliferative DR; n = 33), and group 3 (severe/very severe NPDR or proliferative DR; n = 57). Results. A significant deterioration of HbA1c, an increase in total cholesterol, systolic, diastolic blood pressure, and diabetic nephropathy with the progression of retinopathy were found. DR progression was correlated with diabetes duration, HbA1c, hypertension, total cholesterol, and the presence of nephropathy. In patients without nephropathy, statistical analyses showed that progression of retinopathy increased significantly with higher BMI (gr. 1: 24.03 ± 3.52, gr. 2: 25.36 ± 3.44, gr. 3: 26.93 ± 3.24; P < 0.01). A positive correlation between BMI and a significant deterioration of HbA1c, an increase in cholesterol, triglycerides, and hypertension was observed. Conclusion. BMI in correlation with HbA1c, cholesterol, and hypertension appears to be associated with the progression of DR in type 1 diabetic patients without nephropathy. However, additional studies are required to investigate the pathogenic role of obesity and weight loss in retinal diabetic complications particularly relating to nephropathy.

Body mass index: a risk factor for retinopathy in type 2 diabetic patients.

The aim of the study was to investigate whether body mass index (BMI) independently or in correlation with other risk factors is associated with diabetic retinopathy (DR) progression. The study included 545 patients with type 2 diabetes. According to DR status, they were divided into three groups: group 1 (no retinopathy; n = 296), group 2 (mild/moderate nonproliferative DR; n = 118), and group 3 (severe/very severe NPDR or proliferative DR; n = 131). Patients without DR were younger than those with signs of retinopathy at time of diabetes onset whilst diabetes duration was longer in groups with severe NPDR and PDR. DR progression was correlated with diabetes duration, BMI, HbA1c, hypertension, and cholesterol. Statistical analyses showed that the progression of retinopathy increased significantly with higher BMI (gr. 1: 26.50 ± 2.70, gr. 2: 28.11 ± 3.00, gr. 3: 28.69 ± 2.50; P < 0.01). We observed a significant deterioration of HbA1c and a significant increase in cholesterol and hypertension with an increase in BMI. Correlation between BMI and triglycerides was not significant. Thus, BMI in correlation with HbA1c cholesterol and hypertension appears to be associated with the progression of DR in type 2 diabetes and may serve as a predictive factor for the development of this important cause of visual loss in developed countries.

Inflammation, haemostatic disturbance, and obesity: possible link to pathogenesis of diabetic retinopathy in type 2 diabetes.

PURPOSE: The pathogenesis of diabetic retinopathy (DR) is insufficiently understood but may possibly involve chronic, low-grade inflammation. The aim of this cross-sectional study was to investigate the relationship between inflammatory and haemostatic markers, other markers of endothelial dysfunction and anthropometric parameters, and their association with DR in patients with type 2 diabetes. METHODS: According to the DR status patients were divided into three groups: no retinopathy, mild/moderate nonproliferative (NPDR), and severe NPDR/proliferative retinopathy (PDR). RESULTS: The groups did not differ in the levels of inflammatory and haemostatic markers, other markers of endothelial dysfunction, and anthropometric parameters. After dividing the patients according to the level of obesity (defined by BMI, WC, and WHR) into three groups ANOVA showed the differences in C-reactive protein according to the WC (P = 0.0265) and in fibrinogen according to the WHR (P = 0.0102) as well as in total cholesterol (P = 0.0109) and triglycerides (P = 0.0133) according to the BMI. Logistic regression analyses showed that diabetes duration and prolonged poor glycemic control are the main predictors of retinopathy in patients with type 2 diabetes. CONCLUSION: Interrelations between obesity, inflammation, haemostatic disturbance, and other risk factors may possibly play an important additional role in endothelial dysfunction involved in the pathogenesis of diabetic retinopathy.

Inflammation and pharmacological treatment in diabetic retinopathy.

Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, is estimated to be the leading cause of new blindness in the working population of developed countries. Primary interventions such as intensive glycemic control, strict blood pressure regulation, and lipid-modifying therapy as well as local ocular treatment (laser photocoagulation and pars plana vitrectomy) can significantly reduce the risk of retinopathy occurrence and progression. Considering the limitations of current DR treatments development of new therapeutic strategies, it becomes necessary to focus on pharmacological treatment. Currently, there is increasing evidence that inflammatory processes have a considerable role in the pathogenesis of DR with multiple studies showing an association of various systemic as well as local (vitreous and aqueous fluid) inflammatory factors and the progression of DR. Since inflammation is identified as a relevant mechanism, significant effort has been directed to the development of new concepts for the prevention and treatment of DR acting on the inflammatory processes and the use of pharmacological agents with anti-inflammatory effect. Inhibiting the inflammatory pathway could be an appealing treatment option for DR in future practices, and as further prospective randomized clinical trials accumulate data, the role and guidelines of anti-inflammatory pharmacologic treatments will become clearer.

Influence of hypertension and type 2 diabetes mellitus on cerebrovascular reactivity in diabetics with retinopathy.

BACKGROUND AND OBJECTIVES: Cerebrovascular reactivity (CVR) provides information on the intracerebral arterioles capacity to react to vasodilatory stimuli. The current study aimed to investigate the influence of hypertension and type 2 diabetes mellitus on CVR in diabetics with retinopathy. DESIGN AND SETTING: Retrospective analysis of data prospectively collected over a 1-year period. SUBJECT AND METHODS: Subjects were classified into four groups each comprised of 30 participants: diabetic retinopathy with hypertension (DRH), diabetic retinopathy without hypertension (DR), hypertension without diabetes mellitus (H), and healthy controls without diabetes and hypertension (C). CVR was estimated in relation to the increase in the mean flow velocity compared with the basal velocity in both middle cerebral arteries during hypercapnia. RESULTS: In the DRH group, the mean (SD) increase in CVR was 8.8 (2.49) cm/s, in the H group 14.4 (2.59) cm/s and in the DR group 9.7 (2.97) cm/s. The analysis of variance showed significant differences among the groups in blood flow velocity after a breath-holding test (F=89.83; df=3.116; P < .001). CONCLUSIONS: Diabetes mellitus influences CVR more than hypertension.

IL-12 concentrations in the aqueous humor and serum of diabetic retinopathy patients.

BACKGROUND: Previous studies suggest that inflammation plays an important part in the pathogenesis of diabetes. Cytokines may have a role in both positive and negative control of immunological reactions. Among many cytokines, interleukin 12 (IL-12) is known to be a strong pro-inflammatory cytokine. METHODS: A total of 76 participants were enrolled in this study and classified into four groups: 23 diabetic patients with non-treated retinopathy, 17 diabetic patients with treated retinopathy, 12 diabetic patients without retinopathy, and 24 healthy control patients. Serum and aqueous humor samples were taken for the analysis of IL-12 concentration. RESULTS: The aqueous humor IL-12 concentration was significantly elevated in the patients with non-treated diabetic retinopathy (χ(2)(3, n = 76) = 27.137; p < 0.001). No significant differences in IL-12 serum concentrations between the groups were found (F = 0.405, p = 0.750). Correlation analysis of IL-12 concentrations in the serum and aqueous humor showed a linear association between the two variables only in non-diabetic patients (p = 0.003). CONCLUSIONS: This is the first study to show a significantly higher concentration of pro-inflammatory cytokine IL-12 in the aqueous humor of non-treated diabetic retinopathy patients in comparison with diabetic patients treated for retinopathy, without retinopathy, or with healthy individuals. Because the serum levels of IL-12 did not differ considerably between the studied groups, it is plausible that this is due to its local production and secretion.

The incidence of stroke at Department of Neurology, Dubrovnik General Hospital in 2008.

Data on all patients admitted in 2008 to the Department of Neurology, Dubrovnik General Hospital, were retrospectively analyzed. In a total of 663 patients, there were 247 (37.25%) stroke patients. Ischemic stroke was diagnosed in 217 (87.85%) and hemorrhagic stroke in 30 (12.15%) patients. In the cohort of stroke patients, there were 136 (55.00%) women and 111 (45.00%) men. The group of patients with ischemic stroke consisted of 124 (57.15%) women and 93 (42.85%) men, and the group of those with hemorrhagic stroke of 12 (40%) women and 18 (60%) men. The majority of patients with ischemic stroke (89.86%) and hemorrhagic stroke (76.66%) were over 60 years of age. Only 9 (4.14%) patients with ischemic stroke and 5 (16.66%) patients with hemorrhagic stroke were employed. The mortality rate was 20.24% in the overall stroke group and 19.35% in the ischemic stroke group. In the group of patients with hemorrhagic stroke, 26.66% of patients died at our Department, however, additional 20% of patients with this type of stroke were transferred to the Hospital Intensive Care Unit or to Departments of Neurosurgery in Split and Zagreb, so precise data on the disease outcome in these patients were missing. Eighteen (7.29%) patients were from other countries, mostly from Bosnia and Herzegovina. The majority of them had ischemic stroke (83.33%) and 12 (66.66%) patients were over 60 years of age.