Martina Tomić

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.

Diagnostic Procedures and Management of Dry Eye

Dry eye disease or dysfunctional tear syndrome is among the most frequent diagnoses in ophthalmology. It is a multifactorial disease of the ocular surface and tear film which results in ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Risk factors for dry eye syndrome include age, sex (female gender), race, contact lens wear, environment with low humidity, systemic medications, and autoimmune disorders. The aim of this paper is to present the systematic classification, epidemiology, diagnostic procedures, and advances in the management of dry eye disease. The recent improvements in comprehending the underlying etiologic factors will inevitably improve future classifications and diagnostic abilities leading to more effective therapeutic options. Treatment of this highly prevalent condition can drastically improve the quality of life of individuals and prevent damage to the ocular surface.

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.

Maternal immune system adaptation to pregnancy - a potential influence on the course of diabetic retinopathy

BackgroundProgression of diabetic retinopathy occurs at least temporarily during pregnancy. Although the cause of this progression is not entirely understood, the immune phenomenon and chronic inflammation may play a significant role. During pregnancy in order to avoid fetus rejection, certain components of the immune system that are knowingly implicated in the pathogenesis of diabetic retinopathy are activated including generalized leukocyte activation and an increase in certain cytokine plasma levels. Activated leukocytes with up regulated adhesion molecules have an increased potential to bind to the endothelium cells of blood vessels. Leukocyte-endothelial interaction and the consequent leukostasis with capillary occlusion, ischemia and vascular leakage have a substantial role in the development of diabetic retinopathy. Furthermore, certain increased cytokines are known to cause blood-retinal-barrier breakdown whilst others promote angiogenic and fibrovascular proliferation and thereby can also be implicated in the pathogenesis of this diabetic complication.Presentation of the hypothesisWe hypothesized that the activation of the immune system during gestation may have an influence on the course of retinopathy in pregnant diabetic women.Testing the hypothesisWe suggest two prospective follow up studies conducted on women with type 1 diabetes mellitus. The first study would include a group of non-pregnant women and a group of diabetic women undergoing normal pregnancy matched for age and duration of diabetes. In the second study pregnant women would be divided into two groups: one with normal pregnancy and the other with preeclampsia. The procedure and data collection in both studies will be identical: a complete ophthalmological examination, glycaemic control, blood pressure measurement and venous blood samples for the determination of plasma levels of cytokines (TNF-alpha, IL-1beta, IL-6, IL-8) and adhesion molecules (ICAM-1, VCAM-1).Implications of the hypothesisConsidering the present assumption, the gestational immune activation could be suggested as a potential risk factor for the development and progression of retinopathy in diabetic women. A better understanding of immunomodulatory effects of pregnancy on diabetic retinopathy pave the way for further investigations of the mechanism of its pathogenesis and could be essential for novel approaches to the treatment of this serious sight threatening complication of diabetes mellitus.

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.

Influence of BAK-Preserved Prostaglandin Analog Treatment on the Ocular Surface Health in Patients with Newly Diagnosed Primary Open-Angle Glaucoma

Purpose. Primary open-angle glaucoma (POAG), a chronic, degenerative optic neuropathy, requires persistent decrease of intraocular pressure so as to prevent visual impairment and blindness. However, long-term use of topical ocular medications may affect ocular surface health. Purpose of this study was to evaluate the influence of BAK-preserved prostaglandin analog treatment on the ocular surface health in patients with newly diagnosed POAG. Methods. 40 newly diagnosed POAG patients were included in this prospective study. Intraocular pressure (IOP), tear break-up time (TBUT), and ocular surface disease index (OSDI) were assessed at baseline and 3-month after starting treatment with BAK-preserved travoprost 0.004%. Results. IOP decreased in all patients from baseline to 3-month final visit (23.80 ± 1.73 mmHg versus 16.78 ± 1.27 mmHg; P < 0.001). Mean TBUT decreased from 11.70 ± 1.86 seconds at baseline to 8.30 ± 1.29 seconds at 3-month final visit (<0.001). Mean OSDI score increased from 31.63 ± 18.48 to 44.41 ± 16.48 (P < 0.001). Conclusions. This study showed that BAK-preserved travoprost 0.004% is an effective medication in newly diagnosed POAG patients, but its long-term use may negatively influence ocular surface health by disrupting the tear film stability. Further studies are needed to better understand the clinical effects of different preservative types and concentrations on the ocular surface.

Cataract Surgery in Eyes with Pseudoexfoliation (PEX) Syndrome

Pseudoexfoliation (PEX) syndrome is a common age-related systemic disorder characterized by a huge production and deposition of fibrillogranular amyloid-like extracellular material within many ocular tissues. Pseudoexfoliation is a risk factor for glaucoma and also correlated to an increased incidence of cataract formation. Cataract surgery in eyes with pseudoexfoliation is connected with many complications and presents challenges that require careful preoperative planning and intraoperative care to ensure safe surgery and successful postoperative outcome. Zonular weakness and poor pupillary dilation are two major risk factors for surgical complications and poor visual acuity after surgery. With proper preparation and use of specialized adjunctive devices, phacoemulsification (PHACO) is the preferred procedure of cataract extraction in this group of patients. Postoperatively pseudoexfoliation patients require frequent and detailed follow-up to monitor for complications such as intraocular pressure rise, inflammation and intraocular lens dislocation. In conclusion, with appropriate preoperative, intraoperative and postoperative care the risks of complications can be minimized and favourable outcomes can be achieved in cataract surgery in eyes with pseudoexfoliation syndrome.

Does maternal immune system alternation during pregnancy influence the progression of retinopathy in diabetic women

Diabetic retinopathy often progresses at least to some degree during pregnancy, however, the exact mechanism for this is still not entirely clear. The influence of immune phenomenon in the pathogenesis of diabetic retinopathy has nevertheless, already been established. During pregnancy, the maternal immunologic system undergoes some modification in order to avoid fetal allograft rejection with an activation of circulating leukocytes and an increase of different cytokine plasma levels.

Inverse Levels of Adiponectin in Type 1 and Type 2 Diabetes Are in Accordance with the State of Albuminuria

Aims. To investigate the behaviour of adiponectin (ApN) in patients with type 1 and type 2 diabetic nephropathy. Methods. ApN and inflammatory and other markers of the metabolic syndrome were compared across diabetes types, albumin excretion rate (AER), and creatinine clearance (CrCl) categories in 219 type 1 and type 2 diabetic patients. Results. Significant differences among ApN levels according to AER were found in both types of diabetes (F = 8.45, df = 2, P < 0.001). With the progression of albuminuria, ApN increased in type 1 and decreased in type 2 diabetes. Patients with decreased CrCl had higher ApN levels than those with normal CrCl in either type of diabetes (F = 12.7, df = 1, P < 0.001). The best model for ApN (R 2 = 0.9002) obtained from stepwise regression in type 1 diabetes included CrCl, BMI, WBC, CRP, and age, while in type 2 diabetes (R 2 = 0.2882) it included ppPG, LDL, and UA. Conclusion. ApN behaved differently in relation to albuminuria, increasing with its progression in type 1 diabetes and decreasing in type 2 diabetes. It was however increased in the subgroups with decreased CrCl in both types of diabetes. Albuminuria seems to be more important than renal insufficiency in the definition of ApN levels in type 1 and type 2 diabetes.

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.