Assessment of Retinal Microangiopathy in Patients with Balkan Endemic Nephropathy Using Optical Coherence Tomography Angiography-A Pilot Study.

Background and Objectives: It is well known that alterations in microvascular structure and function contribute to the development of ocular, renal, and cardiovascular diseases. Accordingly, the presence of fundus vascular changes in patients suffering from chronic kidney disease (CKD) and Balkan endemic nephropathy (BEN) may provide information of prognostic value regarding the progression of renal disease. This study aimed to examine the associations between clinical characteristics and retinal optical coherence tomography angiography (OCTA) parameters in patients with BEN and compare them with those in CKD. Materials and Methods: This pilot study, conducted from March 2021 to April 2022, included 63 patients who were divided into two groups: the first group consisted of 29 patients suffering from BEN, and the second was a control group of 34 patients with CKD. Demographic, laboratory, clinical, and medication data were noted for all the patients included in this study. Each eye underwent OCT angiography, and the results were interpreted in accordance with the practical guide for the interpretation of OCTA findings. Results: Statistically significantly higher levels of total serum protein and triglycerides were recorded in the BEN group than in the CKD group, while the level of HDL cholesterol was lower. Based on the performed urinalysis, statistically significantly higher values of total protein and creatinine were detected in patients with CKD compared to the BEN group. It was demonstrated that the OCTA vascular plexus density of certain parts of the retina was in significant association with systolic and diastolic blood pressure, creatinine clearance, urinary creatinine, total cholesterol, diabetes mellitus type 2, age, body mass index, total serum and urinary protein, sCRP, and diuretic and antihypertensive treatment. Conclusions: In comparison with CKD, BEN leads to more significant disturbances in retinal vasculature density.

Lateral frontal galeal-cutaneous flap for reconstruction after orbital exenteration for advanced periorbital skin cancer.

BACKGROUND: Orbital exenteration (OE) is one of the most disfiguring procedures leading to significant deformity. Defect reconstruction is challenging, especially in elderly patients. Herein, experiences with orbital exenteration and primary reconstruction with lateral frontal galeal-cutaneous flap based on superficial temporal artery were reviewed. METHODS: Data on patients treated for nonmelanoma skin cancer invading the orbit during a 10-year period were analyzed. The patient demographics, tumor features, reconstructive techniques used, complications, and survival were recorded with a median follow-up of 27.5 months. RESULTS: Included in the study were 26 patients in whom OE was performed, comprising 14 males and 12 females, with a mean age of 75.29 years (range: 61-87). The majority of the patients were treated for basal cell carcinoma with medial cantus as the primary site. All of the defects were closed using a lateral frontal galeal-cutaneous flap based on the superficial temporal artery, and in 2 patients, a temporalis muscle pedicle flap was used as an additional flap for reconstruction of the orbital roof in order to separate the brain from the empty orbit, and it was then covered with the same galeal-cutaneous flap. In 19 patients, the frontal area was closed primarily, and in 7 patients, skin graft was used for the secondary defect. There was no flap loss. Tumor-related death was registered in 3 patients (inoperable recurrent tumors) (11.5%), 7 died from complications that were unrelated to the tumors (2 were operated for recurrent orbital tumors), and 16 survived. DISCUSSION: The preferred method for reconstruction after OE at our university affiliated center is lateral frontal galeal-cutaneous flap based on the superficial temporal artery. Flap harvesting is simple, safe, and obtains enough tissue to cover the defects, even after extended exenteration. The complication rate is low. The simultaneous use of this flap with pedicle temporalis muscle flap is suggested only for reconstruction of the scull base after anterior cranial fossa resection.

Ganglion Cell-Inner Plexiform Layer Thickness in Different Glaucoma Stages Measured by Optical Coherence Tomography.

AIM: To compare ganglion cell (GCL) and inner plexiform layer (IPL) thickness in patients at different stages of primary open-angle glaucoma (POAG), determine their sensitivity and specificity values, and correlate thickness values with mean deviations (MD). METHODS: This prospective, cross- sectional study was conducted in a group of patients with confirmed POAG who were compared to an age- and gender-matched control group. Glaucomatous damage was classified according to the Hodapp-Parrish-Anderson scale: glaucoma stage 1 (early), glaucoma stage 2 (moderate), and glaucoma stage 3 (severe). The average, minimum, and all 6 sectoral (superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal) GCL + IPL thicknesses were measured and compared between groups. RESULTS: The average GCL + IPL thickness of 154 eyes of 93 patients in glaucoma stages 1, 2, 3, and 94 eyes of 47 persons in the control group were 76.79 ± 8.05, 65.90 ± 7.92, 57.38 ± 10.00, and 86.01 ± 3.68 µm, respectively. There were statistically significant differences in the average, minimum, and all 6 sectoral GCL + IPL values among the groups. The areas under the receiver operating characteristic curve for average and minimum GCL + IPL thickness values were 0.93 and 0.94, respectively, sensitivity 91.5 and 88.3%, and specificity 98.9 and 100%, respectively. Both thickness values showed significant correlations with MD. Each micrometer decrease in the average GCL + IPL thickness was associated with a 0.54-dB loss in MD. CONCLUSION: GCL + IPL layer thickness is a highly specific and sensitive parameter in differentiating glaucomatous from healthy eyes showing progressive damage as glaucoma worsens. Loss of this layer is highly correlated with overall loss of visual field sensitivity.

Lactate dehydrogenase and oxidative stress activity in primary open-angle glaucoma aqueous humour.

Lactate dehydrogenase (LDH) and lactate are some of the hypoxy biochemical parameters. Extracellular activity of this enzyme increases under the condition of oxidative stress, since the cell integrity can be disrupted during the lipid peroxidation process. Subsequently that leads to the increase level of the lactic acid and lactic acid salts. The objective of this investigation is establishing the level of LDH, LDH1 (HBDH) and the lactate concentration in aqueous humour in patients with primary open-angle glaucoma. Biochemical analysis have been made by enzymatic-colometric method (lactate) and UV-kinetic method (LDH and HBDH) in aqueous humour of 30 patients (42 eyes) with primary open-angle glaucoma (POAG) and 30 patients (40 eyes) with cataract (the control group). The increased values of lactate and the activity of LDH and HBDH enzyme in aqueous humour of POAG patients in correlation with the control group are the results not only of oxidative stress but also of hypoxy and the mitochondry oxidative function (p<0,001). The increased activity of the examined biochemical parameters in the aqueous humour of the POAG patients points to the fact that other mechanisms, besides IOP, have a role in glaucoma pathogenesis.

Ocular surface disease incidence in patients with open-angle glaucoma.

Introduction: Ocular surface disease (OSD) is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbances, tear film instability with potential damage to the ocular surface, accompanied by increased tear film osmolarity and inflammation of the ocular surface. It is a consequence of disrupted homeostasis of lacrimal functional unit. The main pathogenetic mechanism stems from tear hyperosmolarity and tear film instability. The etiological classification is hyposecretory (Sy-Sjögren and non-Sjögren) and evaporative (extrinsic and intrinsic) form. Delphi panel classification grades disease stages. Antiglaucoma topical therapy causes exacerbation or occurrence of symptoms of dry eye due to main ingredients or preservatives (benzalkonium chloride ­ BAK), which are dose- and time-dependent. BAK reduces the stability of the lipid layer of tears, the number of goblet cells, induces apoptosis and inflammatory infiltration. Objective: The aim of this study was the analysis of the OSD incidence in open-angle glaucoma patients caused by topical medicamentous therapy. Methods: Retrospective analysis of examined patients with open-angle glaucoma was used. Results: Increased incidence of moderate and advanced OSD Index degrees in the group of primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma. According to the Delphi Panel Scale the most common grade is IIb (POAG and pseudoexfoliative glaucoma). Evaporative form of OSD prevailed in all treatment groups. High percentage of dry eye in patients with higher concentrations of preservatives applied was noticed. Conclusion: OSD should be timely diagnosed and treated. Dry eye has an impact on surgical outcome and postoperative visual acuity, and in order to improve patient compliance and quality of life, symptoms of dry eye should be addressed and medications with lower concentrations of preservatives should be applied.

Ocular fundus abnormalities in patients with Balkan endemic nephropathy and other chronic kidney diseases.

AIM: The aim of this study was to examine the ocular fundus pathology in patients with Balkan endemic nephropathy (BN) and chronic kidney diseases (CKD). METHODS: The study included 51 patients with BN from the South Morava River region in Serbia, and 102 subjects with different stages of chronic renal diseases, matched according to age and gender, obtained from a database used in a recently published study. All patients had visited Outpatient Department of the Clinic of Nephrology, Clinical Center Nis. All patients underwent routine ophthalmic examinations. RESULTS: There were significantly more (P < 0.001) patients with age-related macular degeneration (AMD) in the group with BN (31.37 %) than in those with CKD (5.88 %). Multivariate logistic regression analysis confirmed that the significant factors related to AMD in the group with BN were albuminuria (P < 0.05) and proteinuria (P < 0.05); in CKD patients, the level of HDL (P < 0.05), while negative correlation with the level of triglyceride was registered (P < 0.05). There was no association between estimated glomerular filtration rate and AMD. The significant factors related to retinopathy in the group with BN are age (P < 0.05) and serum creatinine values (P < 0.05), in patients with CKD increasing age (P < 0.001) and DM (P < 0.05). CONCLUSION: Ocular fundus pathology in patients with BN is similar to the pathology of other CKD, but with significantly more AMD (about four times), probably related to the genetic/epigenetic factors.

Ocular and systemic factors associated with glaucoma in chronic kidney disease patients.

The goal of this study was to examine, the relationship between chronic kidney disease (CKD) and glaucomatous optic disc neuropathy in a cohort of patients from the south-east Serbia and to determine whether limited screening for glaucoma in specific subgroups of patients with CKD is reasonable and justifiable. This cross-sectional study included 328 subjects with various stages of CKD. All patients had visited the Outpatient Department of the Nephrology Clinic, Clinical Center Nis, Serbia. All patients underwent routine ophthalmic examinations. Glaucoma diagnosis based on elevated intraocular pressure (IOP), the presence of excavation of the optic nerve head (C/D ratio), and characteristic glaucomatous visual field loss (MD-mean deviation, PSD-pattern standard deviation). CKD was defined as kidney damage or glomerular filtration rate (GFR) of <60 ml/min/1.73 m(2) for >3 months. A total number of 328 CKD patients, 33 (10.1 %) with primary open angle glaucoma and 28 (8.5 %) with ocular hypertension (OH), were included in the study. Patients with CKD and glaucoma had significantly higher mean values of C/D ratio (0.59), visual field mean deviations (dB)-MD (p < 0.001), and visual field pattern standard deviations (dB)-PSD (p < 0.001) than patients with CKD and OH. Stepwise multivariate linear regression analysis confirmed that the most significant factors related to IOP are age (p < 0.05), AHT (p = 0.01), and eGFR (p = 0.001). Multivariate regression analysis also confirmed that the most significant factors related to cup-to-disc ratio are number of years of smoking (p < 0.05), AHT, and sCr (p < 0.01). In conclusion, the prevalence of glaucoma among CKD patients in the cohort from south-east Serbia is 10.1 %. Patients with CKD and glaucoma, eGFR and current cigarette smoking are associated with IOP level, MD, and PSD of visual field and C/D ratio.

Ocular melanoma: an overview of the current status.

Ocular melanoma is the second most common type of melanoma after cutaneous and the most common primary intraocular malignant tumor in adults. Large majority of ocular melanomas originate from uvea, while conjunctival melanomas are far less frequent. Incidence of uveal melanoma has remained stable over last three decades. Diagnosis is in most cases established by clinical examination with great accuracy. Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye, but survival rates have remained unchanged. Recent advances in cytogenetics and genetics enhanced prognostication and enabled to determine tumors with high metastatic potential. However, due to lack of effective systemic therapy, prognosis of patients with metastasis remains poor and metastatic disease remains the leading cause of death among patients with uveal melanoma. Conjunctival melanoma is rare, but its incidence is increasing. It mostly occurs among white adults. In majority of cases it originates from preceding primary acquired melanosis. Current standard treatment for conjunctival melanoma is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy and topical application of chemotherapeutic agent. Rarity of this tumor limits conduction of controlled trials to define the best treatment modality. As well as for uveal melanoma, prognosis of patients with metastasis is poor because there is no effective systemic therapy. Better understanding of underlying genetic and molecular abnormalities implicated in development and progression of ocular melanomas provides a great opportunity for development of targeted therapy, which will hopefully improve prognosis of patients with metastatic disease.

Prevalence and early detection of abdominal aortic aneurysm in pseudoexfoliation syndrome and pseudoexfoliation glaucoma.

PURPOSE: The goals of this study were to demonstrate the frequency of infrarenal abdominal aortic aneurysm (AAA) in patients with pseudoexfoliation (PEX) syndrome (PEXS) and PEX glaucoma (PEXG), and to determine whether limited screening for AAA in specific subgroups of patients with PEX is reasonable and justifiable. MATERIALS AND METHODS: This prospective study comprised 60 patients with PEXS and 60 with PEXG (examined group), and 60 patients with primary open-angle glaucoma (POAG) and 60 with cataract (control group). Clinical ophthalmic examination included slit-lamp biomicroscopy of the anterior segment and direct slit-lamp gonioscopy (using a Goldmann three-mirror lens) of the anterior chamber angle. All patients underwent routine Color Doppler duplex ultrasonography of the infrarenal aorta and iliac arteries. RESULTS: There was a statistically significant difference (p < 0.05) between the PEXG group and control group vis-a-vis presence of AAA, which occurred more frequently in patients with greater amounts of angle pigmentation (p < 0.05). Univariate logistic regression analysis indicated statistically significant associations between AAA and PEX (p < 0.01), angle pigmentation (p < 0.05), gender (p < 0.01), diabetes mellitus (DM) (p < 0.05), and arterial hypertension (AHT) (p < 0.01). Multivariate regression analysis, adjusted to gender and age, showed that the most important clinical parameters related to AAA in patients with PEXS and PEXG are gender, presence of PEX, DM, and AHT (p < 0.05). CONCLUSION: The frequency of AAA is significantly higher in patients with PEXS and PEXG than in patients with POAG or cataract. Restricted screening for AAA in male PEXS patients, who also have elevated degrees of angle pigmentation, arterial hypertension, and DM, is clinically warranted.

Transforming growth factor beta1, matrix-metalloproteinase-2 and its tissue inhibitor in patients with pseudoexfoliation glaucoma/syndrome.

BACKGROUND/AIM: Transforming growth factor-beta1 (TGF-beta1), oxidative stress and imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may play an important role in pathogenesis of pseudoexfoliation syndrome/glaucoma (PEX Sy/Gl). The aim of the study was to measure concentrations of TGF-beta1, MMP-2, TIMP-2 in the aqueous humor in the examined group, as well as to compare the biochemical findings with the following clinical parameters: degree of chamber angle pigmantation, presence of pseudoexfoliation and the value of intraocular pressure (IOP). METHODS: Aqueous samples from 30 patients with cataract, 30 patients with PEX Sy, 36 patients with PEX Gl, and 42 patients with primary open-angle glaucoma (POAG) were collected during phacoemulsification cataract surgery. TGF beta1, MMP-2, TIMP-2 Fluotokine Multi Analyze Profiling kits and Luminex technology were used to simultaneously measure TGF beta1, MMP-2 and TIMP-2. RESULTS: TGF-beta1, MMP-2, TIMP-2 were detected in human aqueous from all the groups with the highest level in the group with PEX Gl. Statistically, a significant correlation between the levels of TGF beta1, MMP-2, TIMP-2 in the aqueous humor of the patients with PEX Gl and the IOP value was confirmed (p < 0.05). In this group, the positive correlations between the TGF beta1 concentration in the aqueous humor and the presence of pseudoexfoliation (p < 0.01), on the one hand, and between the TIMP-2 level and the presence of pseudoexfoliation (p < 0.05), on the other, were reported. A statistically significant positive correlation of TGF-beta1 and MMP-2, and the degree of chamber angle pigmentation in the PEX Gl group was confirmed (p < 0.05). In the POAG group, TIMP-2 values were in a negative correlation with the degree of pigmentation (p < 0.05), and the IOP value (p < 0.05). CONCLUSION: TGF beta1 and MMP-2 affect the degree of chamber angle pigmentation and the degree of pseudoexfoliation in patients with pseudoexfoliative glaucoma.

Anticardiolipin antibodies in patients with Behcet's disease.

The aims of this study are to determine anticardiolipin antibodies in patients with Sy Behcet and to determine correlation between the levels of anticardiolipin antibodies in serum in patients with clinic systemic and ocular manifestations. The study was conducted on 11 patients with Behcet disease (group I), and on 11 healthy subjects (group II). Anticardiolipin antibodies -aCL were determined by the standard ELISA method, where 1GPL= 1 microgram/ml IgG aCL and 1 MPL= 1 microgram/ ml IgM, and were considered negative < 10 GPL or MPL, low positive (10-40 GPL and MPL), or high positive (>40 GPL and MPL). In the group of 11 patients with the diagnosis Sy Behcet, 6 of them were (54.5%) with values of anticardiolipin antibodies over 10 positive. In the control group of the healthy examinees aCl were positive in 2 cases (18.2%). There are no statistically significant differences in the presence of systemic clinic characteristics between aCl positive and negative patients. All the patients with SY Behcet in whom anticardiolipn antibodies were found have extremely severe visual damage which is not present in the group of those patients where the values of aCl were low. The difference is statistically significant. The level of anticardiolipin antibodies is increased in the patients with Behcet. There are no statistically significant differences in the presence of systemic clinical characteristics between aCL positive and negative patients. Visual acuity in patients with SY Behcet is statistically significantly much lower in patients who had increased values of aCL.

Helicobacter pylori: an underestimated factor in acute anterior uveitis and spondyloarthropathies?

Acute anterior uveitis (AAU) is the most common form of intraocular inflammation, but its aetiology is still unclear. Fifty percent of AAU patients are HLA-B27-positive, and half of these also have spondyloarthropathies (SpA). Numerous serological studies have shown elevated levels of serum antibodies to various Gram-negative bacteria in HLA-B27-positive AAU and SpA patients. Antigenic similarities between these bacteria and host components (HLA-B27) have already been shown. Still, the mechanism underlying these diseases has not been clarified. Among the Gram-negative bacteria, Helicobacter pylori has not been screened in AAU patients. The purpose of our study was to see if this common human pathogen somehow interferes with AAU. In addition Chlamydia trachomatis, Yersinia enterocolitica 03 and 09, Salmonella sp. and Proteus OX19 were also examined. A total of 60 patients consisting of 4 groups (15 patients with AAU, 15 with SpA, 15 with AAU+SpA and 15 healthy control persons) were examined. A high percentage of the serological results of all investigated bacteria was positive: 80% in the AAU, 93.3% in the SpA and 100% in the AAU+SpA group, while it amounted to 66.7% in the control group (p < 0.05). H. pylori showed the highest percentage of positivity in all 3 patient groups (66.7% in the AAU, 73.3% in the SpA and 80% in the AAU+SpA group). In contrast, 26.7% of the controls were anti-H.-pylori-positive, thus showing a statistically significant difference between the patients and the control group (p < 0.05). HLA-B27/B7-CREG positivity was detected in 53.3% of the AAU, 66.7% of the SpA and 93.3% of the AAU+SpA patients and in none of the controls. Our results suggest that H. pylori might be a candidate participating in the development of AAU and SpA. They also support the theory of genetic (HLA-B27) and exogenous factors (Gram-negative bacteria) as probable background of these diseases.