Gordana Zlatanovic

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.

Efficacy of TNF-α antagonist and other immunomodulators in the treatment of patients with ophthalmologic manifestations of Behcet's disease and HLA B51 positive vasculitis

BACKGROUND/AIM Behcets disease is genetically conditioned, immune-mediated multisystem occlusive vasculitis of small blood vessels, espesially venules, of unknown etiology. The aim of this study was to analyze the clinical features, disease activity and therapy of the patients with ophthalmologic manifestation of Behcets disease. METHODS In this study symptoms and signs of the disease were analyzed both prospectively and retrospectively during the active manifestation of the disease. The diagnosis was reached according to the International Criteria for Behcets Disease (2006). The treatment effects were evaluated based on the presence of the best corrected visual acuity and the inflammation of the vitreous humour before and after the application of our therapeutic method. The applied therapeutic modality consisted of the primary application of corticosteroid therapy in the active stage of the disease complemented with the choice of drugs from the immunosuppressive group. In this study there drugs were cyclosporine or methotrexate. A treatment refractory patients with poor vision prognosis were treated with a third drug, the biological preparation infliximab, a tumor necrosis factor-alpha (TNF-alpha) antagonist. RESULTS The mean age of 11 patients with ophthalmologic manifestation of Behcets disease was 50.6 years. HLA B-5 (51) was positive in 81% of the patients while 36% of the patients had positive pathergy test. Changes in affected eyes included vitritis (100%), posterior uveitis (45%), panuveitis (54%), retinal vasculitis (54%), cystoid macular edema (54%), and cystoid degeneration (18%). Increased intraocular pressure was observed in 27% of the patients. There was no statistically significant variation in disease activity parameters in any of the patients (p > 0.05). A statistically significant improvement in visual acuity (p < 0.05) and a high statistically significant decrease of inflammation of the worst affected eyes (p = 0.001) were detected. CONCLUSION Our therapeutic method is useful for producing the optimal therapeutic plan for the acute--chronic stage of the difficult ophtamological manifestation of Behcets desease as well as the prevention of relapse. However the high cost of the therapy and the potential complications should be taken into consideration when prescribing this therapy, especially a TNF-alpha antagonist.

Therapeutical approach to dry eye syndrome

INTRODUCTION Dry eye disease or dysfunctional tear syndrome is among the most frequently established diagnoses in ophthalmology. It can be defined as a disorder of the tear film resulting in changes in the ocular surface. MECHANISMS IN DEVELOPMENT OF DRY EYE DISEASE There are many factors causing dry eye and they, can be related to deficiency in any of the components of the tear film. It has been suggested that dry eye is an inflammatory disorder that affects the ocular surface and lacrimal gland. Inflammation is the most important mechanism of corneal and conjunctival cell damage, which is responsible for the symptoms and signs of ocular surface pathology. Hormonal imbalance (particularly androgens), neural dysfunction, increased levels of pro-inflammatory cytokines and loss of immune homeostasis of the lacrimal gland and ocular surface could be possible mechanisms in the pathogenesis of dry eye disease. DISCUSSION The aim of this paper was to review the advances in the pathogenesis and management of the dry eye disease. The appropriate dry eye treatment presupposes knowledge of all existing pharmacologic and non-pharmacologic therapeutic modalities. The mainstay of therapy is still artificial tears, with anti-inflammatory therapy and punctual occlusion therapy as second and third line therapies.

Retinal ganglion cell/inner plexiform layer thickness in patients with Parkinson’s disease

Introduction: The aim of the paper was to analyze the changes in the macular ganglion cell layer and inner plexiform layer (GCL-IPL) thickness in patients with Parkinsons disease. Material and methods: The study enrolled 46 patients with established diagnosis of Parkinsons disease and 46 healthy subjects. Both groups were age- and gender-matched. An OCT protocol, namely standardized Ganglion Cell Analysis algorithm was used to measure the thickness of the macular GCL-IPL layer. The average, minimum, and six sectoral (superotemporal, superior, superonasal, inferonasal, inferior, inferotemporal) GCL-IPL thicknesses were measured from the elliptical annulus centered on the fovea. Results: The mean value of the clinical severity of Parkinsons disease was between 2 and 3, according to the Hoehn and Yahr scale. Statistically significant thinning of the GCL-IPL layer was registered in average and minimum GCL-IPL thickness, as well as in the sectoral layer thicknesses in patients with Parkinsons disease in comparison to the controls. There was no correlation between structural changes in the retina and disease duration or severity. A statistically significant difference in thickness between the different stages of the disease was registered only in the inferior sector. Conclusions: Parkinsons disease is accompanied by thinning of the GCL-IPL complex of macula even in the earliest stages. This may indicate a possible retinal dopaminergic neurodegeneration. There is no correlation between duration or severity of Parkinsons disease with thinning of the GCL-IPL complex. .

Foveal Avascular Zone in Normal Tension Glaucoma Measured by Optical Coherence Tomography Angiography

Aim To measure diameter of foveal avascular zone (FAZ), FAZ area, and vessel density using Optical Coherence Tomography Angiography (OCT-A) in patients with normal tension glaucoma (NTG) and to establish the possible role of OCT-A in diagnosis and follow-up of patients with NTG. Methods Twenty-one eyes of 21 patients with NTG and 30 eyes of 30 healthy subjects underwent complete ophthalmic examination as well as OCT-A on ZEISS AngioPlex. 3 × 3 macula scans were used to measure vertical, horizontal, and maximum diameter of FAZ by two graders. Mean values and interobserver variability were analyzed. Image J was used for analysis of FAZ area and vessel density. Results Mean vertical diameter (t = 5.58, p < 0.001), horizontal diameter (t = 3.59, p < 0.001), maximum diameter (t = 5.94, p < 0.001), and FAZ area (t = 5.76, p < 0.001) were statistically significantly enlarged in the NTG group compared to those in the control group. Vessel density (t = −5.80, p < 0.001) was statistically significantly decreased in the NTG group compared to that in the control group. Conclusion OCT-A could have an important role in the future in diagnosis of patients with NTG. In patients with NTG, there is larger FAZ area, while the vessel density is reduced in comparison to the control group.

Vitreoretinal interface changes after uncomplicated phacoemulsification

Online first: January 30, 2018 SUMMARY Introduction/Objective The aim of this work was to examine the incidence of posterior vitreous detachment (PVD) after uncomplicated phacoemulsification, as well as the importance of optical coherence tomography (OCT) in detecting early changes on vitreoretinal interface. Methods PVD was evaluated in 120 eyes of 120 patients aged between 50 and 70 years by the combination of OCT and ultrasonography immediately prior and one, six, and 12 month after the phacoemulsification cataract surgery with intraocular lens implantation. Results The mean age was 57 ± 8.8 years in female and 58.6 ± 8.8 years in male subjects. The progress statuses were compared after cataract surgery at three time-points: after one, six, and 12 months. Significant progression of PVD in time was confirmed (χ2 = 78.32, p < 0.001). The Wilcoxon test determined that after six months (p < 0.001) and 12 months (p < 0.001) the disease progression was statistically significant in comparison to measurements after one month. In addition, after 12 months, in relation to progression status established after six months, there was significant progression of the disease (p < 0.001). Conclusion Vitreous body detachment after phacoemulsification surgery is common, and OCT plays a very important role in detecting initial changes on the vitreoretinal interface.

Refractive errors in premature infants with retinopathy of prematurity after anti-vascular endothelial growth factor (anti-VEGF) therapy

Background/Aim. Retinopathy of prematurity (ROP) is a vasoproliferative retinopathy which affects the blood vessels of the retina during its development. The aim of this study was to evaluate the incidence and the degree of refractive errors in premature infants with severe ROP treated with anti-vascular endothelial growth factor (anti-VEGF) (bevacizumab). Methods. This prospective study included 21 patients (42 eyes) nine months old who received intravitreal injection of anti-VEGF therapy. The control group consisted of 45 patients (90 eyes) who were subjected to laser treatment. In cycloplegia each patient underwent retinoscopy, keratorefractometry, and A-scan ultrasonography. Results. Myopia was present in 47.62% of the eyes in the study group and in 33.33% of the eyes in the control group, but there were no statistically significant differences between these groups. Seven (16.67%) eyes in the study group and 17 (18.89%) eyes in the control group were discovered to have high myopia (SE–spherical equivalents < -3.0 D – dioptre). Clinically significant hypermetropia was higher in the study group (47.62%) than in the control group (34.44%), but with no statistically significant difference. In addition, high hypermetropia was significantly greater in the control group (15.56%) than in the study group (11.90%) (p < 0.001). Astigmatism was more common in the control group than in the study group (81.11% vs 71.43%, respectively), especially high astigmatism (56% vs 43%, respectively). Also the more common form of astigmatism was with the rule (WTR) both in the study and the control group (42.86% vs 55.56%, respectively). Anisometropia was significantly greater in the control group (24.44%) than in the study group (9.52%) (p < 0.05). The children from the study group had significantly greater lens thickness, and a shorter anterior chamber depth than children from the control group (p < 0.01). There was no significant difference in the axial length of the eye between the groups. Conclusion. At the 9-month follow-up myopia was present in the patients with severe ROP treated with anti-VEGF, but high myopia was present to a lesser degree than in the laser treated patients. This difference is possibly related to anterior segment development. Research into the longer-term refractive outcomes is necessary with observation of the biometric components, visual acuity, and the visual field in order to monitor the real effects of this therapy.

Efficacy of infliximab in treatment of refractory panuveitis associated with Behçet disease

Introduction Behçet disease (BD) is a chronic multi-system disorder with manifestations in the ocular, urological, articular, and vascular systems. Tumor necrosis factor alpha is believed to play a pivotal role in BD. Therapeutic blockade of its activity by infliximab is a novel therapeutic approach and has successfully led to remission of the disease. The aim is to report two cases of refractory BD-associated panuveitis (PU) treated with infliximab. The patients were followed for 12 months. The main therapy assessment parameters were the best corrected visual acuity (BCVA) in the better eye, slit lamp and fluorescein angiography (FAG) from baseline findings and from the final examination. Case outline A male patient (45 years old, 25 years of BD history) and a female patient (45 years old, 15 years of BD history), both with posterior synechia, 3+ flare and complicated cataract, while the female also had hypopyon, were treated with infliximab administered at the dose of 5 mg/kg at weeks 0, 2, 6, and 14. The results for the male patient were as follows (baseline vs. the final examination): BCVA – 0.5 vs. 0.8; cellular reaction – 3+ vs. 1+; FAG – 1/2 vs. 0. The results for the female patient were as follows: BCVA – 0.1 vs. 0.3; FAG – 2/3 vs. 0. After 12 months, relapses or side-effects were not observed. Conclusion Infliximab is an effective and promising drug in treating refractory BD-associated PU. It promptly reduces acute symptoms of PU, but it still remains to be seen if a long-term remission in a great number of patients will be achieved.

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.

The Effect of LASIK Procedure on Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-Inner Plexiform Layer Thickness in Myopic Eyes

Purpose To evaluate the effect of applied suction during microkeratome-assisted laser in situ keratomileusis (LASIK) procedure on peripapillary retinal nerve fiber layer (RNFL) thickness as well as macular ganglion cell-inner plexiform layer (GC-IPL) thickness. Methods 89 patients (124 eyes) with established myopia range from −3.0 to −8.0 diopters and no associated ocular diseases were included in this study. RNFL and GC-IPL thickness measurements were performed by spectral domain optical coherence tomography (SD OCT) one day before LASIK and at 1 and 6 months postoperatively. Results Mean RNFL thickness prior to LASIK was 93.86 ± 12.17 μm while the first month and the sixth month postoperatively were 94.01 ± 12.04 μm and 94.46 ± 12.27 μm, respectively. Comparing results, there is no significant difference between baseline, one month, and six months postoperatively for mean RNFL (p > 0.05). Mean GC-IPL thickness was 81.70 ± 7.47 μm preoperatively with no significant difference during the follow-up period (82.03 ± 7.69 μm versus 81.84 ± 7.64 μm; p > 0.05). Conclusion RNFL and GC-IPL complex thickness remained unaffected following LASIK intervention.