Avni Murat Avunduk

Cyclosporine Effects on Clinical Findings and Impression Cytology Specimens in Severe Vernal Keratoconjunctivitis

Purpose: To investigate the possible effects of topical cyclosporine eye drops 2% (CsA) on conjunctival immune cells obtained by impression cytology technique and to determine the clinical relevance of this effect if present. Methods: Ten consecutive patients with severe, resistant, and active vernal keratoconjunctivitis (VKC) were included in this study. All of them were treated with 2% of topical CsA drops. Symptom and clinical scores and conjunctival impression cytology specimens were obtained both before and following treatment. Impression cytology specimens were stained with anti-CD8+, CD4+, CD45RA+, and CD23+ antibodies and the percentages of positive cells were counted. The results were compared and correlation analyses were performed between clinical and laboratory data. Results: Significant reductions were observed with respect to the percentages of CD4+ and CD23+ cells in the conjunctival impression cytology specimens and clinical and symptom scores following treatment with topical CsA, while no change occurred in the percentages of CD8+ and CD45RA+ cells. The percentages of CD4+ and CD23+ cells showed good correlations with symptom and clinical scores. Conclusion: Topical CsA treatment is a very effective alternative in severe VKC cases in clinical ground and clinical efficacy of topical CsA treatment in severe, resistant VKC cases can be (at least partly) related to reduction of the CD23+ and CD4+ cell populations on the conjunctival surface.

The Comparison of Intraocular Pressure Reductions after Isometric and Isokinetic Exercises in Normal Individuals

The lowering effect of physical exercise on intraocular pressure (IOP) has been reported both in healthy people and those with glaucoma, but a comparison of the lowering effect of isometric and isokinetic exercises on IOP has not been conducted in any study. Our aims were to investigate the relationship between intensity of exercise and IOP, and whether a significant difference in IOP lowering effect existed between isometric and isokinetic exercises. Sixty-seven patients with an age range of 23–40 who had no ocular disease were randomly divided into two groups. While 31 patients in the first group, group A, performed isokinetic exercise with the Cybex 6000 dynamometer, 32 patients in the second group, group B, had isometric exercises with the same machine. IOP was measured in the right eye of patients with Shiøtz tonometer just before and 10 min following exercise. Exercise intensity and total energy consumption were determined by the machine for each patient. While IOP values measured before exercise, the degree of exercise applied, and total energy consumption did not differ significantly between groups, both isometric and isotonic exercises lowered IOP significantly. As a result, isometric and isokinetic exercises lowered IOP in ophthalmologically normal subjects with direct relationship to exercise intensity and total energy consumption. Since the pressure lowering effect of isokinetic exercise was more significant, it might prove useful to glaucomatous patients.

Mechanisms and comparison of anti-allergic efficacy of topical lodoxamide and cromolyn sodium treatment in vernal keratoconjunctivitis

PURPOSE To explore the mechanism of action of topical lodoxamide and cromolyn sodium treatment in vernal keratoconjunctivitis (VKC) and to compare the efficacy of these drugs to each other. DESIGN Single-investigator, masked, randomized, clinical trial. PARTICIPANTS Twenty male and 10 female patients between the ages of 6 and 19 years, who were diagnosed as having active VKC, were enrolled in this study. INTERVENTIONS The patients were randomly divided into two equal groups (groups A and B). Group A patients received topical lodoxamide ophthalmic solution 0.1% (LOS); topical cromolyn sodium ophthalmic solution 4% (CSO) was prescribed to group B patients in a dose of two drops four times daily. MAIN OUTCOME MEASURES The eye symptom severity scores and clinical signs of the patients were evaluated both in the pre- and post-treatment periods. In addition to the clinical data, conjunctival impression cytologic specimens were obtained from patients both before and after treatment. Impression cytologic specimens were stained using immunohistochemical methods to detect the percentages of CD4(+), CD8(+), CD45RA(+), and CD23(+) cells. Statistical analyses were performed within and between groups. RESULTS The percentages of CD4(+) and CD23(+) cells in tear samples of patients in groups A and B were significantly higher in the pretreatment stage than post-treatment stage. In the post-treatment stage, group A patients had significantly lower CD4(+) and CD23(+) cell values compared with group B patients. Patient symptom scores and clinical signs were at a significantly lower level after treatment with either LOS or CSO in both groups A and B compared with their pretreatment values. Moreover, group A patients had significantly lower symptom scores and clinical signs than group B patients in the post-treatment stage. CONCLUSIONS Clinical superiority of LOS over CSO may be linked to its greater effect on the CD4(+) cells, because CD4(+) cells plays a pivotal role in the pathogenesis of VKC.

The One-Month Effects of Topical Betaxolol, Dorzolamide and Apraclonidine on Ocular Blood Flow Velocities in Patients with Newly Diagnosed Primary Open-Angle Glaucoma

Purpose: This double-masked, prospective and randomized clinical trial was planned to investigate with color Doppler imaging the 1-month vascular effects of betaxolol, dorzolamide and apraclonidine treatment on patients with newly diagnosed primary open-angle glaucoma (POAG). Methods: 22 consecutive patients with newly diagnosed POAG between the ages of 46 and 72 years were enrolled in this study. All patients were newly diagnosed cases and had not received any antiglaucoma medication before. Patients who had a systemic vascular disease (including systemic hypertension) or were taking β-blockers, nitrates or calcium channel blockers were excluded from the study. The patients were randomly divided into three groups. Groups A and B contained 7 patients, group C contained 8 patients. Group A patients were treated with topical betaxolol, group B patients received topical dorzolamide eye drops, and group C patients were treated with topical apraclonidine eye drops. Peak systolic velocities (PSV), end-diastolic velocities (EDV) and resistive indices (RI) in the right ophthalmic arteries (OA), central retinal arteries (CRA) and posterior ciliary arteries (PCA) were measured at baseline by using color Doppler imaging on a masked basis. On days 15 and 30 of treatment, the same measurements were repeated. The inter- and intragroup results were compared statistically. Results: Compared to pretreatment measurements, topical betaxolol therapy significantly decreased PSV only in the PCA and only on day 30 of treatment (p = 0.011). On days 15 and 30, dorzolamide decreased RI measurements in the PCA compared to pretreatment measurement (p = 0.013 and p = 0.011, respectively). Apraclonidine also decreased PSV in the OA on days 15 and 30 of treatment when compared to pretreatment values (p = 0.013 and p = 0.012, respectively). When 15-day measurements were compared between the groups, PSV in the OA were significantly higher in dorzolamide-treated patients compared to other groups (p = 0.01 and p = 0.011). On day 30 of treatment, PSV in the OA was also higher in the dorzolamide-treated group than the other groups (p = 0.012 and p = 0.01). Additionally, apraclonidine-treated patients had a significantly lower EDV in the OA than the other groups (p = 0.013 and p = 0.01). The RI in the OA was also significantly lower in the apraclonidine-treated group compared to the other groups (p = 0.01 and p = 0.011). Conclusion: Our study suggests that dorzolamide has the most advantageous 1-month effects on blood flow velocity in the retrobulbar arterial circulation of POAG patients. Betaxolol seems superior to apraclonidine in this regard. Our data may help the clinician when treating patients with POAG medically. Further studies using a larger population size may clarify our results.

Comparison of efficacy of oral valacyclovir and topical acyclovir in the treatment of herpes simplex keratitis: a randomized clinical trial.

Thirty eyes of 28 patients with herpetic disease were included in the study. Group 1 patients (15 eyes of 15 subjects) received topical acyclovir (ACV) ointment. Oral valacyclovir (VACV) was prescribed to group 2 (15 eyes of 13 patients). The anterior segment of each eye was carefully examined by slit lamp and scored. Each patient was also instructed to grade his/her subjective symptoms. The corneal lesion healed significantly faster in the group 2 eyes compared to the group 1 eyes. Photophobia score on day 3 and slit-lamp score on day 10 were at significantly lower levels in group 2 compared to group 1. In herpetic keratitis, oral VACV can be a good alternative to ACV ointment therapy.

Analysis of Tears in Patients with Atopic Keratoconjunctivitis, Using Flow Cytometry

Atopic keratoconjunctivitis (AKC) is a chronic allergic eye disease. Although the pathogenesis is not fully understood, some impairment in cell-mediated immunity was suggested by histopathological findings in conjunctival specimens obtained from affected individuals. T-cell infiltration and an enhanced T-helper/T-suppressor cell ratio in conjunctival biopsy specimens were observed previously by immunofluorescence procedures. We analyzed the cells in tears of patients with AKC using flow cytometry (FCM) and compared the results to those of normal subjects to identify the role of T lymphocytes in the pathogenesis of the disease. The tear samples of the patients and normal subjects were collected with capillary tubes, and the surface receptors of cells were detected with FCM. Statistical analyses were performed with Student’s t test. The percentages of T cells, activated B cells, and T-helper/T-suppressor cell ratios were found to be higher in the tears of patients with AKC than in controls. We propose that a decreased T-suppressor cell concentration in tears may enhance immunoglobulin-E production of B cells, and the signs and symptoms are provoked by inflammatory mediators liberated from mast cell degranulation.

Flow Cytometrical Analysis of Adhesion Molecules, T-Lymphocyte Subpopulations and Inflammatory Markers in Pterygium

Background/Aim: Pterygium is a relatively frequent ocular surface disease with an unexplained etiopathogenesis. Our study was carried out with the aim to identify the presence of inflammatory cells and mediators such as T-lymphocyte subgroups (CD4 and CD8), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and human leukocyte antigen-DR (HLA-DR) in pterygium tissue. Methods: Pterygium tissue, obtained from 24 patients, and normal conjunctival tissue, from the nasal bulbar conjunctiva obtained from 14 patients operated for ocular perforations or vitrectomy, were separated into epithelial and stromal components under the microscope and suspended with phosphate-buffered saline solution to form a suspension. Cell suspensions were treated with specific antibodies for ICAM-1, VCAM-1, and HLA-DR and T-lymphocyte subgroups and evaluated with flow cytometry. The obtained data were compared statistically. Results: When compared to the control tissue samples, higher rates of ICAM-1-positive cells, VCAM-1-positive cells and HLA-DR-positive cells were recorded in pterygium tissue samples. CD4 and CD8 lymphocytes were also found to be at higher levels when compared to the control group. There was a statistically significant difference between the two groups. Conclusion: When compared with normal conjunctival tissue, pterygium tissue had increased levels of T-lymphocyte infiltration and inflammatory markers demonstrating the possible contribution of cellular immunity to the pathogenesis.

Effect of Melatonin and Zinc on the Immune Response in Experimental Toxoplasma Retinochoroiditis

Objectives: To investigate the possible effect of melatonin (MEL) and zinc on the immune response to Toxoplasma gondii retinochoroiditis in the rat model of infection and to establish the possible value of artificial MEL and/or zinc supplementation as adjunctive therapeutic agents in the treatment of T. gondii retinochoroiditis. Methods: Eighty-four Sprague-Dawley male rats were divided into 12 equal groups. All groups, except controls were infected with T. gondii parasite by intraperitoneal injection. Combinations of zinc-deficient diet, pinealectomy (Px), and artificial zinc and MEL were supplied during a 1-month period. At the end of the experiment, retinal and choroidal total lymphocytes, CD3+, CD4+, and CD8+ cell numbers were counted in histological sections. Results: The highest amount of cellular infiltration (lymphocytes, CD3+, CD4+, CD8+ cells) in the choroid and retina was detected in infected + MEL + zinc-treated rats, and the least amount of cellular infiltration was observed in Px + zinc-deficient diet-treated rats. Although single zinc or MEL supplementation had no significant impact on the cellular infiltration in the retina and choroid in Px rats, combined therapy significantly improved these responses. Conclusion: Artificial supplementation of MEL and zinc should be considered as an adjunctive therapy to classic treatment of Toxoplasma retinochoroiditis especially in immunosuppressed and elderly patients if our data are confirmed in a clinical setting.

Acromegaly presenting with diabetic ketoacidosis, associated with retinitis pigmentosa and octreotide-induced bradycardia: a case report and a review of the literature.

Carbohyrate intolerance is a common feature of acromegaly. Frank diabetes mellitus is seen in about 10–20% of patients. There is no report of acromegaly presenting with diabetic ketoacidosis (DKA), associated with retinitis pigmentosa (RP), in the literature. We report the occurrence of DKA and RP in a patient with acromegaly. A 39-year-old Turkish man was admitted to the emergency ward with a 1-mo history of thirst, polyuria, weight loss of 10 kg, and loss of consciousness for 2 d. Physical examination revealed findings suggestive of acromegaly, including coarse facial features and enlargement of his hands and feet. At ophthalmological examination, funduscopy showed RP. Laboratory studies confirmed the diagnoses of DKA and acromegaly. Magnetic resonance imaging disclosed the presence of a pituitary adenoma. During the medical treatment with octreotide, symptomatic sinusoidal bradycardia was developed (pulse rate 45 bpm, and blood pressure 70/40 mmHg). Octreotide therapy was stopped. Pituitary adenoma was removed surgically. For treatment of DKA, insulin need was very high in the first days after the onset of ketoacidosis, but decreased after initiation of treatment with octreotide and after successful operation. Insulin was stopped 7 d after surgery. Follow-up showed normalization of growth hormone levels and plasma glucose levels. Only six other cases of DKA associated with acromegaly and only three other cases of RP associated with acromegaly were found in the medical literature. In conclusion, to our knowledge, the present case is a first report of DKA and RP in patient with acromegaly.

Characterization of T lymphocyte subtypes in endotoxin-induced uveitis and effect of pentoxifylline treatment

Purpose. The aims of the study were twofold: 1) to investigate the role of T lymphocyte subtypes in the pathogenesis of endotoxin-induced uveitis (EIU) and 2) to study the possible beneficial effect of pentoxifylline, an inhibitor of neutrophil motility, and Tumor Necrosis Factor-a on this disease. Methods. Forty-two inbred male Lewis rats were divided into seven equal groups. 200 µg of Escherichia coli 055: B55 lipopolysaccharide (LPS) was injected in one hind footpad of the Group 2, 3, 4, 5, 6, and 7 rats. Group 5, 6, and 7 rats also received concomitant intraperitoneal pentoxifylline (PTX) during food pad injection of LPS. Group 1 rats were used as controls with intra-peritoneal normal saline injection. Eight, 24, and 48 hours after treatment, the rats were euthanized. Neutrophil leukocyte, mononuclear cells, and CD4+, CD8+, and CD45RA+ cell infiltration in the anterior uveal tissue were determined either by hematoxylin-eosin or monoclonal antibody staining. Tumor Necrosis Factor-a (TNF-a) levels were also measured in the aqueous and blood samples. We compared the numbers of infiltrating cells in the different groups. Results. We found that peak infiltration of lymphocyte, neutrophils, and CD4+ cells occurred at 24 hours. However, CD8+ and CD45RA+ cell number reached their highest levels at 48 hours. There was no inflammatory cell infiltration in the control rats. Concomitant pentoxifylline treatment did not affect any of these parameters, although it effectively reduced TNF-a concentrations in the anterior chamber and the serum. Conclusion. We conclude that, 1) T lymphocytes might be involved in the pathogenesis of endotoxin-induced uveitis. 2) The potential role of pentoxifylline in the treatment of human uveitis is questionable. However, these are initial findings and need confirmation by additional studies.