Cem Evereklioglu

Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration

Background: Nitric oxide (NO), hydroxyl radical (OH.), superoxide anion (O2−) and hydrogen peroxide (H2O2) are free-radicals released in oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) are antioxidant enzymes, mediating defense against oxidative stress. Excess NO and/or defective antioxidants cause lipid peroxidation, cellular dysfunction and death. Age-related maculopathy (ARM) or degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. The etiology is unclear and the molecular factors contributing this disease remain to be specified. Aims: This multicenter, double-blind, cross-sectional study aimed to investigate plasma NO and lipid peroxidation levels with relation to antioxidant enzyme activities in erythrocyte and plasma of patients with ARMD compared with healthy control subjects. Methods: NO, lipid peroxidation (measured as plasma malondialdehyde [MDA] levels) and the catalytic activity of SOD, GSHPx and CAT were measured in a group of 41 patients with maculopathy (19 men, 22 women; 67.12 ± 3.70 years) and compared with 25 age- and sex-matched healthy control subjects without maculopathy (12 men, 13 women; 68.04 ± 3.02 years). NO and MDA levels were measured in plasma, CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Color fundus photographs were used to assess the presence of maculopathy, and the patients were divided into two groups using clinical examination and grading of photographs; early-ARM (n = 22) and late-ARMD (n = 19). Results: All patients with maculopathy had significantly (p<0.001) higher plasma NO levels over control subjects (mean ± SD, 48.58 ± 8.81 vs. 28.22 ± 3.39 μmol/l). Plasma MDA levels in patients and control subjects were 4.99 ± 1.00 and 2.16 ± 0.24 μmol/l, respectively, and the difference was significant (p<0.001). On the other hand, SOD and GSHPx activities were significantly lower in both RBCs and plasma of patients with maculopathy than in control subjects (RBCs-SOD, 3509.30 ± 478.22 vs. 5033.30 ± 363.98 U/g Hb, p<0.001; plasma-SOD, 560.95 ± 52.52 vs. 704.76 ± 24.59 U/g protein, p<.001; RBCs-GSHPx, 663.43 ± 41.74 vs. 748.80 ± 25.50 U/g Hb, p<0.001; plasma-GSHPx, 98.26 ± 15.67 vs. 131.80 ± 8.73 U/g protein, p<0.001). RBCs-CAT levels were not different between groups (131.68 ± 12.89 vs. 133.00 ± 13.29 k/g Hb, p=0.811). Late-ARMD patients had significantly lower antioxidant enzyme levels and higher MDA levels when compared with early-ARM patients (for each, p<0.001). In addition, plasma NO and MDA levels were negatively correlated with SOD and GSHPx activities. Conclusions: This study demonstrated for the first time that NO, the most abundant free-radical in the body, might be implicated in the pathophysiology of ARMD in association with decreased antioxidant enzymes and increased lipid peroxidation status.

Comparison of secondary implantation of flexible open-loop anterior chamber and scleral-fixated posterior chamber intraocular lenses

Purpose: To analyze and compare the outcomes and complication rates of secondary implantation of flexible, open‐loop, anterior chamber intraocular lenses (AC IOLs) and single‐piece, scleral‐fixated, posterior chamber IOLs (PC IOLs). Setting: Departments of Ophthalmology, Gaziantep University Medical Faculty, Research Hospital, Gaziantep, and Inönü University Medical Faculty, Research Hospital, Malatya, Turkey. Methods: This study comprised 124 eyes of 113 aphakic patients (61 men, 52 women) with insufficient capsule support who had secondary IOL implantation from January 1997 to June 2001. In Group 1 (n = 73 eyes), a flexible, open‐loop AC IOL was implanted and in Group 2 (n = 51 eyes), a single‐piece, scleral‐fixated PC IOL. The mean follow‐up was 34 months (range 6 to 53 months) and took place at several different clinical settings. The mean interval between the initial cataract operation and secondary IOL implantation was 63 months (range 6 months to 12 years). The postoperative outcomes, safety, efficacy, and complication rates were analyzed, and the preoperative and postoperative best spectacle‐corrected visual acuities (BSCVAs) were compared. Results: The postoperative mean BSCVA was 20/34.8 ± 45.2 (SD) in Group 1 and 20/32.1 ± 33.7 in Group 2; the difference was not significant (P = .718). A BSCVA of 20/40 or better was achieved in 62 eyes (84.9%) in Group 1 and 45 eyes (88.2%) in Group 2. A BSCVA of 20/25 or better was achieved in 40 eyes (54.8%) and 33 eyes (64.7%), respectively. The difference between the 2 groups was not significant (P = .472). Complications occurred in 25 eyes (34.2%) in Group 1 and 13 eyes (25.5%) in Group 2 (P > .05). The most frequent complications in Group 1 were early transient corneal edema, intraocular pressure elevation, cystoid macular edema, hyphema, secondary glaucoma, and iris capture or pupil decentration and in Group 2, suture erosion, a tilted or decentered IOL, fibrin reaction, and vitreous prolapse into the anterior chamber. Conclusions: The AC IOLs and PC IOLs were safe and effective for secondary implantation to correct aphakia. Secondary implantation of the scleral‐fixated PC IOL seemed to provide a more favorable outcome and a lower complication rate than the open‐loop AC IOL in complicated cataract cases with inadequate capsule and zonular support. As scleral‐fixated PC IOL implantation is technically more difficult than AC IOL implantation, the decisive factor in choosing a secondary IOL is surgical experience. Long‐term comparison of both techniques is required.

Decreased nitric oxide production in primary open-angle glaucoma

Purpose Raised intraocular pressure (IOP) is the major risk factor responsible for optic nerve damage in primary open-angle glaucoma (POAG). The trabecular meshwork acts as a valve in aqueous outflow and relaxes with nitric oxide (NO) agonists. Since NO is synthesized by endothelium and smooth muscle elsewhere in the body, this study investigated the NO levels in the aqueous humor of patients with POAG compared with cataract patients. Materials and Methods Aqueous humor samples were taken by paracentesis from 16 consecutive patients with POAG (9 male and 7 female; mean age 69.0 ± 3.4 yrs) and 14 age and sex-matched controls with cataract (8 male and 6 female; mean age 66.7 ± 4.1 yrs) during elective surgery. As an indicator for NO, aqueous total nitrite levels (end - product of NO) were measured by Greiss reaction. The Mann-Whitney U test was used for statistical analysis and P <0.05 was considered significant. Results The mean age and sex in two groups were comparable. The mean aqueous humor NO levels were significantly (P = 0.001) lower in patients with glaucoma (72.72 ± 11.21 μmol/L) than in patients with cataract and no glaucoma (86.92 ± 11.23 μmol/L). Conclusions Decreased NO production in patients with POAG indicates that NO-producing cells may be lost as the disease progresses. The control of NO levels in the eye might be a therapeutic target in glaucoma.

Intravitreal triamcinolone acetonide injection as primary treatment for diabetic macular edema.

Purpose To evaluate the effectiveness of intravitreal triamcinolone injection on the course of diabetic macular edema. Methods Forty-eight eyes of 48 diabetic patients were treated with 8 mg of intravitreal triamcinolone injection as the primary therapy for diabetic macular edema. The main outcome measures included best-corrected visual acuity, fundus fluorescein angio- graphy, macular edema map values of Heidelberg Retinal Tomograph II (HRT II), and intraocular pressures before and after intravitreal injection. Results The visual acuity increased in 41 of 48 eyes (85.4%) during a mean follow-up time of 7.5 months. The mean baseline best-corrected logMAR (logarithm of minimal angle of resolution) value for visual acuities of the patients before intravitreal triamcinolone injection was 1.17±0.20. After treatment, it was 0.85±0.29 at 1 month, 0.73±0.30 at 3 months, and 0.74±0.31 at 6 months, and the differences were significant when compared with baseline values (for each, p<0.001). The mean edema map values significantly decreased by 36% at the 6-month examinations when compared with preinjection values (p<0.001). Average intraocular pressure rose 24.3%, 29.1%, and 11.8% from baseline at the 1-, 3-, and 6-month follow-up intervals. Intraocular pressure elevation exceeding 21 mmHg was observed in 8 of 48 eyes (16.6%), but was controlled with topical antiglaucomatous medications in all eyes. Conclusions Intravitreal triamcinolone application provides significant improvement in visual acuity of diabetic patients and clinical course of macular edema, and may therefore be a promising approach in the primary treatment of diabetic macular edema.

Managing the symptoms of Behçet’s disease

Behçet’s disease (BD) is a chronic, relapsing, systemic inflammatory vasculitis of unknown aetiology with a myriad of immunological and pathological consequences. Patients with BD are clustered along the ancient silk road, extending from Far-East Asia to Turkey. The disease affects both genders of all ages from infants to the elderly. It is a long-term, cyclical disease and such patients may have symptom-free periods of weeks, months or years that are interrupted by exacerbations of varying intensities lasting a few days, weeks or months. Clinical features include oral aphthae, genital ulcers, ocular inflammation, skin lesions, as well as articular, vascular, neurological, pulmonary, gastrointestinal, renal and genitourinary manifestations. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size or thrombophilia according to the site of involvement. BD may start with just one or two small symptoms but other symptoms may gradually appear over the years. Recurrent ocular inflammation, which occurs in ∼ 50% of cases, is the major morbidity that may eventually lead to blindness. The treatment of BD is usually symptomatic and palliative. Therefore, the main objectives are to relieve symptoms associated with mucocutaneous lesions and arthritis, to modify the course of the disease, to control inflammatory eye disease, clinically suppress the inflammation and vasculitis, to prevent recurrences and thus, prevent irreversible damage. The choice of treatment is based on the severity of systemic involvement, clinical presentation and the site affected. The preferred treatment modalities are combined drug therapy and include topical therapies as well as systemic corticosteroids, NSAIDs, colchicine, dapsone and immunosuppressive and cytotoxic agents. Such therapies are tailored to the individual patient depending on clinical manifestations. Thalidomide, tacrolimus, IFN-α and anti-TNF monoclonal antibody have recently attracted attention as novel therapeutic approaches.

Clinical features of Behçet's disease in children.

Background  Behçets disease (BD) is a systemic inflammatory vasculitis of young adults with unknown etiology.

The efficacy of intravitreal triamcinolone acetonide on macular edema in branch retinal vein occlusion

Purpose To evaluate the effectiveness of intravitreal triamcinolone acetonide as primary treatment of macular edema in branch retinal vein occlusion. Methods Fifteen eyes of 15 patients with macular edema due to branch retinal vein occlusion (Group 1) who received 8 mg/0.2 ml of intravitreal triamcinolone injection as primary treatment were retrospectively evaluated. The control group (Group 2) consisted of 19 eyes of 19 patients who had received laser treatment for macular edema. The main outcome measures included best-corrected visual acuity, intraocular pressure, and macular edema map values of Heidelberg Retinal Tomograph II. Results In Group 1, mean visual acuity improved significantly from a mean logMAR (logarithm of minimal angle of resolution) value of 0.98±0.19 at baseline to a maximum of 0.24±0.24 during a mean follow-up time of 6.3 months. In the control group, the mean baseline logMAR visual acuity before laser treatment was 1.02±0.22, and it was 0.50±0.28 at 6-month examinations. Mean improvement in visual acuity at 1–, 3–, and 6-month examinations was significantly higher in Group 1 when compared with the control group (for each, p<0.001). The mean edema map value of Group 1 significantly decreased by 40% at 6-month examinations when compared with preinjection value (p<0.001). In Group 1, mean increase in intraocular pressure elevation was 19.8% at the 1-month, 26.9% at 3-month, and 5.7% at 6-month visits, but intraocular pressures were under control with topical antiglaucomatous medications. Conclusions Intravitreal triamcinolone acetonide injection may be a new and promising approach as initial therapy for macular edema due to branch retinal vein occlusion.

Pattern VEP is a useful technique in monitoring the effectiveness of occlusion therapy in amblyopic eyes under occlusion therapy

PurposeTo evaluate the effectiveness and clinical significance of pattern visual evoked potential (P-VEP) parameters on visual acuity in amblyopic patients under occlusion therapy.MethodsA total of 34 consecutive children with anisometropic amblyopia were included in this study. All patients underwent a full initial ophthalmologic and orthoptic evaluation. P-VEP test was performed in all cases and binocular vision was tested and recorded with Worth’s four-dot test and Bagolini striated glasses at each visit. Part-time occlusion therapy was performed by using adhesive patches.ResultsThe mean (±SEM) cycloplegic refractive error was +5.6 ± 0.6 diopters (D) in the amblyopic eyes and +1.8 ± 0.2 D in the normal eye. The mean levels of best-corrected visual acuity were statistically differed between each measurement for occlusion therapy (for each, p < 0.05). The ratio of the patients with binocular vision increased after 6 months occlusion therapy and the difference was statistically significant (p<0.05). In addition, P100 amplitude improved at each visit and the difference was significant when compared with baseline values (for each,p < 0.05).ConclusionsP100 amplitude of the P-VEP test parallels the improvement in subjective visual acuity in amblyopic eyes under occlusion therapy. Therefore, this test may be useful in monitoring the visual acuity in the preverbal or non-verbal patched patients.

Pattern electroretinogram for monitoring the efficacy of intravitreal triamcinolone injection in diabetic macular edema

Purpose: To investigate the efficacy of intravitreal triamcinolone (IVT) by evaluation of pattern electroretinogram (PERG) in diabetic patients with clinically significant macular edema (CSME). Methods: Forty eyes of 40 diabetic patients were treated with 8 mg of IVT injection as primary therapy for CSME. The main outcome measures included best-corrected visual acuity, fundus fluorescein angiography, P50 amplitudes of pattern electroretinogram (PERG) and intraocular pressures before and after injection. Results: The mean follow-up time was 6.1 months. Mean visual acuity improved significantly from a mean LogMAR value of 1.14 ± 0.16 at baseline to a maximum of 0.73 ± 0.30. The mean baseline P50 amplitude of PERG before intravitreal injection was 1.5 ± 0.9 μV. After the treatment, it was 2.l ± 1.1 μV at 1-month, 2.4 ± 1.0 μV at 3-month and 2.1 ± 0.9 μV at last visit and the differences were significant when compared with baseline values (for each, p < 0.001). Temporary increases in intraocular pressures were controlled with topical antiglaucomatous medications, if required. Conclusion: IVT injection provides rapid improvement in visual acuity of diabetic patients with CSME that has been supported by P50 amplitudes of PERG. P50 amplitudes of PERG may be used as novel predictive value in the evaluation of the effectiveness of IVT injection.

Urinary nitric oxide levels are increased and correlated with plasma concentrations in patients with Behçet's disease: is it a new urinary activity marker?

SUMMARY:  Nitric oxide (NO) is a free radical and serves many functions within the kidney. Excess NO causes glomerular injury. Behçets disease (BD) is a systemic immunoinflammatory vasculitis, affecting every organ in the body including the kidneys (subclinic glomerulonephritis). We investigated the role of urinary total nitrite levels (end product of NO) in BD and evaluated whether urinary concentrations were correlated with its plasma levels or disease activity. Thirty‐six consecutive Behçets patients (19 men, 17 women; 35.9 years), and 20 age‐ and sex‐matched healthy control volunteers (12 men, eight women; 33.2 years) were divided into an active (n = 16) and inactive (n = 20) period. Urinary and serum NO levels (µmol/mg urinary creatinine) were higher in BD patients (4.1 ± 0.3) than control subjects (1.7 ± 0.2; P < 0.001). Serum NO levels in Behçets patients and control subjects were 51.3 ± 9.8 and 21.7 ± 7.3 µmol/L, respectively (P < 0.001). Active patients had higher urinary NO excretion (4.9 ± 0.3) than inactive patients (3.3 ± 0.3; P < 0.01). Urinary NO levels were correlated with its serum levels (r2 = 0.69, P < 0.001). Higher urinary NO levels found in BD may be produced by the kidney as a result of an inflammatory stimulation. As excess NO is toxic to the tissues, increased NO levels may play a role in mediating subclinic glomerular injury of such patients. However, we could not determine the exact site(s) of NO synthesis by the kidney, such as the glomeruli, blood vessels and/or the tubular cells. Whatever the source, urinary NO levels may be used as a new activity marker in the diagnosis and follow up of BD by serial measurements.