İclal Yücel

Oxidative and nitrative stress markers in glaucoma.

Glaucoma is a progressive optic neuropathy and is the leading cause of blindness in the United States and other industrialized countries. Elevated pressure in the eye is a risk factor for glaucoma and indeed experimental studies of induced pressure elevation in nonhuman primates results in typical glaucomatous optic nerve damage. However, normal intraocular pressure can also lead to loss of vision in glaucoma. Although the initiating causes leading to glaucoma are unknown, oxidative and nitrative stress appears to play a role in the progressive neuronal death that is characteristic of glaucomatous optic nerve damage. Increased markers of oxidative stress that have been reported in glaucoma include protein nitrotyrosine, carbonyls in proteins, lipid oxidation products and oxidized DNA bases. Studies have also highlighted the role of nitric oxide in glaucoma by reporting the presence of inducible nitric oxide synthase in the iris-ciliary body, retina and in the glaucomatous optic nerve head of experimental rat models. This review discusses the role of reactive oxygen and nitrogen species in the pathogenesis of glaucoma and examines the relevance of antioxidants in neurodegeneration associated with the disease. It is concluded that oxidative and nitrative stress have a pathogenic role in glaucoma.

Assessment of optic nerve head topographic parameters with a confocal scanning laser ophthalmoscope

Aim: To assess the disc area, age, sex, laterality (side of the eyes) and refractive error dependent differences in optic nerve head topographic parameters in a normal population.

Outbreak of toxic anterior segment syndrome associated with glutaraldehyde after cataract surgery.

PURPOSE: To present clinical findings of a cluster of cases of toxic anterior segment syndrome (TASS) after uneventful phacoemulsification cataract surgery. SETTING: Department of Ophthalmology, Akdeniz University, Antalya, Turkey. METHODS: Six eyes of 6 patients developed TASS after uneventful phacoemulsification cataract surgery with implantation of a 3‐piece acrylic IOL performed by 2 ophthalmologists on the same day. Clinical findings included corneal edema, Descemets membrane folds, anterior chamber reaction, fibrin formation, and irregular, dilated, and unreactive pupils. RESULTS: Glutaraldehyde 2% solution was used inadvertently by the operating room staff who cleaned and sterilized reusable ocular instruments before autoclaving. None of the affected corneas improved. Additional surgical procedures were required and included penetrating keratoplasty, trabeculectomy, and glaucoma tube implantation. CONCLUSIONS: Glutaraldehyde in concentrations generally used for cold sterilization is highly toxic to the corneal endothelium. The operating room staff involved in sterilizing instruments should be well educated about and careful to follow the protocols to properly clean and sterilize reusable ocular instruments.

Effect of hypercholesterolemia on inducible nitric oxide synthase expression in a rat model of elevated intraocular pressure

PURPOSE This study was performed to examine the effect of hypercholesterolemia on inducible nitric oxide synthase (NOS-2) expression and oxidative tissue injury in an experimental rat model of elevated IOP. METHODS Wistar rats were maintained on either regular chow or a high-cholesterol diet for 24 weeks. Intraocular pressure (IOP) was elevated in hypercholesterolemic rats by unilaterally cauterizing three episcleral vessels. Rats were divided into four experimental groups as follows; hypercholesterolemia, hypercholesterolemia+elevated IOP, elevated IOP and control. NOS-2 distribution, lipid peroxidation and retinal nerve fiber layer (RNFL) thickness was evaluated in all experimental groups at the end of 24 weeks. RESULTS Light microscopic evaluation of retinas in hypercholesterolemic rats revealed breaks and discontinuation in focal areas in the outer nuclear layer (ONL). NOS-2 positive staining was observed throughout the outer plexiform layer (OPL), inner plexiform layer (IPL) and ganglion cell layer (GCL) in rats with elevated IOP and/or hypercholesterolemia. Calculated values of RNFL thickness in hypercholesterolemic rats were significantly higher than those in the control and elevated IOP group. Vitreous malondialdehyde (MDA) levels detected in elevated IOP (3.51+/-0.31 nmol/mg protein) and hypercholesterolemia+elevated IOP (5.14+/-1.28 nmol/mg protein) groups were significantly higher than those detected in hypercholesterolemic (1.92+/-1.43 nmol/mg protein) and control (1.89+/-0.24 nmol/mg protein) groups. CONCLUSION The presented data confirms hypercholesterolemia as a risk factor in the development of glaucomatous optic neuropathy (GON) and suggests that increased circulating cholesterol may exacerbate disease progression by inducing NOS-2 expression and elevating oxidant tissue injury.

Deep anterior lamellar keratoplasty using big-bubble technique for treatment of corneal stromal scars.

Purpose: To report the clinical outcomes of deep anterior lamellar keratoplasty (DALK) in patients with anterior corneal stromal scars associated with various etiologies. Methods: A total of 79 eyes of 79 patients with corneal stromal scars sparing the Descemet membrane and the endothelium underwent DALK by using big-bubble technique. The main outcome measures of the study were the ability to successfully complete DALK, intraoperative and postoperative complications, best spectacle-corrected visual acuity, refraction, and graft clarity. Results: Seventy-two of the surgical procedures were carried out as DALK, and the mean follow-up time was 28.1 ± 17.9 months (range, 12-78 months). The most frequent indication for DALK surgery was postherpetic keratitis (44%). Complete Descemet membrane exposure via big bubble (descemetic DALK) could be achieved in 57 cases (79%). Fifteen eyes (21%) required layer-by-layer manual dissection (predescemetic DALK). Best spectacle-corrected visual acuity of 6/12 or better was present in 59 eyes (82%) postoperatively. The mean spherical equivalent and topographic astigmatism were −3.32 ± 2.13 (range, −9.13 to +4.75) and −2.97 ± 1.94 (range, −8.0 to +4.50) diopter, respectively. There were 2 instances of stromal graft rejection, which responded to medical therapy. Conclusions: DALK big-bubble technique may be a valuable and safe treatment in patients with corneal stromal scar with healthy endothelium. The visual and refractive outcomes are comparable to standard penetrating keratoplasty, avoiding the risk of endothelial rejection.

Effect of Pregnancy on Intraobserver and Intertechnique Agreement in Intraocular Pressure Measurements

Aim: To evaluate the effect of pregnancy on intraobserver and intertechnique agreement for intraocular pressure (IOP) measurements. Material and Methods: Right eyes of 88 healthy women who were likely to become pregnant and of 94 healthy age-matched females were included in the study. Complete ocular examinations were performed on each eye. IOP measurements were obtained by Goldmann, Schiötz and non-contact tonometers (NCT) during 3-week exam periods before (within 6 weeks of conception) and during pregnancy (first, second and third trimesters) for pregnant cases, and in similar time intervals for control subjects. In each exam period, three readings with each of three separate tonometers were obtained, at least 1 day apart. Intraobserver and intertechnique agreements for IOP measurements were assessed. Results: The mean visual acuity, keratometry and refractive error of both control and pregnant subjects did not change significantly during the study (all p values >0.01). In late pregnancy, pregnant cases demonstrated significant decreases in IOP measurements obtained with each of the three tonometers, and in intraobserver agreement with Goldmann and Schiötz tonometers (all p values <0.01). Intertechnique agreement of both Goldmann and Schiötz tonometers with NCT decreased significantly in the third trimester. Both intraobserver and intertechnique agreement in IOP measurements of control subjects were not found to change significantly during the study (all p values >0.01). Conclusion: IOP significantly decreased in the third trimester of pregnancy. Perfect intraobserver agreement in IOP readings of pregnant subjects was obtained with NCT. This may suggest that NCT is a viable option for IOP measurements during the follow-up of pregnant patients at risk for glaucoma.

Conversion to deep anterior lamellar keratoplasty (DALK): learning curve with big-bubble technique.

BACKGROUND AND OBJECTIVE To report the perioperative complications and clinical outcomes of 50 deep anterior lamellar keratoplasty (DALK) cases. PATIENTS AND METHODS Fifty eyes of 50 patients with pathologies involving the corneal stroma and sparing the Descemets membrane and endothelium were included consecutively in this prospective, noncomparative interventional case series study. DALK was performed using the big-bubble technique. RESULTS The most frequent indication for DALK surgery was keratoconus (26 eyes), followed by corneal dystrophy (10 eyes) and superficial corneal scar (14 eyes). The average follow-up period was 12.0 ± 3.9 months. DALK was completed in 41 cases (82%). A big bubble was achieved successfully in 37 cases (74%). Descemets membrane perforations occurred in 14 (28%) eyes, 8 of which were macroperforation and necessitated conversion to penetrating keratoplasty. Complications tended to decrease throughout the study. Postoperative best-corrected visual acuity of 0.5 or better was present in 30 of 41 (73.2%) eyes that underwent DALK. There was no episode of graft rejection. CONCLUSION DALK big-bubble technique may be a valuable procedure during transition from penetrating keratoplasty to anterior lamellar keratoplasty. It provided acceptable visual and refractive outcome even during the learning period in a variety of corneal lesions.

Nitrotyrosine formation and apoptosis in rat models of ocular injury.

This study was performed to examine inducible nitric oxide synthase (NOS-2) expression, nitrotyrosine formation and apoptosis in rats with elevated intraocular pressure (IOP) and/or ocular inflammation. Ocular inflammation was induced via injection of intra-vitreal lipopolysaccharide (LPS) while IOP was elevated by episcleral vessel cauterization. Animals were randomized to one of the following conditions: elevated IOP, LPS, elevated IOP+LPS, and control. Immunohistochemical staining and western blot analysis of retinal lysates revealed NOS-2 and nitrotyrosine immunoreactivity in all disease groups. NOS-2 expression and protein nitration was significantly greater in rats with elevated IOP+LPS compared to elevated IOP, LPS, and control groups. Nitrite levels in the retina affirmed significantly increased levels of nitric oxide generation in LPS-treated rats with elevated IOP (346 ± 23.8 μM) vs LPS-treated, elevated IOP and control groups (195.6 ± 12.6, 130 ± 2.5 and 76.6 ± 15.6 μM, respectively). Retinal TUNEL staining showed apoptosis in all diseased groups. Percent of apoptotic cells was significantly greater in the elevated IOP+LPS group compared to LPS-treated or elevated IOP groups. Presented data illustrates that both elevated IOP and ocular inflammation augment NOS-2 expression, retinal protein nitration and apoptosis in rats.

Evaluation of topical ciclosporin 0.05% for prevention of rejection in high-risk corneal grafts.

Aim: To evaluate the efficacy of combined treatment with commercially available 0.05% topical ciclosporin and topical corticosteroid compared with treatment with topical corticosteroids only after high-risk keratoplasty. Patients and methods: A total of 47 high-risk keratoplasties were randomly divided into two groups based on the postoperative immunosuppression. Twenty-five eyes (group 1) were treated with 0.05% ciclosporin and dexamethasone 0.1%, and 22 eyes (group 2) were treated with dexamethasone only. The clinical outcome of penetrating keratoplasty was evaluated by the rate of rejection-free graft survival and graft survival evaluation by the Kaplan–Meier logrank test. Results: The average length of follow-up was 20.2 (SD 7.1) months in group 1 and 18.5 (6.6) months in group 2 (p = 0.421). Rejection-free graft survival rates were 60.8% in group 1 and 54.5% in group 2 (Kaplan–Meier logrank test, p = 0.474). In group 1, the graft survival rate was 73.9%; in group 2, the graft survival rate was 68.1%. The difference in the graft survival rates between the groups was also not statistically significant (Kaplan–Meier logrank test, p = 0.518). Conclusion: In high-risk corneal grafts, the efficacy of 0.05 percent commercially available topical ciclosporin combined with dexamethasone topically was not better than that of dexamethasone alone in preventing rejection.

Transmission electron microscopy and autofluorescence findings in the cornea of diabetic rats treated with aminoguanidine

BACKGROUND The accumulation of advanced glycation end products (AGEs) has been implicated in the pathogenesis of diabetic keratopathy. The present study was aimed to understand if aminoguanidine (AG), an AGE inhibitor, was protective against the development of corneal complications in a diabetic rat model. METHODS Wistar rats were divided into three experimental groups: control, diabetic, and AG-treated diabetic. Diabetes was induced in rats via a single intraperitoneal injection (60 mg/kg) of streptozocin (STZ) and AG was administered in drinking water at a dose of 1 g/L. All animals were sacrificed at the end of 10 weeks and corneas from diabetic and nondiabetic rats were analyzed via transmission electron microscopy (TEM). Corneal autofluorescence measurements were also performed in all experimental groups. RESULTS Electron microscopic evaluation revealed that aminoguanidine treatment in diabetic rats prevented the formation of intracellular spaces between neighbouring cells in the superficial corneal epithelium. Hyperglycemia-induced degeneration of intracellular organelles and formation of cytoplasmic vacuoles in the corneal stroma was also prevented with the treatment of AG. Corneal autofluorescence detected in the diabetic group (5.98 +/- 2.17 Fi/mg protein) was found to be significantly greater than the control (3.92 +/- 0.56 Fi/mg protein) and the AG-treated diabetic group (4.18 +/- 0.59 Fi/mg protein) (p < 0.05). INTERPRETATION The presented data provide evidence that AG is preventive against corneal alterations in experimental diabetes.