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Plasma and vitreous homocysteine concentrations in patients with proliferative diabetic retinopathy.

Purpose: An increase in plasma concentrations of homocysteine (Hcy) in proliferative diabetic retinopathy (PDR) has been described. The aim of this study was to investigate vitreous Hcy levels in patients with PDR. Methods: Plasma and vitreous samples were obtained simultaneously at the time of vitreoretinal surgery from 20 patients with PDR and 12 nondiabetic patients with nonproliferative ocular diseases. Hcy levels were determined by high-performance liquid chromatography. Results: The mean vitreous and plasma Hcy concentrations for the diabetic group were 3.64 ± 0.65 &mgr;mol/L and 16.04 ± 2.75 &mgr;mol/L, respectively. The mean intravitreal and plasma Hcy concentrations for the control group were 1.08 ± 0.45 &mgr;mol/L and 9.18 ± 3.91 &mgr;mol/L, respectively. Both plasma and vitreous Hcy concentrations for the diabetic group were significantly higher than those for the control group (P < 0.001). A statistically significant correlation between vitreous and plasma Hcy concentrations was present only for the diabetic group (r = 0.525; P = 0.017). Conclusion: Vitreous Hcy concentrations were elevated in patients with PDR probably due to breakdown of the blood–retina barrier.

Effects of Amniotic Membrane Transplantation and Mitomycin C on Wound Healing in Experimental Glaucoma Surgery

Purpose: To evaluate the effects of mitomycin C and amniotic membrane transplantation on the modulation of wound healing after glaucoma filtration surgery. Methods: Trabeculectomy was performed in 3 groups of 10 rabbit eyes each. Sponges soaked in mitomycin C were applied to the first group, and amniotic membranes were transplanted around the scleral flap in the second group; the third group was the control. The arithmetic means of fibroblast and macrophage numbers per square centimetre were calculated. Results: The mean numbers of fibroblasts and macrophages were decreased significantly in the mitomycin C group, compared with the controls (p < 0.0001). Cell counts in the amniotic membrane group were also lower than the ones in the control group for fibroblasts and macrophages (p < 0.0001, p < 0.01, respectively). The difference between the two treatment groups was statistically significant for fibroblasts (p < 0.0001), but not significant for macrophages (p > 0.05). Conclusion: In spite of the fact that amniotic membrane transplantation is less effective than mitomycin C for depressing wound healing after trabeculectomy, it might be a safer alternative in selected cases when considering severe adverse effects of antimetabolites.

Nitric oxide and octreotide in retinal ischemia-reperfusion injury.

This experimental study was performed to investigate the role of ischemia–reperfusion injury on retinal nitric oxide activity and to determine whether octreotide, the synthetic analogue of natural somatostatin, modifies the nitric oxide activity during retinal ischemia–reperfusion in a quinea pig model. Three groups of seven pigmented male quinea pigs were formed; Control, Ischemia and the Ischemia/Octreotide groups. 90 minutes of pressure-induced retinal ischemia and 24 h of reperfusion were established in the ischemia and ischemia/octreotide groups. Saline for the ischemia group and 50 μg/kg of octreotide for the ischemia/octreotide group were administered intraperitoneally five times with 6-h intervals. At the end of the reperfusion period both eyes of the animals of the three groups were enucleated. One eye of each animal was randomly selected for biochemical assay and the other for histopathological analysis. Retinal nitrate levels were measured and histopathological changes were evaluated in the groups. The mean retinal nitrate levels of the control, ischemia and ischemia/octreotide groups were 157.6±25.2, 106.4±20.1 and 96.4±17.7 μmol/l, respectively. Nitrate levels decreased significantly both in the ischemia (p<0.01) and ischemia/octreotide (p<0.01) groups versus control. In the ischemia group, retinal histopathological changes, which were different from the control group, were prominent edema, polymorphonucleated leukocytes infiltration and vacuolated spaces in the inner retina. No significant change was observed in the histopathological specimens of the ischemia/octreotide group. Significant increase in the thickness of the inner plexiform layer of the retina of the ischemia group was observed versus the control and ischemia/octreotide groups (p<0.01 and p<0.01, respectively).The thickness of the inner plexiform layer of the retina of the ischemia/octreotide group did not change versus the control group. It was concluded that nitric oxide activity decreased during retinal ischemia–reperfusion and, although octreotide prevented the histopathological damage, it could not ameliorate the nitric oxide activity of the retina.

L-Carnitine in Experimental Retinal Ischemia-Reperfusion Injury

The effect of L-carnitine on retinal ischemia-reperfusion injury was evaluated in guinea pigs. 90 min of pressure-induced retinal ischemia followed by 24 h of reperfusion was established in both eyes of 2 groups of animals receiving either L-carnitine (100 mg/kg repeated in 5 doses) or saline intraperitoneally. After enucleation of all the eyes, including those of a control group, malonyldialdehyde (MDA) levels and the thickness of the retinal tissue were measured in 3 groups. The mean MDA value and the tissue thickness of the L-carnitine-treated group were statistically insignificant versus the control group (p > 0.05 and p > 0.05, respectively). However, these values were significantly different in the group receiving saline versus the control group and that receiving L-carnitine (p < 0.001, p < 0.001 and p < 0.001, p < 0.001 respectively). L-Carnitine might be an alternative drug for ischemia-reperfusion injury of the retina.

The Impact of Tacrolimus on Vascular Endothelial Growth Factor in Experimental Corneal Neovascularization

Purpose: To investigate the impact of tacrolimus on vascular endothelial growth factor (VEGF) in experimental corneal neovascularization (NV) immunohistochemically. Material and Methods: Five groups of seven Wistar albino rats were formed. A silver nitrate cauterization technique was used to induce corneal NV in the study groups, excluding Group 1 (Control Group). Rats in group 1 did not receive any treatment. Rats in group 2 (sham 1) were administered 1 ml of saline intraperitoneally once a day and those in group 3 (sham 2) received one drop of saline four times a day. Rats in group 4 were administered 0.3 mg/kg tacrolimus intraperitoneally once a day. For group 5, 0.3 mg/ml tacrolimus was installed four times a day. Digital photography for each cornea was performed and the percentage area of the NV on the total corneal surface was calculated. The intensity of VEGF immunostaining in the epithelial, the stromal, and endothelial layers was performed in a semi quantitative fashion. Results: The mean percentages of the neovascularized areas of intraperitoneally and topically tacrolimus-treated groups were lesser than those of the sham groups (p = 0.002, p = 0.038, respectively). The mean intensity of the epithelial VEGF immunostaining of the intraperitoneally tacrolimus-treated group was less than that of its sham group (p = 0.002), while the mean intensity of the stromal VEGF staining of the topically tacrolimus-treated group was lesser than that of its sham group (p = 0.042). The intensities of the endothelial VEGF immunostaining of the intraperitoneally and topically tacrolimus-treated groups were less than those of the sham groups (p = 0.038, p = 0.032). Conclusion: Systemic and topical administration of tacrolimus may be beneficial in the prevention of corneal NV because of its effect on VEGF.

The impact of tacrolimus on growth factors in experimental proliferative vitreoretinopathy.

Purpose To investigate the effect of intravitreal tacrolimus on an animal model of proliferative vitreoretinopathy (PVR) and on growth factors implicated in its pathogenesis. Methods Twenty-one guinea pigs were randomly assigned to one of three groups of seven animals each: no-PVR/saline group (no PVR/intravitreal saline-injected group), PVR/saline group (dispase-induced PVR group, treated with control injections of intravitreal saline), and PVR/tacrolimus group (treatment group, dispase-induced PVR group treated with intravitreal tacrolimus injections). At the end of the experiment, eyes were enucleated and the identification of the stages of PVR was carried out. While a halves of the enucleated globes were evaluated histopathologically for PVR formation, the retinas of the other halves of globes were used for the preparation of retinal homogenates. The transforming growth factor-&bgr;, platelet-derived growth factor, and fibroblast growth factor levels in homogenized retina tissues were measured by the enzyme-linked immunosorbent assay method. Results When assessing the average PVR stages in terms of severe PVR rates, the PVR/tacrolimus group had significantly improved when compared with the PVR/saline group. The PVR/tacrolimus group demonstrated significantly decreased levels of transforming growth factor-&bgr;, platelet-derived growth factor, and fibroblast growth factor when compared with the PVR/saline group and also demonstrated significant improvement in epiretinal membrane formation and retinal fold in the presence of histopathologic levels. The difference in degradation of photoreceptor cells between the PVR/tacrolimus and the PVR/saline groups was not statistically significant. Conclusion This study suggests that intravitreal tacrolimus application may suppress PVR development and that tacrolimus may merit investigation for the prophylaxis of PVR.

Protective effects of pentoxifylline in retinal ischemia/reperfusion injury.

We studied the effect of pentoxifylline on retinal lipid peroxidation and histopathologic changes due to ischemia/reperfusion (I/R). A total of 15 pigmented male guinea pigs were divided into 3 equal groups as control, sham and treatment groups. After application of high intraocular pressure for 90 min for the induction of retinal ischemia, 24-hour reperfusion was established in the sham and treatment groups. In the treatment and sham groups, either 45 mg/kg of pentoxifylline or saline was given 3 times at 8-hour intervals. Biochemical assay and histopathologic evaluation were performed on one randomly selected eye of each animal which was enucleated at the end of the reperfusion period, and retinal malondialdehyde (MDA) levels and thickness of the retinal tissue were determined for each group. The mean MDA level of the sham group was significantly higher versus the control and treatment groups (p < 0.001). When compared with the control group, the mean MDA level of the treatment group was slightly higher, but the difference was not statistically significant (p > 0.05). In comparison with the control group there was a significant increase in the thickness of the retina in the sham group (p < 0.0001), and no significant difference was found in the retinal thickness of the treatment group (p > 0.05). Pentoxifylline might have a preventive effect on the I/R injury of the retina.

spontaneous corneal perforation in a patient with lamellar ichthyosis and dry eye

We report spontaneous corneal perforation in a patient with lamellar ichthyosis. The patient presented with complaints of pain, redness, diminished vision, and discharge in her right eye for 15 days. Visual acuities were light perception in the right and 20/400 in the left eye. Cicatricial ectropion in both lower eyelids and 2 mm perforation site in the center of the right cornea were observed. Lamellar ichthyosis was suspected because of scaling and excessive dryness of entire body skin and was confirmed by skin biopsy. Amniotic membrane transplantation and transient tarsorraphy was performed and systemic anti-ichthyosis therapy was started. The follow-up visits were not possible because of patient inconsistency. In patients with cicatricial ectropion secondary to ichthyosis, corneal health should be closely monitored because of the perforation risk.

Effects of octreotide acetate and amniotic membrane on wound healing in experimental glaucoma surgery

Wound healing affects the success of glaucoma filtering surgery. Antimetabolites and antifibrotic agents are used in the modulation of surgical trauma. This study is performed to evaluate the effects of amniotic membrane and octreotide acetate on wound healing . Thirty pigmented rabbits were divided into three groups each including 10 animals. Trabeculectomy and topical postoperative prednisolone sodium phosphate four times daily for 7 days were applied to one eye of all the rabbits. After trabeculectomy, octreotide 10 μg three times daily applied topically to the octreotide group for 14 days and amniotic membrane transplantation was performed by suturing amniotic membrane between scleral flap and sclera to the amniotic membrane group. The operated eyes of the rabbits were enucleated on the 14th day of the operation and histopathological specimens were obtained from the bleb sites and they were evaluated by light microscope. Fibroblast and macrophage number per cm2 were counted and the average values were calculated. Compared with the control group, the fibroblasts and macrophages significantly decreased in the other two groups (p < 0.0001, p < 0.0001, respectively). The mean number of fibroblasts was lower than those of the control and amniotic membrane groups (p < 0.0001, p < 0.0001, respectively). Similarly the mean macrophage number was significantly lower in the octreotide group versus the control and amniotic membrane groups (p < 0.0001, p < 0.01, respectively). Octreotide administration and amniotic membrane transplantation might be alternative treatments in modulating the wound healing after trabeculectomy.

Trimetazidine for prevention of induced ischemia and reperfusion of guinea pig retina.

Objective: Trimetazidine (TMZ) has been used to protect against ischemia/reperfusion (I/R) injury of many tissues. We aimed to evaluate the effect of TMZ during retinal I/R in a guinea pig model. Study design/patients and methods: An experimental study in retinal I/R. Three groups of five guinea pigs were studied to include a control, placebo, and drug test groups. Prior to the application of 90 minutes of high intraocular pressure (IOP) to induce retinal ischemia followed by 24 hours of reperfusion, we applied intraperitoneal saline to the placebo group and 3 mg/kg of TMZ for the drug test group and repeated the injections at intervals of six hours for four cycles. Both eyes of the animals were enucleated at the end of the reperfusion period. Biochemical assay and histopathologic evaluation was performed on one randomly selected eye of each animal. The level of retinal-free malondialdehyde (MDA) and retinal layer thicknesses were determined and comparisons were then made with the control group. Results: The mean free MDA level increased in the placebo group (P = 0.006) but not in the drug group (P > 0.05). We observed polymorphonucleated leukocyte infiltration, retinal edema and hydropic degeneration in the retina of the placebo group. However, significant histopathologic change was not observed in specimens of the drug group. Conclusions: This study suggests TMZ has a beneficial effect on retinal lipid peroxidation and histopathologic changes due to I/R injury.