Harun Çakmak

The one‐eye trial and fellow eye response to prostaglandin analogues

Background:  To determine if the intraocular pressure (IOP) reduction in one‐eye trial correlates with the IOP reduction in the fellow eye when IOP variability during office hours is taken into account.

Change in tear film characteristics in visual display terminal users.

Purpose To evaluate changes in symptoms and tear film characteristics in young computer users. Methods Fifty-one computer users and 26 controls were evaluated at the beginning and the end of the working day. Subjects with ocular or systemic disease, history of ocular surgery, use of contact lenses or glasses with antireflective surfaces, and use of topical or systemic medications were excluded from the study. Computer use duration, Ocular Surface Disease Index (OSDI) questionnaire, tear osmolarity, Schirmer test, tear break-up time (TBUT), and ocular surface vital dye staining were performed prevocationally and postvocationally. Results The mean age was 31.2 ± 6.3 years in computer users and 33.7 ± 5.8 in controls. The mean reported computer use was 6.9 ± 2.7 hours/day in computer users and 0.4 ± 0.5 hours/day in controls. The mean prevocational and postvocational values in computer users for OSDI, osmolarity, TBUT, and Schirmer test were 23.2 ± 16.6 and 27.0 ± 17.6, 306.6 ± 14.9 and 311.0 ± 12.5 mOsm/L, 13.9 ± 4.0 and 13.2 ± 3.8 seconds, 22.7 ± 11.8 and 20.6 ± 12.5 mm, respectively. The vocational change was significant for all parameters in the computer user group but not in the control group. The osmolarity-based dry eye diagnosis was 27.4% in the computer users while it was 15.4% in the control group. Oxford score was only grade 1 in 5.9% of visual display terminal users and did not change at the end of the day. Conclusions Both symptoms and signs of dry eye increased significantly with computer use. Approximately 1 of every 3-4 computer users was found to have dry eye with higher tear osmolarity values.

Effects of sunitinib and bevacizumab on VEGF and miRNA levels on corneal neovascularization

Abstract Aim: To evaluate the effects of sunitinib (0.5 mg/ml) and bevacizumab (5 mg/ml) on VEGF-A, VEGFR-2 and microRNA (miRNA) levels on corneal neovascularization (CNV). Methods: In this study, CNV was induced by silver nitrate application to the cornea, and 40 Albino male rats were equally divided into four subgroups: Group 1 (sunitinib): After silver nitrate application to the cornea, 0.5 mg/ml sunitinib eyedrop was administered twice daily for two weeks (n = 10). Group 2 (bevacizumab): After silver nitrate application to the cornea, 5 mg/ml bevacizumab eyedrop was administered twice daily for two weeks (n = 10). Group 3 (control): After silver nitrate application to the cornea, normal saline eyedrop was administered twice daily for two weeks (n = 10). Group 4 (vehicle): After silver nitrate application to the cornea, 1% DMSO eyedrop was administered twice daily for two weeks (n = 10). After two weeks from the silver nitrate application, corneas were evaluated by hand-held biomicroscope for their vascularization status. Then, corneas were excised and the expression levels of VEGFR-2, VEGF-A and the common miRNA markers for neovascularization (miR-15 b, miR-16, miR-23a, miR-126, miR-188, miR-210, miR-221, miR-222, miR-410 and miR-423) were evaluated by real-time PCR. Results: It was seen that the CNV was decreased in sunitinib- and bevacizumab-administered groups compared to the control and DMSO groups. Also, in comparison with the control group; VEGF-A expression was downregulated by nearly 0.75 times in sunitinib group and nearly 0.52 times in bevacizumab group. VEGFR-2 expression was downregulated by 0.89 times in sunitinib group and 0.68 times in bevacizumab group, compared to the control group. miR-15 b, miR-16 and miR-126 levels were statistically lower in sunitinib and bevacizumab groups, but miR-188 and miR-410 levels were two-fold higher compared to the control group. The miR-210 level was found higher only in sunitinib group compared to the control group. There were no statistically significant changes in miR-23a, miR-221, miR-222 and miR-423 levels among the groups. Conclusion: Topical application of bevacizumab (5 mg/ml) and sunitinib (0.5 mg/ml) decreases the levels of VEGFR-2 and VEGF-A in CNV. Further studies are needed for detailed analysis of genes which are targeted by up- or downregulated miRNAs in this study.

Comparison of pre-treatment and post-treatment use of selenium in retinal ischemia reperfusion injury

AIM To investigate the effects of selenium in rat retinal ischemia reperfusion (IR) model and compare pre-treatment and post-treatment use. METHODS Selenium pre-treatment group (n=8) was treated with intraperitoneal (i.p.) selenium 0.5 mg/kg for 7d and terminated 24h after the IR injury. Selenium post-treatment group (n=8) was treated with i.p. selenium 0.5 mg/kg for 7d after the IR injury with termination at the end of the 7d period. Sham group (n=8) received i.p. saline injections identical to the selenium volume for 7d with termination 24h after the IR injury. Control group (n=8) received no intervention. Main outcome measures were retina superoxide dismutase (SOD), glutathione (GSH), total antioxidant status (TAS), malondialdehyde (MDA), DNA fragmentation levels, and immunohistological apoptosis evaluation. RESULTS Compared to the Sham group, selenium pre-treatment had a statistical difference in all parameters except SOD. Post-treatment selenium also resulted in statistical differences in all parameters except the MDA levels. When comparing selenium groups, the pre-treatment selenium group had a statistically higher success in reduction of markers of cell damage such as MDA and DNA fragmentation. In contrast, the post-selenium treatment group had resulted in statistically higher levels of GSH. Histologically both selenium groups succeeded to limit retinal thickening and apoptosis. Pre-treatment use was statistically more successful in decreasing apoptosis in ganglion cell layer compared to post-treatment use. CONCLUSION Selenium was successful in retinal protection in IR injuries. Pre-treatment efficacy was superior in terms of prevention of tissue damage and apoptosis.

The effects of topical everolimus and sunitinib on corneal neovascularization

Abstract Purpose: To evaluate the effects of topical everolimus and sunitinib on corneal neovascularization (CNV). Methods: CNV was induced by application of silver nitrate to the cornea for all groups. Rats were divided into four groups of 10 rats each, and two corneas were obtained from each rat. Group I received 1 mg/ml everolimus, Group II received 0.5 mg/ml sunitinib, Group IV received no treatment (control group) and Group IV received 1% Dimethylsulfoxide (DMSO). All treatments were administrated twice daily for 2 weeks. The right corneas were used for extracellular signal-regulated kinase 1/2 (ERK 1/2) protein analysis by western blot analysis and the left corneas were used for ERK 1/2 and vascular endothelial growth factor-receptor (VEGFR-2) gene expression analysis by quantitative real-time PCR. Results: VEGFR-2 mRNA expression levels (ΔCt, median, min-max) were reduced in the everolimus 1.0 (0.25–1.81) and sunitinib 1.06 (0.24–2.68) treated groups compared with the control 4.74 (1.02–14.74) and DMSO groups 7.41 (0.72–13.10). The expression of ERK 1/2 protein and mRNA levels were reduced in everolimus group compared with the control group (p < 0.05). These differences were not seen between the sunitinib and control groups. Conclusıon: Topical administration of both everolimus and sunitinib reduced VEGFR-2 levels and inhibited CNV. In additon, everolimus reduced ERK 1/2 levels and seems to be more effective than sunitinib on CNV.

The temperament and character personality profile of the glaucoma patient

BackgroundTo determine the temperament and character profile of glaucoma patients.MethodsA total of 234 patients (104 with primary open angle glaucoma, and 130 control subjects without any ocular disease) were selected for this prospective, cross-sectional study. All the participants underwent a comprehensive ophthalmological examination, including the best corrected visual acuity, intraocular pressure measurement, gonioscopy, and visual field analysis. All the participants were given the Turkish version of the Temperament and Character Inventory (TCI). The TCI is a self-reported evaluate, with 240 true/false items measuring four domains of temperament; harm avoidance (HA), persistence (PS), novelty seeking (NS), reward dependence (RD), and three domains of character; self-transcendence (ST), cooperativeness (C), self-directedness (SD).ResultsThe glaucoma patients achieved the higher scores than the controls for the HA and SD dimensions (p < 0.001 and p = 0.033). The glaucoma patients scored lower than the controls for the NS, P and ST dimensions (p < 0.001, p < 0.001 and p = 0.002). There were no differences in the RD and C scores between the patients and the controls (p = 0.944 and p = 0.343). There was no correlation between the duration of illness and the TCI dimensions. Disease severity was positively associated with HA (r = 0,220, p = 0,025) and the anticipatory worry (r = 0.227, p = 0.021) dimension.ConclusionsGlaucoma patients had a different personality profile to healthy individuals. This may affect treatment compliance and is also important when coping with maladaptive patient attitudes.

Medical control of intraocular pressure with brinzolamide 1% after phacoemulsification

BACKGROUND To compare the effectiveness of only 1 drop of topical brinzolamide 1% with dosing every 12 hours and with no ocular hypotensive medication following clear corneal phacoemulsification surgery. METHODS This prospective, randomized, double-blind study was composed of 60 eyes of 60 patients who underwent uneventful clear corneal phacoemulsification surgery under topical anesthesia. There were no intraoperative complications. Eyes were randomized to receive only 1 drop of topical brinzolamide 1% immediately after surgery, 1 drop of brinzolamide 1% every 12 (q12h) hours starting immediately after speculum removal, or no ocular hypotensive medication (control group). Intraocular pressure (IOP) was measured preoperatively and at 4 to 6 hours and 18 to 24 hours postoperatively by a Perkins tonometer. RESULTS Preoperative IOP was not significantly different among the 3 groups. IOPs of both the brinzolamide 1 drop group (p = 0.000) and the brinzolamide q12h group (p = 0.001) were significantly lower than those of the control group at 4 to 6 hours postoperatively. The same result was observed at 18 to 24 hours postoperatively in the brinzolamide q12h group (p = 0.001) but not the brinzolamide 1 drop group (p = 0.489). The brinzolamide q12h group had significantly lower IOP compared with the brinzolamide 1 drop group (p = 0.000) at 18 to 24 hours postoperatively. None of the eyes in the medication groups, but 1 eye (5%) in the control group, had postoperative IOP elevation > or =30 mm Hg at 4 to 6 hours; such an elevation was not encountered at postoperative 18 to 24 hours. Preoperative to postoperative IOP increase of >5 mm Hg at 4 to 6 hours postoperatively was seen in 4 (20%), 4 (20%), and 14 (70%) eyes in the brinzolamide 1 drop group, the brinzolamide q12h group, and the control group, respectively. INTERPRETATION The current study reveals that 1 drop of brinzolamide 1% is sufficient to control IOP within the first 4 to 6 hours following uneventful phacoemulsification, whereas 12-hour dosing is necessary for prolonged control of IOP.

Diurnal blood pressure parameters in normal tension glaucoma, primary open angle glaucoma, and healthy subjects

Objective: The pathophysiology of glaucoma is still undisclosed. Cardiovascular hemodynamic changes are hypothesized to contribute to glaucoma. This study aimed to determine the differences in the diurnal blood pressure (BP) of patients with normal tension glaucoma (NTG), primary open angle glaucoma (POAG), and controls without glaucoma. Methods: A total of 129 patients were included in this study. The day–night average systolic and diastolic BPs, the day–night average pulse pressures (PPs), the day–night average heart rates, and the percentage of BP decline at night were obtained from the Holter devices and compared. Study design: Prospective, randomized, case-control study. Results: This study included 43 NTG patients (Group 1), 44 POAG patients (Group 2), and 42 healthy subjects without glaucoma (Group 3). The age (p=0.138) and sex (p=0.216) distributions between the groups were similar. The average day–night PP values of Group 1 were 49.17±9.90 and 46.07±10.84 mm Hg, respectively, while their total average PP was 48.48±9.60, their total average systolic BP was 120.02±12.65, and their night average systolic BP was 111.93±15.87 mm Hg. In Group 2, the average day and night PP values were 54.83±10.35 and 51.73±9.10 mm Hg, respectively, their total average PP was 54.00±9.87, their total average systolic BP was 126.75±11.50, and their night average systolic BP was 119.21±12.38 mm Hg. These differences were statistically significant and the corresponding p values were 0.040, 0.040, 0.037, 0.033, and 0.038. Conclusion: NTG patients have low diurnal BP parameters, which may reduce their optic nerve perfusion and may be responsible for their glaucomatous visual field damage.

The effect of methimazole-induced postnatal hypothyroidism on the retinal maturation and on the Sirtuin 2 level

Abstract Purpose: To investigate the effect of methimazole-induced postnatal hypothyroidism on the retinal maturation and to study Sirtuin 2 (SIRT2) level in the hypothyroidic rat retina. Methods: Twenty newborn Wistar albino rat pups were used in this prospective, randomized study. Wistar albino rats, weight 250–300 g, were impregnated (without addition of any drug) and were fed normally. Rat pups were randomly divided into two groups and were fed with breast milk. After weaning till they were 90 days of age, rat pups received the same water as their lactating mothers drank. Group 1 (methimazole (MMI)-induced hypothyroidy group), rats were given MMI-water, whereas, in Group 2, normal tap water. When the pups were 90 days of age, 20 rat pups were decapitated and the eyes were isolated. Eyes were investigated using histological, histomorphometric and immunohistochemistrical techniques. Results: No histological difference was seen between the groups stained with hematoxylin and eosin. In both groups the retinal layer structures and cells were observed as normal. The examples in the groups had a normal distribution for retinal thickness (pixel) measure. The mean value (mean ± std. deviation) was 554.7 ± 228.4 in the control group and 494.7 ± 129.4 in the hypothyroidy group. There was no significance between the groups in terms of retinal thickness (p = 0.231). However, immunohistochemistry revealed that SIRT2 was weaker stained in the ganglion cell layer and visual cell layer in the hypothyroidy group compared to the control group. Conclusion: Postnatal hypothyroidism altered the retinal cytoarchitecture and layering which are regulated by thyroid hormones (THs) during retinal maturation in the postnatal period. THs may act by the induction of the SIRT family proteins or through their receptors. Postnatal screenings for THs levels are very important to provide normal retinal development.

Long Term Results of Visual Field Progression Analysis in Open Angle Glaucoma Patients Under Treatment

Purpose : To evaluate visual field progression with trend and event analysis in open angle glaucoma patients under treatment. Materials and Methods : Fifteen year follow-up results of 408 eyes of 217 glaucoma patients who were followed at Adnan Menderes University, Department of Ophthalmology between 1998 and 2013 were analyzed retrospectively. Visual field data were collected for Mean Deviation (MD), Visual Field Index (VFI), and event occurrence. Results : There were 146 primary open-angle glaucoma (POAG), 123 pseudoexfoliative glaucoma (XFG) and 139 normal tension glaucoma (NTG) eyes. MD showed significant change in all diagnostic groups (p<0.001). The difference of VFI between first and last examinations were significantly different in POAG (p<0.001), and XFG (p<0.003) but not in NTG. VFI progression rates were -0.3, -0.43, and -0.2 % loss/year in treated POAG, XFG, and NTG, respectively. The number of empty triangles were statistically different between POAG-NTG (p=0.001), and XFG-NTG (p=0.002) groups. The number of half-filled (p=0.002), and full-filled (p=0.010) triangles were significantly different between XFG-NTG groups. Conclusion : Functional long-term follow-up of glaucoma patients can be monitored with visual field indices. We herein report our fifteen year follow-up results in open angle glaucoma.