Comparison of the Effects of Eight Different Topical Non-Steroidal Anti-Inflammatory Drugs on Reducing Intravitreal Injection-induced Pain.

PURPOSE: To compare topical nonsteroidal anti-inflammatory drug (NSAID) efficacy on intravitreal injection (IVI)-induced pain reduction, and determine the most efficient topical NSAID. METHODS: This randomized controlled study included 662 eyes of 662 patients. Based on the types of NSAID administered before IVI, eight subgroups were formed. In the control group, a sterile saline solution was applied instead of NSAIDs. The visual analog scale (VAS) was used to assess pain scores after IVI. The VAS scores were noted immediately and 6 hours following injection (6th hour). RESULTS: Nepafenac 0.3%, 0.1%, and bromfenac had the lowest scores, immediately after and after 6 hours, with no significant differences. Diclofenac and ketorolac had higher VAS scores than the first trio but lower scores than the control group. Flurbiprofen, pranoprofen, and indomethacin did not significantly affect immediate pain; however, at the 6th hour, the VAS scores were significantly reduced. CONCLUSION: Nepafenac 0.3%, 0.1%, and bromfenac were the most effective NSAIDs for pain reduction. Although some NSAIDs did not have a significant effect on immediate pain, they all provided significant benefit at the 6th hour.

Evaluation of the effect of intravitreal injections on corneal epithelial, scleral and limbal region changes in diabetic retinopathy by AS-OCT.

PURPOSE: The aim of the study is to evaluate the effects of diabetic retinopathy and intravitreal injections on the corneal, limbal and scleral areas. METHODS: Patients with diabetes mellitus at different diagnosis and treatment levels were compared among themselves and with the control group in terms of corneal, limbal and scleral aspects with the help of anterior segment optical coherence tomography. In addition, clinical tests such as tear break-up time, Schirmer test-I and ocular surface disease index questionnaire were applied to the patients and the difference between the groups was investigated. RESULTS: When the groups were examined in terms of BUT, SCH-I and OSDI, there was a statistically significant difference between control group and diabetic group(p < 0.05). In the limbal region, all measurements are higher than in patients with diabetic eye involvement. Thinning was detected in the scleral area with intravitreal injection (p < 0.05). CONCLUSION: It should be known that DM may cause undesirable changes in the limbal region, and the importance of non-invasive detection with AS-OCT should not be forgotten. Since intravitreal injections for DME cause thinning of the sclera, it can cause various complications, and it may be recommended to change the quadrant in repetitive injection applications.

Evaluation of the structural changes of uveitis patients by optical biometry.

Objective (Aim): To observe the ocular structural changes in active and inactive uveitis patients. Methods: This retrospective study involved 30 patients (32 eyes) with anterior and intermediate uveitis cases and 54 eyes of 54 cases in a control group, who were admitted to the Ophthalmology Department at Trakya University. In the study group, 14 patients were females, 16 patients were males and in the control group 26 volunteers were females, and 28 volunteers were male of the 54 volunteers. Anterior chamber depth, axial length, intraocular pressure, lens thickness, central corneal thickness, steep and flat values in keratometry, corrected visual acuity in both eyes, anterior chamber cells, and vitreous cells were measured and compared between three groups (two uveitis groups - active and inactive - and control group). Results: In the comparison of the median values of axial length, central corneal thickness, and steep and flat values of keratometry, the values of the patients with active uveitis were higher than the ones in the control group in each parameter, but no significant difference was observed. The anterior chamber depth parameter value was higher, the lens thickness value was lower in patients with active uveitis than the values in the control group and the differences were statistically significant (p<0,05). No significant structural differences in the values of the active and inactive group patients (p>0,05) were observed. Conclusions: Only lens thickness and anterior chamber depth parameters were statistically significant in patients with active uveitis, compared with the inactive uveitis group. Anterior chamber depth measurement values were higher and lens thickness measurement values were lower in patients with active uveitis when compared with the control group. Abbreviations: AAU = Acute anterior uveitis, CAU = Chronic Anterior Uveitis, AC = Anterior Chamber, IOP = Intraocular Pressure, IVCM = in vivo Confocal Microscopy, AS-OCT = Anterior Segment Optical Coherence Tomography, UBM = Ultrasound Biomicroscopy, LFP = Laser Flare Photometry, KP = Keratic Precipitates, OCT = Optical Coherence Tomography, AL = Axial Length, ACD = Anterior Chamber Depth, LT = Lens Thickness, CCT = Central Corneal Thickness, Ks = Steep Value of Keratometry, Kf = Flat Value of Keratometry, AUP = Active Uveitis Patients, IUP = Inactive Uveitis Patients, SUN = Standardization of Uveitis Nomenclature.

Association of Changes in Thickness of Limbal Epithelial and Stroma with Corneal Scars Detected by High-Resolution Anterior Segment Optic Coherence Tomography.

AIM: To investigate the corneal central and limbal thickness in cornea scar patients using high-resolution anterior segment optical coherence tomography (AS-OCT) and to determine the changes in the limbal region due to the corneal scar. Also, to evaluate tear film parameters in scar patients. METHODS: Thirty patients with central corneal scar and 30 control subjects. The control subjects were healthy individuals who came to our clinic for routine ophthalmological examination. They were enrolled in this matched case-control study. Central epithelial thickness (ET), stromal thickness (ST), limbal epithelial thickness (LET), and limbal stromal thickness (LST) were analyzed using high-resolution AS-OCT. For evaluation of the ocular surface, the following techniques were used: tear break-up time (BUT) employing standard sterile strips of fluorescein sodium, Schirmer test-I (SCH), and the Ocular Surface Disease Index (OSDI) Questionnaire. RESULTS: The mean central ET of the patient group was 51.5 ± 12.4 µm, while the mean central ET of the control group was 59.2 ± 9.0 µm. There was a statistically significant difference between patients and controls (p = 0.008). The mean LST of the patients was 747.9 ± 115.7 µm, and the mean LST of the controls was 726.3 ± 79.7 µm. There was a statistically significant difference between patients and controls according to BUT (p = 0.009) and SCH (p = 0.04). However, there was no significant difference between OSDI results of patients and controls (p = 0.08). CONCLUSION: Corneal monitoring with high-resolution AS-OCT is a simple, noninvasive, useful technique for corneal scar patients. Cornea scars cause decreased ET. This result could be associated with lower tear film parameters in scar patients. The scar length is associated with higher intraocular pressure (IOP) values. Decreased LET and increased LST were detected in scar patients.

Prognostic factors associated with the course of vitreomacular traction in eyes with age-related macular degeneration.

CLINICAL RELEVANCE: Vitreomacular traction(VMT) is a clinical syndrome that can cause decreased vision and may affect the treatment response in cases of age-related macular degeneration(AMD). Factors affecting the course of VMT in AMD cases will guide the clinician in terms of patient management. BACKGROUND: The aim of this study was to determine the prevalence of VMT in patients with AMD, to evaluate the natural course of VMT, and to investigate factors associated with the prognosis of VMT in eyes with AMD. METHODS: This retrospective case series was conducted with 55 eyes of 46 patients who were diagnosed as having AMD accompanying with VMT. Demographic data, complete ophthalmologic examination findings, type of AMD, receiving an intravitreal injection(IVI), number of IVIs, and the presence of complete spontaneous release were obtained from the medical records of the patients. The horizontal length of VMT(HLVMT), central macular thickness(CMT), the horizontal length of choroidal neovascularization(HLCNV) were evaluated from spectral-domain optical coherence tomography(SD-OCT) images. RESULTS: Spontaneous release was observed in 7(28%) eyes of the exudative AMD group and 10(33.3%) eyes of the nonexudative AMD group. On the last visit, the HLVMT was increased in 22(40%) of the eyes and a decrease in HLVMT was observed in 8(14.5%) of the eyes. In the remaining 12(21.8%) eyes had unchanged HLVMT. In all eyes with CNV, the area of VMT corresponded in 100% with localization of the CNV complex. No significant difference was found between the eyes with spontaneous release and persistent traction in terms of the type of AMD, IVI, HLVMT, age, gender, and crystalline lens status. CONCLUSION: In this study, VMT was observed at higher rates in eyes with exudative AMD compared to the eyes with nonexudative AMD. However, spontaneous release rates were found close to those with idiopathic VMT independently of the type of AMD, HLVMT, and IVI.

MicroRNA-184 attenuates hypoxia and oxidative stress-related injury via suppressing apoptosis, DNA damage and angiogenesis in an in vitro age-related macular degeneration model.

Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide, particularly in developed countries. Recently, microRNAs (miRs) have become popular research area to develop new treatment options of AMD. However, interaction between hsa-miR-184 and AMD remain largely unexplored. In this study, sub-lethal levels of Deforoxamine Mesylate salt (DFX) and H2O2 were applied to ARPE-19 cells to establish a severe in vitro AMD model, via durable hypoxia and oxidative stress. We found that up-regulation of miR-184 level in AMD can suppress hypoxia-related angiogenic signals through HIF-1α/VEGF/MMPs axis. Also, miR-184 suppressed the hypoxia sensor miR-155 and genes in the EGFR/PI3K/AKT pathway, which is an alternative pathway in angiogenesis. To investigate the mechanism behind this protective effect, we evaluated the impact of miR-184 on retinal apoptosis in a model of AMD. miR-184 inhibited retinal apoptosis by upregulating BCL-2 and downregulating pro-apoptototic BAX, TRAIL, Caspase 3 and 8 signals as well as p53. Taken together, miR-184 attenuates retinal cell damage induced by severe AMD pathologies through suppressing hypoxia, angiogenesis and apoptosis. The safety profile of miR-184 was observed to be similar to Bevacizumab, which is in wide use clinically, but miR-184 was found to provide a more effective therapeutic potential by regulating simultaneously multiple pathologies.

Melatonin prevents blood-retinal barrier breakdown and mitochondrial dysfunction in high glucose and hypoxia-induced in vitro diabetic macular edema model.

Diabetic macular edema (DME) is a leading cause of blindness in diabetic retinopathy. Prolonged hyperglycemia plus hypoxia contributes to DME pathogenesis. Retinal pigmented epithelial cells comprise the outer blood-retinal barrier and are essential for maintaining physiological functioning of the retina. Melatonin acts as an antioxidant and regulator of mitochondrial bioenergetics and has a protective effect against ocular diseases. However, the role of mitochondrial dysfunction and the therapeutic potential of melatonin in DME remain largely unexplored. Here, we used an in vitro model of DME to investigate blood-retinal barrier integrity and permeability, angiogenesis, mitochondrial dynamics, and apoptosis signaling to evaluate the potential protective efficacy of melatonin in DME. We found that melatonin prevents cell hyper-permeability and outer barrier breakdown by reducing HIF-1α, HIF-1ß and VEGF and VEGF receptor gene expression. In addition, melatonin reduced the expression of genes involved in mitochondrial fission (DRP1, hFis1, MIEF2, MFF), mitophagy (PINK, BNip3, NIX), and increased the expression of genes involved in mitochondrial biogenesis (PGC-1α, NRF2, PPAR-γ) to maintain mitochondrial homeostasis. Moreover, melatonin prevented apoptosis of retinal pigmented epithelial cells. Our results suggest that mitochondrial dysfunction may be involved in DME pathology, and melatonin may have therapeutic value in DME, by targeting signaling in mitochondria.

Agreement of Anterior Segment Parameters Between Schiempflug Topography and Swept-Source Optic Coherence Based Optic Biometry in Keratoconus and Healthy Subjects.

PURPOSE: The aim of this study is to compare anterior segment parameters, including corneal thickness (CCT), keratometry and anterior chamber depth (ACD), and white to white corneal diameter (WTW), obtained by Pentacam Schiempflug imaging and intraocular lens (IOL) Master 700 swept-source optic coherence tomography biometry in keratoconus patients and healthy subjects. METHODS: This prospective cross-sectional instrument agreement analysis includes 88 eyes of 50 keratoconus patients and 87 eyes of 50 healthy subjects. Biometry was performed using IOL Master 700, and topography was performed using Pentacam. The keratometry values (Kf, Ks, Km, and Kmax), ACD, WTW, CCT, axial length (AL), anterior chamber angle (ACA), and lens thickness (LT) were evaluated. Levels of agreement between devices were evaluated by Bland-Altman plots with 95% limits of agreement. RESULTS: Intraocular lens Master 700 showed higher WTW, ACD, pupil diameter, and CCT values than Pentacam in both the keratoconus and control groups. However, there were no statistically significant differences in flat keratometry (Kf) and steep keratometry (Ks) values between the groups. CONCLUSION: Pentacam and IOL Master 700 may be used interchangeably in normal eyes and keratoconus eyes for the measurement of keratometry values and axis; however, these two devices should not be considered interchangeable for WTW, ACD, pupil diameter, and CCT measurements in both keratoconus patients and healthy subjects.

Corneal epithelium and limbal region alterations due to glaucoma medications evaluated by anterior segment optic coherence tomography: a case-control study.

AIM: To investigate the corneal epithelial and limbal epithelial alterations in patients under topical glaucoma treatment using anterior segment-OCT (AS-OCT) and to determine the changes of the limbal region due to the preservatives and glaucoma drugs, that can progress to limbal stem cell deficiency (LSCD). Limbal thickness was measured by AS-OCT to evaluate limbal cell deficiency. METHODS: Forty-seven patients using topical medication for glaucoma, and 48 control subjects were enrolled in this matched case-control study. The patients were divided into four groups according to the treatment regimens. Group 1: One-drug regimen, Group 2: Two-drug regimen, Group 3: Three-drug regimen, Group 4: Four-drug regimen For the ocular surface evaluation; tear break-up time with standard fluorescein sodium sterile strip application, Schirmer test-I, Ocular Surface Disease Index Questionnaire, and AS-OCT were performed. RESULTS: A total of 95 subjects were included: 47 eyes of 47 patients with glaucoma medication and 48 eyes of 48 healthy subjects. There was a statistically significant difference between patients and controls according to BUT, SCH, and OSDI (p < 0.001). The mean central corneal epithelium thickness was 48.5 ± 5.3 in patients and 54.5 ± 5.9 in controls (p < 0.001). The mean central total corneal thickness was 529.2 ± 41.2 in patients and 536 ± 35.3 in controls (p = 0.335). The mean limbal epithelium thickness was 64.1 ± 9.1 in patients and 76 ± 11.5 in controls (p < 0.001). CONCLUSION: Using at least one glaucoma drug caused limbal area injury, changed ocular surface measurements, and significantly reduced the limbal epithelial thickness where the stem cells reside. The limbal epithelial thickness measurement by AS-OCT seems to be an innovative, non-invasive, and promising technique for detecting and staging corneal damage in topical glaucoma therapy.

Neferine inhibits epidermal growth factor-induced proliferation and migration of retinal pigment epithelial cells through downregulating p38 MAPK and PI3K/AKT signalling.

Purpose: Proliferative vitreoretinopathy (PVR) occurs in approximately 5-10% of patients after retinal detachment surgery. Neferine is a bis-benzylisoquinoline alkaloid found in the green seed embryos (Nelumbo nucifera) of the lotus flower and has various properties, such as being antithrombotic, antioxidant, neuroprotective, anticancerous, and anti-inflammatory. Although the effects of neferine on the proliferation and migration of cancer cells have been partially shown, their possible role and the mechanism of action on PVR remain unclear.Materials and methods: To mimic a PVR model in vitro, retinal pigment epithelial (RPE) cells were exposed to epidermal growth factor (EGF) and treated with various concentrations of neferine. Cell viability was determined by MTT test. Cell-cycle phase distribution and cell migration were examined by image-based cytometry and wound healing test, respectively. Messenger RNA (mRNA) and protein expression were determined by RT-qPCR and Western blotting, respectively.Results: Stimulation of the cells with EGF significantly increased the rate of proliferation, whilst treatment with low concentrations of neferine-reduced proliferation to a level equal to that seen in untreated cells. Neferine significantly downregulated EGF-increased cell viability, and survivin mRNA expression was depressed to the basal level. In addition, neferine treatment contributed to cell proliferation loss by upregulating p21 and p27 expression leading to cycle arrest at the G1 phase. The treatment significantly inhibited cell migration by upregulating the expression of epithelial markers, such as E-cadherin and occludin, and decreased MMP2, MMP9, α-SMA, and vimentin. Neferine treatment markedly reduced phosphotidyl inositol 3-kinase (PI3K), AKT, p-p38 mitogen-activated protein kinase (MAPK), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) protein expression.Conclusion: It can be considered that neferine may be a potential candidate molecule in the treatment of PVR by inhibiting cell proliferation and the migration of EGF-induced RPE cells through the modulation of various transcriptional activities.

The Role of Melatonin in Oxidative Stress, DNA Damage, Apoptosis and Angiogenesis in Fetal Eye under Preeclampsia and Melatonin Deficiency Stress.

Aim: The aim of this study was to investigate the possible mechanisms of ocular damage induced by pinealectomy (PNX) and preeclampsia (PE), and to determine the cellular and molecular effects of melatonin treatment on oxidative stress, DNA damage, molecular chaperone responses, induction of apoptosis and angiogenesis in the fetal eye of both PNX and PNX+PE animals. Material and Methods: We analysed therapeutic potential of melatonin on fetal eye damage in PNX and PNX+PE animals using Malondialdehyde (MDA), Random Amplified Polymorphic DNA (RAPD), qRT-PCR and Western blot assays. Results: Our study presents three preliminary findings: (a) in fetal eye tissues, PNX and PNX+PE significantly induce oxidative damage to both DNA and protein contents, leading to a dramatic increase in caspase-dependent apoptotic signalling in both mitochondrial and death receptor pathways; (b) the same conditions trigger hypoxia biomarkers in addition to significant overexpression of HIF1-α, HIF1-ß, MMP9 and VEGF genes in the fetal eye; (c) finally, melatonin regulates not only the expression of genes encoding antioxidant enzymes and increase in DNA damage as well as lipid peroxidation but also limits programmed cell death processes in the fetal eye of PNX and PNX+PE animals . Furthermore, melatonin can relatively modulate genes in the HIF1 family, TNF-α and VEGF, thus acting as a direct anti-angiogenic molecule. In conclusion, both PNX and PNX+PE induce ocular damage at both cellular and molecular levels in fetal eye tissue of rats. Conclusion: Our results clearly indicate the potential of melatonin as a preventative therapeutic intervention for fetal ocular damage triggered by both PNX and PNX+PE.

Comparison of topical nepafenac 0.1% with intravitreal dexamethasone implant for the treatment of Irvine-Gass syndrome.

AIM: To compare safety and efficacy of intravitreal dexamethasone (IVD) implant with topical nepafenac (TN) 0.1% in previously untreated Irvine-Gass syndrome (IGS) in clinical practice. METHODS: This was a retrospective study of 62 eyes with IGS after phacoemulsification with posterior chamber intraocular lens (IOL) implantation. None of the patients used treatment before IVD or TN. Best-corrected visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study chart (ETDRS), slit-lamp, intraocular pressure (IOP) measurement, fundus examination, spectral-domain optical coherence tomography (OCT) and fundus florescein angiography were performed to all subjects at baseline, 1, 3 and 6mo. RESULTS: The mean BCVA of the IVD group was 49.3±6.8, and the mean BCVA of the TN group was 32.9±7.3 ETDRS letters in post-treatment month 6. The mean central macular thickness (CRT) of IVD group was 266.6±53.5 µm and the mean CRT of TN group was 364.9±56.3 µm in post-treatment month 6. Baseline BCVA has correlation with final BCVA in TN group however there was no correlation between baseline BCVA and final BCVA in IVD group. CONCLUSION: IVD is found to be better than TN in controlling pseudophakic macular edema and improving visual acuity. IVD group also has significantly lower CRT however IOP is not significantly different between two groups in post-treatment month 6.

Retinal ganglion cell complex and peripapillary retinal nerve fiber layer thicknesses following carotid endarterectomy.

PURPOSE: To examine changes in retinal ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (RNFL) thicknesses by optical coherence tomography (OCT) in contralateral and ipsilatateral eyes of carotid artery stenosis (CAS) patients before and after carotid endarterectomy (CEA). METHODS: Forty-two consecutive patients diagnosed with CAS (70-99% stenosis rate) who underwent CEA were included in this prospective cross-sectional study. The indication for CEA was based on the Asymptomatic Carotid Atherosclerosis Study. Doppler ultrasonography and computed tomography angiography were performed to calculate CAS. All the subjects underwent an ophthalmological examination, including best corrected visual acuity (BCVA), intraocular pressure (IOP) measurements, biomicroscopy, fundoscopy, and OCT before and after the surgery. RESULTS: The mean preoperative intraocular pressure was 15.2 ± 2.1 mmHg in the ipsilateral eye and 15.8 ± 2.7 in the contralateral eye. The mean postoperative intraocular pressure in the ipsilateral and contralateral eye was 18.6 ± 3.0 and 19.3 ± 3.8, respectively. The intraocular pressure was significantly higher in postoperative eyes (p = 0.0001). There was a statistically significant decrease in peripapillary RNFL thickness in superior quadrants postoperatively in ipsilateral eyes. The retinal GCC layer thickness was not significantly different before and after CEA in ipsilateral and contralateral eyes. CONCLUSIONS: Carotid endarterectomy results in thinning of the superior peripapillary RNFL thickness. To the best of our knowledge, this is the first study to examine peripapillary RNFL and GCC thicknesses before and after CEA.

Comparison of corneal endothelial cell analysis in patients with uveitis and healthy subjects.

PURPOSE: The aim of this study is to investigate the effect of uveitis in corneal endothelial cell number and morphology by non-contact specular microscopy. METHODS: Our cross-sectional study was performed on 56 eyes of uveitis patients and 53 eyes of healthy subjects. Non-contact specular microscopy was performed to all subjects. The cell density (CD), coefficient of variation, cell minimum area (Min) and cell maximum area (Max), the average of cell size (AVG), percent of hexagonality (HEX%), central corneal thickness (CCT), intraocular pressure (IOP) during uveitis and during remission were measured and compared between two groups. RESULTS: The mean endothelial cell analysis of the patients was 2540 ± 619 cells/mm2, and the mean endothelial cell analysis of the control group was 2834 ± 413 cells/mm2. The difference was statistically significant between the groups (p = 0.01). There was a statistically significant difference between two groups in terms of Max, Min, AVG, and HEX values. However, there was no difference in terms of CCT between two groups. There was a significant negative correlation between CD and IOP during uveitis attack. There was a significant negative correlation between the anterior chamber cell value and CD. CONCLUSION: Our results suggested that uveitis affected endothelial cell density, cell size and shape but not the corneal thickness without being influenced by the duration and number of attacks. Increased IOP during uveitis and anterior chamber cell value had an important role on CD in patients with uveitis.

Metabolic Syndrome May Exacerbate Macular and Retinal Damage in Psoriasis Vulgaris.

Purpose: To evaluate whether cases with both psoriasis and metabolic syndrome are prone to retinal and macular changes. Materials and Methods: A total of 174 eyes of 87 subjects were evaluated. Of the 87 subjects, 24 had psoriasis, 19 had psoriasis and metabolic syndrome, 18 had metabolic syndrome only and 26 were healthy subjects. Biochemical analysis, anthropometric, blood pressure and optical coherence tomography measurements and thickness analysis were obtained for each case. Results: The superior retinal nerve fibre layer thickness was significantly lower in the psoriasis and metabolic syndrome group than in the psoriasis group. For all parafoveal quadrants, the ganglion cell complex thickness was statistically significantly lower in the psoriasis group than in the healthy group. The central macula was thinnest in the healthy group among the four groups. Conclusions: Psoriasis can cause retinal changes, and metabolic syndrome may cause additional damage in the retina and macula in cases with psoriasis.

Esculetin Protects Human Retinal Pigment Epithelial Cells from Lipopolysaccharide-induced Inflammation and Cell Death.

PURPOSE: Age-related macular degeneration (AMD) is the most common cause of visual loss. The dry AMD is characterized by retinal pigment epithelium (RPE) death and changes in AMD lead to severe loss of vision. Coumarin-derived esculetin has a number of therapeutic and pharmacological effects such as anti-inflammatory and antioxidant with various mechanisms. The purpose of this study was to investigate the effects of esculetin treatment on lipopolysaccharide (LPS)-induced inflammation, oxidative stress, and cell survival. MATERIAL AND METHODS: Human RPE cells (ARPE-19) were incubated for 24-72 h with 5 µg/ml LPS to induce inflammation and oxidative stress. Esculetin (5 µM) was used to protect the cells from LPS-induced damage. The cell viability was evaluated by quantitative 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Interleukin 6 (IL-6), IL-12, and vascular endothelial growth factor (VEGF) levels were determined by enzyme-linked immunosorbent assay (ELISA). IL-1ß, tumor necrosis factor receptor (TNFR), TNF-related apoptosis-inducing ligand (TRAIL), catalase, glutathione peroxidase (GPx), superoxide dismutase 1 (CuZnSOD) and SOD2 (MnSOD) mRNA expressions were analyzed by RT-quantitative polymerase chain reaction. Apoptosis was monitored by cell-based cytometer. NF-kappa B (NF-κB) p65/RelA levels were determined by ELISA, and NF-κB protein expression and extracellular signal-regulated kinase (ERK1/2) phosphorylation were evaluated by Western blot analysis. RESULTS: Esculetin treatment significantly suppressed LPS-induced cell death mediated by apoptosis and necrosis in a concentration-dependent manner. While LPS caused significant inflammation with cytokine increase in cells, esculetin reduced the expression of LPS-induced cytokines, VEGF, TNFR, and TRAIL. Furthermore, exposure to LPS increased the expression of GPx and mitochondrial MnSOD, leading to oxidative stress in the cells. Esculetin treatment attenuated phosphorylation of ERK1/2 and NF-κB expression mediated by LPS. CONCLUSIONS: These results suggest that esculetin may be an alternative treatment option for endotoxin-induced inflammation and oxidative stress, which therefore may inhibit the development of LPS-mediated AMD.

Effects of cisplatin-5-fluorouracil combination therapy on oxidative stress, DNA damage, mitochondrial apoptosis, and death receptor signalling in retinal pigment epithelium cells.

AIM: Combination therapies of cisplatin with 5-FU (PF) are an effective solution and have been widely used for the treatment of various categories of cancer including anal, gastrointestinal, and oral cancer, as well as head and neck tumors. The effects of combined PF treatment on vital intracellular signalling pathways in nontargeted cells remain unclear. The aim of this study is to explain the possible mechanisms by which combined PF treatment results in retinal toxicity and to investigate the effects of PF on important vital signalling pathways in ARPE 19 retinal pigmented epithelial cells. MATERIALS AND METHODS: We analysed the cellular and molecular effects of PF on cell viability, oxidative stress, gene repair response, and induction of apoptosis in ARPE 19 cells using molecular probe fluorescent staining, cell cytometer, RAPD, qRT-PCR, and western blot assays. RESULTS: We determined that PF causes excessive generation of reactive oxygen species (ROS) and prevents ROS scavenging by suppressing antioxidant systems. We found induction of DNA damage, particularly mismatch and double strand break repair, in ARPE 19 cells treated with PF. In this study, PF also induced both the intrinsic apoptosis pathway and death receptor signalling in ARPE 19 cells. CONCLUSIONS: Our data proved that PF causes cytotoxicity and genotoxicity, at both the cellular and molecular levels, in ARPE 19 cells following particularly prolonged treatment (48 h). Additionally, our results suggest key molecular signals for prevention strategies that can be developed to reduce the severe side effects of PF chemotherapy.

Comparison of long-term results of trabeculectomy to treat pseudoexfoliative glaucoma and primary open angle glaucoma.

AIM: To compare the long term outcome of trabeculectomy in patients with pseudoexfoliative glaucoma (PEG) and primary open angle glaucoma (POAG) in terms of surgical success. METHODS: The success of the trabeculectomy was evaluated by three criteria. Criterion A: intraocular pressure (IOP) ≤21 mm Hg and decrease in IOP ≥20%; Criterion B: IOP ≤18 mm Hg and decrease in IOP ≥30%; Criterion C: IOP ≤15 mm Hg and decrease in IOP ≥50%. Patients that met these criteria without medical treatment were considered to be completely successful, while those that met these criteria with medical treatment were considered partially successful. Significance levels of differences between the POAG and PEG groups in the Kaplan-Meier survival curves were calculated with the log-rank test. RESULTS: Sixty-four eyes from 64 patients with PEG and 51 eyes from 51 patients with POAG were evaluated. No significant differences were detected between the PEG and POAG groups according to full or partial success relative to each of the three criteria (A: P=0.73, 0.32; B: P=0.73, 0.31; C:P=0.90, 0.27). CONCLUSION: There is no difference in the long-term success of trabeculectomy between PEG and POAG patients whose clinical characteristics are otherwise the same.

Effects of Selective Serotonin Reuptake Inhibitors on Macular Ganglion Cell Complex Thickness and Peripapillary Retinal Nerve Fiber Layer Thickness.

PURPOSE: To evaluate macular ganglion cell complex (GCC) thickness and peripapillary retinal nerve fiber layer (RNFL) thickness in patients treated with SSRIs. METHODS: The present study included 62 eyes of 31 patients who were using SSRIs and 60 eyes of 30 healthy, age- and gender-matched control subjects. All patients underwent a full ophthalmological examination in which macular thickness, GCC thickness, and peripapillary RNFL thickness were measured using optical coherence tomography (OCT). The Mann-Whitney U test was used to compare the patients' group with the age- and gender-matched control group. Pearson correlation analyses were also performed to assess the relationships between macular thickness, GCC thickness, RNFL thickness, and the duration of SSRI usage. RESULTS: The mean duration of SSRI usage was 29.96 ± 27.19 (range 6-120) months. The foveal thickness was 253.48 ± 22.77µm in the patients' group and 266.60 ± 20.64 µm in the control group; the difference between the groups was statistically significant. In addition, the perifoveal GCC thickness in the inferonasal and inferotemporal quadrant were significantly smaller thinner in the patient group (Mann-Whitney U test, p = 0.021and p = 0.013, respectively). CONCLUSIONS: Our results suggest a relation between SSRIs and decreased retinal GCC thickness and RNFL thickness. Future long-term prospective studies should elucidate the actual effect of SSRIs on GCC and RNFL thickness.