Decreased perifoveal ganglion cell complex thickness - a first sign for macular damage in patients using hydroxychloroquine.

Aim: To examine ganglion cell complex (GCC) thickness detected by optical coherence tomography (OCT) in patients using hydroxychloroquine (HCQ), without any structural and functional macular changes to evaluate the initial symptoms of macular toxicity for early diagnosis before clinical evaluation. Methods: Eighty eyes of forty patients (Group 1) and forty eyes of twenty healthy volunteer persons (Group 2) were included in the study. Detailed ophthalmologic and mydriatic fundus examination were applied to all patients and volunteers (controls). Spectral domain OCT, visual field (VF) and color vision test were performed. Measurements of macula thickness, GCC thickness (involving nerve fiber layer, ganglion cell layer and inner plexiform layer) and peripapillary retinal nerve fiber layer (RNFL) were performed with OCT. Patients with retinal pigment epithelial changes, VF paracentral scotoma and defected color vision were excluded from the planned study. Results: Perifoveal GCC layer thickness in all quadrants was significantly thinner in group 1 compared to group 2 (p=0.017, p=0.001, p=0.019, p=0.001). The mean global inferior hemifield and nasal quadrant RNFL thickness were lower than in the control groups (p=0,012, p=0,009, p=0,005, respectively). Conclusion: Changes in the thickness of nerve fiber layer and ganglion cell layer detected by optical coherence tomography can be thought to be used as a diagnostic aid for the early diagnosis of hydroxychloroquine-toxic maculopathy Abbreviations: GCC = Ganglion cell complex, OCT = Optical coherence tomography, HCQ = Hydroxychloroquine, BCVA = Best-corrected visual acuity, IOP = Intraocular pressure, VF = Visual field, RNFL = Retinal nerve fiber layer, SD OCT = Spectral-domain optical coherence tomography, mfERG = Multifocal electroretinogram, FAF = Fundus autofluorescence, IS/ OS = Inner segment-outer segment junction, SITA = Swedish Interactive Threshold Algorithm, RA = Rheumatoid arthritis, SLE = Systemic lupus erythematosus, SS = Sjogren syndrome.

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.

Diplopia in Cases With Type 1 Duane Retraction Syndrome.

Objective In this study, we aimed to investigate the prevalence of diplopia in cases with type 1 Duane retraction syndrome (DRS). Materials and methods This study was a retrospective review of cases involving patients presenting diagnosed with DRS over a period of 24 years. Among these cases, 28 had type 1 DRS and fulfilled the inclusion criteria. The cases were evaluated in terms of age, gender, affected eye, concomitant ocular motility disorders, presence of amblyopia, manifest shift, abnormal head position (AHP), fusion, and stereopsis. Results Sixteen of the patients (57.1%) in the study were female, and 12 (42.8%) were male; the mean age of the patients was 18.9 years (range: 7-67 years). The right eye was affected in six of the cases (21.4%), and the left eye in 22 (78.6%) of the cases. On examination, diplopia was not observed in 21 (75%) cases, but it was detected in seven (25%). AHP was present in five of the seven cases with diplopia and not present in two, and all seven of the diplopic cases had fusion, while three had stereopsis. The level of stereopsis in all diplopic cases was 400 sn/ark. When the clinical findings of patients with diplopia and those without diplopia were compared, a statistically significant difference was observed only in terms of AHP. Conclusions Although diplopia is not one of the clinical features of DRS, it must be noted that in cases with type 1 DRS, diplopia may occur in directions in which the movement of the eyeball is limited. In the presence of this finding, which might mimic sixth nerve palsy, patient history must be diligently taken, other clinical findings of DRS must be thoroughly examined, and an MRI should be performed when necessary for an easier diagnosis.

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.

NATURAL COURSE OF VITREOMACULAR TRACTION IN EYES WITH DIABETIC RETINOPATHY AND FACTORS ASSOCIATED WITH SPONTANEOUS RELEASE.

PURPOSE: The aim of this study was to determine the natural course of vitreomacular traction (VMT) in patients with diabetic retinopathy and to evaluate the factors associated with VMT relief. METHODS: Seventy-four eyes of 65 patients with VMT accompanying diabetic retinopathy were evaluated retrospectively. The presence of intravitreal injection and the presence of panretinal photocoagulation were obtained from the medical records of the patients. Spontaneous release of VMT, the horizontal length of vitreomacular traction, the presence of hyperreflective retinal spots, the presence of the epiretinal membrane, and the grade of VMT were evaluated from the spectral-domain optical coherence tomography images. Factors associated with the spontaneous release of VMT were evaluated by logistic regression analysis. RESULTS: Spontaneous release was observed in 28 eyes (37.8%). The horizontal length of VMT was lower in the release of the VMT group compared with the persistent VMT group (P = 0.03). The persistent VMT group had a higher rate of hyperreflective retinal spots and epiretinal membrane compared with the release of the VMT group (respectively; P = 0.003 and P = 0.031). No statistically significant difference was observed between the release of VMT and persistent VMT groups in terms of intravitreal injection and panretinal photocoagulation treatment (respectively; P = 0.938 and P = 0.36). The absence of hyperreflective retinal spots was the most important prognostic factor for the spontaneous release of VMT (P = 0.029). CONCLUSION: Spontaneous release of VMT observed higher rates of patients without hyperreflective retinal spots, epiretinal membrane, and patients with lower horizontal length of VMT.

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.

Optical biometry-based axial length alterations after intravitreal dexamethasone implant / Alterações do comprimento axial com base na biometria óptica após o implante de dexametasona intravítrea

ABSTRACT Purpose: To investigate changes in axial length after intravitreal dexamethasone implantation in patients with macular edema. Methods: We performed a prospective comparative study of 46 patients with unilateral macular edema, due to diabetic retinopathy, retinal vein occlusion, and non-infectious uveitis, who underwent dexamethasone implantation. The fellow eyes of the patients were considered the control group. The central macular thickness was measured by spectral-domain optical coherence tomography, and axial length was measured by IOLMaster 700 optical coherence biometry. We compared axial length and central macular thickness values within the groups. Results: In the study group, the baseline central macular thickness was 460.19 ± 128.64 mm, significantly decreasing to 324.00 ± 79.84 mm after dexamethasone implantation (p=0.000). No significant change in central macular thickness measurements was seen in the control group (p=0.244). In the study group, the baseline axial length was 23.16 ± 0.68 mm, significantly increasing to 23.22 ± 0.65 mm after dexamethasone implantation (p=0.039). However, the control group exhibited no significant change in axial length (p=0.123). Conclusions: In addition to significantly reducing central macular thickness measurements, intravitreal dexamethasone implantation also significantly changes optical biometry-based axial length measurements.

RESUMO Objetivo: Investigar alterações no comprimento axial após implante de dexametasona intravítrea em pacientes com edema macular. Métodos: Foi realizado um estudo prospectivo e comparativo de 46 pacientes com edema macular unilateral, devido à retinopatia diabética, oclusão da veia retiniana e uveíte não infecciosa, que foram submetidos ao implante de dexametasona. Os olhos contralateral de cada paciente foram considerados o grupo controle. A espessura macular central foi medida por tomografia de coerência óptica de domínio espectral, e o comprimento axial foi medido por meio de biometria de coerência óptica de domínio espectral e o comprimento axial foi medido pela biometria de coerência óptica com IOLMaster 700. Comparamos o comprimento axial e os valores da espessura macular central dentro dos grupos. Resultados: No grupo de estudo, a espessura macular basal foi de 460,19 ± 128,64 mm, diminuindo significativamente para 324,00 ± 79,84 mm após o implante de dexametasona (p=0,000). Nenhuma mudança significativa nas medidas da espessura macular central foi observada no grupo controle (p=0,244). No grupo de estudo, o comprimento axial basal foi de 23,16 ± 0,68 mm, aumentando significativamente para 23,22 ± 0,65 mm após o implante de dexametasona (p=0,039). No entanto, o grupo controle não apresentou alteração significativa no comprimento axial (p=0,123). Conclusões: Além de reduzir significativamente as medidas da espessura macular central, o implante de dexametasona intravítrea também altera significativamente as medidas de comprimento axial baseadas na biometria óptica.

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.

Optical biometry-based axial length alterations after intravitreal dexamethasone implant.

PURPOSE: To investigate changes in axial length after intravitreal dexamethasone implantation in patients with macular edema. METHODS: We performed a prospective comparative study of 46 patients with unilateral macular edema, due to diabetic retinopathy, retinal vein occlusion, and non-infectious uveitis, who underwent dexamethasone implantation. The fellow eyes of the patients were considered the control group. The central macular thickness was measured by spectral-domain optical coherence tomography, and axial length was measured by IOLMaster 700 optical coherence biometry. We compared axial length and central macular thickness values within the groups. RESULTS: In the study group, the baseline central macular thickness was 460.19 ± 128.64 mm, significantly decreasing to 324.00 ± 79.84 mm after dexamethasone implantation (p=0.000). No significant change in central macular thickness measurements was seen in the control group (p=0.244). In the study group, the baseline axial length was 23.16 ± 0.68 mm, significantly increasing to 23.22 ± 0.65 mm after dexamethasone implantation (p=0.039). However, the control group exhibited no significant change in axial length (p=0.123). CONCLUSIONS: In addition to significantly reducing central macular thickness measurements, intravitreal dexamethasone implantation also significantly changes optical biometry-based axial length measurements.

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.

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.

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.

Increased Fibrinogen to Albumin Ratio in Ischemic Retinal Vein Occlusions.

PURPOSE: To demonstrate the relationship between ischemia and plasma fibrinogen and serum albumin levels in cases of retinal vein occlusion (RVO). METHODS: This study included 44 patients with central RVO (CRVO), 68 patients with branch RVO (BRVO), and 54 age- and sex-matched controls, for a total of 166 subjects. All of the subjects underwent full ophthalmologic examinations and complete physical examinations, including a detailed medical history and blood count, and biochemical parameters. RESULTS: The mean fibrinogen to albumin ratios were 92.5 ± 36.1 for the patients with CRVO, 84.5 ± 31.5 for the patients with BRVO, and 68.4 ± 12.2 for the control group. Overall, the patients with CRVO and patients with BRVO with ischemia had higher fibrinogen to albumin ratios and higher fibrinogen levels. Moreover, significant positive correlations were found between ischemia and the fibrinogen to albumin ratio (r = 0.732, p = 0.001) and the fibrinogen level (r = 0.669, p = 0.001). CONCLUSIONS: The fibrinogen to albumin ratio is significantly associated with ischemic RVO. Instead of complicated and invasive methods, such as a retinal angiogram, the fibrinogen to albumin ratio could be a useful initial diagnostic test to predict ischemia in RVO.