Circulating miRNAs and their functional genetic variants in pseudoexfoliative glaucoma: potential of miR-146a-5p as a diagnostic biomarker.

PURPOSE: The etiology and pathogenesis of pseudoexfoliation syndrome (PEX) and its advancement into pseudoexfoliative glaucoma (PEG) are not fully understood. In this study, we aimed to evaluate the possible role played by two circulating microRNAs (miR-146a-5p and miR-196a-5p) in plasma and their functional genetic variants MIR146A rs2910164 and MIR196A2 rs11614913 in susceptibility to PEG or PEX. METHODS: Plasma miRNA relative expression of 27 patients with PEG, 25 patients with PEX and 27 controls was determined using quantitative RT-PCR, and fold change was calculated using the 2-ΔΔCt method. Genotyping of 300 patients with PEG, 300 patients with PEX, and 300 controls was performed using a PCR-restriction fragment length polymorphism analysis. RESULT: Plasma miR-146a-5p relative expression was significantly elevated in patients with PEG (3.9-fold) (P < .000) and patients with PEX (2.7-fold) relative to controls (P = .001). The diagnostic ability of plasma miR-146a-5p expression fold change was good for discriminating PEG vs. controls (AUC = 0.897, P < .000), and the optimal decision threshold was 1.83 (sensitivity = 74%, specificity = 93%). Plasma miR-196a-5p relative expression did not differ significantly between study groups. No significant difference in terms of the minor allele frequency or the distribution of genotypes for MIR146A rs2910164 G/C or MIR196A2 rs11614913 C/T was observed between study groups. CONCLUSIONS: Circulating miR-146a-5p can contribute to the risk of PEX/PEG. Therefore, we propose that plasma miR-146a-5p can be developed as a potential biomarker for the minimally invasive diagnoses of PEX/PEG and as a potential therapeutic target with further studies.

Comparison of the vessel density measurements of the macula, optical disc, and peri-papillary region between ocular hypertension patients and healthy controls.

OBJECTIVE: To evaluate Optical Coherence Tomography Angiography (OCT-A) findings in patients with Ocular Hypertension (OHT) and compare them with healthy individuals. METHODS: Thirty-four patients with ocular hypertension (OHT) and 22 healthy individuals were included in the study. Foveal thickness, retinal vascular density in superficial and deep capillary plexus and choriocapillaris, foveal avascular zone (FAZ), acircularity index (AI), foveal vessel density (FD), non-flow area, capillary and all vessel densities in the peripapillary area and the disc were automatically measured using the Angiovue software of OCT-A and compared between groups. RESULTS: The comparison of the macular OCT-A findings did not reveal a significant difference between the two groups in terms of central macular thickness, superficial and deep capillary plexus vessel density (p>0.05). The foveal avascular zone width was significantly higher in OHT subjects compared to the control group (0.30±0.08 µ and 0.25±0.11 µ, respectively; p = 0.04). The comparison of optic nerve OCT-A findings revealed that the whole-field vessel density (wVD) (p = 0.007), peripapillary vessel density (pVD) (p = 0.001), inferior, superior and temporal radial peripapillary capillary plexus vessel density (p = 0.006, p = 0.008, p = 0.02) and the mean retinal nerve fiber layer thickness (p = 0.02) were significantly lower in the OHT group. CONCLUSIONS: Our findings suggest that the decrement in the optic disc vascular density and foveal avascular zone width was significantly higher in OHT subjects. The possible effect or role of these microvascular changes in terms of glaucoma development should be examined through further studies.

Macular Choroidal Thickness in Patients with Ocular Hypertension as Assessed Using Enhanced Depth Imaging Optical Coherence Tomography.

OBJECTIVES: The aim of this study was to evaluate the macular choroidal thickness (CT) in patients with ocular hypertension (OHT) using spectral domain optical coherence tomography (SD-OCT) and compare the results with healthy individuals. METHODS: Thirty eyes of 30 patients newly diagnosed with OHT and 24 eyes of 24 healthy controls were included in this cross-sectional study. After a detailed ophthalmological examination, macular CT was measured with enhanced depth imaging optical coherence tomography (EDI-OCT) (Cirrus HD-OCT, Carl Zeiss Meditec AG, Jena, Germany) at the fovea and at positions 500 µ, 1000 µ, 1500 µ nasal and temporal to the fovea. The Mann-Whitney U test was used to compare the CT measurements between groups. The correlation between the mean deviation, pattern standard deviation, and retinal nerve fiber layer thickness (RNFL) and CT was evaluated with the Spearman correlation coefficient. Statistical significance was accepted as p<0.05. RESULTS: The mean CT in the OHT group was significantly thinner than that of the controls at locations 1000 µ (250.13±69.53µ vs 275.92±47.34µ; p=0.02) and 1500µ (236.03±65.44µ vs 265.46±47.56µ; p=0.009) temporal to the fovea. The CT at the other measurement points was also thinner in eyes with OHT, but the difference failed to reach statistical significance. A moderately negative correlation was detected between the mean deviation and CT at locations 1000µ (r=-0.42; p=0.03) and 1500µ (r=-0.44; p=0.02) temporal to the fovea There was a moderate correlation between the average RNFL thickness and CT at locations 500µ (r=0.44; p=0.03), 1000µ (r=0.42; p=0.04) and 1500µ (r=0.56; p=0.005) temporal to the fovea. CONCLUSION: In the present study, the macular CT was thinner in patients with OHT and this thinning was statistically significant at the temporal macula. A longitudinal, prospective study involving multiple EDI-OCT measurements is required to further understand the relationship.

Association of Lysyl Oxidase-Like 1 Gene Polymorphism in Turkish Patients With Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma.

PURPOSE: To investigate the genetic association of lysyl oxidase-like 1 (LOXL1) gene polymorphisms in patients with pseudoexfoliation (PEX) syndrome and PEX glaucoma of Turkish descent. METHODS: Three LOXL1 single nucleotide polymorphisms (SNPs) (rs1048661, rs3825942, and rs2165241) were analyzed in 109 Turkish patients (44 patients with PEX syndrome, 65 patients with PEX glaucoma) and 47 healthy subjects. RESULTS: "A" allele of SNP rs3825942 was underrepresented in control group compared with the glaucoma [odds ratio (OR)=4.5, confidence interval (CI): 95%] and syndrome (OR=4.5, CI: 95%) groups. "AA+AG" genotype of SNP rs3825942 was more frequent in the syndrome group (OR=10, CI: 95%) rather than the control group. "GT" genotype of SNP rs1048661 was presented less frequently in the control group compared with the glaucoma group (OR=4.25, CI: 95%). "T" allele of SNP rs1048661 was more frequent in glaucoma group (OR=2.05, CI: 95%) compared with control group. "T" allele of SNP rs2165241 was more frequent in the syndrome (OR=2.59, CI: 95%) and the glaucoma group (OR=3.78, CI: 95%) compared with the control group. "TT" genotype of SNP rs2165241 was underrepresented in control group compared with the syndrome (OR=3.85, CI: 95%) and the glaucoma (OR=6.58, CI: 95%) group. CONCLUSIONS: Findings of this current study indicate a different LOXL1 gene expression pattern compared with a recent study that was also performed in the Turkish population. Other gene replication studies are required to accurately assess genetic factors in the pathogenesis of PEX syndrome and glaucoma.

The Relation of White-on-White Standard Automated Perimetry, Short Wavelength Perimetry, and Optic Coherence Tomography Parameters in Ocular Hypertension.

PURPOSE: The purpose of this study is to examine the demographics, clinical properties, and the relation between white-on-white standard automated perimetry (SAP), short wavelength automated perimetry (SWAP), and optical coherence tomographic (OCT) parameters of patients with ocular hypertension. MATERIALS AND METHODS: Sixty-one eyes of 61 patients diagnosed with ocular hypertension in the Ankara Numune Education and Research Hospital ophthalmology unit between January 2010 and January 2011 were included in this study. All patients underwent SAP and SWAP tests with the Humphrey visual field analyser using the 30.2 full-threshold test. Retinal nerve fiber layers (RNFL) and optic nerve heads of patients were evaluated with Stratus OCT. RESULTS: Positive correlation was detected between SAP pattern standard deviation value and average intraocular pressure (P=0.017), maximum intraocular pressure (P=0.009), and vertical cup to disc (C/D) ratio (P=0.009). Positive correlation between SWAP median deviation value with inferior (P=0.032), nasal (P=0.005), 6 o'clock quadrant RNFL thickness (P=0.028), and Imax/Tavg ratio (P=0.023) and negative correlation with Smax/Navg ratio (P=0.005) were detected. There was no correlation between central corneal thickness and peripapillary RNFL thicknesses (P>0.05). CONCLUSIONS: There was no relation between SAP median deviation, pattern standard deviation values and RNFL thicknesses and optic disc parameters of the OCT. By contrast significant correlation between several SWAP parameters and OCT parameters were detected. SWAP appeared to outperform achromatic SAP when the same 30-2 method was used.

Evaluation of Carotid Intima Media Thickness and Renal Artery Resistive Index in Patients With Pseudoexfoliation Syndrome: A Prospective Case-Control Study.

PURPOSE: To investigate the significance of renal artery resistance and carotid intima media thickness (CIMT) parameters in patients with pseudoexfoliation syndrome (PES). MATERIALS AND METHODS: In this prospective case-control study, 37 patients were involved and grouped as PES (n=19) and control groups (n=18). Ophthalmological evaluation included visual acuity, intraocular pressure, central corneal thickness measurement, and optic disc evaluation. In addition, renal artery resistive index and CIMT measurements were taken for all patients and compared between the groups. RESULTS: The 2 groups were similar with respect to age, sex, and family history of glaucoma. The mean CIMT in the PES group was found to be significantly higher compared with the control group (0.73±0.02 vs. 0.59±0.06 mm, P=0.003). Renal artery resistive indices were found to be higher in the PES group than in the control group, however, the difference was not significant (P=0.46). A moderate positive correlation between CIMT and renal artery resistive indices was detected (r=0.447, P=0.01). However, a higher correlation rate was detected when the analysis was made in the PES group only (r=0.603, P=0.01). CONCLUSIONS: CIMT increases in PES patients and also the renal artery resistance index has a tendency to increase. Patients with PES should be informed about potential systemic consequences of this syndrome.

The evaluation of the retrobulbar orbital fat tissue and optic nerve with strain ratio elastography.

AIM: The aim of this study was to evaluate the diagnostic performance of strain ratio elastography in the assessment of retrobulbar orbital fat tissue. MATERIALS AND METHODS: The retrobulbar fat tissue of 14 eyes in 14 participants was scanned by sonoelastography. All the participants had permanent vision loss secondary to glaucoma in at least one eye. The elasticity scores were determined and the strain ratio was based on the comparison of the average strain measured in the retrobulbar fat tissue around the optic nerve at the same depth. RESULTS: The mean strain values for the optic nerve (B) and the retrobulbar fat tissue (A) were 0.78+/-0.61 and 1.43+/-0.99, respectively (p=0.005). The mean strain ratio (B/A) was 0.56+/-0.24. CONCLUSION: This preliminary study showed that by providing strain values and ratios of different orbital tissues sonoelastography may have a potential use in the diagnosis and follow-up of orbital inflammatory and infiltrative diseases.

Plasma homocysteine, folic acid, and vitamin B12 levels in patients with pseudoexfoliation syndrome, pseudoexfoliation glaucoma, and normotensive glaucoma.

OBJECTIVE: The aim of this study was to evaluate the levels of plasma homocysteine (Hcy), vitamin B12, and folic acid in patients with pseudoexfoliation glaucoma (PEXG), pseudoexfoliation syndrome (PEXS), PEXS plus normotensive glaucoma (NTG). MATERIAL AND METHODS: In total, 24 patients with PEXG, 35 patients with PEXS, 18 patients with PEXS plus NTG, and 35 control subjects were enrolled into study. Their Hcy levels were measured by high performance liquid chromatography (HPLC); the levels of vitamin B12 and folic acid were measured by a competitive electrochemiluminescence immunoassay. RESULTS: Higher plasma Hcy levels and lower folic acid and vitamin B12 levels were found in all 3 patients' groups compared with the control group (all P<0.001, expect for folic acid in the PEXG group, P=0.03). Although plasma Hcy levels in the PEXG and PEXS groups were similar, the PEXS plus NTG group had significantly higher Hcy levels compared with these groups (P=0.019 and P=0.032, respectively). CONCLUSIONS: Our study showed that there was an association between hyperhomocysteinemia and PEXS either with or without glaucoma. The patients with PEXS plus NTG had higher plasma Hcy levels than the patients with PEXS or PEXG and the healthy controls. The treatment of hyperhomocysteinemia by taking low-cost vitamin B12 and folic acid preparations may prevent additional vascular problems.

Nd:YAG laser goniopuncture in viscocanalostomy: penetration in non-penetrating glaucoma surgery.

The objective was to evaluate the results of Nd:YAG laser goniopuncture after viscocanalostomy and to investigate the rate of penetration in non-penetrating surgery. Results of viscocanalostomy and incidence of goniopuncture were retrospectively investigated in 33 eyes of 33 patients. Success was defined as an intraocular pressure (IOP) below 19 mmHg with an at least 30% decrease compared to the last preoperative measurement. General success rates after a mean follow-up of 33.5 +/- 11.3 months were 79 and 46%, with and without medications, respectively. Mean IOP levels, which were 37.7 +/- 9.9 mmHg at the diagnosis without treatment and 27.7 +/- 11.3 mmHg at the last preoperative measurement with medical treatment, significantly decreased to 12.7 +/- 4.8 mmHg at the last follow-up visit (P < 0.001 for both comparisons). Twelve eyes (36%) with IOPs higher than 18 mmHg during follow-up underwent laser goniopuncture. Mean IOP, which was 26.0 +/- 4.6 mmHg before goniopuncture, decreased to 11.5 +/- 4.0 mmHg immediately after the procedure (P = 0.002). Early goniopunctures (before month 3) were performed in six eyes, and late goniopunctures (after month 10) were performed in the remaining six eyes. Success rates of laser-applied eyes at the last visit were 75 and 33%, with and without medications, respectively (P = 0.568). No significant difference was found between eyes with and without goniopunctures in terms of success rates, IOP levels, and IOP reduction rates. According to the results of this study, laser goniopuncture is indicated in a significant proportion of patients following viscocanalostomy and may substantially improve the outcome of surgery.

Normotensive glaucoma and risk factors in normotensive eyes with pseudoexfoliation syndrome.

PURPOSE: To evaluate the prevalence of normotensive glaucoma (NTG) in patients with pseudoexfoliation (PEX) syndrome. METHODS: In this prospective study, 178 eyes of 178 patients with PEX syndrome who had no previous history of antiglaucomatous treatment were evaluated in terms of NTG prevalence. NTG diagnosis was based on the presence of glaucomatous optic nerve head damage with glaucomatous visual field defects, open angles, and intraocular pressure (IOP) levels less than 22 mm Hg. Two groups of normotensive pseudoexfoliative eyes with or without glaucomatous findings were compared in terms of age, sex, the presence of systemic diseases and mean IOP, maximum IOP, and IOP fluctuation levels. RESULTS: The IOP levels were below 22 mm Hg in 109 of the 178 eyes, and 24% (n=27) of those eyes were diagnosed as NTG. There were no significant differences between the eyes with or without glaucoma in terms of age, sex, and the presence of systemic diseases (P>0.05). The mean IOP, maximum IOP, and IOP fluctuation levels were significantly higher in eyes with NTG when compared with eyes without glaucoma (P<0.05). Univariate analysis revealed that significant risk factors associated with NTG in patients with PEX syndrome were higher mean IOP (> or =14 mm Hg), higher maximum IOP (> or =18 mm Hg), and greater IOP fluctuation (> or =4 mm Hg). In multivariate analysis, these factors were higher maximum IOP and greater IOP fluctuation range (P=0.003, P<0.001, respectively). CONCLUSIONS: There are glaucomatous findings in a significant proportion of normotensive patients with PEX syndrome. The high maximum IOP levels and greater IOP fluctuation range may be contributory factors in the pathogenesis of NTG in patients with PEX syndrome.

A case of postganglionic Horner syndrome after catheterization of internal jugular vein confirmed with pharmacological tests.

Horner syndrome, consisting of ipsilateral miosis, upper eye lid ptosis, and facial anhidrosis, has been reported as a rare complication of internal jugular vein catheterization. In this paper, we describe a nine-year-old girl presenting with postganglionic Horner syndrome, in whom right-sided ptosis and miosis occurred after ipsilateral percutaneous internal jugular venous catheterization.

The effect of paclitaxel on conjunctival wound healing: a pilot study.

PURPOSE: To compare the effects of mitomycin C (MMC) and paclitaxel entrapped within Carbopol 980 hydrogel (CH) on conjunctival wound healing. METHODS: Twenty rabbits were randomized into 2 groups. In group 1, limbal-based conjunctival flaps were created in both eyes. In this stage, eyes were randomized for 4 different processes. In process 1, a dry cellulose sponge soaked with 0.2 mg/mL of MMC was applied to the scleral surface. A cellulose sponge soaked with balanced saline solution was applied in the same manner in process 2. In process 3, paclitaxel 1 mg/mL entrapped within CH was placed between the conjunctiva and sclera. In process 4, CH without paclitaxel was applied in the same manner. The conjunctiva was then sutured. All procedures were applied in the same manner in both eyes of animals in group 2. Eyes from group 1 were sampled at the seventh day, and the sampling was also carried out in group 2 on day 14. The inflammatory response and fibrosis were evaluated with light microscopy. RESULTS: Among 4 different processes, lower cell counts and fibrosis scores were found in eyes treated with MMC and paclitaxel compared with balanced saline solution and CH groups (P<0.05). There was no difference between eyes treated with MMC and paclitaxel in terms of these histopathologic parameters (P>0.05). CONCLUSIONS: Paclitaxel was shown to provide MMC-like antifibrotic effects during conjunctival wound healing, particularly when delivered with CH and might be a promising alternative as an adjunctive antimetabolite in glaucoma filtration surgery.

Comparison of the effects of travoprost, latanoprost and bimatoprost on ocular circulation: a 6-month clinical trial.

PURPOSE: To study the effect of three prostaglandin F(2)-alpha (PG) analogues on retrobulbar blood flow velocity in previously untreated patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT), using colour Doppler ultrasound. METHODS: Sixty newly diagnosed patients with POAG or OHT were randomly assigned to travoprost 0.004% (n = 12 with POAG, n = 8 with OHT), latanoprost 0.005% (n = 11 with POAG, n = 9 with OHT) and bimatoprost 0.03% (n = 13 with POAG, n = 7 with OHT) treatment groups in a double-masked fashion. At baseline examination, blood pressure, heart rate and intraocular pressure (IOP) were recorded. Peak-systolic and end-diastolic velocities were measured in the ophthalmic (OA), central retinal (CRA) and temporal short posterior ciliary arteries (PCA). The resistive index (RI) and ocular perfusion pressure (OPP) were determined for each treatment group. After a treatment period of 6-months, all procedures were repeated. RESULTS: There were no significant differences in age (53 +/- 14 years in the travoprost group, 51 +/- 14 years in the latanoprost group, 53 +/- 11 years in the bimatoprost group), gender (11 men, nine women; 11 men, nine women; 13 men, seven women, by group, respectively), or clinical diagnosis (POAG or OHT) among treatment groups (p > 0.05). A significant decrease in IOP (baseline: 26.4 +/- 3.3 mmHg, 26.8 +/- 1.3 mmHg, 25.8 +/- 1.8 mmHg, respectively; month 6: 20.9 +/- 1.9 mmHg, 20.8 +/- 2.4 mmHg, 18.3 +/- 1.2 mmHg, respectively; p < 0.0001) and an increase in OPP (baseline: 33.7 +/- 3.8 mmHg, 33.5 +/- 3.2 mmHg, 33.9 +/- 2.6 mmHg, respectively; month 6: 40.2 +/- 3.5 mmHg, 39.9 +/- 3.1 mmHg, 41.7 +/- 2.6 mmHg, respectively; p < 0.0001) were verified in all three groups during the study period. Mean baseline RI values for the CRA in the travoprost group and the OA in the latanoprost group were both 0.7 +/- 0.1 mmHg and both values were statistically significantly lower at 6 months (0.6 +/- 0.1 mmHg in both groups; p = 0.002, p < 0.0001, respectively). In the bimatoprost group there was no statistically significant difference in haemodynamic parameters over the study period (p > 0.05). CONCLUSIONS: Our results suggest that the three PG analogues significantly reduce IOP and increase OPP in patients with POAG or OHT. Topical travoprost and latanoprost significantly reduce the RI of the CRA and OA, respectively. We were unable to determine any effect of topical bimatoprost on ocular haemodynamics.

Bilateral ocular ischemic syndrome as an initial manifestation of Takayasu's arteritis associated with carotid steal syndrome.

Bilateral anterior ischemic optic neuropathy and bilateral ocular ischemic syndrome have been rarely reported as initial manifestations of Takayasu's arteritis (TA). Appearance of ocular symptoms in TA is closely related to extension and severity of involvement of the aorta and its major branches. Here we reported a case of 'carotid steal syndrome' secondary to TA in a 45 year old Turkish man, who had severe ocular and brain ischemia, presented initially with symptoms of ocular ischemic syndrome.

Axenfeld-Rieger syndrome associated with truncus arteriosus: a case report.

The aim of this presentation was to report a case with Axenfeld-Rieger syndrome (ARS) associated with truncus arteriosus (TA). We present a 14-year-old boy with ARS in whom the diagnosis was confirmed by ophthalmologic examination and developmental defects of the teeth and facial bones. Echocardiography revealed TA. With this case demonstrating the association between ARS and TA, the range of reported cardiac malformations is enlarged and the importance of cardiologic evaluation is emphasized in patients with ARS.

Glaucomatous damage in normotensive fellow eyes of patients with unilateral hypertensive pseudoexfoliation glaucoma: normotensive pseudoexfoliation glaucoma?

BACKGROUND: The objective of the study was to investigate the prevalence of glaucomatous damage in normotensive fellow eyes of patients with unilateral high-tension pseudoexfoliation (PX) glaucoma. METHODS: Initial examination records of 111 patients with unilateral PX glaucoma with intraocular pressure (IOP) > or = 22 mmHg in the hypertensive eye and IOP < or = 21 mmHg in the normotensive fellow eye without any prior antiglaucomatous treatment were retrospectively studied. Visual field and optic disc examination results were evaluated for glaucomatous damage in the normotensive eyes. RESULTS: Glaucomatous changes were detected in 45 of the 111 fellow eyes (40%). The damage was mild in 25 eyes (22%), moderate in 18 eyes (16%), and severe in 2 (2%). The factors significantly associated with glaucomatous findings in the normotensive eyes were clinical detection of PX, higher age (> or =70 years), higher maximal IOP (> or =18 mmHg) and wider IOP fluctuation (> or =6 mmHg) in the univariate analyses. In the multivariate analysis, associated factors remained as higher maximal IOP (odds ratio = 7.92, confidence interval = 2.82-22.23, P < 0.001) and wider IOP fluctuation (odds ratio = 5.67, confidence interval = 2.05-15.74, P = 0.001). CONCLUSION: Normotensive fellow eyes of patients with unilateral high-tension PX glaucoma are under significant risk of glaucomatous damage, related with the level and the fluctuation range of IOP.