Yusuf Çağlar

Correlation between retinal morphological and functional findings and clinical severity in Parkinson’s disease

Background To measure the parapapillary retinal nerve fiber layer and macular thickness and macular volume in vivo and to evaluate whether retinal structural changes and visual cortical responses may be related to the clinical severity of the PD. Methods We included 17 patients with Parkinson’s disease and 11 healthy subjects of a similar age. Unified Parkinson’s disease rating scale scores in Parkinson’s disease and control subjects were assessed for clinical evaluation. The retinal nerve fiber layer thickness, macular thickness and volume were measured by commercially available optical coherence tomography Model 3000xa0unit. Peak latencies of P100 component were measured by pattern visual evoked potential examination. Results The mean retinal nerve fiber layer average thickness was significantly reduced in Parkinson’s disease patients (98.76xa0±xa010.90xa0μm) when compared with those of control subjects (114.54xa0±xa05.72) (Pxa0<xa00.05). The retinal thickness reduction was statistically significant in superior inner macula; temporal, nasal and inferior quadrants of outer macula (Pxa0<xa00.05)(Tablexa02). The mean total macular volume of Parkinson’s disease patients (6.82xa0±xa00.32xa0mm3) was significantly reduced when compared with those of control subjects (7.09xa0±xa00.23xa0mm3). Highly significant inverse correlation between foveal retinal thickness and total and motor subscores of Unified Parkinson’s disease rating scale was observed in Parkinson’s disease patients, respectively (rxa0=xa0−0.660; Pxa0=xa00.004), (rxa0=xa0−0.625, Pxa0=xa00.007). There was a moderate nearly significant inverse correlation between total macular volume and P100 latency in PD (rxa0=xa0−0.328; Pxa0=xa00.058). Conclusions In Parkinson’s disease patients there is a reduction of retinal nerve fiber layer thickness, macular thickness and volume evaluated in vivo by optical coherence tomography. Reduced foveal thickness which is not found to be statistically different from normal is correlated to the severity of disease.

Ocular hemodynamics in pseudoexfoliation syndrome and pseudoexfoliation glaucoma

OBJECTIVEnTo evaluate orbital blood flow velocities by using color Doppler imaging in patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma.nnnDESIGNnProspective, comparative case series.nnnPARTICIPANTSnTwenty-eight patients with pseudoexfoliation syndrome (n = 14) or pseudoexfoliation glaucoma (n = 14) and 14 healthy control participants were included.nnnINTERVENTIONnColor Doppler imaging was used with a 7.5-MHz probe. Evaluation of the ophthalmic, central retinal, short posterior nasal, and temporal ciliary arteries was performed, and peak systolic and end diastolic flow velocities were measured. Resistive indices were calculated.nnnRESULTSnWhen compared with the control participants, patients with pseudoexfoliation syndrome showed statistically significant decreases in the mean peak systolic velocity of the central retinal artery (11.21 +/- 2.19 cm/second; P < 0.05), and end diastolic velocities of the central retinal artery (3.00 +/- 1.03 cm/second; P < 0.005), and short posterior temporal ciliary arteries (3.50 +/- 1.74 cm/second; P < 0.005), whereas mean resistive indices of the ophthalmic artery (0.75 +/- 0.06 cm/second; P < 0.005) and central retinal artery were found to have increased (0.70 +/- 0.05 cm/second; P < 0.01). Patients with pseudoexfoliation glaucoma, when compared with the control participants, showed statistically significant decreases in the mean peak systolic and end diastolic velocities and increased mean resistive indices in all vessels measured (P < 0.05). Compared with the patients with pseudoexfoliation syndrome, patients with pseudoexfoliation glaucoma showed statistically significant decreases in the mean peak systolic velocities of the ophthalmic artery (30.07 +/- 4.00 cm/second; P < 0.05) and short posterior nasal ciliary arteries (2.35 +/- 0.09 cm/second; P < 0.05), and in the mean end diastolic velocities of the ophthalmic artery (6.28 +/- 2.12 cm/second; P < 0.05), and short posterior nasal ciliary arteries (2.35 +/- 0.09 cm/second; P < 0.05). The differences in the mean resistive indices were not statistically significant between the patients with pseudoexfoliation syndrome and the ones with pseudoexfoliation glaucoma.nnnCONCLUSIONSnThe findings suggest that hemodynamic parameters in the retrobulbar vessels were altered in patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma; however, these alterations were more prominent in the latter group.

Homocysteine and nitric oxide levels in plasma of patients with pseudoexfoliation syndrome, pseudoexfoliation glaucoma, and primary open-angle glaucoma

PurposeTo evaluate plasma total homocysteine (tHcy) and nitric oxide (NO) marker levels in patients with pseudoexfoliation syndrome (PXS), pseudoexfoliation glaucoma (PXG), primary open-angle glaucoma (POAG), and normal controls.MethodsThis cross-sectional, prospective study involved 19 patients with POAG, 18 with PXS, 22 with PXG, and 20 control subjects. Fasting tHcy levels of all study participants were determined using a fluorescence polarization immunoassay method. Quantitation of total nitrate was based on the Griess reaction, in which a chromophore with a strong absorbance at 545xa0nm is formed by reaction of nitrite with a mixture of naphthylethylenediamine and sulphanilamide.ResultsThe mean plasma homocysteine level was statistically significantly elevated in the PXS (p=0.033) and the PXG (p=0.023) groups but not in the POAG group (p=0.996) when compared with the control group. Multiple logistic regression analyses comparing the various patient groups with the single control group indicated that elevation in plasma homocysteine concentration was a significant risk factor for PXS (odds ratio per 1xa0μmol/l increase in homocysteine concentration=2.05, 95% CI=1.19–3.52) and PXG (odds ratio per 1xa0μmol/l increase in homocysteine concentration=1.36, 95% CI=1.00–1.85) but was not a significant risk factor for POAG (odds ratio per 1xa0μmol/l increase in homocysteine concentration=0.99, 95% CI=0.78–1.26). NO markers levels were found to be slightly higher in PXS and PXG patients than control and POAG patients but the differences were not statistically significant (p=0.151). Multiple logistic regression analyses comparing the various patient groups with the single control group indicated that elevation in NO marker concentration was not a significant risk factor for PXS (odds ratio per 1xa0μmol/l increase in NO concentration=1.00, 95% CI=0.99–1.01), PXG (odds ratio per 1xa0μmol/l increase in NO concentration=1.00, 95% CI=0.99–1.00) and POAG (odds ratio per 1xa0μmol/l increase in NO concentration=0.99, 95% CI=0.99–1.00). No statistically significant correlations were observed between plasma tHcy and NO markers in study groups (p>0.05).ConclusionElevated levels of homocysteine in pseudoexfoliation patients with and without glaucoma may partly explain the increased risk of vascular disease among patients with pseudoexfoliation. No significant difference was found in plasma NO markers among the POAG, PXS, PXG, and the control subjects.

A comparison of travoprost, latanoprost, and the fixed combination of dorzolamide and timolol in patients with pseudoexfoliation glaucoma.

Purpose To compare the intraocular pressure (IOP) lowering effect and safety of latanoprost, travoprost given every evening, and the fixed combination dorzolamide + timolol (DTFC) given twice daily in pseudoexfoliation glaucoma (PXG). Methods This randomized, prospective, investigator-masked study has been conducted with 50 PXG patients. Patients were assigned to one of three groups: travoprost 0.004%, fixed combination of dorzolamide 2%+timolol 0.5%, or latanoprost 0.005% for 6 months. At baseline and 0.5, 1, 2, 3, 4, 5, and 6 months of therapy, IOP (8 am, 10 am, 4 pm), blood pressures, and pulse rates were measured, and ophthalmologic examination was performed. The side effects were recorded at each visit. Results Forty-two of the 50 patients initially enrolled completed this study. Withdrawn patients included one (latanoprost) for lack of efficacy, five (three travoprost, one latanoprost, one DTFC) for adverse events, and two (one latanoprost, one DTFC) for loss of follow-up. Each of the three drugs considerably reduced the IOP in PXG cases throughout the 6 months. Mean IOP reduction at 6 months was –9.3±2.9 mmHg in the travoprost group, -8.2±1.2 mmHg in the latanoprost group, and 11.5±3.3 mmHg in the DTFC group. Comparing the groups, DTFC is more effective than latanoprost and travoprost in lowering IOP (p<0.05). There was no difference between travoprost and latanoprost. The most common treatment-related adverse event was conjunctival hyperemia. Intensity of ocular hyperemia was greater in the travoprost group compared with the latanoprost and DTFC groups (p<0.05). There were no significant effects on systemic safety parameters. Conclusions The results demonstrated that DTFC is more effective in reducing IOP than latanoprost and travoprost. Latanoprost and travoprost had similar ocular hypotensive effects in patients with PXG. All three drugs were well tolerated; there were fewer ocular side effects attributable in the latanoprost group.

The Impact of Subconjuctivally Injected EGF and VEGF Inhibitors on Experimental Corneal Neovascularization in Rat Model

Aim and scope: To investigate the inhibitory effect of subconjunctival application of VEGF antibodies bevacizumab, ranibizumab, pegaptanib, and HER2 antibody trastuzumab on corneal neovascularization in a rat model of experimental corneal neovascularization. Material and method: Thirty male Wistar albino rats were included in the study. A chemical burn was induced in central cornea of one eye of the rats by a 75% silver nitrate and 25% potassium nitrate stick. Rats were randomly divided into five groups so that each group contained 6 subjects. Right after the chemical burn, 0.1u2009ml serum physiologic was injected subconjuctivally in control group (group 1). 1.25u2009mg/0.05u2009ml bevacizumab was injected in group 2; 1.2u2009mg/0.1u2009ml trastuzumab was injected in group 3; 0.5u2009mg/0.05u2009ml ranibizumab was injected in group-4; and 0.3u2009mg/0.1u2009ml pegaptanib was injected in group 5. On the 8th day of the experiment, rat corneas were photographed by digital photo-camera. Later, eyes of the sacrificed rats were enucleated and corneal speciements were histopathologically analyzed. The percentages of neovascularization on corneal photographs were examined with digital image analysis. Results: The percentage of corneal neovascularization in all treatment groups was found to be significantly lower than the control group (pu2009<u20090.05). Bevacizumab was found to be more effective than all other agents (pu2009<u20090.05). While the degree of inflammation and vascularization in bevacizumab and trastuzumab groups were significantly lower than the control group (pu2009<u20090.05), the difference was not significant in ranibizumab and pegaptanib groups (pu2009>u20090.05). In all treatment groups, fibroblast intensity was significantly lower than the control group. In terms of corneal thickness, no significant difference was observed between treatment and control groups (pu2009>u20090.05). Conclusion: Bevacizumab, ranibizumab, pegaptanib, and trastuzumab were found effective for the inhibition of corneal NV. In our study we detected that the most effective agent was bevacizumab.

Homocysteine levels in plasma and sensorineural hearing loss in patients with pseudoexfoliation syndrome.

Purpose To determine the incidence and severity of hearing loss in different frequencies in patients with Pseudoexfoliation. Furthermore, possible links between homocysteine and Pseudoexfoliation were evaluated. Methods Seventy-five consecutive patients with Pseudoexfoliation and 75 sex- and age-matched subjects without Pseudoexfoliation as control group were included in this prospective case-control study. Pure-tone audiometry was obtained in all subjects in both groups. Blood samples were obtained from 70 patients with Pseudoexfoliation after overnight fasting for levels of homocysteine and analyzed by routine laboratory measurements. Results Fifty-two (69%) patients with Pseudoexfoliation and 39 (52%) controls had sensorineural hearing loss in speech frequencies. The difference between Pseudoexfoliation and control group with regard to the frequency of sensorineural hearing loss in speech frequencies was statistically significant (p=0.03). No relationship was found between the degree of glaucomatous damage and hearing threshold variables in the patients with Pseudoexfoliation glaucoma. Plasma homocysteine levels showed no significant difference when patients with Pseudoexfoliation and hearing loss were compared with patients with Pseudoexfoliation and normal hearing threshold (p=0.5). Hyperhomocysteinemia was found in 58% (29/50) of Pseudoexfoliation patients with hearing loss, and 55 % (11/20) of Pseudoexfoliation patients with normal hearing threshold (p=0.8). No statistically significant correlation was found between plasma homocysteine and hearing loss in patients with Pseudoexfoliation. Conclusions These findings suggest an association between sensorineural hearing loss and Pseudoexfoliation in patients with Pseudoexfoliation and glaucoma. The severity of hearing loss was not correlated with the degree of glaucomatous damage. There is no association between increased homocysteine levels and hearing loss in patients with Pseudoexfoliation.

Diurnal intraocular pressure variation in pseudoexfoliation syndrome

Purpose To describe and compare the diurnal intraocular pressure (IOP) variation in patients with pseudoexfoliation syndrome (PXS) and normal subjects. Methods The authors prospectively investigated 19 PXS patients (10 bilateral and 9 unilateral) and 25 age- and sex-matched normal subjects. One eye of each control subject and bilateral PXS patient was selected randomly, and pseudoexfoliative eyes of unilateral cases were enrolled in this study. All patients were admitted to the authors ophthalmology department and underwent diurnal IOP testing (six measurements over 24 hours). Results The mean IOP of PXS patients at all time intervals was significantly higher than the control group (p<0.05). Likewise, a significant difference in the maximum IOP, range of IOP, and minimum IOP, as well as the standard deviation of the pressure at each time point, existed between groups (p<0.05). Normal individuals did not show diurnal variation greater than 5 mmHg. Of patients with PXS, 55.6% showed diurnal variation greater than 5 mm Hg. In addition, in 10% of patients with PXS, the diurnal variations were equal to or higher than 10 mmHg. Conclusions Variations in IOP during the daily 24-hour cycle in patients with PXS were higher than control groups. Significant fluctuations in the diurnal curve of IOP in PXS may be an important factor in predicting eyes that may develop pseudoexfoliative glaucoma. IOP fluctuation could influence the diagnostic and prognostic evaluation of PXS.

THE EFFECT OF CAFFEINE ON RETROBULBAR HEMODYNAMICS

Background: To investigate the acute effect of caffeine on intraocular pressure and retrobulbar blood flow velocity. Methods: In this randomized, double-masked, placebo-controlled, prospective study, we examined the effects of single 300-mg oral administration of caffeine on retrobulbar arteries hemodynamics by using color Doppler ultrasonography imaging in healthy human volunteers. The subjects were divided into two groups; group 1 received a 300-mg caffeine tablet and group 2 received placebo. Measurements were obtained in two eyes at baseline, and 1 hr after acute ingestion of caffeine. Blood pressure, pulse rate, and intraocular pressure were monitored. Results: When compared with placebo, no significant change in mean blood pressure or intraocular pressure was observed after administration of caffeine. No significant differences were detected in the peak systolic and end diastolic velocities of retrobulbar arteries, compared with baseline values. Resistive index of ophthalmic, central retinal, and short posterior nasal ciliary artery were significantly increased after oral application of caffeine in group 1 (p < 0.05). Conclusion: The vascular resistance of the retrobulbar vessels appears to be altered by caffeine consumption. Further studies are needed to investigate the effects of caffeine on hemodynamics in patients with glaucoma.

Effects of subconjunctivally injected bevacizumab, etanercept, and the combination of both drugs on experimental corneal neovascularization.

OBJECTIVEnTo compare the effect of subconjunctivally injected bevacizumab, etanercept and the combination of both drugs on experimental corneal neovascularization in rats.nnnDESIGNnExperimental study.nnnPARTICIPANTSn28 male Wistar-Albino rats.nnnMETHODSnRight corneas of rats were cauterized by silver nitrate sticks. Rats were divided randomly and equally into 4 groups so that each group contained 7 subjects. Immediately after the cauterization, 0.05 ml normal saline was injected subconjunctivally in group 1 (control group); 0.05 ml (1.25 mg) bevacizumab was injected subconjunctivally in group 2; 0.05 ml (1.25 mg) etanercept was injected subconjunctivally in group 3; 0.05 ml (1.25 mg) bevacizumab and 0.05 ml (1.25 mg) etanercept was injected subconjunctivally in group 4. The rats were euthanized on the 8th day, and digital photographs were obtained before the eyes were enucleated. The area of corneal neovascularization was calculated from digital photographs. Corneal sections were analyzed by histopathologically.nnnRESULTSnThe burn stimulus score was +1 or higher in all eyes. The difference of the neovascularization score between groups was found to be statistically significant (p = 0.001). The area of corneal neovascularization was 79.8% in group 1, 43.2% in group 2, 54.5% in group 3, and 34.8% in group 4. In group 4, corneal neovascularization was inhibited more than in the other groups. Histologic examination showed that the treatment groups had less neovascularization, inflammation, and fibroblast activity than the control group (p< 0.05).nnnCONCLUSIONSnOur study has shown that etanercept does have some antiangiogenic and anti-inflammatory effects in treatment of corneal neovascularization. The combination of bevacizumab and etanercept may be a promising approach in the treatment of corneal neovascularization.

The short-term effect of adding brimonidine 0.2% to timolol treatment in patients with open-angle glaucoma.

Brimonidine, a highly selective α2-adrenoceptor agonist, was studied to determine its ocular hypotensive effect and side effects in patients with elevated intraocular pressure (IOP) while on continuing therapy with timolol. This was a prospective, randomized, placebo-controlled study in 15 patients with primary open-angle or pseudoexfoliation glaucoma on therapy receiving timolol 0.5% twice daily, with IOP greater than or equal to 22 mm Hg in one eye. IOP measurements, blood pressure and pulse rate were assessed on 2 days at a baseline and 1, 2, 4, 6 and 8 h later. A single drop of brimonidine 0.2% or placebo was added to treatment with timolol. The reductions in IOP at all time intervals observed with brimonidine + timolol were significantly greater than those with timolol + placebo. The maximum mean net decrease in IOP was 19.23 ± 10.60% at 4 h. Statistically significant decreases in systemic blood pressure and pulse rate without clinical symptoms were observed in the group receiving brimonidine + timolol. This study suggests that a combination of brimonidine and timolol may have potential in the treatment of glaucoma. Further clinical trials with brimonidine are indicated to assess its further role as adjunctive agent.