Nurşen Yüksel

Ocular hemodynamics in pseudoexfoliation syndrome and pseudoexfoliation glaucoma

OBJECTIVE To evaluate orbital blood flow velocities by using color Doppler imaging in patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma. DESIGN Prospective, comparative case series. PARTICIPANTS Twenty-eight patients with pseudoexfoliation syndrome (n = 14) or pseudoexfoliation glaucoma (n = 14) and 14 healthy control participants were included. INTERVENTION Color 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. RESULTS When 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. CONCLUSIONS The 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.

The Effects of Menopause and Hormone Replacement Therapy on Quality and Quantity of Tear, Intraocular Pressure and Ocular Blood Flow

Objective: To evaluate the effects of menopause and hormone replacement therapy (HRT) on the quality and amount of tear, intraocular pressure (IOP) and retrobulbar blood flow velocities. Patients and Methods: Twenty women aged between 40 and 50 years, free of ocular and systemic diseases and planning to receive HRT were recruited as the study group. Twenty-four healthy, age-matched but still menstruating women were enrolled as controls. On the first day of study basal and reflex Schirmer test, tear break-up time and IOP measurements (at 08.00, 12.00 and 16.00 h) were performed for all groups. On the second day of the study, the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistivity index (RI) of the ophthalmic (OA), central retinal (CRA), nasal (NSPCA) and temporal short posterior ciliary (TSPCA) arteries were determined by color Doppler imaging. The menopausal group received HRT for 2 months, when all measurements were repeated for the 15 women who had received HRT on a daily basis. Results: The quality and amount of tear decreased (p < 0.01), IOP (p < 0.01) and RI of the CRA, TPCA and NPCA (p < 0.05) increased in postmenopausal women compared with the control group. After 2 months of HRT, the quality and amount of tear had increased (p < 0.001) and the IOP had decreased (p < 0.001). The PSV of the CRA and TSPCA had decreased (p < 0.05), as had the RI in the CRA (p < 0.001), NSPCA and TSPCA (p < 0.05). Conclusion: We conclude that age-induced changes on quality and amount of tear, IOP and retrobulbar blood flow are intensified by the menopause and that it may be possible to decrease the menopausal effects on these parameters by HRT.

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.

Cystoid macular edema associated with latanoprost after uncomplicated cataract surgery.

PURPOSE To report clinically symptomatic and angiographically documented cystoid macular edema (CME) associated with the use of latanoprost in two pseudophakic eyes after uncomplicated cataract surgery. METHODS Retrospective review of two patients who had history of latanoprost use and uncomplicated cataract surgery and described blurred vision in the first postoperative month. RESULTS Ocular examination revealed CME, which was confirmed by fluorescein angiography. The visual acuities of patients improved and the CME was angiographically resolved after discontinuation of latanoprost and the initiation of nonsteroidal anti-inflammatory eye-drops and oral acetazolamide. CONCLUSIONS Until a causal relationship between CME and latanoprost is proved or disproved, caution in its use in pseudophakic patients would be prudent.Purpose To report clinically symptomatic and angiographically documented cystoid macular edema (CME) associated with the use of latanoprost in two pseudophakic eyes after uncomplicated cataract surgery. Methods Retrospective review of two patients who had history of latanoprost use and uncomplicated cataract surgery and described blurred vision in the first postoperative month. Results Ocular examination revealed CME, which was confirmed by fluorescein angiography. The visual acuities of patients improved and the CME was angiographically resolved after discontinuation of latanoprost and the initiation of nonsteroidal anti-inflammatory eye-drops and oral acetazolamide. Conclusions Until a causal relationship between CME and latanoprost is proved or disproved, caution in its use in pseudophakic patients would be prudent.

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.

The effect of subconjunctival platelet-rich plasma on corneal epithelial wound healing.

Objective: Single-dose subconjunctival platelet-rich plasma (sPRP) injections with or without antibiotic treatment were investigated for their effect on corneal epithelial wound healing in a rabbit model. Materials and Methods: A total of 24 rabbits were used in this study. After collecting intracardiac blood samples from 16 rabbits, platelet-rich plasma was obtained by centrifugation. Animals were divided into 3 groups. A mechanical corneal epithelial defect of 7-mm diameter was created on the central cornea of the right eye of each animal. Group 1 (n = 8) received only sPRP, whereas group 2 (n = 8) received sPRP with topical antibiotic throughout the study. The third group (n = 8) served as the control group. Each animal was examined daily under biomicroscope for 10 days. Epithelial defect was measured in horizontal and vertical diameter with a 1/100 sensitive micrometer, and area of the defect was calculated. One animal was sacrificed in each group on the third and seventh day, and all remaining animals were sacrificed on the 10th day. Corneal histopathology was investigated for epithelial regeneration, presence of inflammation, and structural integrity of fibroblasts. All data were statistically analyzed for difference between the study groups. Results: Group 1 had a significantly smaller size in horizontal and vertical defect diameters on each day as compared with the control group. Healing of the epithelial defect in group 1 was found to be significantly different than that in the control group (P < 0.05). No significant difference was observed between group 2 and control group except for the first day. Group 1 had a significantly better healing process after the fourth day as compared with group 2. Histopathological investigations revealed a steady fibroblast migration, quicker epithelial regeneration, and less inflammation in group 1 as compared with the other 2 groups. Discussion and Conclusions: sPRP seems to improve corneal epithelial wound healing. However, antibiotic and sPRP combination may have a retarded healing effect as compared with platelet-rich plasma alone.

Neuroprotective effects of intravitreally transplanted adipose tissue and bone marrow–derived mesenchymal stem cells in an experimental ocular hypertension model

BACKGROUND AIMS The purpose of this study was to investigate the neuroprotective effects of bone marrow bone marrow-derived and adipose tissue-derived mesenchymal stromal cells (MSCs) that were intravitreally transplanted in an experimental ocular hypertension (OHT) model. METHODS An OHT rat model was generated by means of intracameral injection of hyaluronic acid into the anterior chamber. MSCs labeled with green fluorescence protein were transplanted intravitreally 1 week after OHT induction. At the end of the second and fourth weeks, retinal ganglion cells were visualized with the use of a flat-mount retina method and were evaluated by means of immunofluorescence staining against green fluorescence protein, vimentin, CD105, and cytokines (interleukin [IL]-1Ra, prostaglandin E2 receptor, IL-6, transforming growth factor-β1, interferon-γ and tumor necrosis factor-α). RESULTS The retinal ganglion cell numbers per area were significantly improved in stem cell-treated OHT groups compared with that in the non-treated OHT group (P < 0.05). The results of immunohistochemical analyses indicated that a limited number of stem cells had integrated into the ganglion cell layer and the inner nuclear layer. The number of cells expressing proinflammatory cytokines (interferon-γ and tumor necrosis factor-α) decreased in the MSC-transferred group compared with that in the OHT group after 4 weeks (P < 0.01). On the other hand, IL-1Ra and prostaglandin E2 receptor expressions were increased in the rat bone marrow-derived MSC group but were more significant in the rat adipose tissue-derived MSC group (P < 0.01). CONCLUSIONS After intravitreal transplantation, MSCs showed a neuroprotective effect in the rat OHT model. Therefore, MSCs promise an alternative therapy approach for functional recovery in the treatment of glaucoma.

Magnetic Resonance Imaging of the Brain in Patients with Pseudoexfoliation Syndrome and Glaucoma

Purpose: To evaluate ischemic changes in brain magnetic resonance images in patients with pseudoexfoliation syndrome (PXS) and pseudoexfoliation glaucoma (PXG) and compare them with age- and sex-matched control subjects. Methods: This case-control study involved 16 consecutive patients with PXS, 21 patients with PXG and 18 healthy age- and sex-matched control subjects. Each subject underwent a comprehensive ophthalmological examination. In all participants, an axial T1-, T2- and proton-density-weighted and coronal cerebral 1.5-tesla magnetic resonance imaging (MRI) scan was made. White matter hyperintensities (WMH) were considered present if these were hyperintense on both proton-density- and T2-weighted images and not hypointense on T1-weighted images. White matter lesions were classified into two parts as the subcortical and periventricular regions. We used a validated rating scale of subcortical WMH: 0 = absent, 1 = punctuate foci, 2 = beginning confluence of foci and 3 = large confluent areas. Periventricular white matter lesions were classified on a scale of 0 (no white matter lesions), 1 (pencil-thin periventricular lining), 2 (thick lining) or 3 (large confluent white matter lesions). Results: The proportions of persons with WMH were 93.7% for patients with PXS, 95.2% for patients with PXG and 55.5% for control subjects. The numbers of white matter lesions in patients with PXS and PXG were significantly greater than in the control subjects (p < 0.05). White matter lesions at subcortical locations in patients with PXG were significantly more frequent than in the control subjects (80.9 vs. 33.3%; p < 0.05). The proportion of patients with subcortical WMH was 56.2% in PXS; no significant difference was found in subcortical WMH between PXS and controls. The proportions of patients with periventricular WMH were 93% in PXS, 90.4% in PXG and 44.4% in controls. White matter lesions at periventricular locations in patients with PXG and PXS were significantly more frequent than in the control subjects (p < 0.05). The difference between the pseudoexfoliation groups and controls with regard to the size of periventricular and subcortical white matter lesions was statically significant (p < 0.05). When patients with PXS were compared with PXG patients, there was no statistically significant difference in the number, size and scale of white matter lesions. Conclusion: We found a significantly higher prevalence of MRI-defined WMH in patients with a clinical diagnosis of pseudoexfoliation with or without glaucoma versus control subjects. We think that the findings in this study may shed light on a possible link between ischemic brain lesions and pseudoexfoliation, which is not related with the presence of glaucomatous optic neuropathy. Further investigations are required to resolve the underlying associations.

Comparison of Blood Flow Velocities of the Extraocular Vessels in Patients with Pseudoexfoliation or Primary Open-Angle Glaucoma

Purpose: To evaluate orbital blood flow velocities in patients with pseudoexfoliation glaucoma (PXG) or primary open-angle glaucoma (POAG). Methods: Blood flow velocities in the ophthalmic, central retinal, and posterior ciliary arteries were evaluated by color Doppler imaging in 26 patients with PXG, 28 patients with POAG and 30 age-matched normal control subjects. The results were compared. Results: Compared to the control subjects, patients with PXG showed statistically significant decreases in the mean peak systolic and end-diastolic velocities and increased mean resistive indices in all vessels except for the ophthalmic artery mean peak systolic velocity (p < 0.05). Patients with POAG, when compared to the control subjects, showed statistically significant decreases in the mean end-diastolic velocities and increased mean resistive indices in all vessels measured (p < 0.05). No statistically significant differences were found in the mean blood flow parameters between POAG and PXG. Conclusion: Blood flow velocities of the retrobulbar vessels are decreased in patients with PXG. Reduced blood flow velocities may be secondary as well as contributory to exfoliative glaucomatous damage. Although there was no significant difference in the mean blood flow parameters between POAG and PXG, alterations of retrobulbar vessels might be associated with different pathogenic mechanisms of PXG.

Analysis of Retinal Nerve Fiber Layer Thickness in Patients with Pseudoexfoliation Syndrome Using Optical Coherence Tomography

Objective: To evaluate the retinal nerve fiber layer (RNFL) thickness in patients with unilateral pseudoexfoliation syndrome (PXS) without glaucoma by using optical coherence tomography (OCT). Methods: 22 patients with unilateral PXS were evaluated. Group 1 included the eyes with the pseudoexfoliation, group 2 included the fellow eyes; 18 age-matched normal control eyes were assessed in group 3. The mean and segmental RNFL thickness in eyes with pseudoexfoliation and their fellow eyes in patients with unilateral PXS was compared to age-matched control subject eyes. Results: The RNFL in patients with PXS were significantly thinner than controls in all quadrants except the nasal quadrant with regard to segmental analysis (p < 0.05). This RNFL loss was apparent at 7, 10 and 11 o’clock of the PXS eyes with regard to clock hour position (p < 0.05). In the fellow eyes, no significant difference in RNFL measurement was found except the temporal quadrant when compared with the controls. In the analysis with regard to clock hour position, no significant reduction in RNFL thickness was found except in the 11-o’clock segment. In PXS eyes, RNFL thicknesses at the inferior quadrant and the 1-, 2- and 5-o’clock segments were significantly lower than in non-PXS eyes (p < 0.05). Conclusions: This study suggests that PXS without glaucoma may be associated with a thinner RNFL compared with those of age-matched control subjects and non-PXS fellow eyes. Further studies are needed to clarify the relationship between the decrease in RNFL thickness and the development of glaucomatous damage in eyes with pseudoexfoliation.