Günther Weigert

Effects Of Lutein Supplementation On Macular Pigment Optical Density And Visual Acuity In Patients With Age-related Macular Degeneration

PURPOSE There is evidence from several large-scale clinical trials that reduced intake of lutein, a major component of the macular pigment, is a risk factor for the development of AMD. In the present study (LISA; Lutein Intervention Study Austria) it was hypothesized that lutein supplementation increases macular pigment optical density (MPOD). In addition, an investigation was conducted into whether lutein supplementation improves visual acuity (VA) and macular function (mean differential light threshold; MDLT), as assessed with microperimetry. METHODS One hundred twenty-six patients with AMD (AREDS [Age-related Eye Disease Study] stages 2, 3, and 4) were included in this randomized (2:1), placebo-controlled, double-masked parallel group study. Lutein or placebo was administered for 6 months. MPOD was measured with a custom-built reflectometer. VA was assessed with ETDRS (Early Treatment Diabetic Retinopathy Study) charts, and MDLT was assessed with a microperimeter. RESULTS Lutein significantly increased MPOD by 27.9% ± 2.9% (P < 0.001 versus placebo). No significant effect of lutein supplementation on MDLT or VA was seen, although a tendency toward an increase was seen for both parameters (MDLT, P = 0.096 versus placebo; VA, P = 0.070 versus placebo). A significant correlation was found, however, between the increase in MPOD after 6 months and the increase in MDLT after 6 months (r = 0.25, P = 0.027), as well as between the increase in MPOD after 6 months and the increase in VA after 6 months (r = 0.27, P = 0.013). CONCLUSIONS The present study demonstrates that lutein supplementation increases MPOD, as assessed with an objective METHOD The correlation between the change in MPOD and the change in VA and MDLT indicates that patients who show a pronounced increase in MPOD also benefit in terms of visual function. (ClinicalTrials.gov number, NCT00879671.).

Intravitreal bevacizumab (Avastin) therapy versus photodynamic therapy plus intravitreal triamcinolone for neovascular age-related macular degeneration: 6-month results of a prospective, randomised, controlled clinical study

Aims: To compare functional and anatomical outcomes of intravitreal bevacizumab (Avastin) and verteporfin (photodynamic) therapy (PDT) combined with intravitreal triamcinolone (IVTA) in patients with neovascular age-related macular degeneration (AMD). Methods: Twenty-eight patients with neovascular AMD were enrolled in a prospective, randomised, controlled clinical trial. All patients randomly assigned to 1 mg intravitreal bevacizumab (0.04 ml) received three initial treatments at 4-week intervals. In further follow-up retreatment was based on optical coherence tomography (OCT). Patients randomly assigned to standard PDT received a same-day intravitreal injection of 4 mg triamcinolone (Kenalog). Retreatment was based on fluorescein angiography at 3-month intervals. Functional and anatomical results were evaluated using the Early Treatment Diabetic Retinopathy Study protocol vision charts, fluorescein angiography and OCT. Results: In the bevacizumab-treated group mean visual acuity (VA) improved to a 2.2 line gain at 6 months follow-up. Eyes treated in the PDT plus IVTA group had a stable mean VA at month 6 compared with baseline. There was a statistically significant difference (p = 0.03, analysis of variance (ANOVA)) between both groups as early as one day after initial treatment. The reduction in central retinal thickness (CRT) showed no significant difference between both groups (p = 0.3, ANOVA). Mean CRT was reduced from 357 μm at baseline to 239 μm at month 6 in bevacizumab-treated patients and from 326 μm to 222 μm, respectively, in PDT plus IVTA-treated patients. No significant local or systemic safety concerns were detected up to month 6. Conclusion: Intravitreal bevacizumab showed promising 6-month results in patients with neovascular AMD. Functional outcomes appear not only to be dependent on a reduction in CRT but also on the treatment modality used.

Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension

Background: There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). Methods: One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. Results: Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p<0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p<0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p<0.001 versus timolol). Conclusions: This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma.

Choroidal blood flow and progression of age-related macular degeneration in the fellow eye in patients with unilateral choroidal neovascularization.

PURPOSE Cardiovascular risk factors such as smoking, hypertension, and atherosclerosis seem to play an important role in the development of choroidal neovascularization (CNV). Recent studies have also provided evidence suggesting that choroidal and retinal blood flow is decreased in patients with AMD. On the basis of these results, the hypothesis for this study was that lower choroidal blood flow is associated with an increased risk of CNV in patients with AMD. METHODS Forty-one patients with unilateral choroidal neovascular AMD were included in this observational longitudinal study. The fellow eyes of the patients served as study eyes. Subfoveal choroidal blood flow (FLOW) and fundus pulsation amplitude (FPA) were assessed with laser Doppler flowmetry and laser interferometry, respectively. A multivariate COX-regression model was used to test the hypothesis that low choroidal perfusion parameters are associated with the development of CNV. RESULTS Of the 37 patients that were followed up until the end of the study, 17 developed CNV and 20 did not. The univariate COX-regression analysis shows that lower FLOW, systolic blood pressure, intraocular pressure, and FPA are risk factors for development of CNV. Moreover, the more advanced the AMD in the study eye, the higher the risk for CNV to develop in the fellow eye. Multivariate COX regression analysis indicated that only FLOW (P = 0.0071), FPA (P = 0.0068), and staging (P = 0.031) had statistically significant influences on the progression to CNV. CONCLUSIONS The present study indicates that lower choroidal perfusion is a risk factor for the development of CNV in the fellow eye of patients with unilateral CNV.

Evaluation of anterior chamber inflammatory activity in eyes treated with intravitreal bevacizumab.

Purpose: To evaluate the effect of intravitreal bevacizumab on anterior chamber inflammatory activity. Methods: Sixty-one consecutive patients with neovascular age-related macular degeneration were examined before, 1 day, and 1 week after intravitreal administration of 1 mg of bevacizumab (0.04 mL) for neovascular age-related macular degeneration. The intravitreal injection was performed under sterile conditions. Twenty-one fellow eyes served as controls. The anterior chamber inflammatory activity was evaluated using biomicroscopy and the laser flare meter (Kowa FM-500, Kowa Company, Ltd., Tokyo, Japan). Results: None of the 61 consecutive patients had a significant, clinically detectable inflammatory response within 1 week of follow-up. Anterior chamber inflammatory activity measured by the laser flare meter ranged from 1.9 counts/ms to 70.0 counts/ms (mean ± SD, 13.2 ± 16.9 counts/ms; 95% confidence interval [CI], 7.8–18.6) before treatment. One day and 1 week after injection, values were between 3.2 counts/ms and 30.0 counts/ms (mean ± SD, 9.1 ± 6.2 counts/ms; 95% CI, 7.2–11.1) and 2.0 counts/ms and 25.1 counts/ms (mean ± SD, 7.3 ± 4.6 counts/ms; 95% CI, 5.8–8.8), respectively. There was a significant reduction of anterior chamber flare at 1 week compared with baseline (P = 0.031). The control eyes had constantly low flare measures. Conclusion: No inflammatory response was detected clinically and by the laser flare meter after intravitreal bevacizumab administration. The slight reduction in anterior chamber flare could be due to the known antiinflammatory effect of anti–vascular endothelial growth factor therapy.

Correlation of flicker-induced and flow-mediated vasodilatation in patients with endothelial dysfunction and healthy volunteers.

OBJECTIVE Flicker-induced vasodilatation is reduced in patients with vascular-related diseases, which has at least partially been attributed to endothelial dysfunction of retinal vessels. Currently, the standard method to assess endothelial function in vivo is flow-mediated vasodilatation (FMD). Thus, the present study was performed to investigate whether a correlation exists between flicker-induced vasodilatation and FMD in patients with known endothelial dysfunction and healthy subjects. RESEARCH DESIGN AND METHODS In the present study, 20 patients with type 1 diabetes, 40 patients with systemic hypertension (systolic blood pressure 140–159 mmHg; diastolic blood pressure 90–99 mmHg) and/or serum cholesterol levels ≥0.65 mmol/l, and 20 healthy control subjects were included. The flicker response was measured using the Dynamic Retinal Vessel Analyzer. FMD was determined using a high-resolution ultrasound system, measuring brachial artery diameter reactivity during reperfusion after arterial occlusion. RESULTS The flicker response of both retinal arteries and veins was significantly reduced in the two patients groups. Likewise, FMD was significantly reduced in patients compared with healthy control subjects. However, only a weak correlation between flicker-induced vasodilatation and FMD was observed. CONCLUSIONS The study confirms that flicker responses and FMD are reduced in the selected patient groups. Whether the weak correlation between FMD and flicker is due to the different stimulation type, the different vascular beds measured, or other mechanisms has yet to be investigated.

Response of Retinal Vessels and Retrobulbar Hemodynamics to Intravitreal Anti-VEGF Treatment in Eyes with Branch Retinal Vein Occlusion

PURPOSE To investigate whether intravitreal ranibizumab (0.05 mL) treatment affects retinal vessel diameters and retrobulbar blood velocities in patients with acute branch retinal vein occlusion (BRVO). METHODS Thirty patients with clinically significant macular edema secondary to BRVO were included. The duration of the study was three months. Patients were studied before and one week, one month, two months, and three months after the first ranibizumab injection. Depending on the clinical requirements, up to three ranibizumab injections were administered. Retinal vessel diameters were measured using a retinal vessel analyzer. Flow velocities in the retrobulbar central retinal artery were measured using color doppler imaging. Best-corrected visual acuity was assessed using ETDRS charts. Measurements were done in the affected as well as in the contralateral eye. RESULTS Three patients were lost for follow up. In the remaining 27 patients, significant vasoconstriction was observed in retinal veins (P < 0.001 versus baseline) and in retinal arteries (P = 0.001 versus baseline) of the affected eyes. In addition, a significant reduction in flow velocities was observed in the BRVO eyes over time (peak systolic velocity: P = 0.003, end diastolic velocity: P = 0.003). The reduction in retinal vessel diameters and flow velocities did not correlate with changes in visual acuity or number of re-treatments. In the contralateral eyes no change in retinal blood flow parameters was seen. CONCLUSIONS BRVO is an ischemic retinal disease. Given that ranibizumab treatment reduces retinal perfusion in these eyes the potential long-term effects of this vasoconstriction need to be considered.

Effect of Dual Endothelin Receptor Blockade on Ocular Blood Flow in Patients with Glaucoma and Healthy Subjects

PURPOSE Several lines of evidence indicate that altered blood flow regulation may contribute to the pathogenesis of glaucomatous optic neuropathy. Recent data support the hypothesis that the endothelin system is involved in the processes that lead to vascular dysregulation in glaucoma. This study was conducted to test the hypothesis that bosentan, a dual endothelin receptor antagonist, increases ocular blood flow in patients with glaucoma. METHODS Fourteen patients with primary open-angle glaucoma and 14 sex- and age-matched healthy volunteers were included. Both groups received bosentan 500 mg daily for 8 days. Ocular hemodynamics were assessed at baseline and on the last study day. Retinal vessel diameters and retinal red blood cell velocity were recorded with a retinal vessel analyser and laser Doppler velocimetry, respectively. Choroidal and optic nerve head blood flow were measured with laser Doppler flowmetry. RESULTS Retinal arteries and veins showed a significant dilatation after administration of bosentan in both groups (+5%-8%). Retinal blood velocity and retinal blood flow increased up to +45% after administration of bosentan in both patients and healthy subjects. Administration of bosentan increased choroidal (+12%-17%) and optic nerve head blood flow (+11%-24%) in both groups. The effect of bosentan on ocular blood flow parameters was comparable between the two groups. CONCLUSIONS The data from the present study indicate that dual inhibition of endothelin receptors increases ocular blood flow in patients with glaucoma and healthy subjects. Further studies are needed to study the dose-response relationship of this effect and to characterize the role of endothelin receptor subtypes.

Randomised clinical trial of intravitreal Avastin vs photodynamic therapy and intravitreal triamcinolone: long-term results

PurposeTo compare 1-year functional and anatomic outcomes of intravitreal bevacizumab (IVB) and photodynamic therapy plus intravitreal triamcinolone (PDT+IVTA) combination in patients with neovascular age-related macular degeneration (AMD).MethodsIn this prospective, randomised, controlled clinical trial, 28 patients were included. All patients were randomised 1 : 1 to 0.04 ml/1 mg of IVB or PDT plus same day 0.1 ml/4 mg IVTA (PDT+IVTA). Follow-up examinations were performed in monthly intervals in IVB group and every 3 months in PDT+IVTA group. Main outcomes were change in mean visual acuity (VA), mean central retinal thickness (CRT) and the mean number of treatments.ResultsAt month 12, mean VA improved to a 1.5-line gain in IVB group, and lost three letters in PDT+IVTA group (P=0.02). Mean CRT was reduced from 357 μm at baseline to 244 μm at month 12 in IVB group and from 326 μm to 254 μm, respectively, in PDT+IVTA group (P=0.8). The mean number of treatments was 6.8 in the IVB group vs1.9 in the PDT+IVTA group. No significant local or systemic safety concerns were detected during follow-up time.ConclusionsPatients treated with IVB showed a significant better VA outcome compared with the PDT+IVTA group despite the fact that both modalities showed equal potency in reducing CRT during a 12-month period.

Effect of dorzolamide and timolol on ocular pressure: blood flow relationship in patients with primary open-angle glaucoma and ocular hypertension.

PURPOSE The authors have reported previously that a study population, consisting of patients with glaucoma and ocular hypertension, is characterized by an impaired association between ocular blood flow parameters and systemic blood pressure, indicative of abnormal autoregulation. Here they report on the effects of dorzolamide and timolol on ocular pressure/flow relationships to test the hypothesis that these drugs improve autoregulation. METHODS One hundred forty patients with primary open-angle glaucoma or ocular hypertension were included in a clinical trial in a controlled, randomized double-masked study in two parallel groups. Seventy patients were randomly assigned to receive timolol, and 70 patients were randomly assigned to receive dorzolamide for a 6-month period. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. The association between blood flow parameters and systemic blood pressure was compared before and after the 6-month treatment period. RESULTS Before treatment a significant association was observed between ocular blood flow parameters and systemic blood pressure in both parallel groups (r = 0.23-0.42). All regression lines between ocular hemodynamic parameters and systemic blood pressure were less steep after treatment with either dorzolamide or timolol (r = 0.03-0.24). CONCLUSIONS The present study indicates that intraocular pressure reduction with timolol or dorzolamide is associated with normalization of the ocular pressure/flow relationship. Whether this is related to the beneficial effects of IOP-lowering therapy in glaucoma remains to be established. (ClinicalTrials.gov number, NCT00991822.).