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

PURPOSE: To 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). METHODS: In 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. RESULTS: At 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 microm at baseline to 244 microm at month 12 in IVB group and from 326 microm to 254 microm, respectively, in PDT+IVTA group (P=0.8). The mean number of treatments was 6.8 in the IVB group vs 1.9 in the PDT+IVTA group. No significant local or systemic safety concerns were detected during follow-up time. CONCLUSIONS: Patients 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.

Reduced fluence versus standard photodynamic therapy in combination with intravitreal triamcinolone: short-term results of a randomised study.

BACKGROUND: To compare early treatment effect of reduced fluence versus standard photodynamic therapy (rPDT, sPDT, respectively) in combination with intravitreal triamcinolone (IVTA) in neovascular age-related macular degeneration. METHODS: Forty patients received either sPDT (group A, n = 20) or rPDT (group B, n = 20) each followed by same-day 4 mg IVTA. Patients were examined at baseline, day 1, week 1, 4 and 12. Main outcomes were visual acuity, central retinal thickness (CRT), choroidal perfusion and macular sensitivity (MS). RESULTS: Baseline characteristics were well balanced in both groups (p>0.05). At week 12, patients in group A had a mean loss of -3.7 letters compared with a gain of 3.4 letters in group B (p = 0.04, between both groups). Both treatment groups showed a similar course regarding CRT as well as MS (p>0.05). In 70% (14/20) of group A and 15% (3/20) of group B, a choroidal hypoperfusion in the area of treatment was observed after treatment (p<0.001). In 70% of group A and 55% of group B, a repeat treatment was indicated at week 12 (p = 0.55). CONCLUSIONS: At month 3, the rPDT+IVTA group showed a significantly better visual outcome, less alteration of the choroid and a trend for lower recurrence rate than the sPDT+IVTA group. Further follow-up of this study will provide information on long-term functional results and treatment durability.

Effects of high-dose prednisolone on optic nerve head blood flow in patients with acute optic neuritis.

BACKGROUND: In this study, patients with optic neuritis were treated with high-dose prednisolone. Little information is available about the effects of this treatment on ocular blood flow. We set out to investigate the effects of high-dose prednisolone on optic nerve head (ONH) blood flow in patients with acute optic neuritis. METHODS: Thirteen patients with acute optic neuritis were included in the study. 1000 mg of prednisolone was infused intravenously over 30 minutes on 3 consecutive days. On each study day, ONH blood flow was measured using laser Doppler flowmetry. The ocular hemodynamic measurements were performed on the unaffected eye of the patients with unilateral acute optic neuritis before and immediately after cessation of the infusion. Intraocular pressure (IOP) and systemic blood pressure was measured before and after the infusion on each study day. Data was analyzed using a repeated measures ANOVA model. RESULTS: Prednisolone increased ONH blood flow in the patients under study (p = 0.04), although the effects were in generally small. No significant change in mean arterial pressure (p = 0.70) or IOP (p = 0.20) could be detected in the patients treated with high-dose prednisolone. CONCLUSIONS: A small but significant increase in ONH blood flow resulted from infusion of high-dose prednisolone. Further studies are required to investigate whether this effect contributes to the therapeutic efficacy of cortisone in patients with optic neuritis.

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 microm at baseline to 239 microm at month 6 in bevacizumab-treated patients and from 326 microm to 222 microm, 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.

[Intravitreal bevacizumab versus verteporfin and intravitreal triamcinolone acetonide in patients with neovascular age-related macula degeneration]. / Intravitreales Bevacizumab vs. Verteporfin und intravitreales Triamcinolon Acetonid bei Patienten mit neovaskulärer AMD.

AIM: The aim of this study was to compare intravitreal bevacizumab (IVB) and verteporfin therapy in combination with 4 mg intravitreal triamcinolone (PDT-IVTA) in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: A total of 30 eyes of 30 patients with neovascular AMD were included in a prospective, randomized study. Ten eyes received PDT-IVTA with a standard light fluence of 50 J/cm(2) (SPDT-IVTA), ten were treated with PDT-IVTA with a reduced light fluence of 25 J/cm(2) (RPDT-IVTA) and ten received IVB. The main outcome was evaluated using early treatment diabetic retinopathy study (ETDRS) visual acuity, fluorescein angiography and optical coherence tomography (OCT) at baseline as well as at day 1, week 1, 1 month and 3 months after therapy. RESULTS: At the beginning of therapy, the distribution of the groups was balanced. After 3 months, the SPDT-IVTA group showed a non-significant vision loss of seven letters (p<0.3) while a vision loss of 0.5 letters (p<0.9) was found in the RPDT-IVTA group. At the same time, the IVB group had a vision improvement of 11.8 letters (p<0.001). This vision improvement was statistically significant compared to the results of both PDT-IVTA groups (p<0.005). Central retinal thickness (CRT) decreased up to month 3 in the SPDT-IVTA group by 132 microm, in the RPDT-IVTA group by 78 mum and in the IVB group by 138 microm, (p<0.05 in the three groups). No significant difference in the decrease of CRT was found between the treatment groups after 3 months. CONCLUSION: IVB shows significantly better results in vision improvement in the short-term compared to the two PDT-IVTA groups. Within 3 months, all groups showed a comparable decrease in CRT. Long-term follow-up is required to evaluate the safety and treatment efficacy of all treatment modalities.

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.

Response of choroidal blood flow to carbogen breathing in smokers and non-smokers.

AIM: To investigate a potential difference in ocular vascular reactivity during carbogen breathing in optic nerve head, choroid, and retina between healthy smokers and non-smokers. METHODS: 25 (13 smokers and 12 non-smokers) healthy male volunteers participated in this observer masked, two cohort study. During inhalation of carbogen (5% CO(2) and 95% O(2)) over 10 minutes measurements were taken using laser Doppler flowmetry to assess submacular choroidal and optic nerve head blood flow, laser interferometry to assess fundus pulsation amplitudes, and retinal vessel analyser (RVA) to assess retinal vessel diameters. RESULTS: At baseline choroidal blood flow was higher (p = 0.018, ANOVA) in smokers than in non-smokers. During administration of carbogen the response in choroidal blood flow was significantly different between the two groups: there was an increase in non-smokers after carbogen breathing (p = 0.048) compared with relatively stable blood flow in smokers (p = 0.049 between groups, ANOVA). A similar response pattern was seen for fundus pulsation amplitude, which increased notably after carbogen breathing in non-smokers but not in smokers (p<0.001 between groups, ANOVA). Optic nerve head blood flow and retinal vessel diameters were reduced in both groups to a comparable degree during carbogen breathing. CONCLUSION: The study indicated abnormal choroidal vascular reactivity in chronic smokers. These early haemodynamic changes may be related to the increased risk to smokers of developing ocular vascular diseases. The specific mechanisms underlying abnormal choroidal vascular reactivity in chronic smokers remain to be characterised.