Macular Degeneration: Prager F

Prager F, Michels S, Kriechbaum K, Georgopoulos M, Funk M, Geitzenauer W, Polak K, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Waehringer Guertel 18-20, 1190 Wien, Austria. · Br J Ophthalmol. · Pubmed #19074916 No free full text.

Abstract: AIMS: The aim of the study was to evaluate functional and anatomical changes after intravitreal bevacizumab (Avastin) in eyes with persistent macular oedema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). METHODS: Twenty-nine consecutive eyes with macular oedema secondary to BRVO (21 eyes) or CRVO (eight eyes) were included in a prospective clinical trial. Eyes were treated with three initial intravitreal bevacizumab injections of 1 mg at a monthly interval. Retreatment was based on central retinal thickness (CRT) based on optical coherence tomography. If continuous injections were indicated up to month 6, the dose was increased to 2.5 mg. RESULTS: After 12 months of follow-up, mean visual acuity increased from 50 letters (20/100) at baseline to 66 letters (20/50(+1); +16 letters; p<0.001) at month 12 and CRT decreased from 558 mum at baseline to 309 mum at month 12 (-249 mum; p<0.001). Patients received a mean of eight out of 13 possible injections. No drug-related systemic or ocular side effects following intravitreal bevacizumab treatment were observed. Fluorescein angiography revealed no progression of avascular areas. CONCLUSIONS: Intravitreal therapy using bevacizumab appears to be a safe and effective treatment in patients with macular oedema secondary to retinal vein occlusion. However, the main limitations of this treatment modality are its short-term effectiveness and high recurrence rate.

Funk M, Kriechbaum K, Prager F, Benesch T, Georgopoulos M, Zlabinger GJ, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. · Invest Ophthalmol Vis Sci. · Pubmed #19060280 No free full text.

Abstract: PURPOSE: To investigate concentrations of growth factors and inflammatory cytokines in eyes with central (CRVO) and branch (BRVO) retinal vein occlusion before and during therapy with bevacizumab and to identify associations with disease activity. METHODS: In a prospective clinical trial, 13 eyes of patients with CRVO (n = 5) or BRVO (n = 8) were included. Bevacizumab was administered intravitreously at baseline and months 1 and 2. Retreatments were given at monthly visits if OCT showed edema or when vision loss occurred. Aqueous humor samples were taken each time injections were performed. Follow-up was 15 months. Samples from patients with cataract served as the control. Multiplex bead assays were used for measurement of 28 growth factors and cytokines. RESULTS: During therapy with bevacizumab, VEGF levels were reduced to below detection in the first 2 months. Whenever criteria for retreatment were met, VEGF was measurable again. The decrease in VEGF was associated with a decrease in central retinal thickness (CRT) and improvement in visual acuity (VA). Significantly increased concentrations of VEGF, IL-6, IL-8, IP-10, MCP-1, and PDGF-AA were observed in aqueous humor samples of patients with CRVO compared with the control samples. CONCLUSIONS: VEGF levels were significantly elevated in patients with CRVO compared with control subjects. Intravitreal injections of bevacizumab resulted in a substantial decrease of VEGF under physiologic levels and remained low under the loading dose of three consecutive monthly retreatments. Macular edema was related to VEGF levels in the aqueous humor.

Geitzenauer W, Michels S, Prager F, Rosenfeld PJ, Kornek G, Vormittag L, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Austria. · Retina. · Pubmed #18784625 No free full text.

Abstract: BACKGROUND: To compare safety, visual acuity (VA), and anatomic outcomes of 2.5 mg/kg and 5 mg/kg intravenous bevacizumab in patients with neovascular age-related macular degeneration. METHODS: In an institutional cohort study, 16 patients (2 cohorts, 27 eyes) with neovascular age-related macular degeneration were treated with 5 mg/kg intravenous bevacizumab and 2.5 mg/kg, respectively. All patients received 3 initial intravenous infusions at 2-week intervals. The main outcome measures were VA, optical coherence tomography, and fluorescein angiography. RESULTS: No serious systemic or ocular adverse events were identified. By Day 7, mean VA increased from 56 letters (20/80(+1)) at baseline to 60 letters (20/63) in the 5 mg/kg group and mean central retinal thickness decreased by 83 microm. In the 2.5 mg/kg group, mean VA increased from 55 letters (20/80) to 66 letters (20/50(+1)) and mean central retinal thickness decreased by 93 microm. By Month 3, VA improved by 10 letters compared to baseline in the 5 mg/kg group and by 9 letters in the 2.5 mg/kg group. Central retinal thickness was reduced by 128 microm in the 5 mg/kg group and by 127 microm in the 2.5 mg/kg group. These benefits were sustained through 6 months. No statistically significant difference was found between both treatment groups regarding safety, VA, and anatomic outcomes. CONCLUSION: Similar VA, optical coherence tomography, and angiographic improvements were observed in both treatment groups up to 6 months. Further follow-up is required to evaluate the long-term durability and safety of both treatment regimens.

Kriechbaum K, Michels S, Prager F, Georgopoulos M, Funk M, Geitzenauer W, Schmidt-Erfurth U. · University Eye Hospital Zürich, Frauenklinikstrasse 24, CH-8091 Zurich, Switzerland. · Br J Ophthalmol. · Pubmed #18211942 No free full text.

Abstract: OBJECTIVE: To evaluate efficacy and safety of intravitreal bevacizumab (Avastin) in eyes with macular oedema secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). METHODS: Twenty-eight consecutive patients (28 patients, 29 eyes, 8 CRVO, 21 BRVO) were enrolled in the study. Three intravitreal injections of 1 mg bevacizumab (0.04 ml) were administered at 4-week intervals; further retreatment was based on optical coherence tomography (OCT) findings. Follow-up examinations were done at days 1, 7 and 28 and at monthly intervals thereafter. RESULTS: Mean baseline central retinal thickness (CRT) in OCT was 558 microm (range 353-928 microm) and mean BCVA was 20/100. One day after the first injection, CRT significantly decreased to 401 microm (p<0.01). Three injections reduced macular oedema to 328 microm CRT (p<0.01) and improved BCVA to 20/50 (p<0.01). At 6 months, CRT was 382 microm (p<0.01), and BCVA was stable at 20/50(-2) (p<0.01), FA showed no evidence of increased avascular zones. CONCLUSION: Intravitreal injections of bevacizumab appear to be a safe and effective therapy in the treatment of macular oedema secondary to retinal vein occlusion.

Bolz M, Michels S, Geitzenauer W, Prager F, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. · Br J Ophthalmol. · Pubmed #17050580 No free full text.

Abstract: BACKGROUND: To evaluate the effect of systemic bevacizumab (Avastin) therapy on pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD) and to identify prognostic factors for PED regression and improvement in best corrected visual acuity (BCVA). Study design: Prospective uncontrolled pilot study. METHODS: Nine patients (nine eyes) received three systemic bevacizumab treatments at 2 week intervals and were examined at baseline, weeks 1, 2, 4, 6 and month 3 by using optical coherence tomography (Stratus OC, Carl Zeiss Meditec, Dublin, California, USA). Changes in maximum PED height and greatest linear diameter (GLD) were planimetrically analysed by using Adobe Photoshop CS and correlated with retinal morphological changes and changes in BCVA. RESULTS: Systemic bevacizumab therapy was well tolerated. Mean maximum PED height decreased significantly by 21% as early as 1 week (-96 microm (SD 48.8), p<0.01). At 3 months follow-up, two PEDs resolved completely, mean maximum PED height decreased significantly by 39% (-179 microm (SD 178), p = 0.02) and mean PED GLD by 24% (-714 microm (SD 1010), p = 0.07). Mean BCVA improved significantly by week 2 (+8.7 letters (SD 5.7), p<0.01) and at 3 months with 12.7 letters (SD 6.4) (p<0.01). CONCLUSION: In the examined nine patients, systemic bevacizumab therapy showed evidence for an effect on PED secondary to neovascular AMD in terms of a decrease in lesion height and diameter. A high PED at baseline was found to be a negative predictive factor for visual outcome.

Prager F, Michels S, Simader C, Geitzenauer W, Schmidt-Erfurth U. · Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria. · Retina. · Pubmed #18463510 No free full text.

Abstract: OBJECTIVE: To evaluate changes in central retinal sensitivity in patients with neovascular age-related macular degeneration after systemic bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) therapy. METHODS: For all eyes, the central 12 x 12 degrees visual field was recorded using the MP 1 Microperimeter (Nidek, Gamagori, Japan) at baseline and 1 week, 1 month, 3 months, and 6 months after initial treatment. Patients received systemic anti-vascular endothelial growth factor (VEGF) therapy with three initial bevacizumab infusions at 2-week intervals. Retreatment during follow-up was performed only in cases of choroidal neovascularization recurrence. Seven patients (12 eyes) received bevacizumab infusions at a dose of 5 mg/kg, and 7 patients (9 eyes), at a dose of 2.5 mg/kg. RESULTS: Of 41 stimulation points, a mean absolute scotoma of 15 missed stimulation points was measured at baseline, which decreased to 10 missed stimulation points at month 3 (-5; P = 0.005) and to 11 stimulation points at month 6 (-4; P = 0.106). The mean absolute scotoma size (in % of total tested area) decreased from 33% to 22% (-11%; P = 0.011) at month 3 and to 23% (-10%, P = 0.123) at month 6. Mean differential light threshold increased significantly throughout the observation period from 3.8 dB at baseline to 5.5 dB (+1.7 dB; P = 0.012) at month 6. CONCLUSIONS: Systemic bevacizumab therapy induced a significant increase in mean retinal sensitivity at month 6 of follow-up and a significant decrease of mean absolute scotoma size at month 3. The MP 1 Microperimeter proved to be a valuable tool in the evaluation of functional benefits and retinal safety of anti-VEGF therapy with systemic bevacizumab.

Weigert G, Michels S, Sacu S, Varga A, Prager F, Geitzenauer W, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Vienna, Austria. · Br J Ophthalmol. · Pubmed #18303156 No free full text.

Abstract: 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.

Stifter E, Michels S, Prager F, Georgopoulos M, Polak K, Hirn C, Schmidt-Erfurth U. · Department of Ophthalmology, Medical University of Vienna, Austria. · Am J Ophthalmol. · Pubmed #17916314 No free full text.

Abstract: PURPOSE: To evaluate functional and anatomic effects of intravitreal bevacizumab (Avastin; Roche Pharma, Vienna, Austria) in patients with neovascular age-related macular degeneration (AMD) with large submacular hemorrhages. DESIGN: Retrospective, clinical study. METHODS: Twenty-one eyes of 19 AMD patients with choroidal neovascularization and large submacular hemorrhage involving the fovea comprising more than 50% of the total lesion area were evaluated. All patients completed at least four months of follow-up; 12 patients fulfilled 12 months or more of follow-up. Patients were treated with up to six intravitreal bevacizumab injections (1 mg/0.04 ml) at a minimum of four-week intervals. Changes from baseline visual acuity (VA) scores, retinal measurements by optical coherence tomography (OCT), angiographic lesion characteristics, and hemorrhage size were analyzed. A safety assessment was performed at all visits. RESULTS: Intravitreal bevacizumab injections were well tolerated in all patients. At month 4, VA was stable or improved (visual loss of 3 acuity lines or fewer) in 100% and improved by at least 3 lines in 9.5%. Comparable results were found at month 12. On average, the central foveal thickness decreased significantly by 55 microm four weeks after the first injection (P < .001) and by 52 microm at month 4 (P = .002). A significant anatomic improvement also was found for maximum retinal thickness, minimum retinal thickness, and foveal volume (P < .05) and was maintained during four months of follow-up. Mean size of hemorrhage was significantly reduced from 19.7 mm(2) at baseline to 2.5 mm(2) at the four-month follow-up (P < .001). CONCLUSIONS: Intravitreal bevacizumab seems to be a promising therapeutic option in eyes with neovascular AMD and large submacular hemorrhages, with a stabilization in VA and anatomic improvement.

Kiss C, Michels S, Prager F, Geitzenauer W, Schmidt-Erfurth U. · Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria. · Acta Ophthalmol Scand. · Pubmed #17408387 No free full text.

Abstract: Two patients with choroidal neovascularization secondary to age-related macular degeneration (AMD) developed a retinal pigment epithelial (RPE) tear following intravitreal injection of ranibizumab. One patient developed the RPE tear within 2 weeks of the injection, the other within 6 weeks of a second injection. Both patients presented with vision loss of one line at diagnosis of the RPE tear. During long-term follow-up, visual acuity improved in one patient by one line and deteriorated in the second patient by three lines. RPE tears may occur after intravitreal injection of ranibizumab in patients with neovascular AMD, probably because of the rapid regression of the fibrovascular membrane.

Geitzenauer W, Michels S, Prager F, Kornek G, Vormittag L, Rosenfeld P, Schmidt-Erfurth U. · Klinik für Augenheilkunde und Optometrie, Medizinische Universität Wien, Allgemeines Krankenhaus, Wien. · Klin Monatsbl Augenheilkd. · Pubmed #17063425 No free full text.

Abstract: PURPOSE: The purpose of this study was to evaluate the early treatment response following systemic and intravitreal bevacizumab therapy in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: In a prospective cohort study 12 eyes with neovascular AMD were treated with 5 mg/kg systemic bevacizumab, and 13 eyes with 1 mg intravitreal bevacizumab. Systemic therapy was given three times at 2-week intervals, intravitreal therapy up to three times at 4-week intervals. Patients were evaluated according to best corrected visual acuity (VA) and optical coherence tomography (OCT) at baseline as well as at week 1, week 4 and week 12 after therapy. Fluorescein angiography (FA) was performed at baseline and week 12. RESULTS: Systemic and intravitreal bevacizumab therapy showed a treatment response within one week. Visual acuity improved at week 1 by 4.9 letters from baseline in the systemic and by 6.9 letters in the intravitreal treatment group. Central retinal thickness (CRT), as measured by OCT decreased by 51.9 microm and 176.4 microm, respectively. At month 3 a persistent treatment effect was detectable. Mean gain in visual acuity was 11 letters in the systemic and 8.3 letters in the intravitreal group, CRT had decreased by 100 microm and 153.8 microm, respectively. Leakage as evaluated by FA was significantly reduced or absent in all patients. CONCLUSION: The early treatment responses following systemic and intravitreal bevacizumab appear to be similar. Both groups show improvement in VA and decrease in CRT within 1 week and up to 3 months. Long-term follow-up is required to evaluate the safety and treatment durability of both treatment modalities using bevacizumab.

Kiss C, Michels S, Prager F, Weigert G, Geitzenauer W, Schmidt-Erfurth U. · Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria. · Retina. · Pubmed #17031286 No free full text.

Abstract: 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.