Franz Prager

INTRAVITREAL BEVACIZUMAB (AVASTIN) FOR MACULAR OEDEMA SECONDARY TO RETINAL VEIN OCCLUSION: 12-MONTH RESULTS OF A PROSPECTIVE CLINICAL TRIAL

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 μm at baseline to 309 μm at month 12 (−249 μm; 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.

Intravitreal Avastin for macular oedema secondary to retinal vein occlusion: a prospective study

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 µm (range 353–928 µm) and mean BCVA was 20/100. One day after the first injection, CRT significantly decreased to 401 μm (p<0.01). Three injections reduced macular oedema to 328 μm CRT (p<0.01) and improved BCVA to 20/50 (p<0.01). At 6 months, CRT was 382 μm (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.

Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab.

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.

Characteristics of severe intraocular inflammation following intravitreal injection of bevacizumab (Avastin

Background/aims: To report a series of severe intraocular inflammatory events following intravitreal injections of bevacizumab (Avastin). This procedure is performed on a rapidly increasing number worldwide, and rare complications such as intraocular inflammation, endophthalmitis or intraocular haemorrhage are gaining in importance in clinical routine. Methods: This is a single-centre retrospective interventional case series of eight patients with severe intraocular inflammation after intravitreal injection of bevacizumab at one referral centre consecutively seen out of approximately a total of 2500 injections performed in that time period. Patients who developed severe intraocular inflammation after intravitreal injection were evaluated clinically, including slit-lamp examination, best-corrected Snellen visual acuity (VA), slit-lamp photography, optical coherence tomography and fluorescein angiography prior to the event and during follow-up. Results: Patients noticed a painless drop in VA up to 2 days following the injection. All patients had a marked anterior chamber reaction with increased flare and cells, but no hypopyon. Typical posterior segment findings included vitreous cellular infiltrates of pseudogranulomatous aspect. Due to their initial clinical aspect suspicious of an endophthalmitis, three cases were treated with systemic antibiotics, but the final diagnosis was uveitis. Five cases showed a characteristic pseudogranulomatous vitreous infiltration as seen in vitritis and were treated only topically. Conclusions: Characteristic features of an inflammation induced by bevacizumab injection include an early onset with painless loss in VA mostly without conjunctival or ciliary injection. Patients respond to systemic or topical cortisone treatment with slow recovery but without permanent damage. Vitreous haemorrhage and infectious endophthalmitis might be differentiated by time course and symptoms.

Imaging of the Retinal Pigment Epithelium in Age-Related Macular Degeneration Using Polarization-Sensitive Optical Coherence Tomography

Purpose. Spectral-domain optical coherence tomography (SD-OCT) provides new insights into the understanding of age-related macular degeneration (AMD) but limited information on the nature of hyperreflective tissue at the level of the retinal pigment epithelium. Therefore, polarization-sensitive (PS) SD-OCT was used to identify and characterize typical RPE findings in AMD. Methods. Forty-four eyes of 44 patients with AMD were included in this prospective case series representing the entire AMD spectrum from drusen (n = 11), geographic atrophy (GA; n = 11), neovascular AMD (nAMD; n = 11) to fibrotic scars (n = 11). Imaging systems were used for comparative imaging. A PS-SD-OCT instrument was developed that was capable of recording intensity and polarization parameters simultaneously during a single scan. Results. In drusen, PS-SD-OCT identified a continuous RPE layer with focal elevations. Discrete RPE atrophy (RA) could be observed in two patients. In GA, the extension of the RA was significantly larger. Residual RPE islands could be detected within the atrophic zone. PS-SD-OCT identified multiple foci of RPE loss in patients with nAMD and allowed recognition of advanced RPE disease associated with choroidal neovascularization. Wide areas of RA containing residual spots of intact retinal pigment epithelium could be identified in fibrotic scars. Conclusions. PS-SD-OCT provided precise identification of retinal pigment epithelium in AMD. Recognition of these disease-specific RA patterns in dry and wet forms of AMD is of particular relevance to identify the status and progression of RPE disease and may help to better estimate the functional prognosis of AMD.

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.

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.

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.

Association of Retinal Sensitivity and Morphology during Antiangiogenic Treatment of Retinal Vein Occlusion over One Year

PURPOSE Evaluation of the association between functional and anatomic retinal changes during anti-vascular endothelial growth factor (VEGF) therapy with bevacizumab (Avastin) in patients with cystoid macular edema secondary to retinal vein occlusion (RVO) using microperimetry and spectral domain optical coherence tomography (SD-OCT). DESIGN Prospective, uncontrolled study (EUDRACT NR-2005-003288-21). PARTICIPANTS Twenty-eight patients with cystoid macular edema secondary to RVO. METHODS Patients initially received 3 consecutive intravitreal injections of 1.25 mg bevacizumab at 4-week intervals. Further treatment was based on morphologic (OCT) and functional best-corrected visual acuity (BCVA) findings. During the 1-year follow-up, a rigorous standardized evaluation was performed monthly. Macular function was documented by microperimetry (Nidek, MP1 Microperimeter) and BCVA based on the Early Treatment in Diabetic Retinopathy Study (ETDRS). Morphologic parameters included central retinal thickness (CRT) as measured by conventional OCT (Stratus), and central subfield thickness (CST), mean retinal thickness (MRT), and retinal volume (RV) measured by SD-OCT. MAIN OUTCOME MEASURES Imaging of retinal morphology using OCT and SD-OCT and evaluation of retinal function assessed with microperimetry and ETDRS charts during 12 months of anti-VEGF treatment. RESULTS Within 6 months, the mean area of absolute scotoma was reduced from 21.4% of the central visual field to 6.4% and remained at this level until month 12 (7.4%). Mean BCVA improved from 51 to 66 letters on ETDRS charts. The CRT, CST, and MRT decreased significantly (P<0.002) and remained stable during the follow-up. The RV values did not improve significantly under therapy. Statistical analysis using a linear effects model revealed significant associations between the functional and morphologic outcomes, most notably between BCVA, macular sensitivity, CRT (Stratus OCT), CST, and MRT (Cirrus OCT) values. CONCLUSIONS Central retinal morphology, especially CRT and CST measured by conventional and SD-OCT, and retinal function improved significantly during treatment of RVO with a flexible dosing regimen of intravitreal bevacizumab. Functional (central visual acuity and visual field) and morphologic parameters (retinal thickness) were significantly related. These associations highlight the value of OCT imaging for assessing this disease entity.

Effect of systemic bevacizumab therapy on retinal pigment epithelial detachment

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 OCT™, 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 µm (SD 48.8), p<0.01). At 3 months follow-up, two PEDs resolved completely, mean maximum PED height decreased significantly by 39% (−179 µm (SD 178), p = 0.02) and mean PED GLD by 24% (−714 µm (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.