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.

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 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.

[Three-dimensional optical coherence tomography for evaluating the retinal architecture before and after surgery for vitreomacular traction.] / Untersuchung von vitreomakulären Traktionen vor und nach Membranpeeling mittels hochauflösendem Raster-OCT.

PURPOSE: To investigate the morphology of the vitreoretinal interface before and after delamination of epiretinal membranes using three-dimensional volumetric high-resolution optical coherence tomography (HROCT). METHODS: Extension and intensity of vitreomacular traction due to epiretinal membranes (ERM) and the architecture of retinal layers in 14 eyes of 14 patients were evaluated preoperatively using high-resolution raster scanning OCT (Cirrus prototype, resulting in a 6x6-mm field, 2 mm in depth). Additionally, stratus OCT, visual acuity testing, and fundus photography were performed. Standardized prospective follow-up was done continuously at 1, 4, and 7 days and 1 and 3 months postoperatively. RESULTS: The ERM appeared tightly adherent to the retinal surface in 85% of cases, but nevertheless could be differentiated from the retinal surface in 100%. Vertical traction forces from the ERM to the intraretinal layers were found in 93% of cases. Structural alteration of the retina was seen neither immediately following surgery nor during follow-up. After a mean of 4 weeks, the retinal structural integrity had recovered with resolution of the traction-induced deviations seen preoperatively. Mean preoperative visual acuity increased from 0.4+/-0.2 Snellen preoperatively to 0.5+/-0.2 Snellen after 3 months. Mean retinal thickness decreased from 482+/-84 mum to 328+/-80 mum after 3 months (HROCT). CONCLUSIONS: Three-dimensional HROCT imaging enables unprecedented in vivo identification of the extension and dynamics of epiretinal traction. Epiretinal membranes are clearly delineated in the en face view, and the distribution of traction forces throughout the intraretinal layers is identified down to the level of the retinal pigment epithelium. During follow-up, quantification of substantial release in retinal traction was possible and correlated to conventional OCT findings.

[High-resolution optical coherence tomography to evaluate vitreomacular traction before and after membrane peeling]. / Untersuchung vitreomakulärer Traktionen vor und nach Membranpeeling mittels hochauflösendem Raster-OCT.

AIM: Morphological assessment of the vitreomacular interface and intraretinal architecture using three-dimensional high-resolution optical coherence tomography (HROCT) before and after surgical delamination of epiretinal membranes and the internal limiting membrane (ILM). METHOD: The extent and intensity of traction of the epiretinal membrane (ERM) and the morphology of the individual retinal layers were investigated preoperatively in 14 eyes of 14 patients using three-dimensional HROCT (Cirrus prototype, scanned area 6x6 mm, depth 2 mm). In addition, visual acuity and ophthalmological findings (including stratus OCT) were documented. Standardized follow-up examinations were performed prospectively adhering to a protocol on days 1, 4, and 7 as well as 1 and 3 months after surgery. RESULTS: The ERM adhered closely to the retina in 85% of cases, but in 100% it was still clearly distinguishable from the retinal surface as a separate structure when using HROCT. Vertical traction through the ERM to the deepest retinal layers could be shown on HROCT in 93% of the cases. Structural alterations of the retina were not detectable either directly after surgery or subsequently. After an average of 4 weeks, the architecture of the layers was reorganized with complete regression of the preoperative tractional aberrations. The mean preoperative Snellen visual acuity of 0.4+/-0.2 increased to an average of 0.5+/-0.2. The mean preoperative retinal thickness was 482+/-84 microm and after 3 months 328+/-80 microm (HROCT). CONCLUSIONS: Examination with high-resolution optical coherence tomography allows three-dimensional visualization of the dynamics of epiretinal tractions that had not previously been obtainable. Epiretinal membranes can be clearly distinguished and their tractional effects can be traced through all retinal layers up to the pigment epithelium. As a result of the postoperative elimination of the tractions, the morphological alterations of the individual retinal layers recede already after 1 month.

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 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 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.

Value of polarisation-sensitive optical coherence tomography in diseases affecting the retinal pigment epithelium.

OBJECTIVES: To evaluate pathological changes of retinal pigment epithelium (RPE) by polarisation-sensitive optical coherence tomography (PS-OCT). METHODS: Forty-four eyes (22 patients) with significant pathologies of the RPE were evaluated using PS-OCT. A transversal scanning time domain OCT system was used for two-dimensional cross-sectional imaging of retinal polarisation properties. RESULTS: The RPE scrambles the polarisation state of backscattered light (ie, acts as a depolarising layer), while the polarisation state of transmitted light is maintained. In patients with RPE pathologies irregularity, elevation, thickening or absence of the RPE is readily visualised by exploiting the depolarisation information. Polarisation scrambling in the sensory retina can be found in cases with advanced dry age-related macular degeneration. Sclera and fibrosis show characteristic birefringence in PS-OCT. CONCLUSION: PS-OCT allows tissue identification based on polarisation scrambling and birefringence, providing additional information on RPE pathologies. It is a promising new tool for diagnosis, disease follow-up and evaluation of new treatment strategies.

Automatic segmentation in three-dimensional analysis of fibrovascular pigmentepithelial detachment using high-definition optical coherence tomography.

BACKGROUND/AIMS: A limited number of scans compromise conventional optical coherence tomography (OCT) to track chorioretinal disease in its full extension. Failures in edge-detection algorithms falsify the results of retinal mapping even further. High-definition-OCT (HD-OCT) is based on raster scanning and was used to visualise the localisation and volume of intra- and sub-pigment-epithelial (RPE) changes in fibrovascular pigment epithelial detachments (fPED). Two different scanning patterns were evaluated. METHODS: 22 eyes with fPED were imaged using a frequency-domain, high-speed prototype of the Cirrus HD-OCT. The axial resolution was 6 mum, and the scanning speed was 25 kA scans/s. Two different scanning patterns covering an area of 6 x 6 mm in the macular retina were compared. Three-dimensional topographic reconstructions and volume calculations were performed using MATLAB-based automatic segmentation software. RESULTS: Detailed information about layer-specific distribution of fluid accumulation and volumetric measurements can be obtained for retinal- and sub-RPE volumes. Both raster scans show a high correlation (p<0.01; R2>0.89) of measured values, that is PED volume/area, retinal volume and mean retinal thickness. Quality control of the automatic segmentation revealed reasonable results in over 90% of the examinations. CONCLUSION: Automatic segmentation allows for detailed quantitative and topographic analysis of the RPE and the overlying retina. In fPED, the 128 x 512 scanning-pattern shows mild advantages when compared with the 256 x 256 scan. Together with the ability for automatic segmentation, HD-OCT clearly improves the clinical monitoring of chorioretinal disease by adding relevant new parameters. HD-OCT is likely capable of enhancing the understanding of pathophysiology and benefits of treatment for current anti-CNV strategies in future.

[New perspectives in diagnostic. High-resolution optical coherence tomography for age-related macular degeneration]. / Neue Perspektiven in der Diagnostik. Hochauflösende optische Kohärenztomographie bei altersbedingter Makuladegeneration.

BACKGROUND: Recent advances in optical coherence tomography (OCT) have made it possible to increase resolution and scan velocities so that even greater central areas of the retina can be scanned. The aim of this study is to describe the possibilities offered by this new technology for age-related macular degeneration. MATERIAL AND METHODS: The study included 20 patients with confirmed active choroidal neovascularization (CNV) as well as pigment epithelial detachment (PED). Three-dimensional imaging was performed with a high-definition raster scanning OCT system (HD-OCT) with an axial resolution of 6 microm and a scan velocity of up to 20,000 A-scans/s. The scanned area measured 6 x 6 mm with a depth of 2 mm. Two-dimensional imaging was carried out with a StratusOCT (Carl Zeiss Meditec). RESULTS: Comparison of the individual slices showed improved identification of intra- and subretinal structures with the HD-OCT. Demarcation of pathological changes in individual retinal layers is possible with the HD-OCT. Summation images permit accurate localization of a scan. Topographic and volumetric evaluations enable analysis of individual compartments in the entire scanned area and are suitable for monitoring treatment of CNV with anti-VEGF therapy. The raster method decreases the dependence on exploratory methods that have been necessary until now to generate retinal thickness maps. CONCLUSIONS: This report presents initial experience in using a raster scanning HD-OCT system in patients with neovascular age-related macular degeneration and describes new evaluation functions that aid in obtaining more precise assessment of treatment effect and its impact on the retinal ultrastructure. The results of this study clearly show that development of high-resolution OCT systems in conjunction with development of novel treatment options for exudative diseases offers promising perspectives.

[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.

[Early effects of systemic and intravitreal bevacizumab (avastin) therapy for neovascular age-related macular degeneration]. / Frühe Effekte nach systemischer und intravitrealer Bevacizumab (Avastin)-Therapie bei neovaskulärer altersbedingter Makuladegeneration.

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.