Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial.

BACKGROUND: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. MATERIALS AND METHODS: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. RESULTS: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. CONCLUSIONS: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.

[Precision pulse capsulotomy : The new capsulorhexis?] / Präzisionspulskapsulotomie : Die neue Kapsulorhexis?

The manual capsulorhexis created by Neuhann is still the standard procedure for opening the anterior capsule for cataract surgery. A limitation is the inaccuracy in the size and placement of the opening due to manual execution. In addition to the femtosecond laser a possible improvement in the standardization of capsulorhexis is provided by the Zepto procedure (precision pulse capsulotomy, PPC). In this case a 5.25 mm rhexis is created in a standardized fashion with a flexible suction adapter in which a nitinol ring is located. Whether the strength of PPC is comparable or better than that of the manual technique and how it behaves in terms of capsule shrinkage has not yet been finally clarified.

Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer.

Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.

Economic burden of clinical trials in lung cancer in a German Comprehensive Cancer Center.

OBJECTIVES: The recent success of individualized lung cancer therapy has triggered fundamental changes in clinical research strategies. To date there is a strong focus on early proof of concept trials in genetically preselected small patient subgroups. This analysis focuses on the economic burden caused by such trials for advanced lung cancer patients in a German Comprehensive Cancer Center (CCC). METHODS: The profit margins between recruiting groups with ≤3 and >3 patients were compared. Clinical and economic data from clinical trials for advanced lung cancer (LC), pharma-sponsored trials (PhST) as well as investigator initiated trials (IIT), conducted between 2011 and 2015 at the Center for Integrated Oncology (CIO) Cologne, were analyzed using a profit-center calculation model. RESULTS: 161 patients were enrolled in 27 clinical trials. The key economic parameter determining costs and payments was the 'trial visits'. In comparison of the two groups (A≤3; B>3 patients enrolled) we found negative profit margins for the low recruiting group (€ -1444). Concerning the number of visits significant differences were found between PhST and IIT (p=0.009). Additionally, sub-analysis show structural differences in cost composition by conducting PhST and IIT. CONCLUSION: Trials with low patient numbers and IIT, do not cover the cost. To ensure adequate, cost-covering compensation by pharmaceutical companies CCCs have to thoroughly calculate the cost of early proof of concept trials. The findings of this study also underline the need for novel structures in public funding for investigator-initiated clinical trials in precision medicine.

[Switching Therapy from Ranibizumab and/or Bevacizumab to Aflibercept in Neovascular Age-Related Macular Degeneration (AMD): One-Year Results]. / Das klinische Ergebnis eines Therapiewechsels von Ranibizumab und/oder Bevacizumab zu Aflibercept bei neovaskulärer altersabhängiger Makuladegeneration (AMD).

BACKGROUND: The presented study is a retrospective evaluation of switching therapy from ranibizumab and/or bevacizumab to aflibercept in neovascular age-related macular degeneration in patients who had previously given an insufficient response to therapy with ranibizumab and/or bevacizumab. PATIENTS AND METHODS: 96 eyes with neovascular age-related macular degeneration (AMD) were included, which had been pretreated with ranibizumab and/or bevacizumab (T&E), but had responded insufficiently. An injection interval of less than six weeks or permanently persisting intra- and/or subretinal fluid or persistent pigment epithelial detachments (PED) were defined as an insufficient response. The patients were followed for 12 months after switching therapy to aflibercept. The change in central retinal thickness (CRT) was defined as the primary endpoint. Other endpoints were the axial height of PEDs and the injection interval. RESULTS: The primary endpoint, the average CRT, was significantly decreased twelve months after switching therapy to aflibercept (Wilcoxon Nemenyi-McDonald-Thompson post-hoc analysis - 31.36 µm; SD ± 70.64 µm; p < 0.001). Another morphological endpoint, the average axial height of PEDs, also decreased significantly (- 34.10 µm; SD ± 91.90 µm, p < 0.001) from 207.82 µm (SD ± 148.12 µm) at baseline to 173.72 µm (SD ± 132.30 µm) at month 12. Moreover, the average injection interval increased significantly (p < 0.001; Friedman test) from 1.30 months (SD ± 0.19 months) before switching therapy to 1.67 months (SD ± 0.19 months) at month 12 after switching therapy to aflibercept. However, the best corrected visual acuity (BCVA) as a functional endpoint did not significantly improve (+ 0.36 ETDRS letters = 0.0972 p; SD ± 16.94 ETDRS letters). CONCLUSION: In patients with neovascular AMD, who had initially exhibited an inadequate response to ranibizumab and/or bevacizumab, switching therapy to aflibercept improves clinical outcome measures. Besides morphological improvements, such as the decrease of the CRT and the axial height of PEDs, the average injection interval was prolonged. However, visual acuity did not improve.

SS18-SSX fusion protein-induced Wnt/ß-catenin signaling is a therapeutic target in synovial sarcoma.

Synovial sarcoma is a high-grade soft tissue malignancy characterized by a specific reciprocal translocation t(X;18), which leads to the fusion of the SS18 (SYT) gene to one of three SSX genes (SSX1, SSX2 or SSX4). The resulting chimeric SS18-SSX protein is suggested to act as an oncogenic transcriptional regulator. Despite multimodal therapeutic approaches, metastatic disease is often lethal and the development of novel targeted therapeutic strategies is required. Several expression-profiling studies identified distinct gene expression signatures, implying a consistent role of Wnt/ß-catenin signaling in synovial sarcoma tumorigenesis. Here we investigate the functional and therapeutic relevance of Wnt/ß-catenin pathway activation in vitro and in vivo. Immunohistochemical analyses of nuclear ß-catenin and Wnt downstream targets revealed activation of canonical Wnt signaling in a significant subset of 30 primary synovial sarcoma specimens. Functional aspects of Wnt signaling including dependence of Tcf/ß-catenin complex activity on the SS18-SSX fusion proteins were analyzed. Efficient SS18-SSX-dependent activation of the Tcf/ß-catenin transcriptional complex was confirmed by TOPflash reporter luciferase assays and immunoblotting. In five human synovial sarcoma cell lines, inhibition of the Tcf/ß-catenin protein-protein interaction significantly blocked the canonical Wnt/ß-catenin signaling cascade, accompanied by the effective downregulation of Wnt targets (AXIN2, CDC25A, c-MYC, DKK1, CyclinD1 and Survivin) and the specific suppression of cell viability associated with the induction of apoptosis. In SYO-1 synovial sarcoma xenografts, administration of small molecule Tcf/ß-catenin complex inhibitors significantly reduced tumor growth, associated with diminished AXIN2 protein levels. In summary, SS18-SSX-induced Wnt/ß-catenin signaling appears to be of crucial biological importance in synovial sarcoma tumorigenesis and progression, representing a potential molecular target for the development of novel therapeutic strategies.

Intravitreal anti-VEGF therapy for retinal macroaneurysm.

BACKGROUND: We evaluated the effect of intravitreal anti-vascular endothelial growth factor therapy using bevacizumab or ranibizumab for retinal macroaneurysms with macular exudation. METHODS: In a retrospective interventional case series patients with retinal macroaneurysms were treated with either 1.25 mg intravitreal bevacizumab or 0.5 mg ranibizumab as first-line therapy. Patients were imaged by fluorescein angiography and optical coherence tomography. Retreatment was performed in case of persistent intraretinal or subretinal fluid in optical coherence tomography. RESULTS: Ten patients (10 eyes) with macroaneurysm involving the macula were treated with an average of 3.0 intravitreal anti-vascular endothelial growth factor injections. Mean best corrected visual acuity of all patients improved by 17 letters from baseline to the last follow-up visit. In 7 out of 10 patients, the fovea was affected by a secondary edema. In cases with foveal involvement, central retinal thickness decreased from 366 µm at baseline to 266 µm at the last follow-up visit. In the course of treatment 8 out of 10 patients showed evidence of marked regression of macular exsudation. CONCLUSION: Intravitreal anti-vascular endothelial growth factor therapy appears to be a promising treatment alternative to laser treatment in cases of retinal macroaneurysms with macular exudation.

Extra short dental implants supporting an overdenture in the edentulous maxilla: a proof of concept.

OBJECTIVES: This study investigates the outcome of short implants additionally placed with longer implants to support a maxillary overdenture. MATERIALS AND METHODS: Twelve patients received six implants to support a maxillary overdenture. Only one patient still had two molars in the maxilla, while the others had no remaining teeth. The status of the opposing arch was diverse. The distal implant in each quadrant was 6 mm in height (S) and the middle implants ranged between 10 and 14 mm (L). All implants were placed following a one-stage procedure and early loaded (6 weeks). Clinical and radiological parameters were assessed 6, 12 and 24 months after loading. RESULTS: One short implant failed 2 weeks after surgery, probably due to early mobilization by the provisional prosthesis. The mean bone loss on the rough part of the implant was 0.7 mm (S) vs. 1.3 mm (L) during the first year and 0.3 mm (S) vs. 0.2 mm (L) during the second year after loading. The mean implant stability quotient values were 67 (S) vs. 70 (L) at placement and 75 (S) vs. 78 (L) after 1 year. At the 2-year follow- up, all prostheses were still stable and comfortable. CONCLUSION: An overdenture on six implants, of which two have a reduced length, might represent a successful treatment option. No significant difference could be found between both implant lengths at 2 years' follow-up. However, bone loss with short implants may increase the likelihood of failure.

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.

Management of extensive subfoveal haemorrhage secondary to neovascular age-related macular degeneration.

BACKGROUND: To evaluate the clinical outcomes of subfoveal haemorrhages secondary to neovascular age-related macular degeneration (AMD), which were treated with intravitreal recombinant tissue plasminogen activator (rTPA)/gas and anti-vascular endothelial growth factor (anti-VEGF) drug or with an intravitreal anti-VEGF monotherapy. METHODS: This is a retrospective pilot study. Patients who received intravitreal rTPA/gas and anti-VEGF injections (n=20, bevacizumab or ranibizumab) were included in group A. Patients who refused prone positioning after rTPA/gas injections and were treated with an anti-VEGF monotherapy (bevacizumab) alone were included into group B (n=10). Changes in baseline visual acuity (VA, Snellen), central retinal thickness (CRT) and haemorrhage size were analysed. RESULTS: Mean baseline VA was 0.15+/-0.2 and 0.25+/-0.17 in groups A and B, respectively. At month 4, significant improvement in mean VA was observed in group A (mean difference: +0.1+/-0.14; P=0.003), and a stabilization in group B (mean difference: +0.008+/-0.2; P=0.94). CRT decreased significantly by 70 microm in group A (P=0.001) and by 84 microm in group B (P=0.03). The mean size of subfoveal haemorrhage in groups A and B was 20.2 mm(2) and 19.1 mm(2) at baseline and 0.0 mm(2) and 2.0 mm(2) at month 4, respectively. The anti-VEGF treatment rate was 1.6 in group A and 3.0 in group B. CONCLUSION: In patients with extensive subfoveal haemorrhage secondary to neovascular AMD, the combination therapy of rTPA/pneumatic displacement and anti-VEGF results in mean improvement of VA and stabilization of morphological parameters. If rTPA and pneumatic displacement combination is contraindicated, an anti-VEGF monotherapy may be performed to prevent further visual loss.

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.

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.

[Intravitreal anti-VEGF therapy for capillary hemangioblastomas in von Hippel-Lindau disease]. / Intravitreale anti-VEGF-Therapie von retinalen kapillären Hämangioblastomen bei von-Hippel-Lindau-Erkrankung.

BACKGROUND: Up-regulated expression of the vascular endothelial growth factor (VEGF) in von Hippel-Lindau (VHL) disease has been postulated to induce retinal hemangioblastoma. Intravitreal injections of anti-VEGF drugs might provide a new therapeutic option in this condition. METHODS: In a single case decision a patient with active retinal hemangioblastomas due to VHL disease received repeated intravitreal injections of 0.5 mg ranibizumab. RESULTS: Subsequent to intravitreal anti-VEGF therapy, the signs of activity of the retinal hemangioblastomas slowly regressed. CONCLUSIONS: Intravitreal anti-VEGF therapy might, as monotherapy or as combination therapy, offer a new treatment option for retinal hemangioblastoma.

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.

[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.

Anecortave acetate for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: Anecortave acetate is a novel angiostatic cortisene being evaluated clinically for treatment of exudative age-related macular degeneration (ARMD). A randomized, placebo-controlled, efficacy and safety dose duration study of anecortave acetate for depot suspension (3 mg, 15 mg, 30 mg) in this patient population was completed in June 2003. As part of this trial, 128 patients with subfoveal choroidal neovascularization (CNV) secondary to ARMD were enrolled and treated for up to 2 years by 18 clinical sites in the United States and European Union. METHODS: Study patients were evaluated clinically with detailed ophthalmic examinations, general physical examinations, assessments of best-corrected logMAR visual acuity, and angiographic evaluations. The Digital Angiography Reading Center (New York City, NY) assessed lesion eligibility while the clinical investigators assessed overall patient eligibility prior to treatment. As part of this study, study medication was delivered as a posterior juxtascleral depot using a specially designed curved cannula at 6-month intervals if in the masked investigator's opinion the patient's lesion could benefit from additional treatment. RESULTS: The 2-year efficacy results of this placebo-controlled study demonstrated that RETAANE 15 mg (anecortave acetate for depot suspension) was statistically superior to placebo for stabilization of vision (<3 logMAR line change from baseline) and for inhibition of neovascular lesion growth. There were no serious treatment-related safety issues associated with either the study medication or the procedure for administration. CONCLUSIONS: Anecortave acetate 15 mg for depot suspension is clinically efficacious compared to placebo for treatment of subfoveal exudative ARMD lesions when administered at 6-month intervals as a posterior juxtascleral depot.

[Treatment of neovascular age-related macular degeneration with Ranibizumab/Lucentis]. / Therapie der neovaskulären altersbedingten Makuladegeneration mit Ranibizumab/Lucentis.

Vascular endothelial growth factor (VEGF) is considered to play an essential role in the pathogenesis of age-related macular degeneration due to its vascular permeability-inducing and angiogenic properties. Ranibizumab, a small antibody fragment designed to competitively bind all VEGF isoforms, passes after intravitreal injection all retinal layers reaching the retinal pigment epithelium-choroid complex. Experimental animal models showed the drug to be safe and effective. Subsequently, Phase I/II clinical trials conducted in patients with neovascular AMD demonstrated a good safety profile, and a significant functional benefit. Ranibizumab therapy repeated every four weeks for the treatment of neovascular AMD is currently in Phase III clinical trials. Combination therapy trials aiming for improved treatment durability and effectiveness are currently ongoing as well as new treatment strategies using intermittent, optical coherence tomography (OCT) guided therapy. Anti-VEGF therapy using Ranibizumab is a promising new treatment option for neovascular AMD.

[Expression of angiogenic factors by photodynamic therapy]. / Expression angiogener Faktoren durch photodynamische Therapie.

PURPOSE: The purpose of this study was to evaluate the impact of photodynamic therapy (PDT) on the regulation of angiogenic factors such as vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in human eyes. METHODS: Eyes of patients with untreatable malignancy served as the study eyes (n = 2), age-matched donor eyes were used as controls (n = 2). Standard Verteporfin-PDT was applied to intact areas of the posterior pole. One week after PDT the eyes were examined by ophthalmoscopy as well as fluorescein (FA) and indocyanine green angiography (ICGA). After enucleation the eyes were processed for LM/EM histology. Immunolabeling using specific antibodies against VEGF and PEDF was performed in PDT-treated areas, untreated collateral areas of study eyes and untreated areas of control eyes. RESULTS: All PDT-treated areas demonstrated a typical choroidal hypofluorescence on FA/ICGA. In LM/EM histology a selective damage of choriocapillary endothelial cells was found. VEGF expression was localized only to choriocapillary endothelial cells and focally in larger choroidal vessels of PDT-treated areas. Untreated areas of study eyes and controls were VEGF-negative. PEDF staining was observed in retinas and RPE of all eyes, but only choroidal endothelial cells of PDT-treated areas showed a PEDF-positive reactivity. CONCLUSION: PDT not only induces structural and angiographic, but also biological effects in human eyes. VEGF and PEDF expression can be documented in choroidal endothelial cells following PDT and could have an impact on the recovery process after treatment.