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Biomedical subjects

U Schmidt-Erfurth

Publications and source records attributed to U Schmidt-Erfurth.

At least 19 recordsLinked to original sources

[Early effects of systemic and intravitreal bevacizumab (avastin) therapy for neovascular age-related macular degeneration].

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.

Aged↗

Increased expression of vascular endothelial growth factor associated with accumulation of lipids in Bruch's membrane of LDL receptor knockout mice.

AIM: To investigate the pathogenesis of age related macular degeneration (ARM) with respect to lipid accumulation within Bruch's membrane (BrM) in a knockout model with low density lipoprotein (LDL) receptor deficiency. METHODS: LDL receptor deficient mice and C57BL/6 controls were fed a standard diet or a high fat (HF) diet. Plasma total cholesterol (pTC) was determined. Eyes were examined by transmission electron microscopy. Immunohistochemical staining for VEGF was performed. RESULTS: pTC were highest in LDL receptor deficient mice after HF diet and elevated after standard diet compared to controls with and without HF diet. While BrM of controls did not exhibit any visible changes, membrane bound translucent particles were seen in all BrM of knockout mice. The amount of these particles was substantially increased and membranes were thickened after HF diet. VEGF staining was positive in knockout mice only and was located in retinal pigment epithelial cells, the outer plexiform layer, and photoreceptor inner segments. Most intensive VEGF expression was documented after HF diet. CONCLUSION: LDL receptor deficient mice exhibit an accumulation of lipid particles in BrM which is further increased after fat intake. VEGF expression is found in the outer retinal layers of LDL receptor deficient mice and appears to correlate with the amount of lipid particles present in BrM.

Animals↗

[Photodynamic therapy for choroidal hemangioma. Long-term results].

AIM: Evaluation of functional and anatomical long-term results of patients with symptomatic choroidal hemangioma treated with photodynamic therapy (PDT). PATIENTS AND METHODS: All 8 patients suffered from progressive loss of vision caused by exudation into the macular area. PDT with a verteporfin dose of 6 mg/m(2) body surface area and a light dose of 100 J/cm(2) at 692 nm was carried out. Two to four treatments were applied at 6 week intervals using a single laser spot. Standardized evaluation was used before and at 6-week intervals after each treatment and at 3, 6 and 12 months. In the further follow-up control intervals were extended up to 1 year in the case of stable anatomical and functional results. RESULTS: All patients showed complete regression of the tumor. The tumor height was reduced from an average of 3.64 mm to undetectable. One patient showed a stable visual acuity, seven patients a significant increase. Central scotometry showed withdrawal of scotomas from the macula. No patient showed any sign of recurrence during the follow-up of up to 60 months. CONCLUSION: The long-term results of patients with active choroidal hemangioma demonstrate that PDT is a most effective and safe treatment option. Complete tumor regression is combined with good functional recovery.

Adult↗

[Accumulation of lipid particles in Bruch's membrane of LDL receptor knockout mice as a model of age-related macular degeneration].

BACKGROUND: Atherosclerosis is a suspected risk factor for the development of neovascular age-related macular degeneration (AMD). METHODS: We used a well-established murine knockout model with low-density lipoprotein (LDL) receptor deficiency for atherosclerotic vascular pathogenesis to evaluate changes in Bruch's membrane due to high cholesterol levels. Blood cholesterol levels were modified by the diet fed (standard rodent diet or high-fat diet western type). Animals were sacrificed and plasma cholesterol levels were determined. Eyes were examined by transmission electron microscopy (TEM). RESULTS: Plasma total cholesterol levels were highest in LDL receptor-deficient mice after high-fat diet and elevated in LDL receptor-deficient mice after standard diet compared to control mice with and without special high-fat diet. While Bruch's membranes of control animals did not exhibit any visible changes by TEM even after a high-fat diet, membrane-bound translucent particles were seen in all membranes in knockout mice. The amount of these particles was substantially increased and membranes were thickened in knockout animals following high-fat diet with additional deposits of non-membrane-bound particles. CONCLUSION: LDL receptor-deficient mice exhibited a degeneration of Bruch's membrane with accumulation of lipid particles, which is further increased after fat intake due to elevated blood lipid levels. In our opinion, this animal model is suitable for investigating more aspects in the pathogenesis of neovascular AMD.

Animals↗

[Three-dimensional imaging of photodynamic effects and spontaneous course in choroidal neovascularization].

PURPOSE: Photodynamic therapy (PDT) induces occlusive and regenerative effects in choroidal neovascularization (CNV) and physiological choroid. The process of vascular alteration is documented quantitatively and qualitatively by three-dimensional angiography. METHOD: In a prospective, randomized trial 30 patients with subfoveal CNV due to age-related macular degeneration (AMD) were treated with PDT or placebo. Fluorescence series with 32 tomographic images over a 4-mm depth were analyzed topographically and reproduced in a three-dimensional display. RESULTS: At initial presentation CNV lesions were documented as a well-defined prominence in all patients. In the verteporfin group CNV height continuously decreased with each interval. In the placebo group CNV slightly increased in height during the first 6 months and remained stable at about 90% of the initial prominence at long-term follow-up. After 12 months 44% of the patients in the verteporfin group developed an additional choroidal defect. CONCLUSION: Three-dimensional angiography offers a reliable documentation of CNV progression and regression during PDT. A decrease in CNV size is associated with an increase in choroidal perfusion defects.

Choroidal Neovascularization↗

[Expression of angiogenic factors by photodynamic therapy].

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.

Capillaries↗

[Chorioretinal anastomosis as unfavourable prognostic factor during photodynamic therapy].

BACKGROUND: The aim of this study was the documentation of chorioretinal anastomosis in neovascular age-related macular degeneration (AMD) and correlation with functional and angiographic results following photodynamic therapy (PDT). METHOD: A total of 100 patients presenting with neovascular AMD and indication for PDT based on the presence of predominantly classic choroidal neovascularization (CNV), underwent ophthalmoscopic and angiographic screening for chorioretinal anastomosis. Conventional PDT using verteporfin was performed according to the recommended standard procedure. The pre- and post-treatment status at 3 and 6 months post-PDT in all patients and at 1 week in selected patients was documented with respect to the central visual acuity test (ETDRS), ophthalmoscopy as well as fluorescein (FA) and indocyanine green angiography (ICGA). RESULTS: A primary chorioretinal anastomosis was found in 6% ( n=12) of all eyes with CNV and classic PDT indication. Mean visual loss within the first 6 months after therapy was 3 lines indicating lack of visual stabilization according to the PDT study criteria.Furthermore, an increase in visual acuity could not be documented in any case. Angiography demonstrated continuous progression of CNV size although PDT had been uneventful. The characteristic initial occlusion of the CNV with homogeneous hypofluorescence was absent angiographically at 1 week post-PDT. The anastomosis was detected by ICGA in all eyes and by ophthalmoscopy or optical coherence tomography (OCT) in most eyes. DISCUSSION: Chorioretinal anastomosis is not a rare finding associated with predominantly classic CNV. The presence of anastomosis appears to be an unfavourable prognostic factor during PDT. If a chorioretinal shunt is suspected evaluation by ICGA and/or OCT should be performed and the indication for PDT should be rediscussed.

Aged↗

[Photodynamic therapy: extended indication].

OBJECTIVE: Evaluation of efficacy of photodynamic therapy (PDT) for classic choroidal neovascularization (CNV) beyond the common indication. METHODS: A group of 256 patients was treated with photodynamic therapy from January to December 2000. Ten of these patients had a predominantly classic CNV due to angioid streaks (5), parafoveal telangiectasia (2), or chorioretinitis (3). In two patients an idiopathic origin of the CNV was presumed. Another 21 patients showed a juxtafoveal classic membrane (12) or a recurrence after laser photocoagulation (9). Visual acuity was evaluated, also in correlation to age and CNV size. Continuous follow-up of CNV and leakage size was performed with fluorescein angiography. RESULTS: Overall 85% of the patients showed visual stabilization or improvement during an average observation period of 10.5 months. A correlation was found between age and visual improvement favoring younger patients; however, no correlation was found between visual improvement and CNV size. CNV and leakage size decreased moderately over the 9-month follow-up from 1.81/3.45 mm(2) to 1.61/2.60 mm(2). CONCLUSION: PDT shows efficacy for classic choroidal neovascularization beyond the common indication.

Choroidal Neovascularization↗

Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma.

AIM: To investigate the safety and efficacy of photodynamic therapy with verteporfin in patients with choroidal haemangioma. METHODS: A non-randomised, prospective clinical investigation of 19 patients with symptomatic circumscribed choroidal haemangioma was performed. Unsuccessful pretreatment (external beam irradiation, laser photocoagulation) was performed in four patients. Patients were included when (1) subretinal exudation involving the fovea, (2) a decrease in visual function, and (3) additional symptoms (for example, metamorphopsia) were present. Photodynamic therapy (PDT) was performed with verteporfin at a concentration of 6 mg/m(2) body surface area and a light dose of 100 J/cm(2) at 692 nm. RESULTS: The mean follow up time was 10.6 months (2-24 months). The mean number of treatment sessions was 2.15 (range 1-5). Visual acuity improved by at least one line in 73.3%, by at least two lines in 42.1%, was stable in 21.1%, and decreased by one line in 5.2% of the patients. Exudation was completely resolved in 94.8% of the cases. Regression of tumour height was documented in all 19 tumours. Patients receiving any pretreatment before PDT, a visual acuity of 0.1 and less, a history of more than 30 months, and no significant response after the first PDT session, did not show any significant improvement. Cox regression analysis revealed that the number of PDT treatment sessions was inversely associated with the improvement in visual acuity of at least two lines. No recurrences and no local or systemic side effects were observed during the follow up time. CONCLUSION: PDT using verteporfin is a safe and effective therapy for the treatment of symptomatic choroidal haemangioma even in tumours located beneath the fovea.

Adult↗

[Photodynamic therapy of subfoveal choroid neovascularization. Analysis of fixation behavior].

BACKGROUND: In a prospective, randomized, placebo-controlled clinical trial, we have analyzed the pattern of fixation in patients with subfoveal choroidal neovascularization in age-related maculopathy, who have been treated with photodynamic therapy (Verteporfin). MATERIALS AND METHODS: The patients in this study were participating in the TAP trial at a study center (Lübeck). The TAP study inclusion criteria have been applied and photodynamic therapy was carried out by the TAP study standard protocol. For microperimetric analysis we used the Scanning Laser Ophthalmoscope 101 (Rodenstock). Fixation was classified into foveal and excentric fixation. In addition we quantified the area of fixation (mm2). All patients had a follow-up of 2 years. RESULTS: Out of 33 patients in the Verteporfin group, 29 showed central fixation at baseline and only 11 out of 33 had foveal fixation after 24 months. The area of fixation in this group was measured at baseline at 0.44 mm2, at 1.76 mm2 after 6 months and at 2.4 mm2 after 12, 18 and 24 months, respectively. In the placebo group 11 out of 13 patients had foveal fixation at baseline and after 24 months 2 out of 13 demonstrated central fixation. The area of fixation increased from 0.76 mm2 at baseline up to 2.4 mm2 after 6 months, to 4.9 mm2 after 12 months, to 7.1 mm2 after 18 months and finally after 24 months up to 9.61 mm2. CONCLUSIONS: Photodynamic therapy with Verteporfin does not prevent loss of central fixation in patients with subfoveal choroidal neovascularization in age-related maculopathy, however PDT has a significant stabilizing effect on the development of the area of fixation.

Aged↗

[Macular holes. A treatable disease picture with unsolved problems].

Macular holes have a special position in the paradigmatic change of vitreoretinal surgery during the past 10 years. While the rationale for existence of retinal and vitreal surgery is based largely on invasive mechanical intervention in cases of large-surface epiretinal tractions, e.g., in diabetic traction amotio or detached retina with PVR, the intention of surgical treatment for macular holes is to employ a minimally invasive method, using less direct mechanical manipulation and taking into consideration physical and cell biological aspects to induce local repair processes. Whereas the classification according to Gass is still completely based on the perspective of epiretinal traction via retracted vitreal material, newer theories, relying on more subtle diagnostic examination techniques, assume a complex interaction of tractive and proliferative effects.

Epiretinal Membrane↗

[Changes in neovascular membranes and normal choroid blood vessels after multiple photodynamic therapy treatments].

PURPOSE: ICG angiography (ICGA) was used to document the effect of repeated PDT (verteporfin) on size and leakage of choroidal neovascularisation in age-related macular degeneration (AMD) and treatment-related side effects on the choroid. METHODS: Forty-two patients were followed over 24 months in a clinical trial for PDT in AMD. The ICGAs were performed every 3 months with a confocal laser scanning system. Patients received repeated verteporfin treatment. At each control visit, the patients were retreated if leakage was present in fluorescein angiography (FA). RESULTS: A continuous, highly significant reduction in CNV size and leakage area was found over 24 months. The initial CNV size dropped by 23% from 3.86 mm2 to 2.98 mm2. The leakage area in the late phase of the angiogram decreased by 30.3% from 5.0 mm2 to 3.5 mm2. A significant side effect of PDT on the choroid was documented by an increased hypofluorescent area in ICGA. The maximum size of the hypofluorescent area was reached after 12 months. At month 24, the choroidal fluorescence showed recovery in respect to area and intensity of fluorescence. But hypofluorescence surrounding the CNV lesion was already present in 40 out of 42 eyes before treatment. CONCLUSION: The ICGA confirms that repeated PDT treatments lead to a significant reduction in CNV size and leakage area over as long as 2 years. CNV lesions are surrounded by choriocapillary hypofluorescence in ICGA. PDT causes further hypoperfusion of the choroid but in the long-term significant recovery of choroidal perfusion was shown.

Capillary Permeability↗

[Spontaneous course of classical, subfoveal choroid neovascularization in age-related macular degeneration].

In a prospective, double-blind study, 19 patients with a classical subfoveal choroidal neovascularisation due to AMD were followed-up over a period of 2 years. Every 3 months a standardised visual acuity test, a contrast sensitivity test and fluorescein-angiography were performed. Overall, visual acuity dropped from 20/125 initially down to 20/250 after 2 years. Contrast sensitivity decreased from 23 down to 19 recognised letters. The functionally superior group 1 (n = 7) with a visual acuity of 20/65 at baseline, improved up to 20/50 after 2 years, while group 2 (n = 12) with a baseline visual acuity of 20/125 showed a decrease down to 20/400 after 24 months. Contrast sensitivity stabilised or improved in 10 patients from 22 to 25 letters, while in 9 patients the score dropped from 23 down to 8 recognised letters. The results underline the unfavourable functional prognosis of classical subfoveal lesions in AMD. However, stabilisation is possible depending on baseline visual acuity which is critical whenever results of nonplacebo-controlled studies have to be assessed. Moreover these results suggest that the urgency of a therapeutical intervention might be overestimated. As treatment, a fairly gentle, primarily atraumatic, CNV-selective strategy should be chosen, so that the self-limiting potential of this disease can be utilised in addition to the therapeutic effect.

Aged↗

Photodynamic therapy with verteporfin: a new treatment in ophthalmology.

Photodynamic therapy (PDT) with verteporfin is a new treatment modality in ophthalmology that has previously shown its effectiveness in treatment of a variety of neoplastic pathologies. In this therapeutic approach, the photosensitizer verteporfin is activated by non-thermal laser light to obtain closure of neovascular structures. Preclinical and clinical studies have indicated that PDT is a safe, selective, and effective treatment for choroidal neovascularization in age-related macular degeneration. No significant damage to the neurosensory retina was found, which explains why PDT does not cause loss of visual acuity and may be used in a larger population than laser photocoagulation. This review summarizes the mechanisms of action of PDT, and the results of preclinical and clinical studies in ophthalmology.

Choroidal Neovascularization↗