Macular pigment density at the site of altered fundus autofluorescence

Background: The purpose of our study was to determine whether abnormalities of increased or decreased fundus autofluorescence (FAF) are associated with local changes in macular pigment (MP) optical density in patients with age-related maculopathy (ARM) and macular degeneration (ARMD). Methods: FAF imaging and MP measurement was performed through dilated pupils using a modified confocal scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Germany) according to a standard protocol. Two-wavelength autofluorescence method was employed for determination of local macular pigment optical density (LMPOD). Image analysis and measurement of LMPOD at the area of altered FAF was performed using Heidelberg Eye Explorer Software. Mean values of LMPOD at the site of FAF abnormality were compared to an adjacent location with normal background FAF of the same image. Results: Sixty-three eyes of 63 patients (28 male, 35 female, mean age 75.8 ± 8.8years) were included in this analysis. Group 1 comprised 31 cases with focal increased FAF. Mean LMPOD in the area of increased FAF was 0.073 ± 0.083 compared to 0.075 ± 0.074 in the adjacent area of normal FAF. Group 2 comprised 32 cases of focal decreased FAF. Mean LMPOD in the area of decreased FAF was -0.004 ± 0.088 compared 0.053 ± 0.075 in the adjacent area of normal FAF. The site of increased FAF showed no significant difference in LMPOD (p = 0.927) compared to adjacent areas of normal FAF, while areas of decreased FAF revealed significantly lower LMPOD (p = 0.001) compared to adjacent areas of normal FAF. Conclusions: Focal increases of FAF due to ARM or ARMD did not lead to change in LMPOD. Presumably, retinal layers containing MP are unaffected by these processes. For lesions exhibiting focal decreased FAF, a reduction of LMPOD cannot be excluded. Further studies are needed to investigate MP in the course of diseas

Multimodal imaging in macular diagnostics: combined OCT-SLO improves therapeutical monitoring

Background: Digital imaging methods are a centrepiece for diagnosis and management of macular disease. A recently developed imaging device is composed of simultaneous confocal scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT). By means of clinical samples the benefit of this technique concerning diagnostic and therapeutic follow-up will be assessed. Methods: The combined OCT-SLO-System (Ophthalmic Technologies Inc., Toronto, Canada) allows for confocal en-face fundus imaging and high resolution OCT scanning at the same time. OCT images are obtained from transversal line scans. One light source and the identical scanning rate yield a pixel-to-pixel correspondence of images. Three-dimensional thickness maps are derived from C-scan stacking. Results: We followed-up patients with cystoid macular edema, pigment epithelium detachment, macular hole, venous branch occlusion, and vitreoretinal tractions during their course of therapy. The new imaging method illustrates the reduction of cystoid volume, e.g. after intravitreal injections of either angiostatic drugs or steroids. C-scans are used for appreciation of lesion diameters, visualisation of pathologies involving the vitreoretinal interface, and quantification of retinal thickness change. Conclusion: The combined OCT-SLO system creates both topographic and tomographic images of the retina. New therapeutic options can be followed-up closely by observing changes in lesion thickness and cyst volumes. For clinical use further studies are neede

Quantitative assessment of the long-term effect of photodynamic therapy in patients with pathologic myopia

Background: In patients with classic subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM), photodynamic therapy (PDT) has been shown to stabilize the visual acuity. We have analyzed the long-term visual prognosis after PDT in patients with CNV secondary to PM. Methods: In a retrospective study we reviewed the clinical charts of 102 patients. PDT was performed following the procedures described in the VIP and TAP study protocols. Follow-up examinations and PDT treatment were scheduled in 3-month intervals. Indications for retreatment were an active leaking CNV in combination with visual disturbances or visual loss. To assess treatment effects we analyzed the number of letters read on the ETDRS charts. The primary efficacy outcome was the proportion of eyes that had fewer than eight letters loss or gain at 24 months. Secondary efficacy outcomes included the proportion of eyes that had fewer than 15 letters loss or gain and the proportion of eyes that had fewer than 30 letters loss or gain at month 24. Results: One hundred and two patients were included into the study. Mean follow-up was 32.5±5.7 months. Patients received an average of 2.2 treatments from study entry through the last follow-up, resulting in a total of 221 PDT sessions throughout the study. At 24 months 46% lost at least eight letters. A loss of at least 15 (30) letters was observed in 25% (8%). Improvement of at least eight letters was noted in 8%. Larger improvements of at least 15 letters occurred only in 4% of study eyes. Conclusion: Our study suggests that PDT can increase the chance of stabilizing or improving vision compared with the placebo arm of VIP tria

Caspase-3-independent photoreceptor degeneration by N-methyl-N-nitrosourea (MNU) induces morphological and functional changes in the mouse retina

Background: Retinal degeneration is followed by significant changes in the structure and function of photoreceptors in humans and several genetic animal models. However, it is not clear whether similar changes occur when the degeneration is induced pharmacologically. Therefore, our aim was to investigate the influence of retinotoxic N-methyl-N-nitrosourea (MNU) on the function, morphology and underlying molecular pathways of programmed cell death. Methods: C57/BL6 mice were injected with different doses of MNU, and function was determined by analysing optokinetic reflex measurements and cued water maze results at several time points post-injection. Morphometric measurements were also taken from H&E-stained paraffin eye sections. TUNEL-positive cells and caspase-3 and -6 were detected by immunohistochemistry. To assess the molecular changes leading to cell death, qRT-PCR from neurosensory retina mRNA was performed. Results: The application of MNU led to an instant decrease in function and a delayed decrease in the thickness of the retinal outer nuclear layer. These responses were observed in the absence of any structural changes in the retinal pigment epithelium. The degeneration of the photoreceptor cell layer was highest with 60mg/kg MNU. The assessment of TUNEL-positive cells visualised cell death after treatment, but no detectable caspase-3 activity was observed concomitant with these changes. qRT-PCR revealed the possible involvement of the inflammatory mediator caspase-1 and endoplasmic reticulum stress-mediated apoptosis by caspase-12. Conclusion: MNU leads to the dose-dependent degeneration of photoreceptor cells in mice by caspase-3-independent pathways and is, therefore, a suitable model to study retinal degeneration in an animal mode

Forstliche Genressourcen im Freistaat Sachsen: Erhaltung, Förderung und nachhaltige Nutzung

Die Broschüre beschreibt den erreichten Sachstand der forstlichen Generhaltung und zeigt die Wege auf, die in Zukunft im Freistaat Sachsen beschritten werden sollen. Die Veröffentlichung richtet sich an die Beschäftigten in der Forstwirtschaft, dem Naturschutz und den Umweltwissenschaften, an interessierte Bürgerinnen und Bürger sowie an Entscheidungsträger in Politik und Verwaltung. Redaktionsschluss: 30.06.202

Treatment of Exudative Age-Related Macular Degeneration with a Designed Ankyrin Repeat Protein that Binds Vascular Endothelial Growth Factor: a Phase I/II Study

PURPOSE: To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN: Phase I/II, open-label, multicenter, dose-escalation study. METHODS: Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS: Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for >= 4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS: A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. larger-scale studies are warranted to confirm these observations. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).PURPOSE: To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN: Phase I/II, open-label, multicenter, dose-escalation study. METHODS: Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS: Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for >= 4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS: A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. larger-scale studies are warranted to confirm these observations. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/)

VISUAL ACUITY OUTCOMES OF RANIBIZUMAB TREATMENT IN PATHOLOGIC MYOPIC EYES WITH MACULAR RETINOSCHISIS AND CHOROIDAL NEOVASCULARIZATION

PURPOSE To investigate visual and morphological outcome in eyes with MRS and choroidal neovascularization (CNV) secondary to pathologic myopia treated with intravitreal (IVT) ranibizumab. METHODS Post hoc analysis of the patients included in the RADIANCE trial (n = 277) was performed to evaluate the impact of MRS on the functional outcome in patients with myopic choroidal neovascularization (mCNV) undergoing intravitreal ranibizumab injections. RESULTS Prevalence of MRS in pathologic myopia population is 6%. Respective patients were generally older than patients without MRS. Study eyes with MRS at baseline (BL) showed an initially poor treatment response after 3 months (mean change in best corrected visual acuity (BCVA) was 2.8 ± 12.4 letters, P = 0.009). After 12 months of treatment however, the mean change in BCVA was 7.1 ± 14.5 early treatment diabetic retinopathy study (ETDRS) letters (P = 0.025). Patients with MRS at baseline received more intravitreal injections than the other RADIANCE patients without MRS (MRS, n = 15 eyes: 5.8 ± 2.1 vs. RADIANCE non-MRS [n = 207 eyes]: 4.0 ± 2.9; P = 0.0001). CONCLUSION Improvement of visual acuity is delayed and reduced after 3 months intravitreal ranibizumab in eyes with MRS and myopic choroidal neovascularization compared to eyes without MRS. More ranibizumab injections are needed in eyes with MRS to gain comparable BCVA at Month 12.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially