[Show abstract][Hide abstract] ABSTRACT: Background/aims:
We examined the effect of human complement sera (HCS) on retinal pigment epithelial (RPE) cells with respect to pro-inflammatory mediators relevant in early age-related macular degeneration (AMD).
RPE cells were treated with complement-containing HCS or with heat-inactivated (HI) HCS or C7-deficient HCS as controls. Cells were analysed for C5b-9 using immunocytochemistry and flow cytometry. Interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) were quantified by ELISA and RT-PCR. Tumour necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), were analysed by Western blotting. The intracellular distribution of nuclear factor (NF)-x03BA;B was investigated by immunofluorescence.
A concentration-dependent increased staining for C5b-9 but no influence on cell viability was observed after HCS treatment. ELISA and RT-PCR analysis revealed elevated secretion and expression of IL-6, IL-8, and MCP-1. Western blot analysis showed a concentration-dependent increase in ICAM-1, VCAM-1, and TNF-α in response to HCS, and immunofluorescence staining revealed nuclear translocation of NF-x03BA;B.
This study suggests that complement stimulates NF-x03BA;B activation in RPE cells that might further create a pro-inflammatory environment. All these factors together may support early AMD development.
Ophthalmic Research 10/2015; 54(4):195-203. DOI:10.1159/000439596 · 1.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
We investigate the association between morphologic findings in optical coherence tomography angiography (OCTA) as a new method offering the visualization of deeper layers of retinal vasculature and fluorescein angiography (FA) and macular pigment imaging and in Type 2 macular telangiectasia.
Fourty-two eyes of 21 patients with macular telangiectasia (38-68 years, 14 female) were examined by FA and OCTA and 24 eyes additionally with dual-wavelength autofluorescence. Early and late FA, macular pigment density images, and (after segmentation of retinal vasculature into superficial and deep capillary network and outer) OCTA images were graded into standardized categories. Agreement between the methods was evaluated statistically.
In OCTA, a reduction of density of superficial capillaries, dilated vessels in the deep capillary network, anastomoses toward the superficial capillary network, and "new" vessels in the outer retina layers can be detected. The described anatomical features, especially in the deep capillary plexus and outer retina corresponded well with changes in FA. Classes of macular pigment distribution correlated most with classes of changes in OCTA superficial capillary plexus.
Progressive changes in macular telangiectasia apparent in FA and macular pigment imaging are most obvious in the deep capillary network and outer retina in OCTA. Optical coherence tomography angiography offers a noninvasive technology to analyze vascular changes in the retina and choroid of patients with macular telangiectasia.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Macular telangiectasia is associated with neurodegenerative changes including focal outer retinal atrophy and a loss of macular pigment (MP). We aimed to investigate whether an association between spectral domain optical coherence tomography neurodegenerative signs and MP abnormalities can be detected.
Forty-seven eyes of 27 macular telangiectasia Type 2 patients (mean age 66.7 years, range 50-82 years, 12 male) were investigated. An MP pattern was recorded using a dual-wavelength autofluorescence method and classified according to severity (I-III). Outer plexiform, inner nuclear, and photoreceptor layer thickness values were measured in Spectralis spectral domain optical coherence tomography scans. Thickness values were compared with those of a control group of 14 healthy age-matched eyes.
Macular pigment redistribution was found to be Class I in 11 eyes, Class II in 28 eyes, and Class III in 8 eyes. More advanced stages of MP loss were associated with a greater, statistically significant thinning of the outer plexiform and inner nuclear layer complex and photoreceptor layers (P ≤ 0.001). Lower absolute levels of MP were also associated with a thinning of the photoreceptor layer. Thinning was restricted to within the parafovea, more severe at temporal eccentricities.
Our findings support the hypothesis that in macular telangiectasia Type 2 cellular degenerative processes leading to a thinning of these layers also result in reduction and redistribution of MP.
[Show abstract][Hide abstract] ABSTRACT: Recent developements in OCT technology using high speed acquisition and calculation of consecutive scans (SSADA = split spectrum amplitude decorrelation algorithm) have resulted in the possibility to demonstrate retinal and choroidal vessels in the macula. This new technology of "OCT angiography" thus allows the non-invasive and rapid (within seconds) reconstruction of the three-dimensional structure of the retinal and choroidal vascularisation. There are still limitations caused by movement artefacts, superposition of superficial retinal vessels at the RPE level or insufficient three-dimensional imaging, but the first experience with this new method and especially the correlations with the current standard diagnostic procedure fluorescein angiography shows that especially for vascular changes which are predominantly in one retinal layer (e.g., the inner retina) like in diabetic retinopathy or retinal vein occlusions, a very good correlation can be seen. Also in MacTel type 2 patients the proposed vascular changes in the deeper capillary network of the retina can be visualised very well with OCT angiography. In contrast, more three-dimensional vascular changes like the neovascular complex in exsudative AMD need a more sophisticated diagnostic analysis strategy, which has still to be developed. However, the first experience also demonstrates that fluorescein angiographic differentiation can also be seen in OCT angiography. In addition, the new technology gives additional information about the choroidal and outer retinal changes in these pathologies, which may result in a better understanding of the underlying pathologies.
Georg Thieme Verlag KG Stuttgart · New York.
[Show abstract][Hide abstract] ABSTRACT: Hintergrund Selbst unter konsequenter Anti-VEGF („vascular endothelial growth factor“)-Therapie zeigen sich bei neovaskulärer altersabhängiger Makuladegeneration (AMD) oft Reaktivierungen der Läsion. Die vorliegende Fallserie untersucht, ob ein Wechsel des Präparates von Ranibizumab zu Aflibercept sicher ist und Unterschiede hinsichtlich der Wirksamkeit beobachtet werden können. Patienten und Methoden Bei 56 konsekutiven Patienten mit erneuter Aktivität der AMD, gemäß morphologischen Kriterien der Spectral-Domain-optischen Kohärenztomographie (SD-OCT)-Untersuchung, wurde nach 6 bis maximal 41 Injektionen (im Mittel 18,9, SD 6,3) ein Wechsel von Ranibizumab zu Aflibercept vorgenommen. Bei allen Kontrollen und vor jeder Injektion wurde neben der klinischen Untersuchung der Visus (LogMAR) erhoben und eine SD-OCT (Volumenscan) durchgeführt. Ergebnisse Der mittlere Visusverlauf war unter beiden Therapien stabil. Morphologisch zeigte sich eine stärkere Reduktion der Netzhautdicke nach dem Therapiewechsel (innerhalb von 1000 μm und foveolär) gegenüber der initialen Behandlung. Sowohl die Änderung der subretinalen Flüssigkeit als auch die Höhe einer assoziierten Pigmentblattanhebung (PED) wiesen keinen signifikanten Unterschied auf. Die Analyse der morphologischen Veränderungen auf der Ebene der Photorezeptoren zeigte eine Abnahme der Diskontinuität sowohl in der ellipsoiden Bande als auch im Bereich der Membrana limitans externa (ELM). Zusammenfassung Bei Patienten mit erneuter und/oder hoher Läsionsaktivität kann durch einen Wechsel des Präparates eine erneute funktionelle Stabilisierung trotz mehrfacher Vorbehandlung erreicht werden. Morphologisch fanden sich zudem Hinweise auf eine Regression des intraretinalen Ödems und Verbesserungen auf der Ebene der Photorezeptoren. Im Rahmen einer klar definierten Behandlungsstrategie ist der Wechsel von einem Anti-VEGF-Präparat auf einen ähnlichen Wirkstoff sicher. Vor einer definitiven Bewertung sind prospektiv kontrollierte Studienbedingungen erforderlich, bevor der klinische Nutzen eines Wechsels verifiziert werden kann.
Der Ophthalmologe 12/2014; 112(5). DOI:10.1007/s00347-014-3137-6 · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Even during consistent anti-vascular endothelial growth factor (VEGF) therapy a reactivation of exudative age-related macular degeneration (AMD) lesions can be observed in many patients. The present case series examined whether a switch from ranibizumab to aflibercept is safe and whether differences in potency can be observed.
In 56 consecutive patients with recurrent activity of AMD according to the morphological criteria of the spectral domain optical coherence tomography (SD-OCT) examination, a change to aflibercept was made after 6-41 (mean 18.9, SD 6.3) injections with ranibizumab. In all controls and before each injection logMAR visual acuity was measured and a SD-OCT (volume scan) was performed in addition to the clinical examination.
The mean visual acuity was stable under both therapies. The analysis of the morphological parameters showed a greater reduction of the retinal thickness after the change in therapy (mean retinal thickness within 1000 μm and central foveal thickness) compared to the initial treatment. The changes in the subretinal fluid as well as the height of an associated pigment epithelial detachment (PED) did not show any significant differences. The analysis of the morphological parameters at the level of the photoreceptors showed a decrease in discontinuity in the ellipsoid layer and also in the external limiting membrane (ELM).
In patients with recurrent or high SD-OCT-based activity of exudative AMD lesions, a switch of the treatment strategy from ranibizumab to aflibercept can achieve a new functional stability in spite of multiple pretreatment. We found morphological indications of a regression of intraretinal edema and improvement in the photoreceptor area. In the context of a well-defined treatment strategy, a switch from anti-VEGF therapy to a similar active substance is safe. Before a definitive evaluation can be made, prospective controlled conditions are required to verify the clinical benefits of the switch.
[Show abstract][Hide abstract] ABSTRACT: Macular telangiectasia Type 2 is a bilateral, progressive potentially blinding retinal disease characterized by both vascular and neurodegenerative signs that have been documented using different imaging techniques. The correlation between macular telangiectasia Type 2 signs from various imaging modalities is unknown. Our aim was to investigate the relationship of various macular telangiectasia Type 2 signs using fundus fluorescein angiography, optical coherence tomography and dual-wavelength autofluorescence images.
Participants were selected from the macular telangiectasia Type 2 Natural History Observation Study, based on a confirmed diagnosis and the availability of images. Signs in fundus fluorescein angiography, dual-wavelength autofluorescence, and optical coherence tomography images were graded according to standardized categories, and agreement among the multimodel imaging was assessed statistically.
One hundred and ninety-one eyes of 96 patients were examined. Significant correlations were found between early and late fundus fluorescein angiography (ρ = 0.82, P < 0.0001), luteal pigment loss and early/late fundus fluorescein angiography signs (ρ = 0.52, P < 0.0001 and ρ = 0.62, P < 0.0001, respectively), inner and outer segment break length and pigment loss (Class 1 vs. 2/3, P < 0.0001; Class 2 vs. 3, P = 0.04). Correlation between pigment loss and retinal spaces/atrophic retinal restructuring was fair (κ = 0.25-0.33). Bilateral symmetry was slight to substantial (κ = 0.18-0.62).
Our data demonstrate the relative extent of neurodegenerative and vascular signs; it may be useful for designing systems for staging disease severity using multimodal imaging and may also provide clues to the pathogenesis of the disease.
[Show abstract][Hide abstract] ABSTRACT: Macular telangiectasia type 2 is characterized by atrophic alterations of the central retina which is accompanied by a defined vascular phenotype. The disease manifests within an oval central retinal area the size of approximately two disc diameters, with a topographic predisposition temporal to the foveal center. Funduscopy reveals reduced retinal transparency, crystalline deposits, mildly ectatic capillaries, thickened venules and retinal pigment plaques. Secondary neovascularization and macular holes may occur during the disease course. Fluorescein angiography usually shows a diffuse leakage and often ectatic capillaries. On optical coherence tomography (OCT) examination, hyporeflective cavities and focal atrophy of the photoreceptor layer represent a frequent finding. A characteristic sign is an increased (para) central signal on fundus autofluorescence imaging due to a reduced density of macular pigment.
Der Ophthalmologe 09/2014; 111(9):819-28. DOI:10.1007/s00347-014-3082-4 · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Macular telangiectasia type 2 is characterized by neurodegenerative as well as vascular and retinal alterations. Previous therapeutic approaches mainly targeted the vascular changes; however, this did not prove to be beneficial except for secondary neovascularization which may be successfully treated with intravitreal vascular endothelial growth factor inhibitors. As the natural history of the disease is primarily characterized by the neurodegenerative processes, new therapeutic strategies, such as neuroprotective agents are already being explored in clinical trials.
Der Ophthalmologe 09/2014; 111(9):834-8. DOI:10.1007/s00347-014-3084-2 · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Are there any morphological parameters in pigment epithelial detachment (PED) in eyes with age-related macular degeneration (AMD), which could identify the development of tears (RIP) in the retinal pigment epithelium (RPE) before initiation of anti-vascular endothelial growth factor (VEGF) therapy?
Retrospectively, the spectral domain optical coherence tomography (SD-OCT), FLA and near infrared (NIR) images of 98 eyes with PED in exudative AMD before treatment (ranibizumab or bevacizumab) were analyzed. Eyes in which a tear in the RPE (RIP group) could be observed during treatment were compared to eyes without the development of RIP (PED group) in the following morphological parameters of PED: height, number of peaks, presence of hyporeflective fissures at the base of the PED, structure of the RPE, presence of floating structures in the PED with maximum hyperreflectivity, amount and localization of hyperreflectivity in the PED and hyperreflectivity in the NIR images.
In the 80 eyes of the PED group the mean PED height was 373.7± 197 µm and in the 18 eyes of the RIP group the mean PED height was higher (694.2± 284.3 µm, p < 0.0001). A difference was also seen in the number of peaks per PED (PED group 43%, RIP group 72%, p = 0.039) and in the hyperreflectivity in NIR images (PED group 68%, RIP group 94%, p = 0.033). There were no significant differences in the other morphological parameters. A classification into four types of PED was found by the parameters height and number of peaks. The PED type with a height > 350 µm and one peak (RIP 43%) developed tears more often (p = 0.001) than the PED type < 350 µm with one peak (RIP 0%, p = 0.001). A trend in the visual acuity over 156 weeks was seen: in PED types with heights > 350 µm there was a lower increase in the visual acuity than in PED types < 350 µm (rm ANOVA p = 0.18; ɛ HH = 0.88). Furthermore, in PED types > 350 µm with multiple peaks the total number of injections necessary was higher than in the other PED types (p = 0.032).
Morphological parameters, such as PED height, number of peaks per PED in OCT images and hyperreflectivity in NIR images are prognostic factors for RPE tears in exudative AMD. The PED height and number of peaks per PED are useful for classification of PED in the daily routine.
Der Ophthalmologe 07/2014; 112(1). DOI:10.1007/s00347-014-3098-9 · 0.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: Genetic factors contribute to the development and progression of age-related macular degeneration (AMD). We aimed to assess the association of drusen as phenotypic characteristics of early AMD and their progression with polymorphisms in the CFH, ABCA1, and ARMS2 genes. Methods: In the Münster Aging and Retina Study (MARS), drusen were detected in 406 patients with early AMD and 170 healthy controls according to the International Classification using fundus photographs, with a follow-up examination after 2.6 years (median). Six drusen features were assessed: drusen number (</≥20); confluence of drusen (</≥50 %), largest drusen size (</≥175 μm); area occupied by drusen (</≥10 %); most frequent drusen size (</≥175 μm), and presence of soft, indistinct drusen (no/yes). Based on these features, an unweighted summary drusen severity score (DSS; categorized in "low", "intermediate" and "high") was calculated. The relationship of each drusen feature and the DSS with CFH rs1061170, ABCA1 rs1883025, and ARMS2 rs10490924 at baseline and after 2.6 years was analyzed using multivariate logistic regression models. Results: Cross-sectionally, each drusen feature was associated with a higher frequency of the CFH and ARMS2 risk variants. Compared to healthy eyes, the CFH risk variant was more common in eyes with early as well as advanced drusen features, while the ARMS2 variant was only associated with advanced drusen. After 2.6 years, 43 % of the eyes showed a progression of at least 1 unit in the DSS. The progression from low to higher DSS was inversely associated with ABCA1 (OR=0.54), and the progression from intermediate to high DSS was positively related to CFH rs1061170 (OR=2.3; p<0.05 for each). Conclusions: Variants in CFH, ABCA1, and ARMS2 genes are related to the presence and progression of drusen in early AMD. CFH and, inversely, ABCA1 seem to be involved in early drusen development, while the role of ARMS2 is more pronounced in advanced stages of early AMD.
Albrecht von Graæes Archiv für Ophthalmologie 06/2014; 252(8). DOI:10.1007/s00417-014-2690-7 · 1.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The introduction and approval of Ocriplasmin as an intravitreally applicable drug in the pharmocological treatment of vitreomacular traction represents a new therapeutic approach possibly avoiding vitreoretinal surgery. With our article we report our first experience wih Ocriplasmin in clinical practice.
The indication for intravitreal therapy with Ocriplasmin was provided for symptomatic VMT or macular hole with VMT in 20 patients since March 2013. Surgery was planned in cases with remaining symptoms. Before IVI we performed SD-OCT. Best visual acuity (BCVA) was evaluated preoperatively, 7 and 28 days after treatment and finally every month in 14 treated eyes. SD-OCT images were analysed before treatment and later on with every follow-up examination. In addition to functional and morphological changes we analysed all side effects.
The mean BCVA at the beginning of treatment was 0.3 and 0.4 before injection. The indications for treatment were as follows: symptomatic VMT in 10 patients and 4 patients suffering from full thickness macular hole stage 2. In 3 patients spontaneous regression of VMT could be observed with increasing of vision from 0.3 to 0.5. In one patient his macular hole was closed and BCVA increased from 0.2 to 0.6 within 7 days. Two patients showed significant enlargement of their macular holes after 7 days and finally underwent surgery. A massive cystoid macular oedema occurred in one patient. No change in the SD-OCT image could be observed 28 days after treatment. The mean visual acuity improved to 0.6 during a follow-up period of 90 days. Photopsia and disturbing vitreous opacities up to 28 days post injection could be regarded as minor side effects.
Our first clinical experience with intravitreous injection of Ocriplasmin were performed to confirm the presumed therapeutic effect in patients suffering from VMT. Small macular holes could frequently be closed. The possibility of special side effects must be taken in consideration just as the possibility of spanteous improvement before performing IVI with Ocriplasmin. Further prospective studies must be recommended to be right about Ocriplasmin injections.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Macular pigment optical density (MPOD) and age-related macular degeneration (AMD) are thought to be associated; however, the details are not yet understood clearly. This study aimed at investigating how retinal anatomic structures relate with the spatial MPOD distribution in single eyes.
In a subgroup of the third follow-up examination of the Münster Aging and Retina Study (MARS) cohort (mean age, 78.4 years), 124 single eyes of 79 participants with early AMD were examined. The MPOD was assessed using 2-wavelength autofluorescence (AF). Retinal thickness (RT) and fovea pit profile slopes were measured using optical coherence tomography (OCT). The results were analyzed for interocular correlation in 58 pairs of eyes, and for the association of MPOD distribution patterns with RT using uni- and multivariate statistical methods.
The interocular correlations for several measures of RT and RT layers were high (P < 0.001). The RT was inversely and significantly related to MPOD at 1.0° and at 2.0° from the foveal center, but not to central MPOD. After controlling for sex, age, smoking, and spherical equivalent, RT was significantly thinner (-39.7 μm, P < 0.001) in eyes with ring-like compared to normal MPOD distribution. In particular, a thinner layer between internal and external limiting membrane showed strong associations with ring-like structures.
Higher values of MPOD at 1° and 2°, as well as a ring-like distribution of MPOD were associated significantly with thinner maculae, due to thinner inner retinal layers. The MPOD distribution was unrelated to the slope of the foveal pit or the choroidal thickness. Our results suggest that the retinal section between the internal and external limiting membrane is involved in the spatial distribution of MPOD.
[Show abstract][Hide abstract] ABSTRACT: To quantitatively analyze the distribution of macular pigment (MP) over a period of 5 years and for monitoring progression of macular telangiectasia.
Macular pigment concentration (autofluorescence, excitation wavelengths: 488 and 514 nm) was determined at baseline and after 5 years in 43 eyes of 22 subjects (46-80 years; mean, 65.6 years; 10 men) participating in the macular telangiectasia project.
Mean MP density at 0.5° declined in the segment (one eighth of a circle) with the highest MP optical density (-0.04 density units; P= 0.015), where density units (DU), and also averaged in the 2 segments that divided segments with detectable MP from those in which MP was no longer detectable (-0.04 density units; P = 0.0005). In the first segment mentioned, 2° values decreased to a lesser extent and not significantly. The diameter of MP loss expanded horizontally from 2.64 mm to 2.74 mm (P = 0.0001) but not vertically. Macular pigment density in the "halo" of peripheral MP at a mean of 5.44° (4.53-6.21°) increased (+0.01 DU; P= 0.01).
Five years of follow-up resulted in central (0.5°) reduction and peripheral (4.53-6.21°) accumulation of MP. Longer period of follow-up may disclose significant changes in paracentral locations. The area of central MP loss expands in particular in a horizontal direction and less vertically. Centrifugal movement of MP during disease may explain our findings.
[Show abstract][Hide abstract] ABSTRACT: This article reports the case of a 72-year-old woman with pigment epithelial detachment with occult choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD) which developed under anti-vascular endothelial growth factor (VEGF) therapy of a tear in the retinal pigment epithelium (RPE). In the area of free RPE autofluorescence was completely absent and the microperimetry in this area showed an absolute scotoma. The visual acuity was 0.1. After continuation of anti-VEGF therapy because of persistent subretinal and intraretinal fluid over 3 years an increased autofluorescence was observed and the microperimetry showed an increase in central retinal sensitivity. The central visual acuity improved to 0.5 and in this area a whitish subretinal tissue formed morphologically. In the spectral domain optical coherence tomography (SD-OCT) image this structure was hyperreflective which might suggest a certain regeneration process of the RPE under anti-VEGF-therapy.
Der Ophthalmologe 09/2013; 111(5). DOI:10.1007/s00347-013-2883-1 · 0.50 Impact Factor