11 research outputs found

    Progression of lamellar hole-associated epiretinal proliferation and retinal changes during long-term follow-up

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    Purpose: To report on progression of lamellar hole-associated epiretinal proliferation (LHEP) in eyes with lamellar macular holes (LMH) using spectral-domain optical coherence tomography (SD-OCT), and to correlate with intraretinal changes and visual function.Methods: From a retrospectively reviewed series of 167 eyes with non-full-thickness macular holes, we exclusively included a subgroup of 34 eyes with LMH and LHEP by SD-OCT evaluation. In these eyes, area of LHEP, intraretinal changes of defect diameter, central retinal thickness, defects of the ellipsoid zone and occurrence of a contractive epiretinal membrane were analysed. Additionally, clinical data were documented.Results: Area of LHEP significantly increased during a mean follow-up period of 40.5 months (median 52 months). Analysing intraretinal changes, a significant enlargement of minimum and maximum horizontal lamellar hole diameter was found that correlated with the area of LHEP. Defects of the ellipsoid zone were seen in 65% of the eyes at baseline and in 85% at the end of follow-up. Increase of maximum horizontal hole diameter and ellipsoid zone defects correlated with a decline of visual acuity. Fifty per cent of patients with LMH and LHEP also demonstrated extrafoveal typical contractive epiretinal membranes with retinal folds.Conclusions: Long-term follow-up revealed an increase of the area of LHEP in eyes with LMH that correlated with the enlargement of lamellar hole diameter and ellipsoid zone defects. Our data delineate the progression of intraretinal changes in association with a decline of visual function in this subgroup of LMH eyes

    Prognostic value of improvement endpoints in pulmonary arterial hypertension trials: A COMPERA analysis

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    BACKGROUND: The prognostic value of improvement endpoints that have been used in clinical trials of treatments for pulmonary arterial hypertension (PAH) needs to be further investigated. METHODS: Using the COMPERA database, we evaluated the prognostic value of improvements in functional class (FC) and absolute or relative improvements in 6-min walking distance (6MWD) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). In addition, we investigated multicomponent endpoints based on prespecified improvements in FC, 6MWD and NT-proBNP that have been used in recent PAH trials. Finally, we assessed the predictive value of improvements determined by risk stratification tools. The effects of changes from baseline to first follow-up (3-12 months after initiation of PAH therapy) on consecutive survival were determined by Kaplan-Meier analysis with Log-Rank testing and Cox proportional hazard analyses. RESULTS: All analyses were based on 596 patients with newly diagnosed PAH for whom complete data were available at baseline and first follow-up. Improvements in FC were associated with improved survival, whereas absolute or relative improvements in 6MWD had no predictive value. For NT-proBNP, absolute declines conferred no prognostic information while relative declines by ≥35% were associated with better survival. Improvements in multicomponent endpoints were associated with improved survival and the same was found for risk stratification tools. CONCLUSION: While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD, and NT-proBNP were associated with improved survival. These tools should be further explored as outcome measures in PAH trials. © 2022 The Author

    Wirkungen und Nebenwirkungen von Ocriplasmin – ein Update

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    ZusammenfassungDie pharmakologische Vitreolyse mit Ocriplasmin ist eine effektive, nicht operative Therapieoption zur Behandlung der vitreomakulären Traktion (VMT) ≤ 1500 µm einschließlich assoziiertem Makulaforamen mit einem Durchmesser von ≤ 400 µm. Sowohl klinische Phase-III-Studien als auch nach Zulassung von Ocriplasmin durchgeführte Studien konnten zeigen, dass eine Verbesserung der Sehschärfe durch die intravitreale Injektion des Medikaments erreicht werden kann und die VMT in 78% der Fälle durch die Behandlung gelöst wird. Grundlage einer erfolgreichen Behandlung mit Ocriplasmin ist eine gezielte Selektion der Patienten, die nach beschriebenen prädiktiven Faktoren empfohlen wird. Die Nebenwirkungen nach Ocriplasmin-Injektion sind meist passager und selbstlimitierend. Ihr Auftreten ist jedoch nicht selten. Visusminderung sowie strukturelle SD-OCT- und ERG-Veränderungen sind mit einer erfolgreichen Ablösung der VMT verbunden. Hierbei erscheint besonders wichtig, Patienten vor Injektion von Ocriplasmin über potenzielle subjektive Funktionsbeeinträchtigungen aufzuklären. Bei persistierender VMT oder persistierendem Makulaforamen nach pharmakologischer Vitreolyse ergeben sich keine funktionellen und morphologischen Nachteile für die behandelten Patienten verglichen mit jenen, die ausschließlich operiert wurden und keine vorangegangene Ocriplasmin-Injektion erhalten hatten.</jats:p

    Idiopathic pulmonary arterial hypertension phenotypes determined by cluster analysis from the COMPERA registry

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    The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO; &lt;45% vs ≥45% predicted), smoking status, and presence of comorbidities (obesity, hypertension, coronary heart disease, and diabetes mellitus). A hierarchical agglomerative clustering algorithm was performed using Ward&apos;s minimum variance method. The clusters were analyzed in terms of baseline characteristics; survival; and response to pulmonary arterial hypertension (PAH) therapy, expressed as changes from baseline to follow-up in functional class, 6-minute walking distance, cardiac biomarkers, and risk. Three clusters were identified: Cluster 1 (n = 106; 12.6%): median age 45 years, 76% females, no comorbidities, mostly never smokers, DLCO ≥45%; Cluster 2 (n = 301; 35.8%): median age 75 years, 98% females, frequent comorbidities, no smoking history, DLCO mostly ≥45%; and Cluster 3 (n = 434; 51.6%): median age 72 years, 72% males, frequent comorbidities, history of smoking, and low DLCO. Patients in Cluster 1 had a better response to PAH treatment than patients in the 2 other clusters. Survival over 5 years was 84.6% in Cluster 1, 59.2% in Cluster 2, and 42.2% in Cluster 3 (unadjusted p &lt; 0.001 for comparison between all groups). The population of patients diagnosed with IPAH is heterogenous. This cluster analysis identified distinct phenotypes, which differed in clinical presentation, response to therapy, and survival. © 2020 The Author

    Correlative Microscopy of Lamellar Hole-Associated Epiretinal Proliferation

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    Purpose. To describe morphology of lamellar hole-associated epiretinal proliferation (LHEP) removed from eyes with lamellar macular holes (LMH). Methods. Based on optical coherence tomography data, 10 specimens of LHEP were removed from 10 eyes with LMH during standard vitrectomy. Specimens were prepared for correlative light and electron microscopy (CLEM) using an immunonanogold particle of 1.4 nm diameter that was combined with a fluorescein moiety, both having been attached to a single antibody fragment. As primary antibodies, we used antiglial fibrillary acidic protein (GFAP), anti-CD45, anti-CD64, anti-α-smooth muscle actin (α-SMA), and anticollagen type I and type II. Results. In LHEP, GFAP-positive cells possess ultrastructural characteristics of fibroblasts and hyalocytes. They represent the major cell types and were densely packed in cell agglomerations on vitreous collagen strands. Epiretinal cells of LHEP rarely demonstrated contractive properties as α-SMA-positive myofibroblasts were an infrequent finding. Conclusion. CLEM indicates that epiretinal cells in LHEP might originate from the vitreous and that remodelling processes of vitreous collagen may play an important role in pathogenesis of eyes with LMH

    Functional and Morphological Correlations before and after Video-Documented 23-Gauge Pars Plana Vitrectomy with Membrane and ILM Peeling in Patients with Macular Pucker

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    Purpose. To assess functional and morphological alterations following video-documented surgery for epiretinal membranes. Methods. Forty-two patients underwent video-documented 23-gauge vitrectomy with peeling of epiretinal (ERM) and inner limiting membrane (ILM). Patient assessment was performed before and 3 and 6 months including best corrected visual acuity (BCVA), slit lamp biomicroscopy, SD-OCT, and central 2° and 18° microperimetry. In addition, all video-documented areas of peeling on the retinal surface were evaluated postoperatively using an additional focal 2° microperimetry. Retinal sensitivity and BCVA were correlated with morphological changes (EZ and ELM) in the foveal region and in regions of membrane peeling. Results. Overall, BCVA increased from 0.6 (±0.2) to 0.2 (±0.2) logMAR after 6 months with an increase in retinal sensitivity (17.9 ± 2.7 dB to 26.8 ± 3.1 dB, p0.05). In contrast, overall postoperative retinal sensitivity was significantly decreased in patients with a visual acuity gain lower than 2 lines (p<0.05) correlating with EZ defects seen in OCT. Conclusions. Mechanical trauma of epiretinal membrane and ILM peeling due to the use of intraocular forceps may affect the outer retinal structure. Nevertheless, these changes seem to have no significant impact on postoperative functional outcome

    Vitrectomy For Intermediate Age-Related Macular Degeneration Associated With Tangential Vitreomacular Traction A Clinicopathologic Correlation

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    Purpose: To describe the morphologic characteristics of the vitreomacular interface in intermediate age-related macular degeneration associated with tangential traction due to premacular membrane formation and to correlate with optical coherence tomography (OCT) findings and clinical data. Methods: Premacular membrane specimens were removed sequentially with the internal limiting membrane from 27 eyes of 26 patients with intermediate age-related macular degeneration during standard vitrectomy. Specimens were processed for immunocytochemical staining of epiretinal cells and extracellular matrix components. Ultrastructural analysis was performed using transmission electron microscopy. Spectral domain optical coherence tomography images and patient charts were evaluated in retrospect. Results: Immunocytochemistry revealed hyalocytes and myofibroblasts as predominant cell types. Ultrastructural analysis demonstrated evidence of vitreoschisis in all eyes. Myofibroblasts with contractile properties were observed to span between folds of the internal limiting membrane and vitreous cortex collagen. Retinal pigment epithelial cells or inflammatory cells were not detected. Mean visual acuity (Snellen) showed significant improvement from 20/72 +/- 20/36 to 20/41 +/- 20/32 (P < 0.001) after a mean follow-up period of 19 months (median, 17 months). During this period, none of the eyes required anti-vascular endothelial growth factor therapy. Conclusion: Fibrocellular premacular proliferation in intermediate age-related macular degeneration predominantly consists of vitreous collagen, hyalocytes, and myofibroblasts with contractile properties. Vitreoschisis and vitreous-derived cells appear to play an important role in traction formation of this subgroup of eyes. In patients with intermediate age-related macular degeneration and contractile premacular membrane, release of traction by vitrectomy with internal limiting membrane peeling results in significantly functional and anatomical improvement
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