Retrospective, observational study in patients receiving a dexamethasone intravitreal implant 0.7 mg for macular oedema secondary to retinal vein occlusion

PURPOSE To retrospectively evaluate the re-injection interval, efficacy and safety of dexamethasone (DEX) intravitreal implant 0.7 mg in the treatment of macular oedema (ME) due to retinal vein occlusion (RVO) in Germany in 2009-2012. METHODS Retrospective, multicentre, anonymised observational study of data collected from the first DEX implant 0.7 mg injection through 3-6 months following the last injection. Data were included if the patient was \textgreater18 years old, had a diagnosis of ME secondary to branch or central RVO, and received at least 2 DEX implant 0.7 mg injections during routine practice. RESULTS Data from 87 patients were analysed. Mean time to re-injection between first and second treatments was 5.03 months in the total RVO population, and 5.46 and 4.52 months for the branch and central RVO subpopulations, respectively. An intraocular pressure increase of \textgreater25 mm Hg was recorded in 20% of patients, and 34% of patients began treatment with anti-glaucoma medication, but surgery was not needed for this condition. CONCLUSIONS DEX implant 0.7 mg was found to be well tolerated and effective with repeat treatments in clinical practice

Evidence from Studies with Heat-Stressed Caco-2 Cells, C. elegans and Growing Broilers

Climatic changes and heat stress have become a great challenge in the livestock industry, negatively affecting, in particular, poultry feed intake and intestinal barrier malfunction. Recently, phytogenic feed additives were applied to reduce heat stress effects on animal farming. Here, we investigated the effects of ginseng extract using various in vitro and in vivo experiments. Quantitative real-time PCR, transepithelial electrical resistance measurements and survival assays under heat stress conditions were carried out in various model systems, including Caco-2 cells, Caenorhabditis elegans and jejunum samples of broilers. Under heat stress conditions, ginseng treatment lowered the expression of HSPA1A (Caco-2) and the heat shock protein genes hsp-1 and hsp-16.2 (both in C. elegans), while all three of the tested genes encoding tight junction proteins, CLDN3, OCLN and CLDN1 (Caco-2), were upregulated. In addition, we observed prolonged survival under heat stress in Caenorhabditis elegans, and a better performance of growing ginseng-fed broilers by the increased gene expression of selected heat shock and tight junction proteins. The presence of ginseng extract resulted in a reduced decrease in transepithelial resistance under heat shock conditions. Finally, LC-MS analysis was performed to quantitate the most prominent ginsenosides in the extract used for this study, being Re, Rg1, Rc, Rb2 and Rd. In conclusion, ginseng extract was found to be a suitable feed additive in animal nutrition to reduce the negative physiological effects caused by heat stress. View Full-Tex

Retinal Vascular Occlusion after COVID-19 Vaccination : More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study

Background: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case– control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. Results: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case–control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk

Resultate nach Rückumstellung von intravitrealem Aflibercept auf Ranibizumab bei persistierender Aktivität einer altersbedingten Makuladegeneration

Zusammenfassung Hintergrund In der vorliegenden Fallserie sollte die Wirksamkeit einer Therapierückumstellung von intravitrealem Aflibercept auf Ranibizumab bei Patienten mit persistierender Aktivität einer altersbedingten Makuladegeneration untersucht werden. Patienten und Methoden Es wurde eine kleine Patientengruppe (17 Augen von 17 Patienten) untersucht, bei der zuerst eine Therapieumstellung von Ranibizumab auf Aflibercept und schließlich eine Therapierückumstellung auf Ranibizumab erfolgte. Als primäre Endpunkte wurden die Visusentwicklung und Veränderung der zentralen Netzhautdicke im SD-OCT festgelegt. Sekundärer Endpunkt war die Analyse prädiktiver Faktoren mit günstigem Effekt auf die Therapierückumstellung. Hierfür wurden das Geschlecht der Patienten, der Ausgangsvisus und die Netzhautdicke vor Therapierückumstellung sowie die jeweilige Anzahl der Vorinjektionen untersucht. Ergebnisse Der durchschnittliche Visus vor Therapieumstellung betrug 0,64 ± 0,36 logMAR, vor Therapierückumstellung 0,87 ± 0,40 logMAR mit einer leichten, jedoch nicht signifikanten Verbesserung auf 0,85 ± 0,58 logMAR nach Therapierückumstellung (p = 0,896). Die zentrale Netzhautdicke vor Therapieumstellung betrug 448,6 ± 181,5 µm. Diese verringerte sich auf 343,8 ± 161,3 µm nach Therapieumstellung (p = 0,614) und knapp nicht statistisch signifikant auf 299,1 ± 155,8 µm nach Therapierückumstellung (p = 0,133). Insgesamt konnte bei 8 Patienten (47%) eine Visusverbesserung erreicht werden, wohingegen bei 5 Patienten (30%) trotz Therapierückumstellung eine progrediente Visusverschlechterung zu beobachten war. Die Analysen der prädiktiven Faktoren ergaben, dass Männer durchschnittlich von einer Therapierückumstellung hinsichtlich der Visusentwicklung profitierten, während diese bei Frauen im Mittel keinen Einfluss auf die progrediente Visusminderung hatte. Hierbei zeigte sich im Vergleich vor und nach Therapierückumstellung ein signifikanter Unterschied (p = 0,016) zugunsten der Männer. Schlussfolgerungen Eine Therapierückumstellung von Aflibercept auf Ranibizumab könnte bei Patienten mit persistierender Aktivität einer altersbedingten Makuladegeneration, welche nicht mehr von der Therapieumstellung profitierten, eine Verbesserung der morphologischen Parameter und Visusstabilisierung ermöglichen.</jats:p

Anatomical and Functional Results of Endotamponade with Heavy Silicone Oil – Densiron® 68 – in Complicated Retinal Detachment

Background: High-density silicone oils are newly developed long-term tamponade agents for the treatment of complicated retinal detachment in the inferior retina. Previous studies describe satisfying anatomical and functional results. In this study we examined the largest cohort so far for a 9-month follow-up and performed a comparison to conventional silicone oil. Methods: Our study documents results and adverse effects after vitreoretinal surgery and endotamponade with Densiron® 68 in 99 cases of complicated retinal detachment. A 9-month follow-up was performed. Data of 21 patients with intraocular conventional silicone oil tamponade in complicated retinal detachment were retrospectively analyzed and served as control. Results: Anatomical success was achieved in 78 of 89 eyes (87.6%) with completed follow-up; visual acuity did not change significantly (from mean preoperative logMAR 1.88 to postoperative logMAR 1.96 (p = 0.9). Compared to control a higher anatomical success but a similar number of adverse effects were observed with heavy silicone oil in vitreous. Nevertheless, patients who received Densiron 68 twice due to redetachment showed a significantly higher rate of intraocular inflammation with the tamponade agent in situ. Conclusion: Our results support the hypothesis of Densiron 68 as potent tamponade agent for complicated retinal detachment in the inferior retinal segments especially in eyes where a previous operation failed.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

The Oxygen Saturation in the Retinal Vessels of Patients with Diabetes Mellitus – The Search for Determinants

Abstract Introduction Oxygen saturation in retinal vessels can be non-invasively measured by a new method. It is known that oxygen extraction is lowered in diabetic retinopathy. In the cross-sectional study presented here, it has been investigated whether diabetes-specific changes and typical accompanying diseases could influence the measurements in oximetry. Methods During a time span of seven months, 237 diabetics were included who came to our clinic for an intravitreal injection, who met the inclusion criteria, who showed no exclusion criteria and gave written consent. 203 eyes of 203 patients were evaluated. The oxygen saturation (SO2) was measured in digitally stored fundus images taken with a fundus camera (Zeiss 450 FF). In its illumination beam, a filter was inserted with two transmission maxima at 584 nm and 610 nm (bandwidth 10 nm). With the program “Oximetry” (Imedos Systems, Jena, Germany), the venous and the arterial SO2 were measured. The values were stored in a spreadsheet. Diabetes related data, clinical parameters and accompanying diseases were documented in the predefined scheme. Results In the whole patient sample, the venous oxygen saturation (vSO2) was 69 ± 12%, the arterial saturation (aSO2) 99 ± 5% and the arteriovenous difference 31 ± 9%. A statistically significant association could not be found between the measurement values of oximetry and age, duration of diabetes and HbA1c (Kruskal-Wallis ANOVA: p &gt; 0.05). The differences in oximetry values between units of analysis (UOA) e.g. hypertension and non units of analysis (NOA) were analysed. Descriptive testing showed significant differences in vSO2% in the following units of analysis: allergies n = 47: UOA vs. NUOA: 64 vs. 69 (t test: p &lt; 0.02); sartan therapy n = 46: UOA vs. NUOA: 64 vs. 70 (p = 0.003); state after intravitreal injections n = 144: 68 vs. 71 (p = 0.02). Oxygen extraction from the retinal capillaries was improved in patients who had injections with VEGF inhibitors. An improvement in oxygen extraction is also seen in patients with allergies and hypertension in comparison to those without these units of analysis. Conclusion The clinically observed improvement in the retinal state situation after intravitreal injections with VEGF inhibitors may be seen in association with the improved oxygen extraction. It seems reasonable to study whether a switch to sartans in the therapy of hypertension may improve retinal function.</jats:p

Follow-up study on the long-term effectiveness of the home-visiting program “ProKind” : study protocol for a randomized controlled trial

Background: The Nurse-Family Partnership (NFP) is an evidence-based home visiting program shown to improve maternal and child outcomes. Pro Kind is the first German adaptation of NFP, implemented between 2006 and 2012. While earlier evaluations demonstrated short- and medium-term benefits, no European trial has yet assessed long-term effects into adolescence. Objectives: This study protocol outlines the third phase of the Pro Kind randomized controlled trial (RCT), designed to evaluate the program’s effectiveness 14–16 years post-intervention. Primary aims are to assess adolescent and maternal outcomes related to mental health, parenting, risk behaviors, and life satisfaction, as well as potential long-term economic effects. Methods: The original RCT enrolled 755 pregnant women with psychosocial risk factors, randomly assigned to an intervention (n = 394) or control group (n = 361). The intervention comprised structured home visits from midwives or tandem teams (midwife + social worker) from pregnancy until the child’s second birthday. The 15-year follow-up combines self-report data (via online interviews and questionnaires) and administrative records on employment, social benefits, and criminal justice involvement. Discussion: This study represents the first long-term follow-up of an NFP adaptation in Europe. While U.S. trials of NFP provide evidence of the program’s effectiveness, these results cannot be generalized to European welfare contexts. This underscores the need for long-term evaluations of NFP adaptations in Europe to generate evidence that can inform policy and ensure evidence-based decision making

Intra-individual variability and circadian rhythm of vascular endothelial growth factors in subjects with normal glucose tolerance and type 2 diabetes.

Increased levels of systemic vascular endothelial growth factors (VEGFs) in patients with diabetes are associated with increased risk of microvessel disease. On the other hand, low VEGF levels after intravitreal antibody application may be associated with acute cardiovascular complications and treatment failure. Individual levels of systemic VEGF vary in a wide range depending on analytical methods and quality of diabetes control. So far only limited information exists on intraindividual fluctuations over longer periods and circadian rhythms. We analysed the intraindividual variance of VEGF-A, VEGF-C and placental growth factor (PLGF) in CTAD (citrate-theophylline-adenine-dipyridamol) plasma as well as VEGF-A in serum over a period of 6 months in patients with stable controlled type 2 diabetes (10 M, 10 F) and age and sex matched subjects with normal glucose tolerance (NGT). Furthermore, circadian levels of VEGFs were controlled hourly from 7:30 a.m. to 7:30 p.m. under standardized metabolic ward conditions. In addition, the relationship to metabolic, hormonal and inflammatory biomarkers was analyzed. VEGF-A, VEGF-C and PLGF remained stable in plasma and VEGF-A in serum over 6 months in both groups. No circadian change was observed in VEGF-A serum and plasma concentrations. A minor decrease of VEGF-C plasma levels was evident after 5 p.m. in both groups and a significant peak of PLGF concentrations occurred after lunch, which was more pronounced in T2DM. In multivariate analysis, only serum VEGF-A correlated to diabetes duration, whereas VEGF-C only correlated to HbA1c and fasting blood glucose. We did not observe significant intraindividual variances for VEGF-A in serum and VEGF-A, VEGF-C and PLGF in CTAD plasma over a period of 6 months. Taken together, a single morning measurement of systemic VEGF levels after 7:30 am appears to be a reliable parameter for the individual risk associated with abnormal VEGF concentrations in blood.NCT02325271