To describe 10-year trends in visual outcomes, anatomical outcomes and treatment burden of patients receiving antivascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related ...macular degeneration (nAMD).
Retrospective cohort study of treatment-naïve, first-affected eyes with nAMD started on ranibizumab before January 1, 2009. The primary outcome was time to best-corrected visual acuity (BCVA) falling ≤35 ETDRS letters after initiating anti-VEGF therapy. Secondary outcomes included time to BCVA reaching ≥70 letters, proportion of eyes with BCVA ≥70 and ≤35 letters in 10 years, mean trend of BCVA and central retinal thickness over 10 years, and mean number of injections.
For our cohort of 103 patients, Kaplan-Meier analyses demonstrated median time to BCVA reaching ≤35 and ≥70 letters were 37.8 (95% CI 22.2 to 65.1) and 8.3 (95% CI 4.8 to 20.9) months after commencing anti-VEGF therapy, respectively. At the final follow-up, BCVA was ≤35 letters and ≥70 letters in 41.1% and 21%, respectively, in first-affected eyes, while this was the case for 5.4% and 48.2%, respectively, in a patient's better-seeing eye. Mean injection number was 37.0±24.2 per eye and 53.6±30.1 at patient level (63.1% of patients required injections in both eyes).
The chronicity of nAMD disease and its management highlights the importance of long-term visual prognosis. Our analyses suggest that one in five patients will retain good vision (BCVA ≥70 ETDRS letters) in the first-affected eye at 10 years after starting anti-VEGF treatment; yet, one in two patients will have good vision in their better-seeing eye. Moreover, our data suggest that early treatment of nAMD is associated with better visual outcomes.
Application of artificial intelligence (AI) to macular optical coherence tomography (OCT) scans to segment and quantify volumetric change of anatomical and pathological features during intravitreal ...treatment for neovascular age-related macular degeneration (AMD).
Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database.
2115 eyes from 1883 patients that started anti-vascular endothelial growth factor (anti-VEGF) treatment between 1st June 2012 and 30th June 2017.
The Moorfields Eye Hospital neovascular AMD database was queried for first and second eyes that received anti-VEGF treatment and had an OCT scan at baseline and at 12 months. Follow-up scans were input into the AI system to derive volumetric outputs for the following variables: intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), subretinal hyperreflective material (SHRM), hyperreflective foci (HRF), neurosensory retina (NSR) and retinal pigment epithelium (RPE). Volumes were studied at different time points and comparisons made with respect to baseline volume groups. Cross-sectional comparisons between time points were conducted using Mann-Whitney U test.
Mean volumes of analysed features decreased significantly from baseline to both four and 12 months, in both first and second-treated eyes. Pathological features that reflect exudation, including pure fluid components (IRF and SRF) and those with a mixture of fluid and fibrovascular tissue (PED and SHRM), displayed similar response to treatment over 12 months. Mean PED and SHRM volumes showed less pronounced but also substantial decreases over the first two months, reaching a plateau post loading phase, and minimal change to 12 months. Both NSR and RPE volumes showed gradual reductions over time, and not as substantial as exudative features.
We report the results of a quantitative analysis of change in retinal segmented features over time, enabled by an AI segmentation system. Cross-sectional analysis at multiple time points demonstrated significant associations between baseline OCT-derived segmented features and the volume of biomarkers at follow-up. Demonstrating how certain OCT biomarkers progress with treatment and the impact of pre-treatment retinal morphology on different structural volumes may provide novel insights into disease mechanisms and aid personalization of care. Data will be made public for future studies.
We aimed to evaluate the effect of levels of physically effective neutral detergent fiber from forage (NDFfor) on confined cattle’s metabolism and ingestive behavior. Four crossbred steers (514.0 ± ...4.54 kg BW) rumen-cannulated were used. The animals were randomly distributed in a 4×4 Latin square design, and the treatments were diets with 9.5%, 5.5%, 2.5%, and 0.0% NDF from whole plant corn silage. The trial was divided into 4 periods of 21 days. The dry matter, organic matter (OM), crude protein, neutral detergent fiber (NDF), physically effective NDF 8mm (peNDF8mm) and NDF1.18mm intakes, and the digestibility of OM and NDF showed a quadratic behavior. The rumen pH values showed a decreasing linear, and the time at pH below 5.8 increased linearly in the diets with lower NDFfor. The production of volatile fatty acids and the proportions of propionate and butyrate showed an increasing quadratic behavior. On the other hand, the proportion of acetate fitted a decreasing quadratic equation. With the lower participation of forage in the diets, the time spent on rumination activity decreased in a quadratic way, and the time spent in idleness increased in a quadratic way. The corn silage can be reduced to 135 g/kg DM in the diet to obtain a minimum of 5.5% of NDF from roughage.
Our hypothesis was that different whole oilseeds included in the diet for steers confined could alter the diversity of rumen bacteria compared to a diet without oilseeds or an exclusively forage ...diet. It was aimed to evaluate the effects of oilseeds inclusion in the diet on bacterial diversity in the solid fraction of the ruminal content of steers, by gene sequences of the conserved 16S rDNA region. Six crossbred steers castrated males, fitted with ruminal cannula were used in a 6 × 6 Latin square design, using 21-day period. At the start of the experiment, the live weight of the animals averaged 416 ± 9.7 kg (mean ± SD). A total of 2,180,562 16S rDNA sequences were generated for the Bacteria domain by MiSeq sequencing. The bacterial diversity was composed of 24 bacterial phyla, with the most abundant being Firmicutes, Bacteroidetes, and Proteobacteria. Other phyla with less diversity were also identified including Eurychaeota, Tenericutes, SR1 Absconditalbacteria, Synergistetes, Actinobacteria, Saccharibacteria, Elusimicrobia, Cyanobacteria, Verrucomicrobia, Fusobacteria, Lentisphaerae. The similarity in the bacterial community averaged 50% for all the experimental diets. Steers-fed corn silage exhibited a great diversity of bacteria of the Firmicutes phylum. The steers-fed oilseeds in the diet had a great diversity of bacteria from the phylum Bacteroidetes and Proteobacteria. The inclusion of whole oilseeds in the steer diets can alter the rumen bacteria population by up to 50% of total diversity.
To evaluate the predictive usefulness of quantitative imaging biomarkers, acquired automatically from OCT scans, of cross-sectional and future visual outcomes of patients with neovascular age-related ...macular degeneration (AMD) starting anti-vascular endothelial growth factor (VEGF) therapy.
Retrospective cohort study.
Treatment-naive, first-treated eyes of patients with neovascular AMD between 2007 and 2017 at Moorfields Eye Hospital (a large, United Kingdom single center) undergoing anti-VEGF therapy.
Automatic segmentation was carried out by applying a deep learning segmentation algorithm to 137 379 OCT scans from 6467 eyes of 3261 patients with neovascular AMD. After applying selection criteria, 926 eyes of 926 patients were analyzed.
Correlation coefficients (R
values) and mean absolute error (MAE) between quantitative OCT (qOCT) parameters and cross-sectional visual function, as well as the predictive value of these parameters for short-term visual change, that is, incremental visual acuity (VA) resulting from an individual injection, as well as VA at distant time points (up to 12 months after baseline).
Visual acuity at distant time points could be predicted: R
= 0.80 (MAE, 5.0 Early Treatment Diabetic Retinopathy Study ETDRS letters) and R
= 0.7 (MAE, 7.2 ETDRS letters) after injection at 3 and at 12 months after baseline (P < 0.001 for both), respectively. Best performing models included both baseline qOCT parameters and treatment response. Furthermore, we present proof-of-principle evidence that the incremental change in VA from an injection can be predicted: R
= 0.14 (MAE, 5.6 ETDRS letters) for injection 2 and R
= 0.11 (MAE, 5.0 ETDRS letters) for injection 3 (P < 0.001 for both).
Automatic segmentation enables rapid acquisition of quantitative and reproducible OCT biomarkers with potential to inform treatment decisions in the care of neovascular AMD. This furthers development of point-of-care decision-aid systems for personalized medicine.
It aimed to evaluate the effects of different whole oilseeds in lipid-rich diets on nutrient intake, apparent digestibility, ingestive behavior, and ruminal and blood parameters of steers. A control ...diet (without oilseed) and four diets containing whole oilseeds (cotton, canola, sunflower, and soybean) were tested. All diets used the whole-plant corn silage at 400 g/kg as roughage. Five diets, being a control diet (without oilseed) and four diets containing whole oilseeds (cotton, canola, sunflower, and soybean), were tested. All diets used the whole-plant corn silage at 400 g/kg as roughage. Five rumen fistulated crossbreed steers, in a 5 × 5 Latin square design were distributed using five periods of 21 days. The steers fed cottonseed and canola diets had lower dry matter intakes (6.6 kg/day). Steers showed higher averages of time in rumination for treatments with sunflower, soybean, and cottonseed (406, 362, and 361 min/day, respectively). There was no treatment effect for the ruminal pH and ammonia (NH
3
) variables. There was an effect of the treatment on the volatile fatty acid concentrations. The animals that received soybean showed a higher plasma urea concentration (50.7 mg/dL). Animals fed the control diet showed lower serum cholesterol levels (111.8 mg/dL) than those fed diets containing whole cottonseed, canola, sunflower, and soybean (152.7, 137.1, 146.9, and 138.2 mg/dL, respectively). We recommended using whole soybean or sunflower seeds to formulate lipid-rich diets with 70 g/kg of ether extract for crossbreed steers in the feedlot.
The aim of this study was to evaluate bacterial species and diversity of methanogenic Archaea in the solid fraction of the ruminal content, through the gene sequences of the conserved 16S rDNA ...region, in response to the following diets: canola, cottonseed, sunflower, soybean, corn silage, and control diet. Six rumen-fistulated crossbred steers, with body weight (BW) of 416.33 ± 93.30 kg, were distributed in a 6 × 6 Latin square design. Regardless of the diet provided, amylolytic, proteolytic, and lactic bacteria were identified in the rumen fluid. Cellulolytic bacteria were predominant for all diets, reaching 47.75% of operational taxonomic units (OTUs) in animals fed with the cottonseed diet. Amylolytic bacteria reach 62.51% of OTU in animal fed sunflower diet, while proteolytic bacteria correspond to 65.96% of OTU in this same diet. Also,
Megasphaera elsdenii
bacterium was identified for all diets, with a greater percentage of OTU in steers fed the cottonseed diet. The diversity analysis of the species identified the methanogenic Archaea
Methanobrevibacter ruminantium
in all diets. We conclude that the control and corn silage diets have the most similar bacterial flora; diets with oilseeds had 47.5% similarity in rumen flora bacteria species. Animals fed with soybean showed a reduced number of methanogenic Archaea in the rumen content, which could be an alternative feed for cattle due to their low potential for energy losses with the production of methane.
The study aimed at the effect of different regrowth ages on chemical, productive, and morphological characteristics, in addition to the kinetics of gas production and in vitro digestibility of ...grasses of the genus
Brachiaria
. The treatments consisted of two regrowth ages (21 and 35 days) and two grass species (
Brachiaria brizantha
and
B. ruziziensis
), in plat with a dimension of 10 × 10 with four replications, totaling 16 plats in a completely randomized design. The regrowth age did not change the leaf:stem ratio of the grasses. Ruziziensis-grass had higher crude protein (CP) content in leaves than Marandu-grass (14.0% versus 10.9% respectively). Marandu-grass leaf had higher NDF content than Ruziziensis-grass (65.0 and 58.3%, respectively) and ADF content (39.6 and 33.2%, respectively). The accumulation rate is high in Marandu-grass regardless of the age of regrowth; however, the in vitro digestibility of dry matter of Ruziziensis-grass is better both in the leaf and in the stem. The regrowth age did not influence the dry matter (DM) and neutral detergent fiber (NDF) in vitro digestibility (ivD) of the leaves. The ivDNDF of leaves of both types of grass were similar. There was an increase in the ivDDM of stem when the regrowth age was 21 days. The DM degradation rate was higher in Marandu-grass at both regrowth ages, and the total gas production was higher at 21 days. The parameters evaluated in the dual-pool logistic model showed interaction for age and cultivar, except for fractions λ (lag time) and total gas production. Marandu-grass presented a greater volume of gas for the rapidly degradable fraction and a lower degradation rate. There was a significant interaction for the parameters evaluated in the models between ages and grasses. The exponential model showed interaction in all fractions. Grasses had reduced CP content and increased fibrous fraction as a function of age, with no reduction in leaf DM and NDF digestibility. The Ruziziensis-grass has higher digestibility at the regrowth ages evaluated, while Marandu-grass has higher yields. We recommend adjusting the in vitro degradation kinetics by the dual-pool logistic model.
The epiretinal membrane is a fibrocontractile tissue that forms on the inner surface of the retina, causing visual impairment ranging from mild to severe, and even retinal detachment. Müller glial ...cells actively participate in the formation of this membrane. Current research is constantly seeking for new therapeutic approaches that aim to prevent or treat cellular dysfunctions involved in the progression of this common fibrosis condition. The Rho GTPases signaling pathway regulates several processes associated with the epiretinal membrane, such as cell proliferation, migration, and contraction. Rho kinase (ROCK), an effector of the RhoA GTPase, is an interesting potential therapeutic target. This study aimed to evaluate the effects of a ROCK inhibitor (Y27632) on human Müller cells viability, growth, cytoskeletal organization, expression of extracellular matrix components, myofibroblast differentiation, migration, and contractility. Müller cells of the MIO-M1 lineage were cultured and treated for different periods with the inhibitor. Viability was evaluated by MTT assay and trypan blue exclusion method, and growth was evaluated by growth curve and BrdU incorporation assay. The actin cytoskeleton was stained with fluorescent phalloidin, intermediate filaments and microtubules were analyzed with immunofluorescence for vimentin and α-tubulin. Gene and protein expression of collagens I and V, laminin and fibronectin were evaluated by rt-PCR and immunofluorescence. Chemotactic and spontaneous cell migration were studied by transwell assay and time-lapse observation of live cells, respectively. Cell contractility was assessed by collagen gel contraction assay. The results showed that ROCK inhibition by Y27632 did not affect cell viability, but decreased cell growth and proliferation after 72 h. There was a change in cell morphology and organization of F-actin, with a reduction in the cell body, disappearance of stress fibers and formation of long, branched cell extensions. Microtubules and vimentin filaments were also affected, possibly because of F-actin alterations. The inhibitor also reduced gene expression and immunoreactivity of smooth muscle α-actin, a marker of myofibroblasts. The expression of extracellular matrix components was not affected by the inhibitor. Chemotactic cell migration showed no significant changes, while cell contractility was substantially reduced. No spontaneous migration of MIO-M1 cells was observed. In conclusion, pharmacological inhibition of ROCK in Müller cells could be a potentially promising approach to treat epiretinal membranes by preventing cell proliferation, contractility and transdifferentiation, without affecting cell viability.
•The Rho-ROCK pathway modulates several events in human Müller cells.•The pharmacological inhibition of ROCK alters cytoskeletal organization and decreases contractility in Müller cells.•ROCK inhibition does not affect the production of collagens type I and V, laminin and fibronectin.•ROCK may be a potential therapeutic target for epiretinal membranes.
PDF
