Anti-VEGF injection frequency correlates with visual acuity outcomes in pro re nata neovascular AMD treatment.

Clinical trials report substantial gains in visual acuity (VA) for eyes treated with intravitreal anti-VEGF for neovascular AMD (nAMD). In clinical reality, VA outcomes are more variable. Here we investigate pro-re nata treatment frequencies and VA in a real-life cohort of 1382 eyes (1048 patients). Patients with nAMD and one year complete follow-up treated with pro-re nata anti-VEGF between 2009 and 2016 were included. Injection frequency and VA was analyzed clustered by year of first treatment. Baseline parameters were compared between years. Median injection frequency in the first year was 5 with an IQR (interquartile range) of 5 for patients treated in 2009 and 8 with an IQR of 3 for patients treated from 2012 onwards. Median VA outcomes at one year were -5 to ±0 letters for patients treated between 2009 and 2013 and ±0 to +2 letters for patients treated from 2013 onwards. This cohort comprises all severities and subtypes of nAMD. 39% of patients had baseline VA outside the range for the MARINA or ANCHOR clinical trials. Higher treatment frequency was associated with improved VA in our real-life nAMD cohort. With adequate injection frequency, almost 90% of eyes had stable or improved VA over one year. Median VA gains, however, were lower compared to clinical trials. This may be due to a wider range of baseline characteristics in real-life cohorts.

OCT Angiography of the Choriocapillaris in Central Serous Chorioretinopathy: A Quantitative Subgroup Analysis.

INTRODUCTION: To quantify optical coherence tomography angiography (OCTA) signal changes at the level of the choriocapillaris (CC) in patients with different stages of central serous chorioretinopathy (CSC) and to explore any correlation between subretinal fluid (SRF) and retinal pigment epithelium (RPE) alterations and the OCTA CC signal. METHODS: One hundred one CSC eyes and 42 healthy control eyes were included in this retrospective study. CSC patients were allocated into four groups: acute, non-resolving, chronic atrophic and inactive CSC. CC OCTA images (AngioPlex®, Zeiss) were automatically quantified using an image-processing algorithm. Spatial correlation analysis of OCTA signals was performed by overlapping macular edema heatmaps and fundus autofluorescence images with corresponding OCTA images. RESULTS: Active CSC subgroups demonstrated significantly more increased and decreased flow pixels in the CC compared with controls (p < 0.0001). No significant OCTA changes were seen within the active CSC groups or between the inactive and healthy subgroup. Spatial correlation analysis revealed a decreased OCTA signal in the SRF area and an increased signal outside the SRF area in acute CSC. Areas of RPE atrophy co-localized with areas of increased choriocapillaris OCTA signal, while areas with RPE alterations exhibited a normal signal compared with unaffected RPE. CONCLUSION: The decreased OCTA signal in the area of SRF in acute CSC could be evidence of localized CC hypoperfusion or due to shadowing artifacts. The missing CC OCTA changes in altered RPE adjacent to atrophy argues against CC injury. Studies with higher resolution and optimized image acquisition are warranted to further validate our findings.

Michael adducts of palmitoylascorbic acid: effects on the oxidative burst of neutrophils and the production of tumor necrosis factor-alpha in monocytes.

The effects of Michael adducts of 6-O-palmitoyl-L-ascorbic acid (compounds 1-4) on the phosphorylation-dependent response of stimulated monocytes and neutrophils was investigated. The pyranosyl derivative 3 increased the production of tumor necrosis factor-alpha in human monocytes stimulated with lipopolysaccharide (LPS). Compound 3 also enhanced the release of tumor necrosis factor-alpha from nonstimulated monocytes. Michael adducts 1-4 inhibited the formation of reactive oxygen species in fMLP-stimulated human neutrophils as measured by luminol chemiluminescence. Treatment with 6-O-palmitoyl-L-ascorbic acid (compound 5) also led to a decreased luminescence response of neutrophils. Results are discussed with respect to the inhibitory activity of Michael adducts of ascorbic acids towards protein phosphatases PP1/PP2A.

Effects of lysophospholipids on the generation of reactive oxygen species by fMLP- and PMA-stimulated human neutrophils.

In this study, the effects of exogenous lysophospholipids--lysophosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine--on the kinetics of reactive oxygen species (ROS) production by human neutrophils are described. The ROS production by human neutrophils was monitored by luminol-amplified chemiluminescence after cell stimulation with the chemotactic tripeptide, fMLP, or with the phorbol ester, PMA. The interaction of lysophospholipids with the membrane of human neutrophils was additionally tested by mass spectrometry. Lysophosphatidylcholine showed the most pronounced effect on the chemiluminescence pattern, as well as the intensity of the fMLP and PMA-stimulated cells, whereas lysophosphatidic acid showed a slight priming effect when fMLP was used for stimulation. In the case of fMLP-stimulated cells, lysophosphatidylcholine inhibited the first phase and enhanced the second phase of chemiluminescence, whereas the chemiluminescence of PMA-stimulated neutrophils was inhibited in a concentration-dependent manner. We conclude that lysophosphatidylcholine is able to interact with protein kinase C-dependent signalling pathways leading to NADPH oxidase activation.