Brolucizumab in Pretreated Neovascular Age-Related Macular Degeneration: Case Series, Systematic Review, and Meta-Analysis.

BACKGROUND Recalcitrant neovascular age-related macular degeneration (rnAMD) despite intensive intravitreal anti-neovascular endothelial growth factor (VEGF) treatment, can be handled by switching to another anti-VEGF agent. This first systematic review and meta-analysis presents long-term data after switching from another anti-VEGF agent to brolucizumab. METHODS Retrospective case series over two years of patients switched to brolucizumab, and a systematic review and meta-analysis of peer-reviewed studies presenting patients switched to brolucizumab. Weighted mean differences based on the random-effects models were calculated for best-corrected visual acuity (BCVA) and central subfield thickness (CST). RESULTS The systematic review draws on 1200 eyes switched to brolucizumab. The meta-analysis showed a clinically irrelevant decrease in BCVA after one and two months, together with significant decreases in CST for up to one year after the switch but lacking power over 2 years. Of twelve eyes (twelve patients) in our case series, five continued treatment for two years without experiencing significant changes. CONCLUSIONS After switch to brolucizumab, a significant morphological improvement with CST reduction was shown in eyes with rnAMD. The small worsening of BCVA may be owing to the chronically active nature of rnAMD. Brolucizumab thus remains a treatment option in rnAMD despite its potential side effects

Outer retinal features in OCT predict visual recovery after primary macula-involving retinal detachment repair.

PURPOSE To find predictive markers for the visual potential in optical coherence tomography (OCT) one month after surgical repair of macula-involving rhegmatogenous retinal detachment (miRD) with and without internal limiting membrane (ILM) peeling. METHODS This retrospective single-center, single-surgeon cohort study included 74 patients who underwent pars plana vitrectomy (PPV) for primary miRD between January 2013 and August 2020 with follow-up examinations for at least 6 months. Patients developing recurrent detachments, media opacities, or with an axial length over 27 mm were excluded from the analysis. LogMAR visual (VA) and LogRAD reading acuity (RA) ± standard deviation (SD), and OCT measurements 6 months after surgery were compared to OCT and VA measurements one month after surgery using multiple linear regression analysis for predictions. RESULTS VA increased from 0.34 ± 0.25 at one month to 0.22 ± 0.21 after 6 months [p < 0.001; effect size = -0.662, 95% confidence interval (CI): -(0.99-0.33)]. The continuity of the external limiting membrane (ELM) and ellipsoid zone (EZ) increased between 1 and 6 months. Subfoveal ELM integrity after one month predicted VA [adjusted R2 of 8.0%, F(2, 71) = 4.17, p = 0.018] and RA [adjusted R2 of 29%, F(2, 27) = 6.81, p = 0.002] after 6 months. EZ integrity had a less pronounced predictive effect on VA and RA. ELM integrity after 1 month correlated with better reading acuity after 6 months (p = 0.016). CONCLUSION VA and morphological OCT parameters improve between 1 and 6 months after surgery for miRD. The grade of ELM is a better predictor for RA than for VA, explaining more variance

Cynomolgus monkey's choroid reference database derived from hybrid deep learning optical coherence tomography segmentation.

Cynomolgus monkeys exhibit human-like features, such as a fovea, so they are often used in non-clinical research. Nevertheless, little is known about the natural variation of the choroidal thickness in relation to origin and sex. A combination of deep learning and a deterministic computer vision algorithm was applied for automatic segmentation of foveolar optical coherence tomography images in cynomolgus monkeys. The main evaluation parameters were choroidal thickness and surface area directed from the deepest point on OCT images within the fovea, marked as the nulla with regard to sex and origin. Reference choroid landmarks were set underneath the nulla and at 500 µm intervals laterally up to a distance of 2000 µm nasally and temporally, complemented by a sub-analysis of the central bouquet of cones. 203 animals contributed 374 eyes for a reference choroid database. The overall average central choroidal thickness was 193 µm with a coefficient of variation of 7.8%, and the overall mean surface area of the central bouquet temporally was 19,335 µm2 and nasally was 19,283 µm2. The choroidal thickness of the fovea appears relatively homogeneous between the sexes and the studied origins. However, considerable natural variation has been observed, which needs to be appreciated

The effect of extracellular nucleotides on cytokine production and phagocytosis of macrophages

Bacterial sepsis is a severe clinical condition, leading to severe sepsis, septic shock, and death. The complex pathophysiology of sepsis is not yet fully understood. Cytokines, released by immune cells such as macrophages, play an important role in the pathophysiology of sepsis. Kupffer cells are the largest population of macrophages in the body. Purinergic signaling, mediated by different nucleosides and nucleotides, and purinergic receptors, has been shown to have various effects on cytokine release, inflammatory processes and the immune system. In our work with in vitro experiments we studied the effect of extracellular nucleotides on the release of TNFα by primary murine Kupffer cells, and the effect of extracellular nucleotides on the phagocytosis of murine RAW 264.7 and human U-937 cell culture macrophages. Secretion of TNFα was measured using ELISA, phagocytosis of bio particles was measured using a plate reader phagocytosis assay and flow cytometry. Our experiments show, that extracellular LPS stimulate release of TNFα in murine Kupffer cells and that extracellular nucleotides inhibit this effect in a dose dependent matter. Our other experiments show phagocytosis of fluorescence labeled bio particles by both macrophage cell lines RAW 264.7 and U-937 in a dose dependent manner. The experiments could not show an effect of extracellular nucleotides on phagocytosis of cell culture macrophages

Rezidivprophylaxe der Zytomegalievirus-Uveitis mit topischem Ganciclovir

PURPOSE ytomegalovirus (CMV) can cause recurrent or chronic hypertensive anterior uveitis in immunocompetent patients. Antiviral treatment options include topical ganciclovir or systemic valganciclovir. However, recurrences are common after stopping treatment. We evaluated the efficacy of long-term topical ganciclovir therapy as prophylaxis for recurrent activity. METHODS AND PATIENTS Retrospective analysis of all CMV uveitis patients seen between 2011 and 2018 at Zurich University Hospital. Inclusion criteria were suspected viral anterior uveitis and a positive CMV polymerase chain reaction of the anterior chamber (AC) tap. After diagnosis, topical therapy with ganciclovir gel 5 × daily was started and tapered according to clinical activity. Topical steroids and glaucoma medication were used according to clinical assessment. An active episode was defined as increase in AC inflammatory activity and/or a uveitis-related rise in intraocular pressure (IOP) greater than 25 mmHg. Episodes were analysed before and after initiation of ganciclovir therapy. RESULTS Six patients, median age 51 (range 24 - 62) years old, were included. All patients had hypertensive unilateral anterior uveitis and presented with small to medium sized endothelial precipitates and with 0.5+ to 2+ AC cells. Median IOP in the affected eye at initial presentation was 43 mmHg (range 36 - 60). Median time from first episode to diagnosis was 19.5 (range 5 - 193) months. Median number of episodes before ganciclovir treatment was 4 (2 - 20), corresponding to a mean of 3.04 episodes per year. Median follow-up time after initiation of ganciclovir medication was 26 (range 4 to 62) months. Median number of episodes under treatment was 1 (range 0 - 6), corresponding to a mean of 0.19 episodes per year (p = 0.04, 2-sided paired t-test). The median (range) for the individually chosen long-term prophylactic dose was ganciclovir gel 2 (0 - 4) times daily, and topical steroids 1 (0 - 2) times daily. Lower doses lead to recurrences in 3 patients (50%). Glaucoma and cataract surgery were performed in 2 patients (33%). CONCLUSION Although a rare entity in Central Europe, the important feature of CMV uveitis is its hypertensive and recurrent nature. In our cases, topical ganciclovir was found to be an effective treatment. Inflammatory activity was well controlled by using an individually assessed prophylactic dose. Larger studies assessing long-term prophylaxis are desirable