Preventive Inflammation Management with Steroids before Retreatment with Anti-VEGF after Severe Inflammation due to Brolucizumab.

PURPOSE: We report two successful cases of treatment by steroids after severe inflammation due to an intravitreal injection (IVI) of brolucizumab and their retreatment with another type of anti-vascular endothelial growth factor (VEGF), with steroid treatments to prevent severe inflammatory recurrence in patients with exudative age-related macular degeneration (AMD). CLINICAL CASES, CASE 1: An 88-year-old woman with exudative AMD in her left eye who had persistent subretinal fluid despite receiving an IVI, including ranibizumab and, subsequently, aflibercept. A switch to brolucizumab was decided. Two weeks after the third dose, she had a visual loss decreasing from 20/40 to counting fingers at 50 cm. Fundus examination revealed retinal whitening and perivenous sheathing. Fluoresceine angiography confirmed retinal arterial occlusion. Differential diagnoses were ruled out. She was treated with intravenous methylprednisolone and prednisolone eye drops. Three months after the treatment, visual acuity improved to 20/80 with no intraocular inflammation but subretinal fluid recurred. IVI of ranibizumab was rescheduled with preventive treatment by oral and local prednisolone without any inflammation recurrence. CASE 2: An 80-year-old man with exudative AMD in his right eye who had persistent subretinal fluid despite an IVI of aflibercept. Switching him to brolucizumab was decided. Two months after the third dose, he had blurred vision with no pain. Visual acuity decreased from 20/20 to 20/25. Examination showed 1+ anterior chamber cells and hyalitis. We confirmed the diagnosis of anterior uveitis with hyalitis. Differential diagnoses were ruled out. Treatment by prednisolone eye drops was initiated every 30 minutes for 1 day with a gradual decrease for 6 weeks. One week later, visual acuity improved to 20/20 with no inflammation. Three weeks later, subretinal fluid due to AMD increased. The patient was retreated by aflibercept with prednisolone eye drops, 48 hours before and after the IVI, with no recurrence of inflammation. DISCUSSION: Brolucizumab is one of the latest FDA-approved anti-VEGF agents for wet AMD. Since its wider use, few cases of severe ocular inflammation have been reported in post-marketing analysis. Because wet AMD recurrences should be expected after intraocular inflammation, insight is needed into treatment tolerance in cases that received further IVI retreatment. CONCLUSION: Our cases demonstrate that an IVI reinjection with a different anti-VEGF drug for exudative AMD recurrence can be safely reperformed. The use of local steroids could be effective in preventing recurrence of ocular inflammation after severe intraocular inflammation due to brolucizumab.

Six Cases of Retinal Vascular Anomalies after Coronavirus Disease 2019: A Case Series.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) and its rapid spread has resulted in unexplored clinical ophthalmological manifestations. This report aims to describe a series of retinal vascular anomalies diagnosed with the use of fluorescein angiography, following contraction of COVID-19. HISTORY AND SIGNS: Symptoms reported by patients were central scotoma (one case), inferior scotoma (one case), and a sensation of mild loss of vision during the COVID-19 follow-up (four cases). Best-corrected visual acuity was preserved in all patients, apart from one, who had a visual acuity of 0.4, decimal scale (6/15, Snellen) in the left eye. THERAPY AND OUTCOME: Clinical manifestations included bilateral retinal vasculitis (two cases), branch retinal vein occlusion (one case), branch retinal artery occlusion (one case), hemi-central retinal vein occlusion (one case), and optic disc edema due to central retinal vein occlusion (one case) occurring 0 - 8 months after COVID-19 contraction. Serological testing was performed in every patient to exclude any other recognized cause of retinal vascular occlusion and inflammation and to confirm immunity against the novel coronavirus. None of the patients required any ocular treatment. CONCLUSIONS: Arterial and venous occlusive as well as inflammatory retinal vascular pathologies can occur both during and after the acute phase of COVID-19 as manifestations of ocular long-term effects of COVID-19 and should be included in the differential diagnosis of retinal occlusive pathologies. This case series suggests that careful investigations, including fundoscopy and fluorescein angiography, should be required in patients with visual complaints, both in the acute and long-term follow-up of COVID-19.

Cell patterning by secretion-induced plasma membrane flows.

Cells self-organize using reaction-diffusion and fluid-flow principles. Whether bulk membrane flows contribute to cell patterning has not been established. Here, using mathematical modeling, optogenetics, and synthetic probes, we show that polarized exocytosis causes lateral membrane flows away from regions of membrane insertion. Plasma membrane­associated proteins with sufficiently low diffusion and/or detachment rates couple to the flows and deplete from areas of exocytosis. In rod-shaped fission yeast cells, zones of Cdc42 GTPase activity driving polarized exocytosis are limited by GTPase activating proteins (GAPs). We show that membrane flows pattern the GAP Rga4 distribution and that coupling of a synthetic GAP to membrane flows is sufficient to establish the rod shape. Thus, membrane flows induced by Cdc42-dependent exocytosis form a negative feedback restricting the zone of Cdc42 activity.

Yeast haspin kinase regulates polarity cues necessary for mitotic spindle positioning and is required to tolerate mitotic arrest.

Haspin is an atypical protein kinase that in several organisms phosphorylates histone H3Thr3 and is involved in chromosome segregation. In Saccharomyces cerevisiae, H3Thr3 phosphorylation has never been observed and the function of haspin is unknown. We show that deletion of ALK1 and ALK2 haspin paralogs causes the mislocalization of polarisome components. Following a transient mitotic arrest, this leads to an overly polarized actin distribution in the bud where the mitotic spindle is pulled. Here it elongates, generating anucleated mothers and binucleated daughters. Reducing the intensity of the bud-directed pulling forces partially restores proper cell division. We propose that haspin controls the localization of polarity cues to preserve the coordination between polarization and the cell cycle and to tolerate transient mitotic arrests. The evolutionary conservation of haspin and of the polarization mechanisms suggests that this function of haspin is likely shared with other eukaryotes, in which haspin may regulate asymmetric cell division.