Delayed Corneal Epithelial Healing after Intravitreal Bevacizumab: A Clinical and Experimental Study

Purpose: To report corneal epithelial defects (CEDs) and delayed epithelial healing after intravitreal bevacizumab (IVB) injection and to describe delayed corneal epithelial healing with topical administration of bevacizumab in an experimental rabbit model. Methods: A retrospective chart review was performed on 850 eyes of 850 patients with neovascular eye disease and diabetic macular edema who had received 1.25 to 2.5 mg IVB. In the experimental arm of the study, photorefractive keratectomy was used to create a 3 mm CED in the right eyes of 18 New Zealand rabbits which were then randomized to three equal groups. All rabbits received topical antibiotics, additionally those in group A received topical bevacizumab and animals in group B were treated with topical corticosteroids. The rate of epithelial healing was assessed at different time points using slitlamp photography. Results: In the clinical study, seven eyes of seven subjects developed CEDs the day after IVB injection. All of these eyes had preexisting corneal edema. The healing period ranged from 3 to 38 days (average 11 days) despite appropriate medical management. In the experimental study, topical bevacizumab and corticosteroids both significantly hindered corneal epithelial healing at 12 and 24 hours. Conclusion: Bevacizumab was demonstrated to cause CEDs in clinical settings. Moreover, corneal epithelial healing was delayed by topical application of bevacizumab, in the experimental model. These short-term results suggest that corneal edema may be considered as a risk factor for epithelial defects after IVB

Significance of Myelin Oligodendrocyte Glycoprotein Antibodies in CSF: A Retrospective Multicenter Study

Background and Objectives: Although the diagnosis of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is based on serum MOG antibodies (MOG-Abs) positivity, patients with coexisting or restricted MOG-Abs in the CSF have been reported. The aim of this study is to characterize the relevance of CSF MOG-Abs positivity in clinical practice. Methods: Eleven medical centres retrospectively collected clinical and laboratory data of adult and pediatric patients with suspected inflammatory CNS disease and MOG-Abs positivity in serum and/or CSF, using live cell-based assays. Comparisons were performed using parametric or non-parametric tests, as appropriate. Potential factors of unfavourable outcomes were explored by Cox proportional hazard models and logistic regression. Results: The cohort included 255 patients: 139 (55%) females and 132 (52%) children (i.e. <18 year-old). Among them, 145 patients (56.8%) had MOG-Abs in both serum and CSF (MOG-Abs seropositive and CSF positive), 79 (31%) only in serum (MOG-Abs seropositive and CSF negative), and 31 (12%) only in CSF (MOG-Abs seronegative and CSF positive). MOG-Abs seronegative and CSF positive predominated in adults (22% vs 3% of children), presented more commonly with motor (n=14, 45%) and sensory symptoms (n=13, 42%), and all but 4 (2 MS, 1 polyradiculoneuritis, 1 Susac syndrome) had a final diagnosis compatible with MOGAD. When comparing seropositive patients according to MOG-Abs CSF status, MOG-Abs seropositive and CSF positive patients had a higher EDSS at nadir during the index event (median 4.5, IQR 3.0-7.5 vs. 3.0, IQR 2.0-6.8, p=0.007) and presented more commonly with sensory (45.5% vs. 24%, p=0.002), motor (33.6% vs 19%, p=0.021), and sphincter symptoms (26.9% vs 7.8%, p=0.001) than MOG-Abs seropositive and CSF negative. At last follow-up, MOG-Abs seropositive and CSF positive cases had more often persistent sphincter dysfunction (17.3% vs 4.3%, p=0.008). Compared with seropositive patients, those MOG-Abs seronegative and CSF positive had higher disability at last follow-up (p≤0.001) and MOG-Abs seronegative and CSF positive status was independently associated with an EDSS ≥3.0. Conclusion: Paired serum and CSF MOG-Abs positivity is common in MOGAD and is associated with a more severe clinical presentation. CSF only MOG-Abs positivity can occur in patients with a phenotype suggestive of MOGAD and is associated with a worse outcome. Taken together, these data suggest a clinical interest in assessing CSF MOG-Abs in patients with a phenotype suggestive of MOGAD, regardless of the MOG-Abs serostatus