Vacuum-assisted staged omphalocele reduction: A preliminary report.

Introduction: Omphalocele represents a rare congenital abdominal wall defect. In giant omphalocele, due to the viscero-abdominal disproportion, gradual reintegration of eviscerated organs is often associated with medical challenges. We report our preliminary experience combining staged gravitational reduction with vacuum (VAC) therapy as a novel approach for treatment of giant omphalocele. Patients and methods: Retrospective chart review of six patients (five females) born between September 2018 and May 2022 who underwent staged reduction of giant omphalocele in conjunction with VAC therapy was conducted. Treatment was performed at two German third-level Pediatric Surgery Departments. Biometric and periprocedural data were assessed. Main outcome measure was the feasibility of VAC therapy for giant omphalocele. Data are reported as median and interquartile range (Q1-Q3). Results: Gestational age was 37 (37-38) weeks, and birth weight was 2700 (2500-3000) g. VAC dressing was changed every 3 (3-4) days until abdominal fascia closure at the age of 9 (3-13) days. Time to first/full oral feeds was 3 (1-5)/20 (12-24) days with a hospital stay of 22 (17-30) days. Follow-up was 8 (5-22) months and complications were of minor extent (none: n = 2; Clavien-Dindo I: n = 3; Clavien-Dindo II: n = 1), comprising a delayed neo-umbilical cord rest separation (n = 2) and/or concomitant neo-umbilical site infection (n = 2) with no repeat surgery. Conclusion: In neonates with giant omphalocele, VAC constitutes a promising and technically feasible enhancement of the staged gravitational reduction method. This study shows evidence that VAC may accelerate restoration of the abdominal wall integrity in giant omphalocele, thus minimizing associated comorbidities inherent to a prolonged hospitalization.

Progressive Retinal and Optic Nerve Damage in a Mouse Model of Spontaneous Opticospinal Encephalomyelitis.

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are antibody mediated CNS disorders mostly affecting the optic nerve and spinal cord with potential severe impact on the visual pathway. Here, we investigated inflammation and degeneration of the visual system in a spontaneous encephalomyelitis animal model. We used double-transgenic (2D2/Th) mice which develop a spontaneous opticospinal encephalomyelitis (OSE). Retinal morphology and its function were evaluated via spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) in 6- and 8-week-old mice. Immunohistochemistry of retina and optic nerve and examination of the retina via RT-qPCR were performed using markers for inflammation, immune cells and the complement pathway. OSE mice showed clinical signs of encephalomyelitis with an incidence of 75% at day 38. A progressive retinal thinning was detected in OSE mice via SD-OCT. An impairment in photoreceptor signal transmission occurred. This was accompanied by cellular infiltration and demyelination of optic nerves. The number of microglia/macrophages was increased in OSE optic nerves and retinas. Analysis of the retina revealed a reduced retinal ganglion cell number and downregulated Pou4f1 mRNA expression in OSE retinas. RT-qPCR revealed an elevation of microglia markers and the cytokines Tnfa and Tgfb. We also documented an upregulation of the complement system via the classical pathway. In summary, we describe characteristics of inflammation and degeneration of the visual system in a spontaneous encephalomyelitis model, characterized by coinciding inflammatory and degenerative mechanisms in both retina and optic nerve with involvement of the complement system.

Binding patterns and functional properties of human antibodies to AQP4 and MOG on murine optic nerve and retina.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-inflammatory CNS disease affecting spinal cord and optic nerves, mediated by autoantibodies against aquaporin-4 (AQP4) and myelin-oligodendrocyte-glycoprotein (MOG). Effects of those immunoglobulins (Ig) on retina and optic nerve are incompletely understood. We investigated AQP4-IgG and MOG-IgG sera on retina and optic nerve ex vivo and in 2D2 mice, which harbor a transgenic MOG-specific T-cell receptor. Some sera reacted with murine retina and optic nerve showing distinct binding patterns, suggesting different epitopes being targeted in both subgroups. Transfer of total IgG from a MOG-IgG positive patient to 2D2 mice did neither enhance disability nor induce functional or histological alterations in the retina.

Laquinimod protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model.

BACKGROUND: The oral immunomodulatory agent laquinimod is currently evaluated for multiple sclerosis (MS) treatment. Phase II and III studies demonstrated a reduction of degenerative processes. In addition to anti-inflammatory effects, laquinimod might have neuroprotective properties, but its impact on the visual system, which is often affected by MS, is unknown. The aim of our study was to investigate potential protective effects of laquinimod on the optic nerve and retina in an experimental autoimmune encephalomyelitis (EAE) model. METHODS: We induced EAE in C57/BL6 mice via MOG35-55 immunization. Animals were divided into an untreated EAE group, three EAE groups receiving laquinimod (1, 5, or 25 mg/kg daily), starting the day post-immunization, and a non-immunized control group. Thirty days post-immunization, scotopic electroretinograms were carried out, and mice were sacrificed for histopathology (HE, LFB), immunohistochemistry (MBP, Iba1, Tmem119, F4/80, GFAP, vimentin, Brn-3a, cleaved caspase 3) of the optic nerve and retina, and retinal qRT-PCR analyses (Brn-3a, Iba1, Tmem119, AMWAP, CD68, GFAP). To evaluate the effect of a therapeutic approach, EAE animals were treated with 25 mg/kg laquinimod from day 16 when 60% of the animals had developed clinical signs of EAE. RESULTS: Laquinimod reduced neurological EAE symptoms and improved the neuronal electrical output of the inner nuclear layer compared to untreated EAE mice. Furthermore, cellular infiltration, especially recruited phagocytes, and demyelination in the optic nerve were reduced. Microglia were diminished in optic nerve and retina. Retinal macroglial signal was reduced under treatment, whereas in the optic nerve macroglia were not affected. Additionally, laquinimod preserved retinal ganglion cells and reduced apoptosis. A later treatment with laquinimod in a therapeutic approach led to a reduction of clinical signs and to an improved b-wave amplitude. However, no changes in cellular infiltration and demyelination of the optic nerves were observed. Also, the number of retinal ganglion cells remained unaltered. CONCLUSION: From our study, we deduce neuroprotective and anti-inflammatory effects of laquinimod on the optic nerve and retina in EAE mice, when animals were treated before any clinical signs were noted. Given the fact that the visual system is frequently affected by MS, the agent might be an interesting subject of further neuro-ophthalmic investigations.