An elusive case of malignant optic nerve glioma with a suprasellar mass.

A 67-year-old man with multiple comorbidities presented with 3 weeks of orbital pain, proptosis, and no light perception vision in the left eye. Examination was notable for a left orbital apex syndrome with CN III, VI palsies, an optic neuropathy, and central retinal vein occlusion. Magnetic resonance imaging of the orbits was notable for extensive enhancement, enlargement, and T2 hyperintensity of the optic nerve, with perineural sheath enhancement, and chiasmal hyperintensity. Inflammatory workup and lumbar puncture were unremarkable. No improvement was seen after a 3-day course of intravenous solumedrol. Initial optic nerve biopsy revealed necrotic nerve tissue, macrophage infiltration, increased vascularization, and peripheral gliosis. The volume of tissue was inadequate for genomic analysis. The patient was lost to follow-up but returned 5 months later with right-sided vision loss. Repeat neuroimaging showed a new suprasellar mass and progressive expansion and enhancement of both optic nerves. Biopsies of the suprasellar mass and left nerve at this time were consistent with a high-grade glial neoplasm, WHO grade IV. This is a rare case of glioblastoma involving the optic nerves and suprasellar region. In such cases, molecular profiling can improve diagnosis and may provide for targeted treatments in the future.

Primary Graft Failure, Infection, and Endothelial Cell Density in Corneal Transplants With Increased Death-to-Preservation Time.

PURPOSE: To ascertain whether death-to-preservation time (DPT) is associated with donor endothelial cell density (ECD), primary graft failure (PGF), and infection. METHODS: Donor corneas aged older than 10 years with ECD 2000 to 4500 cells/mm2 were procured between 2011 and 2018 by a single eye bank. Donor corneas were analyzed retrospectively for the main outcome measures of PGF, infection, and ECD. Means and proportions of study parameters were compared between corneas with long and short DPT, defined as greater or less than 14 hours, respectively, excluding corneas with a history of intraocular surgery or diabetes. Multivariate analyses were performed using logistic regression, adjusting for donor age at time of death, history of diabetes mellitus, and history of cataract surgery. RESULTS: Among 12,015 corneas, those with long DPT had a statistically but not clinically significant higher ECD than that of corneas with short DPT (2754 vs. 2724 cells/mm2, P < 0.01). There was no difference in PGF and infections in corneas with long versus short DPT (0.28% vs. 0.26%, P = 0.86; 0.43% vs. 0.29%, P = 0.51, respectively). CONCLUSIONS: Longer DPT is not associated with a clinically meaningful reduction in donor ECD, PGF, or infection.

Impact of Glaucoma and Dry Eye on Text-Based Searching.

PURPOSE: We determine if visual field loss from glaucoma and/or measures of dry eye severity are associated with difficulty searching, as judged by slower search times on a text-based search task. METHODS: Glaucoma patients with bilateral visual field (VF) loss, patients with clinically significant dry eye, and normally-sighted controls were enrolled from the Wilmer Eye Institute clinics. Subjects searched three Yellow Pages excerpts for a specific phone number, and search time was recorded. RESULTS: A total of 50 glaucoma subjects, 40 dry eye subjects, and 45 controls completed study procedures. On average, glaucoma patients exhibited 57% longer search times compared to controls (95% confidence interval [CI], 26%-96%, P < 0.001), and longer search times were noted among subjects with greater VF loss (P < 0.001), worse contrast sensitivity (P < 0.001), and worse visual acuity (P = 0.026). Dry eye subjects demonstrated similar search times compared to controls, though worse Ocular Surface Disease Index (OSDI) vision-related subscores were associated with longer search times (P < 0.01). Search times showed no association with OSDI symptom subscores (P = 0.20) or objective measures of dry eye (P > 0.08 for Schirmer's testing without anesthesia, corneal fluorescein staining, and tear film breakup time). CONCLUSIONS: Text-based visual search is slower for glaucoma patients with greater levels of VF loss and dry eye patients with greater self-reported visual difficulty, and these difficulties may contribute to decreased quality of life in these groups. TRANSLATIONAL RELEVANCE: Visual search is impaired in glaucoma and dry eye groups compared to controls, highlighting the need for compensatory strategies and tools to assist individuals in overcoming their deficiencies.

Evaluation of a field test for antibodies against Chlamydia trachomatis during trachoma surveillance in Nepal.

PURPOSE: Testing for antibodies to Chlamydia trachomatis has potential as a surveillance tool. Our evaluation compares lateral flow assays (LFAs) during surveillance surveys in Nepal with Multiplex bead array (MBA). Fifty children were randomly sampled from each of 15 random clusters in two districts of Nepal. Finger prick blood samples were collected from 1509 children and tested onsite for anti-Pgp3 antibodies by LFA. The LFA was read at 30min as negative, positive, or invalid. Tests results were also rated as difficult to read ("equivocal"). Blood was processed at Johns Hopkins University using the MBA. RESULTS: The LFA had agreement of 40.0% for MBA-positive samples and 99.3% for MBA-negative samples. Inter-reader reliability was kappa=0.65 (95% CI=0.56-0.74). If the equivocal results (7%) could be decreased, reliability could be improved. CONCLUSIONS: Further optimization and testing of the LFA test are needed to improve agreement with MBA and the interpretation of the results.

Serotonin potentiates transforming growth factor-beta3 induced biomechanical remodeling in avian embryonic atrioventricular valves.

Embryonic heart valve primordia (cushions) maintain unidirectional blood flow during development despite an increasingly demanding mechanical environment. Recent studies demonstrate that atrioventricular (AV) cushions stiffen over gestation, but the molecular mechanisms of this process are unknown. Transforming growth factor-beta (TGFß) and serotonin (5-HT) signaling modulate tissue biomechanics of postnatal valves, but less is known of their role in the biomechanical remodeling of embryonic valves. In this study, we demonstrate that exogenous TGFß3 increases AV cushion biomechanical stiffness and residual stress, but paradoxically reduces matrix compaction. We then show that TGFß3 induces contractile gene expression (RhoA, aSMA) and extracellular matrix expression (col1α2) in cushion mesenchyme, while simultaneously stimulating a two-fold increase in proliferation. Local compaction increased due to an elevated contractile phenotype, but global compaction appeared reduced due to proliferation and ECM synthesis. Blockade of TGFß type I receptors via SB431542 inhibited the TGFß3 effects. We next showed that exogenous 5-HT does not influence cushion stiffness by itself, but synergistically increases cushion stiffness with TGFß3 co-treatment. 5-HT increased TGFß3 gene expression and also potentiated TGFß3 induced gene expression in a dose-dependent manner. Blockade of the 5HT2b receptor, but not 5-HT2a receptor or serotonin transporter (SERT), resulted in complete cessation of TGFß3 induced mechanical strengthening. Finally, systemic 5-HT administration in ovo induced cushion remodeling related defects, including thinned/atretic AV valves, ventricular septal defects, and outflow rotation defects. Elevated 5-HT in ovo resulted in elevated remodeling gene expression and increased TGFß signaling activity, supporting our ex-vivo findings. Collectively, these results highlight TGFß/5-HT signaling as a potent mechanism for control of biomechanical remodeling of AV cushions during development.