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Since the first description of swelling of the optic nerve head in patients with increased intracranial pressure, our understanding of its pathogenesis has undergone significant changes. Early theories postulated that the swelling was caused by excessive extracellular fluid, but these views were disproved when electron microscopy showed that the swelling arose from dilated optic nerve axons, and autoradiography demonstrated blocked axonal transport at the posterior lamina cribrosa. This led to the currently prevailing view that the axonal swelling is caused by the damming back of axoplasm. However, this theory cannot account for the extent of swelling, its rate of development, and the variety of morphological changes in papilledema. It also cannot explain the differing patterns of swelling in papilledema and acute glaucoma despite identically located blockages of axonal transport. We conducted a biomechanical analysis, in which we calculated the stresses induced in a cylindrical nerve by external compression and the effect of these stresses on the nerve’s axons and the axoplasm within them. We propose a new theory in which the axial gradient of tissue pressure causes displacement of axoplasm from the extraocular to the intraocular segment of the nerve, accounting for the intraocular axonal swelling. In addition, a sharply localized axial shear stress disrupts the axonal cytoskeleton to block axonal transport. Although the pressure gradient and the shear stress are both caused by the external compression of the nerve, they differ in their relative magnitudes across the nerve cross-section. The proposed hypothesis resolves the difficulties with the damming back hypothesis.

Vascular development and maintenance are controlled by a complex transcriptional program, which integrates both extracellular and intracellular signals in endothelial cells. Here we study the roles of three closely related SoxF family transcription factors-Sox7, Sox17, and Sox18 -in the developing and mature mouse vasculature using targeted gene deletion on a mixed C57/129/CD1 genetic background. In the retinal vasculature, each SoxF gene exhibits a distinctive pattern of expression in different classes of blood vessels. On a mixed genetic background, vascular endothelial-specific deletion of individual SoxF genes has little or no effect on vascular architecture or differentiation, a result that can be explained by overlapping function and by reciprocal regulation of gene expression between Sox7 and Sox17. By contrast, combined deletion of Sox7, Sox17, and Sox18 at the onset of retinal angiogenesis leads to a dense capillary plexus with a nearly complete loss of radial arteries and veins, whereas the presence of a single Sox17 allele largely restores arterial identity, as determined by vascular smooth muscle cell coverage. In the developing retina, expression of all three SoxF genes is reduced in the absence of Norrin/Frizzled4-mediated canonical Wnt signaling, but SoxF gene expression is unaffected by reduced VEGF signaling in response to deletion of Neuropilin1 (Npn1). In adulthood, Sox7, Sox17, and Sox18 act in a largely redundant manner to maintain blood vessel function, as adult onset vascular endothelial-specific deletion of all three SoxF genes leads to massive edema despite nearly normal vascular architecture. These data reveal critical and partially redundant roles for Sox7, Sox17 and Sox18 in vascular growth, differentiation, and maintenance.

Syphilis produces myriad nonspecific signs and symptoms. For example, optic disk swelling might be seen in patients with syphilis as a result of cranial hypertension (papilloedema), inflammatory optic neuritis with papillitis, or optic perineuritis. We report a case involving differential diagnosis of syphilitic bilateral papillitis mimicking papilloedema.

Purpose of Review Mild papilledema may be difficult to distinguish by clinical observation from pseudopapilledema. An accurate diagnosis is critical to avoid invasive workup and unwarranted treatment. In this review, we focus on the development and subsequent role of optical coherence tomography (OCT) in detecting and differentiating optic nerve head drusen (ONHD) from papilledema and other causes of acquired swelling of the optic disc. Recent Findings Newer OCT technologies which permit deeper penetration to improve detection of ONHD were also reviewed. Enhanced depth imaging (EDI) spectral-domain OCT and swept-source (SS) OCT are currently recognized as the most reliable and sensitive tools to diagnose ONHD. Summary OCT devices currently available provide a means to quantify drusen dimensions, to evaluate the integrity of neighboring structures and to monitor axonal and neuronal damage, yielding additional information to better understand the relationship between the morphological features of drusen, and their effects on the structure and function of the optic nerve.

Headache is a common complaint in children who present at the pediatric emergency department (PED). Serious conditions such as intracranial tumors and idiopathic intracranial hypertension (IIH) should be rapidly ruled out. Ophthalmoscopy for the presence of papilledema has long been considered critical to the assessment of headaches in children; however, the yield of this procedure is poorly validated. This retrospective study implemented a computerized search of the medical records of a single tertiary center to identify all children aged 2–18 years who presented at the PED complaining of headache between 2007 and 2017. The clinical, demographic, radiographic, and laboratory data were analyzed. Of the 948 children aged 2–18 years who presented at the PED complaining of headache, 536 had an ophthalmoscopy examination carried out by an ophthalmologist. Forty-one had papilledema, of whom 7 had an intracranial tumor, 15 had IIH, and 9 had optic nerve head drusen. Of the 495 children without papilledema, 3 had intracranial tumor, and 11 had IIH. The sensitivity and specificity of papilledema for the diagnosis of intracranial tumor were 70% and 93.5%, respectively, with an NPV and PPV of 99.4% and 17.1%, respectively. The sensitivity and specificity of papilledema for the diagnosis of intracranial pathology in general were 61.1% and 96.2%, respectively, with an NPV and PPV of 97.2% and 53.7%, respectively.   Conclusion : Assessment by ophthalmoscopy for papilledema in children presenting to the PED with headache had high sensitivity and high specificity, thus reinforcing the importance of ophthalmoscopy as a screening tool in these children. What is Known: • Headache is a common complaint in children. Serious intracranial pathologies need to be rapidly excluded. • Ophthalmoscopy for the presence of papilledema is commonly used as a screening tool for intracranial pathology, but this procedure is poorly validated. What is New: • Ophthalmoscopy for the assessment of papilledema in children who present with headache to the pediatric emergency department is shown to exhibit sensitivity and specificity for the diagnosis of intracranial pathology.

The mechanism underlying the effects of anti-vascular endothelial growth factor (VEGF) antibody in retinal vein occlusion (RVO) treatment is poorly understood, partly due to the lack of RVO animal models that mimic clinical pathology. The aims of this study were to establish a suitable RVO model, clarify the pathogenic mechanisms, and evaluate the effects of anti-VEGF antibody in the model. Mouse retinal veins were occluded by laser photocoagulation after rose bengal injection. Reduction of the b/a wave amplitude ratio, retinal nonperfusion, cystoid edema, and hard exudates were observed after occlusion, and expression of RVO-related genes was altered. Administration of anti-VEGF antibody immediately, or 7 days, after occlusion resulted in reduction and increase of the nonperfused area, respectively. We conclude that the present model will be useful for clarification of the pathogenic mechanisms, and that the timing of anti-VEGF antibody administration is important for the successful amelioration of retinal nonperfusion.

Spaceflight associated neuro‐ocular syndrome (SANS) is hypothesized to develop as a consequence of the chronic headward fluid shift that occurs in sustained weightlessness. We exposed healthy subjects (n = 24) to strict 6° head‐down tilt bed rest (HDTBR), an analog of weightlessness that generates a sustained headward fluid shift, and we monitored for ocular changes similar to findings that develop in SANS. Two‐thirds of the subjects received a daily 30‐min exposure to artificial gravity (AG, 1 g at center of mass, ~0.3 g at eye level) during HDTBR by either continuous (cAG, n = 8) or intermittent (iAG, n = 8) short‐arm centrifugation to investigate whether this intervention would attenuate headward fluid shift‐induced ocular changes. Optical coherence tomography images were acquired to quantify changes in peripapillary total retinal thickness (TRT), retinal nerve fiber layer thickness, and choroidal thickness, and to detect chorioretinal folds. Intraocular pressure (IOP), optical biometry, and standard automated perimetry data were collected. TRT increased by 35.9 µm (95% CI, 19.9–51.9 µm, p < 0.0001), 36.5 µm (95% CI, 4.7–68.2 µm, p = 0.01), and 27.6 µm (95% CI, 8.8–46.3 µm, p = 0.0005) at HDTBR day 58 in the control, cAG, and iAG groups, respectively. Chorioretinal folds developed in six subjects across the groups, despite small increases in IOP. Visual function outcomes did not change. These findings validate strict HDTBR without elevated ambient CO2 as a model for investigating SANS and suggest that a fluid shift reversal of longer duration and/or greater magnitude at the eye may be required to prevent or mitigate SANS. Spaceflight associated neuro‐ocular syndrome (SANS) is hypothesized to develop as a consequence of the chronic headward fluid shift that occurs in sustained weightlessness. To investigate this condition, healthy subjects were exposed to strict 6º head‐down tilt bed rest (HDTBR), a spaceflight analog that causes a chronic headward fluid shift and can lead to the development of optic disc edema in some participants. For the first time, we demonstrate that chorioretinal folds develop during HDTBR, along with signs of optic disc edema, similar to findings that occur in astronauts during spaceflight. However, ocular changes were not mitigated in subjects who were exposed for 30 min per day to continuous or intermittent artificial gravity (AG) via centrifugation during HDTBR. These findings validate strict HDTBR without elevated ambient CO2 as a model for investigating these ocular changes and suggest that a fluid shift reversal of longer duration and/or greater magnitude at the eye than used here may be required to prevent or mitigate spaceflight associated neuro‐ocular syndrome findings.

To assess the usefulness of spectral-domain optical coherence tomography (SD-OCT) peripapillary retinal nerve fiber layer (RNFL) thickness measurement in discriminating early phase optic disc edema (ODE) from pseudoedema (PODE). Hospital-based, multicenter, cross-sectional study involving external patients referred for recent identification of \"presumed ODE\". Patients underwent SD-OCT optic nerve head (ONH) RNFL thickness measurement at their first evaluation. In 155 of these, the causative etiology was subsequently ascertained and the respective eyes (one per patient) were assigned to the ODE (95 eyes) or PODE (60 eyes) group. Admission SD-OCT data were retrieved and used for the analysis. ROC curve analysis was used to calculate specificity, sensitivity and predictive value (PV) of the RNFL values. The PODE group was significantly younger than the ODE group (p = 0.007). The average and any single-quadrant RNFL thickness was significantly higher in the ODE group compared with the PODE and control groups. The average and the inferior quadrant thicknesses tested the most powerful parameters to differentiate ODE from PODE. A cutoff value of ≥ 110 μm for the average area, or of ≥ 150 μm for the inferior quadrant was associated with maximal sensitivity and specificity with positive PV greater than 80%. The SD-OCT evaluation of the peripapillary RNFL achieved good specificity, sensitivity and positive PV in discriminating between ODE and PODE. Despite the correct differential diagnosis between these categories still relies on a careful medical history taking and other ancillary testing, we proved the usefulness of SD-OCT RNFL measurement in supporting the diagnostic process.

Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R) injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury. Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg) or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG) just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB) extravasation was determined to assess blood-retinal barrier (BRB) disruption and the structure of tight junctions (TJ) was examined by transmission electron microscopy. Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1) and occludin protein expression and decreased VEGF/PEDF ratio. Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio.

To investigate differences in clinical features based on magnetic resonance imaging (MRI) in idiopathic isolated optic neuritis patients. We retrospectively analyzed 68 eyes of 59 patients diagnosed with optic neuritis and showed inflammatory findings indicative of optic neuritis on MRI. We investigated clinical features, such as the presence of accompanying pain, visual acuity, and optic disc swelling. Optic disc swelling was classified as normal, mild, or severe. The MRI results were divided into intraorbital, intracanalicular, and whole optic nerve according to the lesion, and these were compared and analyzed with clinical features. The study included 29 men and 30 women, with a mean age of 42.6 ± 16.6 years. Among 59 patients, 48 (81.4%) complained of pain. Optic disc swelling was not observed in 48.5% of patients (33 eyes). Inflammatory changes were the most common in the intraorbital region (33 eyes), intracanalicular region (20 eyes), and the entire optic nerve (15 eyes). There was no statistical difference in the pain pattern according to the location of the lesion ( p  = .677), but when inflammation was present in the entire optic nerve, optic disc swelling was severe ( p  = .023). The initial and final visual acuity did not significantly correlate with the MRI pattern, presence of pain, or optic disc swelling ( p  = .156, p  = .714, and p  = .436). The MRI contrast enhancement pattern was associated with optic disc swelling but was not associated with pain or initial visual acuity. It should be noted that it is insufficient to judge the clinical features of optic neuritis based on MRI findings.