Optic nerve sheath diameter in severe preeclampsia with neurologic features versus controls.

BACKGROUND: Optic nerve sheath diameters (ONSD) have been validated as an accurate screening tool to detect elevated intracranial pressure in hypertensive encephalopathy. The neurologic manifestations of preeclampsia and/or eclampsia mimic those of hypertensive encephalopathy. This study was performed to assess the incidence of elevated optic nerve sheath diameters of patients with severe preeclampsia and neurologic criteria compared to non-preeclamptic patients. The secondary objective was to determine baseline optic nerve sheath diameters in patients with severe preeclampsia without neurologic criteria and preeclampsia without severe features. METHODS: Single site cohort study including 62 pregnant women 18 years or older and 20 weeks or further gestation. Patients with preeclampsia without severe features, preeclampsia with severe features by non-neurologic criteria, preeclampsia with severe features with neurologic criteria, and patients without preeclampsia were enrolled via convenience sampling. One blinded reviewer measured sheath diameters; baseline demographics and pregnancy data were collected by chart review. Statistical analysis was completed with STATA/IC 16. Categorical variables were compared by the χ2 test. Continuous variables were presented as mean ± standard deviation, and discrete variables were presented as medians and compared by Kruskal-Wallis testing. Normality was confirmed by Shapiro-Wilk testing. Linear and logistic regression were used to test the association between the preeclampsia groups and optic nerve sheath diameters. Models were presented as unadjusted and adjusted for BMI, gestation, hypertension, diabetes, parity, and gravidity. RESULTS: The incidence of optic nerve sheath diameters > 5.8 mm was 43.8% in the severe preeclampsia with neurologic features cohort, and 42.1% in the control cohort, with a relative risk of 1.04. Patients with severe preeclampsia without neurologic features had sheath diameters of 5.75 mm ± 1.09 mm; non-severe preeclampsia patients had sheath diameters of 5.54 mm ± 1.26 mm. CONCLUSIONS: We did not find a significant elevated optic nerve sheath diameter relative risk between severe preeclampsia patients with neurologic features and non-preeclampsia control patients. This is the first study to assess a North American population utilizing ACOG criteria for severe and non-severe preeclampsia, with severe cohorts additionally stratified by neurologic criteria.

Infrared- and white-light retinal sensitivity in glaucomatous neuropathy.

Glaucoma causes irreversible neuropathy, which, untreated, may lead to blindness. In this case-control study, we measured two-photon infrared (IR) light sensitivity in glaucomatous eyes to propose a new method to quantify the visual loss. In total, 64 patients were recruited with an equal distribution between glaucoma and control groups. Retinal sensitivity to IR light was assessed using a two-photon excitation device. A fundus-driven microperimeter was used to measure retinal sensitivity to visible light. The retinal nerve fiber layer (RNFL) thickness was quantified automatically with optical coherence tomography. The IR sensitivity of glaucoma and control eyes differed significantly (P = .003): 9.8 (6.5 to 13.1) dB vs. 10.9 (8.2 to 13.0) dB. Although in the visible-light microperimetry, retinal sensitivity was decreased in glaucoma (17.0, range: 6.9 to 20.0 dB) compared to the controls (17.7, range: 11.6 to 20.0 dB), this difference did not reach the significance level. A significant thinning of the RNFL in the glaucoma group was observed (P < .001). IR sensitivity significantly correlated with the RNFL in three of the four assessed quadrants instead of only one in visible-light microperimetry. Although further research is needed, this proof-of-concept study suggests that IR-light sensitivity can be used to support the detection of glaucomatous neuropathy.

The age factor in optic nerve regeneration: Intrinsic and extrinsic barriers hinder successful recovery in the short-living killifish.

As the mammalian central nervous system matures, its regenerative ability decreases, leading to incomplete or non-recovery from the neurodegenerative diseases and central nervous system insults that we are increasingly facing in our aging world population. Current neuroregenerative research is largely directed toward identifying the molecular and cellular players that underlie central nervous system repair, yet it repeatedly ignores the aging context in which many of these diseases appear. Using an optic nerve crush model in a novel biogerontology model, that is, the short-living African turquoise killifish, the impact of aging on injury-induced optic nerve repair was investigated. This work reveals an age-related decline in axonal regeneration in female killifish, with different phases of the repair process being affected depending on the age. Interestingly, as in mammals, both a reduced intrinsic growth potential and a non-supportive cellular environment seem to lie at the basis of this impairment. Overall, we introduce the killifish visual system and its age-dependent regenerative ability as a model to identify new targets for neurorepair in non-regenerating individuals, thereby also considering the effects of aging on neurorepair.

An inducible rodent glaucoma model that exhibits gradual sustained increase in intraocular pressure with distinct inner retina and optic nerve inflammation.

Glaucoma is a chronic and progressive neurodegenerative disease of the optic nerve resulting in loss of retinal ganglion cells (RGCs) and vision. The most prominent glaucoma risk factor is increased intraocular pressure (IOP), and most models focus on reproducing this aspect to study disease mechanisms and targets. Yet, current models result in IOP profiles that often do not resemble clinical glaucoma. Here we introduce a new model that results in a gradual and sustained IOP increase over time. This approach modifies a circumlimbal suture method, taking care to make the sutures 'snug' instead of tight, without inducing an initial IOP spike. This approach did not immediately affect IOPs, but generated gradual ocular hypertension (gOHT) as the sutures tighten over time, in comparison to loosely sutured control eyes (CON), resulting in an average 12.6 mmHg increase in IOP at 17 weeks (p < 0.001). Corresponding characterization revealed relevant retinal and optic nerve pathology, such as thinning of the retinal nerve fiber layer, decreased optokinetic response, RGC loss, and optic nerve head remodeling. Yet, angles remained open, with no evidence of inflammation. Corresponding biochemical profiling indicated significant increases in TGF-ß2 and 3, and IL-1 family cytokines in gOHT optic nerve tissues compared to CON, with accompanying microglial reactivity, consistent with active tissue injury and repair mechanisms. Remarkably, this signature was absent from optic nerves following acute ocular hypertension (aOHT) associated with intentionally tightened sutures, although the resulting RGC loss was similar in both methods. These results suggest that the pattern of IOP change has an important impact on underlying pathophysiology.

Chronic social defeat stress causes retinal vascular dysfunction.

PURPOSE: The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss. METHODS: Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively. The ET-1 and α-SMA levels were determined in retina. Retinal vascular autoregulation, functional response to various vasoactive agents and vascular mechanics were measured using video microscopy. RESULTS: No significant difference in IOP levels was observed during and after CSD between CSD mice and controls. CSD stress caused hypercortisolemia 2 days post-CSD. However, increased corticosterone levels went back to normal 8 months after CSD. CSD-exposed mice developed adrenal hyperplasia 3 days post-CSD, which was normalized by 8 months. RGC and axon survival were similar between CSD mice and controls. However, CSD stress caused irreversible, impaired autoregulation and vascular dysfunction of retinal arterioles in CSD mice. In addition, impaired maximal dilator capacity of retinal arterioles was observed 8 months post-CSD rather than 3 days post-CSD. Remarkably, ET-1 levels were increased 3 days post-CSD while α-SMA levels were decreased 8 months post-CSD. CONCLUSIONS: We found that CSD stress does not cause IOP elevation, nor loss of RGCs and their axons. However, it strikingly causes irreversible impaired autoregulation and endothelial function in murine retinal arterioles. In addition, CSD changed vascular mechanics on a long-term basis. Increased ET-1 levels and loss of pericytes in retina vessels may involve in this process.

The evaluation of intracranial pressure evaluation by optic nerve sheath diameter measurement on bedside ultrasonography after ischemic stroke.

INTRODUCTION: We aimed to predict intracranial pressure(ICP)after cerebral ischemic stroke by measuring diameter of the optic nerve sheath(ONSD)with bedside ultrasonography(US). In order to see the ICP changes,it was planned to record delta ICP changes at the 3rd and 5th day follow-up of the patients METHOTS: Patients aged 18 years or older who were admitted to the emergency department(ED)with stroke symptoms for one year were included.Demographic data,time elapsed since the onset of symptoms,neurogical status assesment scales,ONSD values measured by US in three time periods(the day the patient was admitted to the ED,the 3rd and 5th days of hospitalization),MDCT findings when the patient was admitted,ONSD values in MDCT,whether they received tissue plasminogen activator(tPA)and whether they underwent decompression surgery were recorded. RESULTS: The average age of the 82 patients was 67.5(range 33-89)years.Forty-two patients(51.2%)were male.On both the right and left sides,ONSD on the 3rd day was larger(>5 mm)than on first day(p < 0.05). ONSD on the 5th day was larger than on the first day(p > 0.05). All ONSD results measured using both US and MDCT showed a positive correlation between the same eye and contralateral eye measurements(p < 0.05). DISCUSSION: CT is the most critical radiological method for stroke patients.Transport to radyology unit in unstable patients carries risk and is not recommended.Optic nerve US can be used in the early diagnosis of ICP increase and provides early treatment.The ease of use and safety in unstable patients have increased its popularity. CONCLUSION: We believe that measuring ONSD using US is an appropriate choice on ICP management in stroke patients.

Neuroglobin effectively halts vision loss in Harlequin mice at an advanced stage of optic nerve degeneration.

Mitochondrial diseases are among the most prevalent groups of inherited neurological disorders, affecting up to 1 in 5000 adults. Despite the progress achieved on the identification of gene mutations causing mitochondrial pathologies, they cannot be cured so far. Harlequin mice, a relevant model of mitochondrial pathology due to apoptosis inducing factor depletion, suffer from progressive disappearance of retinal ganglion cells leading to optic neuropathy. In our previous work, we showed that administering adeno-associated virus encompassing the coding sequences for neuroglobin, (a neuroprotective molecule belonging to the globin family) or apoptosis-inducing factor, before neurodegeneration onset, prevented retinal ganglion cell loss and preserved visual function. One of the challenges to develop an effective treatment for optic neuropathies is to consider that by the time patients become aware of their handicap, a large amount of nerve fibers has already disappeared. Gene therapy was performed in Harlequin mice aged between 4 and 5 months with either a neuroglobin or an apoptosis-inducing factor vector to determine whether the increased abundance of either one of these proteins in retinas could preserve visual function at this advanced stage of the disease. We demonstrated that gene therapy, by preserving the connectivity of transduced retinal ganglion cells and optic nerve bioenergetics, results in the enhancement of visual cortex activity, ultimately rescuing visual impairment. This study demonstrates that: (a) An increased abundance of neuroglobin functionally overcomes apoptosis-inducing factor absence in Harlequin mouse retinas at a late stage of neuronal degeneration; (b) The beneficial effect for visual function could be mediated by neuroglobin localization to the mitochondria, thus contributing to the maintenance of the organelle homeostasis.

Systemic treatment with 7,8-Dihydroxiflavone activates TtkB and affords protection of two different retinal ganglion cell populations against axotomy in adult rats.

PURPOSE: To analyze responses of different RGC populations to left intraorbital optic nerve transection (IONT) and intraperitoneal (i.p.) treatment with 7,8-Dihydroxyflavone (DHF), a potent selective TrkB agonist. METHODS: Adult albino Sprague-Dawley rats received, following IONT, daily i.p. injections of vehicle (1%DMSO in 0.9%NaCl) or DHF. Group-1 (n = 58) assessed at 7days (d) the optimal DHF amount (1-25 mg/kg). Group-2, using freshly dissected naïve or treated retinas (n = 28), investigated if DHF treatment was associated with TrkB activation using Western-blotting at 1, 3 or 7d. Group-3 (n = 98) explored persistence of protection and was analyzed at survival intervals from 7 to 60d after IONT. Groups 2-3 received daily i.p. vehicle or DHF (5 mg/kg). Retinal wholemounts were immunolabelled for Brn3a and melanopsin to identify Brn3a+RGCs and m+RGCs, respectively. RESULTS: Optimal neuroprotection was achieved with 5 mg/kg DHF and resulted in TrkB phosphorylation. The percentage of surviving Brn3a+RGCs in vehicle treated rats was 60, 28, 18, 13, 12 or 8% of the original value at 7, 10, 14, 21, 30 or 60d, respectively, while in DHF treated retinas was 94, 70, 64, 17, 10 or 9% at the same time intervals. The percentages of m+RGCs diminished by 7d-13%, and recovered by 14d-38% in vehicle-treated and to 48% in DHF-treated retinas, without further variations. CONCLUSIONS: DHF neuroprotects Brn3a + RGCs and m + RGCs; its protective effects for Brn3a+RGCs are maximal at 7 days but still significant at 21d, whereas for m+RGCs neuroprotection was significant at 14d and permanent.

In vivo evaluation of outer retinal function and structure after retrobulbar optic nerve crush by lateral orbitotomy in goats.

Large animal model of optic nerve crush (ONC) plays an important role in translating novel therapeutic strategies developed in rodent model to clinical application. Due to the poor accessibility of the optic nerve (ON) in humans and large animals, lateral orbitotomy is needed to expose the retrobulbar ON. This study was to explore the effects of ONC and ON exposure with lateral orbitotomy (sham surgery) on the outer retinal function and structure in goats by using standard flash electroretinogram (FERG) and spectral-domain optical coherence tomography (SD-OCT). We found that ONC led to a transient reduction in FERG amplitudes at 1 week post injury (wpi), which recovered gradually over 2 months afterwards. Sham surgery alone also caused a similar pattern of amplitude reduction in FERG, although not as significantly as ONC did. Transient outer retinal thickening following ONC occurred at 4 wpi (when progressive thinning of the ganglion cell complex began), peaked at 8 wpi, then recovered gradually at 12 wpi. In contrast, outer retinal thickness remained unchanged statistically 3 months after sham surgery. Fundus fluorescein angiography showed that neither ONC nor ON exposure with lateral orbitotomy significantly caused any significant delay or absence of central retinal vascular filling. In summary, ONC with lateral orbitotomy affects outer retinal function and structure transiently.

Comparison between wide-field digital imaging system and the red reflex test for universal newborn eye screening in Brazil.

PURPOSE: To compare neonatal eye screening using the red reflex test (RRT) versus the wide-field digital imaging (WFDI) system. METHODS: Prospective cohort study. Newborns (n = 380, 760 eyes) in the Maternity Ward of Irmandade Santa Casa de Misericórdia de São Paulo hospital from May to July 2014 underwent RRT by a paediatrician and WFDI performed by the authors. Wide-field digital imaging (WFDI) images were analysed by the authors. Validity of the paediatrician's RRT was assessed by unweighted kappa [κ] statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: While WFDI showed abnormalities in 130 eyes (17.1%), RRT was only abnormal in 13 eyes (1.7%). Wide-field digital imaging (WFDI) detected treatable retina pathology that RRT missed including hyphema, CMV retinitis, FEVR and a vitreous haemorrhage. The sensitivity of the paediatrician's RRT to detect abnormalities was poor at 0.77% (95% confidence interval, CI, 0.02%-4.21%) with a PPV of only 7.69% (95% CI, 1.08%-38.85%). Overall, there was no agreement between screening modalities (κ = -0.02, 95% CI, -0.05 to 0.01). The number needed to screen to detect ocular abnormalities using WFDI was 5.9 newborns and to detect treatable abnormalities was 76 newborns. CONCLUSION: While RRT detects gross abnormalities that preclude visualization of the retina (i.e. media opacities and very large tumours), only WFDI consistently detects subtle treatable retina and optic nerve pathology. With a higher sensitivity than the current gold standard, universal WFDI allows for early detection and management of potentially blinding ophthalmic disease missed by RRT.

Optic nerve regeneration screen identifies multiple genes restricting adult neural repair.

Adult mammalian central nervous system (CNS) trauma interrupts neural networks and, because axonal regeneration is minimal, neurological deficits persist. Repair via axonal growth is limited by extracellular inhibitors and cell-autonomous factors. Based on results from a screen in vitro, we evaluate nearly 400 genes through a large-scale in vivo regeneration screen. Suppression of 40 genes using viral-driven short hairpin RNAs (shRNAs) promotes retinal ganglion cell (RGC) axon regeneration after optic nerve crush (ONC), and most are validated by separate CRISPR-Cas9 editing experiments. Expression of these axon-regeneration-suppressing genes is not significantly altered by axotomy. Among regeneration-limiting genes, loss of the interleukin 22 (IL-22) cytokine allows an early, yet transient, inflammatory response in the retina after injury. Reduced IL-22 drives concurrent activation of signal transducer and activator of transcription 3 (Stat3) and dual leucine zipper kinase (DLK) pathways and upregulation of multiple neuron-intrinsic regeneration-associated genes (RAGs). Including IL-22, our screen identifies dozens of genes that limit CNS regeneration. Suppression of these genes in the context of axonal damage could support improved neural repair.

Liraglutide, 7,8-DHF and their co-treatment prevents loss of vision and cognitive decline in a Wolfram syndrome rat model.

Wolfram syndrome (WS) is a monogenic progressive neurodegenerative disease and is characterized by various neurological symptoms, such as optic nerve atrophy, loss of vision, cognitive decline, memory impairment, and learning difficulties. GLP1 receptor agonist liraglutide and BDNF mimetic 7,8-dihydroxyflavone (7,8-DHF) have had protective effect to visual pathway and to learning and memory in different rat models of neurodegenerative disorders. Although synergistic co-treatment effect has not been reported before and therefore the aim of the current study was to investigate liraglutide, 7,8-DHF and most importantly for the first time their co-treatment effect on degenerative processes in WS rat model. We took 9 months old WS rats and their wild-type (WT) control animals and treated them daily with liraglutide, 7,8-DHF or with the combination of liraglutide and 7,8-DHF up to the age of 12.5 months (n = 47, 5-8 per group). We found that liraglutide, 7,8-DHF and their co-treatment all prevented lateral ventricle enlargement, improved learning in Morris Water maze, reduced neuronal inflammation, delayed the progression of optic nerve atrophy, had remyelinating effect on optic nerve and thereby improved visual acuity in WS rats compared to WT controls. Thus, the use of the liraglutide, 7,8-DHF and their co-treatment could potentially be used as a therapeutic intervention to induce neuroprotection or even neuronal regeneration.

Structural and Functional Change in Albino Rat Retina Induced by Various Visible Light Wavelengths.

The effects of visible light, from short to long wavelengths, on the retina were investigated functionally and histologically. The left eyes of Sprague-Dawley albino rats (6-weeks old, n = 6 for each wavelength) were exposed to seven narrow-band wavelengths (central wavelengths, 421, 441, 459, 501, 541, 581, and 615 nm) with bandwidths of 16 to 29 nm (half bandwidth, ±8-14.5 nm) using a xenon lamp source with bandpass filters at the retinal radiant exposures of 340 and 680 J/cm2. The right unexposed eyes served as controls. Seven days after exposure, flash electroretinograms (ERGs) were recorded, and the outer nuclear layer (ONL) thickness was measured. Compared to the unexposed eyes, significant reductions in the a- and b-wave ERG amplitudes were seen in eyes exposed to 460-nm or shorter wavelengths of light. The ONL thickness near the optic nerve head also tended to decrease with exposure to shorter wavelengths. The decreased ERG amplitudes and ONL thicknesses were most prominent in eyes exposed to 420-nm light at both radiant exposures. When the wavelengths were the same, the higher the amount of radiant exposure and the stronger the damage. Compared to the unexposed eyes, the a- and b-waves did not decrease significantly in eyes exposed to 500-nm or longer wavelength light. The results indicate that the retinal damage induced by visible light observed in albino rats depends on the wavelength and energy level of the exposed light.

Cytokine-chemokine and cognitive profile of multiple sclerosis patients with predominant optic nerve and spinal cord involvement.

Context/Objective: Clinical disease activity in multiple sclerosis (MS) may manifest as predominant involvement of optic nerves and spinal cord, as exemplified by opticospinal multiple sclerosis (OSMS) often encountered in Asian countries. Our aim was to compare the clinical features, neuropsychological profile and cytokine/chemokine levels of patients with conventional MS (CMS) and MS presenting predominantly with spinal cord and optic nerve attacks (MS-SCON).Design: Cross-sectional study.Setting: MS Outpatient Clinic.Participants: Fourteen MS-SCON patients, 20 CMS patients without myelitis and optic neuritis attacks and 21 healthy individuals.Outcome measures: IL-8, IL-10, IFN-γ, IL-17 and TNF-α levels were measured by multiplex assay and CXCL2 and CXCL5 levels were measured by ELISA. A panel of neuropsychological tests, Beck depression inventory, 9-hole peg and timed 25-foot walk tests were employed.Results: CMS and MS-SCON patients showed similar clinical features. Both CMS and MS-SCON patients displayed reduced IL-8 and CXCL2 and increased TNF-α levels, while IL-10 and CXCL5 levels were identical among all groups.Conclusion: Neuropsychological and motor function test performances of CMS and MS-SCON patients were highly comparable. CMS and MS-SCON present with similar clinical, neuropsychological and immunological features. Therefore, optic nerve and spinal cord-dominant form of MS does not necessarily establish a distinct entity in our region. Cognitive networks of the central nervous system may be damaged during the disease course of MS, despite the absence of cerebral or cerebellar clinical attacks.

Strain Specific Responses in a Microbead Rat Model of Experimental Glaucoma.

PURPOSE: A major challenge in glaucoma research is the lack of reproducible animal models of RGC and optic nerve damage, the characteristic features of this condition. We therefore examined the glaucomatous responses of two different rat strains, the Brown Norway (BN) and Lister Hooded (LH) rats, to high intraocular pressure (IOP) induced by injection of magnetic beads into the anterior chamber. METHODS: Magnetic microsphere suspensions (20 µl of 5-20 mg/ml) were injected into the anterior chamber of BN (n = 9) or LH (N = 15) rats. Animals from each strain were divided into three groups, each receiving a different dose of microspheres. IOP was measured over 4 weeks using a rebound tonometer. Retinal ganglion cell (RGC) damage and function were assessed using scotopic electroretinograms (ERGs), retinal flatmounts and optic nerve histology. ANOVA and Student's t-tests were used to analyse the data. RESULTS: A significant elevation in IOP was observed in BN rats receiving injections of 20 mg (37.18 ± 12.28 mmHg) or 10 mg microspheres/ml (36.95 ± 13.63 mmHg) when compared with controls (19.63 ± 4.29 mmHg) (p < .001) over 2 weeks. This correlated with a significant impairment of RGC function, as determined by scotopic ERG (p < .001), reduction in axon number (p < .05) and lower RGC density (P < .05) in animals receiving 20 mg or 10 mg microspheres/ml as compared with controls. LH rats receiving similar microsphere doses showed reduced scotopic ERG function (p < .001) after 2 weeks. No changes in IOP was seen in this strain, although a reduction in axon density was observed in optic nerve cross-sections (p < .05). Initial changes in IOP and ERG responses observed in BN rats remained unchanged for a duration of 7 weeks. In LH animals, ERG responses were decreased at 1-2 weeks and returned to control levels after 5 weeks. CONCLUSIONS: Although this model was easily reproducible in BN rats, the phenotype of injury observed in LH rats was very different from that observed in BN animals. We suggest that differences in the glaucomatous response observed in these two strains may be ascribed to anatomical and physiological differences and merits further investigation.

Combined association of massive choroidal and optic nerve invasion as a prognostic relevance in primary retinoblastoma: A 10-year study.

PURPOSE: To determine the significance of both massive choroidal invasion and optic nerve invasion (retrolaminar [(RL]+cut end [CE]) as a criterion for classifying high metastatic potential retinoblastoma and their relationship with other known histopathological high-risk features. METHODS: A retrospective review of 650 eyes diagnosed as retinoblastoma over a 10-year period. In our study, there is male predominance and a higher percentage of the poorly differentiated tumors. The age of most of the patients ranges from 1 month to 8 years with a median age of 2 years. RESULTS: There were 24% of eyes with massive choroidal invasion and 18% of eyes with optic nerve invasion up to the cut end. On performing Cox-proportional hazard analysis, it was found that massive choroidal invasion in association with optic nerve invasion up to the cut end was an independent prognostic parameter. On Kaplan-Meier analysis, overall survival had reduced in patients having both massive choroidal invasion and an optic nerve cut end invasion along with orbital invasion (P < .05). CONCLUSION: The presence of massive choroidal invasion in association with optic nerve cut end invasion (RL+CE) could be used as a better prognostic predictor in assessing retinoblastoma patients with high metastatic potential and need to be kept for longer follow up.

Adduction-Induced Strain on the Optic Nerve in Primary Open Angle Glaucoma at Normal Intraocular Pressure.

PURPOSE/AIM: The optic nerve (ON) becomes taut during adduction beyond ~26° in healthy people and patients with primary open angle glaucoma (POAG), but only retracts the globe in POAG. We used magnetic resonance imaging (MRI) to investigate this difference. MATERIALS AND METHODS: MRI was obtained in 2-mm quasi-coronal planes in central gaze, and smaller (~23-25°) and larger (~30-31°) adduction and abduction in 21 controls and 12 POAG subjects whose intraocular pressure never exceeded 21 mmHg. ON cross-sections were analyzed from the globe to 10 mm posteriorly. Area centroids were used to calculate ON path lengths and changes in cross-sections to calculate elongation assuming volume conservation. RESULTS: For both groups, ON path was nearly straight (<102.5% of minimum path) in smaller adduction, with minimal further straightening in larger adduction. ON length was redundant in abduction, exceeding 103% of minimum path for both groups. For normals, the ON elongated 0.4 ± 0.5 mm from central gaze to smaller adduction, and 0.4 ± 0.5 mm further from smaller to larger adduction. For POAG subjects, the ON did not elongate on average from central gaze to smaller adduction and only 0.2 ± 0.4 mm from smaller to larger adduction (P = .045 vs normals). Both groups demonstrated minimal ON elongation not exceeding 0.25 mm from central gaze to smaller and larger abduction. The globe retracted significantly more during large adduction in POAG subjects than normals (0.6 ± 0.7 mm vs 0.2 ± 0.5 mm, P = .027), without appreciable retraction in abduction. For each mm increase in globe axial length, ON elongation in large adduction similarly increased by 0.2 mm in each group. CONCLUSIONS: The normal ON stretches to absorb force and avert globe retraction in adduction. In POAG with mild to severe visual field loss, the relatively inelastic ON tethers and retracts the globe during adduction beyond ~26°, transfering stress to the optic disc that could contribute to progressive neuropathy during repeated eye movements.

Optic nerve sheath diameter by ultrasound is a good screening tool for high intracranial pressure in traumatic brain injury.

OBJECTIVES: This study aimed to determine the role of ONSD measurement by US for diagnosis of high ICP in TBI patients. METHODS: ONSD measurement by US was performed in adult TBI patients within 1 h of planned CT brain, while CT signs of high ICP were determined. Invasive ICP measurement was performed simultaneously in patients who had intraventricular device in situ. High ICP was determined as ICP > 22 mmHg. RESULTS: A total of 48 patients were enrolled. Twenty-eight patients had positive CT criteria for high ICP, while 20 patients were negative. The mean value of ONSD was 0.63 ± 0.06 cm in positive group compared with 0.55 ± 0.07 cm in negative one with significant difference (p < 0.001). A total of 22 patients had intraventricular device. Thirteen patients had high ICP, while 9 patients had normal ICP. The mean value of ONSD was 0.66 ± 0.05 cm in high ICP group compared with 0.58 ± 0.08 cm in normal one with significant difference (p = 0.004). ONSD with cut-off value > 0.61 cm predicted high ICP with sensitivity of 84.62% and specificity of 66.67% with significant AUC of 0.85 (p = 0.006). CONCLUSION: ONSD measurement by ultrasound is a good screening tool for high ICP in traumatic brain injury patients.

Optic Nerve Topography in Multiple Sclerosis Diagnosis: The Utility of Visual Evoked Potentials.

OBJECTIVE: To assess the added value of the optic nerve region (by using visual evoked potentials [VEPs]) to the current diagnostic criteria. METHODS: From the Barcelona clinically isolated syndrome (CIS) cohort, patients with complete information to assess dissemination in space (DIS), the optic nerve region, and dissemination in time at baseline (n = 388) were selected. Modified DIS (modDIS) criteria were constructed by adding the optic nerve to the current DIS regions. The DIS and modDIS criteria were evaluated with univariable Cox proportional hazard regression analyses with the time to the second attack as the outcome. A subset of these patients who had at least 10 years of follow-up or a second attack occurring within 10 years (n = 151) were selected to assess the diagnostic performance. The analyses were also performed according to CIS topography (optic neuritis vs non-optic neuritis). RESULTS: The addition of the optic nerve as a fifth region improved the diagnostic performance by slightly increasing the accuracy (2017 DIS 75.5%, modDIS 78.1%) and the sensitivity (2017 DIS 79.2%, modDIS 82.3%) without lowering the specificity (2017 DIS 52.4%, modDIS 52.4%). When the analysis was conducted according to CIS topography, the modDIS criteria performed similarly in both optic neuritis and non-optic neuritis CIS. CONCLUSION: The addition of the optic nerve, assessed by VEP, as a fifth region in the current DIS criteria slightly improves the diagnostic performance because it increases sensitivity without losing specificity.

Mesoscopic cortical network reorganization during recovery of optic nerve injury in GCaMP6s mice.

As the residual vision following a traumatic optic nerve injury can spontaneously recover over time, we explored the spontaneous plasticity of cortical networks during the early post-optic nerve crush (ONC) phase. Using in vivo wide-field calcium imaging on awake Thy1-GCaMP6s mice, we characterized resting state and evoked cortical activity before, during, and 31 days after ONC. The recovery of monocular visual acuity and depth perception was evaluated in parallel. Cortical responses to an LED flash decreased in the contralateral hemisphere in the primary visual cortex and in the secondary visual areas following the ONC, but was partially rescued between 3 and 5 days post-ONC, remaining stable thereafter. The connectivity between visual and non-visual regions was disorganized after the crush, as shown by a decorrelation, but correlated activity was restored 31 days after the injury. The number of surviving retinal ganglion cells dramatically dropped and remained low. At the behavioral level, the ONC resulted in visual acuity loss on the injured side and an increase in visual acuity with the non-injured eye. In conclusion, our results show a reorganization of connectivity between visual and associative cortical areas after an ONC, which is indicative of spontaneous cortical plasticity.