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1.  Retinal Vessel Diameter Assessment in Papilledema by Semi-Automated Analysis of SLO Images: Feasibility and Reliability 
Purpose.
To report feasibility and reliability of a semi-automated image analysis method for retinal vessel diameter measurements in subjects with papilledema before and after treatment.
Methods.
Scanning laser ophthalmoscopy (SLO) was performed in seven normal, five pseudopapilledema, and seven papilledema subjects. In four papilledema subjects, SLO was performed both before and following treatment. Two observers measured diameters of superior and inferior retinal arteries and veins from SLO images using two methods: manual analysis and semi-automated customized analysis. Vessel measurements were compared between observers and between image analysis methods. Retinal vein and artery diameters for each subject were compared between papilledema, pseudopapilledema, and normal subjects, and before and following treatment for papilledema subjects.
Results.
Interobserver reliability was 0.97 (Pearson's correlation, r) and 0.90 for semi-automated and manual measurements, respectively. Correlation coefficient of manual and semi-automated measurements was 0.85. Retinal vein diameter in papilledema subjects was larger than in pseudopapilledema and normal subjects (P = 0.03, 0.04, Mann-Whitney). Papilledema subjects had a decrease in retinal vein diameter following treatment for and resolution of papilledema (P = 0.04, Wilcoxon signed rank). Retinal artery diameters were not significantly different between papilledema and pseudopapilledema or normal groups, and did not significantly change following papilledema treatment.
Conclusions.
A feasible and reliable semi-automated image analysis method for measurement of retinal artery and vein diameters from SLO images of elevated optic nerves is reported. Further studies are needed to determine the clinical utility of retinal vein diameter measurements as a marker for diagnosis and treatment of papilledema.
Retinal vessel diameters measured from scanning laser ophthalmoscopic images using semi-automated image analysis are feasible and reliable. Retinal vein diameters are larger in papilledema subjects before treatment than in pseudopapilledema, normal, and papilledema subjects after treatment.
doi:10.1167/iovs.13-13621
PMCID: PMC3979275  PMID: 24609623
papilledema; idiopathic intracranial hypertension; retinal blood vessels
2.  Parenchymal Anaplastic Astrocytoma presenting with Visual Symptoms due to Bilateral Optic Nerve Sheath Involvement 
A 23 year old man presented with transient visual obscurations and was found to have optic nerve edema and a thalamic lesion that did not enhance on magnetic resonance imaging. Lumbar puncture opening pressure was normal. Subsequent magnetic resonance images demonstrated optic nerve sheath enhancement. Pathological diagnosis of the thalamic mass was anaplastic astrocytoma (WHO grade III). Visual symptoms were attributed to spread of high grade parenchymal glioma to the optic nerve sheaths causing intraorbital optic nerve compression.
doi:10.1097/WNO.0b013e318298fab2
PMCID: PMC3808272  PMID: 23838764
anaplastic astrocytoma; optic nerve edema; leptomeningeal spread
3.  De novo malignant optic chiasm glioma with initial clinical response to steroids 
Malignant optic nerve glioma (MONG) is a rare but uniformly fatal disease that remains poorly understood. We describe a notable case of this rare disease occurring in the optic chiasm. Normal brain imaging and normal ophthalmic examination two years prior to diagnosis provide evidence for de novo genesis of MONG in our patient. Early response to steroids highlights the degree to which MONG can initially mimic inflammatory optic neuropathies and chiasmal syndromes. Our case also demonstrates a poor outcome with MONG even with current advanced therapy for glioblastoma including radiotherapy plus concomitant and adjuvant temozolomide (the EORTC/NCIC regimen) and bevacizumab.
doi:10.3109/01658107.2012.658594
PMCID: PMC3769187  PMID: 24031101
4.  Acute Optic Neuropathy associated with an Intracranial Mass in a Patient with POEMS syndrome 
A 43 year old man with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) including long standing optic disc swelling had sudden painless vision loss in the left eye. Brain magnetic resonance imaging (MRI) revealed an intracranial mass adjacent to the left optic nerve and enhancement of the optic nerve. The mass decreased in size following chemotherapy for myeloma with some recovery of vision. This represents a unique case of optic neuropathy due to presumed plasmacytoma in osteosclerotic IgA myeloma and POEMS syndrome.
doi:10.1097/WNO.0b013e318234db5d
PMCID: PMC3725956  PMID: 21956018
optic neuropathy; POEMS; intracranial mass; optic disc edema
5.  ORBITAL CONGESTION COMPLICATING TREATMENT OF CEREBRAL VASCULAR ANOMALIES 
World neurosurgery  2013;82(0):239.e13-239.e17.
BACKGROUND
The decision between conservative management and invasive treatment of juxtaorbital intracranial vascular anomalies can be challenging. Whereas arteriovenous malformations (AVMs) can lead to vision loss and are potentially life threatening if they rupture, invasive endovascular and surgical procedures also carry risks.
CASE DESCRIPTIONS
Two patients developed blinding orbital congestion soon after successful treatment of cerebral vascular anomalies. The first patient, a 36 year-old man, underwent partial embolization followed by resection of a congenital frontal lobe AVM. The second patient, a 62 year-old woman, underwent embolization of a peri-orbital/skull base dural arteriovenous malformation. Following intervention, both patients developed unilateral vision loss proptosis, chemosis, complete ophthalmoplegia, and elevated intraocular pressure. The first patient suffered from acute orbital compartment syndrome in the absence of any acute localized hemorrhage or thrombosis. The second patient experienced refractory acute glaucoma from orbital congestion, secondary hyphema and angle closure due to superior ophthalmic vein and cavernous sinus thromboses.
CONCULSIONS
These cases highlight the potential orbital congestion to worsen acutely after invasive treatment of juxtaorbital cerebral vascular anomalies, and suggest diverse mechanisms of resultant visual and orbital compromise. The first case represents the first report of orbital compartment syndrome following resection of a congenital AVM.
doi:10.1016/j.wneu.2013.01.093
PMCID: PMC3766429  PMID: 23369940
arteriovenous malformation; dural arteriovenous fistula; orbital compartment syndrome
6.  Association of race with visual outcomes following acute optic neuritis: an analysis of the Optic Neuritis Treatment Trial 
JAMA ophthalmology  2014;132(4):421-427.
Importance
Retrospective studies have demonstrated disparate outcomes following acute optic neuritis in individuals of African descent compared with Caucasians. However, published analyses of the prospectively collected Optic Neuritis Treatment Trial (ONTT) data did not identify an association between worse visual outcomes and African race.
Objective
To investigate the association among race, gender, and age with visual outcomes following acute optic neuritis through application of longitudinal data analysis techniques to the ONTT data set.
Design
Secondary analysis of the ONTT (a prospective, randomized, controlled trial) data set. Our models included effects of treatment (placebo, oral prednisone, IV methylprednisolone), time and treatment-time interaction as well as demographic covariates of age, gender and race.
Setting
ONTT data were collected at multiple centers in the United States.
Participants
Black(n=58) and White(n=388) subjects presenting with acute optic neuritis who enrolled in the ONTT within 8 days of symptom onset were included in analyses.
Main outcome measures
logMAR visual acuity (VA) and contrast sensitivity (CS) in the affected eye were modeled using two-stage mixed effect regression techniques. All available follow-up data from baseline to 15–18 years were included.
Results
The data did not identify a relationship of age, gender, or treatment groups with VA or CS outcomes. Race was significantly related to CS (p<0.001) and VA (p<0.001) over a 15 year period following acute optic neuritis with black race being associated with worse scores for both.
Conclusions and Relevance
Race appears to be associated with contrast sensitivity and visual acuity outcomes in affected eyes following acute optic neuritis. To our knowledge, this is the largest cohort of black subjects with optic neuritis that has been analyzed, and the first evidence from a prospectively collected data set that supports a hypothesis of race-dependent visual outcomes in optic neuritis.
doi:10.1001/jamaophthalmol.2013.7995
PMCID: PMC4115276  PMID: 24557028
optic neuritis; outcomes; vision; race; longitudinal analysis
7.  Isolated Third, Fourth and Sixth Cranial Nerve Palsies From Presumed Microvascular Versus Other Causes: A Prospective Study 
Ophthalmology  2013;120(11):10.1016/j.ophtha.2013.04.009.
Purpose
To estimate the proportion of patients presenting with isolated third, fourth or sixth cranial nerve palsies of presumed microvascular origin versus other causes.
Design
Prospective, multi-center observational case series.
Participants
One hundred and nine patients, 50 years of age or older with acute isolated ocular motor nerve palsy.
Testing
Magnetic resonance imaging (MRI) of the brain
Main outcome measures
Causes of acute isolated ocular motor nerve palsy (presumed microvascular or other) as determined with early MRI and clinical assessment.
Results
Among 109 patients enrolled in the study, there were 22 patients with cranial nerve III palsy, 25 patients with cranial nerve IV palsy and 62 patients with cranial nerve VI palsy. A cause other than presumed microvascular ischemia was identified in 18 patients (16.5 %, 95% confidence interval (CI): 10.7–24.6%). The presence of one or more vasculopathic risk factors (diabetes, hypertension, hypercholesterolemia, coronary artery disease, myocardial infarction, stroke and smoking) was significantly associated with a presumed microvascular cause (p=0.003, Fisher’s exact test). Vasculopathic risk factors were also present in 61% of patients (11/18) with other causes. In the group of patients who had vasculopathic risk factors only, with no other significant medical condition, 10% of patients (8/80) were found to have other causes including midbrain infarction, neoplasms, inflammation, pituitary apoplexy and giant cell arteritis (GCA). Excluding patients with third cranial nerve palsies and those with GCA the incidence of other causes for isolated fourth and sixth cranial nerve palsies was 4.7% (3/64).
Conclusions
In our series of patients with acute isolated ocular motor nerve palsies, substantial proportion of patients had other causes including neoplasm, GCA and brainstem infarction. Brain MRI and laboratory work–up has a role in the initial evaluation of older patients with isolated acute ocular motor nerve palsies regardless of whether vascular risk factors are present or not.
doi:10.1016/j.ophtha.2013.04.009
PMCID: PMC3795864  PMID: 23747163
8.  IgG4-related inflammatory pseudotumor of the central nervous system responsive to mycophenolate mofetil 
Orbital apex and skull base masses often present with neuro-ophthalmic signs and symptoms. Though the localization of these syndromes and visualization of the responsible lesion on imaging is typically straightforward, definitive diagnosis usually relies on biopsy. Immunohistochemistry is important for categorization and treatment planning. IgG4 –related disease is emerging as a pathologically defined inflammatory process that can occur in multiple organ systems. We present two patients with extensive inflammatory mass lesions of the central nervous system with immunohistochemistry positive for IgG4 and negative for ALK-1 as examples of meningeal based IgG4-related inflammatory pseudotumors. In both patients, there was treatment response to mycophenolate mofetil.
doi:10.1016/j.jns.2012.04.010
PMCID: PMC3366053  PMID: 22546342
IgG4-related disease; mycophenolate mofetil; intracranial mass; optic neuropathy; inflammatory pseudotumor
9.  Cross-sectional evaluation of clinical neuro-ophthalmic abnormalities in an amyotrophic lateral sclerosis population 
Journal of the neurological sciences  2011;314(1-2):97-101.
Objective
Ocular motility abnormalities may be a marker of neuro-degeneration beyond motor neurons in amyotrophic lateral sclerosis (ALS). We formally compared clinical neuro-ophthalmic abnormalities in ALS patients and a control population.
Methods
Patients attending a multidisciplinary ALS clinic (n = 63, age 60.8 +/− 16.4 years) and their caregivers serving as controls (n = 37, ages 55.0 +/− 12.7 years) participated in this cross-sectional study. Visual acuity was assessed. Video recordings of a standardized ocular motility exam including gaze fixation, voluntary saccades, reflex saccades, smooth pursuit, eyelid opening and Bell's phenomenon were rated by two senior neuro-ophthalmologists who were masked to subject group.
Results
Visual acuity was lower in ALS patients versus control subjects (OR 0.81 (0.71–0.93), p = 0.003, logistic regression). Inter- and intra-rater reliability for ocular motility examination ratings were good (Cohen's Kappa > 0.6). Findings observed only in ALS subjects included gaze impersistence (14%, p = 0.01), moderately or severely restricted voluntary upgaze (13%, p = 0.01), and moderate or severe eyelid opening apraxia (27%, p = 0.0002). Accounting for age, moderately or severely saccadic horizontal smooth pursuits distinguished ALS from control subjects (OR 3.6 (1.2– 10.9), p = 0.02, logistic regression).
Conclusions
Clinical findings of decreased visual acuity, gaze impersistence, voluntary upgaze restriction, eyelid opening apraxia, and saccadic horizontal smooth pursuits are more frequent in patients with ALS than in similar-aged controls. These findings are potential clinical markers of neurodegeneration beyond upper and lower motor neuron disease in ALS. Further study is warranted regarding their application to disease categorization and outcomes assessment.
doi:10.1016/j.jns.2011.10.016
PMCID: PMC3441141  PMID: 22192877
Prevalence study; Eye movements; Vision; Amyotrophic lateral sclerosis
10.  Local Low-Dose Lovastatin Delivery Improves the Bone-Healing Defect Caused by Nf1 Loss of Function in Osteoblasts 
Journal of Bone and Mineral Research  2010;25(7):1658-1667.
Postfracture tibial nonunion (pseudoarthrosis) leads to lifelong disability in patients with neurofibromatosis type I (NF1), a disorder caused by mutations in the NF1 gene. To determine the contribution of NF1 in bone healing, we assessed bone healing in the conditional mouse model lacking Nf1 specifically in osteoblasts. A closed distal tibia fracture protocol and a longitudinal study design were used. During the 21- to 28-day postfracture period, callus volume, as expected, decreased in wild-type but not in mice, suggesting delayed healing. At these two time points, bone volume (BV/TV) and volumetric bone mineral density (vBMD) measured by 3D micro–computed tomography were decreased in callus-bridging cortices and trabecular compartments compared with wild-type controls. Histomorphometric analyses revealed the presence of cartilaginous remnants, a high amount of osteoid, and increased osteoclast surfaces in calluses 21 days after fracture, which was accompanied by increased expression of osteopontin, Rankl, and Tgfβ. Callus strength measured by three-point bending 28 days after fracture was reduced in versus wild-type calluses. Importantly, from a clinical point of view, this defect of callus maturation and strength could be ameliorated by local delivery of low-dose lovastatin microparticles, which successfully decreased osteoid volume and cartilaginous remnant number and increased callus BV/TV and strength in mutant mice. These results thus indicate that the dysfunctions caused by loss of Nf1 in osteoblasts impair callus maturation and weaken callus mechanical properties and suggest that local delivery of low-dose lovastatin may improve bone healing in NF1 patients. © 2010 American Society for Bone and Mineral Research.
doi:10.1002/jbmr.42
PMCID: PMC3154004  PMID: 20200958
neurofibromatosis type I; NF1; fracture; healing; pseudoarthrosis; lovastatin; µCT
11.  Noninvasive Measurement of Cerebral Blood Flow and Blood Oxygenation Using Near-Infrared and Diffuse Correlation Spectroscopies in Critically Brain-Injured Adults 
Neurocritical care  2010;12(2):173-180.
Background
This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation.
Methods
Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBFDCS), and changes in oxy-hemoglobin (ΔHbO2), deoxy-hemoglobin (ΔHb), and total hemoglobin concentration (ΔTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBFXeCT) and were then compared to rCBFDCS. Spearman’s rank coefficients were employed to test for associations between rCBFDCS and rCBFXeCT, as well as between rCBF from both modalities and NIRS parameters.
Results
rCBFDCS and rCBFXeCT showed good correlation (rs = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBFDCS and ΔHbO2/ΔTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.
Conclusions
DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.
doi:10.1007/s12028-009-9305-x
PMCID: PMC2844468  PMID: 19908166
Near-infrared spectroscopy; Diffuse correlation spectroscopy; Cerebral blood flow; Xenon CT; Neurocritical care

Results 1-11 (11)