- Papilledema, pseudotumor cerebrii, idiopathic intracranial hypertension
- optic neuritis
Board of Directors, North American Neuro-Ophthalmology Society (2017 - 2021)
Chair, abstract committee, North American Neuro-ophthalmology Society (2016 - 2020)
Vice chair, neuro-ophthalmology & neuro-otology section, American Academy of Neurology (2016 - 2018)
Chair, Neuro-ophthalmology & neuro-otology section, American Academy of Neurology (2018 - 2020)
Honors & Awards
Sybil Harrington Special Scholar Award, Research to Prevent Blindness (2015)
Young Investigator of the Year, North American Neuro-ophthalmology Society (2015)
Teacher of the year, Chicago Curriculum in Ophthalmology (2012, 2014)
Zeritsky prize for research by a resident, University of Pennsylvania (2009)
Biomedical engineering pre-doctoral fellowship, Whitaker Foundation (1998-2003)
Science and Technology Award, Canadian Federation of University Women (1998)
Boards, Advisory Committees, Professional Organizations
Assistant Editor, Neuro-ophthalmology (2013 - 2019)
Associate Editor, Frontiers in Neurology, Neuro-ophthalmology (2018 - Present)
Review Editor, Current Eye Research (2016 - Present)
Fellow, American Academy of Neurology (2016 - Present)
Fellow, North American Neuro-ophthalmology Society (2016 - Present)
Graduate Certificate, University of Illinois School of Public Health, Clinical and Translational Research (2014)
fellowship, University of Illinois at Chicago, Medical Education (2011)
fellowship, University of Pennsylvania, Neuro-ophthalmology (2010)
board certification, American Board of Psychiatry and Neurology, Adult Neurology (2010)
residency, University of Pennsylvania, Neurology (2009)
Internship:Massachusetts General Hospital Internal Medicine Residency (2006) MA
MD, Harvard Medical School (2005)
PhD (joint program), Harvard-MIT Division of Health Sciences and Technology, Medical Engineering & Medical Physics (2003)
PhD, Harvard University, Engineering Sciences (2003)
B.Sc. (eng), University of Guelph (Canada), Biological Engineering (1997)
Current Research and Scholarly Interests
Permanent vision loss caused by papilledema, the swelling of the optic nerve heads due to elevation in intracranial pressure (ICP), occurs in 50% of people with idiopathic intracranial hypertension (IIH) as well as individuals with high ICP from other neurological and neurosurgical diseases. One reason that blindness results from IIH, which is a treatable disease, is lack of timely, accurate clinical markers with which to identify those who are at risk of losing vision.
My research program seeks to identify and develop such markers through studies of papilledema physiology in humans affected by IIH. My current studies focus on humans with IIH because this accurately captures both the disease of interest and the target population. The conceptual frameworks that underlie my research program are drawn from my doctoral level engineering training. Using a mechanical (structural) framework I am evaluating the effect of changing intra-cerebral and intra-optic nerve forces from ICP and papilledema on the shape of the optic nerve and retinal blood vessels. Using an electrical (functional) framework I am evaluating patterns of visual pathway dysfunction in papilledema using non-invasive techniques of electrophysiology, pupillary light response and psychophysics. Markers based on both of these frameworks have the potential to capture the dynamics of pathophysiological changes associated with evolving and resolving papilledema with less delay than currently used clinical markers.
My aim is to develop non-invasive structural and functional markers of papilledema physiology that predict visual outcomes in IIH and guide tailored intervention that will improve visual outcomes and prevent blindness. The short-term objective of my research program is to evaluate candidate markers with regards to differences between untreated IIH, treated IIH and normal patients, changes over time in IIH patients receiving treatment, and differences between IIH patients with and without vision loss. The long-term objective of my research program is to elucidate markers of papilledema physiology that can be studied non-invasively and to ascertain their ability to predict future visual function in IIH and guide clinical management.
Other areas of active research include study of peri-operative vision loss and visual pathway based diagnosis of neuro-degenerative diseases. I am actively involved in clinical trials through the Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC).
Efficacy & Safety of RPh201 Treatment in Patients With Previous Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)
This study is designed as a double-masked, randomized, placebo-controlled, pivotal, clinical study to evaluate the efficacy and safety of subcutaneous (SC) administration of RPh201 in participants with previous NAION. All participants enrolled in the study will have a documented history of NAION for at least 12 months and at most, five years prior to enrollment.
Phase 2/3, Randomized, Double-Masked, Sham-Controlled Trial of QPI-1007 in Subjects With Acute Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)
This study will determine the effect of QPI-1007 on visual function in subjects with recent-onset NAION and assess the safety and tolerability of intravitreal injections of QPI-1007 in this population. This study will also evaluate the structural changes in the retina following administration of QPI-1007.
Stanford is currently not accepting patients for this trial. For more information, please contact Mariana Nunez, 650-497-7846.
Surgical Idiopathic Intracranial Hypertension Treatment Trial
Randomized trial of adults (≥18 years old) with idiopathic intracranial hypertension and moderate to severe visual loss without substantial recent treatment who are randomly assigned to (1) medical therapy, (2) medical therapy plus ONSF, or (3) medical therapy plus VPS. The primary outcome is visual field mean deviation change at first of Month 6 (26 weeks) or time of treatment failure of the eligible eye(s), followed by a continuation study to assess time to treatment failure. The determination of eligible eye(s) is based on meeting the eligibility criteria at baseline.
Stanford is currently not accepting patients for this trial. For more information, please contact Mariana Nunez, 650-497-7846.
Physiologically Based Markers of Idiopathic Intracranial Hypertension, Stanford University
Permanent visual impairment due to papilledema, an optic neuropathy characterized by optic nerve swelling, occurs in approximately half of patients with IIH. There is a significant clinical need for non-invasive biomarkers that will advance diagnosis and management of IIH. The objective of my research is to establish physiologically based markers of retinal ganglion cell(RGC) function and retinal/cerebral vasculature as markers of IIH that detect abnormalities, monitor treatment and distinguish peripheral vision outcomes. I have demonstrated that retinal vein diameter changes over the course of disease. Through collaboration with Dr. Ali Alaraj, an endovascular neurosurgeon, we have defined characteristic changes in cerebral venous blood flow and pressure in IIH patients. Through collaboration with Dr. McAnany, a psychophysics expert, we have demonstrated alterations in objective markers of optic nerve function that correlate with other measures of disease in IIH patients. These results are laying the scientific and technical foundation for the development of these markers as clinical tools and clinical trial outcome measures. Furthermore, the results are advancing scientific understanding of the pathophysiology underlying papilledema and other optic neuropathies.
Palo Alto, Ca
Risk factors for peri-operative vision loss, Stanford University, University of Illinois at Chicago, University of Chicago
Perioperative visual loss (POVL) is a devastating complication, with no known treatment or prevention,
most commonly due to ischemic optic neuropathy (ION), and retinal arterial occlusion (RAO), and less commonly
cortical blindness. We reported in 2009 that POVL had an estimated incidence of 3-10 cases/10,000
procedures in two of the highest volume surgical procedures.1 The resulting severe visual impairment costs >
$27,000/y, or $675,000 during the estimated remainder of a middle-aged individual’s life from increased health
care spending alone. Lost productivity costing > $250,000, and frequent litigation further increase costs. The
emotional toll of sudden, unexpected visual loss is immeasurable. It is imperative to understand the risk factors
for POVL in order to develop means to prevent these blinding complications. In collaboration with the University of Illinois at Chicago and University of Illinois at Chicago we are studying risk factors and developing a predictive model for perioperative visual loss (POVL) in spinal fusion and cardiac surgery.
Palo Alto, Ca
- Steven Roth, Professor, University of Illinois at Chicago
- Charlotte Joslin, Associate Professor, University of Illinois at Chicago
- Daniel Rubin, Assistant Professor, University of Chicago
Visual pathway based markers of neuro-degenerative disease
Clinical and post-mortem observations of pathological effects spreading beyond the motor system in some people with ALS have led to a shift from the classical characterization of ALS as a disease exclusively of motor neurons to that of a multisystem disorder. During my fellowship training in neuro-ophthalmology I led the largest characterization of clinical eye movement disorders in this population and discovered previously undocumented afferent visual dysfunction. Collaboration with Dr. Amani Fawzi at Northwestern University has indicated that retinal pathology may account for this observation. We have surveyed different tests of afferent visual function to determine which are abnormal in ALS patients and which has the best correlation with visual system pathology in ALS patients.
Current efforts involve infrastructure development to improve access to ophthalmic imaging in the neurosciences clinic to facilitate studies of ophthalmic markers of neurodegenerative disease and efforts to develop pupillometry apparatus with which to study diagnostic potential in neuro-degenerative disease.
- Daniel Joyce, School of Medicine
Neuro-ophthalmology clinical research
The rarity of many neuro-ophthalmic diseases is a barrier to effective clinical outcomes research. This barrier can be overcome through collaborations between investigators and institutions to increase sample size, and through application of advanced statistical techniques to clinical trial data sets to maximize data analysis efficiency. I am actively involved in the NIH sponsored Neuro-ophthalmology Research Disease Investigator Consortium. Current active treatment trials are studying nonarteritic anterior ischemic optic neuropathy, idiopathic intracranial hypertension, and Lebers hereditary optic neuropathy.
Palo Alto, CA
Retinal vessel diameter changes after 6 months of treatment in the Idiopathic Intracranial Hypertension Treatment Trial.
The British journal of ophthalmology
BACKGROUND/AIMS: Prior studies support an association between increased retinal venule diameter and elevated intracranial pressure (ICP). The purpose of this study was to test the hypothesis that retinal venule diameters decrease in association with long-term therapy for high ICP in subjects with idiopathic intracranial hypertension (IIH).METHODS: This is a retrospective analysis of multicentre randomised controlled trial data. Standardised procedures were used to measure area of optic nerve head elevation (ONHA) and diameters of 4 arterioles and 4 venules 2.7mm from the optic disc centre on fundus photos collected at baseline and after 6 months of randomised treatment with placebo+dietor acetazolamide+diet in subjects participating in the IIH Treatment Trial (IIHTT) (n=115). Change in arteriole (Da) and venule (Dv) diameters from baseline to 6 months was studied as a function of IIH, haemodynamic and demographic variables.RESULTS: Dv decreased following 6 months of therapy (8.1m, 5.9%,p<0.0005) but Da did not change. Dv change was associated with ONHA change (p<0.0005, r=0.47) and this association persisted in multiple variable models.CONCLUSIONS: Retinal venule diameter decreased, and arteriole diameter did not change in association with treatment for elevated ICP with a weight loss intervention and placebo or acetazolamide in IIHTT participants. Further study is needed to determine how retinal vessel measurements can be combined with other clinical observations to inform disease management.
View details for DOI 10.1136/bjophthalmol-2019-314648
View details for PubMedID 31949093
- Anterior Optic Neuropathy in a Patient With Cyclical Fevers. JAMA ophthalmology 2020
Update on the Diagnosis and Treatment of Idiopathic Intracranial Hypertension.
Seminars in neurology
2019; 39 (6): 682–91
Advances in ophthalmic diagnostics and results of interventional clinical trials are shifting diagnosis and management of idiopathic intracranial hypertension (IIH) to be more technology- and evidence-based. In this article, the evidence supporting current diagnostic criteria, evaluation, and medical and surgical management of IIH are reviewed.
View details for DOI 10.1055/s-0039-1698744
View details for PubMedID 31847039
- Methods for Quantifying Optic Disc Volume and Peripapillary Deflection Volume Using Radial Optical Coherence Tomography Scans and Association With Intracranial Pressure FRONTIERS IN NEUROLOGY 2019; 10
Predicting Risk of Perioperative Ischemic Optic Neuropathy: A Study Using the US National Inpatient Sample
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
View details for Web of Science ID 000488800703152
Effect of posterior optic nerve and sheath boundary conditions on globe deformation in high intracranial pressure (ICP) states
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
View details for Web of Science ID 000488800704178
Repeatability of the Photopic Negative Response in Stable Optic Neuropathy using a Handheld Electroretinogram System
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
View details for Web of Science ID 000488800700161
Development of Portable Pupillometer for Assessment of Optic Nerve Disease
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
View details for Web of Science ID 000488800700178
Patient Specific Models of Eye Geometry in High Intracranial Pressure States Based on Magnetic Resonance Images
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
View details for Web of Science ID 000488800700172
- Perioperative Visual Loss in Cardiac Surgery JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA 2019; 33 (5): 1420–29
Development of Portable Pupillometer for Assessment of Neurological Disease
LIPPINCOTT WILLIAMS & WILKINS. 2019
View details for Web of Science ID 000475965900373
Big Data Research in Neuro-Ophthalmology: Promises and Pitfalls.
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
BACKGROUND: Big data clinical research involves application of large data sets to the study of disease. It is of interest to neuro-ophthalmologists but also may be a challenge because of the relative rarity of many of the diseases treated.EVIDENCE ACQUISITION: Evidence for this review was gathered from the authors' experiences performing analysis of large data sets and review of the literature.RESULTS: Big data sets are heterogeneous, and include prospective surveys, medical administrative and claims data and registries compiled from medical records. High-quality studies must pay careful attention to aspects of data set selection, including potential bias, and data management issues, such as missing data, variable definition, and statistical modeling to generate appropriate conclusions. There are many studies of neuro-ophthalmic diseases that use big data approaches.CONCLUSIONS: Big data clinical research studies complement other research methodologies to advance our understanding of human disease. A rigorous and careful approach to data set selection, data management, data analysis, and data interpretation characterizes high-quality studies.
View details for PubMedID 30688751
Predicting Risk of Perioperative Ischemic Optic Neuropathy in Spine Fusion Surgery: A Cohort Study Using the National Inpatient Sample.
Anesthesia and analgesia
Ischemic optic neuropathy (ION) is a rare complication of anesthesia and surgery that causes vision loss in spine fusion. We sought to develop a predictive model based on known preoperative risk factors for perioperative ION to guide patient and physician preoperative decision-making.In the National Inpatient Sample (NIS) for 1998-2012, discharges for posterior thoracic, lumbar, and sacral spine fusion were identified and classified by ION status. Variables were selected without weighting via variable clustering using Principal Component Analysis of Mixed Data (PCA-MIX). Hierarchical clustering with 4 clusters was performed, and the variable with largest squared loading in each cluster was chosen. By splitting our sample into a training and testing data set, we developed and internally validated a predictive model. The final model using variables known preoperatively was constructed to allow determination of relative and absolute risk of developing perioperative ION and was tested for calibration and discrimination.The final predictive model based on hierarchical clustering contained 3 preoperative factors, age, male or female sex, and the presence of obstructive sleep apnea (OSA). The predictive model based on these factors had an area under the receiver operating characteristic curve (AUC) of 0.65 and good calibration. A score cutoff of >1 had 100% sensitivity, while score of 3 had 96.5% specificity. The highest estimated absolute risk (844.5/million) and relative risk of ION (46.40) was for a man, age 40-64 years, with OSA.The predictive model could enable screening for patients at higher risk of ION to provide more accurate risk assessment and surgical and anesthetic planning for perioperative ION in spine fusion.
View details for DOI 10.1213/ANE.0000000000004383
View details for PubMedID 31490255
- Association Between Peripapillary Bruch's Membrane Shape and Intracranial Pressure: Effect of Image Acquisition Pattern and Image Analysis Method, a Preliminary Study FRONTIERS IN NEUROLOGY 2018; 9
- Update on Perioperative Ischemic Optic Neuropathy Associated With Non-ophthalmic Surgery FRONTIERS IN NEUROLOGY 2018; 9
Mechanical Factors contributing to ocular globe flattening in states of elevated intracranial pressure: A Finite Element Analysis
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
View details for Web of Science ID 000442912506185
Photopic Negative Response as a Marker for Optic Neuropathy using a Handheld Electroretinogram Device
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
View details for Web of Science ID 000442932800234
Retinal venule diameters decreased following 6 months of treatment for high intracranial pressure in Idiopathic Intracranial Hypertension Treatment Trial participants
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
View details for Web of Science ID 000442912502011
Retinal Vessel Diameters Change Within 1 Hour of Intracranial Pressure Lowering
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
2018; 7 (2): 6
We tested the hypotheses that retinal venule diameter (Dv) is associated with baseline intracranial pressure (ICP) level and that Dv is reduced shortly after ICP lowering.Dv and arteriole diameter (Da) were extracted from scanning laser ophthalmoscopic images in 40 eyes of 20 adult human subjects (10 with and 10 without papilledema) immediately before and after measurement of ICP (range, 10-55 cm H2O) and ICP lowering by cerebrospinal fluid (CSF) drainage via lumbar puncture (LP). Generalized estimating equations (GEE) modeled the relationship between baseline ICP, Da and Dv before LP. Additional GEE modeled the relationship between initial ICP and change in Da and Dv (post-LP - pre-LP) following ICP lowering.Test-retest variability of diameter measurements ranged from 0.1 to 2.9 μm (0.1%-2.72%). Neither Da nor Dv pre-LP was associated with baseline ICP level (P = 0.140 Dv, P = 0.914 Da, GEE). Da and Dv change after ICP lowering was associated with baseline ICP, with vessel diameters increasing with lower baseline ICP and decreasing with elevated initial ICP (P = 0.030 baseline ICP vs. Dv change, P = 0.012 baseline ICP vs. Da change, GEE models).Retina arteriole and venule diameters change immediately following ICP lowering. The direction of change is dependent on the initial ICP; both increased in subjects with high ICP and both decreased in subjects with normal ICP.The relationship between initial ICP and direction of retinal vessel size change following ICP lowering suggests a potential effect of ICP on cerebral and ocular hemodynamics that is relevant when considering the use of retinal vessel measurements as a clinical marker of ICP change.
View details for PubMedID 29576930
Perioperative Retinal Artery Occlusion: Incidence and Risk Factors in Spinal Fusion Surgery From the US National Inpatient Sample 1998-2013.
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
2018; 38 (1): 36–41
Retinal artery occlusion (RAO) is a rare but devastating complication of spinal fusion surgery. We aimed to determine its incidence and associated risk factors.Hospitalizations involving spinal fusion surgery were identified by searching the National Inpatient Sample, a database of hospital discharges, from 1998 to 2013. RAO cases were identified using ICD-9-CM codes. Using the STROBE guidelines, postulated risk factors were chosen based on literature review and identified using ICD-9-CM codes. Multivariate logistic models with RAO as outcome, and risk factors, race, age, admission, and surgery type evaluated associations.Of an estimated 4,784,275 spine fusions in the United States from 1998 to 2013, there were 363 (CI: 291-460) instances of RAO (0.76/10,000 spine fusions, CI: 0.61-0.96). Incidence ranged from 0.35/10,000 (CI: 0.11-1.73) in 2001-2002 to 1.29 (CI: 0.85-2.08) in 2012-2013, with no significant trend over time (P = 0.39). Most strongly associated with RAO were stroke, unidentified type (odds ratio, OR: 14.33, CI: 4.54-45.28, P < 0.001), diabetic retinopathy (DR) (OR: 7.00, CI: 1.18-41.66, P = 0.032), carotid stenosis (OR: 4.94, CI: 1.22-19.94, P = 0.025), aging (OR for age 71-80 years vs 41-50 years referent: 4.07, CI: 1.69-10.84, P = 0.002), and hyperlipidemia (OR: 2.96, CI: 1.85-4.73, P < 0.001). There was an association between RAO and transforaminal lumbar interbody fusion (OR: 2.95, CI: 1.29-6.75, P = 0.010). RAO was more likely to occur with spinal surgery performed urgently or emergently compared with being done electively (OR: 0.40, CI: 0.23-0.68, P < 0.001).Patient-specific associations with RAO in spinal fusion include aging, carotid stenosis, DR, hyperlipidemia, stroke, and specific types of surgery. DR may serve as an observable biomarker of heightened risk of RAO in patients undergoing spine fusion.
View details for PubMedID 28665867
View details for PubMedCentralID PMC5764807
Update on Perioperative Ischemic Optic Neuropathy Associated With Non-ophthalmic Surgery.
Frontiers in neurology
2018; 9: 557
Perioperative visual loss (POVL) is a rare, serious complication of non-ophthalmic surgeries. Ischemic optic neuropathy (ION), and retinal arterial occlusion (RAO) are the main causes (1, 2). Less frequent are cortical blindness (3), acute glaucoma (4), and choroidal and vitreous hemorrhage (5). ION is the most common cause for which the neurologist or neuro-ophthalmologist is consulted as it is associated either with a normal ophthalmic exam (posterior ION, PION), or less often, with optic nerve (ON) head swelling (anterior ION, AION). The presumed cause is impaired blood supply to the optic nerve (Figure 1). The most common surgical procedures complicated by ION are cardiac surgery and spinal fusion. Retrospective studies, surveys, and case reports are the basis of most knowledge regarding peri-operative ION (poION), with cohort and case-control studies helping to identify candidate risk factors (6, 7). Animal models have provided insight regarding mechanisms (8). This mini-review is an update on the latest advancements regarding poION in non-ophthalmic surgeries in epidemiological, clinical, and animal studies.
View details for PubMedID 30042726
View details for PubMedCentralID PMC6048244
- OCT in Central Nervous System Diseases (Book Review) NEURO-OPHTHALMOLOGY 2018; 42 (1): 48
Comparison of cross sectional optical coherence tomography images of elevated optic nerve heads across acquisition devices and scan protocols.
Eye and vision (London, England)
2018; 5: 17
Background: Optic nerve head measurements extracted from optical coherence tomography (OCT) show promise for monitoring clinical conditions with elevated optic nerve heads. The aim of this study is to compare reliability within and between raters and between image acquisition devices of optic nerve measurements derived from OCT scans in eyes with varying degrees of optic nerve elevation.Methods: Wide angle line scans and narrow angle radial scans through optic nerve heads were obtained using three spectral domain(SD) OCT devices on 5 subjects (6 swollen optic nerves, 4 normal optic nerves). Three raters independently semi-manually segmented the internal limiting membrane(ILM) and Bruch's membrane(BM) on each scan using customized software. One rater segmented each scan twice. Segmentations were qualitatively and quantitatively compared. Inter-rater, intra-rater and inter-device reliability was assessed for the optic nerve cross sectional area calculated from the ILM and BM segmentations using intraclass correlation coefficients and graphical comparison.Results: Line scans from all devices were qualitatively similar. Radial scans for which frame rate could not be adjusted were of lower quality. Intra-rater reliability for segmentation and optic nerve cross sectional area was better than inter-rater reliability, which was better than inter-device reliability, though all ICC exceeded 0.95. Reliability was not impacted by the degree of optic nerve elevation.Conclusions: SD-OCT devices acquired similar quality scans of the optic nerve head, with choice of scan protocol affecting the quality. For image derived markers, variability between devices was greater than that attributable to inter and intra-rater differences.
View details for PubMedID 30009195
Electroretinography in idiopathic intracranial hypertension: comparison of the pattern ERG and the photopic negative response.
Documenta ophthalmologica. Advances in ophthalmology
2018; 136 (1): 45–55
To evaluate the relationship between electrophysiological measures of retinal ganglion cell (RGC) function in patients who have idiopathic intracranial hypertension (IIH).The pattern electroretinogram (pERG) and photopic negative response (PhNR) were recorded from 11 IIH patients and 11 age-similar controls. The pERG was elicited by a contrast-reversing checkerboard. The PhNR, a slow negative component following the flash ERG b-wave, was recorded in response to a long-wavelength flash presented against a short-wavelength adapting field. The PhNR was elicited using full-field (ffPhNR) and focal macular (fPhNR) stimuli. Additionally, Humphrey visual field mean deviation (HVF MD) was measured and ganglion cell complex volume (GCCV) was obtained by optical coherence tomography.The ffPhNR, fPhNR, and pERG amplitudes were outside of the normal range in 45, 9, and 45% of IIH patients, respectively. However, only mean ffPhNR amplitude was reduced significantly in the patients compared to controls (p < 0.01). The pERG amplitude correlated significantly with HVF MD and GCCV (both r > 0.65, p < 0.05). There were associations between ffPhNR amplitude and HVF MD (r = 0.58, p = 0.06) and with GCCV (r = 0.52, p = 0.10), but these did not reach statistical significance. fPhNR amplitude was not correlated significantly with HVF MD or GCCV (both r < 0.40, p > 0.20).Although the fPhNR is generally normal in IIH, other electrophysiological measures of RGC function, the ffPhNR and pERG, are abnormal in some patients. These measures provide complementary information regarding RGC dysfunction in these individuals.
View details for PubMedID 29139045
View details for PubMedCentralID PMC5812802
Quantitative Association Between Peripapillary Bruch's Membrane Shape and Intracranial Pressure.
Investigative ophthalmology & visual science
2017; 58 (5): 2739-2745
The purpose of this study was to determine if there is a quantitative relationship between chronic intracranial pressure (ICP) and peripapillary Bruch's membrane (pp-BM) shape and to determine whether change in pp-BM shape can be detected within 1 hour after ICP lowering by lumbar puncture (LP).In this study, 30° nasal-temporal optical coherence tomography B-scans were obtained within 1 hour before and after LP in 39 eyes from 20 patients (age = 23-86 years, 75% female, ICP [opening pressure] = 10-55 cm H2O). A total of 16 semi-landmarks defined pp-BM on each image. Geometric morphometric analysis identified principal components of shape in the image set. Generalized estimating equation models, accounting for within-subject correlation, were used to identify principal components that were associated with chronic ICP (comparing pre-LP images between eyes) and/or acute ICP changes (comparing pre- and post-LP images within eyes). The pp-BM width and anterior pp-BM location were calculated directly from each image and were studied in the same manner.Principal component 1 scalar variable on pre-LP images was associated with ICP (P < 0.0005). Principal component 4 magnitude changed within eyes after LP (P = 0.003). For both principal components 1 and 4, lower ICP corresponded with a more posterior position of pp-BM. Chronic ICP was associated with both pp-BM width (6.81 μm/cm H2O; P = 0.002) and more anterior location of temporal and nasal pp-BM margins (3.41, 3.49 μm/cm H2O; P < 0.0005, 0.002).This study demonstrates a quantitative association between pp-BM shape and chronic ICP level. Changes in pp-BM shape are detectable within 1 hour of lowering ICP. pp-BM shape may be a useful marker for chronic ICP level and acute ICP changes. Further study is needed to determine how pp-BM shape changes relate to clinical markers of papilledema.
View details for DOI 10.1167/iovs.17-21592
View details for PubMedID 28549088
View details for PubMedCentralID PMC5455169
The Longitudinal Idiopathic Intracranial Hypertension Trial: Outcomes from Months 6 - 12.
American journal of ophthalmology
To determine whether the beneficial effects of acetazolamide (ACZ) in improving vision at 6 months continues to month 12 in participants of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).non-randomized clinical study METHODS: In the IIHTT, subjects were randomly assigned to placebo-plus-diet or maximally tolerated dosage of acetazolamide-plus-diet. At 6 months subjects transitioned from study drug to ACZ. This resulted in the following groups 1) ACZ to ACZ; n = 34; 2) placebo to ACZ; n = 35; 3) ACZ to no treatment; n = 16; and 4) placebo to no treatment; n = 11. 96 IIHTT subjects had evaluations at 6 and 12 months. Our main outcome measure was change from month 6 to month 12 in visual field mean deviation with secondary measures being change in papilledema grade, ETDRS scores and quality of life (QoL) measures.The ACZ to ACZ group improved 0.35 dB , p=0.05; placebo subjects with no ACZ improved 0.81 dB MD, p = 0.07 at 12 mos. The other groups improved 0.35 to 0.46 dB MD. Mean improvements in papilledema grade occurred most markedly in the group that exchanged placebo for ACZ (0.91 units, p < 0.001). QoL and headache disability scores showed significant improvements in the placebo group added ACZ.Improvements in MD continued from month 6 to month 12 of the IIHTT in all treatment groups -most marked in the placebo group tapered off study drug. Adding ACZ to the placebo group significantly improved papilledema grade, headache and QoL measures.
View details for DOI 10.1016/j.ajo.2017.01.004
View details for PubMedID 28104417
Diagnostic Challenge: Sequential Unilateral Cranial Neuropathies Due to Perineural Spread of Carcinoma
2017; 41 (4): 227–31
An 86-year old man developed sequential dysfunction of trigeminal (V1), facial, abducens, trigeminal (v2), oculomotor, and hypoglossal cranial nerves on the right over 20 months. Magnetic resonance imaging (MRI) showed a lesion in the right cavernous sinus. Although there was clinical suspicion that this was related to perineural spread of an extracranial tumour, a primary lesion was not discovered. Stereotactic biopsies of the intracranial lesion were non-diagnostic, and the patient succumbed to his tumour following a period of rapid growth. Postmortem examination showed the intracranial lesion to be a carcinoma with squamous features. This case highlights the challenges of diagnosis of intracranial perineural spread and the potential for transformation from indolent to aggressive tumour behaviour.
View details for DOI 10.1080/01658107.2017.1304968
View details for Web of Science ID 000415700200012
View details for PubMedID 29344066
View details for PubMedCentralID PMC5762146
Cerebral Venous Thrombosis with Papilloedema Secondary to Skull Base Plasmacytoma
2017; 41 (5): 284–86
A 60-year-old woman with history of multiple myeloma was in remission after stem cell transplant 6 years prior. She was undergoing work-up for headaches that were thought to be secondary to a right mastoiditis seen on magnetic resonance imaging (MRI). On routine eye exam, papilloedema was noted. A lumbar puncture was performed, with elevated opening pressure with normal constituents. She was an atypical age for idiopathic intracranial hypertension, and her mastoiditis raised concern for secondary cerebral venous sinus thrombosis. Magnetic resonance venography (MRV) was performed showing poor flow in the right sigmoid sinus, and computed tomography venography (CTV) showed lack of contrast enhancement distal to the right sigmoid sinus, consistent with occlusion. There was also an enhancing mass inferior to the right occipital bone. Biopsy confirmed recurrent plasma cell myeloma. She was treated with chemotherapy, radiation, and warfarin for presumed cerebral venous sinus thrombosis.
View details for PubMedID 29339964
View details for PubMedCentralID PMC5762173
Visual consequences of medications for multiple sclerosis: the good, the bad, the ugly, and the unknown.
Eye and brain
2017; 9: 13–21
Multiple sclerosis (MS) is associated with vision changes both due to MS effects on visual pathways and due to medication effects on the visual pathways. Distinguishing the causes of vision change are critical to appropriate diagnosis and management. The incidence, presentation, and treatment of fingolimod-associated macular edema, alemtuzumab-associated thyroid orbitopathy, and progressive multifocal leukoencephalopathy in MS patients are reviewed. Evidence for beneficial effects of acute, chronic, and symptomatic MS medications on vision is presented.
View details for PubMedID 28721111
Validation of Simplified Visual Acuity Testing Protocols in Amyotrophic Lateral Sclerosis.
Neuro-ophthalmology (Aeolus Press)
2017; 41 (5): 247–52
High- and low-contrast visual acuity (HCVA, LCVA) are potential quantitative markers of neurological dysfunction in amyotrophic lateral sclerosis (ALS). The complex nature and duration of gold standard (GS) protocols precludes widespread use in neurology settings. This study compares simplified to GS visual acuity (VA) protocols. Monocular HCVA and LCVA were measured in ALS (n= 10) and control (n= 4) subjects using six protocols, varying by two chart and three refraction methods. Intraclass correlation coefficients between simplified and GS protocols ranged from 0.83 to 0.98 (HCVA, excellent agreement) and 0.56 to 0.75 (LCVA, moderate agreement). Differences between LCVA and GS protocols exceeded test-retest reliability. Simplified HCVA protocols using LCD (liquid crystal display) tablet charts and/or pinhole correction produced valid measurements. None of the modified LCVA testing protocols produced valid measurements.
View details for DOI 10.1080/01658107.2017.1305422
View details for PubMedID 29339958
View details for PubMedCentralID PMC5762169
Diffuse Colour Discrimination as Marker of Afferent Visual System Dysfunction in Amyotrophic Lateral Sclerosis.
Neuro-ophthalmology (Aeolus Press)
2017; 41 (6): 310–14
Abnormalities of the inner and intermediate retinal structures in patients with amyotrophic lateral sclerosis (ALS) have been described using optical coherence tomography and histopathology. Colour vision is a potential marker of these structural changes. The purpose of this study is to test the hypothesis that colour vision impairment is associated with ALS. Monocular (right eye) colour vision was assessed in subjects with definite or probable ALS (n= 25, aged 50-80 years) and control (n= 21, aged 46-89 years) subjects with corrected near visual acuity of at least 20/40 using the L'Anthony D15 color test (desaturated), scored by c-index, a measure of diffuse colour discrimination. Of ALS subjects, 16/25 (64%) had impaired colour vision (c-index >1.8). Comparing with our normal subjects and accounting for age, 72% (n= 18) of ALS subjects had colour vision below the 50th percentile, 52% (n= 13) had colour vision below the 25th percentile, 24% (n= 6) had colour vision below the 10th percentile, and 8% (n= 2) had colour vision below the 2nd percentile. In multivariate models of ln(c-index) and age, the intercept was higher and the slope was flatter in ALS subjects, suggesting that colour vision deficits are more prominent in younger ALS patients. Diffuse colour discrimination deficits are detected in ALS subjects at younger ages than in control subjects. Further study is needed to confirm these findings and to determine if the ALS colour discrimination abnormalities correlate with structural markers of retinal involvement and ALS disease severity.
View details for DOI 10.1080/01658107.2017.1326153
View details for PubMedID 29344070
View details for PubMedCentralID PMC5764062
Perioperative Retinal Artery Occlusion: Risk Factors in Cardiac Surgery from the United States National Inpatient Sample 1998-2013.
2017; 124 (2): 189–96
To study the incidence and risk factors for retinal artery occlusion (RAO) in cardiac surgery.Retrospective study using the National Inpatient Sample (NIS).The NIS was searched for cardiac surgery. Retinal artery occlusion was identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Postulated risk factors based on literature review were included in multivariate logistic models.Diagnosis of RAO.A total of 5 872 833 cardiac operative procedures were estimated in the United States from 1998 to 2013, with 4564 RAO cases (95% confidence interval [95% CI], 4282-4869). Nationally estimated RAO incidence was 7.77/10 000 cardiac operative procedures from 1998 to 2013 (95% CI, 7.29-8.29). Associated with increased RAO were giant cell arteritis (odds ratio [OR], 7.73; CI, 2.78-21.52; P < 0.001), transient cerebral ischemia (OR, 7.67; CI, 5.31-11.07; P < 0.001), carotid artery stenosis (OR, 7.52; CI, 6.22-9.09; P < 0.001), embolic stroke (OR, 4.43; CI, 3.05-6.42; P < 0.001), hypercoagulability (OR, 2.90; CI, 1.56-5.39; P < 0.001), myxoma (OR, 2.43; CI, 1.39-4.26; P = 0.002), diabetes mellitus (DM) with ophthalmic complications (OR, 1.89; CI, 1.10-3.24; P = 0.02), and aortic insufficiency (OR, 1.85; CI, 1.26-2.71; P = 0.002). Perioperative bleeding, aortic and mitral valve surgery, and septal surgery increased the odds of RAO. Negatively associated with RAO were female gender (OR, 0.77; CI, 0.66-0.89; P < 0.001), thrombocytopenia (OR, 0.79; CI, 0.62-1.00; P = 0.049), acute coronary syndrome (OR, 0.72; CI, 0.58-0.89; P = 0.003), atrial fibrillation (OR, 0.82; CI, 0.70-0.95; P = 0.01), congestive heart failure (OR, 0.73; CI, 0.60-0.88; P < 0.001), DM 2 (OR, 0.74; CI, 0.61-0.89; P = 0.001), and smoking (OR, 0.82; CI, 0.70-0.97; P = 0.02).Risk factors for RAO in cardiac surgery include giant cell arteritis, carotid stenosis, stroke, hypercoagulable state, and DM with ophthalmic complications; associated with lower risk were female gender, thrombocytopenia, acute coronary syndrome, atrial fibrillation, congestive heart failure, DM 2, and smoking. Surgery in which the heart was opened (e.g., septal repair) versus surgery in which it was not (e.g., CABG) and perioperative bleeding increased the risk of RAO.
View details for PubMedID 27914836
Ischemic Optic Neuropathy in Cardiac Surgery: Incidence and Risk Factors in the United States from the National Inpatient Sample 1998 to 2013.
Ischemic optic neuropathy is the most common form of perioperative visual loss, with highest incidence in cardiac and spinal fusion surgery. To date, potential risk factors have been identified in cardiac surgery by only small, single-institution studies. To determine the preoperative risk factors for ischemic optic neuropathy, the authors used the National Inpatient Sample, a database of inpatient discharges for nonfederal hospitals in the United States.Adults aged 18 yr or older admitted for coronary artery bypass grafting, heart valve repair or replacement surgery, or left ventricular assist device insertion in National Inpatient Sample from 1998 to 2013 were included. Risk of ischemic optic neuropathy was evaluated by multivariable logistic regression.A total of 5,559,395 discharges met inclusion criteria with 794 (0.014%) cases of ischemic optic neuropathy. The average yearly incidence was 1.43 of 10,000 cardiac procedures, with no change during the study period (P = 0.57). Conditions increasing risk were carotid artery stenosis (odds ratio, 2.70), stroke (odds ratio, 3.43), diabetic retinopathy (odds ratio, 3.83), hypertensive retinopathy (odds ratio, 30.09), macular degeneration (odds ratio, 4.50), glaucoma (odds ratio, 2.68), and cataract (odds ratio, 5.62). Female sex (odds ratio, 0.59) and uncomplicated diabetes mellitus type 2 (odds ratio, 0.51) decreased risk.The incidence of ischemic optic neuropathy in cardiac surgery did not change during the study period. Development of ischemic optic neuropathy after cardiac surgery is associated with carotid artery stenosis, stroke, and degenerative eye conditions.
View details for PubMedID 28244936
High and Low Contrast Visual Acuity Are Not Affected in Amyotrophic Lateral Sclerosis
2016; 11 (12)
The afferent visual system may be affected by neuro-degeneration in amyotrophic lateral sclerosis (ALS) based on observations of visual function impairment and retinal inclusions on histopathology in ALS patients. To test the hypothesis that visual acuity is impaired in ALS, we compared three measures of visual acuity in ALS patients (n = 25) attending a multidisciplinary ALS clinic and age matched control subjects (n = 25). Bilateral monocular and binocular visual acuities were assessed using high contrast (black letters on white background) and low contrast (2.5%, 1.25% grey letters on white background) visual acuity charts under controlled lighting conditions following refraction. Binocular summation was calculated as the difference between binocular and best monocular acuity scores. There were no associations between binocular or monocular high contrast visual acuity or low contrast visual acuity and amyotrophic lateral sclerosis diagnosis (generalized estimating equation models accounting for age). Binocular summation was similar in both amyotrophic lateral sclerosis and control subjects. There was a small magnitude association between increased duration of ALS symptoms and reduced 1.25% low contrast visual acuity. This study does not confirm prior observations of impaired visual acuity in patients with amyotrophic lateral sclerosis and does not support this particular measure of visual function for use in broad scale assessment of visual pathway involvement in ALS patients.
View details for DOI 10.1371/journal.pone.0168714
View details for Web of Science ID 000391226900038
View details for PubMedID 28033389
MACULAR DETACHMENT ASSOCIATED WITH ANOMALOUS OPTIC NERVES AND DURAL ECTASIA IN 49, XXXXY SYNDROME.
Retinal cases & brief reports
To present a case of a patient with XXXXY syndrome, anomalous optic nerves, and dural ectasia in conjunction with macular detachment.Case report.A 3-year-old boy with XXXXY chromosomal abnormality presented with bilateral maculopathy. On evaluation, he was found to have anomalous optic disks with serous detachment of the left eye. Magnetic resonance imaging of the brain revealed bilateral optic nerve dural ectasia without evidence of elevated intracranial pressure.XXXXY syndrome, like the related condition of Klinefelter syndrome, can manifest with ocular abnormalities. In the present case, the dural ectasia may have facilitated access of cerebrospinal fluid through anomalous optic nerves, resulting in neurosensory detachment.
View details for PubMedID 27617393
Perioperative Visual Loss in Spine Fusion Surgery: Ischemic Optic Neuropathy in the United States from 1998 to 2012 in the Nationwide Inpatient Sample.
2016; 125 (3): 457-464
Perioperative ischemic optic neuropathy (ION) causes visual loss in spinal fusion. Previous case-control studies are limited by study size and lack of a random sample. The purpose of this study was to study trends in ION incidence in spinal fusion and risk factors in a large nationwide administrative hospital database.In the Nationwide Inpatient Sample for 1998 to 2012, procedure codes for posterior thoracic, lumbar, or sacral spine fusion and diagnostic codes for ION were identified. ION was studied over five 3-yr periods (1998 to 2000, 2001 to 2003, 2004 to 2006, 2007 to 2009, and 2010 to 2012). National estimates were obtained using trend weights in a statistical survey procedure. Univariate and Poisson logistic regression assessed trends and risk factors.The nationally estimated volume of thoracic, lumbar, and sacral spinal fusion from 1998 to 2012 was 2,511,073. ION was estimated to develop in 257 patients (1.02/10,000). The incidence rate ratio (IRR) for ION significantly decreased between 1998 and 2012 (IRR, 0.72 per 3 yr; 95% CI, 0.58 to 0.88; P = 0.002). There was no significant change in the incidence of retinal artery occlusion. Factors significantly associated with ION were age (IRR, 1.24 per 10 yr of age; 95% CI, 1.05 to 1.45; P = 0.009), transfusion (IRR, 2.72; 95% CI, 1.38 to 5.37; P = 0.004), and obesity (IRR, 2.49; 95% CI, 1.09 to 5.66; P = 0.030). Female sex was protective (IRR, 0.30; 95% CI, 0.16 to 0.56; P = 0.0002).Perioperative ION in spinal fusion significantly decreased from 1998 to 2012 by about 2.7-fold. Aging, male sex, transfusion, and obesity significantly increased the risk.
View details for DOI 10.1097/ALN.0000000000001211
View details for PubMedID 27362870
Research Registries: A Tool to Advance Understanding of Rare Neuro-Ophthalmic Diseases.
Journal of neuro-ophthalmology
2016; 36 (3): 317-323
Medical research registries (MRR) are organized systems used to collect, store, and analyze patient information. They are important tools for medical research with particular application to the study of rare diseases, including those seen in neuro-ophthalmic practice.Evidence for this review was gathered from the writers' experiences creating a comprehensive neuro-ophthalmology registry and review of the literature.MRR are typically observational and prospective databases of de-identified patient information. The structure is flexible and can accommodate a focus on specific diseases or treatments, surveillance of patient populations, physician quality improvement, or recruitment for future studies. They are particularly useful for the study of rare diseases. They can be integrated into the hierarchy of medical research at many levels provided their construction is well organized and they have several key characteristics including an easily manipulated database, comprehensive information on carefully selected patients, and comply with human subjects regulations. MRR pertinent to neuro-ophthalmology include the University of Illinois at Chicago neuro-ophthalmology registry, Susac Syndrome Registry, Intracranial Hypertension Registry, and larger-scale patient outcome registries being developed by professional societies.MRR have a variety of forms and applications. With careful planning and clear goals, they are flexible and powerful research tools that can support multiple different study designs, and this can provide the potential to advance understanding and care of neuro-ophthalmic diseases.
View details for DOI 10.1097/WNO.0000000000000391
View details for PubMedID 27389624
View details for PubMedCentralID PMC4988906
Detection of retinal blood vessel changes in multiple sclerosis with optical coherence tomography
BIOMEDICAL OPTICS EXPRESS
2016; 7 (6): 2321-2330
Although retinal vasculitis is common in multiple sclerosis (MS), it is not known if MS is associated with quantitative abnormalities in retinal blood vessels (BVs). Optical coherence tomography (OCT) is suitable for examining the integrity of the anterior visual pathways in MS. In this paper we have compared the size and number of retinal blood vessels in patients with MS, with and without a history of optic neuritis (ON), and control subjects from the cross-sectional retinal images from OCT. Blood vessel diameter (BVD), blood vessel number (BVN), and retinal nerve fiber layer thickness (RNFLT) were extracted from OCT images collected from around the optic nerves of 129 eyes (24 control, 24 MS + ON, 81 MS-ON) of 71 subjects. Associations between blood vessel metrics, MS diagnosis, MS disability, ON, and RNFLT were evaluated using generalized estimating equation (GEE) models. MS eyes had a lower total BVD and BVN than control eyes. The effect was more pronounced with increased MS disability, and persisted in multivariate models adjusting for RNFLT and ON history. Twenty-nine percent (29%) of MS subjects had fewer retinal blood vessels than all control subjects. MS diagnosis, disability, and ON history were not associated with average blood vessel size. The relationship between MS and lower total BVD/BVN is not accounted for by RNFLT or ON. Further study is needed to determine the relationship between OCT blood vessel metrics and qualitative retinal blood vessel abnormalities in MS.
View details for DOI 10.1364/BOE.7.002321
View details for Web of Science ID 000377514000021
View details for PubMedID 27375947
View details for PubMedCentralID PMC4918585
Bariatric Surgery and the Neuro-Ophthalmologist
JOURNAL OF NEURO-OPHTHALMOLOGY
2016; 36 (1): 78-84
As the prevalence of obesity increases, so, too, do the prevalences of weight-related diseases and surgical procedures to promote weight loss. It is important for neuro-ophthalmologists to be familiar with these procedures and possible downstream effects on afferent and efferent visual function.Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, psychiatry, and neurosurgery literature.Bariatric surgery is a safe and effective treatment for weight loss in obese individuals. There is Level IV evidence that it is associated with improvement in idiopathic intracranial hypertension (IIH). Laboratory nutrient deficiencies are common following some types of bariatric procedures. Symptomatic deficiencies are less common but can be devastating. Thiamine deficiency can cause nystagmus and other symptoms in weeks to months after surgery, whereas B12 or copper deficiency can cause optic neuropathy in years to decades following bariatric surgery.Bariatric surgery is a potential treatment for IIH. Postoperative vitamin deficiencies may cause nystagmus, optic neuropathy, nyctalopia, and/or ophthalmoparesis weeks to years after surgery.
View details for DOI 10.1097/WNO.0000000000000332
View details for Web of Science ID 000371534000019
View details for PubMedID 26764529
Cross-Sectional Analysis of Neurocognitive Function, Retinopathy, and Retinal Thinning by Spectral-Domain Optical Coherence Tomography in Sickle Cell Patients.
Middle East African journal of ophthalmology
2016; 23 (1): 79-83
The purpose was to examine the relationship between neurocognitive function and two distinct forms of retinopathy in sickle cell disease.Patients with sickle cell disease (n = 44, age range: 19-56 years, 70% female) were prospectively recruited for this cross-sectional study. Retinopathy was characterized by: (1) Presence of focal retinal thinning on spectral domain optical coherence tomography and (2) determination of the sickle retinopathy stage on funduscopic exam based on Goldberg classification. Neurocognitive function was assessed using the Philadelphia Brief Assessment of Cognition (PBAC), a validated test of cognition. Univariate and multivariate analyses for PBAC score outcomes were performed. Retinal thinning and retinopathy stage were primary variables of interest and age, gender, genotype, education, and history of stroke were covariates.Univariate analysis revealed associations with total PBAC score and age (P = 0.049), history of stroke (P = 0.04), and genotype (P < 0.001). Focal retinal thinning and Goldberg retinopathy stage were not associated with each other in this sample. Neither the presence of focal retinal thinning nor degree of retinopathy was associated with total PBAC score in univariate or multivariate analyses.We find an association between lower cognitive function and older age, history of stroke and sickle cell genotype SS in patients with sickle cell disease. Our data do not provide evidence to support an association between cognitive function and retinopathy in sickle cell patients.
View details for DOI 10.4103/0974-9233.150632
View details for PubMedID 26957844
The Pupillary Light Reflex in Idiopathic Intracranial Hypertension
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2016; 57 (1): 23-29
To evaluate the effects of idiopathic intracranial hypertension (IIH) on rod-, cone-, and melanopsin-mediated pupillary light reflexes (PLRs).Pupillary light reflexes elicited by full-field, brief-flash stimuli were recorded in 13 IIH patients and 13 normal controls. Subjects were dark-adapted for 10 minutes and the PLR was recorded in response to short-wavelength flashes (0.001 cd/m2: rod condition; 450 cd/m2: melanopsin condition). Subjects were then exposed to a rod-suppressing field and 10 cd/m2 long-wavelength flashes were presented (cone condition). Pupillary light reflexes were quantified as the maximum transient constriction (rod and cone conditions) and the post-illumination pupil constriction (melanopsin condition), relative to the baseline pupil size. Diagnostic power was evaluated using receiver operating characteristic (ROC) analysis.The IIH patients had significantly smaller PLRs under the melanopsin (P < 0.001) and rod (P = 0.04) paradigms; a trend for reduced cone-mediated PLRs was also found (P = 0.08). Receiver operating characteristic analysis indicated areas under the curves (AUC) of 0.83 (melanopsin-meditated; P = 0.001), 0.71 (rod-mediated; P = 0.07), and 0.77 (cone-mediated; P = 0.02). The AUC (0.90, P < 0.001), sensitivity (85%), and specificity (85%) were high for ROC analysis performed on the mean of the rod, cone, and melanopsin PLRs.Pupillary light reflex reductions in IIH patients indicate compromised RGC function. PLR measurement, particularly under rod- and melanopsin-mediated conditions, may be a useful adjunct to standard clinical measures of visual function in IIH.
View details for DOI 10.1167/iovs.15-18181
View details for Web of Science ID 000373589500004
View details for PubMedID 26746015
Retinal Vascular Changes are a Marker for Cerebral Vascular Diseases
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
2015; 15 (7)
The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross-sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease, and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion, and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk.
View details for DOI 10.1007/s11910-015-0561-1
View details for Web of Science ID 000356253200003
View details for PubMedID 26008809
The Photopic Negative Response in Idiopathic Intracranial Hypertension
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2015; 56 (6): 3709-3714
To evaluate the photopic negative response (PhNR) as an index of retinal ganglion cell (RGC) function in idiopathic intracranial hypertension (IIH).Amplitude and implicit time of the PhNR, as elicited by full-field, brief-luminance flashes, was measured in IIH (n = 10) and visually normal control (n = 15) subjects. Visual function was assessed in IIH subjects using standard automated perimetry mean deviation (SAP-MD) scores. Optic nerve structure was evaluated using the Frisén papilledema grading scale (FPG). Macula ganglion cell complex volume (GCCV) was extracted from optical coherence tomography images to assess RGC loss.Median PhNR amplitude was significantly lower in IIH subjects compared with control subjects (P = 0.015, Mann-Whitney Rank Sum [MW]), but implicit time was similar (P = 0.54, MW). In IIH subjects, PhNR amplitude and SAP-MD were correlated (Pearson's r = 0.78, P = 0.008). Ganglion cell complex volume was correlated with both SAP-MD (r = 0.72, P = 0.019) and PhNR amplitude (r = 0.77, P = 0.009). Multivariate linear regression models demonstrated that the correlation between GCCV and PhNR amplitude was improved by accounting for FPG in the model (r = 0.94, P < 0.0001), but the correlation between GCCV and SAP-MD was not (r = 0.74, P = 0.009).Photopic negative response amplitude, which can be decreased in IIH subjects, correlates well with a clinical measure of visual function (SAP-MD). In multivariate models, it correlated with both an imaging measure of chronic ganglion cell injury (GCCV) and a clinical measure of acute optic nerve head pathology (FPG). Further studies are needed to determine the clinical utility of PhNR as a marker for diagnosis and monitoring of IIH.
View details for DOI 10.1167/iovs.15-16586
View details for Web of Science ID 000357740200030
View details for PubMedID 26047172
Retinal Vessel Diameter Assessment in Papilledema by Semi-Automated Analysis of SLO Images: Feasibility and Reliability
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2014; 55 (4): 2049-2054
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.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.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.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.
View details for DOI 10.1167/iovs.13-13621
View details for Web of Science ID 000335913100005
View details for PubMedID 24609623
Association of Race/Ethnicity With Visual Outcomes Following Acute Optic Neuritis An Analysis of the Optic Neuritis Treatment Trial
2014; 132 (4): 421-427
IMPORTANCE Retrospective studies have demonstrated disparate outcomes following acute optic neuritis in individuals of African descent compared with individuals of white race/ethnicity. However, published analyses of the prospectively collected Optic Neuritis Treatment Trial (ONTT) data identified no association between worse visual outcomes and black race/ethnicity. OBJECTIVES To investigate the associations of age, sex, and race/ethnicity 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, or intravenous methylprednisolone), time, and treatment × time interaction, as well as demographic covariates of age, sex, and race/ethnicity. SETTING AND PARTICIPANTS The ONTT data were collected at multiple centers in the United States. Patients of black (n = 58) and white (n = 388) race/ethnicity with acute optic neuritis who enrolled in the ONTT within 8 days of symptom onset were included in analyses. MAIN OUTCOMES AND MEASURES The contrast sensitivity and visual acuity (logMAR) in the affected eye were modeled using 2-stage mixed-effects regression techniques. All available follow-up data from baseline to 15 to 18 years were included. RESULTS The data identified no relationship of age, sex, or treatment with contrast sensitivity or visual acuity outcomes. Race/ethnicity was significantly related to contrast sensitivity (P < .001) and visual acuity (P < .001) during a 15-year period following acute optic neuritis, with black race/ethnicity being associated with worse scores for both. CONCLUSIONS AND RELEVANCE Race/ethnicity seems 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 race/ethnicity with acute optic neuritis to be studied and represents the first evidence from a prospectively collected data set to support a hypothesis of race/ethnicity-dependent visual outcomes of acute optic neuritis.
View details for DOI 10.1001/jamaophthalmol.2013.7995
View details for Web of Science ID 000337890500008
View details for PubMedID 24557028
Isolated third, fourth, and sixth cranial nerve palsies from presumed microvascular versus other causes: a prospective study.
2013; 120 (11): 2264-2269
To estimate the proportion of patients presenting with isolated third, fourth, or sixth cranial nerve palsy of presumed microvascular origin versus other causes.Prospective, multicenter, observational case series.A total of 109 patients aged 50 years or older with acute isolated ocular motor nerve palsy.Magnetic resonance imaging (MRI) of the brain.Causes of acute isolated ocular motor nerve palsy (presumed microvascular or other) as determined with early MRI and clinical assessment.Among 109 patients enrolled in the study, 22 had cranial nerve III palsy, 25 had cranial nerve IV palsy, and 62 had cranial nerve VI palsy. A cause other than presumed microvascular ischemia was identified in 18 patients (16.5%; 95% confidence interval, 10.7-24.6). The presence of 1 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 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). By 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).In our series of patients with acute isolated ocular motor nerve palsies, a substantial proportion of patients had other causes, including neoplasm, GCA, and brain stem infarction. Brain MRI and laboratory workup have a role in the initial evaluation of older patients with isolated acute ocular motor nerve palsies regardless of whether vascular risk factors are present.
View details for DOI 10.1016/j.ophtha.2013.04.009
View details for PubMedID 23747163
Cross-sectional evaluation of clinical neuro-ophthalmic abnormalities in an amyotrophic lateral sclerosis population
JOURNAL OF THE NEUROLOGICAL SCIENCES
2012; 314 (1-2): 97-101
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.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.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).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.
View details for DOI 10.1016/j.jns.2011.10.016
View details for Web of Science ID 000301273000018
View details for PubMedID 22192877
Visual and Systemic Outcomes in Pediatric Ocular Myasthenia Gravis
AMERICAN JOURNAL OF OPHTHALMOLOGY
2010; 150 (4): 453-459
To evaluate visual and systemic outcomes in pediatric patients with purely ocular myasthenia gravis (OMG) treated at the Children's Hospital of Philadelphia.Retrospective chart review.Pediatric patients with OMG seen at a single institution over a 16-year period with a minimum follow-up of 1 year were reviewed. Associations of demographic and clinical characteristics with disease resolution, amblyopia, and development of generalized symptoms of myasthenia gravis were analyzed.Thirty-nine patients were identified, with a mean age of 5.4 ± 4.8 years and mean follow-up of 4.8 ± 4.3 years. Fifteen patients were treated with pyridostigmine only, 19 (49%) also received steroids, and 15 (38%) underwent thymectomy. Four patients (10%) received steroid-sparing immunosuppressive therapy. Resolution occurred in 10 patients, and generalized symptoms eventually occurred in 9 patients. Although 10 patients were treated for amblyopia, only 1 had amblyopia at the final visit. There was no correlation between sex or age with amblyopia or development of generalized symptoms. Thymectomy, when performed before the onset of generalized symptoms, showed a trend toward protection from the development of generalized symptoms (P = .07).In our series, 24% of patients had disease resolution and 23% had generalized symptoms. Our larger cohort confirms previous findings that treated and untreated pediatric patients with OMG have a relatively low risk of developing generalized symptoms and that related amblyopia is readily reversible. Although our treatments were more aggressive than those previously reported, our rates of amblyopia and development of generalized symptoms are comparable.
View details for DOI 10.1016/j.ajo.2010.05.002
View details for Web of Science ID 000282867500003
View details for PubMedID 20678749
Noninvasive Measurement of Cerebral Blood Flow and Blood Oxygenation Using Near-Infrared and Diffuse Correlation Spectroscopies in Critically Brain-Injured Adults
2010; 12 (2): 173-180
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.Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBF(DCS)), and changes in oxy-hemoglobin (DeltaHbO(2)), deoxy-hemoglobin (DeltaHb), and total hemoglobin concentration (DeltaTHC), 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 (rCBF(XeCT)) and were then compared to rCBF(DCS). Spearman's rank coefficients were employed to test for associations between rCBF(DCS) and rCBF(XeCT), as well as between rCBF from both modalities and NIRS parameters.rCBF(DCS) and rCBF(XeCT) showed good correlation (r (s) = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBF(DCS) and DeltaHbO(2)/DeltaTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.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.
View details for DOI 10.1007/s12028-009-9305-x
View details for Web of Science ID 000275905800006
View details for PubMedID 19908166
Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis in Children and Adolescents
ANNALS OF NEUROLOGY
2009; 66 (1): 11-18
To report the clinical features of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients < or = 18 years old.Information was obtained by the authors or referring physicians. Antibodies were determined by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) using HEK293 cells ectopically expressing NR1.Over an 8-month period, 81 patients (12 male) with anti-NMDAR encephalitis were identified. Thirty-two (40%) were < or =18 years old (youngest 23 months, median 14 years); 6 were male. The frequency of ovarian teratomas was 56% in women >18 years old, 31% in girls < or =18 years old (p = 0.05), and 9% in girls < or =14 years old (p = 0.008). None of the male patients had tumors. Of 32 patients < or =18 years old, 87.5% presented with behavioral or personality change, sometimes associated with seizures and frequent sleep dysfunction; 9.5% with dyskinesias or dystonia; and 3% with speech reduction. On admission, 53% had severe speech deficits. Eventually, 77% developed seizures, 84% stereotyped movements, 86% autonomic instability, and 23% hypoventilation. Responses to immunotherapy were slow and variable. Overall, 74% had full or substantial recovery after immunotherapy or tumor removal. Neurological relapses occurred in 25%. At the last follow-up, full recovery occurred more frequently in patients who had a teratoma that was removed (5/8) than in those without a teratoma (4/23; p = 0.03).Anti-NMDAR encephalitis is increasingly recognized in children, comprising 40% of all cases. Younger patients are less likely to have tumors. Behavioral and speech problems, seizures, and abnormal movements are common early symptoms. The phenotype resembles that of the adults, although dysautonomia and hypoventilation are less frequent or severe in children. Ann Neurol 2009;66:11-18.
View details for DOI 10.1002/ana.21756
View details for Web of Science ID 000268847600006
View details for PubMedID 19670433