Prognostic value of JAK2V617F mutation in pseudotumor cerebri associated with cerebral venous sinus thrombosis.

OBJECTIVES: To examine the clinical characteristics and prognosis of cerebral venous sinus thrombosis (CVST) that presented as pseudotumor cerebri (PTC) patients with JAK2V617F mutation. METHODS: Medical records of all consecutive patients that presented with PTC and a JAK2V617F mutation who were treated were retrospectively reviewed. Data regarding demographics and ocular presenting symptoms and signs, neurological signs, hematological factors treatment, and prognosis were collected. RESULTS: The most common presenting symptoms were headache (5 patients, 83.3%) and visual obscurations (5 patients, 83.3%). CVST of the sagittal sinus and sigmoid sinus were the most common site of thrombus. Platelet count and hemoglobin count were higher than normal during follow-up. There was significant change in the disk edema degree as well as decline in retinal nerve fiber layer (RNFL) thickness (P < 0.001, P < 0.001, Matched pairs). There was no significant change in visual acuity (VA) or mean deviation (MD) during follow-up (P = 0.95, 0.64, respectively, Matched pairs). CONCLUSIONS: Pseudotumor cerebri resulting from CSVT in our patients with JAK2V617F mutation was frequent in young patients and needed medical and surgical treatment, without improvement in visual functions and in third caused poor visual outcome. Therefore, we believe that a screening test for JAK2V617F mutation should be considered for patients with CVST without known risk factor presenting with PTC, especially when sagittal sinus or sigmoid sinus involvement or thrombocytosis or high hemoglobin are found upon presentation. This might lead to more aggressive management which may improve the visual prognosis of those young patients.

Accuracy of Diagnostic Imaging Modalities for Classifying Pediatric Eyes as Papilledema Versus Pseudopapilledema.

PURPOSE: To identify the most accurate diagnostic imaging modality for classifying pediatric eyes as papilledema (PE) or pseudopapilledema (PPE). DESIGN: Prospective observational study. SUBJECTS: Nineteen children between the ages of 5 and 18 years were recruited. Five children (10 eyes) with PE, 11 children (19 eyes) with PPE owing to suspected buried optic disc drusen (ODD), and 3 children (6 eyes) with PPE owing to superficial ODD were included. METHODS: All subjects underwent imaging with B-scan ultrasonography, fundus photography, autofluorescence, fluorescein angiography (FA), optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL), and volumetric OCT scans through the optic nerve head with standard spectral-domain (SD OCT) and enhanced depth imaging (EDI OCT) settings. Images were read by 3 masked neuro-ophthalmologists, and the final image interpretation was based on 2 of 3 reads. Image interpretations were compared with clinical diagnosis to calculate accuracy and misinterpretation rates of each imaging modality. MAIN OUTCOME MEASURES: Accuracy of each imaging technique for classifying eyes as PE or PPE, and misinterpretation rates of each imaging modality for PE and PPE. RESULTS: Fluorescein angiography had the highest accuracy (97%, 34 of 35 eyes, 95% confidence interval 92%-100%) for classifying an eye as PE or PPE. FA of eyes with PE showed leakage of the optic nerve, whereas eyes with suspected buried ODD demonstrated no hyperfluorescence, and eyes with superficial ODD showed nodular staining. Other modalities had substantial likelihood (30%-70%) of misinterpretation of PE as PPE. CONCLUSIONS: The best imaging technique for correctly classifying pediatric eyes as PPE or PE is FA. Other imaging modalities, if used in isolation, are more likely to lead to misinterpretation of PE as PPE, which could potentially result in failure to identify a life-threatening disorder causing elevated intracranial pressure and papilledema.

Natural History of Conversion of Leber's Hereditary Optic Neuropathy: A Prospective Case Series.

PURPOSE: To illustrate the natural history of Leber's hereditary optic neuropathy (LHON). DESIGN: Prospective observational case series. PARTICIPANTS: The Soave-Brazil pedigree of m.11778G>A/ND4 mitochondrial DNA LHON mutation. METHODS: A prospectively acquired database of the Soave-Brazil pedigree was reviewed. Data from 285 individuals were included in the database over a 15-year period. The pedigree was reviewed for unaffected mutation carriers who converted to affected status, 6 patients with LHON were identified. The medical records were reviewed 1 year preconversion to 1 year postconversion for visual acuity (logarithm of the minimum angle of resolution [logMAR]), Humphrey Visual Field (HVF) mean deviation (MD), and retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus (Carl Zeiss, Oberkochen, Germany) optic coherence tomography (OCT). The RNFL thickness values were normalized for age. Visual acuity, HVF, and processed RNFL data from each of the 12 eyes were then sorted into 2-month time periods relative to the date of conversion, within which they were averaged. MAIN OUTCOME MEASURES: The main outcome measures were visual acuity, HVF MD, and RNFL thickness. RESULTS: Decreased visual acuity preceded conversion by up to 2 months and then declined up to 8 months postconversion. Decrease in HVF MD occurred at least 4 months preceding conversion, after which values decreased until plateau at 6 to 8 months. Average RNFL thickness was above normal baseline thickness in all 4 quadrants as measured by OCT at the time of conversion. Increase in RNFL thickness preceded conversion as early as 4 to 6 months, peaked at conversion, and decreased until individual plateaus. The temporal quadrant was first to be involved, then the inferior and superior quadrants, and the nasal quadrant showed the latest and least changes. CONCLUSIONS: Subclinical changes preceded the date of conversion and may reflect the complicated nature of identifying the date of conversion in LHON. Early increases in RNFL preceding conversion suggest that structural changes precede clinically significant vision loss. Asynchronous quadrant involvement supports a previously published mathematical model. The natural history of LHON is not a subacute process, as previously believed, but progresses more slowly, taking up to 8 months to plateau.

Headache in Idiopathic Intracranial Hypertension: Findings From the Idiopathic Intracranial Hypertension Treatment Trial.

OBJECTIVE: To characterize the phenotype, headache-related disability, medical co-morbidities, use of symptomatic headache medications, and headache response to study interventions in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). METHODS: Patients with untreated IIH and mild vision loss enrolled in the IIHTT and randomized to acetazolamide (ACZ) and weight loss or placebo (PLB) and weight loss had prospective assessment of headache disability using the Headache Impact Test-6 (HIT-6) questionnaire. Subjects with headache at the baseline visit were assigned a headache phenotype using the International Classification for Headache Disorders version 3 beta (ICHD-3b). Medication overuse was determined using the participants' reported medication use for the preceding month and ICHD-3b thresholds for diagnosing medication overuse headache. We investigated relationships between headache disability and various other clinical characteristics at baseline and at 6 months. RESULTS: Headache was present in 139 (84%) of the 165 enrollees at baseline. The most common headache phenotypes were migraine (52%), tension-type headache (22%), probable migraine (16%), and probable tension-type headache (4%). Fifty-one (37%) participants overused symptomatic medications at baseline, most frequently simple analgesics. A similar amount of improvement in the adjusted mean (± standard error) HIT-6 score occurred in the ACZ (-9.56 ± 1.05) and PLB groups (-9.11 ± 1.14) at 6 months (group difference -0.45, 95% CI -3.50 to 2.60, P = .77). Headache disability did not correlate with any of the studies, variables of interest, which included: the lumbar puncture opening pressure at baseline or at 6 months, body mass index, the amount of weight lost, papilledema grade, perimetric mean deviation, or the use of hormonal contraception. Headache disability was significantly associated with patient-reported quality of life in the physical, mental, and visual domains. CONCLUSIONS: Headache was common, of varied character, disabling, and associated with poorer quality of life in our cohort of patients with mild visual impairment. The lack of correlation between headache disability and cerebrospinal fluid (CSF) pressure at baseline and at the end of the randomized phase of the study implies that headache in IIH may be related to factors other than intracranial hypertension, and that specific headache treatment is needed in addition to therapies directed at lowering CSF pressure.

Transarterial Embolization of a Spontaneous Intraorbital Arteriovenous Fistula With n-BCA Glue.

Arteriovenous fistulae of the orbit are exceedingly rare. They are high-flow vascular malformations involving a fistula from the ophthalmic artery to one of the draining ophthalmic veins. Presenting symptoms can mimic those of carotid cavernous fistulae or of ophthalmic venous varices, and include diplopia, proptosis, chemosis, decreased visual acuity, and retro-orbital pain. Very few case reports are published on the treatment of this aggressive vascular malformation, and they uniformly describe techniques involving a transvenous access for the embolization of the fistula. To the best of authors' knowledge, they report the first case of transarterial embolization of an intraorbital AVF.

Unmet need for corrective eyeglasses: results from a Los Angeles County Hospital survey.

To investigate the socioeconomic challenges encountered by patients from Los Angeles County Ophthalmology Clinic, California, United States, in obtaining prescription eyeglasses. A retrospective survey study. Patients sent for refraction in June 2009 were asked to rate their satisfaction with their eyeglasses. If they did not obtain eyeglasses, they were asked the reason e.g., cost, lost prescription, etc. Fifty-five percent (54/99) of patients who received a prescription did not obtain eyeglasses. The most common reason was cost (67 %). Eighty-eight percent of patients had some form of health insurance; however, 100 % were lacking eyeglasses coverage. The mean visual acuity pre-refraction was 20/80 versus 20/30 post-refraction (p < 0.001). It is well known that refractive error is a major cause of blindness worldwide, which negatively impacts the patient and their community. However, it is infrequently addressed that these conditions persist in parts of the develop world, including the United States. Los Angeles County Hospital is an example of an environment with many low-income patients in need of refractive correction who are limited mainly by cost in attaining eyeglasses. Furthermore, insurance organizations that cover low-income patients provide minimal or no coverage for prescription eyeglasses.

Prospective, Randomized Trial Comparing Simulator-based versus Traditional Teaching of Direct Ophthalmoscopy for Medical Students.

OBJECTIVE: To compare results of simulator-based vs traditional training of medical students in direct ophthalmoscopy. DESIGN: Randomized controlled trial. METHODS: First-year medical student volunteers completed 1 hour of didactic instruction regarding direct ophthalmoscopes, fundus anatomy, and signs of disease. Students were randomized to an additional hour of training on a direct ophthalmoscope simulator (n = 17) or supervised practice examining classmates (traditional method, n = 16). After 1 week of independent student practice using assigned training methods, masked ophthalmologist observers assessed student ophthalmoscopy skills (technique, efficiency, and global performance) during examination of 5 patient volunteers, using 5-point Likert scales. Students recorded findings and lesion location for each patient. Two masked ophthalmologists graded answer sheets independently using 3-point scales. Students completed surveys before randomization and after assessments. Training groups were compared for grades, observer- and patient-assigned scores, and survey responses. RESULTS: The simulator group reported longer practice times than the traditional group (P = .002). Observers assigned higher technique scores to the simulator group after adjustment for practice time (P = .034). Combined grades (maximum points = 20) were higher for the simulator group (median: 5.0, range: 0.0-11.0) than for the traditional group (median: 4.0, range: 0.0-9.0), although the difference was not significant. The simulator group was less likely to mistake the location of a macular scar in 1 patient (odds ratio: 0.28, 95% confidence interval: 0.056-1.35, P = .013). CONCLUSIONS: Direct ophthalmoscopy is difficult, regardless of training technique, but simulator-based training has apparent advantages, including improved technique, the ability to localize fundus lesions, and a fostering of interest in learning ophthalmoscopy, reflected by increased practice time.

Isolated trochlear palsy secondary to Lyme neuroborreliosis.

The objective of the study is to report the first case of isolated trochlear palsy secondary to Lyme neuroborreliosis in an adult. A 22-year-old male presented with history of flu-like illness and headache, accompanied by vertical binocular diplopia, worse on downgaze and better in upgaze and right head tilt. Physical examination revealed trochlear palsy on the left side with a compensatory head tilt to the opposite side. A subsequent workup for trochlear palsy was conducted, including hematological and cerebral spinal fluid serum studies, and magnetic resonance imaging of the brain. Immunoglobulin (Ig)M and IgG antibodies against Borrelia burgdorferi were positive in serum and cerebral spinal fluid (CSF). Symptoms of double vision completely resolved after 3 weeks of antibiotic treatment with intravenous ceftriaxone. CSF studies, in addition to clinical symptoms of vertical double vision and a positive Parks 3-step test, are a good diagnostic tool for B. burgdorferi. Resolution of symptoms was noted after a complete course of intravenous ceftriaxone.

Headache attributable to disorders of the eye.

Sensory innervation to the eye and periocular area arises from the ophthalmic branch of the trigeminal nerve. Thus, ocular, orbital, and systemic disorders may produce head pain with ocular signs and symptoms. Whereas some of these entities have characteristic diagnostic features, others mimic primary headache disorders such as migraine and cluster headache. This article reviews common ocular and neuro-ophthalmic conditions that are accompanied by pain in or near the eye.

Glaucoma detection and evaluation through pattern recognition in standard automated perimetry data.

BACKGROUND: Perimetry remains one of the main diagnostic tools in glaucoma, and it is usually used in conjunction with evaluation of the optic nerve. This study assesses the capability of automatic pattern recognition methods, and in particular the support vector machines (SVM), to provide a valid clinical diagnosis classification of glaucoma based solely upon perimetry data. METHODS: Over 2,200 patient records were reviewed to produce an annotated database of 2,017 eyes. Visual field (VF) data were obtained with HFA II perimeter using the 24-2 algorithm. Ancillary information included treated and untreated intraocular pressure, cup-to-disk ratio, age, sex, central corneal thickness and family history. Ophthalmic diagnosis and classification of visual fields were provided by a consensus of at least two glaucoma experts. The database includes normal eyes, cases of suspect glaucoma, pre-perimetric glaucoma, and glaucoma with different levels of severity, as well as 189 eyes with neurologic or neuro-ophthalmologic defects. Support vector machines were trained to provide multi-level classifications into visual field and glaucoma diagnosis classes. RESULTS: Numerical validation indicates 70-90% expected agreement between multi-stage classifications provided by the automated system, using a hierarchy of SVM models, and glaucoma experts. Approximately 75% accuracy for the classification of glaucoma suspect and pre-perimetric glaucoma (which by definition do not exhibit glaucomatous defects) indicates the ability of the numerical model to discern subtle changes in the VF associated with early stages of glaucoma. The Glaucoma Likelihood Index provides a single number summary of classification results. CONCLUSIONS: Automatic classification of perimetry data may be useful for glaucoma screening, staging and follow-up.

Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber hereditary optic neuropathy (LHON).

PURPOSE: To determine the profile of neurodegeneration in Leber hereditary optic neuropathy (LHON). METHODS: We quantitated serum levels of phosphorylated neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients and 59 carriers with LHON, both molecularly characterized as harboring the G to A mutation at nucleotide 11,778 of the mitochondrial genome. The association of subject characteristics to pNF-H levels was studied with multiple regression; pNF-H data were square-root transformed to effect normality of distribution of residuals. Relationships between the square-root of pNF-H and age and sex were investigated within groups with Pearson correlation and the two-sample t-test. Linear regression was used to assess the difference between groups and to determine if the relationship of age was different between affected individuals and carriers. Results of plotting pNF-H levels by age suggested a nonlinear, quadratic association so age squared was used in the statistical analysis. ANCOVA was used to assess the influence of age and group on pNF-H levels. RESULTS: In the carrier group, there was a significant correlation of square-root pNF-H (mean=0.24 ng/ml(2)) with age (r=0.30, p=0.022) and a stronger correlation with quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml(2)) for the affected group, correlations were of similar magnitude, although they were not statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45). There was no correlation between age and pNF-H levels (mean=0.34 ng/ml(2)) in the off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There was no difference between sexes and pNF-H levels in any of the groups (affected, p=0.65; carriers, p=0.19; off-pedigree, p=0.93). CONCLUSIONS: Elevated pNF-H released into the serum of some affected LHON patients may suggest that axonal degeneration occurs at some point after loss of visual function. Increases in pNF-H levels of carriers with increasing age, not seen in off-pedigree controls, may suggest subtle subclinical optic nerve degeneration.

Male prevalence of acquired color vision defects in asymptomatic carriers of Leber's hereditary optic neuropathy.

PURPOSE: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease resulting in loss of central vision and dyschromatopsia, caused by mitochondrial DNA point mutations. However, only a subset of the mutation carriers becomes affected, with a higher penetrance in males. This study was conducted to investigate chromatic losses in asymptomatic carriers of the LHON mutation. METHODS: Monocular chromatic discrimination was studied with the Cambridge Colour Test (CCT; Cambridge Research Systems, Ltd., Rochester, UK) along the protan, deutan, and tritan cone isolation axes in 46 LHON carriers (15 men) belonging to the same LHON maternal lineage and 74 age-matched control subjects (39 men). Inclusion criteria were absence of ophthalmic complaints and clear ocular media. A detailed neuro-ophthalmic examination was performed in all the LHON carriers. RESULTS: The differences in threshold between carriers and control subjects were significant for the three cone isolation axes at P < 0.0001. Sixty-five percent of the carriers had abnormal protan and/or deutan thresholds; some of those with higher thresholds also had elevated tritan thresholds (13%). The male thresholds were higher and more frequent than those of the women for the protan and deutan axes (ANOVA; P < 0.05), but not for tritan thresholds. In the most severe losses, the women had instances of diffuse defect whereas all the men displayed a red-green defect. CONCLUSIONS: Male LHON asymptomatic carriers had color vision losses with the red-green pattern of dyschromatopsia typical of patients affected with LHON, which includes elevation of tritan thresholds as well. This predominantly parvocellular (red-green) impairment is compatible with the histopathology of LHON, which affects mostly the papillomacular bundle. In contrast with male losses, female losses were less frequent and severe. These gender differences are relevant to understanding LHON pathophysiology, suggesting that hormonal factors may be of great importance.

Chromatic and luminance contrast sensitivities in asymptomatic carriers from a large Brazilian pedigree of 11778 Leber hereditary optic neuropathy.

PURPOSE: To determine whether asymptomatic 11778 LHON carriers demonstrated impairments in (1) chromatic red/green (R/G) and blue/yellow (B/Y) contrast sensitivity functions (CSF) and in (2) luminance contrast sensitivity functions in the spatial CSF (SCSF) and temporal CSF (TCSF) domains. METHODS: Twenty-five carriers (8 male, 17 female; 34.1 +/- 15.1 years of age) of homoplasmic 11778 LHON from the same well-described family and 30 age-matched controls (17 male, 13 female; 29.2 +/- 7.1 years of age) were tested in one eye, randomly selected. Of the 25 eyes tested, 18 had normal fundus, 5 had swelling and microangiopathy, and 2 had temporal pallor. The R/G and B/Y CSFs were obtained after equiluminance correction with bichromatic horizontal sinusoidal gratings at 0.3, 0.7, and 2 cycles per degree (cpd); the SCSFs were obtained with achromatic gratings at 0.3, 2, 6, and 12 cpd; and the TCSFs were obtained at 2, 10, 20, and 33 Hz with sinusoidal modulation of a 2.7 degrees field with a superimposed spatial Gabor function. RESULTS: Differences between carriers and controls were statistically significant for all spatial frequencies of chromatic and luminance SCSFs, but not for the TCSFs. R/G equiluminance settings of carriers differed from those of controls (P < 0.001), requiring higher luminance in the green; B/Y equiluminance settings were not statistically different in carriers and controls. Fundus findings did not correlate with CS results. CONCLUSIONS: Luminance and chromatic spatial CS losses that affected all tested spatial frequencies, are reported in LHON asymptomatic carriers with the mtDNA 11778 mutation. No losses were found in the temporal CSF. An intriguing finding is that the blue system is substantially spared in this LHON family. These represent subclinical visual impairments in otherwise asymptomatic LHON carriers.