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Supplemental Digital Content is Available in the Text., Background: Distinguishing optic disc edema from pseudopapilledema is a common, sometimes challenging clinical problem. Advances in spectral-domain optical coherence tomography (SD-OCT) of the optic nerve head (ONH) has proven to be a cost effective, noninvasive, outpatient procedure that may help. At its core are tools that quantify the thickness of the retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer (GC-IPL). The SD-OCT also provides a set of tools that may be qualitatively interpreted in the same way that we read an MRI. They include the transverse axial, en face, and circular tomogram. Our goal is to describe a practical office-based set of tools using SD-OCT in the diagnosis and monitoring of papilledema, optic disc edema, and pseudopapilledema. Evidence Acquisition: Searches on PubMed were performed using combinations of the following key words: OCT, papilledema, pseudopapilledema, optic disc drusen, retinal folds (RF), and choroidal folds (CF). Results: The principal elements of SD-OCT analysis of the ONH are the RNFL and GC-IPL thickness; however, these metrics have limitations when swelling is severe. Qualitative interpretation of the transverse axial SD-OCT aids in assessing peripapillary shape that may help distinguish papilledema from pseudopapilledema, evaluate atypical optic neuropathies, diagnose shunt failures, and identify outer RF and CF. There is a consensus that the SD-OCT is the most sensitive way of identifying buried optic disc drusen. En face SD-OCT is especially effective at detecting peripapillary wrinkles and outer retinal creases, both of which are common and distinctive signs of optic disc edema that rule out pseudopapilledema. Mechanically stressing the ONH in the adducted eye position, in patients with papilledema, may expose folds and peripapillary deformations that may not be evident in primary position. We also discuss how to optimize the acquisition and registration of SD-OCT images. Conclusions: The SD-OCT is not a substitute for a complete history and a careful examination. It is, however, a convenient ancillary test that aids in the diagnosis and management of papilledema, optic disc edema, and pseudopapilledema. It is particularly helpful in monitoring changes over the course of time and distinguishing low-grade papilledema from buried drusen. The application of the SD-OCT toolbox depends on optimizing the acquisition of images, understanding its limitations, recognizing common artifacts, and accurately interpreting images in the context of both history and clinical findings.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure of unknown cause. IIH has been shown to be associated with female sex as well as obesity. This genome-wide association study was performed to determine whether genetic variants are associated with this condition. METHODS: We analyzed the chromosomal DNA of 95 patients with IIH enrolled in the Idiopathic Intracranial Hypertension Treatment Trial and 95 controls matched on sex, body mass index, and self-reported ethnicity. The samples were genotyped using Illumina Infinium HumanCoreExome v1–0 array and analyzed using a generalized linear mixed model that accounted for population stratification using multidimensional scaling. RESULTS: A total of 301,908 single nucleotide polymorphisms (SNPs) were evaluated. The strongest associations observed were for rs2234671 on chromosome 2 (P = 4.93 × 10(−07)), rs79642714 on chromosome 6 (P = 2.12 ×·10(−07)), and rs200288366 on chromosome 12 (P = 6.23 × 10(−07)). In addition, 3 candidate regions marked by multiple associated SNPs were identified on chromosome 5, 13, and 14. CONCLUSIONS: This is the first study to investigate the genetics of IIH in a rigorously characterized cohort. The study was limited by its modest size and thus would have only been able to demonstrate highly significant association on a genome-wide scale for relatively common alleles exerting large effects. However, several variants and loci were identified that might be strong candidates for follow-up studies in other well-phenotyped cohorts.

Importance Optic neuritis (ON) in children is uncommon. There are limited prospective data for visual acuity (VA) outcomes, associated diseases, and neuroimaging findings. Prospective data from a large sample would be useful for counseling families on treatment decisions and prognosis. Objective To prospectively study children with a first episode of ON, describe VA after 6 months, and ascertain the network's (Pediatric Eye Disease Investigator Group and Neuro-Ophthalmology Research Disease Investigator Consortium) ability to enroll pediatric patients with ON prospectively. Design, Setting, and Participants This nonrandomized cohort study was conducted from September 20, 2016, to July 20, 2018, at 23 sites in the United States and Canada in pediatric ophthalmology or neuro-ophthalmology clinics. A total of 44 children (aged 3-15 years) presented with a first episode of ON (visual loss, pain on eye movements, or both) within 2 weeks of symptom onset and at least 1 of the following in the affected eye: a distance high-contrast VA (HCVA) deficit of at least 0.2 logMAR below age-based norms, diminished color vision, abnormal visual field, or optic disc swelling. Exclusion criteria included preexisting ocular abnormalities or a previous episode of ON. Main Outcomes and Measures Primary outcomes were monocular HCVA and low-contrast VA at 6 months. Secondary outcomes were neuroimaging, associated diagnoses, and antibodies for neuromyelitis optica and myelin oligodendrocyte glycoprotein. Results A total of 44 children (mean age [SD], 10.2 [3.5] years; 26 boys [59%]; 23 White individuals [52%]; 54 eyes) were enrolled in the study. Sixteen patients (36%) had bilateral ON. Magnetic resonance imaging revealed white matter lesions in 23 children (52%). Of these children, 8 had myelin oligodendrocyte glycoprotein-associated demyelination (18%), 7 had acute disseminated encephalomyelitis (16%), 5 had multiple sclerosis (11%), and 3 had neuromyelitis optica (7%). The baseline mean HCVA was 0.95 logMAR (20/200), which improved by a mean 0.76 logMAR (95% CI, 0.54-0.99; range, -0.70 to 1.80) to 0.12 logMAR (20/25) at 6 months. The baseline mean distance low-contrast VA was 1.49 logMAR (20/640) and improved by a mean 0.72 logMAR (95% CI, 0.54-0.89; range, -0.20 to 1.50) to 0.73 logMAR (20/100) at 6 months. Baseline HCVA was worse in younger participants (aged

Introduction Abnormal forces around the optic nerve head (ONH) due to orbital diseases, intracranial hypertension (IH), glaucoma, and space travel, are associated with alterations of the ONH shape. Elevated cerebral and ophthalmic venous pressure can contribute to stress and strain on the ONH and peripapillary retina. We hypothesize that IH and elevated ophthalmic venous pressure without IH cause different ONH and retinal changes. Methods We compared MRI and spectral domain optical coherence tomography (SDOCT) findings in patients with cavernous sinus arteriovenous shunts (CSAVSs), where orbital venous pressure is known to be elevated, with patients with intracranial dural venous sinus thrombosis and secondary IH. We also compared the results to those obtained in the Idiopathic IH (IIH) Treatment Trial. Results Among 18 patients with dural venous sinus thrombosis, the MRI/magnetic resonance venography displayed partial empty sella (61%) and optic nerve sheath distension (67%). None exhibited ophthalmic vein dilation or signs of orbital congestion. SDOCT of these eyes and IIH eyes showed a similar frequency of abnormal thickening of the mean retinal nerve fiber layer, anterior displacement of the basement membrane opening, peripapillary wrinkles, retinal folds (RF), and choroidal folds (CF). Among 21 patients with CSAVSs, MRI showed ipsilateral dilated superior ophthalmic vein (76%) and orbital congestion (52%) without distension of the optic nerve sheath or globe distortion. SDOCT showed CF (19%), one with overlying RF, and no ONH deformations. Conclusions SDOCT findings for dural venous sinus thrombosis are similar to those seen with IIH but distinct from changes due to local ophthalmic venous hypertension. These data support the concept that IH even if due to a vascular cause and local orbital venous hypertension cause different stresses and strains on the ONH.

Introduction Controversy persists on the best treatment to control ocular myasthenia gravis (OMG) and reduce conversion to generalized myasthenia gravis (GMG). We hypothesized that low dose prednisone could accomplish both in a cohort of OMG patients followed after three years. Methods We reviewed the records of 168 patients who presented with OMG. Our study included 103 of the OMG patients who met inclusion criteria, requiring follow up for a minimum of 3 years without disease generalization. Low dose prednisone was defined as ≤7.5 mg per day. The main outcome was having single vision without ptosis blocking vision, measured by binocular single vision (BSV) and upper lid position. We also analyzed late progression to GMG. Results Of 87 patients treated with prednisone, chronic low dose prednisone alone restored BSV in 47 patients (46% of all patients) without GMG. Pyridostigmine monotherapy restored BSV in 11/14 patients (11% of all patients). Other immunomodulatory therapy (OIT) was needed in 38 patients (37%). Medical therapy maintained BSV at last evaluation (mean follow up 8.2 ± 5.0 years) in 93 patients (90%). GMG developed in 10 patients (10%) during the follow-up period. Conclusion In OMG patients who do not generalize before 3 years, chronic long term prednisone at lower doses is moderately effective in maintaining optimum BSV. However, OIT are commonly required in these patients. In these OMG patients receiving prednisone and/or OIT, conversion to GMG after three years of disease is uncommon.

Purpose Archetypal analysis, a form of unsupervised machine learning, identifies archetypal patterns within a visual field (VF) dataset such that any VF is described as a weighted sum of its archetypes (ATs) and has been used to quantify VF defects in glaucoma. We applied archetypal analysis to VFs affected by nonglaucomatous optic neuropathy caused by idiopathic intracranial hypertension (IIH). Methods We created an AT model from 2862 VFs prospectively collected from 330 eyes in the IIH Treatment Trial (IIHTT). We compared baseline IIH AT patterns with their descriptive VF classifications from the IIHTT. Results The optimum IIH AT model yielded 14 ATs resembling VF patterns reported in the IIHTT. Baseline VFs contained four or fewer meaningful ATs in 147 (89%) of study eyes. AT2 (mild general VF depression pattern) demonstrated the greatest number of study eyes with meaningful AT weight at baseline (n = 114), followed by AT1 (n = 91). Other ATs captured patterns of blind spot enlargement, hemianopia, arcuate, nasal defects, and more nonspecific patterns of general VF depression. Of all ATs, AT1 (normal pattern) had the strongest correlation with mean deviation (r = 0.69, P < 0.001). For 65 of the 93 VFs with a dominant AT, this AT matched the expert classification. Conclusions Archetypal analysis identifies quantifiable, archetypal VF defects that resemble those commonly seen in IIH. Translational Relevance Archetypal analysis provides a quantitative, objective method of measuring and monitoring disease-specific regional VF defects in IIH.

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).Nonrandomized clinical study.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. Ninety-six 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 (MD) 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 = .05; placebo subjects with no ACZ improved 0.81 dB MD, P = .07 at 12 months. The other groups improved 0.35-0.46 dB MD. Mean improvements in papilledema grade occurred most markedly in the group that exchanged placebo for ACZ (0.91 units, P .001). QoL and headache disability scores showed significant improvements in the placebo group with 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.

Purpose Recent studies indicate that the amount of deformation of the peripapillary retinal pigment epithelium and Bruch's membrane (pRPE/BM) toward or away from the vitreous may reflect acute changes in cerebrospinal fluid pressure. The study purpose is to determine if changes in optic-nerve-head (ONH) shape reflect a treatment effect (acetazolamide/placebo + weight management) using the optical coherence tomography (OCT) substudy of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) at baseline, 3, and 6 months. Methods The pRPE/BM shape deformation was quantified and compared with ONH volume, peripapillary retinal nerve fiber layer (pRNFL), and total retinal (pTR) thicknesses in the acetazolamide group (39 subjects) and placebo group (31 subjects) at baseline, 3, and 6 months. Results Mean changes of the pRPE/BM shape measure were significant and in the positive direction (away from the vitreous) for the acetazolamide group (P < 0.01), but not for the placebo group. The three OCT measures reflecting the reduction of optic disc swelling were significant in both treatment groups but greater in the acetazolamide group (P < 0.01). Conclusions Change in the pRPE/BM shape away from the vitreous reflects the effect of acetazolamide + weight management in reducing the pressure differential between the intraocular and retrobulbar arachnoid space. Weight management alone was also associated with a decrease in optic nerve volume/edema but without a significant change in the pRPE/BM shape, implying an alternative mechanism for improvement in papilledema and axoplasmic flow, independent of a reduction in the pressure differential. (ClinicalTrials.gov number, NCT01003639.).

PURPOSE Acetazolamide (ACZ) lowers intraocular pressure (IOP), acutely in normal eyes and both acutely and chronically in eyes with glaucoma, and cerebrospinal fluid pressure (CSFp), chronically in patients with idiopathic intracranial hypertension (IIH). We hypothesize chronic daily ACZ would significantly reduce IOP and contribute to a translaminar pressure gradient change reflected by alteration in the CSFp-IOP difference and the deformation of the neural canal in patients with IIH and no glaucoma. PATIENTS AND METHODS Before randomization to ACZ or placebo treatment for 6 months, 165 participants in the IIH Treatment Trial had evaluations that included Goldmann applanation, CSFp measurement, and optical coherence tomography determination of the neural canal deformation. These measures were repeated at the 6-month outcome. RESULTS The IOP was not significantly decreased from baseline at 1, 3, or 6 months in eyes in both treatment groups. At month 6, the amount of ACZ or weight modification did not correlate with any IOP change. The 6-month mean change in neural canal deformation was 0.96 and -0.04 (P=0.001) and in CSFp was -128 and -38 mm H2O (P=0.001), but CSFp-IOP difference change was not significant, in the ACZ and placebo groups, respectively. CONCLUSIONS ACZ does not reduce the IOP in eyes without glaucoma but does decrease the pathologic elevated CSFp, providing evidence that normal systems can compensate for chronic medication effects. The CSFp-IOP is not a direct marker of translaminar pressure gradient and the ACZ normalization of the neural canal deformation appears due to CSFp reduction alone.

Summary Objectives The purpose of this paper is to measure the change in body weight after a 6-month telephone-based weight loss intervention in overweight and obese subjects with idiopathic intracranial hypertension (IIH) and mild visual loss randomized to receive either acetazolamide or placebo. Methods One hundred sixty-five subjects with IIH, aged 29.1 ± 7.5 (mean ± SD) and BMI 39.9 + 8.3 kg/m2, enrolled at 38 academic and private practice sites in North America, participated in this trial. This was a randomized, double-masked, placebo-controlled trial of acetazolamide in subjects with IIH and mild visual loss. All participants received a reduced-sodium, weight-reduction diet and a 6-month telephone-based weight loss intervention. Six-month changes from baseline in body weight, perimetric mean deviation as assessed by automated perimetry and quality of life using the National Eye Institute Visual Function Questionnaire 25 and the 36-item Short Form Health Survey were measured. Results Mean percent weight change at 6 months was −5.9% ± 6.7% of initial body weight overall, −3.5% ± 5.9% in the placebo group and −7.8% ± 6.8% in the acetazolamide group. Weight change was not associated with changes in either mean deviation or quality of life scores. Conclusion Patients with IIH and mild visual loss assigned to either acetazolamide or placebo, all of whom received a 6-month telephone-based weight loss intervention, lost an average of 5.9% of initial body weight, consistent with NHLBI guidelines of 5% to 10% of body weight loss for clinically significant health benefit.

BACKGROUND The demographic associations among patients presenting with myasthenia gravis with only ocular manifestations (OMG) is not clear. METHODS In this 5-center case series, we collected the race, gender, and age at diagnosis of patients diagnosed with myasthenia gravis who had no signs or symptoms of generalized myasthenia gravis (GMG). An a priori sample size calculation determined that 140 patients were required to accept that there was a ≤10-year difference in mean age (equivalence testing: power 90%, α = 0.05). Robust Bayesian analysis and linear regression were applied to evaluate whether age differed by gender or race. RESULTS Of 433 patients included, 258 (60%) were men. Mean age among men was 57 years (SD = 19) and 52 years (SD = 21) among women. The 95% credible interval (CI) (Bayesian equivalent of confidence interval) was 0.8-8.7 years for mean age, and there was a 99.6% probability that the mean difference in age between sexes was

Neuroretinitis is a form of papillitis associated with the delayed onset of an exudative macular star among other inflammatory ocular findings. We describe 4 patients with neuroretinitis who displayed several distinctive and novel findings on spectral-domain optical coherence tomography (OCT) that include "epipapillary infiltrates" and an atypical pattern of inner retinal folds. The recognition of these findings on OCT may help in the early diagnosis of neuroretinitis.

Background/AimFractionated conformal radiotherapy (FCRT) is now used to treat vision-threatening optic nerve sheath meningioma (ONSM), but long-term efficacy and safety data are lacking; the purpose of this study was to assess these key data.MethodsThis is a retrospective chart review with prospective follow-up of adult patients treated with FCRT for primary ONSM at four academic medical centres between 1995 and 2007 with ≥10 years of follow-up after treatment.Results16 patients were identified with a mean post-treatment follow-up of 14.6 years (range: 10.5–20.7 years). The mean age at symptom onset was 47.6 years (range: 36–60 years). FCRT was performed at a mean of 2.3 years after symptom onset (range: 0.2–14.0 years). At last follow-up, visual acuity had improved or stabilised in 14 of the 16 (88%) patients, and 11 (69%) had retained or achieved ≥20/40. The mean deviation on automated perimetry remained stable (−14.5 dB pretreatment vs −12.2 dB at last follow-up; p=0.68, n=10). Two (11%) patients had persistent pain, proptosis or diplopia, compared with six (38%) pretreatment (p=0.11). Two (13%) patients developed radiation retinopathy more than 6 months after completion of therapy, one (50%) of whom had worse visual acuity compared with pretreatment. No patient developed tumour involvement or radiation damage in the fellow eye.ConclusionFCRT stabilises or improves visual function in patients with primary ONSM and is associated with a low risk of significant ocular sequelae. This treatment should be considered instead of surgery in patients with primary ONSM who require intervention due to loss of visual sensory and/or ocular motor function.

We describe four patients who experienced optic neuritis (ON) and seizures and were found to have antibodies to myelin oligodendrocyte glycoprotein (MOG) in serum. The index case was a previously healthy 39-year-old man who developed steroid dependent ON and had a generalized seizure when steroids were tapered. He tested positive for antibodies to MOG. We have reviewed the charts of all 11 anti-MOG antibody positive patients in our practice and found that 4 patients, all of whom had experienced one or more episodes of ON, also had a generalized seizure during the course of their illness. In 2 patients - including the index case - seizure occurred during steroid taper and in 2 others at the time of an episode of acute disseminated encephalomyelitis (ADEM). Association of anti-MOG antibodies and relapsing demyelinating disorders of the central nervous system is increasingly recognized. Testing for anti-MOG antibodies should be considered in patients with optic neuritis and seizures, especially in those with who also have a history of ADEM.

Although we are still early in the evolution of optical imaging of the optic nerve, the available techniques already play an important role in clinical decision making. I would summarize our findings to date as follows: For acute ON: Presentation: OCT shows RNFL swelling, normal GCL + IPL by OCT; 1 month: OCT and SLP show RNFL thinning and swelling, GCL + IPL thinning by OCT; 3 months or later: OCT and SLP show RNFL thinning, further mild GCL thinning by OCT; 6 months: RNFL and GCL + IPL thinning finished. For acute NAION: Presentation: OCT shows RNFL swelling and SLP shows loss of birefringence, normal GCL + IPL by OCT; 1 month: RNFL swelling and thinning by OCT and thinning by SLP, GCL + IPL thinning by OCT; 3 months or later: RNFL and further mild GCL + IPL thinning; 6 months: RNFL and GCL + IPL thinning finished. For IIH Papilledema with mild vision loss: Presentation: OCT shows swelling of RNFL, TRT, and ONH volume; Presentation: OCT shows normal GCL + IPL; Presentation: OCT shows neural canal border inward deflection; 6 months: OCT shows structural shape changes reflecting the effectiveness of treatment.

Purpose To analyze the deformations of the peripapillary retinal pigment epithelium-basement membrane (ppRPE/BM) layer in response to procedures that lower intracranial pressure (ICP). Second, to demonstrate how shape changes may complement the mean retinal nerve fiber layer (RNFL) thickness as a measure of intracranial hypertension (ICH) and papilledema. Methods We used geometric morphometrics on spectral-domain optical coherence tomography images to analyze shape change of the ppRPE/BM layer after several interventions that lower cerebrospinal fluid (CSF) pressure. We also evaluated the effects of pressure-lowering interventions on both the anterior-posterior displacement of ppRPE/BM and the mean RNFL thickness. Forty-one patients with ICH and papilledema were studied before and after lumbar puncture (20), CSF shunt (9), and medical treatment of idiopathic ICH (23). We also compared the shape of 30 normal subjects to 23 patients whose papilledema resolved after medical treatment. Results The ppRPE/BM-layer in ICH and papilledema is characterized by an asymmetric anterior deformation that moves posteriorly and becomes more V-shaped after each pressure-lowering intervention. The differences were statistically significant for all three groups. These shape changes also occur in patients with ongoing ICH who have secondary optic atrophy (without papilledema). Posterior displacement at the margin of the ppRPE/BM layer correlated strongly with overall shape changes. Conclusions The subsurface contour of the ppRPE/BM layer is a dynamic property that changes with CSF pressure-lowering interventions. It can supplement the RNFL thickness as an indirect gauge of ICP and is particularly helpful in patients with secondary optic atrophy. Direct measurements of displacement at the basement membrane opening may serve as a more convenient office-based surrogate for shape analysis.

Eye Movements, Strabismus, Amblyopia, and Neuro-Ophthalmology Baseline OCT Measurements in the Idiopathic Intracranial Hypertension Treatment Trial, Part II: Correlations and Relationship to Clinical Features OCT Sub-Study Committee for the NORDIC Idiopathic Intracranial Hypertension Study Group Icahn School of Medicine at Mount Sinai, NORDIC Headquarters, New York, New York, United States Correspondence: Mark J. Kuper- smith, Departments of Neurology and Ophthalmology, Icahn School of Medicine at Mount Sinai, NORDIC Headquarters, 1000 10th Avenue, New York, NY 10019, USA; mkuper@chpnet.org. See the appendix for the members of the OCT Sub-Study Committee and the NORDIC Idiopathic Intracranial Hypertension Study Group. Submitted: June 5, 2014 Accepted: September 8, 2014 Citation: OCT Sub-Study Committee; for the NORDIC Idiopathic Intracra- nial Hypertension Study Group. Base- line OCT measurements in the Idiopathic Intracranial Hypertension Treatment Trial, part II: correlations and relationship to clinical features. Invest Ophthalmol Vis Sci. 2014;55:8173–8179. DOI:10.1167/ iovs.14-14961 P URPOSE . The accepted method to evaluate and monitor papilledema, Fris´en grading, uses an ordinal approach based on descriptive features. Part I showed that spectral-domain optical coherence tomography (SD-OCT) in a clinical trial setting provides reliable measurement of the effects of papilledema on the optic nerve head (ONH) and peripapillary retina, particularly if a 3-D segmentation method is used for analysis. 1 We evaluated how OCT parameters are interrelated and how they correlate with vision and other clinical features in idiopathic intracranial hypertension (IIH) patients. M ETHODS . A total of 126 subjects in the IIH Treatment Trial (IIHTT) OCT substudy had Cirrus SD-OCT optic disc and macula scans analyzed by using a 3-D segmentation algorithm to derive retinal nerve fiber layer (RNFL) thickness, total retinal thickness (TRT), retinal ganglion cell layer plus inner plexiform layer (GCLþIPL) thickness, and ONH volume. The SD-OCT parameter values were correlated with high- and low-contrast acuity, perimetric mean deviation, Fris´en grading, and IIH features. R ESULTS . At study entry, the average RNFL thickness, TRT, and ONH volume showed significant strong correlations (r ‡ 0.90) with each other. The same OCT parameters showed a strong (r > 0.76) correlation with Fris´en grade and a mild (r > 0.24), but significant, correlation with lumbar puncture opening pressure. For all eyes at baseline, neither visual acuity (high or low contrast) nor mean deviation correlated with any OCT measure of swelling or GCLþIPL thickness. C ONCLUSIONS . In newly diagnosed IIH, OCT demonstrated alterations of the peripapillary retina and ONH correlate with Fris´en grading of papilledema. At presentation, OCT measures of papilledema, in patients with newly diagnosed IIH and mild vision loss, do not correlate with clinical features or visual dysfunction. (ClinicalTrials.gov number, NCT01003639.) Keywords: papilledema, intracranial hypertension, OCT, lumbar puncture n the preceding report, 1 we have shown that spectral-domain optical coherence tomography (SD-OCT) can provide high- quality data in patients with papilledema due to idiopathic intracranial hypertension (IIH), from multiple clinical sites working with an experienced OCT reading center. Optical coherence tomography imaging reliably and reproducibly demonstrates alterations in the optic nerve head (ONH) and retinal layers in IIH, which includes measurement of the average peripapillary retina nerve fiber layer (RNFL) thickness, average total peripapillary retinal thickness (TRT), ONH volume, and the ganglion cell plus inner plexiform layer thickness (GCLþIPL) in the macular region. Moreover, inter- ocular comparisons for all OCT parameters reflecting swelling of the ONH or peripapillary retina were significant and highly correlated. As expected, 90% of eyes (220/244 with Zeiss algorithm–derived RNFL thickness values) of the enrolled subjects exhibited significant (>95th percentile) thickening of the RNFL. Only 7% of the study eyes showed significant thinning (

Eye Movements, Strabismus, Amblyopia, and Neuro-Ophthalmology Baseline OCT Measurements in the Idiopathic Intracranial Hypertension Treatment Trial, Part I: Quality Control, Comparisons, and Variability OCT Sub-Study Committee for the NORDIC Idiopathic Intracranial Hypertension Study Group Icahn School of Medicine at Mount Sinai, NORDIC Headquarters, New York, New York, United States Correspondence: Mark J. Kuper- smith, Icahn School of Medicine at Mount Sinai, NORDIC Headquarters, 1000 10th Avenue, New York, NY 10019, USA; mkuper@chpnet.org. P URPOSE . Optical coherence tomography (OCT) has been used to investigate papilledema in single-site, mostly retrospective studies. We investigated whether spectral-domain OCT (SD- OCT), which provides thickness and volume measurements of the optic nerve head and retina, could reliably demonstrate structural changes due to papilledema in a prospective multisite clinical trial setting. Submitted: June 5, 2014 Accepted: October 13, 2014 M ETHODS . At entry, 126 subjects in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) with mild visual field loss had optic disc and macular scans, using the Cirrus SD-OCT. Images were analyzed by using the proprietary commercial and custom 3D-segmentation algorithms to calculate retinal nerve fiber layer (RNFL), total retinal thickness (TRT), optic nerve head volume (ONHV), and retinal ganglion cell layer (GCL) thickness. We evaluated variability, with interocular comparison and correlation between results for both methods. Citation: OCT Sub-Study Committee for the NORDIC Idiopathic Intracra- nial Hypertension Study Group. Base- line OCT measurements in the Idiopathic Intracranial Hypertension Treatment Trial, part I: quality control, comparisons, and variability. Invest Ophthalmol Vis Sci. 2014;55:8180– 8188. DOI:10.1167/iovs.14-14960 R ESULTS . The average RNFL thickness > 95% of normal controls in 90% of eyes and the RNFL, TRT, ONH height, and ONHV showed strong (r > 0.8) correlations for interocular comparisons. Variability for repeated testing of OCT parameters was low for both methods and intraclass correlations > 0.9 except for the proprietary GCL thickness. The proprietary algorithm–derived RNFL, TRT, and GCL thickness measurements had failure rates of 10%, 16%, and 20% for all eyes respectively, which were uncommon with 3D-segmentation–derived measurements. Only 7% of eyes had GCL thinning that was less than fifth percentile of normal age-matched control eyes by both methods. See the appendix for the members of the OCT Sub-Study Committee for the NORDIC Idiopathic Intracranial Hy- pertension Study Group. C ONCLUSIONS . Spectral-domain OCT provides reliable continuous variables and quantified assessment of structural alterations due to papilledema. (ClinicalTrials.gov number, NCT01003639.) Keywords: papilledema, intracranial hypertension, optical coherence tomography, OCT I diopathic intracranial hypertension (IIH) is a disorder that affects overweight women of childbearing age, 1,2 with a rising incidence in parallel with the current obesity epidemic in the United States. 3 Patients have headaches, pulsatile tinnitus, transient visual obscurations, and diplopia in association with optic disc edema (papilledema). Some degree of vision loss occurs in 86% of patients and 10% develop severe visual loss. 2 The effectiveness of treatment had not been verified by properly designed clinical trials until the implementation of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT), sponsored by the National Eye Institute. This trial has shown that acetazolamide plus weight management improves the visual fields more than weight management plus placebo at the 6-month study outcome. 4 The accepted objective method for evaluating papilledema and monitoring the alterations in the optic nerve head (ONH) is the Fris´en scale, a noncontinuous ordinal grading based on specific features described in fundus photographs or on ophthalmoscopy. 5 The scale has been clinically useful but lacks sensitivity to small changes in the degree of disc edema and varies among observers. 6,7 In contrast, optical coherence tomography (OCT) measurement of the peripapillary retina nerve fiber layer (RNFL) thickness provides a continuous quantitative assessment of papilledema that correlates with Fris´en grading. 6,8,9 Typically, OCT assessments are used to evaluate thinning of the RNFL due to optic nerve injury from many causes. 10–12 Although prior smaller studies of IIH have shown that lower-resolution time-domain OCT imaging of the RNFL thickness can monitor changes in papilledema over time, 13,14 other studies 15 suggest the commercially available algorithms used in both time-domain and newer spectral- domain (SD) OCT units to calculate RNFL thickness can be unreliable and fail with severe papilledema (Mandel G, et al. IOVS 2010;51:ARVO E-Abstract 555). The OCT substudy of the IIHTT was designed to systemat- ically explore potential continuous measures of alterations in the structures of the ONH and macula due to papilledema, and monitor changes in the ONH, peripapillary and macular retinal layer thicknesses during treatment. Since the SD-OCT instru- ment and proprietary two-dimensional segmentation software methods are not designed to measure swelling of the ONH or the peripapillary retina, we evaluated a variety of approaches via a pilot study. We explored SD-OCT parameters and procedures that could be applied across multiple study sites to provide uniform data collection that measured the effects of papilledema (see Supplementary Appendix Pilot study file). In Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783 Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/Journals/IOVS/933678/ on 02/10/2016

We described 3 types of folds in the retina and a crease in the outer retina associated with papilledema owing to idiopathic intracranial hypertension (IIH) at presentation. We report the change in folds relative to treatment of IIH over the 6 months.In this substudy of a randomized clinical trial, study eyes of subjects assigned to acetazolamide (ACZ, n = 44) or placebo (PLB, n = 43) had spectral-domain optical coherence tomography (SDOCT) images of the optic disc and macula regions at baseline and at 3 and 6 months. Images were evaluated for peripapillary wrinkles (PPW), retinal folds (RF), choroidal folds (CF), and creases using transaxial and en face views. The optic nerve head (ONH) shape, retinal nerve fiber layer (RNFL) thickness, ONH volume, and papilledema grade were measured. Outcome was determination of the presence or absence of PPW, RF, CF, and creases.At presentation, except for an increase of PPW in ACZ eyes (64% vs 28%), both treatment groups were matched for all OCT features. At 6 months, ACZ-treated, but not PLB-treated, eyes had fewer folds of all types (P.01), with a 57% reduction in frequency of RF. Creases did not resolve. Resolution of RF, but not of PPW and CF, was associated with significant reduction in RNFL thickness, ONH volume, and papilledema grade.The various types of retinal folds associated with papilledema reflect biodynamic processes and show an ACZ treatment effect. Persistence of these folds despite marked improvement in ONH swelling suggests permanent changes in the affected retinal tissues.

Vitamin A and its metabolites (called retinoids) have been thought to play a role in the development of idiopathic intracranial hypertension (IIH). The IIH Treatment Trial (IIHTT) showed the efficacy of acetazolamide (ACZ) in improving visual field function, papilledema grade, quality of life and cerebrospinal fluid (CSF) pressure. We postulated that IIH patients would demonstrate elevated measures of vitamin A metabolites in the serum and CSF.Comprehensive measures of serum vitamin A and its metabolites were obtained from 96 IIHTT subjects, randomly assigned to treatment with ACZ or placebo, and 25 controls with similar gender, age and body mass index (BMI). These included retinol, retinol binding protein, all-trans retinoic acid (ATRA), alpha- and beta-carotenes, and beta-cryptoxanthin. The IIHTT subjects also had CSF and serum vitamin A and metabolite measurements obtained at study entry and at six months.At study entry, of the vitamin A metabolites only serum ATRA was significantly different in IIHTT subjects (median 4.33nM) and controls (median 5.04nM, p=0.02). The BMI of IIHTT subjects showed mild significant negative correlations with serum ATRA, alpha- and beta-carotene, and beta-cryptoxanthin. In contrast, the control subject BMI correlated only with serum ATRA. At six months, the serum retinol, alpha-carotene, beta-carotene, and CSF retinol were increased from baseline in the ACZ treated group, but only increases in alpha-carotene (p=0.02) and CSF ATRA (p=0.04) were significantly greater in the ACZ group compared with the placebo group. No other vitamin A measures were significantly altered over the six months in either treatment group. Weight loss correlated with only with the change in serum beta-carotene (r=-0.44, p=0.006) and the change in CSF retinol (r=-0.61, p=0.02).Vitamin A toxicity is unlikely a contributory factor in the causation of IIH. Our findings differ from those of prior reports in part because of our use of more accurate quantitative methods and measuring vitamin A metabolites in both serum and CSF. ACZ may alter retinoid metabolism in IIH patients.

Background Treatment with chronic corticosteroids has been associated with frequent significant adverse effects. We hypothesized that a long-term low-dose prednisone regimen for ocular myasthenia gravis (OMG) would have a low rate of major side effects. Methods Consecutive OMG patients from a single institution over a 16-year period and treated with ≥1 month of daily prednisone were included. Steroid-related complications were defined as the development/worsening of conditions requiring alteration to medical therapy. Serious complications included conditions requiring emergency care, hospitalization, or surgery. Results Eighty-three patients with follow-up period ranging from 1 to 271 months (median, 58 months) were included. Fifty-eight (70%) patients had follow-up period of ≥24 months. The maximum prednisone dose ranged from 10 to 60 mg. Tapering to ≤10 mg/d required ≤4 months for all but 2 patients. Median average daily dose following the initial course was 5 mg daily (interquartile range, 4-7.5 mg). During the first 2 years, there were 24.5 complications per 100 person-years. Only one patient had a serious complication within the first 2 years (2-year cumulative risk, 1%), but this individual was not following the recommended regimen. Conclusions Low-dose prednisone for OMG has an acceptable side-effect profile and causes few serious complications (2-year risk, ∼1%). However, patients need monitoring to detect the relatively common, but less serious, complications (2-year risk, ∼39%) to adjust medical therapy in a timely fashion.

Objective Retinal nerve fiber layer (RNFL) loss occurs with MS or after optic neuritis. Acute RNFL alterations at presentation and changes over time have not been well documented. We analyzed regional RNFL changes using 2 methods, ocular coherence tomography (OCT) and scanning laser polarimetry (SLP), to study initial edema and early RNFL loss. Methods 40 subjects with unilateral acute optic neuritis, had prospective OCT and SLP RNFL thickness values organized into 4 quadrants. We compared affected with normal fellow and control eyes to determine RNFL thickening (≥10% of 95th percentile of controls) and thinning (≥10μ less than fellow eye) at presentation, 1 and 3months. Results RNFL thickening occurred in 27/33 eyes (82%) by OCT and in 21/34 eyes (62%) by SLP at baseline. At 1month, RNFL thickening was common even as thinning developed in 15/23 (65%) of eyes by OCT and in 15/28 eyes (54%) by SLP. At 3months, RNL was thinned by OCT in 14/24 (58%) and by SLP in 15/25 (60%) affected eyes (58%). Neither MRI optic nerve lesion nor vision at baseline correlated with optical image findings or vision outcome. Conclusions RNFL swelling, most likely due to axoplasmic stasis from blockade at the lesion site in optic neuritis, is seen with OCT better than SLP. RNFL swelling in some quadrants and loss in others occur at 1month and is well seen with interocular comparison by both methods. Optical imaging provides pathophysiologic as well as quantitative information regarding axonal changes.

BACKGROUND AND PURPOSE: Cortical visual loss is a rare complication of cerebral angiography without a definitive pathophysiology. Given the rapid increase in endovascular procedures used to treat cerebral aneurysms, we explored the prevalence of this complication and whether we could add to the understanding of this disorder. Materials and METHODS: We performed a retrospective review of all procedures performed with the same contrast agent and detachable coils for treatment of posterior circulation aneurysms by 1 endovascular surgery service from 1996 to 2006. All patients were evaluated before and after each procedure by a team that included a neuro-ophthalmologist. RESULTS: Of 137 intra-arterial treatment procedures performed for posterior circulation aneurysms, we identified 4 patients with cerebral vision loss complications. During the same time period, >500 aneurysms of the anterior cerebral circulation were treated without this complication. The visual field loss was unilateral in 2 and bilateral in 2 patients. Recovery was complete in 3 and almost normal in the fourth patient. The amount of contrast used and the duration of the procedure were similar among all patients. The 4 patients had no identified specific risk factors for developing procedure-associated occipital dysfunction, all 4 had undergone prior angiography, and 1 patient had undergone repeat coiling, without complication. CONCLUSION: The 2.9% prevalence of cerebral visual loss with endovascular coil treatment of posterior circulation aneurysms is higher than that for angiography alone. Our patients recovered well with corticosteroid and intravenous hydration treatment. Recognizing the self-limiting nature of this problem might prevent an unneeded intervention.

To identify cutpoints for visual measures at baseline and 1 month predictive of abnormal 6-month vision that could be used as eligibility criteria in a clinical trial to test potential neuroprotection or myelin repair agents in patients with optic neuritis. To determine whether moderate-to-severe dysfunction in one or more visual measures at baseline or 1 month correlates with having major vision loss at 6 months.We used the Optic Neuritis Treatment Trial database to evaluate various cutpoints for baseline and 1-month vision levels that predicted abnormal 6-month vision. For selected cutpoints, we computed a 95% CI for positive predictive value and the required sample size if the cutpoint was to be used for clinical trial eligibility. We evaluated whether the degree of visual loss at baseline, 1 month, or change in visual function from baseline to 1 month correlated with 6-month visual acuity, contrast sensitivity, or threshold visual field.The best cutpoints for baseline and 1 month were visual acuityor= 20/50, contrast sensitivity1.0 log units, and visual field mean deviationor= -15 dB. The same levels of visual dysfunction at 1 month, but not at baseline, correlated with having 6-month moderate-to-severe loss for each of these measures (p = 0.01). A trial could require as few as 100 subjects for an outcome variable of one or more abnormal measures. Cutpoints at 1 month were highly predictive of abnormal 6-month vision, but the proportion of patients who would be eligible for a trial would be small.Provided data can be used either for the clinician to counsel patients on expected visual outcome or for designing studies to test therapies that might reduce the amount of permanent optic nerve damage due to optic neuritis in high-risk patients.

Previous reports suggest an association between the degree of optic nerve head edema and CSF pressure (CSFp) in idiopathic intracranial hypertension (IIH). We hypothesized that CSFp would be associated with Frisen papilledema grade (FPG) and other clinical features, and that FPG would modify the CSFp response to acetazolamide in participants in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). In the IIHTT, eligible patients underwent lumbar puncture (LP) prior to enrollment and were randomly assigned to one of two treatment groups: acetazolamide plus supervised diet or placebo plus supervised diet. Trial eligibility required baseline CSFp ≥250 mm H2O or ≥200 mm H2O with compelling clinical or imaging IIH findings. Associations between CSFp and FPG and other clinical features were examined at baseline. The effect of acetazolamide on 6-month change in CSFp was examined in those with low FPG (grades I–III) and those with high FPG (grades IV–V) at baseline. All 165 enrolled subjects had a baseline LP and 85 had an LP at 6 months. There was an association between CSFp and FPG at baseline: CSFp was more elevated in subjects with high FPG (378 ± 90 mm H2O, n = 50) than in subjects with low FPG (331 ± 77, n = 115, p = 0.002). At 6 months, acetazolamide had a similar effect on CSFp in subjects with high FPG (−79.9 mm H2O) and in subjects with low FPG (−50.9 mm H2O, p = 0.50). We found a modest association between CSFp and FPG. Acetazolamide had a beneficial effect on CSFp regardless of baseline FPG.

Recent studies have shown that the Bruch's membrane (BM) and retinal pigment epithelium (RPE), visualized on spectral-domain optical coherence tomography (SD-OCT), is deformed anteriorly towards the vitreous in patients with intracranial hypertension and papilledema. The BM/RPE shape has been quantified using a statistical-shape-model approach; however, to date, the approach has involved the tedious and time-consuming manual placement of landmarks and correspondingly, only the shape (and shape changes) of a limited number of patients has been studied. In this work, we first present a semi-automated approach for the extraction of 20 landmarks along the BM from an optic-nerve-head (ONH) centered OCT slice from each patient. In the approach, after the manual placement of the two Bruch's membrane opening (BMO) points, the remaining 18 landmarks are automatically determined using a graph-based segmentation approach. We apply the approach to the OCT scans of 116 patients (at baseline) enrolled in the Idiopathic Intracranial Hypertension Treatment Trial and generate a statistical shape model using principal components analysis. Using the resulting shape model, the coefficient (shape measure) corresponding to the second principal component (eigenvector) for each set of landmarks indicates the degree of the BM/RPE is oriented away from the vitreous. Using a subset of 20 patients, we compare the shape measure computed using this semi-automated approach with the resulting shape measure when (1) all landmarks are specified manually (Experiment I); and (2) a different expert specifies the two BMO points (Experiment II). In each case, a correlation coefficient ≥ 0.99 is obtained.

Aim: To establish the clinical profile of simultaneous bilateral optic neuritis in adults, the efficacy of steroid therapy, extent of visual recovery, and neurological outcome. Methods: The authors performed a retrospective review of records of patients referred to a neuro-ophthalmology service with acute bilateral optic neuritis from 2000–4. Exclusion criteria included previous multiple sclerosis or myelopathy, known systemic disorders or medications associated with optic neuropathy, uveitis, or neoplasm. Patients received intravenous methylprednisolone followed by oral prednisone. Visual acuity (logMAR conversion), mean deviation (dB) for visual fields, percentage of Ishihara plates seen, ophthalmoscopy, and neurological evaluation were recorded at baseline and at 6 months or 12 months. Owing to strong correlation for visual loss between eyes, the results for the worse eye in each patient were analysed. Results: 11 men and four women, with an age range of 18–64 years, had bilateral decreased vision, 12 with pain on eye movement. Except for one patient, no aetiology was found. All patients had normal neurological evaluations, average visual acuity 1.71 (SD 0.55), colour vision 2.7% (SD 9.9%), and mean deviation −25.35 dB (SD −7.95 dB). Both optic nerves showed abnormal signal on magnetic resonance imaging. 14 patients improved and their last average visual acuity, colour vision, and mean deviation were 0.36 (SD 0.54), 69% (SD 46%), and −7.05 dB (SD 8.40 dB), respectively. No patient developed a neurological problem during the follow up with a mean of 11 months. Conclusion: Idiopathic acute bilateral optic neuritis without myelopathy occasionally occurs in adults. Vision recovers with corticosteroid therapy and during the first year neurological dysfunction will frequently not occur.

In patients with vein of Galen malformations, high-flow shunting decreases cerebral perfusion. By reducing or eliminating these shunts, transarterial embolization can improve cerebral perfusion and clinical outcomes. Quantifying pre- and postembolization shunt blood flow may help determine the optimal timing and efficacy of embolization and may provide prognostic information. The authors used magnetic resonance imaging noninvasive optimal vessel analysis as a novel modality to measure volumetric blood flow through vein of Galen malformation shunts in a neonate and an infant before and after transarterial embolization.

Purpose To develop new methods for quantifying diplopia and test their validity, test–retest reliability, and responsiveness to treatment. Design Prospective case series. Participants Adult patients with diplopia in 2 tertiary referral practices. Diagnosis included cranial nerve palsies, thyroid eye disease, supranuclear palsies, and ocular myasthenia gravis. Methods The new diplopia questionnaire and cervical range of motion (CROM) diplopia examination were tested in a 15-patient validity study against the standard diplopia field performed on the Goldmann perimeter (each scored 0 [no diplopia] to 100 [constant diplopia in all fields]). The test–retest reliability of the CROM diplopia examination was determined in 27 patients. The responsiveness to treatment of the diplopia questionnaire and the CROM examination was tested in 15 patients who underwent strabismus surgery or received systemic prednisone for ocular myasthenia gravis. Main Outcome Measures Validity was evaluated by the intraclass correlation coefficient (ICC) compared with the standard Goldmann diplopia field. Test–rest reliability was evaluated by the ICC. Responsiveness to treatment was evaluated by comparing pretreatment and posttreatment scores. Results There was excellent agreement between the diplopia questionnaire score and Goldmann diplopia field score (ICC, 0.90) and between the CROM diplopia examination score and Goldmann diplopia field score (ICC, 0.88). Intertester reliability of the CROM diplopia examination score was excellent (ICC, 0.87; 95% confidence interval, 0.74–0.94). Postintervention scores were significantly lower than baseline (P = 0.0003 for CROM and P = 0.0001 for the questionnaire), with a median postintervention improvement of 48 for the CROM diplopia score (quartiles 12–68) and 36 for the diplopia questionnaire (quartiles 20–52). Conclusions Our new diplopia questionnaire and new CROM diplopia examination are valid, reliable, and responsive measures of diplopia severity. The tests are easy to administer and require less expensive and less cumbersome equipment than previously available.

Aim: The optimal treatment of ocular myasthenia gravis (OMG) remains unknown. The authors evaluated the efficacy of prednisone and pyridostigmine in reducing diplopia, ocular motor dysfunction, and ptosis in patients with OMG. Methods: Review of records from a clinical database from one neuro-ophthalmology service of patients presenting with OMG between 1990 and 2002, excluding those who developed generalised MG within the first month after diagnosis. Institutional review board approval was obtained for this study. Participants/interventions: Non-randomised, unmasked, therapy was given. 55 patients with diplopia in primary or downward gaze and clinically demonstrable extraocular muscle dysfunction received prednisone. 34 patients who had contraindications to steroids or who refused treatment with prednisone received pyridostigmine only. Over 5 days the daily prednisone dose was increased to 50–60 mg and then gradually reduced to 10 mg, followed by further reduction as tolerated. The pyridostigmine dose was begun at 180 mg daily and increased as tolerated. Main outcome measures: Follow up evaluations, performed at 1, 3–6, 12, and 24 months, detailed the frequency of ptosis and diplopia and the amount of ocular motor deviation in primary and downward gaze. Results: The prednisone and pyridostigmine groups were similar for age, sex, acetylcholine receptor antibody level, prism cover test results for primary and downward gaze, diplopia in primary and downward gaze, and unilateral ptosis. Bilateral ptosis was present in 32.4% of the pyridostigmine group and 10.9% of the prednisone group (p = 0.02). The prednisone group showed resolution in primary gaze diplopia, downgaze diplopia, unilateral ptosis, and bilateral ptosis in 73.5%, 75.5%, 85.7%, and 98%, respectively at 1 month. The benefit persisted at 3–6, 12, and 24 months except for the bilateral ptosis. The pyridostigmine group showed resolution in primary gaze diplopia, downgaze diplopia, unilateral ptosis, and bilateral ptosis in 6.9%, 17.2%, 50%, and 76.7% of patients after 1 month of treatment. The prism cover results improved (p = 0.003) in the prednisone group only. In the prednisone group, four patients had no response to therapy. Among the 51 prednisone responsive patients, there were 33 recurrences in 26 patients. 12 patients, all prednisone treated, had remissions. Except for three patients who developed diabetes, no patient developed a clinically significant systemic corticosteroid complication. Conclusion: These results suggest that 50–60 mg daily prednisone followed by lower doses (10 mg or less) has the benefit of resolving ptosis and diplopia that lasts for at least 2 years in approximately 70% of patients.

Background Participants enrolled in the Optic Neuritis Treatment Trial have been observed for more than a decade to assess the relationship between optic neuritis and the development of clinically definite multiple sclerosis. Objective To assess neurologic disability 10 to 12 years after an initial episode of optic neuritis. Design Longitudinal follow-up of a clinical trial. Setting Fourteen Optic Neuritis Treatment Trial clinical centers performed standardized neurologic examinations, including an assessment of neurologic disability. Participants One hundred twenty-seven patients who had developed clinically definite multiple sclerosis. Main outcome measures Functional Systems Scale and Expanded Disability Status Scale. Results The disability of most patients was mild, with 65% of patients having an Expanded Disability Status Scale score lower than 3.0. The degree of disability appeared to be unrelated to whether the baseline magnetic resonance imaging scan was lesion-free or showed lesions (P =.51). Among patients with baseline lesions, the degree of disability was unrelated to the number of lesions that were present on the scan (P =.14). Two patients died owing to severe multiple sclerosis, one of whom had no lesions revealed on the baseline scan. Conclusion Most patients who develop clinically definite multiple sclerosis following an initial episode of optic neuritis will have a relatively benign course for at least 10 years.

Background: Hypertrophic pachymeningitis is an uncommon disorder that causes a localized or diffuse thickening of the dura mater and has been associated with rheumatoid arthritis, syphilis, Wegener’s granulomatosis, tuberculosis, and cancer. Few series of the idiopathic variety have been described, particularly with respect to MRI correlation to clinical outcome and treatment. Objective: To investigate the clinical and laboratory evaluation, course, and treatment of patients with idiopathic hypertrophic pachymeningitis (IHP), to correlate the MRI findings with the clinical course, and to review the literature on IHP. Methods: Retrospective case series of 12 patients (9 men, 3 women), with a mean age of 55 years (range 39 to 88 years), who had IHP by imaging studies, meningeal or orbital biopsy, or both. The clinical features, laboratory evaluation, contrast-enhanced MRI, treatment, and clinical outcome were documented for each case. The mean duration of follow-up was 3.5 years (range 3 months to 16 years). Results: The main clinical features at presentation were headache (11 cases), loss of vision (7 cases), diplopia (4 cases), papilledema (2 cases), other cranial nerve involvement (3 cases), ataxia (2 cases), and seizures (1 case). On the initial MRI, the location of abnormal enhancement of the dura mater correlated with the clinical findings and the sphenoid wing area was affected in all patients. The sedimentation rate was elevated in five cases. The CSF had increased protein in six cases and lymphocytosis in four cases. Biopsy of the dura mater in five cases and the orbital soft tissue in one case showed infiltrates of small mature lymphocytes, plasma cells, and epithelioid histiocytes, but no neoplasia, vasculitis, or infectious agents. Cultures of the CSF and biopsy material remained sterile. Corticosteroid therapy improved the vision in 7 of 8 cases and controlled headache in 10 of 11 cases. Five cases had partial improvement of other neurologic symptoms and signs. Recurrence developed with steroid tapering in six cases. One case had progressive deterioration and died. In four cases methotrexate or azathioprine was added with reduction of the steroid dose. Follow-up MRI performed in 11 patients correlated 80% with the clinical state ( p = 0.01). Conclusion: IHP can be suspected on MRI and defined pathologically on biopsy. Untreated, the clinical course is usually marked by severe headache and progressive neurologic deterioration and vision loss. Although initially steroid-responsive, clinical manifestations frequently recur with corticosteroid taper, requiring the addition of immunosuppressive agents in some cases.

PURPOSE To describe the natural history of intraocular hemorrhages related to subarachnoid hemorrhage (SAH) as a result of ruptured intracranial aneurysms. METHODS Retrospective review of patients with cerebral aneurysms examined by a referral neuro-ophthalmology service between 1980 and 1998. Patients with intraocular hemorrhages associated with SAH as a result of ruptured aneurysms were followed up without vitrectomy, unless bilateral vitreous hemorrhage occurred. RESULTS Seventy of 450 patients with cerebral aneurysms had an SAH. Of these, 30 eyes of 19 patients had intraocular hemorrhages. Fourteen eyes had a vitreous hemorrhage; 12 had subhyaloid blood without a vitreous hemorrhage; and four had retinal hemorrhages alone. Two patients died shortly after presentation. Twenty-eight eyes were followed up for a mean of 4.8 years. Initial visual acuity was 20/100 to light perception in eyes with a vitreous hemorrhage, 20/20 to 20/400 in eyes with subhyaloid blood, and 20/20 to 20/40 in eyes with retinal hemorrhages. Three of the 12 eyes with a vitreous hemorrhage underwent vitrectomy. Of the nonoperated eyes, final visual acuity was at least 20/30 in 19 (76%) eyes, 20/40 to 20/60 in four (16%) eyes, and 20/100 in both eyes of one patient with premacular subhyaloid blood. None of the nonoperated eyes developed cataract formation or progression, retinal tears, or retinal detachment. Epiretinal membrane developed in one eye and pigmentary maculopathy developed in five. CONCLUSIONS Except for patients with bilateral vitreous hemorrhages, early vitrectomy may not be necessary in most cases of intraocular hemorrhages associated with nontraumatic SAH.

Objective To provide evidence that venous congestion and drainage patterns are responsible for the manifestations of cavernous sinus area dural arteriovenous malformations (CSdAVMs). Design Retrospective observational case series. Participants Records of 85 patients with complete clinical and angiographic evaluations of CSdAVMs were evaluated for the clinical features of the disorder. A neuroradiologist analyzed patterns of venous drainage to and from the cavernous sinus without knowledge of the clinical features. Four venous drainage patterns (reversal of flow from the CSdAVMs into the anterior cavernous sinus, ophthalmic vein thrombosis, drainage into the inferior petrosal sinus or drainage into the superior petrosal sinus) were statistically tested for their predictive value of signs and symptoms using logistic regression. Main outcome measures The power of prediction of orbital congestion, elevated IOP, extraocular muscle dysfunction, optic neuropathy, venous-stasis retinopathy, choroidal effusion, anterior chamber shallowing, bruits, cranial nerve paresis, and central nervous system dysfunction from four patterns of venous drainage. Results Reversal of drainage into the anterior cavernous sinus and ophthalmic veins was highly predictive ( P = 0) of orbital congestion, which was seen in 77 (91%) patients. In contrast, eight (9%) patients without orbital congestion had shunts that did not drain into the anterior cavernous sinus and ophthalmic veins. Cavernous sinus dural arteriovenous malformation drainage into the anterior cavernous sinus and ophthalmic veins also predicted elevated IOP ( P = 0.0023) and optic neuropathy ( P = 0.047). Ophthalmic vein thrombosis significantly predicted cases with choroidal effusion ( P = 0.002) and anterior chamber shallowing ( P = 0.01). Third nerve paresis could be predicted from flow toward the inferior petrosal sinuses ( P = 0.017). Central nervous system symptoms or dysfunction, occurring in 7 (8%) patients, was predicted by venous drainage into the superior petrosal sinus ( P = 0.0008). Conclusions The clinical features found in patients with CSdVAMs are related to the abnormal venous drainage and can be predicted by these venous drainage patterns. Venous congestion and hypertension seem to cause the clinical dysfunction in this disorder.

Objective Since idiopathic intracranial hypertension (IIH) is most prevalent in obese women of childbearing age, concerns arise regarding the impact of pregnancy on the disorder and the potential teratogenicity of some therapeutic agents. We evaluated the course, management of pregnant IIH patients and the visual and pregnancy outcomes. Methods Case series of pregnant women diagnosed with IIH. IIH symptoms, neuro-ophthalmological findings, IIH management, visual and pregnancy outcomes were documented. Results Among 240 women with IIH, 12 had 16 pregnancies. Ten had headaches, five had transient visual obscurations, and three had diplopia. Visual acuity was severely decreased in one and mildly reduced in three women. Six had marked and six had mild bilateral papilledema. Visual field loss occurred in four women. Visual symptoms and loss improved for the duration of the pregnancy after diagnostic lumbar puncture and salt restricted diet in three. Two additional women needed continuous spinal drainage for two days. One woman was treated with acetazolamide and medical abortion. The one woman with severe vision loss had fenestration of one optic nerve sheath and a lumboperitoneal shunt as well as corticosteroids and was the only case with permanent field loss. After intervention, visual acuity improved in all cases with reduced vision. There were 10 full-term normal deliveries, three missed abortions, one therapeutic abortion and two intrauterine fetal deaths. Conclusions IIH appears to present during the first two trimesters of pregnancy with typical symptoms and findings. Visual outcome is similar as for non-pregnant women. Treatment should be oriented towards dietary control, without ketosis. Repeated spinal fluid drainage, if needed, can be helpful.

Purpose Comparison of treatment outcome in patients with primary optic nerve sheath meningioma (ONSM). Design Retrospective, nonrandomized, comparative interventional case series. Participants Sixty-four patients with at least 50 months of well-documented follow-up. Intervention Observation, surgery only, radiotherapy only, or surgery and radiotherapy. Main outcome measures Visual acuity expressed as ratio, radiographic progression, and treatment complications. Results Sixty-four patients (55 women [85.9%] and nine men [14.1%]) were followed for a mean of 150.2 months (range, 51–516 months; standard deviation [SD], 74.7). The mean age at diagnosis was 47.1 years (range, 17–81 years; SD, 15.4). Fifty-eight patients had unilateral disease and six patients had bilateral disease. Of 59 patients with vision greater than no light perception at diagnosis, 13 patients were observed only, 12 had surgery only (four biopsies or partial resections, eight total resections), 18 received radiation alone, and 16 had surgery and radiation (14 biopsies or partial resections and radiation, two total resections and radiation). Irradiated patients received 4000 to 5500 cGy of conventional multiport or conformal external beam therapy, typically fractionated over 6 weeks. Visual acuity measurements at diagnosis among the four groups were not different (ratio, P = 0.186). Visual acuity at diagnosis was ≥0.5 in 56.3%, 0.4 to 0.050 in 12.5%, and P = 0.004). At last follow-up the acuity was ≥0.5 in 28.1%, 0.4 to 0.050 in 15.6%, and P = 0.002), surgery only (ratio, P = 0.019), and surgery with radiation groups (ratio, P = 0.030). The radiation only group showed a decrease in visual acuity that was not significant (ratio, P = 0.301). Complication rate was 33.3% in radiation only cases, 66.7% in surgery only cases, and 62.5% in surgery with radiation cases. Twenty-one patients (32.8%) showed radiographic progression. Four patients who were observed, seven patients who had surgery alone, and eight patients who had surgery and radiation developed radiographic progression. Two patients who had radiation alone had radiographic progression before treatment. Only two patients treated with radiation only showed radiographic progression after radiotherapy, and both had at least one surgical procedure before the radiotherapy. Conclusions Patients with ONSM receiving radiation alone demonstrated the best visual outcome during the follow-up period. We recommend that fractionated external beam radiation (5000–5500 cGy) be considered as initial treatment in adults in selected cases of ONSM when preservation of visual function is a reasonable therapeutic goal.

Goal: To determine whether aneurysms of the cavernous internal carotid artery (CCA) cause major neurologic morbidity or death. Methods: Retrospective analysis of all patients with a spontaneous CCA evaluated by a referral multidisciplinary neurovascular service from 1981 to 2000. All patients had complete clinical neuro-ophthalmologic and neurologic examinations and magnetic resonance imaging (MRI) or computed tomography (CT) with angiographic diagnostic confirmation. Follow-up evaluations were performed by our service in the majority of patients, and the remaining patients' subsequent examinations were obtained from the referring physicians. Results: One hundred seventy-four patients (mean age 60.7 years, median age 63 years, 161 women, 13 men) had 193 CCA. All 19 patients with bilateral CCAs were female. Twenty-eight patients had 1 or more subarachnoid aneurysms. The presentation included 156 aneurysms with pain or cranial neuropathy or both, 13 with a carotid cavernous fistula (CCF), and 24 asymptomatic CCAs. Two patients, both with a coagulopathy, had a cerebral infarct ipsilateral to the CCA, 1 at presentation and the other 2 years after partial third nerve palsy. One patient had a subarachnoid hemorrhage (SAH) 2.3 years after presentation, and no patient had arterial epistaxis or a CCA-related death. Excluding the 15 patients (16 aneurysms) who had no follow-up or died from SAH due to a subarachnoid aneurysm, 177 aneurysms were followed up for a mean duration of 3.10 years (SD = 3.6). One hundred six never-treated aneurysms were followed for 4.5 years (SD = 3.80, range 0.1-17), and 71 ultimately treated aneurysms were followed for 1.56 years (SD = 2.69, range 0.1-15). The overall rate for SAH was 0.19% and for a CCA-associated cerebral infarct was 0.37% per patient year. There were no correlations with cerebral infarct, SAH, or CCF and diabetes mellitus, hypertension, gender, age, cranial neuropathy, or size of the aneurysm, except for the largest diameter of the aneurysm and CCF ( r = 0.17, P = .018). However, all of the patients with cerebral infarct or SAH and 12 of the 13 CCF had an aneurysm diameter ≥1 cm. Conclusions: CCA is a disorder with strong female gender bias that uncommonly causes major neurologic complications. These data suggest that CCA should not be included in analyses that determine the risk of severe neurologic morbidity, hemorrhage, or death due to intracranial aneurysms. Copyright © 2002 by National Stroke Association

OBJECTIVES: To report atypical features of cavernous carotid aneurysms (CCAs) that can create complex management problems if not recognized. MATERIALS AND METHODS: Retrospective analysis was performed on 202 CCAs in 183 patients, referred to a tertiary neuroophthalmology/neurovascular service. RESULTS: Six cases of CCA with unusual characteristics were identified. Two patients, one with thrombocytosis and the other with disseminated intravascular coagulation, developed cerebral infarcts presumably due to embolism from the CCA. One patient presented with a carotid cavernous fistula (CCF) not initially recognized due to the lack of typical clinical and radiological findings. One patient presented with acute ischemic necrosis of the globe due to ruptured CCA causing a CCF. One patient, with magnetic resonance images and cerebral angiography demonstration of intradural extension of the CCA, presented with a partial third nerve paresis and experienced a subarachnoid hemorrhage more than two years later. One pa...

Importance To our knowledge, there are no large prospective cohorts of untreated patients with idiopathic intracranial hypertension (IIH) to characterize the disease. Objective To report the baseline clinical and laboratory features of patients enrolled in the Idiopathic Intracranial Hypertension Treatment Trial. Design, Setting, and Participants We collected data at baseline from questionnaires, examinations, automated perimetry, and fundus photography grading. Patients (n = 165) were enrolled from March 17, 2010, to November 27, 2012, at 38 academic and private practice sites in North America. All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation between −2 dB and −7 dB. All but 4 participants were women. Main Outcomes and Measures Baseline and laboratory characteristics. Results The mean (SD) age of our patients was 29.0 (7.4) years and 4 (2.4%) were men. The average (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39.9 (8.3). Headache was the most common symptom (84%). Transient visual obscurations occurred in 68% of patients, back pain in 53%, and pulse synchronous tinnitus in 52%. Only 32% reported visual loss. The average (SD) perimetric mean deviation in the worst eye was −3.5 (1.1) dB, (range, −2.0 to −6.4 dB) and in the best eye was −2.3 (1.1) dB (range, −5.2 to 0.8 dB). A partial arcuate visual field defect with an enlarged blind spot was the most common perimetric finding. Visual acuity was 85 letters or better (20/20) in 71% of the worst eyes and 77% of the best eyes. Quality of life measures, including the National Eye Institute Visual Function Questionnaire–25 and the Short Form–36 physical and mental health summary scales, were lower compared with population norms. Conclusions and Relevance The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. Our data show that IIH is almost exclusively a disease of obese young women. Patients with IIH with mild visual loss have typical symptoms, may have mild acuity loss, and have visual field defects, with predominantly arcuate loss and enlarged blind spots that require formal perimetry for detection. Trial Registration clinicaltrials.gov Identifier:NCT01003639

Geometric morphometrics (GM) was used to compare the shape of the peripapillary retinal pigment epithelium-Bruch's membrane (ppRPE) layer imaged on spectral domain optical coherence tomography (SD-OCT) of patients with presumed optic nerve sheath meningiomas (pONSM) and normal subjects.We compared 2 groups: 30 normals to 10 patients (11 eyes) with pONSM. We digitized 20 equidistant semi-landmarks on OCT images of the ppRPE-layer, spanning 2500 μm on each side of the neural canal opening (NCO). Data were analyzed using standard GM techniques including a generalized least squares Procrustes superimposition, principal component analysis (PCA), thin-plate spline, and permutation statistical analysis to evaluate differences in shape. We also analyzed other variables with respect to shape including tumor size-proximity to the globe, age, retinal nerve fiber layer, and optic disc height.All pONSM patients were female (age 37-66 years); 10 had unilateral and 1 had bilateral optic nerve involvement. Ten of the eyes had optic disc edema at presentation, 4 went on to develop shunt vessels, and 4 had optic atrophy. The ppRPE-layer bordering the NCO in normals is V-shaped pointing away from the vitreous; the ppRPE-layer in pONSM is indented causing an inverted-U shaped deformation skewed nasally toward the vitreous. PCA showed a significant difference between normals and pONSM (permutation, n = 10,000, P = 0.001). The size and proximity of the tumor to the globe correlates with the shape of the ppRPE-layer (r = 0.75, P = 0.04). Correlation between shape variables and RNFL thickening (r = 0.51), optic disc height (r = 0.67), and age (r = 0.67) were not statistically significant.The shape of the RPE layer in pONSM is characterized by an inverted-U shape or indentation that differs significantly from normals. It is indistinguishable from the shape we previously reported in papilledema and is not caused by disc edema. The mechanism in pONSM is unknown but may involve a change in the compliance of the nerve and/or localized sequestration of cerebrospinal fluid in the distal optic nerve sheath.