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We previously reported that archetypal analysis (AA), a type of unsupervised machine learning, identified and quantified patterns of visual field (VF) loss in idiopathic intracranial hypertension (IIH), referred to as archetypes (ATs). We assessed whether AT weight changes over time are consistent with changes in conventional global indices, whether visual outcome or treatment effects are associated with select AT, and whether AA reveals residual VF defects in eyes deemed normal after treatment.Analysis of data collected from a randomized controlled trial.Two thousand eight hundred sixty-two VFs obtained from 165 participants during the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).We applied a 14-AT model derived from IIHTT VFs. We examined changes in individual AT weights over time for all study eyes and evaluated differences between treatment groups. We created an AT change score to assess overall VF change from baseline. We tested threshold baseline AT weights for association with VF outcome and treatment effect at 6 months. We determined the abnormal ATs with meaningful weight at outcome for VFs with a mean deviation (MD) of -2.00 dB or more.Individual AT weighting coefficients and MD.Archetype 1 (a normal VF pattern) showed the greatest weight change for all study eyes, increasing from 11.9% (interquartile range [IQR], 0.44%-24.1%) at baseline to 31.2% (IQR, 16.0%-45.5%) at outcome (P 0.001). Archetype 1 weight change (r = 0.795; P0.001) and a global score of AT change (r = 0.988; P0.001) correlated strongly with MD change. Study eyes with baseline AT2 (a mild diffuse VF loss pattern) weight of 44% or more (≥ 1 standard deviation more than the mean) showed higher AT2 weights at outcome than those with AT2 weight of44% at baseline (P0.001). Only the latter group showed a significant acetazolamide treatment effect. Archetypal analysis revealed residual VF loss patterns, most frequently representing mild diffuse loss and an enlarged blind spot in 64 of 66 study eyes with MD of -2.00 dB or more at outcome.Archetypal analysis provides a quantitative approach to monitoring VF changes in IIH. Baseline AT features may be associated with treatment response and VF outcome. Archetypal analysis uncovers residual VF defects not otherwise revealed by MD.

We previously applied archetypal analysis (AA) using visual fields (VF) from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) to derive a model, which quantified patterns (or archetypes [ATs] of VF loss), anticipated recovery, and identified residual VF deficits. We hypothesized that AA could produce similar results using IIH VFs collected in clinical practice. We applied AA to 803 VFs from 235 eyes with IIH from an outpatient neuro-ophthalmology clinic and created a clinic-derived model of ATs, with the relative weight (RW) and average total deviation (TD) for each AT. We also created a combined-derived model from an input dataset containing the clinic VFs and 2862 VFs from the IIHTT. We used both models to decompose clinic VF into ATs of varying percent weight (PW), correlated presentation AT PW with mean deviation (MD), and evaluated final visit VFs considered “normal” by MD ≥ -2.00 dB for residual abnormal ATs. The 14-AT clinic-derived and combined-derived models revealed similar patterns of VF loss previously identified in the IIHTT model. AT1 (a normal pattern) was most prevalent in both models (RW = 51.8% for clinic-derived; 35.4% for combined-derived). Presentation AT1 PW correlated with final visit MD (r = 0.82, p < 0.001 for the clinic-derived model; r = 0.59, p < 0.001 for the combined-derived model). Both models showed ATs with similar patterns of regional VF loss. The most common patterns of VF loss in “normal” final visit VFs using each model were clinic-derived AT2 (mild global depression with enlarged blind spot; 44/125 VFs; 34%) and combined-derived AT2 (near-normal; 93/149 VFs; 62%). AA provides quantitative values for IIH-related patterns of VF loss that can be used to monitor VF changes in a clinic setting. Presentation AT1 PW is associated with the degree of VF recovery. AA identifies residual VF deficits not otherwise indicated by MD.

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/aimsWe previously used archetypal analysis (AA) to create a model that quantified patterns (archetypes (ATs)) of visual field (VF) loss that can predict recovery and reveal residual VF deficits from eyes in the Optic Neuritis Treatment Trial (ONTT). We hypothesised that AA could produce similar results for ON VFs collected in clinical practice.MethodsWe applied AA to a retrospective data set of 486 VFs collected in 1 neuro-ophthalmology service from 141 eyes with acute ON and typical VF defects, to create a clinic-derived AT model. We also used the ONTT-derived AT model to analyse this new dataset. We compared the findings of both models by decomposing VFs into component ATs of varying per cent weight (PW), correlating presentation AT PW with mean deviation (MD) at final visits for each eye and identifying residual deficits in VFs considered normal.ResultsBoth models, each with 16 ATs, decomposed each presentation VF into 0–6 abnormal ATs representative of known patterns of ON-related VF loss. AT1, the normal pattern in both models, correlated strongly with MD for VFs collected at presentation (r=0.82; pConclusionsAA is a quantitative method to measure change and outcome of ON VFs. Presentation AT features are associated with MD at final visit. AA identifies residual VF deficits not otherwise indicated by MD.

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

Background: Retinal nerve fiber layer (RNFL) loss occurs with multiple sclerosis and after optic neuritis. Vision or RNFL changes at presentation of optic neuritis are not predictive of outcome, but vision loss at 1 month correlates with vision deficits at 6 months. We hypothesized that RFNL thinning at 1 month would predict RNFL loss at 6 months. Methods: We prospectively studied the RNFL by optical coherence tomography (OCT) and scanning laser polarimetry (SLP), and determined the threshold field mean deviation, in 25 subjects with acute optic neuritis over a 6-month period. RNFL values, including the amount of thinning at 1-month, were correlated with 6-month outcome. Results: Baseline visual performance and RNFL values were similar for eyes grouped by 1 month RNFL thinning. Eyes with 1 month RNFL thinning had greater and significant RNFL thinning at 6 months, for all quadrants by OCT and for the nasal and inferior quadrants by SLP. RNFL thinning by OCT and SLP at 1 month correlated with 6-month OCT ( r = 0.58; p = 0.006) and SLP ( r = 0.59; p = 0.002) RNFL thinning, respectively. Conclusion: Early RNFL loss at 1 month was predictive of the RNFL thinning at 6 months, which corroborated the importance of the 1-month time point for predicting the outcome of an optic neuritis attack.

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.

Background: Spectral domain optical coherence tomography (SD-OCT) reveals retinal ganglion cell layer plus inner plexiform layer (GCL+IPL) and peripapillary retinal nerve fiber layer (pRNFL) thinning in chronic optic nerve injury. At presentation, swelling of the pRNFL confounds evaluation of early axon loss. Objective: We studied whether the GCL+IPL thins before the pRNFL, the trajectory of GCL+IPL loss and relationship to vision. Methods: We prospectively evaluated 33 eyes (study) with new optic neuritis, using perimetry and SD-OCT with investigative three-dimensional layer segmentation and commercial two-dimensional segmentation to compute the GCL+IPL and pRNFL thickness. Results: At presentation, GCL+IPL thickness (82.4±8.8 µm) did not differ from unaffected fellow eyes (81.2±6.7 µm), via the three-dimensional method, while the two-dimensional method failed in 9% of study eyes. At 1–2 months, there was thinning of the pRNFL in 10% and of the GCL+IPL in 93% of study eyes. GCL+IPL reduction was greatest during the first 2 months. GCL+IPL thinning at 1–2 months correlated with GCL+IPL thinning at 6 months ( r=0.84, P=0.01) and presentation visual acuity ( r=0.48, P=0.006) and perimetric mean deviation ( r=0.52, P=0.003). Conclusion: GGL+IPL is an early biomarker of structural injury in optic neuritis as thinning develops within 1–2 months of onset, prior to pRNFL thinning.

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.