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Background Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in individuals older than 50 years. Demographic, ocular, and systemic risk factors for NAION have been identified, and we sought to determine which, if any, of these factors also increase risk of NAION in the fellow eye. Methods We performed a retrospective chart review of patients with "ischemic optic neuropathy" (based on International Classification of Disease [ICD] codes) seen at a single eye center between 2007 and 2017. Patients who met diagnostic criteria for unilateral NAION without fellow eye optic neuropathy at diagnosis were included. Demographic information, ocular comorbidities, and systemic diagnoses were recorded, in addition to whether the fellow eye developed NAION during the follow-up period. Univariate and multivariate Cox proportional hazard regression were used to calculate hazard ratios (HRs) for fellow eye involvement. Results Three hundred eighteen patients were identified by ICD codes, and 119 were included in the study. Twenty-nine (24%) patients developed NAION in the fellow eye over the mean follow-up period of 3.6 years (range: 1 month-11 years). Significant risk factors for fellow eye NAION included the presence of bilateral optic disc drusen (ODD, HR 2.78, 95% confidence interval [CI] 1.12-6.90, P = 0.02) and noncompliance with continuous positive airway pressure (CPAP) in patients with moderate-to-severe obstructive sleep apnea (HR 4.50, 95% CI 1.79-11.3, P = 0.0015). Conclusions Bilateral ODD and noncompliance with CPAP when indicated are associated with increased risk of NAION in the fellow eye. Patients with these risk factors should be counseled on the potentially devastating visual consequences of bilateral NAION, and compliance with CPAP should be stressed when appropriate.

Importance Ocular hypertension is an important risk factor for the development of primary open-angle glaucoma (POAG). Data from long-term follow-up can be used to inform the management of patients with ocular hypertension. Objective To determine the cumulative incidence and severity of POAG after 20 years of follow-up among participants in the Ocular Hypertension Treatment Study. Design, Setting, and Participants Participants in the Ocular Hypertension Treatment Study were followed up from February 1994 to December 2008 in 22 clinics. Data were collected after 20 years of follow-up (from January 2016 to April 2019) or within 2 years of death. Analyses were performed from July 2019 to December 2020. Interventions From February 28, 1994, to June 2, 2002 (phase 1), participants were randomized to receive either topical ocular hypotensive medication (medication group) or close observation (observation group). From June 3, 2002, to December 30, 2008 (phase 2), both randomization groups received medication. Beginning in 2009, treatment was no longer determined by study protocol. From January 7, 2016, to April 15, 2019 (phase 3), participants received ophthalmic examinations and visual function assessments. Main Outcomes and Measures Twenty-year cumulative incidence and severity of POAG in 1 or both eyes after adjustment for exposure time. Results A total of 1636 individuals (mean [SD] age, 55.4 [9.6] years; 931 women [56.9%]; 1138 White participants [69.6%]; 407 Black/African American participants [24.9%]) were randomized in phase 1 of the clinical trial. Of those, 483 participants (29.5%) developed POAG in 1 or both eyes (unadjusted incidence). After adjusting for exposure time, the 20-year cumulative incidence of POAG in 1 or both eyes was 45.6% (95% CI, 42.3%-48.8%) among all participants, 49.3% (95% CI, 44.5%-53.8%) among participants in the observation group, and 41.9% (95% CI, 37.2%-46.3%) among participants in the medication group. The 20-year cumulative incidence of POAG was 55.2% (95% CI, 47.9%-61.5%) among Black/African American participants and 42.7% (95% CI, 38.9%-46.3%) among participants of other races. The 20-year cumulative incidence for visual field loss was 25.2% (95% CI, 22.5%-27.8%). Using a 5-factor baseline model, the cumulative incidence of POAG among participants in the low-, medium-, and high-risk tertiles was 31.7% (95% CI, 26.4%-36.6%), 47.6% (95% CI, 41.6%-53.0%), and 59.8% (95% CI, 53.1%-65.5%), respectively. Conclusions and Relevance In this study, only one-fourth of participants in the Ocular Hypertension Treatment Study developed visual field loss in either eye over long-term follow-up. This information, together with a prediction model, may help clinicians and patients make informed personalized decisions about the management of ocular hypertension. Trial Registration ClinicalTrials.gov Identifier:NCT00000125.

The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) is a multicenter randomized, double-blind, placebo-controlled study that evaluated the efficacy of a weight reduction and low-sodium diet plus acetazolamide versus the diet plus placebo in reducing or reversing visual field loss in subjects with mild visual loss. We found the acetazolamide group had significantly improved perimetric mean deviation (MD), papilledema grade, quality of life measures, and cerebrospinal fluid (CSF) pressure.1 It is well known that visual field defects in idiopathic intracranial hypertension (IIH) can be improved with treatment2 and can be due to a variety of mechanisms. The main mechanism is thought to be CSF pressure–related disruption of axonal transport3,4 leading to intraneuronal optic nerve ischemia at the level of the optic nerve head. Another common mechanism is enlargement of the blind spot; this type of visual loss, mostly from peripapillary hyperopia, is refractive in origin.5 Less common causes of visual loss are fluid tracking from the optic disc to the fovea (neurosensory detachment) and the refractive visual loss related to choroidal folds.6 A study of patients with highly asymmetric papilledema has suggested a model of visual loss in IIH characterized by a generalized depression of the visual field.7,8 The model predicts visual loss greater in magnitude with increasing visual field eccentricity. This and another study concluded that the amount of visual loss correlates with the severity of optic disc edema— eyes with more optic disc edema generally had more visual loss.7,8 This relationship between degree of papilledema and visual loss suggests that visual loss in IIH occurs due to papilledema and not from a retrolaminar mechanism. Our main outcome measure for the IIHTT was the change in the average perimetric MD from baseline to 6 months. We chose this measure because of evidence that visual loss in IIH occurs across the visual field and increases with eccentricity. Here we report additional visual field outcomes at 6 months in the IIHTT.

Despite modern combination antiretroviral therapy (CART), distal neuropathic pain (DNP) continues to affect many individuals with HIV infection. We evaluated risk factors for new onset DNP in the CNS Antiretroviral Therapy Effects Research (CHARTER) study, an observational cohort. Standardized, semi-annual clinical evaluations were administered at six U.S. sites. DNP was defined by using a clinician-administered instrument standardized across sites. All participants analyzed were free of DNP at study entry. New onset DNP was recorded at the first follow-up visit at which it was reported. Mixed effects logistic regression was used to evaluate potential predictors including HIV disease and treatment factors, demographics, medical comorbidities and neuropsychiatric factors. Among 493 participants, 131 (27%) reported new DNP over 2,306 visits during a median follow-up of 24 months [interquartile range (IQR) 12-42]. In multivariable regression, after adjusting for other covariates, significant entry predictors of new DNP were older age, female sex, current and past antiretroviral treatment, lack of virologic suppression, and lifetime history of opioid use disorder. During follow-up, more severe depression symptoms conferred a significantly elevated risk. The associations with opioid use disorders and depression reinforce the view that the clinical expression of neuropathic pain with peripheral nerve disease is strongly influenced by neuropsychiatric factors. Delineating such risk factors might help target emerging preventive strategies, for example, to individuals with a prior history of opioid use disorder, or might lead to new treatment approaches such as the use of tools to ameliorate depressed mood.

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

The objectives of this study were to present the rationale for the main aspects of the study design and describe the trial methodology for the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).Eligible candidates with mild visual field loss (automated perimetric mean deviation [PMD] -2 to -7 dB) were randomized to receive either acetazolamide or matching placebo tablets. Randomized participants were offered participation in a supervised dietary program. The primary outcome variable, PMD, was measured at 6 months. Additionally, cerebrospinal fluid from subjects and serum from study participants and matched controls were collected for genetic analysis and vitamin A studies. An ancillary optical coherence substudy was added to investigate the changes of papilledema in the optic nerve head and retina that correlate with Frisén grading, visual field deficits, and low-contrast visual acuity.The randomized trial entered 165 participants from March 17, 2010, through November 27, 2012, from the United States and Canada. The primary outcome (month 6) visits were successfully completed by June 15, 2013. Blood specimens were obtained from 165 controls without IIH to investigate vitamin A metabolism and genetic markers of potential risk factors for IIH.The IIHTT is the first randomized, double-masked placebo-controlled trial to study the effectiveness of medical treatment for patients with IIH.

A 68-year-old woman presented with bilateral visual loss as the only clinical manifestation of an occult pancreatic nonsecretory neuroendocrine tumor (NET). The suspected diagnosis of paraneoplastic optic neuropathy was confirmed using immunofluorescence assays to demonstrate the presence of antibodies in the patient's serum that reacted with antigen(s) in the optic nerve and in the pancreatic NET hepatic metastasis. Treatment of the underlying cancer was followed by marked improvement in visual function.

Background The risk of optic disc haemorrhages on visual outcome in idiopathic intracranial hypertension (IIH) is unknown. We report the type and frequency of optic disc haemorrhages and other funduscopic abnormalities at baseline in the study eye of the 133 subjects enrolled in the Idiopathic Intracranial Hypertension Treatment Trial completing 6 months of follow-up. Methods We reviewed optic disc photographs to tabulate the frequency and type of optic disc haemorrhages, other funduscopic abnormalities and papilloedema grades of the study eye at baseline and analyse if their presence is associated with a poor visual outcome. Results 27.2% of subjects had nerve fibre layer haemorrhages in at least one eye. Five of seven, 71% of subjects that met criteria for treatment failure, had nerve fibre layer haemorrhages in at least one eye (Fisher9s exact test: p=0.02). There was a good correlation between presence of nerve fibre layer haemorrhages and Frisen grade (Spearman9s correlation, p=0.002; r=0.271). Subjects with nerve fibre layer haemorrhages had a higher cerebrospinal fluid pressure (40.0 mm water, p=0.04). There was poor correlation between nerve fibre layer haemorrhages at baseline and the perimetric mean deviation change at 6 months. Cotton wool spots were present in 4% of subjects, exudates in 3% and pseudodrusen in 4%. Conclusions Nerve fibre layer haemorrhages are common in patients with IIH with mild visual loss and correlate with the severity of the papilloedema. They occur more frequently in treatment failure subjects and therefore may be associated with poor visual outcomes. Trial registration number NCT01003639, Post-results.

Creutzfeldt-Jakob disease is a rare degenerative disease of the brain characterized by rapid irreversible neurological decline. The Heidenhain variant describes any case of Creutzfeldt-Jakob disease in which visual symptoms predominate in the early stages. The authors report a 63-year-old female who had rapidly progressive bilateral visual field loss since 2 months prior to evaluation. Over the following 2 weeks, the patient developed rapidly progressive visual changes and eventually died. Her case has several unusual features: (1) lack of neurological deficits classically seen with Creutzfeldt-Jakob disease such as myoclonus and ataxia; (2) rapid progression of a clearly documented consecutive homonymous hemianopia over less than 2.5 months from onset of symptoms to death; (3) early symmetric temporal atrophy of the optic nerves and paracentral retinal thinning with optical coherence tomography imaging; (4) negative single-photon emission computed tomography imaging; and (5) negative magnetic resonance i...

Idiopathic intracranial hypertension (IIH) is a rare condition that can lead to significant morbidity from visual loss. The cause of IIH is unknown, but IIH is known to be associated with obesity. Obese patients may be at particularly high risk for suffering vision loss from IIH. The purpose of the present study is to determine the prevalence of undiagnosed or asymptomatic papilledema in a population of morbidly obese individuals and to determine if these patients should undergo routine screening for papilledema.Patients presenting to the UC Davis Bariatric Surgery Clinic between February 2008 and January 2011 who met the National Institutes of Health criteria for bariatric surgery were invited to participate in the study. Those patients who met the inclusion criteria and consented to the study were included. Participants were screened for IIH by nonmydriatic fundus photographs and by concerning symptoms prompting direct referral for neuro-ophthalmologic evaluation. Images were reviewed by a neuro-ophthalmologist, and patients with suspicious optic discs underwent neuro-ophthalmologic evaluation. Patients with findings consistent with IIH were sent for neurological evaluation.A total of 606 patients with an average body mass index of 47 kg/m2 were included in the study. Seventeen of these patients had photographic optic disc findings or symptoms suspicious for IIH. Seven of these patients did not have disc edema on clinical examination. Six patients were not evaluated in the clinic. Four of the 17 patients had subtle optic disc edema confirmed by clinical evaluation and were referred for full neurological workup. These 4 patients had normal neuroimaging, 3 of whom underwent lumbar punctures with borderline high opening pressures. All 4 patients had unremarkable visual field examinations. Fundus abnormalities other than optic disc edema were discovered in 33 patients.Our study suggests that in a morbidly obese patient population, papilledema with significant visual loss is rare. Routine screening with fundus photography of morbidly obese patients likely is not warranted.

BACKGROUND To compare the mean central macular thickness (CMT) and the mean average optic nerve retinal nerve fiber layer (RNFL) thickness in the eyes of patients with a history of optic neuritis and/or multiple sclerosis (MS) using 5 commercially available optical coherence tomography (OCT) instruments. METHODS Cross-sectional study including 46 patients (92 eyes) with a history of optic neuritis and/or MS. Both eyes were imaged on the same day with 5 OCT instruments: 1 time-domain OCT (Stratus) and 4 different Fourier-domain (spectral-domain) OCT (3D OCT-1000, Cirrus, RTVue-100, and Spectralis). RESULTS Twenty-five patients (50 eyes) were included in the final analysis after excluding patients with diabetes, glaucoma, ocular hypertension, or retinal pathology and inadequate scan quality. Randomized block analysis of variance revealed statistically significant differences across instruments (P < 0.001) for both eyes for mean CMT and mean average optic nerve RNFL. When testing for significant differences in measurements from instrument to instrument, some difference was noted between the right and left eyes. CONCLUSIONS Statistically significant differences exist among commercially available OCT instruments in measuring mean CMT and mean average RNFL thickness in patients with optic neuritis and/or MS. These findings likely result from the differences in data acquisition and segmentation algorithm software among OCT instruments. Awareness of these variations among OCT instruments will be important in using these instruments for clinical trials and management of patients with optic neuritis and/or MS.

A 65-year-old woman with rheumatological symptoms and diplopia was diagnosed as suffering from giant cell arteritis. Four years later she presented to us with a steroid responsive optic neuropathy. A presumptive diagnosis of neurosarcoidosis was made because of a gallium-67 single-photon emission tomography scan indicating a positive ‘panda sign’. Subsequent chest computerised tomographic imaging revealed cavitating lung lesions and an open biopsy established the diagnosis of Wegener granulomatosis despite the negative anti-neutrophilic cytoplasmic antibody. At the time of diagnosis the patient had a steroid responsive optic neuropathy and had recently developed a bilateral uveitis. Treatment with cyclophosphamide and corticosteroids produced complete remission with no further progression of disease.

To assess the pattern and the local spatial frequency distribution of visual field defects (VFDs) in eyes with clinically diagnosed optic neuritis (ON) and their currently unaffected fellow eyes, using threshold-related, slightly supraliminal perimetry, ensuring high spatial resolution.Records obtained with the Tübingen Automatic perimeter (TAP, Oculus Inc., Dudenhofen, Germany) and the Octopus 101 perimeter (Haag-Streit Inc, Koeniz, Switzerland), using a standardized grid of 191 static targets within the central 30 degrees visual field, were analysed retrospectively. VFDs were assigned to 15 classes.Visual fields (VF) from 99 patients (26 male and 73 female subjects, aged from 18 to 51 years) with clinically diagnosed, acute ON (52 right eyes, 48 left eyes affected, one bilateral involvement) were evaluated. Central scotomas were the most common finding in associated eyes, covering 41% of all VFDs in affected eyes. Nerve fibre bundle defects were found in 29% and paracentral scotomas in 14% of all VFDs. Fellow eyes were perimetrically normal in 65% of the clinically monocular ONs. Nerve fibre bundle defects were found in 21% and diffuse scotomas in 9% of the fellow eyes.Central scotomas and retinal nerve fibre bundle defects are the most common VFDs in acute ON. Small central and paracentral scotomas that most probably would have been missed by automated thresholding perimetry with its relatively coarse grid could be detected by threshold-related, slightly supraliminal strategy. Of the fellow eyes in clinically apparent monocular optic neuritis, 35% present with visual field defects.

To determine the prevalence of visual field (VF) performance failures (PF) and treatment failures (TFs), and identify factors associated with PFs in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).A total of 165 participants from 38 sites with idiopathic intracranial hypertension (IIH) and mild visual loss were randomized to either acetazolamide-plus diet or placebo-plus diet. The IIHTT Visual Field Reading Center evaluated 2950 Swedish Interactive Threshold Algorithm Standard 24-2 VFs from the enrolled participants. A TF was defined when the participant's VF mean deviation (MD) worsened ≥2 to 3 dB from the average baseline MD (range of -2 to -7 dB) with a second retest confirming the visual deterioration. A PF was determined when the participant's: 1) VF results met TF criteria but were not confirmed on retest, 2) deterioration was confirmed on retest but the IIHTT Adjudication Committee concluded a TF was clinically unlikely.TF was detected in 7/165 (4%) of the participants and PF was detected in 35/165 (21%) of the participants on at least 1 examination. Four of the 35 PFs were adjudicated for TF, however based on clinical review by the adjudication committee and a third retest, they were judged as PFs. Of the 2,950 total IIHTT VF examinations, 2.7% met PF criteria.PF was confirmed in 21% of subjects and in 2.7% of the total number of VF examinations and was reversible on repeat testing. We recommend retesting when perimetric worsening occurs in otherwise clinically stable or improving IIH patients.

To determine the association between change from baseline in the optic nerve head (ONH) and the visual field (VF) during follow-up of ocular hypertension participants in the Ocular Hypertension Treatment Study.Longitudinal randomized clinical trial.One hundred sixty-eight eyes of 152 ocular hypertensive participants ages 40 to 80 years.Cox hazard models were applied to 3232 eyes, which included 81 eyes that reached a study end point by developing a glaucomatous VF (VF end point) and 128 eyes that reached a study end point by developing an optic disc change (optic disc end point).Primary open-angle glaucoma end point as determined by changes in the VF or optic disc.Forty-one eyes reached an end point by both VF and optic disc criteria; 40 eyes reached only a VF end point, and 87 reached only an optic disc end point. Times to reach isolated disc or field end points were similar. Visual field end points were more likely (P0.0001) in eyes that showed the following ONH features: an ONH hemorrhage, thinning of the optic disc rim, or enlargement of the horizontal cup-to-disc (C/D) ratio. Optic disc end points were more likely (P0.0001) in eyes that showed the following VF features: some evidence of a nasal step or a partial arcuate VF defect, or an increase in the pattern standard deviation (PSD).Both the VF and the optic disc must be monitored with equal diligence, because either may show the first evidence of glaucomatous damage. Changes in the ONH based on stereophotographic observation (rim thinning, hemorrhage, or a slight increase in C/D ratio) and VF changes (evidence of a nasal step/partial arcuate defect or an increase in PSD) suggest that these cases have an increased risk of developing glaucoma. Confirmation of such subtle findings should be sought through repeat testing and correlation with other clinical results.

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.

Purpose The Ocular Hypertension Treatment Study (OHTS) seeks to evaluate the safety and efficacy of topical ocular hypotensive medication in preventing or delaying the onset of visual field loss and/or optic nerve damage in ocular hypertensive subjects at risk for developing primary open-angle glaucoma. This study evaluates the baseline visual field test characteristics (visual field status, reliability properties, etc.) of patients who underwent eligibility visual field testing for entry to the OHTS. Design Cross-sectional study of baseline data as part of a longitudinal randomized clinical trial. Participants Two thousand eight hundred nineteen ocular hypertensive individuals, aged 40 to 80 (mean age, 55). Methods Subjects underwent at least two Humphrey Field Analyzer Program 30-2 Full Threshold visual field examinations in both eyes for study eligibility. A third examination was performed if a prior test was abnormal, questionable, or unreliable. For final eligibility, two sets of visual field examinations had to meet OHTS criteria for reliability and had to be classified as "normal." All OHTS visual field tests of potential subjects were submitted for eligibility assessment to the OHTS Visual Field Reading Center. Main Outcome Measures The percentage of visual fields that were normal and reliable according to OHTS criteria. Results Of the subset of 2304 subjects who completed the eligibility assessments, 1828 (79%) were OHTS-eligible based on visual field test requirements. A third eligibility test was required for 11% of all eyes because of unreliable, questionable, or abnormal test results. With the 33% fixation loss cutoff in the OHTS, 97% of all eligibility visual field examinations were reliable and 3% were unreliable. The most frequent cause (69.5%) of unreliability was excessive fixation losses. Conclusions Permitting one repeat test after an abnormal or unreliable test allowed an extra 560 patients to be "eligible" for the study based on visual field tests. A clinical screening review of otherwise normal and reliable tests was not restrictive. The adoption of a 33% fixation loss cutoff significantly reduced the number of required retests and prevented study rejection of 89 patients.

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

To evaluate the signs, symptoms, and immune responses of patients with melanoma-associated retinopathy (MAR) syndrome.We reviewed the clinical and immunologic findings of 62 MAR syndrome patients. They include 25 patients from our institution (11 not previously reported) and 37 patients reported from other institutions.There were 33 men and seven women (no gender information is available for the remaining 22 cases). Age at onset of the visual disturbance averaged 57.5 years (range, 30-78). Visual acuity of 20/60 or better was initially present in 82%. Fundus examination was normal in 44%, optic disc pallor was present in 23%, and retinal vessel attenuation was present in 30%. Vitreous cells were present in 30%. The latency from melanoma diagnosis to recognition of MAR syndrome averaged 3.6 years (range, 2 months to 19 years). Seven patients sustained visual improvement with various treatment regimens, especially with intravenous immunoglobulin and cytoreductive surgery (metastasectomy). Indirect immunohistochemical staining of the bipolar layer was typical, but several other retinal elements were also reactive. Tissue from a metastatic melanoma excised from one of the patients expressed antigens that reacted with antiretinal antibodies.MAR syndrome demonstrates diverse clinical and immunologic features. Treatment, especially intravenous immunoglobulin and cytoreductive surgery (metastasectomy), improves vision in some cases.

PURPOSE: To compare the results of peripheral kinetic visual field testing and central static perimetry for patients enrolled in the Optic Neuritis Treatment Trial to determine (1) whether loss and recovery of visual field sensitivity in the far periphery was different from that observed in the central visual field and (2) whether the far peripheral visual field provided additional useful information that was not available in the central visual field results. METHODS: Both affected and fellow eyes of 448 patients with optic neuritis in the Optic Neuritis Treatment Trial were evaluated according to the trial protocol during the patients' first 3 years in the study. Central static visual field tests were performed with program 30-2 on the Humphrey Field Analyzer, and peripheral kinetic testing consisted of plotting the I 3e and II 4e isopters on the Goldmann perimeter. Both test procedures were conducted according to the trial protocols, and quality control assessments and clinical evaluations were performed on all the visual fields. RESULTS: For both affected and fellow eyes at all 11 visits, there was a greater number of abnormal visual fields in the central static perimetry results than in the peripheral kinetic data. Only 2.9% of affected eyes had an abnormal peripheral visual field with a normal Humphrey mean deviation during year 1. At baseline, 97.1% of affected eyes had an abnormal Humphrey mean deviation on central static testing, whereas only 69.9% had abnormal peripheral kinetic visual fields. Approximately 80% of the I 3e and II 4e isopters for affected eyes that were abnormal at baseline were within normal limits at 30 days, but it took until week 19 for even 70% of the Humphrey mean deviations to return to normal. In addition, the II 4e isopters (more peripheral than the I 3e isopters) that were abnormal at baseline showed a somewhat greater percentage of improvement from baseline through day 30 than the abnormal I 3e isopters. Although this difference is statistically significant, it is probably not clinically significant. For visits after week 19, approximately 25% to 30% of affected eyes had an abnormal Humphrey mean deviation, whereas only 10% to 15% of peripheral kinetic fields were abnormal. CONCLUSIONS: For the affected eye in optic neuritis, the central visual field shows greater abnormalities than the far peripheral visual field. When the results obtained through Humphrey automated central static visual fields and Goldmann peripheral kinetic isopters are compared, the far periphery appears to recover more rapidly and more completely than the central field, at least in more severe cases of optic neuritis. In most cases, recovery in optic neuritis can probably be monitored effectively with automated perimetry of the central visual field alone. However, in cases of severe loss of the central visual field, a peripheral kinetic visual field obtained with a Goldmann perimeter may provide additional information about the patient's vision in the far periphery.

Inner and outer retinal morphology were quantified in vivo for 6 nonglaucomatous and 10 glaucomatous optic neuropathy patients. Custom, ultrahigh-resolution imaging modalities were used to evaluate segmented retinal layer thickness in 3D volumes (Fourier-domain optical coherence tomography), cone photoreceptor density (adaptive optics fundus camera), and the length of inner and outer segments of cone photoreceptors (adaptive optics-optical coherence tomography). Quantitative comparisons were made with age-matched controls, or by comparing affected and nonaffected retinal areas defined by changes in visual fields. The integrity of outer retinal layers on optical coherence tomography B-scans and density of cone photoreceptors were correlated with visual field sensitivity at corresponding retinal locations following reductions in inner retinal thickness. The photoreceptor outer segments were shorter and exhibited greater variability in retinal areas associated with visual field losses compared with normal or less affected areas of the same patient's visual field. These results demonstrate that nonglaucomatous and glaucomatous optic neuropathies are associated with outer retinal changes following long-term inner retinal pathology. © 2011 Macmillan Publishers Limited All rights reserved.

Aims It is well established that glaucoma results in a thinning of the inner retina. To investigate whether the outer retina is also involved, ultrahigh-resolution retinal imaging techniques were utilised. Methods Eyes from 10 glaucoma patients (25–78 years old), were imaged using three research-grade instruments: (1) ultrahigh-resolution Fourier-domain optical coherence tomography (UHR-FD-OCT), (2) adaptive optics (AO) UHR-FD-OCT and (3) AO-flood illuminated fundus camera (AO-FC). UHR-FD-OCT and AO-UHR-FD-OCT B-scans were examined for any abnormalities in the retinal layers. On some patients, cone density measurements were made from the AO-FC en face images. Correlations between retinal structure and visual sensitivity were measured by Humphrey visual-field (VF) testing made at the corresponding retinal locations. Results All three in vivo imaging modalities revealed evidence of outer retinal changes along with the expected thinning of the inner retina in glaucomatous eyes with VF loss. AO-UHR-FD-OCT images identified the exact location of structural changes within the cone photoreceptor layer with the AO-FC en face images showing dark areas in the cone mosaic at the same retinal locations with reduced visual sensitivity. Conclusion Losses in cone density along with expected inner retinal changes were demonstrated in well-characterised glaucoma patients with VF loss.

The Visual Field Reading Center (VFRC) was established to assess visual field testing in the Optic Neuritis Treatment Trial (ONTT), to train and certify ONTT technicians, and to monitor the quality of the visual fields through evaluation of the technical aspects of the visual field testing. We describe the functions of the VFRC personnel and the standardized test protocols developed by the VFRC for Humphrey and Goldmann perimetry. We also describe the VFRC procedures for training and certifying visual field technicians, double-checking the eligibility of ONTT patients, assessing the quality of the visual field data, and processing visual field data. In addition, we describe the principles applied by the director and associate director of the VFRC in their clinical classification of the various localized and diffuse visual field defects observed in the Humphrey and Goldmann visual fields. The VFRC has processed more than 14,000 Humphrey and Goldmann visual field tests. The visual field quality control procedures and visual field defect classification process have been shown to be quite reproducible. Through quality control assessment procedures, we have been able to pinpoint a variety of problems at an early stage and promptly implement corrective measures. The standardized test protocols, technician training and certification procedures, and quality control assessment techniques used by the VFRC for the ONTT may serve as a model for future clinical trials employing visual field data as an outcome measure. These procedures can also be used to enhance visual field reliability in ophthalmological practices.

This paper describes a technique for performing automated kinetic perimetry of the peripheral visual field. The test algorithm incorporates optimal stimulus parameters for kinetic perimetry, a priori information about age-related normal visual field properties, exploratory data sampling procedures, and real-time decision-making processes designed to make the test adaptive, efficient, and interactive. Preliminary testing in 100 eyes (twenty normal eyes, forty eyes with glaucomatous visual field loss, and forty eyes with neuro-ophthalmologic deficits) revealed good qualitative correspondence between automated and manual kinetic perimetry in about 77% of the cases. Another 15% of the automated kinetic perimetry results were very difficult to interpret and 8% revealed findings of no clinical value. Our results suggest that automated kinetic perimetry can provide an efficient means of testing the peripheral visual field, although current test procedures must be refined before they can be regarded as useful reliable clinical tools.

Objective To evaluate visual field abnormalities after an episode of optic neuritis among participants in the Optic Neuritis Treatment Trial. Methods Three readers independently evaluated 10 443 visual fields from 454 patients and classified visual field abnormalities into 21 different monocular categories representing 3 general types of visual loss: diffuse, localized, and artifactual. Classification frequency was determined and reader agreement was evaluated. The association of visual field abnormality classifications with mean deviation, pattern standard deviation, visual acuity, and foveal threshold was assessed. Results At baseline, diffuse loss accounted for 66.2% of the abnormalities in the affected eyes but only 6.2% of the abnormalities in the fellow eyes. During years 1 through 15, the affected and fellow eyes exhibited predominantly localized loss in the nerve fiber bundle region (partial arcuate, paracentral, and arcuate defects). At year 1, 35.7% of the abnormalities in the affected eyes and 34.4% in the fellow eyes consisted of localized defects. At year 15, 39.5% of abnormalities in the affected eyes and 26.3% in the fellow eyes consisted of localized defects. Foveal threshold was highly correlated with visual acuity and contrast sensitivity in the affected eye at baseline (–0.82 vs 0.79, respectively), 6 months (–0.84 vs 0.81), and 1 year (–0.84 vs 0.79). Conclusions Diffuse and central loss were more predominant in the affected eye at baseline, and nerve fiber bundle defects (partial arcuate, paracentral, and arcuate) were the most predominant localized abnormalities in both the affected and fellow eyes during the study.

Background and Methods. The use of corticosteroids to treat optic neuritis is controversial. At 15 clinical centers, we randomly assigned 457 patients with acute optic neuritis to receive oral prednisone (1 mg per kilogram of body weight per day) for 14 days; intravenous methylprednisolone (1 g per day) for 3 days, followed by oral prednisone (1 mg per kilogram per day) for 11 days; or oral placebo for 14 days. Visual function was assessed over a six-month follow-up period. Results. Visual function recovered faster in the group receiving intravenous methylprednisolone than in the placebo group; this was particularly true for the reversal of visual-field defects (P = 0.0001). Although the differences between the groups decreased with time, at six months the group that received intravenous methylprednisolone still had slightly better visual fields (P = 0.054), contrast sensitivity (P = 0.026), and color vision (P = 0.033) but not better visual acuity (P = 0.66). The outcome in the oral-prednisone group did ...

Using high-resolution spectral-domain optical coherence tomography (SD-OCT) and adaptive optics (AO) imaging, photoreceptor damage in a patient with a central macular arteriovenous malformation (AVM) and otherwise unexplained progressive vision loss was demonstrated. This patient presented with a central scotoma, a macular AVM, and no evidence of macular edema, retinal hemorrhage, or subretinal fluid. Fluorescein angiography (FA) did not reveal leakage. Over 28 years, her vision progressively worsened from 20/25 to 20/400. Both time-domain OCT and FA did not reveal any significant retinal abnormality. However, high-resolution SD-OCT imaging revealed clear disorganization of the outer segments and focal photo-receptor disruption adjacent to the AVM. En face AO images further revealed loss of the photoreceptors in these regions. This case demonstrates the unique finding of progressive vision loss in a patient with a congenital retinal AVM, and how high-resolution imaging can detect structural changes of the retina in patients with otherwise unexplained vision loss.

Autoimmune-related retinopathy and optic neuropathy (ARRON) syndrome is characterized by visual loss and often the presence of antibodies against retinal or optic nerve antigens in the absence of cancer. Limited success has been reported in treatment of ARRON syndrome with medications that suppress the immune system. In many patients, current strategies are insufficient to control the disease. A 47-year-old woman with progressive visual and hearing loss attributed to ARRON syndrome that was resistant to conventional therapies underwent autologous hematopoietic stem cell transplantation (HSCT). Clinical manifestations appeared to stabilize. This report suggests that autologous HSCT may have a therapeutic role in ARRON syndrome.

Botulinum A toxin has been used to treat strabismus and a variety of spasmodic neuromuscular diseases. Botulinum toxin treatment of strabismus is not as definitive and stable as the traditional surgical approach, but it has been found most useful in postoperative overcorrection, small deviations, sensory deviations, and acute sixth nerve palsy. This toxin has been effective in the treatment of essential blepharospasm and hemifacial spasm, for which it produces temporary relief of symptoms. In addition, this treatment has been applied to lower lid entropion, myokymia, aberrant regeneration of the seventh nerve, lid retraction, corneal exposure, nystagmus, spasmodic torticollis, and adductor spastic dysphonia.

Background:: New technology allows more precise definition of structural alterations of all retinal layers although it has not been used previously in cases of optic disc drusen. METHODS:: Using Stratus and Fourier domain (FD) optical coherence tomography (OCT) and adaptive optics (AO) through a flood-illuminated fundus camera, we studied the retinas of a patient with long-standing optic disc drusen and acute visual loss at high altitude attributed to ischemic optic neuropathy. RESULTS:: Stratus OCT and FD-OCT confirmed severe thinning of the retinal nerve fiber layer (RNFL). FD-OCT revealed disturbances in the photoreceptor layer heretofore not described in optic disc drusen patients. AO confirmed the FD-OCT findings in the photoreceptor layer and also showed reduced cone density at retinal locations associated with reduced visual sensitivity. CONCLUSIONS:: Based on this study, changes occur not only in the RNFL but also in the photoreceptor layer in optic nerve drusen complicated by ischemic optic neuropathy. This is the first reported application of FD-OCT and the AO to this condition. Such new imaging technology may in the future allow monitoring of disease progression more precisely and accurately. © 2008 Lippincott Williams & Wilkins.

To assess the risk of developing multiple sclerosis (MS) after optic neuritis and the factors predictive of high and low risk.Subjects in the Optic Neuritis Treatment Trial, who were enrolled between July 1, 1988, and June 30, 1991, were followed up prospectively for 15 years, with the final examination in 2006.Neurologic and ophthalmologic examinations at 13 clinical sites.Three hundred eighty-nine subjects with acute optic neuritis.Development of MS and neurologic disability assessment.The cumulative probability of developing MS by 15 years after onset of optic neuritis was 50% (95% confidence interval, 44%-56%) and strongly related to presence of lesions on a baseline non-contrast-enhanced magnetic resonance imaging (MRI) of the brain. Twenty-five percent of patients with no lesions on baseline brain MRI developed MS during follow-up compared with 72% of patients with 1 or more lesions. After 10 years, the risk of developing MS was very low for patients without baseline lesions but remained substantial for those with lesions. Among patients without lesions on MRI, baseline factors associated with a substantially lower risk for MS included male sex, optic disc swelling, and certain atypical features of optic neuritis.The presence of brain MRI abnormalities at the time of an optic neuritis attack is a strong predictor of the 15-year risk of MS. In the absence of MRI-detected lesions, male sex, optic disc swelling, and atypical clinical features of optic neuritis are associated with a low likelihood of developing MS. This natural history information is important when considering prophylactic treatment for MS at the time of a first acute onset of optic neuritis.

Author(s): Choi, Stacey S; Zawadzki, Robert J; Keltner, John L; Werner, John S | Abstract: PurposeTo study the integrity of inner and outer retinal layers in patients with various types of optic neuropathy by using high-resolution imaging modalities.MethodsThree high-resolution imaging systems constructed at the University of California Davis were used to acquire retinal images from patients with optic neuropathy: (1) adaptive optics (AO)-flood-illuminated fundus camera, (2) high-resolution Fourier domain optical coherence tomography (FDOCT), and (3) adaptive optics-Fourier domain optical coherence tomography (AO-FDOCT). The AO fundus camera provides en face images of photoreceptors whereas cross-sectional images (B-scans) of the retina are obtained with both FDOCT and AO-FDOCT. From the volumetric FDOCT data sets, detailed thickness maps of a three-layer complex consisting of the nerve fiber (NF), ganglion cell (GC), and inner plexiform (IP) layers were created. The number of visible cones in the en face images of photoreceptors was then compared with visual sensitivity maps from Humphrey visual field (HVF; Carl Zeiss Meditec, Inc., Dublin, CA) testing, as well as FDOCT and AO-FDOCT images, including the thickness maps of the NF-GC-IP layer complex. Five types of optic neuropathy were studied: (1) optic neuritis with multiple sclerosis (MS), (2) idiopathic intracranial hypertension (pseudotumor cerebri), (3) nonarteritic anterior ischemic optic neuropathy (NAION), (4) optic nerve head drusen with NAION, and (5) systemic lupus erythematosus with MS and arthritis.ResultsWith permanent visual field loss and thinning of the NF-GC-IP layer complex, cone photoreceptors showed structural changes, making them less reflective, which caused the appearance of dark spaces in the en face images (hence, reduced number of visible cones) and indistinct outer retinal layers in OCT images. However, when the visual field loss was only transient, with a normal NF-GC-IP layer complex, there were no detectable abnormalities in cone photoreceptors (i.e., they were densely packed and had distinct photoreceptor layering in the OCT images).ConclusionsCone photoreceptors show structural changes when there is permanent damage to overlying inner retinal layers. There was a positive relation between the thickness of the three-layer inner retinal complex, visual sensitivity, and integrity of the cone mosaic.

To report the impact of visual field quality control (QC) procedures on the rates of visual field unreliability, test parameter errors, and visual field defects attributed to testing artifacts in the Ocular Hypertension Treatment Study (OHTS).OHTS technicians were certified for perimetry and were required to submit 2 sets of visual fields that met study criteria before testing study participants. The OHTS Visual Field Reading Center (VFRC) evaluated 46,777 visual fields completed by 1618 OHTS participants between February 1994 and December 2003. Visual field QC errors, rates of unreliability, and defects attributed to testing artifacts were assessed. The OHTS QC system addressed 3 areas of clinic performance: (1) test parameter errors, (2) patient data errors, and (3) shipment errors. A visual field was classified as unreliable if any of the reliability indices exceeded the 33% limit. Clinical sites were immediately contacted by the VFRC via fax, e-mail, and/or phone and instructed on how to prevent further testing errors on fields with defects attributed to testing artifacts.QC errors (test parameter errors) and unreliability rates.A total of 2.4% (1136/ 46,777) of the visual fields were unreliable and 0.23% (107/46,777) had incorrect test parameters. Visual field defects attributed to testing artifacts occurred in approximately 1% (483/46,777) of the visual fields.Prompt transmission of visual fields to the VFRC for ongoing and intensive QC monitoring and rapid feedback to technicians helps to reduce the frequency of unreliable visual fields and incorrect testing parameters. Visual field defects attributed to testing artifacts were infrequent in the OHTS.

Objective To compare the occurrence of normal visual field (VF) test results following 2 vs 3 consecutive, abnormal, reliable test results in the Ocular Hypertension Treatment Study. Methods The Ocular Hypertension Treatment Study is a prospective, multicenter follow-up study as part of a longitudinal randomized clinical trial. Sixty-four (68 eyes) of 1636 participants developed a VF primary open-angle glaucoma (POAG) end point. We compared the proportion of normal VF test results after a VF POAG end point among eyes whose VF abnormality was confirmed by 2 (n = . eyes) vs 3 (n = 59 eyes) consecutive, abnormal, reliable VF test results. Results The proportion of VF test results that were normal subsequent to a VF POAG end point in eyes whose abnormality was confirmed by 2 consecutive, abnormal, reliable test results was significantly higher (73 [66%] of 110) compared with eyes whose abnormality was confirmed by 3 consecutive, abnormal, reliable test results (46 [12%] of 381) ( P = .01). Conclusions A VF POAG end point confirmed by 3 consecutive, abnormal, reliable VF test results appears to have greater specificity and stability than either 1 or 2 consecutive, abnormal, reliable VF test results. However, some eyes whose VF POAG end point was confirmed by 3 consecutive, abnormal, reliable test results nonetheless had 1 or more normal test results on follow-up.

PURPOSE To assess visual function more than 10 years after an episode of optic neuritis in patients enrolled in the Optic Neuritis Treatment Trial. DESIGN Longitudinal follow-up of a randomized clinical trial. METHODS Vision testing included measures of visual acuity, contrast sensitivity, and visual field. Quality of life was assessed with the National Eye Institute Visual Function Questionnaire. RESULTS Examinations were completed on 319 patients. In most patients, visual function test results in the eyes that experienced optic neuritis at study entry ("affected eyes") were normal or only slightly abnormal after 9.9 to 13.7 years. Visual acuity in the affected eyes was >or=20/20 in 74%, 20/25 to 20/40 in 18%

Objectives (1) To develop a classification system for visual field (VF) abnormalities, (2) to determine interreader and test-retest agreement, and (3) to determine the frequency of various VF defects in the Ocular Hypertension Treatment Study. Methods Follow-up VFs are performed every 6 months and are monitored for abnormality, indicated by a glaucoma hemifield test result or a corrected pattern SDoutside the normal limits. As of January 1, 2002, 1636patients had 2509 abnormal VFs. Three readers independently classified each hemifield using a classification system developed at the VF reading center. Asubset (50%) of the abnormal VFs was reread to evaluate test-retest reader agreement. A mean deviation was calculated separately for the hemifields as an index to the severity of VF loss. Main Outcome Measures A 97% interreader hemifield agreement. Results The average hemifield classification agreement (between any 2 of 3 readers) for 5018 hemifields was 97% and 88% for the 1266 abnormal VFs that were reread(agreement between the first and second classifications). Glaucomatous patterns of loss (partial arcuate, paracentral, and nasal step defects) composed the majority of VF defects. Conclusion The Ocular Hypertension Treatment Study classification system has high reproducibility and provides a possible nomenclature for characterizing VF defects.

BackgroundAge-related changes in the first-order multifocal electroretinogram (mfERG) responses were measured for two different luminance levels (200 and 700 cd.m(-2)). The relative contribution of optical and neural factors to senescent change in response was evaluated.MethodsData were obtained from one eye of each of 71 normal phakic subjects, age 9-80 years. The mfERG responses were recorded with the 7" stimulus-refractor unit (EDI) and VERIS 4.3 using the following protocol: bipolar contact lens, 103 hexagons, consecutive stimulation with 200 and 700 cd.m(-2), pupils > or =6 mm, amplification of 10(5), filter cut-offs at 10 and 300 Hz.ResultsAge-correlated decreases in amplitude and response density and increases in P1 implicit time were found for both luminance levels. The mean response density (nV.deg(-2)) was higher for the 700 cd.m(-2) stimulus, but the rate of change with age was not significantly different from that obtained with the 200 cd.m(-2) stimulus. Implicit time was not significantly different for the two light levels, nor was the rate of change with age. The decrease in response density and the increase in implicit time with age were significant across all retinal regions, dividing the 50 deg stimulus into six concentric rings. Age-related change in response density was greatest for the central retina and decreased with increasing retinal eccentricity.ConclusionLog mfERG response changes linearly as a function of age. Analyses of the effects of reduced ocular media transmission and increased stray light, along with ancillary data obtained from pseudophakes, imply that age-related changes in the mfERG are due to both optical and neural factors.

To characterize visual field (VF) loss at the baseline visit and to evaluate VF quality control (QC) procedures in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).The Visual Field Reading Center (VFRC) evaluated 660 baseline VFs (1320 hemifields) from 165 enrolled patients. Three readers independently classified each superior and inferior hemifield and identified any abnormalities. A subset (20%) of the hemifields was reread to evaluate within- and between-reader agreements. The QC system addressed test parameters, patient data, and shipment errors.The majority (60%) of the baseline hemifields consisted of localized nerve fiber bundle-type VF loss. Approximately one-third (31.5%) of all the classifications consisted of partial arcuate defects combined with an enlarged blind spot, making this the most common type of hemifield classification. Inferior hemifield loss was greater than superior loss for both study and nonstudy eyes. Reader agreements were90% for both inferior and superior hemifields for two out of three readers. Test-retest reliability agreement for individual readers was 95% for both hemifields. There were few QC errors with only 5.48 error points per 100-point VF.The most common type of IIHTT baseline hemifield abnormality was a localized nerve fiber bundle-like defect. Localized inferior hemifield loss was more common than superior hemifield loss. Quality control and within- and between-reader agreement were excellent for the IIHTT (ClinicalTrials.gov number, NCT01003639).

Importance Acetazolamide is commonly used to treat idiopathic intracranial hypertension (IIH), but there is insufficient information to establish an evidence base for its use. Objective To determine whether acetazolamide is beneficial in improving vision when added to a low-sodium weight reduction diet in patients with IIH and mild visual loss. Design, Setting, and Participants Multicenter, randomized, double-masked, placebo-controlled study of acetazolamide in 165 participants with IIH and mild visual loss who received a low-sodium weight-reduction diet. Participants were enrolled at 38 academic and private practice sites in North America from March 2010 to November 2012 and followed up for 6 months (last visit in June 2013). All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation (PMD) between −2 dB and −7 dB. The mean age was 29 years and all but 4 participants were women. Interventions Low-sodium weight-reduction diet plus the maximally tolerated dosage of acetazolamide (up to 4 g/d) or matching placebo for 6 months. Main Outcomes and Measures The planned primary outcome variable was the change in PMD from baseline to month 6 in the most affected eye, as measured by Humphrey Field Analyzer. Perimetric mean deviation is a measure of global visual field loss (mean deviation from age-corrected normal values), with a range of 2 to −32 dB; larger negative values indicate greater vision loss. Secondary outcome variables included changes in papilledema grade, quality of life (Visual Function Questionnaire 25 [VFQ-25] and 36-Item Short Form Health Survey), headache disability, and weight at month 6. Results The mean improvement in PMD was greater with acetazolamide (1.43 dB, from −3.53 dB at baseline to −2.10 dB at month 6; n = 86) than with placebo (0.71 dB, from −3.53 dB to −2.82 dB; n = 79); the difference was 0.71 dB (95% CI, 0 to 1.43 dB; P = .050). Mean improvements in papilledema grade (acetazolamide: −1.31, from 2.76 to 1.45; placebo: −0.61, from 2.76 to 2.15; treatment effect, −0.70; 95% CI, −0.99 to −0.41; P P = .003) and its 10-item neuro-ophthalmic supplement (acetazolamide: 9.82, from 75.45 to 85.27; placebo: 1.59, from 75.45 to 77.04; treatment effect, 8.23; 95% CI, 3.89 to 12.56; P P Conclusions and Relevance In patients with IIH and mild visual loss, the use of acetazolamide with a low-sodium weight-reduction diet compared with diet alone resulted in modest improvement in visual field function. The clinical importance of this improvement remains to be determined. Trial Registration clinicaltrials.gov Identifier:NCT01003639

Objective To measure the short- and long-term variability of automated perimetry in patients with optic neuritis and normal subjects. Design Prospective case-control design of patients with recovered optic neuritis with intraday and interday repetitions to obtain robust variability measurements. Entry criteria included a corrected pattern SD that was worse than the normal 5% probability level and a mean deviation worse than −3 dB but better than −20 dB. Five Humphrey 30-2 full threshold tests were administered during a 7-hour period (1 test every 2 hours) on the same day and at the same periods on 5 separate days. Subjects Seventeen patients with recovered optic neuritis and 10 healthy subjects of similar age. Main Outcome Measures Short-term variability and long-term variability for global visual field data. Results Patients with optic neuritis demonstrated variations in visual field sensitivity that were outside the entire range of variability for normal controls. These variations occurred for multiple tests performed on the same day at specific times and for tests performed at specific times on different days. There were no consistent patterns of sensitivity changes that could be attributed to time of day. The most dramatic fluctuations occurred in a patient whose visual fields varied from normal to a hemianopic defect from one week to another and from a partial quadrant loss to a hemianopic defect at different times on the same day. Seven of the patients with optic neuritis also demonstrated intermittent vertical step defects. Conclusions Patients with resolved optic neuritis can have large variations in visual field results on different days and at different times on the same day. The variations affect both the severity and the pattern of visual field loss and do not appear to be consistent across patients. These data indicate that care must be taken when automated visual field results in patients with optic neuritis are interpreted. Distinguishing systematic changes in sensitivity from variability requires more than a comparison of the current visual field with the most recent previous visual field.

Purpose: To clarify the nosology of autosomal dominant central areolar pigment epithelial dystrophy (CAPED) as previously described. Methods: The authors studied a family of 69 members spanning six generations with a macular dystrophy. Thirty-four patients were examined, and those found to be affected underwent further testing, including visual fields, electrophysiologic studies, and fluorescein angiography. Family history and medical records were used in three additional deceased patients. Results: Eleven patients were identified as having CAPED. The phenotype was inherited in an autosomal dominant fashion. Six of these patients were examined by us and had mid-life onset (at 32–53 years) of progressive visual loss (20/50-counting fingers), occurring over a 3- to 10-year period. These subjects had circumscribed hypopigmented maculae, retinal pigment epithelial window defects on fluorescein angiography, central scotomas, and electrophysiologic studies, ranging from normal to severely abnormal. Three deceased patients were presumed to have CAPED by review of records or family history. Two additional patients examined had mild macular changes but good visual acuity and no significant abnormalities on electrophysiologic studies. The latter two patients are presumed to have had early manifestations of CAPED. Conclusion: This family demonstrates that CAPED is an autosomal-dominant hereditary macular dystrophy which has late-onset and variable expressivity.

Objective: To evaluate the efficacy of short-wavelength automated perimetry (SWAP) in the assessment of patients with neuro-ophthalmologic disorders, especially optic neuropathies. Methods: A modified Humphrey field analyzer was used to perform standard automated perimetry and SWAP, a technique that isolates the activity of short-wavelength-sensitive ("blue") mechanisms. Forty patients (80 eyes) were evaluated by SWAP and standard automated perimetry. Thirteen patients (26 eyes) had recovered from optic neuritis and/or multiple sclerosis, 15 (30 eyes) were in various stages of treatment for pseudotumor cerebri, and 12 (24 eyes) had other miscellaneous neuro-ophthalmologic conditions. Six additional patients (12 eyes) with neuro-ophthalmologic conditions were tested twice on different days during a 2-week period, with the order of SWAP and standard perimetric testing being reversed on the second day. Results: Of the 80 eyes tested, 38 (48%) had SWAP visual fields that were worse than standard automated perimetry results; 29 (36%) showed no difference between standard and SWAP visual fields; and 13 (16%) had standard automated perimetry results that were worse than SWAP visual fields. Of the 26 eyes in patients with optic neuritis and/or multiple sclerosis, 15 (58%) had SWAP results that were worse than standard visual fields. Ten (33%) of the 30 eyes with pseudotumor cerebri had SWAP results worse than standard automated perimetry results, and 13 (54%) of 24 eyes with miscellaneous neuro-ophthalmologic conditions had SWAP results worse than standard automated perimetry results. For the 12 eyes undergoing repeated testing, SWAP visual fields were worse when they were performed last, perhaps indicating that some fatigue effect was present. This was observed for standard visual fields as well, but to a smaller extent. Conclusions: Preliminary findings suggest that SWAP may be useful in detecting certain neuro-ophthalmologic deficits more readily than standard automated visual field testing, especially for optic neuritis and multiple sclerosis. Further evaluations will be necessary to define the effects of fatigue for SWAP visual fields in neuro-ophthalmologic disorders.