Clinical course, imaging, and pathological features of 45 adult and pediatric cases of myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described neuroinflammatory demyelinating disease. OBJECTIVE: To better understand the clinical spectrum, risk factors and outcomes in MOGAD. METHODS: Retrospective cohort study including all subjects harboring anti-MOG antibodies identified in major academic hospitals across the province of Quebec. RESULTS: We identified 45 MOGAD cases. The minimal estimated point-prevalence was 0.52/100 000 in Quebec. Median age at presentation was 32 years (range 1-71) with equal sex ratio. Most frequent ethnic groups were Caucasians and Asians. The most frequent clinical manifestations at onset were optic neuritis (ON), affecting 56% of adults, and acute disseminated encephalomyelitis (ADEM), affecting 33% of children. First MRI was abnormal in 84% of cases. Most CSF samples showed pleocytosis without oligoclonal bands. Two brain biopsies revealed lipid-laden macrophages and reactive astrocytes. Despite steroids, only 38% had fully recovered at 4 weeks after onset. Half of pediatric and two thirds of adult-onset MOGAD subjects experienced relapses. At last follow-up, 69% showed residual deficits, which were moderate to severe in 17% of adults. CONCLUSION: MOGAD has heterogeneous disease course, and it is not a benign disease for a substantial proportion of adults. Best disease-modifying therapies remain to be determined.

A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy.

Major advances in understanding the pathogenesis of inherited metabolic disease caused by mitochondrial DNA mutations have yet to translate into treatments of proven efficacy. Leber's hereditary optic neuropathy is the most common mitochondrial DNA disorder causing irreversible blindness in young adult life. Anecdotal reports support the use of idebenone in Leber's hereditary optic neuropathy, but this has not been evaluated in a randomized controlled trial. We conducted a 24-week multi-centre double-blind, randomized, placebo-controlled trial in 85 patients with Leber's hereditary optic neuropathy due to m.3460G>A, m.11778G>A, and m.14484T>C or mitochondrial DNA mutations. The active drug was idebenone 900 mg/day. The primary end-point was the best recovery in visual acuity. The main secondary end-point was the change in best visual acuity. Other secondary end-points were changes in visual acuity of the best eye at baseline and changes in visual acuity for both eyes in each patient. Colour-contrast sensitivity and retinal nerve fibre layer thickness were measured in subgroups. Idebenone was safe and well tolerated. The primary end-point did not reach statistical significance in the intention to treat population. However, post hoc interaction analysis showed a different response to idebenone in patients with discordant visual acuities at baseline; in these patients, all secondary end-points were significantly different between the idebenone and placebo groups. This first randomized controlled trial in the mitochondrial disorder, Leber's hereditary optic neuropathy, provides evidence that patients with discordant visual acuities are the most likely to benefit from idebenone treatment, which is safe and well tolerated.

Neurosyphilis masquerading as oculomotor nerve palsy in a healthy middle-aged man: Case report and review of the literature.

Acquired isolated oculomotor nerve palsy (ONP) is a commonly encountered clinical entity in ophthalmology. While most cases are due to microvascular ischemia, the diagnosis of ONP requires careful evaluation for alternate life-threatening etiologies. We present a case of isolated complete pupil-involving ONP in a healthy 47-year-old man in whom aneurysmal compression was initially suspected. Investigations later revealed a diagnosis of neurosyphilis. Neurosyphilis is an extremely rare cause of isolated ONP and seldom reported in the literature. Timely recognition of this disease by ophthalmologists can help orient patients to the appropriate neurology and infectious disease services they need.

Bilateral optic neuritis in acute hepatitis C.

A 34-year-old woman developed bilateral optic neuritis 2 weeks after the onset of acute hepatitis C. The strong temporal relationship between the initial clinical manifestations of hepatitis C and the development of optic neuritis provides a basis for thinking that the hepatitis caused the optic neuritis After corticosteroid treatment, the optic neuropathy markedly improved but left behind retinal nerve fiber thinning, as measured by optical coherence tomography, and optic disc pallor. Optic neuritis has been reported in conjunction with hepatitis A and B but not with hepatitis C.

Retinal nerve fiber structure versus visual field function in patients with ischemic optic neuropathy. A test of a linear model.

PURPOSE: To test a linear model relating the regional loss in retinal nerve fiber (RNFL) thickness to the corresponding regional loss in sensitivity with data from patients with previous anterior ischemic optic neuropathy (AION). DESIGN: Case-control study. PARTICIPANTS: Twenty-four individuals with AION and 20 with normal vision were tested. The time since the AION attack ranged from 5.2 months to more than 20.3 years (median, 2.95 years). METHODS: Eyes were tested with standard automated perimetry (SAP) and with optical coherence tomography (OCT), both RNFL thickness scans. The average RNFL thickness of the inferior and superior disc sectors was plotted against the average total deviations (linear units) of the corresponding superior and inferior arcuate field regions, and a linear model was fitted. According to the model, the RNFL thickness R=s(o)T+b, (1), where T is the relative SAP sensitivity loss (on a linear scale; e.g., for -3 dB, T = 0.5), s(o) is the RNFL thickness attributable to axons in the healthy or normal state (T = 1.0), and b is the residual RNFL measured when all sensitivity and axons are lost. MAIN OUTCOME MEASURES: Optical coherence tomography RNFL thickness and SAP sensitivity. RESULTS: The data from the AION patients resembled the data from glaucoma patients previously tested and were described by the linear model. For patients with SAP losses of more than -10 dB in the arcuate region, the RNFL thickness provided an estimate of residual RNFL thickness, b. The median value of b (45.5 microm) was similar to the value for patients with glaucoma. It varied among individuals (range, 30.4-63.3 microm), showing a very weak correlation with patient's age (r = 0.30) and the time since the AION episode (r = 0.26), but an excellent correlation (r(2) = 0.94; P<0.01) with the value of s(o), estimated from the unaffected eyes. CONCLUSIONS: The relationship between a structure (OCT RNFL thickness) and function (SAP sensitivity loss) is the same for patients with AION and glaucoma and can be approximated by a simple linear model. The model may provide a framework for identifying those patients with ganglion cell axons that are malfunctioning but are alive.

Neuro-ophthalmic sarcoidosis: the University of Iowa experience.

PURPOSE: To report a case series of neuro-ophthalmic sarcoidosis manifestations from a predominantly Caucasian Midwest population. DESIGN: Retrospective non-comparative case series and literature review. PARTICIPANTS: Twenty patients with biopsy proven sarcoidosis cases and neuro-ophthalmic manifestations. METHODS: We reviewed 67 consecutive charts with the clinical diagnosis of neurosarcoidosis at the University of Iowa Hospital and Clinics (UIHC) Department of Ophthalmology database in Iowa City, Iowa, seen from 1984 to 2006. MAIN OUTCOME MEASURES: Charts were reviewed for the following: 1) demographic information; 2) neuro-ophthalmic findings; 3) biopsy location and results; 4) pre-existing sarcoidosis; 5) neuroimaging studies (e.g., cranial magnetic resonance imaging and computed tomography scans); 6) cerebrospinal fluid results; 7) sarcoid related testing (serum angiotensin converting enzyme, chest radiograph, chest computed tomography scans, Gallium scan, bronchoalveolar lavage, pulmonary function testing); 8) treatment; and 9) course of disease. RESULTS: Twenty of the 67 charts (30%) had biopsy proven sarcoidosis and neuro-ophthalmic manifestations. Of the 20 included cases, 4 (20%) were men and 16 (80%) were women. Six (30%) patients were African-American and 14 (70%) were Caucasian. The average age at diagnosis was 43.1 years with a standard deviation of 14.1 and a range of 22 to 80 years. Neuro-ophthalmic manifestations included optic neuropathy (14), cranial neuropathy (4), Horner's Syndrome (1), tonic pupil (1), and optic tract involvement (1). Of the 14 patients presenting with optic neuropathy, 8 had optic disc edema, 5 had optic disc pallor and 1 had an optic disc granuloma. Contrast cranial magnetic resonance imaging (MRI) showed pathologic contrast enhancement (16 of 19 cases) involving optic nerve (9), optic chiasm (1), optic radiations (1), cavernous sinus (1), leptomeninges (3), and cerebral parenchyma (3). Chest imaging was abnormal in the course of disease for 12 of 18 and serum angiotensin-converting enzyme was only elevated in 5 of 15 patients tested. All 20 patients were treated with corticosteroids but five required additional immunosuppressive therapy to control disease activity. The neuro-ophthalmic course was relapsing and remitting in 8 cases, stable or resolved in 7, and chronic in 5 patients. After treatment of patients with optic neuropathy, visual acuity at last follow-up visit was improved in 5, worsened in 5, and stable (i.e., within one Snellen acuity line of baseline) in 4. CONCLUSION: In our Midwest retrospective case series of biopsy proven neuro-ophthalmic sarcoidosis, patients were predominately white females with a wide age range. Consideration for the diagnosis of neurosarcoidosis should therefore not be limited by age, gender, or race. Optic neuropathy was the most common manifestation, typically presenting with optic disc edema and severe visual loss. No light perception vision was relatively common and should be considered a "red flag" for the diagnosis. Contrast cranial MRI frequently shows pathologic enhancement of the visual pathway. Serum angiotensin converting enzyme and chest radiography had relatively poor sensitivity for detecting biopsy proven disease in our study and therefore additional testing for tissue diagnosis might still be necessary for extrapulmonary neuro-ophthalmic sarcoidosis. Corticosteroids are the mainstay of therapy but some patients may require additional immunosuppressive therapy.

Visual loss due to Wernicke syndrome following gastric bypass.

PURPOSE: To report a case of Wernicke encephalopathy after gastric bypass surgery resulting in vision loss, ophthalmoplegia, and ataxia, all of which reversed with a single dose of IV thiamine. METHODS: Observational case report. RESULTS: A 34-year-old woman presented with decreased vision and intermittent diplopia after gastric bypass surgery. She was found to have bilateral limitation of horizontal gaze, decreased vision with bilateral central scotoma and mild disc edema OU. Her cranial magnetic resonance imaging (MRI) was normal. A presumptive diagnosis of Wernicke encephalopathy was made. The patient was admitted, and a single dose of IV thiamine reversed the ophthalmoplegia and vision loss within 24 hours. CONCLUSION: Wernicke encephalopathy should be considered in patients with vision loss after gastric bypass surgery. The classic triad of confusion, ataxia, and ophthalmoplegia may not be present and, although uncommon, the findings of optic disc edema and vision loss should not deter the clinician from making the diagnosis. Replacement thiamine if given promptly may rapidly reverse the findings.

Optic disc edema with adjacent cilioretinal artery occlusion in a male with ulcerative colitis.

OBJECTIVE: To report a case of optic disc edema with adjacent retinal ischemia in ulcerative colitis. DESIGN: Photo essay. CASE REPORT: A 36-year-old white man presented with visual loss OD. Past medical history was significant for ulcerative colitis. The patient had suffered presumed non-arteritic anterior ischemic optic neuropathy OS one year prior to the episode OD. Ophthalmoscopic exam showed optic disc edema associated with an area of adjacent retinal ischemia that was confirmed on fluorescein angiography OD. An extensive evaluation for infectious, inflammatory, vasculitic, and hypercoagulable etiologies was negative. The presumptive diagnosis of ulcerative colitis-related ischemic optic neuropathy with simultaneous retinal ischemia was made. The patient was treated with antiplatelet therapy and the vision stabilized but did not recover. CONCLUSION: To our knowledge, this is the first report in the English language literature of a simultaneous ischemic event involving the optic nerve and the adjacent retina in a patient with ulcerative colitis.

Cotton wool spots associated with interferon beta-1 alpha therapy.

PURPOSE: To describe a case of cotton wool spots associated with interferon beta-1a treatment. METHODS: Observational case report. RESULTS: A 40-year-old man with a history of multiple sclerosis was on interferon beta-1a. He presented with cotton wool spots on fundus exam, which resolved and then recurred all while on therapy. Interferon was discontinued after the second episode and again the cotton wool spots resolved. Upon restarting the interferon, no further cotton wool spots have recurred. CONCLUSION: To our knowledge this represents only the third case of interferon beta-1a associated cotton wool patches and the first in the English-language ophthalmic literature. Unlike interferon alpha therapy, interferon beta 1-a retinopathy is presumed to be extremely rare and more common etiologies for cotton wool spots should be excluded in these patients. Given this limited number of cases versus the relatively frequent use of interferon beta-1a in the management of multiple sclerosis, no conclusions regarding causality or screening can be made but the issue probably deserves further study.