Should Aquaporin-4 Antibody Test Be Performed in all Patients With Isolated Optic Neuritis?

BACKGROUND: Optic neuritis (ON) may be the initial manifestation of neuromyelitis optica spectrum disorder (NMOSD). Aquaporin-4 antibody (AQP4 Ab) is used to diagnose NMOSD. This has implications on prognosis and is important for optimal management. We aim to evaluate if clinical features can distinguish AQP4 Ab seropositive and seronegative ON patients. METHODS: We reviewed patients with first episode of isolated ON from Tan Tock Seng Hospital and Singapore National Eye Centre who tested for AQP4 Ab from 2008 to 2017. Demographic and clinical data were compared between seropositive and seronegative patients. RESULTS: Among 106 patients (120 eyes) with first episode of isolated ON, 23 (26 eyes; 22%) were AQP4 Ab positive and 83 (94 eyes; 78%) were AQP4 Ab negative. At presentation, AQP4 Ab positive patients had older mean onset age (47.9 ± 13.6 vs 36.8 ± 12.6 years, P < 0.001), worse nadir VA (OR 1.714; 95% CI, 1.36 to 2.16; P < 0.001), less optic disc swelling (OR 5.04; 95% CI, 1.682 to 15.073; p = 0.004), and higher proportions of concomitant anti-Ro antibody (17% vs 4%, p = 0.038) and anti-La antibody (17% vs 1%, p = 0.008). More AQP4 Ab positive patients received steroid-sparing immunosuppressants (74% vs 19%, p < 0.001) and plasma exchange (13% vs 0%, p = 0.009). AQP4 Ab positive patients had worse mean logMAR VA (visual acuity) at 12 months (0.70 ± 0.3 vs 0.29 ± 0.5, p = 0.051) and 36 months (0.37±0.4 vs 0.14 ± 0.2, p = 0.048) follow-up. CONCLUSION: Other than older onset age and retrobulbar optic neuritis, clinical features are non-discriminatory for NMOSD. We propose a low threshold for AQP4 Ab serology testing in inflammatory ON patients, particularly in high NMOSD prevalence populations, to minimize diagnostic and treatment delays.

Low conversion rate of ocular to generalized myasthenia gravis in Singapore.

INTRODUCTION: Ocular myasthenia gravis (OMG) is a common condition of the neuromuscular junction that may convert to generalized myasthenia gravis (GMG). Our aim in this study was to determine the conversion rate and predictive factors for generalization in OMG, in an Asian population. METHODS: The investigation consisted of a retrospective study of OMG patients with a minimum 2 years of follow-up. RESULTS: Among 191 patients with OMG, 155 had the minimum 2-year follow-up. The conversion rate at median follow-up (40.8 months) was 10.6% (95% confidence interval 7.9%-13.3%), and at the 2-year follow-up it was 7.7% (95% confidence interval 5.6%-9.8%). At baseline, the predictive factors for generalization were positive acetylcholine receptor antibodies (hazard ratio 3.71, P = 0.024), positive repetitive nerve stimulation (RNS) studies (hazard ratio 4.42, P = 0.003), and presence of radiologically presumed or pathologically confirmed thymoma (hazard ratio 3.10, P = 0.013). DISCUSSION: The conversion rate of OMG to GMG in Asian patients is low, as predicted by presence of acetylcholine receptor antibodies, presence of thymoma, and positive RNS studies. Muscle Nerve 57: 756-760, 2018.

A reappraisal of diagnostic tests for myasthenia gravis in a large Asian cohort.

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease characterized by weakness of bodily skeletal muscles. Office-based diagnostic tests such as repetitive nerve stimulation (RNS), single fiber electromyography (SFEMG), and the ice test, are used to refine the differential clinical diagnosis of this disease. Evaluating the clinical sensitivity and specificity of these tests, however, may be confounded by lack of a gold standard, non-blinding, incorporation bias, use of non-representative populations and retrospective data. OBJECTIVE: In this study comprising a large Asian cohort of 127 patients recruited from a Neuro-ophthalmology clinic, we minimized aforementioned confounders and tested the diagnostic value of 3 office-based tests against 2 reference standards of MG by virtue of clinical features, antibody assay and response to treatment. RESULTS: Regardless of the reference standard used, the ice and SFEMG tests displayed a higher sensitivity (86.0 to 97.3%) compared to the RNS test (21.3 to 30.6%). Conversely, the specificity of the ice (31.3%) and SFEMG (21.7% and 17.2%) tests were reduced compared to the RNS test (82.6% and 84.4%). The combined use of the ice test and SFEMG, improved the specificity of MG diagnosis to 63.6% and 64.3%, without affecting the sensitivity of those tests. CONCLUSION: Our findings indicate, in an Asian population, high sensitivity of the SFEMG test and suggest the ice test as a valid, affordable and less technically demanding approach to diagnose MG with ocular involvement. Both ice test and SFEMG alone, however, yielded poor specificity. We suggest that the combination of SFEMG and ice test provides a more reliable diagnosis of MG.

Clinical spectrum of tuberculous optic neuropathy.

PURPOSE: Tuberculous optic neuropathy may follow infection with Mycobacterium tuberculosis or administration of the bacille Calmette-Guerin. However, this condition is not well described in the ophthalmic literature. METHODS: Ophthalmologists, identified through professional electronic networks or previous publications, collected standardized clinical data relating to 62 eyes of 49 patients who they had managed with tuberculous optic neuropathy. RESULTS: Tuberculous optic neuropathy was most commonly manifested as papillitis (51.6 %), neuroretinitis (14.5 %), and optic nerve tubercle (11.3 %). Uveitis was an additional ocular morbidity in 88.7 % of eyes. In 36.7 % of patients, extraocular tuberculosis was present. The majority of patients (69.4 %) had resided in and/or traveled to an endemic area. Although initial visual acuity was 20/50 or worse in 62.9 % of 62 eyes, 76.7 % of 60 eyes followed for a median of 12 months achieved visual acuities of 20/40 or better. Visual field defects were reported for 46.8 % of eyes, but these defects recovered in 63.2 % of 19 eyes with follow-up. CONCLUSION: Visual recovery from tuberculous optic neuropathy is common, if the diagnosis is recognized and appropriate treatment is instituted. A tuberculous etiology should be considered when evaluating optic neuropathy in persons from endemic areas.

Long-term outcome in children with gliomas of the anterior visual pathway.

We performed a retrospective assessment of the long-term visual, neurologic, and systemic outcomes of 47 patients with anterior visual pathway gliomas seen at the Johns Hopkins Hospital. All of the patients had follow-up of at least 10 years or died during the follow-up period. Two patients died before 10 years of follow-up were achieved. The remaining 45 patients (including three patients who subsequently died) had follow-up of 10-28 years (mean, 15.3 years; median, 15 years). Sixteen of the patients in this study, most of whom had neurofibromatosis type 1 (NF1), received no treatment. None of these patients died or developed neurologic morbidity as a result of their tumor. Thirty-one of the patients, most of whom did not have evidence of NF1, received treatment. Many of these patients subsequently developed neurologic, endocrine, or visual morbidity. However, although patients with anterior visual pathway gliomas who were not treated fared better visually, neurologically, and systemically than patients who were treated, patients who required treatment for progression generally had a good overall prognosis, particularly patients with tumors that did not involve the hypothalamus. Most of these patients survived and maintained useful vision in at least one eye. We believe that patients with anterior visual pathway gliomas, particularly those with NF1, should not be treated unless there is clear clinical or neuroimaging evidence of progression.