Prognosis of Ocular Myasthenia Gravis: Retrospective Multicenter Analysis

PURPOSE: To calculate the rate and timing of conversion from ocular myasthenia gravis to generalized myasthenia gravis. DESIGN: Retrospective multicenter analysis. SUBJECTS: Patients included in the study were diagnosed with ocular myasthenia gravis without the presence of generalized disease at onset. METHODS: We conducted a retrospective multicenter analysis. We reviewed charts of 158 patients who met diagnostic criteria for ocular myasthenia gravis. Patients were divided into 2 subgroups: an immunosuppressant treatment group and a nonimmunosuppressant treatment group. Timing of conversion to generalized disease and duration of follow-up also was evaluated. Additional data such as clinical symptoms at presentation, laboratory test results, and chest imaging results also were recorded. MAIN OUTCOME MEASURES: Conversion rates to generalized myasthenia at 2 years, effect of immunosuppression on conversion, and timing of conversion. RESULTS: The 158-patient cohort included 76 patients who received immunosuppressant therapy; the remaining 82 patients did not. The overall conversion rate to generalized disease was 20.9%. At 2 years, generalized myasthenia developed in 8 of 76 patients in the treated group and in 15 of 82 patients in the nonimmunotherapy group (odds ratio, 0.52; 95% confidence interval, 0.20-1.32). Median time for conversion to generalized disease was 20 months in the nonimmunosuppressant group and 24 months in the immunosuppressant group. Conversion occurred after 2 years of symptom onset in 30% of patients. CONCLUSIONS: Conversion rates from ocular to generalized myasthenia gravis may be lower than previously reported both in immunosuppressed and nonimmunosuppressed patients. A subset of patients may continue to convert to generalized disease beyond 2 years from onset of symptoms, and close monitoring should be continued.info:eu-repo/semantics/publishedVersio

Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies

Ability of a neuro-ophthalmologist to estimate retinal nerve fiber layer thickness

John H Pula,1 Jorge C Kattah,1 Hauping Wang,1 John Marshall,1 Eric R Eggenberger21University of Illinois College of Medicine at Peoria, Illinois Neurologic Institute, Peoria, IL, USA; 2Michigan State University, East Lansing, MI, USABackground: Qualitative description of the optic disc has clinical value, but optical coherence tomography (OCT) has provided the ability to quantify retinal nerve fiber layer (RNFL) thickness.Methods: We asked three neuro-ophthalmologists of at least 20 years’ experience to estimate the average OCT RNFL thickness of 37 eyes based on fundus photos.Results: The overall correlation coefficient for RNFL thickness estimation variance between two physicians and between physician and OCT was 0.53. The likelihood that the RNFL thickness estimation between physicians, or between physician and OCT, was within 10 µm of each other was 47%–62%. All physicians had disparities in RNFL thickness estimation greater than 30 µm.Conclusion: This study provides information on the ability of an experienced neuro- ophthalmologist to estimate the RNFL thickness based on fundus photos.Keywords: optical coherence tomography, OCT, RNFL, retinal nerve fiber, estimatio