Ocular Myasthenia Gravis 32 years From Remission to Relapse

Ocular myasthenia gravis (OMG) is an autoimmune autoantibody-mediated disorder of acetylcholine receptors and/or other functionally related molecules at the postsynaptic neuromuscular junction.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Ocular Myasthenia Gravis 32 years From Remission to Relapse Ahmad Kharsa, BS, Subahari Raviskanthan, MBBS, Peter W. Mortensen, MD, Andrew G. Lee, MD O cular myasthenia gravis (OMG) is an autoimmune autoantibody–mediated disorder of acetylcholine receptors and/or other functionally related molecules at the postsynaptic neuromuscular junction. The systemic prognosis of OMG is variable with 50%–80% of cases progressing to generalized MG. In most cases, this progression happens within the first 2 years from the onset of ocular symptoms (1). We report an 82-year-old woman with OMG who had an initial diagnosis 32 years before her MG relapse. To the best of our knowledge, this the longest reported interval in the English language ophthalmic literature between diagnosis and relapse of MG. In 1987, a 49-year-old woman presented with variable and fatigable ptosis and diplopia. She had no systemic symptoms of MG. Her medical, surgical, social, and family histories were unremarkable. Serum antiacetylcholine receptor (AChR) antibodies were positive, and she was diagnosed with OMG. The patient was treated with prednisone for 1 year but developed multiple steroid-related side effects including weight gain and skin changes. The prednisone was tapered, and her ocular symptoms resolved. The patient was stable from 1987 to 2019 without recurrent ptosis, diplopia, or generalized weakness. In April 2019 (32 years after initial diagnosis), the patient returned to the neuro-ophthalmology service with painless, binocular diplopia, and right ptosis. She now had fatigable weakness in the distal upper and lower extremities worse with exertion and alleviated with rest. On neuro-ophthalmic examination, her visual acuity was 20/20 in both eyes. Her pupils were isocoric, and there was no relative afferent pupillary defect. The patient exhibited a School of Medicine (AK), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (SR, PWM, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; Texas A and M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute Houston Methodist Hospital, 6560 Fannin Street, Ste 450, Houston, TX 77030; E-mail: aglee@ houstonmethodist.org Kharsa et al: J Neuro-Ophthalmol 2023; 43: e45-e46 3-mm ptosis of the right upper lid with a Cogan lid twitch sign. MRI of the brain revealed no intracranial abnormalities. Computed tomography (CT) of the chest did not reveal a thymic mass. Repeat serologic testing for AChR antibodies, striational antibodies, and muscle-specific tyrosine kinase antibodies returned negative. Repetitive stimulation on nerve conduction studies revealed significant decrement of the right facial nerve (13%) and right ulnar nerve (14%) consistent with generalized MG. The patient had no other evidence clinically or radiographically for underlying neoplasm to suggest a paraneoplastic etiology for MG. A CT scan of the chest and abdomen was negative. Nerve conduction studies were also suggestive of MG with no other features of paraneoplastic neuropathy or myopathy, and the patient did not develop any cancer during the follow-up period. Initially, the patient was treated with an induction course of intravenous immunoglobulin (IVIG) and regular pyridostigmine. Her symptoms persisted, and she was subsequently commenced on azathioprine as a steroid sparing regimen. At her last review 21 months after her relapse, she continues to have improvement of her symptoms. The clinical course of OMG is variable but typically is characterized by periods of exacerbation, relapse, and remission. Approximately 50% of patients with OMG will progress to generalized MG within 2 years of diagnosis (1). Historical studies of OMG have estimated spontaneous remission to occur in 11%–30% of patients (ranging from a few months to 22 years) (1). Complete stable remission (CSR) is defined as a period of at least 1 year in which the patient has been free of symptoms and signs of MG and for which the patient has not received any disease-modifying therapy for MG (2). Table 1 summarizes cases from the literature with long remissions. Some patients with OMG respond to treatment, and CSR has been described in many patients with OMG (1,2). Other initially corticosteroid responsive patients with OMG however require maintenance of low-dose steroid therapy or immunosuppression (1). The patient’s symptoms and signs did not improve on pyridostigmine for 12 months after her induction dose of IVIG, and she declined additional therapy because of intolerable side effects of steroids. It is not known from the literature whether the disease is less likely to respond to treatment (e.g., steroids, pyridostigmine, or IVIG) in late relapses of MG. e45 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence TABLE 1. Longest remission periods found in the English ophthalmic literature for patients with ocular or generalized myasthenia gravis Author(s) Age of Year Patient Kataoka H, 2011 Furiya Y, Ueno S.3 Al-Hashel J, 2014 Rashad HM, Rousseff RT4 Rollinson RD, 1981 Fenichel GM.5 Rollinson RD, 1981 Fenichel GM.5 Type Symptoms Initial Treatment Duration of Remission Treatment after Relapse 12 GMG Ptosis, diplopia, and Oral prednisone respiratory dysfunction for 6 y 22 years Oral prednisone 33 OMG Ptosis and diplopia Oral pyridostigmine therapy for 5 mo 17 years Oral prednisone 15 OMG Ptosis and diplopia 14 years Oral prednisone 8 OMG Ptosis and diplopia Oral neostigmine therapy for 4 mo Oral pyridostigmine therapy for 3 y 5 years Oral prednisone GMG, generalized myasthenia gravis; OMG, ocular myasthenia gravis. With recent advances in minimal invasive surgery, there has been recent interest to study the role of thymectomy in the induction of CSR in patients with OMG. Recent studies have shown that thymectomy induced CSR in 40%–50% of patients at 5 years follow-up, regardless of the presence of thymic masses (2). In addition, others have shown that early thymectomy combined with early immunosuppression therapy from disease onset was associated with significantly longer periods of CSR and reduced risk of systemic generalization (1,2). Clinicians should be aware that although most patients with OMG generalize within the first 2 years, some patients may recur decades after initial diagnosis. To the best of our knowledge, however, this patient has the longest duration between diagnosis of OMG and the development of generalized MG in the English language ophthalmic literature. STATEMENT OF AUTHORSHIP Conception and design: A. Kharsa, S. Raviskanthan, P. W. Mortensen, A. G. Lee; Acquisition of data: A. Kharsa, S. Raviskanthan, P. W. e46 Mortensen, A. G. Lee; Analysis and interpretation of data: A. Kharsa, S. Raviskanthan, P. W. Mortensen, A. G. Lee. Drafting the manuscript: A. Kharsa, S. Raviskanthan, P. W. Mortensen, A. G. Lee; Revising it for intellectual content: A. Kharsa, S. Raviskanthan, P. W. Mortensen, A. G. Lee. Final approval of the completed manuscript: A. Kharsa, S. Raviskanthan, P. W. Mortensen, A. G. Lee. REFERENCES 1. Wong SH, Huda S, Vincent A, Plant GT. Ocular myasthenia gravis: controversies and updates. Curr Neurol Neurosci Rep. 2014;14:421. 2. Zhu K, Li J, Huang X, Xu W, Liu W, Chen J, Chen P, Feng H. Thymectomy is a beneficial therapy for patients with nonthymomatous ocular myasthenia gravis: a systematic review and meta-analysis. Neurol Sci. 2017;38:1753–1760. 3. Kataoka H, Furiya Y, Ueno S. Complete remission of generalized myasthenia gravis by corticosteroid treatment alone without thymectomy. Case Rep Neurol. 2011;3:239–241. 4. Al-Hashel J, Rashad HM, Rousseff RT. An adult patient with ocular myasthenia and unusually long spontaneous remission. Case Rep Neurol Med. 2014;2014:372769. 5. Rollinson RD, Fenichel GM. Relapsing ocular myasthenia. Neurology. 1981;31:325–326. Kharsa et al: J Neuro-Ophthalmol 2023; 43: e45-e46 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.