By Marc Dinkin, MD
Director of Neuro-Ophthalmology; Associate Professor, Departments of Ophthalmology and Neurology, Weill Cornell Medical College
Dr. Dinkin reports he is a consultant for Serenity Medical, Inc.
In this population-based study of 11 million people in the United Kingdom, the incidence of optic neuritis was 3.7/100,000 person years, and was stable over the time period 1995-2019. The 10-year risk of developing multiple sclerosis in this population was 28.2%.
Braithwaite T, Subramanian A, Petzold A, et al. Trends in optic neuritis incidence and prevalence in the UK and association with systemic and neurologic disease. JAMA Neurol 2020 Oct 5;e203502. doi:10.1001/jamaneurol.2020.3502. [Online ahead of print].
The prospective Optic Neuritis Treatment Trial taught us much about the range and time course of vision loss in optic neuritis (ON), its association with multiple sclerosis, and the effect of intravenous corticosteroids on the speed of recovery.1 However, there were many questions that this landmark 457-patient trial could not answer: What is the prevalence of ON and is it changing over time? Are there systemic inflammatory conditions that are rarely associated with ON? Using the United Kingdom’s Health Improvement Network (THIN), Braithwaite and colleagues set out to answer such questions, studying a cohort of nearly 11 million patients between 1995 and 2019, with a total of 75.2 million person-years’ follow-up. In this large population, they found an incidence of 3.7/100,000 person years (0.77 in children and 4.5 in adults), which was stable during the study period, and a prevalence on the first of each year that ranged from 69.3 to 114.8/100,000 people.
Comparing the 2,894 study patients with ON with study controls without ON, the authors identified higher odds of a baseline diagnosis of neuro-inflammatory disease, including multiple sclerosis (MS), neuromyelitis optica (NMO), and Cogan’s syndrome, as well as systemic inflammatory disease, such as sarcoidosis, vasculitis, Crohn’s disease, granulomatosis with polyangiitis, Sjögren’s syndrome, Behçet disease, and psoriasis. Rates of certain infections — mycoplasma, syphilis, herpes zoster, and Epstein-Barr virus — also were higher in patients with ON. Surprisingly, patients with ON were more likely to have had giant cell arteritis in the past or to develop it in the future than controls. Ocular inflammation, including scleritis and uveitis, also was more likely in ON patients than in controls. Demographic risk factors included female sex, age 21-30 years, Caucasian race, and, more surprisingly, obesity and a history of smoking. The risk of MS over a 10-year period was found to be 28.2%, compared to 0.1% in controls. This was less than the nearly 40% risk of MS at 10 years seen in the Optic Neuritis Treatment Trial.
COMMENTARY
The results of this study add a great deal to our understanding of the epidemiology of ON and some of the systemic and ocular inflammatory conditions and infectious diseases that patients with ON may be at risk to develop. However, its results need to be interpreted with caution because the diagnoses were derived from administrative and billing codes that were also used to ascertain not only “optic neuritis” but also “meningococcal optic neuritis,” “syphilitic retrobulbar neuritis,” and “syphilitic optic atrophy.” Therefore, an association with syphilis is not too surprising. But even had the search been limited to “optic neuritis,” the truth is that many practitioners will label any inflammation of the optic nerve with this moniker for the purposes of billing. This could explain the surprising association of ON with a history of giant cell arteritis, which causes anterior ischemic optic neuropathy and optic atrophy, but occurs in the elderly and would not be expected to precede true optic neuritis. Furthermore, inflammation of the optic disc in the absence of retrobulbar optic nerve enhancement is technically considered a papillitis, but is often coded as “optic neuritis.” This is significant because papillitis may occur along with posterior uveitis or scleritis and is associated with many of the systemic inflammatory diseases found in this study. It is unclear what proportion of the ON cases in the study were papillitis, as opposed to the sort of retrobulbar ON with pain on eye movement that is associated with NMO, MS, and myelin oligodendrocyte glycoprotein. Even the association with smoking and obesity could simply reflect misclassification of nonarteritic anterior ischemic optic neuropathy as optic neuritis. A contamination of the group with non-demyelinating ON cases also would explain the lower risk of future MS than was found in the Optic Neuritis Treatment Trial. Despite these limitations, this study retains great value, as it puts into focus the broad range of inflammatory and infectious diseases that should be considered in patients who present with optic nerve inflammation.
REFERENCE
- Beck RW, Cleary PA, Anderson MM, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med 1992;326:581-588.
