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Original Investigation
October 5, 2020

Trends in Optic Neuritis Incidence and Prevalence in the UK and Association With Systemic and Neurologic Disease

Author Affiliations
  • 1Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom
  • 2The Medical Eye Unit, Guys’ and St Thomas’ Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
  • 3Centre for Rheumatic Diseases, King’s College London, London, United Kingdom
  • 4Neuro-Ophthalmology Department, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
  • 5Neuro-Ophthalmology Department, The National Hospital for Neurology and Neurosurgery, London, United Kingdom
  • 6Queen Square Institute of Neurology, University College London, London, United Kingdom
  • 7Biomedical Research Centre (Moorfields Eye Hospital/University College London), London, United Kingdom
  • 8Birmingham Neuro-Ophthalmology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, United Kingdom
  • 9Health Data Research UK, London, United Kingdom
  • 10Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
JAMA Neurol. Published online October 5, 2020. doi:10.1001/jamaneurol.2020.3502
Key Points

Question  What are trends in optic neuritis (ON) incidence and prevalence and the associations with systemic and neurologic disease?

Findings  This cohort study of more than 11 million patients found an ON incidence of 3.7 per 100 000 person-years, affecting 115 per 100 000 population in 2018 (76 279 people in the United Kingdom). Case-control and matched cohort analyses identify a strong association with multiple sclerosis (MS) and weaker associations with Behçet disease, sarcoidosis, and Sjögren syndrome, among others.

Meaning  The incidence of ON is stable and predominantly associated with MS. Numerous other disease associations, individually rare, indicate that a significant number of patients without MS but with ON require urgent management to preserve sight.

Abstract

Importance  Epidemiologic data on optic neuritis (ON) incidence and associations with immune-mediated inflammatory diseases (IMIDs) are sparse.

Objective  To estimate 22-year trends in ON prevalence and incidence and association with IMIDs in the United Kingdom.

Design, Setting, and Participants  This cohort study analyzed data from The Health Improvement Network from January 1, 1995, to September 1, 2019. The study included 10 937 511 patients 1 year or older with 75.2 million person-years’ follow-up. Annual ON incidence rates were estimated yearly (January 1, 1997, to December 31, 2018), and annual ON prevalence was estimated by performing sequential cross-sectional studies on data collected on January 1 each year for the same period. Data for 1995, 1996, and 2019 were excluded as incomplete. Risk factors for ON were explored in a cohort analysis from January 1, 1997, to December 31, 2018. Matched case-control and retrospective cohort studies were performed using data from January 1, 1995, to September 1, 2019, to explore the odds of antecedent diagnosis and hazard of incident diagnosis of 66 IMIDs in patients compared with controls.

Exposures  Optic neuritis.

Main Outcomes and Measures  Annual point prevalence and incidence rates of ON, adjusted incident rate ratios (IRRs) for risk factors, and adjusted odds ratios (ORs) and adjusted hazard ratios (HRs) for 66 IMIDs.

Results  A total of 10 937 511 patients (median [IQR] age at cohort entry, 32.6 [18.0-50.4] years; 5 571 282 [50.9%] female) were studied. A total of 1962 of 2826 patients (69.4%) with incident ON were female and 1192 of 1290 92.4%) were White, with a mean (SD) age of 35.6 (15.6) years. Overall incidence across 22 years was stable at 3.7 (95% CI, 3.6-3.9) per 100 000 person-years. Annual point prevalence (per 100 000 population) increased with database maturity, from 69.3 (95% CI, 57.2-81.3) in 1997 to 114.8 (95% CI, 111.0-118.6) in 2018. The highest risk of incident ON was associated with female sex, obesity, reproductive age, smoking, and residence at higher latitude, with significantly lower risk in South Asian or mixed race/ethnicity compared with White people. Patients with ON had significantly higher odds of prior multiple sclerosis (MS) (OR, 98.22; 95% CI, 65.40-147.52), syphilis (OR, 5.76; 95% CI, 1.39-23.96), Mycoplasma (OR, 3.90; 95% CI, 1.09-13.93), vasculitis (OR, 3.70; 95% CI, 1.68-8.15), sarcoidosis (OR, 2.50; 95% CI, 1.21-5.18), Epstein-Barr virus (OR, 2.29; 95% CI, 1.80-2.92), Crohn disease (OR, 1.97; 95% CI, 1.13-3.43), and psoriasis (OR, 1.28; 95% CI, 1.03-1.58). Patients with ON had a significantly higher hazard of incident MS (HR, 284.97; 95% CI, 167.85-483.81), Behçet disease (HR, 17.39; 95% CI, 1.55-195.53), sarcoidosis (HR, 14.80; 95% CI, 4.86-45.08), vasculitis (HR, 4.89; 95% CI, 1.82-13.10), Sjögren syndrome (HR, 3.48; 95% CI, 1.38-8.76), and herpetic infection (HR, 1.68; 95% CI, 1.24-2.28).

Conclusions and Relevance  The UK incidence of ON is stable. Even though predominantly associated with MS, ON has numerous other associations with IMIDs. Although individually rare, together these associations outnumber MS-associated ON and typically require urgent management to preserve sight.

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