Epidemiological analysis of inflammatory eye and central nervous system conditions and their risk factors, association with infectious and immune-mediated inflammatory diseases, and health impacts. A UK population-based observational study

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Date of Approval
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Lay Summary

The eye and spinal cord are part of the nervous system and can rarely become inflamed in response to infections, immune system diseases, vaccination or certain medicines. Inflammation can threaten sight, or strength and feeling in the body. Timely diagnosis and treatment can prevent permanent damage, but treatments may cause other health problems. Some tests used to work out the underlying causes, and some treatments, are expensive and it can be challenging to determine which ones are most helpful.

Lack of data on these rare inflammatory conditions of the eye and spinal cord has made it difficult to:
i) anticipate current and future NHS workforce needs;
ii) anticipate future demand for high-cost treatments;
iii) order appropriate tests; and
iv) understand health and vision outcomes.

Our study aims to extend previous research on a smaller dataset from a UK primary care records database to better understand eye and spinal cord inflammation. We will estimate how common these types of inflammation are in the population, and whether that changed during the COVID-19 pandemic. We will estimate how frequently these inflammatory conditions are linked to an underlying disease, vaccine or medicine, consider risk factors for their onset, and their impacts on the eye and general health. These findings could support improvement in NHS healthcare services.

Technical Summary

Background: Tissues within the eye are an extension of the central nervous system (CNS). They may become inflamed in infectious and immune-mediated inflammatory diseases (I-IMIDs), or following COVID-19 vaccination, or medications (e.g bisphosphonates), with irreversible damage and loss of function. Associated I-IMID diagnosis (e.g multiple sclerosis, rheumatoid arthritis, syphilis) may precede presentation or follow months or years later. Treatment also carries risk of complications.

To replicate and extend previous primary care record analyses of uveitis, scleritis, and optic neuritis, to add associated phenotypes including episcleritis, peripheral ulcerative keratitis, and transverse myelitis;
1) To estimate 10-year incidence/prevalence trend (2013-2022), before/during COVID-19 pandemic;
2) To estimate how incidence rate varies by established risk factors including age group, sex, ethnicity, body mass index, smoking, latitude, and vitamin D deficiency;
3) To comprehensively and systematically estimate frequency and strength of association with associated I-IMIDs diagnosed before or after incident eye/CNS inflammation, or with preceding associated medications, or COVID-19 vaccination;
4) To estimate negative health impacts including hazard of ocular complications, sight impairment registration, neurological disability, incident depression/anxiety, diabetes, hypertension, sepsis, fragility fracture, cancer, and infertility.

Methods: Population: Patients aged >1 year with a recorded diagnosis of an inflammatory eye condition (uveitis, scleritis, episcleritis, peripheral ulcerative keratitis, optic neuritis or transverse myelitis). Study designs: Cross-sectional (2013-2022), population cohort, and matched case-control and matched cohort study designs (all years). Statistical analyses: annual incidence, annual point prevalence, multivariable Poisson regression analysis offsetting for person-years, multivariable logistic regression analysis and multivariable Cox proportional hazards regression analysis. Matching 1:4 on age, sex, region and deprivation index. Additional adjustment variables may include ethnicity, BMI, nation, smoking, vitamin D and COVID-19 vaccination status.

The findings could support workfoce planning, estimating demand for immunosuppressives, including high-cost biologics, targeting investigations and referrals, and quantifying health outcomes.

Health Outcomes to be Measured

Primary outcome
• Frequency and strength (odds and/or hazard ratio) of association between incident inflammatory eye and central nervous system conditions (and their subtypes) and I-IMIDs (preceding or following eye/CNS inflammatory condition diagnosis), or preceding covid-19 vaccination, or preceding associated medication.
Key secondary outcomes for inflammatory eye/CNS conditions (and subtypes):
• Annual point prevalence and trend 2013 to 2022;
• Annual incidence rate and trend 2013 to 2022;
• Cumulative incidence rate ratio, by associated risk factor variables;
• Hazard of negative health outcomes of inflammation or its treatment: vision impairment; sight impairment registration; neurological disability (wheelchair use); ocular complications; incident depression/anxiety, diabetes, hypertension, sepsis, fragility fracture, cancer, or infertility.


Tasanee Braithwaite - Chief Investigator - King's College London (KCL)
Benjamin Zuckerman - Corresponding Applicant - King's College London (KCL)
- Collaborator -
Alasdair Warwick - Collaborator - University College London ( UCL )
Alastair Denniston - Collaborator - University of Birmingham
axel petzold - Collaborator - University College London ( UCL )
Chiara Rocchi - Collaborator - Walton Centre NHS
James Galloway - Collaborator - King's College London (KCL)
Mark Russell - Collaborator - King's College London (KCL)
Martin Gulliford - Collaborator - King's College London (KCL)
Nicola Adderley - Collaborator - University of Birmingham
Pavel Loginovic - Collaborator - University of Exeter
Saif Huda - Collaborator - Walton Centre NHS
Tsz Lun Ernest Wong - Collaborator - King's College London (KCL)