Abstract
Scleritis is a severe and extremely painful inflammation of the outer coat of the eye,
commonly leading to visual-threatening complications. The pathogenesis of scleritis is
suggested to be immune-mediated. However, the exact immunological cells and substances involved remain unclear, and research into this topic has been scarce so far. In the clinic, this lack of information complicates the clinical management of scleritis, currently leaving doctors and patients in the dark about their future prognosis.
The work presented in this thesis aims to increase our knowledge of the pathogenesis of
non-infectious scleritis, specifically its immunological origin. Also, the work aims to address
and evaluate current difficulties in the clinical management of patients with scleritis. To fulfill
these aims we prospectively collected a national cohort of scleritis patients in the period of
2020 to 2022 within 5 Dutch University Medical Centers. In addition, we included healthy
controls and relevant disease controls, i.e. uveitis and rheumatoid arthritis (RA) patients. From all included subjects relevant clinical data and biological material was obtained, including scarcely available ocular tissue samples affected by scleritis. Lastly, we prospectively collected optical coherence tomography (OCT) scans of the anterior sclera of healthy individuals of various ages.
In conclusion, the studies described in this thesis provide further evidence for autoimmunity in scleritis by identifying a novel autoantibody in patients with scleritis. We also noticed signs of fibrosis and neovascularization in scleritis, and identified several biomarker candidates. These candidates may provide a novel foundation for future research into scleritis (immune-mediated) pathogenesis, clinical diagnosis and prognosis, and potential therapeutic targets. Lastly, we underline the beneficial effect of the B-cell targeting agent RTX, and provide recommendations how to use RTX after the induction phase. Ultimately, this may improve patient management and enrich the potential for novel treatment modalities for this serious eye disease.
commonly leading to visual-threatening complications. The pathogenesis of scleritis is
suggested to be immune-mediated. However, the exact immunological cells and substances involved remain unclear, and research into this topic has been scarce so far. In the clinic, this lack of information complicates the clinical management of scleritis, currently leaving doctors and patients in the dark about their future prognosis.
The work presented in this thesis aims to increase our knowledge of the pathogenesis of
non-infectious scleritis, specifically its immunological origin. Also, the work aims to address
and evaluate current difficulties in the clinical management of patients with scleritis. To fulfill
these aims we prospectively collected a national cohort of scleritis patients in the period of
2020 to 2022 within 5 Dutch University Medical Centers. In addition, we included healthy
controls and relevant disease controls, i.e. uveitis and rheumatoid arthritis (RA) patients. From all included subjects relevant clinical data and biological material was obtained, including scarcely available ocular tissue samples affected by scleritis. Lastly, we prospectively collected optical coherence tomography (OCT) scans of the anterior sclera of healthy individuals of various ages.
In conclusion, the studies described in this thesis provide further evidence for autoimmunity in scleritis by identifying a novel autoantibody in patients with scleritis. We also noticed signs of fibrosis and neovascularization in scleritis, and identified several biomarker candidates. These candidates may provide a novel foundation for future research into scleritis (immune-mediated) pathogenesis, clinical diagnosis and prognosis, and potential therapeutic targets. Lastly, we underline the beneficial effect of the B-cell targeting agent RTX, and provide recommendations how to use RTX after the induction phase. Ultimately, this may improve patient management and enrich the potential for novel treatment modalities for this serious eye disease.
Original language | English |
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Awarding Institution |
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Supervisors/Advisors |
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Award date | 14 Feb 2024 |
Place of Publication | Rotterdam |
Print ISBNs | 978-94-91811-38-8 |
Publication status | Published - 14 Feb 2024 |