Current insights in the pathogenesis of scleritis

Vergouwen, Daphne P. C.; Rothová, Aniki; Berge, Josianne C. ten; Verdijk, Robert M.; Laar, Jan A. M. van; Vingerling, J. R.; Schreurs, Marco W. J.

doi:10.1016/j.exer.2020.108078

Cited by 33 publications

(24 citation statements)

References 96 publications

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“…Conventional pathological analysis of scleritis has relied on histopathological analysis of clinically removed eyes. The histopathological findings from these clinically removed eyes represent the terminal results of unhealed scleritis modified by various treatments [ 32 , 33 , 34 , 35 ]. Such methods of analysis are inadequate to achieve a sound understanding of the pathogenesis underlying scleritis.…”

Section: Discussionmentioning

confidence: 99%

Immunopathological Analysis of a Mouse Model of Arthritis-Associated Scleritis and Implications for Molecular Targeted Therapy for Severe Scleritis

Nishio

Taniguchi

Takeda

et al. 2021

IJMS

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Scleritis involves inflammation of the sclera, which constitutes 75% of the wall of the eye. This pathology is often seen as an ocular lesion associated with systemic inflammatory diseases. Severe types of scleritis such as posterior scleritis require urgent immunosuppressive treatments, including molecularly targeted therapies to avoid permanent visual impairment. Which molecules should be selected as targets has remained unclear. To clarify the pathogenesis of scleritis and propose appropriate target molecules for therapy, we have established novel animal model of scleritis by modifying the Collagen-II Induced Arthritis (CIA) model. Immunization twice with collagen II emulsified with complete Freund’s adjuvant (CFA) caused arthritis and scleritis. The clinical appearance resembled human diffuse scleritis. Histopathological analysis suggested that macrophages, plasma cells, deposition of immune complexes, and growth of blood and lymphatic vessels are involved in the pathogenesis of CIA-associated scleritis. In addition, we analysed the background diseases of posterior scleritis and responses to molecularly targeted therapies as a case series study. We inferred from both the animal model and case series study that targets should not be T cells, but factors inhibiting macrophage activity such as tumor necrosis factor (TNF) and interleukin (IL)-6, and molecules suppressing antibody-producing cells such as CD20 on B cells should be targeted by molecularly targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Immunopathological Analysis of a Mouse Model of Arthritis-Associated Scleritis and Implications for Molecular Targeted Therapy for Severe Scleritis

Nishio

Taniguchi

Takeda

et al. 2021

IJMS

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“…Scleritis is an infrequent inflammatory disorder of the sclera that may be caused by infectious factors, trauma, drugs or irradiation, and one that frequently accompanies immune-mediated diseases. The immune system appears to play an important role in the pathogenesis of non-infectious scleritis [ 142 ]. Therefore, there is an association between scleritis and vitamin D, which is able to suppress the immune response mainly by the modulation of T lymphocyte activity.…”

Section: Vitamin D Vdr and Calcitriol Analogues In Ocular Diseasesmentioning

confidence: 99%

Vitamin D, the Vitamin D Receptor, Calcitriol Analogues and Their Link with Ocular Diseases

Caban

Lewandowska

2022

Nutrients

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The global prevalence of eye diseases continues to grow, bringing with it a reduction in the activity levels and quality of life of patients, and partial or complete blindness if left untreated. As such, there is considerable interest in identifying more effective therapeutic options and preventive agents. One such agent is vitamin D, known to have a range of anti-cancer, anti-angiogenic, anti-inflammatory and anti-oxidative properties, and whose deficiency is linked to the pathogenesis of a range of cardiovascular, cancer, and inflammatory diseases. This review presents the current stage of knowledge concerning the link between vitamin D and its receptor and the occurrence of eye disease, as well as the influence of analogues of calcitriol, an active metabolite of vitamin D. Generally, patients affected by various ocular disorders have vitamin D deficiency. In addition, previous findings suggest that vitamin D modulates the course of eye diseases and may serve as a marker, and that its supplementation could mitigate some disorders. However, as these studies have some limitations, we recommend further randomized trials to clarify the link between vitamin D and its activity with eye disease.

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“…Both innate and adaptive immunity may be advocated as the driving mechanisms leading to tissue damage, with a pivotal role played by inflammatory cytokines such as TNFa and IL-1, which in turn induce the secretion of matrix metalloproteinases from infiltrating inflammatory cells and stromal scleral fibroblasts [1]. Despite being hard to pinpoint where non-infectious scleritis is exactly situated in the immunological disease continuum [95], it is safe to assume that the pathophysiological mechanisms are largely dependent on the underlying systemic disease, if present. Indeed, many authors believe that non-infectious scleritis associated with systemic disorders represents an immune complex-mediated condition, whereas idiopathic scleritis may arise after a delayed hypersensitivity reaction [96].…”

Section: Closing Remarksmentioning

confidence: 99%

Biologic Therapies and Small Molecules for the Management of Non-Infectious Scleritis: A Narrative Review

et al. 2021

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Scleritis refers to a wide spectrum of ocular conditions ranging from mild to sight-threatening scleral inflammation that may compromise visual function and threaten the anatomical integrity of the ocular globe. Most aggressive forms like necrotizing or posterior scleritis are often difficult-to-treat cases, refractory to conventional treatment. The association with systemic diseases, namely rheumatoid arthritis, Sjögren syndrome, granulomatosis with polyangiitis, and relapsing polychondritis, may have prognostic implications as well. A better understanding of the pathogenesis of ocular inflammatory diseases have paved the way to more effective and targeted treatment approaches. In this regard, a growing body of evidence supports the potential role of biologic agents in the management of non-infectious scleral inflammation, either idiopathic or in a background of immune-mediated systemic disorders. Biologic agents such as anti-tumor necrosis factor agents, interleukin-1 and interleukin-6 inhibitors as well as CD20 blockade have displayed promising results. More specifically, several studies have reported their ability to control scleral inflammation, reduce the overall scleritis relapses, and allow a glucocorticoid-sparing effect while being generally well tolerated. Anecdotal reports have also been described with other biologic agents including abatacept, ustekinumab, daclizumab, and alemtuzumab as well as targeted small molecules such as tofacitinib. Further studies are warranted to fully elucidate the role of biologic agents in non-infectious scleritis and investigate specific areas with the aim to administer treatments in the context of personalized medicine. This review summarizes the available data regarding clinical trials, small pilot studies, and real-life experience of the last two decades reporting the use of biologic agents in the management of non-infectious scleritis.

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Current insights in the pathogenesis of scleritis

Cited by 33 publications

References 96 publications

Immunopathological Analysis of a Mouse Model of Arthritis-Associated Scleritis and Implications for Molecular Targeted Therapy for Severe Scleritis

Immunopathological Analysis of a Mouse Model of Arthritis-Associated Scleritis and Implications for Molecular Targeted Therapy for Severe Scleritis

Vitamin D, the Vitamin D Receptor, Calcitriol Analogues and Their Link with Ocular Diseases

Biologic Therapies and Small Molecules for the Management of Non-Infectious Scleritis: A Narrative Review

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