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

Abstract

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.

Surgery-induced necrotizing scleritis after vitrectomy with removal of dislocated intraocular lens and secondary iris-claw IOL implantation

“…A better understanding of the immunopathogenesis of ocular in ammatory diseases, as well as the development of new molecules, has enriched our therapeutic arsenal and created more effective treatment approaches 10,11 . Monoclonal antibodies against TNF-α (all except Etanercept), IL-1 inhibitors (Anakinra), IL-6 inhibitors (Tocilizumab), and anti-CD20 (Rituximab) targeted-drugs have been shown to control in ammation and reduce scleritis ares, allowing for a corticosteroid-sparing effect 5,8,10,11 . TNF-α inhibitors like Adalimumab or In iximab are used as rst-line biological agents 12,13 .…”

Comparison of Intestinal Microbes in Noninfectious Anterior Scleritis Patients With and Without Rheumatoid Arthritis

“…The mechanisms of these microbes involved in the occurrence of scleritis are not completely clear. It has been proven that increases in IL-1β, TNF-α and IL-6 play a key role in the pathogenesis of scleritis and that biological agents such as antitumor necrosis factor agents and interleukin-1 and interleukin-6 inhibitors control scleral inflammation either in an idiopathic manner or in a background of immune-mediated systemic disorders ( Sota et al, 2021 ). Romboutsia and Turicibacter are positively related to IL-6, IL-1β, TNF-α, IL-23 and IFN-γ ( Bosshard et al, 2002 ; Munyaka et al, 2016 ; Li et al, 2020 ).…”

Plasmapheresis as a viable treatment option for scleritis

“…Currently, mainstay therapy for non-infectious scleritis consists of NSAIDs, steroids and various steroid sparing immunomodulatory therapies. 1 , 2 , 3 Many of these treatments have side effects and/or contraindications. Scleritis can be recalcitrant and is not always responsive to traditional therapy.…”