Abstract
This review is in two sections. The first section summarises 35 conditions, both common and infrequent, causing cicatrising conjunctivitis. Guidelines for making a diagnosis are given together with the use of diagnostic tests, including direct and indirect immunofluorescence, and their interpretation. The second section evaluates our knowledge of ocular mucous membrane pemphigoid, which is the commonest cause of cicatrizing conjunctivitis in most developed countries. The clinical characteristics, demographics, and clinical signs of the disease are described. This is followed by a review and re-evaluation of the pathogenesis of conjunctival inflammation in mucous membrane pemphigoid (MMP), resulting in a revised hypothesis of the autoimmune mechanisms causing inflammation in ocular MMP. The relationship between inflammation and scarring in MMP conjunctiva is described. Recent research, describing the role of aldehyde dehydrogenase (ALDH) and retinoic acid (RA) in both the initiation and perpetuation of profibrotic activity in MMP conjunctival fibroblasts is summarised and the potential for antifibrotic therapy, using ALDH inhibition, is discussed. The importance of the management of the ocular surface in MMP is briefly summarised. This is followed with the rationale for the use of systemic immunomodulatory therapy, currently the standard of care for patients with active ocular MMP. The evidence for the use of these drugs is summarised and guidelines given for their use. Finally, the areas for research and innovation in the next decade are reviewed including the need for better diagnostics, markers of disease activity, and the potential for biological and topical therapies for both inflammation and scarring.
Highlights
It is a great privilege to have been asked to give this lecture and I am very grateful to the Scientific Committee of the College for inviting me to undertake it
In recently published studies[78] we have identified that the aldehyde dehydrogenase (ALDH)/retinoic acid (RA) metabolic pathway regulates this profibrotic activity in ocular membrane pemphigoid (MMP) conjunctival fibroblasts in vitro
We have shown that ALDH is overexpressed in ocular MMP conjunctiva at the gene and protein level, compared with controls, and that ALDH inhibition with disulfiram abolished the profibrotic phenotype in MMP conjunctiva, resulting in the adoption of a normal control phenotype
Summary
It is a great privilege to have been asked to give this lecture and I am very grateful to the Scientific Committee of the College for inviting me to undertake it. Effector cells and proteins Circulating autoreactive T cells to BP180 Neutrophils, macrophages, dendritic cells, Th (CD4), Tc (CD8), plasma cells. (TGFβ FGF and PDGF)
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