From the Guidelines
Matrix metalloproteinases (MMPs) play a crucial role in the pathophysiology of ocular rosacea, contributing to inflammation and tissue damage on the ocular surface.
Role of MMPs in Ocular Rosacea
The elevated MMP activity, particularly MMP-9, in the tear film and ocular tissues of patients with ocular rosacea, breaks down extracellular matrix proteins and disrupts the integrity of the corneal epithelium, leading to symptoms like eye dryness, irritation, and corneal epithelial defects 1.
Mechanism of Action
MMPs are released by inflammatory cells and activated by pro-inflammatory cytokines, contributing to the degradation of tight junction proteins between epithelial cells, compromising the ocular surface barrier function 1.
Treatment Approaches
Treatment approaches that target inflammation, such as tetracycline antibiotics (doxycycline 40-100mg daily), work partly by inhibiting MMP activity, helping to restore ocular surface homeostasis and reduce symptoms in patients with ocular rosacea 1. Some key points to consider:
- The use of doxycycline 40mg daily has been shown to be effective in reducing inflammatory lesions in patients with rosacea 1
- The treatment of ocular rosacea may involve a combination of topical and oral medications, as well as lifestyle modifications 1
- The global ROSacea COnsensus (ROSCO) panel recommends a phenotype-led approach to rosacea management, addressing individual rosacea features 1
From the Research
Role of Matrix Metalloproteinase in Ocular Rosacea
- Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play a crucial role in various inflammatory conditions, including ocular rosacea 2, 3, 4.
- In ocular rosacea, MMP-8 levels and activation are commonly elevated, reflecting increased inflammatory activity 2.
- The mean MMP-8 concentration in tear fluid is statistically significantly higher in ocular rosacea patients than in normal subjects, and decreases after treatment with oral doxycycline 2.
- MMP-8 activation is present only in ocular rosacea samples and is inhibited by oral doxycycline, suggesting that doxycycline effectively reduces pathologically excessive levels and activation of MMP-8 2.
Treatment of Ocular Rosacea
- Topical antimicrobials, oral antibiotics, intense pulsed light, and cyclosporine ophthalmic emulsion are the most efficacious single modality treatments for ocular rosacea 5.
- Doxycycline, a systemic antibiotic, has been shown to be effective in reducing MMP-8 levels and activation, as well as relieving patients' subjective symptoms 2, 6.
- Systemic tetracyclines, such as doxycycline, act multifactorially by decreasing bacterial flora and the expression of matrix metalloproteinases, altering meibum secretion, inhibiting the production of bacterial lipases, and providing an immunomodulatory effect 4.
Matrix Metalloproteinase 9 in Ocular Surface Disorders
- MMP-9 overexpression has been found in various ocular surface diseases, including dry eye disease, corneal ulceration, and microbial keratitis 3.
- MMP-9 is involved in an intricate signal transduction cascade that includes induction by many proinflammatory molecules, and its expression is blunted by a diverse array of molecular factors, such as tissue inhibitors of metalloproteinases and cyclosporine A 3.
- Inhibition of MMP-9 frequently leads to improvement of ocular surface disease, providing potential for new therapeutic modulations of ocular surface diseases mediated by its overexpression 3.