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Objectives: (1) To explore the role and significance of Matrix Metalloproteinase 9 (MMP-9), a proteolytic enzyme, in various ocular surface diseases of inflammatory, infectious, and traumatic etiology (2), to further elucidate the molecular mechanisms responsible for its overexpression in ocular surface disease states, and (3) to discuss possible targets of therapeutic intervention. Methods: A literature review was conducted of primary sources from 1995 onward using search results populated from the US National Library of Medicine search database. Results: MMP-9 overexpression has been found in in vitro and in vivo models of dry eye disease (DED), corneal ulceration, microbial keratitis, corneal neovascularization, ultraviolet light-induced radiation, and a host of additional surface pathologies. MMP-9 is involved in an intricate signal transduction cascade that includes induction by many proinflammatory molecules including interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-a), nuclear factor kappa light chain enhancer of activated B cells (NF-kB), platelet-activating factor, activator protein 1 (AP-1), and transforming growth factor beta (TGF-B). MMP-9 expression is blunted by a diverse array of molecular factors, such as tissue inhibitors of metalloproteinases, cyclosporine A (CyA), PES_103, epigalloccatechin-3-gallate (EGCG), N-acetylcysteine (NaC), ascorbate, tetracyclines, and corticosteroids. Inhibition of MMP-9 frequently led to improvement of ocular surface disease. Conclusions: Novel insights into the mechanistic action of MMP-9 provide potential for new therapeutic modulations of ocular surface diseases mediated by its overexpression.

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Age-related macular degeneration AMD is one of the leading causes of blindness in the elderly population. An advanced form of AMD known as neovascular AMD (nAMD) is implicated as the main attributor of visual loss among these patients. The hallmark feature of nAMD is the presence of neovascular structures known as choroidal neovascular membranes (CNVs), along with fluid exudation, hemorrhages, and subretinal fibrosis. These pathological changes eventually result in anatomical and visual loss. A type of proangiogenic factor known as vascular endothelial growth factor (VEGF) has been known to mediate the pathological process behind nAMD. Therefore, therapy has transitioned over the years from laser therapy that ablates the lesions to using Anti-VEGF to target the pathology directly. In this work, we provide an overview of current and emerging therapies for the treatment of nAMD. Currently approved Anti-VEGF agents include ranibizumab, aflibercept, and brolucizumab. Bevacizumab, also an Anti-VEGF agent, is used to manage nAMD even though this is an off-label use. While Anti-VEGF agents have provided a favorable prognosis for nAMD, they are associated with a substantial financial burden for patients and the healthcare system, due to their high cost as well as the need for frequent repeat treatments and visits. Emerging therapies and studies aim to extend the intervals between required treatments and introduce new treatment modalities that would improve patients’ compliance and provide superior results.

Peripheral ulcerative keratitis (PUK) is a rare but serious ocular condition that is an important clinical entity due to its ophthalmological and systemic implications. It is characterized by progressive peripheral corneal stromal thinning with an associated epithelial defect and can be associated with an underlying local or systemic pro-inflammatory condition, or present in an idiopathic form (Mooren ulcer). Associated conditions include autoimmune diseases, systemic and ocular infections, dermatologic diseases, and ocular surgery. Cell-mediated and autoantibody- mediated immune responses have been implicated in the pathogenesis of PUK, destroying peripheral corneal tissue via matrix metalloproteinases. Clinically, patients with PUK present with painful vision loss, a peripheral corneal ulcer, and often adjacent scleritis, episcleritis, iritis, or conjunctivitis. Diagnostic evaluation should be focused on identifying the underlying etiology and ruling out conditions that may mimic PUK, including marginal keratitis and Terrien marginal degeneration. Treatment should be focused on reducing local disease burden with topical lubrication, while simultaneously addressing the underlying cause with antimicrobials or anti-inflammatory when appropriate. Existing and emerging biologic immunomodulatory therapies have proven useful in PUK due to autoimmune conditions. Surgical treatment is generally reserved for cases of severe thinning or corneal perforation.

The corneal epithelium serves to protect the underlying cornea from the external environment and is essential for corneal transparency and optimal visual function. Regeneration of this epithelium is dependent on a population of stem cells residing in the basal layer of the limbus, the junction between the cornea and the sclera. The limbus provides the limbal epithelial stem cells (LESCs) with an optimal microenvironment, the limbal niche, which strictly regulates their proliferation and differentiation. Disturbances to the LESCs and/or their niche can lead to the pathologic condition known as limbal stem cell deficiency (LSCD) whereby the corneal epithelium is not generated effectively. This has deleterious effects on the corneal and visual function, due to impaired healing and secondary corneal opacification. In this concise review, we summarize the characteristics of LESCs and their niche, and present the current and future perspectives in the management of LSCD with an emphasis on restoring the function of the limbal niche.