PURPOSE: To review cytokine- and chemokine-mediated mechanisms of diffuse lamellar keratitis (DLK) after lamellar corneal surgical procedures. METHODS: Review of the basic science and clinical literature. RESULTS: DLK can occur early or late (months to decades) after all lamellar corneal surgeries, including laser in situ keratomileusis, small incision lenticule extraction, anterior lamellar keratoplasty, and Descemet's stripping automated endothelial keratoplasty. It is most commonly triggered by epithelial injury during or after lamellar surgery, which leads to the release of interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α from the epithelium and into the stroma. These chemokines directly attract inflammatory cells into the cornea from the limbal blood vessels and also bind to receptors on keratocytes and corneal fibroblasts where myriad chemokines are upregulated that also chemotactically attract monocytes, macrophages, granulocytes, lymphocytes, and other bone marrow-derived cells into the corneal stroma. Other factors that can trigger DLK include retained blood in the interface, endotoxins and other toxins, and excessive keratocyte necrosis caused by femtosecond lasers. Infiltrating cells show a preference to enter any lamellar interface in the cornea, regardless of the time since surgery, because of the ease of movement toward the chemotactic attractants relative to the surrounding stroma with intact collagen lamellae and stromal cells that serve as relative barriers impeding motility. The mainstay of treatment is topical corticosteroids, but severe cases may also be treated with flap lift irrigation and systemic corticosteroids. CONCLUSIONS: DLK can occur early or late after any lamellar corneal surgical procedure and is most commonly triggered by epithelial-stromal-bone marrow-derived cellular interactions mediated by corneal cytokines and chemokines. [J Refract Surg. 2020;36(2):124-130.]. Copyright 2020, SLACK Incorporated.
PURPOSE: To review cytokine- and chemokine-mediated mechanisms of diffuse lamellar keratitis (DLK) after lamellar corneal surgical procedures. METHODS: Review of the basic science and clinical literature. RESULTS: DLK can occur early or late (months to decades) after all lamellar corneal surgeries, including laser in situ keratomileusis, small incision lenticule extraction, anterior lamellar keratoplasty, and Descemet's stripping automated endothelial keratoplasty. It is most commonly triggered by epithelial injury during or after lamellar surgery, which leads to the release of interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α from the epithelium and into the stroma. These chemokines directly attract inflammatory cells into the cornea from the limbal blood vessels and also bind to receptors on keratocytes and corneal fibroblasts where myriad chemokines are upregulated that also chemotactically attract monocytes, macrophages, granulocytes, lymphocytes, and other bone marrow-derived cells into the corneal stroma. Other factors that can trigger DLK include retained blood in the interface, endotoxins and other toxins, and excessive keratocyte necrosis caused by femtosecond lasers. Infiltrating cells show a preference to enter any lamellar interface in the cornea, regardless of the time since surgery, because of the ease of movement toward the chemotactic attractants relative to the surrounding stroma with intact collagen lamellae and stromal cells that serve as relative barriers impeding motility. The mainstay of treatment is topical corticosteroids, but severe cases may also be treated with flap lift irrigation and systemic corticosteroids. CONCLUSIONS: DLK can occur early or late after any lamellar corneal surgical procedure and is most commonly triggered by epithelial-stromal-bone marrow-derived cellular interactions mediated by corneal cytokines and chemokines. [J Refract Surg. 2020;36(2):124-130.]. Copyright 2020, SLACK Incorporated.