Topical corticosteroids are effective in reducing anterior segment inflammation but are associated with adverse drug reactions (ADRs) including elevation of intraocular pressure (IOP) and cataract formation. Retrometabolic drug design has advanced the development of new corticosteroids with improved therapeutic indices. Engineered from prednisolone, loteprednol etabonate (LE) has a 17α-chloromethyl ester, in lieu of a ketone group, and a 17β-etabonate group. LE is highly lipophilic and binds with high affinity to the glucocorticoid receptor; any unbound LE is metabolized to inactive metabolites. LE has been studied in several anterior segment inflammatory conditions (giant papillary conjunctivitis, allergic conjunctivitis, anterior uveitis, and keratoconjunctivitis sicca), and in postoperative ocular inflammation and pain. Combined with tobramycin, it is effective in blepharokeratoconjunctivitis. Elevations in IOP are infrequent with LE, and the absence of a C-20 ketone precludes formation of Schiff base intermediates with lens proteins, a common first step implicated in cataract formation with ketone steroids. 1. Introduction The eye is vulnerable to damage from relatively low levels of intraocular inflammation. The blood-aqueous and blood-retinal barriers usually limit penetration of protein and cells from the peripheral circulation, while regulatory molecules and cells in the eye actively suppress immunologic responses [1]. Nevertheless, ocular inflammatory conditions and surgical trauma induce changes in the blood-aqueous and blood-retinal barriers [1–3]. As a result, immune cells and mediators of inflammation enter the eye, resulting in the classical clinical signs and symptoms of ocular inflammation including redness, pain, swelling, and itching [4]. Ocular inflammation, if left untreated, may lead to temporary or permanent loss of vision [5]. Topical corticosteroids are useful for the management of anterior segment inflammation. Corticosteroids elicit numerous potent anti-inflammatory effects [6]. For instance, they suppress cellular infiltration, capillary dilation, the proliferation of fibroblasts, collagen deposition, and eventually scar formation; they stabilise intracellular and extracellular membranes; and they increase the synthesis of lipocortins that block phospholipase A2 and inhibit histamine synthesis in the mast cells. Inhibition of phospholipase A2 prevents the conversion of phospholipids to arachidonic acid, a critical step in the inflammatory cascade. Corticosteroids also increase the enzyme histaminase and modulate transcription
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