Ocular Surface Diseases

The cornea and conjunctiva are exposed to the environment and are thus susceptible to overexposure to light, radiation, chemicals, and airborne pathogens and allergens. Consequently, ocular surface infections, allergies, dryness, and ulcerations represent the major disorders of the cornea and conjunctiva. While these conditions are not blinding by themselves, they severely limit the quality of life for millions of people. Antiallergic Drugs

Allergic conjunctivitis and perennial conjunctivitis are fairly acute ocular surface disorders. However, vernal conjunctivitis, atopic keratonjunctivitis, and giant papillary conjunctivitis are chronic disorders.93 The hallmarks of allergic conjunctivitis are itching, redness, swelling, tearing, and temporary acute photophobia caused by various mast cell mediators released from mast cells when an allergen contacts the conjunctiva. The acute allergic conjunctivitis may develop into a chronic disease if left untreated, and this causes corneal and conjunctival remodeling and ulceration, sometimes accompanied by bacterial infection. Since mast-cell-derived histamine is the major culprit in allergic conjunctivitis, topical ocular antihistamines, such as emedastine, levocabastine, azelastine, and ketotifen, were considered the drugs of choice, often supplemented with vasconstrictors (e.g., oxymetazoline) and edema reducers (nonsteroidal anti-inflammatory agents and corticosteroids). However, with the discovery of a dual pharmacophoric drug, olopatadine,94 it became clear that agents with mast-cell stabilizing and antihistaminic activities are the much preferred drugs of choice in the treatment of allergic conjunctivitis. Olopatadine offers both these activities and has a long duration of action, as its clearance from the histamine-1 receptor is very slow. A single drop of olopatadine was effective against ocular itching for up to 8 hours and was shown to be more efficacious than a 2-week load with nedocromil, a mast-cell stabilizer, in a model of allergic conjunctivitis.

Suitable in vitro models for testing ocular antiallergic and/or antihistaminic drug candidates include the use of isolated human conjunctival mast cells,96 human conjunctival and corneal epithelial cells, and corneal and conjunctival fibroblasts.94 Drugs for Treating Dry Eye

Another series of disorders of the ocular surface is 'dry eye.' Dry eye is characterized by deficits in tear production/ secretion and deficiencies in the quality of tears, thereby causing ocular discomfort, itching, and a foreign body sensation on the ocular surface.95 It has recently been recognized that several aspects of dry eye involve an inflammatory cascade. Sjogren's syndrome (keratoconjunctivis sicca) is a common (affects 0.5% of adult women) autoimmune disorder of the lacrimal and salivary glands that causes ocular dryness. Treatments for dry eye have traditionally sought to reduce the symptoms of dryness by hydrating and lubricating the ocular surface with artificial tears. However, this is rarely sufficient and pharmacotherapy is necessary to prevent corneal and/or conjunctival damage. Therapeutic approaches include use of immune suppressive/anti-inflammatory agents, such as the fungal-derived peptide, cyclosporin, and topical corticosteroids, such as methylprednisolone, loteprednol etabonate, and fluorometholone. However, the relatively low efficacy of cyclosporin and the IOP-raising and cataract forming side effects of steroids limit their utility. Perhaps corticosteroids with reduced liabilities, such as AL-2512, may be more suitable for such treatment. New-generation anti-inflammatory agents, such as nepafenac,66 may also find utility in dry eye treatment in the future. More recent approaches include the use of P2Y2 purinergic agonists, such as INS-365, to increase ocular moisture by promoting water transport across the conjunctiva73 and thereby alleviating the dryness of the ocular surface. Perhaps the most promising therapeutic agents for treating dry eye involve increasing the local release of ocular surface mucins by 15-S-HETE,97 thereby lubricating the ocular surface and retaining moisture. Anti-Inflammatory Drugs

Trauma to the eye, including bacterial infections, causes local inflammation. Thus antibiotics are often prescribed with anti-inflammatory drugs. The most common inflammatory ocular conditions are conjunctivitis, uveitis, and corneal keratitis, which require the use of glucocorticoids and nonsteroidal anti-inflammatory agents that prevent generation of prostaglandins and other autocoids. Rimexolone is an effective ocular inflammatory steroid with a low potential for raising IOP. Loteprednol etabonate is claimed as a 'soft,' easily metabolized steroid with minimal IOP effects. Chronic inflammation of the ocular surface can lead to corneal ulceration and neovascularization, which impair vision. Treatment with angiostatic steroids, such as anecortave acetate, can prevent corneal neovascularization,98 although some other agents may also be useful.88 Nonsteroidal anti-inflammatory agents, such as nepafenac, ketorolac, bromfenac, flubiprofen, and diclofenac, lead the way as drugs of choice for treating ocular inflammation. However, corneal defects are a major cause of concern related to the use of these agents. Anti-Infective Drugs

The greatest hurdle for the treatment of ocular infections such as bacterial keratitis, as with other types of infections, is the emergence of bacterial resistance. Ocular bacterial infections are currently treated with fourth-generation fluoroquinolones, such as moxifloxacin and gatifloxicin.99 Levofloxacin, ciprofloxacin, and ofloxacin are being less frequently prescribed due to the development of bacterial resistance to these somewhat older antibiotics. Future anti-infective products must be broad spectrum, efficacious, prophylactically useful, comfortable, convenient to use, and nontoxic, in particular being free of benzalkonium chloride.99

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Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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