Comparative evaluation of combined 0.03% chloroquine phosphate with 0.1% olopatidine versus 0.1% olopatidine drops in cases of allergic keratoconjunctivitis.

Allergic conjunctivitis is a perennial ocular allergic disease. It is the inflammatory response of the conjunctiva to allergens such as pollen, animal dander, and other environmental allergens. Allergic conjunctivitis comprises of itching, watering, photophobia, lid oedema, conjunctival hyperaemia and palpebral hypertrophy. Only about 10% of individuals with allergic conjunctivitis seek medical attention, and the entity is often underdiagnosed. Redness and itching are the most consistent symptoms. Seasonal allergic conjunctivitis comprises 90% of all the allergic conjunctivitis cases.

Seasonal allergic conjunctivitis (SAC) or hay fever is a common allergic disease typically elicited by airborne allergens such as pollen, grass, weeds and animal dander (Abelson & Schaefer 1993). It is a type 1 hypersensitivity reaction mediated by IgE in response to these environmental antigens. The principal symptom of SAC is ocular itching (Abelson & Schaefer 1993). Other signs and symptoms include conjunctival hyperaemia, tearing, mucus discharge, chemosis and lid oedema.

Mast cells play an important role in the pathophysiology of this condition. When specific allergens bind to sensitized mast cells in the conjunctiva, degranulation of mast cells, and release of preformed (histamine, eosinophil chemotactic factor, tryptase) and newly synthesized mediators (prostaglandins, leukotrines) occur. Hence, typical signs and symptoms of SAC appear. Histamine, which is a preformed agent, is accepted as the predominant mediator (Berdy et al. 1991). On the other hand, prostaglandin D2 is produced by the arachidonic acid pathway, and has a role in the pathogenesis of SAC (Woodward et al. 1995). Prostaglandin D2 has been shown to induce conjunctival hyperaemia, oedema and mucus discharge; prostaglandins, particularly D2 and E2, have a pruritogenic effect on the conjunctiva (Woodward et al. 1995).

Treatment consists of avoidance of the offending antigen and use of saline solution or artificial tears to physically dilute and remove the allergens. Topical decongestants, antihistamines, mast cell stabilizers, nonsteroidal antiinflammatory drugs, and corticosteroids may be indicated. Topically applied ophthalmic agents are the principal treatment method for SAC. Currently available topical drugs include H1 antihistamines such as levocobastine, H1 antihistamine-vasoconstrictor combinations such as antazoline-naphazoline, mast cell stabilizors such as cromolyn sodium and lodoxamide, and non-steroidal anti-inflammatory drugs (NSAIDs) which inhibit prostaglandin synthesis, such as ketorolac tromethamine.  Olopatidine hydrochloride has been indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis.

Chronic inflammation is one of the common mechanisms observed in keratoconjunctivitis, caused by the activation of innate immune components, decrease in tear film stability, and increase in tear osmolarity. This imbalance in tear film stability and hyperosmolarity further triggers the release of pro- inflammatory mediators such as interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-a, chemokines, and matrix metalloproteinases from the ocular surface, thus producing an inflammatory environment. In order to break the vicious circle of surface damage and inflammation, anti-inflammatory treatment is required in patients with moderate-to-severe DED. Currently used treatments such as corticosteroids (adverse effects such as glaucoma, infections, and cataracts) and cyclosporine A (efficacy not consistent, stinging sensation) have limitations.

Chloroquine is a systemic anti-inflammatory agent used in the treatment of rheumatoid arthritis. It has been investigated for use in dry eyes. Chloroquine has been shown to have anti-inflammatory action in in vitro studies in human corneal epithelial cells. Phase I clinical trials demonstrated safety of chloroquine in healthy volunteers. Phase III clinical trials confirmed the efficacy and safety of chloroquine in subjects with DED. Chloroquine significantly improved the signs and symptoms of dry eye disease. It has been shown to be superior to carboxymethyl cellulose (CMC) in efficacy and to have an early onset of improvement and better tolerance profile compared to cyclosporine A. No serious adverse events were reported in subjects treated with Chloroquine so far. Thus, chloroquine eye drops have proven anti-inflammatory action and therapeutic efficacy which makes it a useful therapeutic option in the management of DED

Several studies have reported that use of Chloroquine phosphate drops has improved the sign and symptoms of dry eye and the quality of ocular surface epithelial cells. Thus making Chloroquine drops an important candidate for tear film stability improvement assessment in cases of allergic keratoconjunctivitis.

To the best of our knowledge, there are no reports that compare the efficacy of Olopatidine hydrochloride with Chloroquine phosphate in cases of allergic conjunctivitis. The present study is designed to evaluate the efficacy and safety of 0.1% Olopatidine versus combined 0.03% Chloroquine phosphate and 0.1% Olopatidine in allergic conjunctivitis.