Based on its etiology, glaucoma can be classified into primary and secondary glaucoma. Primary glaucoma, also known as congenital glaucoma, can occur in the absence of other ocular conditions and its underlying causes are not known. However, it is known that increased intraocular pressure (IOP) observed in primary glaucoma is due to the obstruction of aqueous humor flow out of the eye. Secondary glaucoma results from another pre-existing ocular disease such as, uveitis, an intraocular tumor, enlarged cataract, central retinal vein occlusion, trauma to the eye, operative procedures and intraocular hemorrhage. Generally, any interference with the outward flow of aqueous humor from the posterior chamber into the anterior chamber and subsequently, into the canal of Schlemm can lead to secondary glaucoma.
Considering all types of glaucoma together, this ocular disorder occurs in about 2% of all persons over the age of 40. Unfortunately, glaucoma can be asymptomatic for years before progressing to a rapid loss of vision. In cases where surgery is not indicated, topical β-adrenoreceptor antagonists (or β-blockers) have traditionally been the drugs of choice for treating glaucoma. Further, certain prostaglandins and their analogues have been recommended for use in glaucoma management. For example, the prostaglandin analogue bimatoprost (Lumigan®) given at a dose of 0.03%, once daily, is a highly efficacious intraocular pressure (IOP) lowering drug. It has a very high systemic safety margin in studies conducted in laboratory animals. However, bimatoprost as well as many other topical anti-glaucoma medications produce conjunctival hyperemia as a side effect. Conjunctival hyperemia (or “red eye”) refers to vasodilatation of the conjunctival blood vessels. The vasodilatation of the conjunctival blood vessels results in increased blood supply to the vessels or even rupture of the vessels, which causes redness of the eye, reduced visual acuity, severe ocular pain, and photophobia (light sensitivity).
The present invention solves these as well as other problems in the art by, inter alia, providing compositions of sub-therapeutic concentrations of a vasoconstrictor agent (e.g., a beta adrenergic antagonist) in combination with a pharmaceutically effective amount of a prostaglandin agent (e.g., is defined to include prostaglandins, prostaglandin analogs, prostaglandin derivatives or prostamides such as bimatoprost) and methods of using such compositions to treat ophthalmic diseases without causing conjunctival hyperemia.