Eye disorders form a common cause of impairment in subjects of all ages. About 3% of the general population report having trouble seeing even when wearing glasses or contact lenses. This figure becomes magnified when persons older than 45 years of age are examined: 17% of subjects older than 45 years report trouble seeing or being blind in one/both eyes; this represents about 16 million people in this country. When subjects older than 75 are evaluated, one in five is found to have some degree of visual impairment even with corrective lenses.

The above statistics pertain to some degree of visual loss but not to legal blindness. Persons who are blind in both eyes represent 2% of subjects older than 45 years. The annual cost of blindness in this country is $4 billion. Major causes for blindness include macular degeneration, diabetic retinopathy, glaucoma and cataract.

At present, there are more than 30 drugs in clinical trials for ophthalmologic conditions. Clinical trials are most active in the areas of diabetic retinopathy, glaucoma and macular degeneration. In the field of diabetic retinopathy, there are several promising approaches. Novel drugs have been identified that function as advanced glycosylation end-product (AGE) crosslink breakers. The formation of AGE crosslinks is a natural part of the aging process and is vastly accelerated in subjects with diabetes. Increased AGE crosslinks with proteins leads to atherosclerosis, retinopathy, nephropathy and increased risk of coronary artery disease, stroke and dementia. Thus, these agents have potential far beyond the prevention of diabetic complications, such as diabetic retinopathy or nephthropathy. Alteon has two AGE crosslink breakers in clinical trials: ALT-711 and Pimagedine HCl. ALT-711 is in trials for kidney disease, arterial hypertension and eye disorders and Pimagedine is in clinical trials for diabetic nephropathy. In those clinical trials, Pimagedine was found to have significant impact in reducing the incidence of diabetic retinopathy in the diabetic subjects.

Other new therapies include those that inhibit the enzyme PKC-beta. Increased vascular permeability and excessive neovascularization are the root causes of diabetic macular edema and retinopathy. Since Vascular Endothelial Growth Factor mediates these effects through activation of the enzyme PKC-beta, it is thought that inhibitors of this enzyme will produce beneficial effects in these two conditions. Eli Lilly's LY333531 is a selective inhibitor of this enzyme and is being tested in phase III trials in subjects with diabetes. An effective preventive therapy for diabetic macular edema and retinopathy will have a marked impact on reducing the incidence of the two leading causes of blindness in this country.

In the field of glaucoma, the FDA has approved two new drugs in 2001 for the treatment of elevated intraocular pressure: Lumigan (bimatoprost) and Travatan (travoprost). These drugs belong to the prostamide and prostaglandin analogues, respectively. These two drugs offer additional alternatives to patients who have had insufficient responses to other medications.

In the field of ophthalmology, eye-drops are the conventional dosage form for more than 90% of ophthalmic preparations. To improve ocular drug bioavailability, there is a significant effort directed towards the development of new drug delivery systems for ophthalmic administration. For example, extended release and fixed flow devices are undergoing clinical trials to extend the duration of drug action in the eye, particularly in the treatment of glaucoma. Much of the research is also directed at combination drug delivery systems that prolong the contact time of the vehicle at the ocular surface and, at the same time, decrease elimination of the drug.

For the practicing ophthalmologist and for subjects afflicted with disabling ophthalmologic conditions, the developments discussed in this introduction suggest unsurpassed potential. Unfortunately, there is as yet little long-term experience with the newer medications recently approved by the FDA for the management of serious ophthalmologic disorders. With the passage of time, a more definite understanding of the role of each drug will be obtained.