A Phase IV OpenLabelled Prospective Pilot Study of Intravitreal Macugen (Pegaptanib) for Ischaemic Diabetic Macular Oedema (MIDME Study)

Diabetic macular oedema:

A combination of increasing longevity and increasing obesity is causing a rise in the incidence of diabetes and its associated complications such as diabetic retinopathy. Almost all patients with type 1 diabetes mellitus (DM) develop some signs of retinopathy and approximately 60% of patients with type 2 DM develop diabetic retinopathy. Of those with type 2 DM, diabetic macular oedema (DME) is the most common cause of reduced visual acuity. [1]

DME is one of the leading causes of loss of vision in people of a working age in the developed world. It affects the function of the macula, a key part of the retina which is used for central vision. In DME there are abnormal structural changes in the blood vessel walls which lead to leakage of fluid and proteins from the blood vessels. [2, 3] DME can be classified as ischaemic or exudative, based on the dominant underlying problem. In ischaemic DME, the main problem is a reduction in blood flow to the macula which causes reduced central vision and swelling of the retinal tissues in this area. [4] In exudative DME, excessive leakage of fluid from the blood vessels around the macula results in thickening or swelling of the retina and a resultant reduction in central vision. There is often a combination of ischaemia and exudation.

Vascular endothelial growth factor:

A chemical called vascular endothelial growth factor (VEGF) has been implicated as a potential cause of the abnormalities seen in DME. It has been shown to modulate the growth and pattern of blood vessels, the tone and permeability of their walls, and to cause white blood cells to be drawn to the inner walls of blood vessels. [5, 6] The actual roles played by VEGF are in part dependent on the needs of the tissues in which it is acting. [5] Studies of diseases of the eye that involve the abnormal development of new blood vessels, such as neovascular age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR), have demonstrated a central role for VEGF. It has also been implicated in the development of some of the problems associated with central retinal vein occlusion (CRVO) and DME. VEGF exists in a variety of subtypes, called "isoforms", each described by the number of amino acids (the building blocks of proteins) that it contains. The different VEGF isoforms have distinct activities at different sites in the body and its various tissues. [7] This may in part help to explain how VEGF is able to elicit such a variety of functions within blood vessels and beyond. [5]