The localization of HIF expression supports the concept that hypoxia is a major stimulus for the development of submacular wound healing and within this context CNV is but one component of this process.

Extracellular accumulation of fluid resulting in oedema is well tolerated in most tissues of the body, but in the retina, it results in dysfunction of retinal neurons. Collection of fluid in the macula is called macular oedema and when the fovea is involved, it results in decreased visual acuity. Macular oedema occurs in a wide variety of ocular diseases and is one of the most prevalent causes of vision loss in developed countries. It is the most common cause of vision loss in patients with diabetic retinopathy 1 and in other ischaemic retinopathies such as branch and central retinal vein occlusion.2 3 Macular oedema is also a major cause of decreased vision following intraocular surgery. In the literature, the term cystoid macular oedema (CMO) is often used to describe oedema occurring after surgery, 4 because collection of fluid in the macula often results in cystic changes that are visible by ophthalmoscopy. However, cystic changes can occur with any type of macular oedema, and therefore the term post-surgical macular oedema is preferred when referring to oedema occurring after any type of intraocular procedure. Macular oedema is also a frequent complication of uveitis regardless of aetiology 5 and is commonly seen in patients with retinitis pigmentosa.6 Thus, macular oedema is a component of many diVerent types of pathological conditions and is an enormous clinical problem. Macular oedema results from breakdown of the blood-retinal barrierExtravascular accumulation of fluid in the retina is normally prevented by the blood-retinal barrier (BRB). The BRB consists of adaptations of retinal blood vessels (inner BRB) and the retinal pigmented epithelium (RPE; outer BRB) that control access of fluid and solutes to the retina. One adaptation is the presence of tight junctions between adjacent retinal vascular endothelial (RVE) cells and between adjacent RPE cells. Other adaptations include an abatement in vesicular transport in RVE cells compared with vascular endothelial cells in skin 7 8 and asymmetrical distribution of proteins that regulate vectorial transport across RPE cells.

These findings support animal studies that vasculogenesis, in addition to angiogenesis, may contribute to the neovascularization that occurs in AMD.