The eye contains highly vascularised and completely avascular tissues in close apposition. This specialised anatomy requires tight regulation of the balance between vascular quiescence and vascular growth. Growth normally occurs in ocular embryonic development, but is virtually absent from the eye in adult life.1 In eye diseases associated with angiogenesis, this delicate balance is disturbed.1-6 Angiogenesis plays a crucial role in disorders responsible for most blind registration in the Western world—that is, diabetic retinopathy (DR), retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and a large number of other eye conditions.1 5 Because of its importance in wound healing, tumour growth, and other pathological situations, angiogenesis has been extensively studied in the fields of oncology, rheumatology, cardiology, and ophthalmology.7 8 The main interest in these efforts has been the notion that inhibiting angiogenesis may influence the course of tumour growth or other disease.9 10 In ophthalmology, inhibition of angiogenesis may also prove to be of great value.1 4-6 9

Angiogenesis is a tightly controlled process which involves both endothelial cells and pericytes, and is influenced by numerous agonist growth factors, inhibiting factors, and extracellular matrix proteins.7 8 11-14 Its importance in embryonic retinal vascularisation and eye disease (Fig 1) has long been recognised, and it was as early as 1948 that Michaelson suggested that it is the avascular fetal retina itself that produces a diffusible ‘biochemical factor’ capable of inducing vascular ingrowth, the production of which is associated with retinal metabolism.15 Later, when the association of neovascularisation with retinal non-perfusion and ischaemia in pathological conditions such as diabetic retinopathy was recognised, Ashton and colleagues suggested that hypoxia may be the impetus for the production of this presumed factor.16 17