response of the retina to extensive capillary closure. New vessels grow at the interface of perfused and nonperfused retina and are described as new vessels on the disc (NVD) or new vessels elsewhere (NVE). Appearance Depending on the stage of development, new vessels vary in appearance. New vessels usually grow from post-capillary venules and differ from the normal vasculature in that they do not obey the law of fractals. 7.8.1 New Vessels at the Disc (NVD) New vessels at the discs usually arise from the venous circulation on the disc or within 1 disc diameter of the disc NVD are sometimes difficult to distinguish from fine normal small blood vessels. The latter however, always taper to an end and do not loop back to the disc. New vessels always loop back, may form a chaotic net within the loop, and have the top of the loop of wider diameter than the base. New vessel formation at the disc may be a consequence of generalised retinal ischaemia. Macular ischaemia if wide spread, may contribute to NVD formation. Macular ischaemia can be described as be central (involving the foveal avascular zone) or peripheral (involving the temporal vascular arcade watershed zone). 7.8.2 New vessels elsewhere NVE New vessels elsewhere (NVE) may be confused with intra-retinal microvascular anomalies (IRMA). However, new vessels occur along the border between healthy retina and areas of capillary occlusion whereas IRMAs occur within areas of capillary occlusion. Although IRMAs do not always obey the laws of fractals, they never form loops. Any unusual blood vessel forming loops should always be considered to be a new vessel until proven otherwise. 7.8.3 Other sites of new vessels New vessel formation on the iris - NVI (proliferative iridopathy) is uncommon but represents potentially more advanced ischemic changes. NVI indicates more widespread ischaemia and sometimes occurs in association with ocular ischaemia (e.g carotid stenosis, atherosclerosis of the ophthalmic artery etc) or with central retinal artery/vein occlusion. It is useful to perform gonioscopy in such cases to exclude new vessels in the anterior chamber angle (NVA) which can lead to neovascular glaucoma. 7.8.3 New vessel formation on the anterior hyaloid surface is uncommon and usually occurs post-vitrectomy if insufficient laser has been applied to the peripheral retina. 60 7.8.4 Relationship to non-proliferative diabetic retinopathy The speed and site of onset of new vessels formation depends on the extent and nature of the underlying retinal capillary closure. A large, isolated area of occlusion may lead to the early appearance of new vessels compared to the relatively milder retinal changes which may lead to erroneous grading on the screening episode. Similarly, widespread, small clusters of capillary occlusion, may not lead to new vessel formation, until relatively late in the clinical grading stage where such patients present with retinal pallor, venous beading and white lines. The amount of capillary occlusion as identified from clinical features and/or retinal angiogram is a good indicator as to the potential aggressiveness of any new vessel formation. Patients presenting with more severe degrees of nonproliferative retinopathy tend to require more laser than those presenting with milder degrees. 7.9 ANGIOGENESIS AT THE VITREO-RETINAL INTERFACE New blood vessels themselves are asymptomatic. The symptoms arise from complications which occur because of the dynamic interaction at the vitreo-retinal interface. New vessels grow between the inner surface of the retina and the posterior hyaloid face of the vitreous gel which is most strongly adherent to the pars plana, the optic disc and the major retinal arcades in decreasing order. The interaction results in an inflammatory response and scar formation. Initially transparent, the contracting scar elevates the new vessel off the retinal surface (forward new vessels). Further contraction can cause bleeding (vitreous haemorrhage), and if the vitreous is adherent to the retina, it leads to traction retinal detachment.The stronger the adherence of the vitreous to the retina, the more likely a haemorrhage and/or traction to occur. The resulting vitreous haemorrhage may be confined to the potential space between the retina and vitreous gel (pre-retinal or sub-hyaloid haemorrhage) or into the middle of the gel itself (intra-gel vitreous haemorrhage). Pre-retinal or sub-hyaloid haemorrhage can only occur if the vitreous is still attached to the retina and "holding the blood up against it". When the vitreous detaches, the blood falls into the vitreous cavity converting itself into a vitreous haemorrhage. Vitreous haemorrhages often clear the visual axis, as the vitreous detaches further (posterior vitreous detachment) and the blood collects inferiorly If this does not occur the blood must be surgically removed (vitrectomy). 7.10 FIBROUS PROLIFERATION In proliferative retinopathy, new vessels grow on a platform of glial cells. If the new vessel component predominates vitreous haemorrhage is the predominant feature. 61 In cases of repeated vitreaous haemorrhages, glial component becomes predominant. Glial cells associated with new vessels growing along major vascular arcades are particularly at risk of scar contraction, causing the vitreous to pull on the retina and resulting in retinal folds and sometimes in detachment of the retina (traction retinal detachment). Traction retinal detachments are concave and progress only slowly unless a hole forms in the detached retina leading to a combined traction/ rhegmatogenous retinal detachment. 7.11 INACTIVE ANGIOGENESIS New vessels may occasionally auto-infarct spontaneously. Most patients with proliferative retinopathy need treatment either in the form of laser or intra-vitreal injection of anti-vascular endothelial growth factor, to cause involution of the new vessels. Where incomplete regression occurs, inactivity can be inferred by the development of gliosis, reduction in size of the NV, and decrease in the distal lumen. If new vessels persist, another good sign of inactivity is the presence of pan-retinal laser burns in conjunction with the disappearance of retinal haemorrhages, normalisation of retinal venous