Table 2.

Non-proliferative retinopathy lesion types and potential relevance in NPDR diagnosis and characterisation (adapted with permission from ref. [179]).

Lesion type	Description	Relevance in non-proliferative retinopathy diagnosis and characterisation
Microaneurysms and haemorrhages	Occur secondary to capillary wall outpouching as a result of pericyte loss	Number, size and distribution, and turnover of microaneurysms and haemorrhages are important for diagnosis and may help to determine progression rates to sight threatening diabetic retinopathy
	Earliest clinical sign of diabetic retinopathy
	Rupture of microaneurysms results in haemorrhages
Intraretinal microvascular abnormalities	Characterise remodelling of pre-existing vessels or growth of new vessels	Presence of intraretinal microvascular abnormalities is necessary for the diagnosis of moderate to severe non proliferative retinopathy
	Intraretinal microvascular abnormalities are distinctive from the neovascularization observed in proliferative diabetic retinopathy in their larger size and broader arrangement	Unclear whether the distribution of intraretinal microvascular abnormalities is important in assessing severity
	Found adjacent to or surrounding areas of occluded capillaries	Intraretinal microvascular abnormalities originating via angiogenesis may be important for the development of proliferative diabetic retinopathy
	Visible as telangiectasia, dilated capillaries within the retina
Venous beading/loops/reduplications	Venous beading is produced by irregular constriction and dilation of venules in the retina	Evidence linking venous beading to proliferative diabetic retinopathy development is unequivocal
	Venous loops and reduplications are rarer than venous beading and might result from accentuation of a bead, traction from Vitreoretinal adhesions or may be shunt vessels	Venous loops/reduplications do not appear to lead to sight threatening changes in the diseased retina
Cotton Wool spots	Areas of nerve fibre ischaemia or infarction and axonal swelling induced by areas of retinal capillary closure	The early appearance of cotton wool spots helps in the early diagnosis of non-proliferative retinopathy but may lack predictive value for determining retinopathy progression
	Signs of poor retinal perfusion and are easily visualised
	Associated with systemic hypertension, diabetes and are common in diabetic retinopathy and hypertensive retinopathy
Hard exudates	Lipid and lipoprotein deposits, usually found in the outer layers of the retina	The presence of hard exudates plays a vital role in grading diabetic retinopathy into different stages, but their appearance was not found to be associated with diabetic retinopathy progression
	Hard exudates have a ‘waxy’ appearance, with sharply defined borders, and result from leakage from abnormally permeable microaneurysms or capillaries in the retina