Table 2.

Comparing vascular features between retina and brain that are likely to be important in cerebral malaria pathogenesis

Area of comparison	Similarities /differences	Discussion
Vascular geometry	Similarities	First and second generation retinal arterioles are ∼100-µm wide (Nagaoka and Yoshida, 2006), deep white matter arterioles are 100 to 170-µm wide (Nonaka et al., 2003b), arterioles in the putamen are ∼100 to 150-µm wide (Nonaka et al., 1998).
		Retinal perifoveal capillaries are ∼5.4-µm wide (Wang et al., 2011), cerebral grey matter capillaries are ∼6.5-µm wide (Lauwers et al., 2008), capillaries in the putamen ∼5 to 7-µm wide (Wolfram-Gabel and Maillot, 1994).
		The largest retinal venules are 130-µm to 150-µm wide (Nagaoka and Yoshida, 2006), cerebral grey and white matter venules range up to 125 µm (Duvernoy et al., 1981).
		Retina (Pournaras et al., 2008), cerebral grey (Cassot et al., 2010) and white matter (Figs 7 and 9 in Nonaka et al., 2003b) all have ∼90° branches from relatively long straight trunks. Caudate and putamen have retrograde arteriolar branching. Basal ganglia venous branches join at right angles (Nonaka et al., 1998).
	Differences	First generation retinal arterioles are ∼100-µm wide (Nagaoka and Yoshida, 2006), cerebral grey matter penetrating arterioles are 20- to 65-µm wide (Duvernoy et al., 1981; Reina-de La Torre et al., 1998).
		The largest retinal venules are 130- to 150-µm wide (Nagaoka and Yoshida, 2006), principal veins in the putamen can be up to ∼500-µm wide (Wolfram-Gabel and Maillot, 1994).
		Retinal arteriolar and venular length between bifurcations is similar to the length of entire penetrating arterioles or venules in grey matter.
Vascular topology	Similarities	Strahler order in the macula is ∼3.5, in cerebral grey matter it is 3 to 5 (Cassot et al., 2010; Yu et al., 2010).
		Capillary density immediately around the human foveal avascular zone is similar to primate cortex (Tam et al., 2010).
	Differences	Human macular superficial and deep plexus have density 40% and 20% per unit area, whereas human grey matter has density ∼1.5 to 2% brain volume (Cassot et al., 2006; Lauwers et al., 2008; Mendis et al., 2010).
		Arteriole/venule ratio in retina is 1:1, in cerebral grey matter it is 2:1, in basal ganglia it is up to 5:1 (Wolfram-Gabel and Maillot, 1994; Cassot et al., 2010).
Watershed regions	Similarities	Both brain and retina have arterial and venous watershed regions.
		Insufficient venous outflow can cause oedema, haemorrhage, and ischaemia in brain (Teksam et al., 2008) and retina (Browning, 2004).
	Differences	Retinal arteriolar and venular watersheds tend to have the same distribution, e.g. the edge of the foveal avascular zone, and horizontal raphe. In the brain arteriolar and venular watersheds cover different anatomical territories (Miyawaki and Statland, 2003a, b).
		In the retina venous drainage almost always follows arterioles. Variation in cerebral venous drainage is common in children (Widjaja and Griffiths, 2004).
Metabolic demand	Similarities	Metabolic demand per unit tissue for retina and brain is comparable, and higher than any other organ (Wong-Riley, 2010).
		Both retina and brain depend on a constant supply of oxygen and glucose (Mckenna et al., 2006).
		Both inner retina and brain vessels have an arterio-venous O2 difference of ∼40–50% (McLeod, 2010; Seifert and Secher, 2011).
		Retinal metabolism is greatest around the fovea and in retinal layers rich in synapses (Yu and Cringle, 2001; Birol et al., 2007). Cerebral metabolism is greater in grey matter than white matter (Sokoloff, 2003).
	Differences	Cerebral metabolic demand peaks in childhood: cerebral metabolic rate for O2 is 4.3 to 6.2 ml O2/100 g/min (3 to 6 years, whole brain) (Kennedy and Sokoloff, 1957); cerebral metabolic rate for glucose is >30 µmol/100 g/min (1 to 2 years, calcarine cortex, transverse temporal cortex, lenticular nuclei) (Chugani et al., 1987).
		It is not clear if retinal metabolic demand changes significantly after birth.
Blood flow	Similarities	Both retina and brain receive high blood flow volume per unit tissue.
	Differences	Inner retinal blood flow volume is roughly half that of the adult brain (25:50 ml/100 g/min, inner retinal circulation to total brain) (Kety and Schmidt, 1948; Madsen et al., 1993; Sokoloff, 2003; Pournaras et al., 2008).
		Cerebral blood flow is much higher in early childhood compared with adulthood (130 ml/100 g/min, age 2 to 4 years) (Wintermark et al., 2004).
		It is not clear if retinal blood flow undergoes similar changes in childhood.
		Paediatric peak systolic cerebral blood flow velocity is ∼95 cm/s in the middle cerebral artery and ∼4.5 cm/s in the central retinal artery (Geeraerts et al., 2005).