Evidence for an enduring ischaemic penumbra following central retinal artery occlusion, with implications for fibrinolytic therapy

PAMM—Punchy Acronyms May Mislead

“…Other contributory factors may include the relative hypermetabolism of the horizontal cells and plexiform layers supplied by the DCP, and potential oxygenation of the innermost inner retina from the vitreous. 5 As mentioned earlier, the superficial inner retina overlying, and the middle-retinal tissues adjacent to, the middle-retinal infarction seen in MPvW and PAMM are not necessarily free from ischaemic abnormality despite their transparency on fundoscopy and their hyporeflectivity on OCT. Rather, they may constitute part of a hypoxic tissue micro-compartment (or 'ischaemic penumbra') that would require employment of a 'hypoxia marker' for detection and will likely recover its neural function on subsequent reperfusion. 5 As for the current scramble to be in the vanguard of discovery of 'deep capillary ischaemia' by OCT angiography, it should be noted that localised vascular attenuation may be the consequence, and not the cause, of the retinal parenchymal changes seen in PAMM, as also applies in the case of CWS formation.…”

“…Thus, MPvW represents 'anoxic corner' formation at the distal end of Krogh tissue cylinders reflecting countercurrent flow through the interdigitating second-order arteries and veins that radiate towards the fovea. 5 The localisation of ischaemic anoxia and infarction to the middle retina in MPvW and PAMM, sparing the superficial inner retina, does not indicate selective impairment of perfusion through the DCP. Rather, it reflects the DCP's 'subsidiarity' (ie, its late embryological development from the SCP by angiogenesis) and, consequently, a heightened vulnerability of middle-retinal neurons to more generalised ischaemia.…”

“…Of note, in a recently-introduced severity grading system for such 'hypoperfusion maculopathy', the oxygenation status of the superficial inner retina determines the ranking, whether normoxia (grade 1), ischaemic hypoxia (grade 2), or ischaemic anoxia (grade 3). 5 The peri-venous middle-retinal infarction seen in eyes with hypoperfusion maculopathy grades 1 and 2 illustrates the general principle that oxygen delivery to parenchymal cells is not confined to the capillary microcirculation but is dependent on the oxygen tension within the nearest blood vessel(s), whether artery, capillary, or vein. Thus, MPvW represents 'anoxic corner' formation at the distal end of Krogh tissue cylinders reflecting countercurrent flow through the interdigitating second-order arteries and veins that radiate towards the fovea.…”

The Penumbra Obscura Stimulates Iris Neovascularisation after Isolated Central Retinal Artery Occlusion

“…Jung et al [1] are to be congratulated on definitively demonstrating what could only be surmised in the past—that intraocular angiogenesis after central retinal artery occlusion (CRAO) occurs in that small proportion of cases wherein retinal reperfusion fails to materialize [23]. However, your contributors appear to be unsure as to the mechanism whereby neovascularisation of the iris (NVI) arises after “CRAO alone.” While they reject Hayreh's [4] assertion that “chronically hypoxic retina ... is totally missing” after what is otherwise called “isolated CRAO” (and implicating ocular ischemia in NVI development due, for example, to carotid arterial stenosis), the crucial link between isolated CRAO and NVI was not elucidated.…”

“…A recent review of the electrophysiological data from legacy experiments in primates has shown that a transparent mid-peripheral hypoxic tissue compartment–the “penumbra obscura”–evolves within the inner retina after CRAO (Fig. 1) and surrounds the opacified anoxic infarct in the posterior pole [3]. The penumbra obscura is marginally oxygenated by the choroid and is analogous to the ischemic penumbra that surrounds the infarct core in cerebral stroke.…”