Letter to the editor: partial central retinal artery occlusion offers a unique insight into the ischemic penumbra

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

“…Prior to the onset of neovascularisation (say 2e3 weeks after CRAO onset), these eyes show a significantly increased prevalence of "extreme prolongation of the retinal arteriovenous transit time" on FFA in comparison with eyes that don't suffer these angiogenic sequelae (Duker and Brown, 1988). This observation is consistent with the view that eyes that become rubeotic after CRAO are amongst the minority wherein no significant retinal reperfusion transpires (Duker and Brown, 1988;McLeod, 2012McLeod, , 2013. That is to say, in these eyes the obstruction of the CRA lumen is truly "permanent" and isn't circumvented by pial or Nettleship collaterals (Table 1).…”

“…Hypoxia-induced secretion of VEGF and other pro-angiogenic proteins is believed to underlie the iris and/or preretinal neovascularisation in these eyes and to reflect marginal oxygenation of non-perfused inner retina by the choroidal circulation (Subsection 4.2.5.). That is to say, all eyes with the classic CRAO picture are judged to be at risk of neovascularisation unless or until the CRA reopens or collateral flow enables effective tissue reperfusion (McLeod, 2012(McLeod, , 2014. This proposition challenges Hayreh's dictum that there is no biologically plausible rationale for intraocular neovascularisation following isolated CRAO because "chronically hypoxic retina … is totally missing in CRAO" (Hayreh and Podhajsky, 1982;Hayreh, 2011).…”

Concerning central retinal artery occlusion (CRAO) and cerebral stroke

“…2 We agree with McLeod 3 that penumbral retinal tissue viability can persist as half of our patients did not fall into the carotid occlusive disease group. This concurs with Kottow and Hendrickson, 4 who found anterior segment neovascularisation following CRAO, as well as Brown,5 who reported a case of neovascularisation following CRAO due to presumed single mitral valve embolus in the absence of carotid disease.…”

Reply: ‘Central retinal artery occlusion and cerebral stroke’

“…In cerebral stroke using perfusion imaging, various groups have demonstrated that the ischaemic penumbra may persist beyond 24 h. However, randomised controlled trials of reperfusion therapy in acute stroke have demonstrated on that in the majority of individuals, the ischaemic penumbra only extends out to 4.5 h and at maximum, 6 h. 5,6 The misperceptions that the retinal penumbra persists for 24 h, initially backed up by observational data, led to the design of two randomised controlled trials that recruited individual with central retinal artery occlusion of beyond 6 h. The EAGLE study recruited subjects up to 19 h of symptom onset, 7 while our group conducted a randomised controlled trial of intravenous tPA given to individuals within 24 h of symptom onset. 8 Both of these randomised controlled trials were negative studies, however, a signal was seen in individuals who receive tPA within 6 h of symptom onset.…”