title: Evidence for an enduring ischaemic penumbra following central retinal artery occlusion, with implications for fibrinolytic therapy.
abstract: The rationale behind hyperacute fibrinolytic therapy for cerebral and retinal arterial occlusion is to rescue ischaemic cells from irreversible damage through timely restitution of tissue perfusion. In cerebral stroke, an anoxic tissue compartment (the "infarct core") is surrounded by a hypoxic compartment (the "ischaemic penumbra"). The latter comprises electrically-silent neurons that undergo delayed apoptotic cell death within 1-6 h unless salvaged by arterial recanalisation. Establishment of an equivalent hypoxic compartment within the inner retina following central retinal artery occlusion (CRAO) isn't widely acknowledged. During experimental CRAO, electroretinography reveals 3 oxygenation-based tissue compartments (anoxic, hypoxic and normoxic) that contribute 32%, 27% and 41% respectively to the pre-occlusion b-wave amplitude. Thus, once the anoxia survival time (≈2 h) expires, the contribution from the infarcted posterior retina is irreversibly extinguished, but electrical activity continues in the normoxic periphery. Inbetween these compartments, an annular hypoxic zone (the "penumbra obscura") endures in a structurally-intact but functionally-impaired state until retinal reperfusion allows rapid recovery from electrical silence. Clinically, residual circulation of sufficient volume flow rate generates the heterogeneous fundus picture of "partial" CRAO. Persistent retinal venous hypoxaemia signifies maximal extraction of oxygen by an enduring "polar penumbra" that permeates or largely replaces the infarct core. On retinal reperfusion some days later, the retinal venous oxygen saturation reverts to normal and vision improves. Thus, penumbral inner retina, marginally oxygenated by the choroid or by residual circulation, isn't at risk of delayed apoptotic infarction (unlike hypoxic cerebral cortex). Emergency fibrinolytic intervention is inappropriate, therefore, once the duration of CRAO exceeds 2 h.
authors.affiliation: Academic Department of Ophthalmology, Manchester Royal Eye Hospital, Oxford Road, Manchester M13 9WL, United Kingdom; Manchester Vision Regeneration (MVR) Lab at NIHR/Wellcome Trust Manchester CRF, Manchester Academic Health Science Centre and Centre for Ophthalmology and Vision Research, Institute of Human Development, University of Manchester, Manchester, United Kingdom. Electronic address: david.mcleod@nhs.net.
authors.forename: David
authors.initials: D
authors.lastname: McLeod
authors.affiliation: Macular Pigment Research Group, West Campus, Waterford Institute of Technology, Waterford, Ireland; Institute of Eye Surgery, Whitfield Clinic, Cork Road, Waterford, Ireland. Electronic address: sbeatty@wit.ie.
authors.forename: Stephen
authors.initials: S
authors.lastname: Beatty
mesh_terms: D000818:Animals; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy / Q000209:etiology*; D012039:Regional Blood Flow / Q000502:physiology; D012160:Retina / Q000503:physiopathology; D015356:Retinal Artery Occlusion / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D015912:Thrombolytic Therapy / Q000379:methods*
chemical_list: D005343:Fibrinolytic Agents
keywords: Fibrinolytic therapy; Hypoperfusion maculopathy; Intraocular angiogenesis; Ischaemic penumbra; Krogh tissue cylinder; Retinal artery occlusion