229 Br J Ophthalmol: first published as 10.1136/bjo.2004.058347 on 21 January 2005. Downloaded from PERSPECTIVE Why cotton wool spots should not be regarded as retinal nerve fibre layer infarcts

D McLeod ......

Br J Ophthalmol 2005;89:229–237. doi: 10.1136/bjo.2004.058347 Cotton wool spots (CWSs) comprise localised its axon. For several days after localised axonal damage, both orthograde and retrograde axo- accumulations of axoplasmic debris within adjacent plasmic transport will continue unabated in bundles of unmyelinated ganglion cell axons. Their undamaged axon segments causing axon end formation is widely held to reflect focal ischaemia from bulbs to appear on each side of the point of injury. When large clusters of cytoid bodies arise terminal arteriolar occlusion, but credible evidence in this way, they will expand the retinal nerve supporting this view is lacking. CWSs are here purported fibre layer (RNFL) and may protrude into the to be nothing more than sentinels of retinal nerve fibre vitreous (fig 2). layer pathology, hence their recommended redesignation ‘‘cotton wool sentinels.’’ After branch arteriolar occlusion, THE PREVAILING VIEWPOINT: ‘‘THE FOCAL ISCHAEMIA HYPOTHESIS’’ CWSs evolve as boundary sentinels of infarction, their Look at most textbooks, periodicals, or websites uniform width suggesting a glial constraint to axonal and you will find that CWSs are perceived to be expansion. In pre-proliferative , CWSs synonymous with focal retinal ischaemia, a view promulgated since the middle of the last form a C-shaped chain nasal to the disc and around the century.4 Thus, CWSs are often construed as macula where they constitute sentinels of ischaemia microinfarcts occupying the downstream terri- affecting the entire retinal mid-periphery. The tory of occluded retinal arterioles and, since the average size of a CWS is approximately 10% of polymorphous CWSs evolving during acute panretinal the area of the optic disc,5 the arterioles in hypoperfusion represent sentinels of an ischaemic question are generally thought to be the terminal penumbra. Those surrounding the disc in Purtscher’s (or pre-capillary) arterioles. These vessels tend to branch from higher order arterioles at right traumatic angiopathy are sentinels of neuronal damage angles and are at, or below, the limit of from transient venous hyperdistension that overwhelms the ophthalmoscopic resolution.6 protection afforded by peripapillary axonal An alternative iteration of the ‘‘focal ischaemia hypothesis’’ invokes localised infarction in the http://bjo.bmj.com/ decompartmentalisation. RNFL in the absence of significant damage to the ...... inner half of the deep to this layer.478In the context of , Friedenwald (1949) speculated that the deeper otton wool spots (CWSs) are conspicuous vessels might be less susceptible to spasm, or the lesions of the innermost retina that were inner retina deep to the RNFL may be less first observed in hypertensive retinopathy vulnerable to ischaemia, or the deep capillary bed C on September 28, 2021 by guest. Protected copyright. soon after the invention of the ophthalmoscope. might have more collateral connections.4 They are potential components of the fundus Subsequently, Henkind (1967) postulated that picture in a wide variety of systemic diseases, or CWS formation reflects selective impairment of they may accompany signs of retinal vascular perfusion through the capillaries that supply the occlusion. As such, CWSs often coexist with thickest part of the stratum opticum where other retinopathic features like haemorrhages, ...... CWSs are for the most part located.69 Accord- lipid exudates or oedema, or they may be ingly, the radial peripapillary capillary plexus Professor David McLeod, ‘‘isolated.’’ They may be discovered singly (fig 1) Research Group in Eye & (RPCP) was