The expanding spectrum of aetiologies causing retinal microcystic macular change.

In this issue of Brain, John Kisimbi et al. (2013) describe spectral domain optical coherence tomography (OCT) findings in a cohort of patients with Tanzanian endemic optic neuropathy, a disorder of unknown aetiology, leading to severe bilateral subacute optic neuropathy. They describe severe retinal nerve fibre layer (RNFL) thinning and concomitant microcystic macular changes in 12.5% of this cohort. The authors describe a parafoveal annular or semi-lunar pattern of the microcystic (perhaps a misnomer but the term will be used for consistency in the literature) changes with a pre-dilection for the nasal aspect of the macula visible using en face infrared imaging. This distribution of microcystic macular change is consistent with that described in previous contexts (Abegg et al., 2012; Kaufhold et al., 2013; Wolff et al., 2013). The current study by Kisimbi et al. (2013) adds Tanzanian endemic optic neuropathy to a growing list of aetiologies causing microcystic macular changes. Histopathological changes similar in appearance to microcystic macular change were described as early as 1963 by John Van Buren, who observed cystic changes in the retinal inner nuclear layer of non-human primates following optic nerve injury. Similar changes to the inner nuclear layer of human eyes with optic nerve lesions were subsequently demonstrated by Gills and Wadsworth (1966). A more recent study demonstrated inner nuclear layer cavitation and cystic changes in rhesus macaques with bilateral idiopathic optic atrophy (Fortune et al., 2005). Microcystic macular changes on OCT were described in patients with multiple sclerosis and correlated with disease severity (Gelfand et al., 2012; Saidha et al., 2012). These studies were followed by a flurry of Letters to the Editor demonstrating morphologically similar microcystic macular changes in a variety of inflammatory and non-inflammatory optic neuropathies. Microcystic macular changes have now been described in multiple sclerosis, neuromyelitis optica, Leber's hereditary optic neuropathy, dominant optic atrophy, isolated relapsing optic neuropathy, NF-1-related optic chiasmal glioma, glaucoma, trauma and hydro-cephalus (Abegg et al. Furthermore, microcystic changes are also described in patients undergoing internal limiting membrane removal for epima-cular membrane—possibly secondary to damage to the RNFL and the ganglion cell layer (Sigler et al., 2013). Several different theories have been advanced to explain the pathophysiology of retinal microcystic changes. One of the most attractive explanations, is retrograde trans-synaptic degeneration. Retrograde trans-synaptic degeneration in the visual pathways secondary to occipital lobe damage was demonstrated by Jindahra et al. (2012). By extension, this could be hypothesized to …