Reply: Microcystic macular degeneration from optic neuropathy: not inflammatory, not trans-synaptic degeneration

Sir, we read the letter by Barboni et al. (2013) with great interest. They report microcystic changes in the inner nuclear layer on optical coherence tomography in 10 of ‘several hundred’ patients with hereditary, ‘non-inflammatory’ optic neuropathies [Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy]. More clinical information about these cases would certainly be helpful in analysing why some of these patients demonstrated microcystic changes in the inner nuclear layer on optical coherence tomography but most did not. Given that a disease phenotype indistinguishable from multiple sclerosis is well described in carriers of LHON mutations (‘Harding’s disease’; Harding et al., 1992); and has also been reported in association with an OPA1 mutation in dominant optic atrophy (Verny et al., 2008), we recognize that some patients with these conditions may manifest with an overlap syndrome with characteristic features found in multiple sclerosis. We additionally agree that prominent vitreous traction can lead to microcystic changes in the inner nuclear layer on optical coherence tomography, but, as discussed in our paper, traction did not explain the finding of microcystic changes in the inner nuclear layer in the patients with multiple sclerosis in our study. All patients with traction were in fact excluded. As for the assertion that microcystic pathology in the inner nuclear layer on optical coherence tomography ‘is unlikely to be useful as a marker of multiple sclerosis,’ we agree that microcystic abnormalities in the inner nuclear layer are not unique to multiple sclerosis and that more study is needed to understand the mechanism. However, we would also refer readers to the recent report by Saidha et al. (2012) confirming associations of microcystic macular oedema with markers of multiple sclerosis disease severity and describing a novel association of increased inner nuclear layer thickness, with or without visible microcystic changes on optical coherence tomography, with inflammatory disease activity in multiple sclerosis.

Funding

American Academy of Neurology Clinical Research Training Fellowship (to J.M.G.); National Institutes of Health (KL2 RR-024130), Howard Hughes Medical Institute Physician Scientist Early Career Award (57006497) and Debbie and Andy Rachleff Distinguished Professorship of Neurology (to A.J.G.).