Transsynaptic Retinal Degeneration in Optic Neuropathies: Optical Coherence Tomography Study

Abstract

PURPOSE.Recently demonstrated neuronal loss in the inner nuclear layer of the retina in multiple sclerosis (MS) and glaucoma raises the question of a primary (possibly immune-mediated) or secondary (transsynaptic) mechanism of retinal damage in these diseases. In the present study we used optical coherence tomography to investigate retrograde retinal transsynaptic degeneration in patients with long-standing and severe loss of ganglion cells due to optic neuropathy. METHODS. Fifteen eyes of glaucoma patients with visual field defect limited to upper hemifield and 15 eyes of MS patients with previous episode of optic neuritis (ON) and extensive loss of ganglion cells were imaged using spectral-domain optical coherence tomography and compared with two groups of age-matched controls. Combined retinal ganglion cell layer/ inner plexiform layer (GCL/IPL) thickness and inner nuclear layer (INL) thickness were analyzed. RESULTS. In the glaucoma group there was a significant (P ϭ 0.0005) reduction of GCL/IPL thickness in the lower (affected) retina compared with normal controls; however INL thickness was not statistically reduced (P ϭ 0.49). In the MS group reduction of GCL/IPL thickness in both hemifields of ON eyes was also significant (P ϭ 0.0001 and P Ͻ 0.0001 for inferior and superior retina respectively). However, similar to the glaucomatous eyes, there was no significant reduction of INL thickness in both hemifields (P ϭ 0.25 and P ϭ 0.45). CONCLUSIONS. This study demonstrates no significant loss of INL thickness in parts of the retina with long-standing and severe loss of retinal ganglion cells. (Invest Ophthalmol Vis Sci.

A novel automated segmentation method for retinal layers in OCT images proves retinal degeneration after optic neuritis

“…Similar to the findings observed in global study cohorts of patients with CIS,4 17 18 the thickness of the GCL/IPL layer was found to be significantly thinner in ON+ versus ON− eyes (Mann–Whitney U test, p<0.001). The INL, ONL-IS and OS-RPE thicknesses were, however, thicker in ON+ eyes compared with ON− eyes (Mann–Whitney U test, p<0.001; p<0.01 and p<0.05, respectively) (figure 3A).…”

“…In line with these findings, thinning of the RNFL and the GCL/IPL after ON has been demonstrated previously4 8 17 19–21 and was observed not only in MS but also in patients with CIS,4 17 suggesting that it is a direct consequence of ON. It also persists over time following the ON episode 20 21.…”

Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning – an ultrahigh-field MR pilot study

“…A more speculative explanation is trans-synaptic retrograde degeneration, a phenomenon controversially discussed for decades [31][32][33][34][35][36][37][38][39][40], induced by optic radiation damage causing retinal thinning detectable by OCT. In our study, the association between focal tissue destruction in the OR and thinning of the RNFL remained significant even when considering exclusively patients without a history of ON, indicating that retinal axonal degeneration in MS occurs partially independent of ON -a notion also supported by previous OCT studies [14][15][16]41].…”

Current and Future Potential of Retinal Optical Coherence Tomography in Multiple Sclerosis with and Without Optic Neuritis

“…Of the in vivo studies using OCT, only Saidha et al reported thinning of the INL and OPL in a subgroup of MS eyes without MSON and suggested this thinning was the results of a primary retinal process [69]. On the other hand, several other studies reported no thinning, or preservation of the INL [51,70,71].…”