Retinal Layer Segmentation in Patients with Multiple Sclerosis Using Spectral Domain Optical Coherence Tomography Elena Garcia-Martin, PhD,1,2 Vicente Polo, PhD,1,2 Jose M. Larrosa, PhD,1,2 Marcia L. Marques, MD,1,2,3 Raquel Herrero, MD,1,2 Jesus Martin, PhD,2,4 Jose R. Ara, PhD,2,4 Javier Fernandez, PhD,1,2 Luis E. Pablo, PhD1,2 Purpose: To evaluate the thickness of the 10 retinal layers in the paramacular area of patients with multiple sclerosis (MS) compared with healthy subjects using the new segmentation technology of spectral domain optical coherence tomography (OCT). To examine which layer has better sensitivity for detecting neurodegeneration in patients with MS. Design: Observational, cross-sectional study. Participants: Patients with MS (n ¼ 204) and age-matched healthy subjects (n ¼ 138). Methods: The Spectralis OCT system (Heidelberg Engineering, Inc., Heidelberg, Germany) was used to obtain automated segmentation of all retinal layers in a parafoveal scan in 1 randomly selected eye of each participant, using the new segmentation application prototype. Main Outcome Measures: The thicknesses of 512 parafoveal points in the 10 retinal layers were obtained in each eye, and the mean thickness of each layer was calculated and compared between patients with MS and healthy subjects. The analysis was repeated, comparing patients with MS with and without previous optic neuritis. Correlation analysis was performed to evaluate the association between each retinal layer mean thickness, duration of disease, and functional disability in patients with MS. A logistic regression analysis was performed to determine which layer provided better sensitivity for detecting neurodegeneration in patients with MS. Results: All retinal layers, except the inner limiting membrane, were thinner in patients with MS compared with healthy subjects (P < 0.05). Greater effects were observed in the inner retinal layers (nerve fiber, ganglion cells, inner plexiform, and inner nuclear layers) of eyes with previous optic neuritis (P < 0.05). The retinal nerve fiber layer and ganglion cell layer thicknesses were inversely correlated with the functional disability score in patients with MS. The ganglion cell layer and inner plexiform layer thicknesses could predict axonal damage in patients with MS. Conclusions: Analysis based on the segmentation technology of the Spectralis OCT revealed retinal layer atrophy in patients with MS, especially of the inner layers. Reduction of the ganglion cell and inner plexiform layers predicted greater axonal damage in patients with MS. Ophthalmology 2014;121:573e579 ª 2014 by the American Academy of Ophthalmology.

Visual loss is one of the main causes of disability in patients with multiple sclerosis (MS), a neurodegenerative disease. Several studies report a correlation between axonal loss in the optic nerve and the extent of functional disability in patients with MS.1e3 The retinal nerve fiber layer (RNFL) comprises axons of the retinal ganglion cells that convey visual information from the retina to the lateral geniculate nucleus; until these axons exit the eye, they do not acquire a protective myelin sheath. Ganglion cells and their axons, besides being the main retinal component around the optic nerve (90% of retinal thickness), are also present at the macula (30%e35%) and can be quantified by ocular imaging technologies such as optical coherence tomography (OCT), which is a noninvasive, rapid, objective, and reproducible method for evaluating the RNFL.4 Optical coherence tomography allows crosssectional imaging of the retina and optic disc based on the interference patterns produced by low coherence light  2014 by the American Academy of Ophthalmology Published by Elsevier Inc.

reflected from retinal tissues. Measurements of RNFL thickness and magnetic resonance imaging parameters are only slightly correlated, however, and some authors suggest that the retinal ganglion cell layer is a more sensitive retinal layer for detecting axonal loss in MS.5,6 Improvements in OCT technology were recently introduced, including a prototype of specific software that allows for automated differentiation and quantification of the 10 retinal layers using the Spectralis OCT (Heidelberg Engineering, Inc., Heidelberg, Germany). We describe the analysis of the parafoveal areas of patients with MS and age- and sex-matched healthy subjects using this prototype. To our knowledge, this is the first study in which automated retinal segmentation was used to evaluate the RNFL structure in patients with MS in vivo. The strength of this study is that we systematically compared each parafoveal retinal layer of the patients with MS with that of healthy controls. ISSN 0161-6420/14/$ - see front matter http://dx.doi.org/10.1016/j.ophtha.2013.09.035

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Methods The design of this study followed the Declaration of Helsinki principles. The study protocol was approved by the Clinical Research Ethics Committee of Aragon (Zaragoza, Spain), and informed written consent was obtained from all participants. The required inclusion criteria were as follows: best-corrected visual acuity of 20/40 or better, refractive error within 5.00 diopters equivalent sphere and 2.00 diopters astigmatism, and transparent ocular media (nuclear color/opalescence, cortical, or posterior subcapsular lens opacity

Retinal layer segmentation in patients with multiple sclerosis using spectral domain optical coherence tomography.

To evaluate the thickness of the 10 retinal layers in the paramacular area of patients with multiple sclerosis (MS) compared with healthy subjects usi...
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