Heterogeneous Pattern of Retinal Nerve Fiber Layer in Multiple Sclerosis. High Resolution Optical Coherence Tomography: Potential and Limitations

Abstract

BackgroundRecently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction of RNFL be detected in all MS patients, even in early disease courses and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along the visual pathways, which are both very common in MS, limit the predication of diffuse axonal degeneration in the whole CNS? The purpose of our study was to determine the baseline characteristics of clinical definite relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT technique.MethodologyForty-two RRMS and 17 SPMS patients with and without history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls were analysed prospectively with the high resolution spectral-domain OCT device (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference images and eye tracking mode. Furthermore we performed tests for visual and contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color vision (Lanthony D-15), the Humphrey visual field and visual evoked potential testing (VEP).Principal FindingsAll 4 groups (RRMS and SPMS with or without ON) showed significantly reduced RNFL globally, or at least in one of the peripapillary sectors compared to age-/sex-matched healthy controls. In patients with previous ON additional RNFL reduction was found. However, in many RRMS patients the RNFL was found within normal range. We found no correlation between RNFL reduction and disease duration (range 9–540 months).ConclusionsRNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels).

MR Spectroscopy in Multiple Sclerosis - A New Piece of the Puzzle or Just a New Puzzle

“…Up till now, a reliable specific para-clinical marker neither for the diagnosis nor for monitoring disease activity of MS could yet be established (e.g. Aboul-Enein et al, 2010;Gilmore et al, 2010;Kuhle et al, 2007;Serbecic et al, 2010Serbecic et al, , 2011.…”

“…Fourteen MRS studies were published with no significant NAA changes in the NAWM in a total of 184 CIS or 263 RRMS patients (Davie et al, 1997;Sarchielli et al, 1998;Brex et al, 1999;Kapeller et al, 2002;Fernando et al, 2004;Ruiz-Pena et al, 2004;Vrenken et al, 2005;Mathiesen et al, 2005;Srinivasan et al, 2005;Khan et al, 2005;Khan et al, 2008;Kirov et al, 2008;Bellmann-Strobl et al, 2009;Aboul-Enein et al, 2010).…”

Optical Coherence Tomography in Patients with Relapsing-Remitting Multiple Sclerosis without Optic Neuritis: A 20-Month Longitudinal Study

“…Some studies have shown the presence of subclinical optic neuropathy in MS patients, which can be diagnosed by performing not only OCT, but such multiple tests as visual evoked potentials, visual field examination, visual acuity, and colour vision. [25][26][27] According to the literature, in the early stages of ON in MS patients, RNFL and macular thinning or thickening (swelling) can occur, along with different structural changes in optic disc morphology. 27,28 The retina in MS patients passes through stages of minimal demyelination, remyelination, and gliosis, which can be verified only by biopsy.…”

“…[25][26][27] According to the literature, in the early stages of ON in MS patients, RNFL and macular thinning or thickening (swelling) can occur, along with different structural changes in optic disc morphology. 27,28 The retina in MS patients passes through stages of minimal demyelination, remyelination, and gliosis, which can be verified only by biopsy. 29 Some researchers consider that OCT is relatively insensitive for revealing acute axon damage at the time of acute presentation and even later, and that non-neural tissue components in RNFL may obscure subtle degrees of axonal loss in MS. 11,30 We think that some of our patients without pronounced visual symptoms or complaints could have had subclinical changes in the optic nerve during the follow-up period.…”

“…27,28 The retina in MS patients passes through stages of minimal demyelination, remyelination, and gliosis, which can be verified only by biopsy. 29 Some researchers consider that OCT is relatively insensitive for revealing acute axon damage at the time of acute presentation and even later, and that non-neural tissue components in RNFL may obscure subtle degrees of axonal loss in MS. 11,30 We think that some of our patients without pronounced visual symptoms or complaints could have had subclinical changes in the optic nerve during the follow-up period. It is known that thinning of the RNFL below 75 mm (injury threshold) might lead to a corresponding decline in objective visual function.…”