High Resolution Spectral Domain Optical Coherence Tomography (SD-OCT) in Multiple Sclerosis: The First Follow Up Study over Two Years

“Non-invasive, faster and less expensive than MRI” and “the eye is a window to the brain” are recent slogans promoting optical coherence tomography (OCT) as a new surrogate marker in multiple sclerosis (MS). Indeed, OCT allows for the first time a non-invasive visualization of axons of the central nervous system (CNS). Reduction of retina nerve fibre layer (RNFL) thickness was suggested to correlate with disease activity and duration. However, several issues are unclear: Do a few million axons, which build up both optic nerves, really resemble billions of CNS neurons? Does global CNS damage really result in global RNFL reduction? And if so, does global RNFL reduction really exist in all MS patients, and follow a slowly but steadily ongoing pattern? How can these (hypothesized) subtle global RNFL changes be reliably measured and separated from the rather gross RNFL changes caused by optic neuritis? Before generally being accepted, this interpretation needs further critical and objective validation.We prospectively studied 37 MS patients with relapsing remitting (n = 27) and secondary progressive (n = 10) course on two occasions with a median interval of 22.4±0.5 months [range 19–27]. We used the high resolution spectral domain (SD-)OCT with the Spectralis 3.5 mm circle scan protocol with locked reference images and eye tracking mode. Patients with an attack of optic neuritis within 12 months prior to the onset of the study were excluded.Although the disease was highly active over the observation period in more than half of the included relapsing remitting MS patients (19 patients/32 relapses) and the initial RNFL pattern showed a broad range, from normal to markedly reduced thickness, no significant changes between baseline and follow-up examinations could be detected.These results show that caution is required when using OCT for monitoring disease activity and global axonal injury in MS

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

BACKGROUND: Recently 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. METHODOLOGY: Forty-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 FINDINGS: All 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). CONCLUSIONS: RNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels)

RNFL thickness in MS-associated acute optic neuritis using SD-OCT: critical interpretation and limitations

PURPOSE: Axonal loss is considered a key prognostic factor in diagnosing and monitoring the progress of multiple sclerosis (MS). The purpose of our research was to determine whether the measurement of retinal nerve fibre layer thickness (RNFLT) as measured with high-resolution spectral-domain optical coherence tomography (SD-OCT) differs between optic nerve injury following acute optic neuritis (ON) or following unregistered subclinical axonal damage in patients with MS.METHODS: High-resolution SD-OCT measurements of RNFLT were initially carried out in the acute phase of ON and again after 3 months, in 25 patients with clinical definite MS and 25 sex- and age-matched healthy controls, all at the University Eye Hospital, Vienna.RESULTS: Conventional OCT-based RNFLT analysis correctly identified all three patients with initial RNFL swelling. However, only two of three acute ON eyes with a history of ON were registered with RNFLT decrease in seven peripapillary sectors (PPs). The remaining have only been revealed using RNFLT symmetry comparison. Two of 22 (9%) first-episode ON eyes were labelled as pathologic. The number and metric RNFL values of pathologically labelled PPs remained unchanged after 3 months. Our age- and sex-match-based measurement model, with patients with MS being plotted individually and towards the fellow eye, identified all acute ON eyes (with a history of prior ON) with RNFLT reduction in 11 PPs. A global RNFL loss was registered in 36.4% (eight of 22 eyes). However, in 72%, or 16 of 22 ON eyes presenting with first episode of acute ON, a segmental RNFL loss was initially registered in 39 PPs upon baseline examination. The number of PPs with identified axonal decrease increased to a total of 48 PPs within the observational period.CONCLUSIONS: Spectral-domain optical coherence tomography imaging of identical scanning locations, combined with an optimized scan centring around the optic disc, offers the technological potential of detecting prior, subtle, clinically unregistered optic nerve injury within MS individuals. Significant discrepancy in RNFLT to the potential ON eye may be achieved by comparing OCT metrics with the fellow eye and a sufficient number of age and sex-matched controls.</p

High-resolution spectral domain-optical coherence tomography in multiple sclerosis, Part II – the total macular volume. The first follow-up study over 2 years

BACKGROUND: Recent studies investigating the use of optical coherence tomography (OCT) in multiple sclerosis (MS) patients have resulted in wide-ranging and often contradictory outcomes. This is mainly due to the complex etiology and heterogeneity of MS, physiological variations in the retinal nerve fiber layer (RNFL) and/or total macular volume (TMV), and limitations in methodology. It remains to be discovered whether any retinal changes in MS develop continuously or in a stepwise fashion, and whether these changes occur in all or a subset of patients. High-resolution spectral domain-OCT devices (SD-OCT) would be required to detect subtle retinal changes and longitudinal studies would have to be carried out to investigate retinal changes over time. In addition, if the hypothesis is correct, then retinal and global brain tissue changes should be detected in a substantial majority of MS patients and detection should be possible with a high degree of disease activity and/or long disease course.METHODOLOGY: In order to address the factors above, 37 MS patients (relapsing-remitting, n = 27; secondary progressive, n = 10) were examined prospectively on two occasions with a median interval of 22.4 ± 0.5 months [range 19-27]. SD-OCT was utilized with the Spectralis 3.5 mm circle scan protocol (with locked reference images and eye-tracking mode). None of the patients had optic neuritis 12 months prior to study entry or during the observation period.PRINCIPAL FINDINGS: The initial TMV pattern differed between study participants, but remained relatively unchanged over the 2-year observation period despite high disease activity or long disease course. The TMV correlated well with the RNFL.CONCLUSION: The significance of differences in TMV (and RNFL) between study participants remains unclear. Until these differences have been explored further, OCT data in MS patients should be interpreted with caution.</p

Corrigendum: "High-resolution spectral domain-optical coherence tomography in multiple sclerosis, part II – the total macular volume. The first follow-up study over 2 years”

[This corrects the article on p. 20 in vol. 5, PMID: 24605107.]. </p

CROP - The Clinico-Radiologico-Ophthalmological Paradox in Multiple Sclerosis: Are patterns of retinal and MRI changes heterogeneous and thus not predictable?

BACKGROUND: To date, no direct scientific evidence has been found linking tissue changes in multiple sclerosis (MS) patients, such as demyelination, axonal destruction or gliosis, with either steady progression and/or stepwise accumulation of focal CNS lesions. Tissue changes such as reduction of the retinal nerve fiber layer (RNFL) and the total macular volume (TMV), or brain- and spinal cord atrophy indicates an irreversible stage of tissue destruction. Whether these changes are found in all MS patients, and if there is a correlation with clinical disease state, remains controversial. The objective of our study was to determine, whether there was any correlation between the RNFL or TMV of patients with MS, and: (1) the lesion load along the visual pathways, (2) the ratios and absolute concentrations of metabolites in the normal-appearing white matter (NAWM), (3) standard brain atrophy indices, (4) disease activity or (5) disease duration.METHODS: 28 MS patients (RRMS, n = 23; secondary progressive MS (SPMS), n = 5) with moderately-high disease activity or long disease course were included in the study. We utilised: (1) magnetic resonance imaging (MRI) and (2) -spectroscopy (MRS), both operating at 3 Tesla, and (3) high-resolution spectral domain-OCT with locked reference images and eye tracking mode) to undertake the study.RESULTS: There was no consistency in the pattern of CNS metabolites, brain atrophy indices and the RNFL/TMV between individuals, which ranged from normal to markedly-reduced levels. Furthermore, there was no strict correlation between CNS metabolites, lesions along the visual pathways, atrophy indices, RNFL, TMV, disease duration or disability.CONCLUSIONS: Based on the findings of this study, we recommend that the concept of 'clinico-radiologico paradox' in multiple sclerosis be extended to CROP-'clinico-radiologico-ophthalmological paradox'. Furthermore, OCT data of MS patients should be interpreted with caution.</p