Risk factors for progressive axonal degeneration of the retinal nerve fibre layer in multiple sclerosis patients
ABSTRACT To quantify structural and functional degeneration in the retinal nerve fibre layer (RNFL) of patients with multiple sclerosis (MS) over a 2-year time period, and to analyse the effect of prior optic neuritis (ON) as well as the duration and incidence of MS relapses.
166 MS patients and 120 healthy controls underwent assessment of visual acuity and colour vision, visual field examination, optical coherence tomography, scanning laser polarimetry and visual evoked potentials (VEPs). All subjects were re-evaluated after a period of 12 and 24 months.
Changes in the optic nerve were detected by structural measurements but not by functional assessments. Changes registered in MS patients were greater than changes in healthy controls (p<0.05). Eyes with previous ON showed a greater reduction of parameters in the baseline evaluation, but RNFL atrophy was not significantly greater in the longitudinal study. Patients with MS relapses showed a greater reduction of RNFL thickness and VEP amplitude compared with non-relapsing cases. Patients with and without treatment showed similar measurement reduction, but the non-treated group had a significantly higher increase in Expanded Disability Status Scale (p=0.029).
MS causes progressive axonal loss in the optic nerve, regardless of a history of ON. This ganglion cell atrophy occurs in all eyes but is more marked in MS eyes than in healthy eyes.
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ABSTRACT: Neurodegeneration plays an important role in permanent disability in multiple sclerosis (MS). The objective of this paper is to determine whether progressive neurodegeneration occurs in MS eyes without clinically evident inflammation. Retinal nerve fiver layer thickness (RNFLT) and ganglion cell-inner plexiform layer thickness (GCIPT) were measured using Cirrus optical coherence tomography (OCT) in 133 relapsing-remitting MS (RRMS) patients (149 non-optic neuritis (ON), 97 ON eyes, last ON ≥6 months). Ninety-three patients were scanned at two visits. Percentages of abnormal GCIPT vs RNFLT (<5% of machine norms) in cross-sectional data were compared. Relations between RNFLT/GCIPT and MS duration (cross-sectional) and follow-up time (longitudinal) were assessed. GCIPT was abnormal in more eyes than RNFLT (27% vs 16% p = 0.004 in non-ON, 82% vs 72% p = 0.007 in ON). RNFLT and GCIPT decreased with MS duration by -0.49 µm/yr (p = 0.0001) and -0.36 (p = 0.005) for non-ON; -0.52 (p = 0.003) and -0.41 (p = 0.007) for ON. RNFLT and GCIPT decreased with follow-up time by -1.49 µm/yr (p < 0.0001) and -0.53 (p = 0.004) for non-ON, -1.27 (p = 0.002) and -0.49 (p = 0.04) for ON. In RRMS eyes without clinically evident inflammation, progressive loss of RNFLT and GCIPT occurred, supporting the need for neuroprotection in addition to suppression of autoimmune responses and inflammation.Multiple Sclerosis 03/2014; 20(10). DOI:10.1177/1352458514523498 · 4.86 Impact Factor
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ABSTRACT: The black void behind the pupil was optically impenetrable before the invention of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal imaging and image processing, especially over the past decade have opened a route to another unexplored landscape, the retinal neurovascular architecture and the retinal ganglion pathways linking to the central nervous system (CNS) beyond. Exploiting these research opportunities requires multidisciplinary teams to explore the interface sitting at the border between ophthalmology, neurology and computing science. It is from the detail and depth of retinal phenotying from which novel metrics and candidate biomarkers are likely to emerge. Confirmation that in vivo retinal neurovascular measures are predictive of microvascular change in the brain and other organs is likely to be a major area of research activity over the next decade. Unlocking this hidden potential within the retina requires integration of structural and functional datasets, i.e. multimodal mapping and longitudinal studies spanning the natural history of the disease process.And with further advances in imaging, it is likely that this area of retinal research will remain active and clinically relevant for many years to come. Accordingly, this review looks at state-of-the-art retinal imaging and its application to diagnosis, characterisation and prognosis of chronic Illness or long-term conditions.British Journal of Radiology 06/2014; 87(1040):20130832. DOI:10.1259/bjr.20130832 · 1.53 Impact Factor
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ABSTRACT: Purpose: To calculate and validate a linear discriminant function (LDF) for Fourier domain optical coherence tomography (OCT) to improve the diagnostic ability of retinal and retinal nerve fiber layer (RNFL) thickness parameters in the detection of Alzheimer's disease (AD). Method: AD patients (n=151) and age-matched, healthy subjects (n=61) were enrolled. The Cirrus and Spectralis OCT systems were used to obtain retinal measurements and circumpapillary RNFL thickness for each participant. A LDF was calculated using all retinal and RNFL OCT measurements. Receiver operating characteristic (ROC) curves were plotted and compared among the LDF and the standard parameters provided by OCT devices. Sensitivity and specificity were used to evaluate diagnostic performance. A validating set was used in an independent population to test the performance of the LDF. Results: The optimal function was calculated using the RNFL thickness provided by Spectralis OCT, using the 768 points registered during peripapillary scan acquisition (grouped to obtain 24 uniformly divided locations): 18.325 + 0.056 x (315º-330º) - 0.122 x (300º-315º) - 0.041 x (285º-300º) + 0.091 x (255º-270º) + 0.041 x (225º-240º) + 0.183 x (195º-210º) - 0.108 x (150º-165º) - 0.092 x (75º-90º) + 0.051 x (30º-45º). The largest area under the ROC curve was 0.967 for the LDF. At 95% fixed specificity, the LDF yielded the highest sensitivity values. Conclusions: Measurements of RNFL thickness obtained with the Spectralis OCT device differentiated between healthy and AD individuals. Based on the area under the ROC curve, the LDF was a better predictor than any single parameter.Investigative ophthalmology & visual science 04/2014; 55(5). DOI:10.1167/iovs.13-13629 · 3.43 Impact Factor