ECTRIMS eLearning

Vitreous haze as a novel marker for neurodegeneration in MS possibly indicating impairment of the retinal glymphatic system
ECTRIMS Learn. Coric D. 10/10/18; 231847; 104
Danko Coric
Danko Coric
Contributions
Abstract

Abstract: 104

Type: Young Scientific Investigators' Session

Abstract Category: Pathology and pathogenesis of MS - OCT

Introduction: Neurodegeneration in multiple sclerosis (MS) is associated with the breakdown of proteins. Clearance of such neurodegenerative waste products is driven by the glymphatic system of the brain. Recently we proposed that the glymphatic system of the brain extends to the retina. The retinal glymphatic system exits to the choroid and to the vitreous. Vitreous deposition of neurodegenerative waste (vitreous haze, VH) can be quantified from OCT raw data by a novel algorithm.
Objective: To investigate the relationship between VH and neurodegeneration in MS.
Methods: A cross-sectional study in 315 patients with MS and 87 healthy controls (HCs). The VH was quantified on OCT macular volume scans using an automated algorithm and all VH scores were log transformed after data extraction. Associations between VH and measures of neurodegeneration were investigated with generalized estimating equations.
Results: VH scores declined with age (β=-0.007, p< 0.001) and longer disease duration (β=-0.009, p=0.004) in MS patients. After controlling for age, there was a significant relationship between VH and grey matter volume (β=0.001, p< 0.001), white matter volume (β=0.001, p=0.002), macular ganglion cell - inner plexiform layer thickness (β=0.008, p< 0.001) and peripapillary retinal nerve fiber layer thickness (β=0.004, p< 0.011). In addition, patients with the highest level of disability showed less VH compared to patients with moderate disability (mean difference 0.16, p=0.020) and a trend towards lower levels of VH compared to patients with mild disability (mean difference 0.14, p=0.053). On a group level however, the VH scores between patients and HCs were similar (mean difference 0.03, p=0.419).
Conclusion: This study suggested that VH may be used as a novel biomarker to indirectly assess neurodegeneration in MS. There are two likely biological explanation for the consistent inverse relationship between VH and structural and functional metrics. There may be progressive impairment of the retinal glymphatic system in MS or a burnt-out stage of neurodegeneration is reached.
Disclosure: DC: nothing to disclose. GO: nothing to disclose. GM: nothing to disclose. AKD: nothing to disclose. PAK: reports speaker fees from Zeiss, Topcon, Heidelberg-Engineering, Haag-Streit, Novartis, Bayer and Allergan; is on the advisory board of Novartis and Bayer; has received consultancy fees from DeepMind and Optos. LJB: reports institutional support for OCT projects from TEVA. BMJU: has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA. DPC: has received speaker fees from Allergan and Santen. AP: reports personal fees from Novartis, grants from Novartis, outside the submitted work; and is part of the steering committee of the OCTiMS study which is sponsored by Novartis and the VUmc received research support. The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.

Abstract: 104

Type: Young Scientific Investigators' Session

Abstract Category: Pathology and pathogenesis of MS - OCT

Introduction: Neurodegeneration in multiple sclerosis (MS) is associated with the breakdown of proteins. Clearance of such neurodegenerative waste products is driven by the glymphatic system of the brain. Recently we proposed that the glymphatic system of the brain extends to the retina. The retinal glymphatic system exits to the choroid and to the vitreous. Vitreous deposition of neurodegenerative waste (vitreous haze, VH) can be quantified from OCT raw data by a novel algorithm.
Objective: To investigate the relationship between VH and neurodegeneration in MS.
Methods: A cross-sectional study in 315 patients with MS and 87 healthy controls (HCs). The VH was quantified on OCT macular volume scans using an automated algorithm and all VH scores were log transformed after data extraction. Associations between VH and measures of neurodegeneration were investigated with generalized estimating equations.
Results: VH scores declined with age (β=-0.007, p< 0.001) and longer disease duration (β=-0.009, p=0.004) in MS patients. After controlling for age, there was a significant relationship between VH and grey matter volume (β=0.001, p< 0.001), white matter volume (β=0.001, p=0.002), macular ganglion cell - inner plexiform layer thickness (β=0.008, p< 0.001) and peripapillary retinal nerve fiber layer thickness (β=0.004, p< 0.011). In addition, patients with the highest level of disability showed less VH compared to patients with moderate disability (mean difference 0.16, p=0.020) and a trend towards lower levels of VH compared to patients with mild disability (mean difference 0.14, p=0.053). On a group level however, the VH scores between patients and HCs were similar (mean difference 0.03, p=0.419).
Conclusion: This study suggested that VH may be used as a novel biomarker to indirectly assess neurodegeneration in MS. There are two likely biological explanation for the consistent inverse relationship between VH and structural and functional metrics. There may be progressive impairment of the retinal glymphatic system in MS or a burnt-out stage of neurodegeneration is reached.
Disclosure: DC: nothing to disclose. GO: nothing to disclose. GM: nothing to disclose. AKD: nothing to disclose. PAK: reports speaker fees from Zeiss, Topcon, Heidelberg-Engineering, Haag-Streit, Novartis, Bayer and Allergan; is on the advisory board of Novartis and Bayer; has received consultancy fees from DeepMind and Optos. LJB: reports institutional support for OCT projects from TEVA. BMJU: has received personal compensation for consulting from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and TEVA. DPC: has received speaker fees from Allergan and Santen. AP: reports personal fees from Novartis, grants from Novartis, outside the submitted work; and is part of the steering committee of the OCTiMS study which is sponsored by Novartis and the VUmc received research support. The research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.

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