Retinal imaging with optical coherence tomography: a biomarker in multiple sclerosis?

Abstract

Multiple sclerosis (MS) is a progressive neurological disorder characterized by both inflammatory and degenerative components that affect genetically susceptible individuals. Currently, the cause of MS remains unclear, and there is no known cure. Commonly used therapies tend to target inflammatory aspects of MS, but may not halt disease progression, which may be governed by the slow, subclinical accumulation of injury to neuroaxonal structures in the central nervous system (CNS). A recognized challenge in the field of MS relates to the need for better methods of detecting, quantifying, and ameliorating the effects of subclinical disease. Simply stated, better biomarkers are required. To this end, optical coherence tomography (OCT) provides highly reliable, reproducible measures of axonal damage and neuronal loss in MS patients. OCT-detected decrements in retinal nerve fiber layer thickness and ganglion-cell layer–inner plexiform layer thickness, which represent markers of axonal damage and neuronal injury, respectively, have been shown to correlate with worse visual outcomes, increased clinical disability, and magnetic resonance imaging-measured burden of disease in MS patients. Recent reports have also suggested that OCT-measured microcystic macular edema and associated thickening of the retinal inner nuclear layer represent markers of active CNS inflammatory activity. Using the visual system as a putative clinical model in MS, OCT measures of neuroaxonal structure can be correlated with functional outcomes to help us elucidate mechanisms of CNS injury and repair. In this review, we evaluate evidence from the published literature and ongoing clinical trials that support the emerging role of OCT in diagnosing, staging, and determining response to therapy in MS patients.

Validation of inter-eye difference thresholds in optical coherence tomography for identification of optic neuritis in multiple sclerosis

“…The ability of both MRI and VEP to establish focal optic nerve lesions is hampered by confounding posterior visual pathway involvement. Contrarily, OCT reliably reflects both symptomatic and asymptomatic damage to the optic nerve (Petzold et al, 2017;Costello and Burton, 2018).…”

“…In MS, thinning of peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) are established markers of neuroaxonal damage (Petzold et al, 2017). While OCT is useful in predicting and monitoring disease progression, it can also be applied to detect clinical and even subclinical damage to the optic nerve (Petzold et al, 2017;Costello et al, 2006;Costello and Burton, 2018). Optic neuritis (ON), a typical manifestation of MS, results in axonal and neuronal damage to the optic nerve, measurable by OCT through reduced thickness of pRNFL and GCIPL, respectively (Petzold et al, 2017;Gabilondo et al, 2015).…”

“…It has been discussed to include the presence of an optic nerve lesion as evidence for establishing DIS in the McDonald criteria for diagnosis of MS (Filippi et al, 2016). OCT offers an intriguing method to objectify a history of clinical or subclinical optic nerve lesion in this context (Costello and Burton, 2018). However, evidence was not yet considered sufficiently specific for inclusion of OCT into the revision of McDonald criteria in 2017.…”

Retinal Nerve Fiber Layer Thickness and Oxidative Stress Parameters in Migraine Patients without Aura: A Pilot Study

“…Since its introduction in the clinical practice, optical coherence tomography (OCT) represents one of the most reliable methods for the evaluation of morphological changes in retinal and optic nerve structure [ 22 ]. OCT changes can indicate the retrograde trans-synaptic neuronal degeneration (RTSD) of the retinal ganglion cells (RGCs) [ 23 ], being useful for the evaluation of the neurodegenerative process associated with various neurological diseases, such as multiple sclerosis [ 24 ], Alzheimer’s disease [ 25 ], Parkinson’s disease [ 26 ], and various type of headache, including migraine [ 23 ]. OCT provides information about the axonal and neuronal loss in the retina, and consequently, offers information in the visual afferent pathways and central nervous system, facilitating the diagnosis and the management of neuro-ophthalmological diseases [ 27 ].…”

Absence of peripapillary retinal nerve-fiber–layer thinning in combined antiretroviral therapy-treated, well-sustained aviremic persons living with HIV

“…However, those findings were heterogeneous, and all studies were hampered by the absence of brain and orbit MRI to exclude optic neuropathy or CSVD (Table 1). Indeed, pRNFL thinning has been associated with optic neuropathies [25], and CSVD-surrogate WMHs in the general population [26,27] and HIV-infected children [28].…”