Assessing the anterior visual pathway in optic neuritis: recent experimental and clinical aspects

Abstract

Purpose of review Multiple sclerosis (MS) and related autoimmune disorders of the central nervous system such as neuromyelitis optica spectrum disorders (NMOSD) are characterized by chronic disability resulting from autoimmune neuroinflammation, with demyelination, astrocyte damage, impaired axonal transmission and neuroaxonal loss. Novel therapeutics stopping or reversing the progression of disability are still urgently warranted. This review addresses research on optic neuritis in preclinical experimental models and their translation to clinical trials. Recent findings Optic neuritis can be used as paradigm for an MS relapse which can serve to evaluate the efficacy of novel therapeutics in clinical trials with a reasonable duration and cohort size. The advantage is the linear structure of the visual pathway allowing the assessment of visual function and retinal structure as highly sensitive outcome parameters. Experimental autoimmune encephalomyelitis is an inducible, inflammatory and demyelinating central nervous system disease extensively used as animal model of MS. Optic neuritis is part of the clinicopathological manifestations in a number of experimental autoimmune encephalomyelitis models. These have gained increasing interest for studies evaluating neuroprotective and/or remyelinating substances as longitudinal, visual and retinal readouts have become available. Summary Translation of preclinical experiments, evaluating neuroprotective or remyelinating therapeutics to clinical studies is challenging. In-vivo readouts like optical coherence tomography, offers the possibility to transfer experimental study designs to clinical optic neuritis trials.

Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis

“…Retinal OCT is increasingly used as an outcome measure for clinical trials of candidate neuroprotective drugs in acute ON [23–26] and MS [27, 28]. Preclinical investigations in experimental ON using in vivo retinal outcomes can be readily transferred to a clinical trial scenario, yet the models best suited to address the different aspects of retinal neurodegeneration by in vivo OCT are still unknown.…”

Neuroprotective Properties of Dimethyl Fumarate Measured by Optical Coherence Tomography in Non-inflammatory Animal Models

“…In the experimental autoimmune encephalomyelitis and optic neuritis (EAEON) model, an animal model for MS, DMF has already been extensively tested (9,20,21). This inflammatory model, inducing prominent retinal degeneration (17), is frequently used to study the protective effects of therapeutics (13). However, an increasing body of evidence suggested effects of DMF beyond the immunomodulatory characteristics (8,9,22).…”

“…Optical coherence tomography (OCT) is a fast, non-invasive, interferometric technique allowing high resolution imaging of the eye's retina in patients and mice (12,13). The in vivo assessments of retinal neurodegeneration hence allow preclinical studies that are directly transferable to clinical trials.…”

“…Furthermore, the retinal degeneration of MS patients not only represents a morphological correlate of the functional visual deficits but also mirrors the overall disability assessed by clinical scores (14). Therefore, the anterior visual pathway is increasingly being used for clinical trials evaluating neuroprotective or remyelinating strategies (13). This makes OCT an ideal tool for visualizing the potential of DMF to prevent from neuroaxonal degeneration.…”

Comparison of different optomotor response readouts for visual testing in experimental autoimmune encephalomyelitis-optic neuritis

“…Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis is reportedly associated with strong optic neuritis (EAEON) resulting in demyelination and axonal damage of the optic nerve and in the following degeneration of the inner retinal layers: retinal nerve fiber layer (axons), ganglion cell layer (neurons), and inner plexiform layer (dendritic arbor) [ 2 – 6 ]. Studies on preclinical models of experimental autoimmune encephalomyelitis optic neuritis (EAEON) are ideally suited to translationally evaluate the promise of clinical ON trials especially since more and more in vivo clinical readouts are being adapted to the preclinical setting [ 7 ]. To investigate the visual function in rodents, the optomotor response (OMR) can be used.…”