Clinical update in optic nerve disorders

Abstract

Optic nerve disorders lead to visual loss and can result: from multiple etiologies, including optic neuritis, anterior ischemic optic neuropathy, glaucoma, Leber’s hereditary optic neuropathy and dominant optic atrophy. The recent advances in imaging technologies often supplement the history and clinical examination for identification of optic neuropathies. Correlation between the structural and functional changes in eye is important to validate these diagnostic techniques. Advancement in the understanding of disease process has led to the development of new potential therapeutic targets that may enable apt management of these conditions. Animal models play a crucial role in understanding the pathophysiology of these disorders, identifying therapeutic targets and testing prospective drugs, which are vital for providing better patient care. In this review, the authors aim to provide a clinical update to the readers about these optic neuropathies in addition to the essential role played by animal research in progressing their current state of knowledge.

Keywords:

• animal models
• anterior ischemic optic neuropathy
• clinical examination
• dominant optic atrophy
• glaucoma
• history
• imaging technologies
• Leber’s hereditary optic neuropathy
• optic nerve disorders
• optic neuritis

Financial & competing interest disclosure

MF Cordeiro is an inventor on patent applications owned by University College London and pertaining to Detection of Apoptosing Retinal cells. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Visual loss associated with conditions affecting the optic nerve such as optic neuritis, anterior ischemic optic neuropathy, glaucoma and Leber’s hereditary optic neuropathy can be diagnosed with a proficient history and clinical examination that can be confirmed using advanced investigations.

• Presence of optic neuritis or non-arteritic anterior ischemic optic neuropathy does not always correlate with a decrease in high-contrast visual acuity. A more efficient way to gauge the presence of optic neuropathy is to measure low-contrast sensitivity.

• Deficit in color vision may indicate subclinical optic neuritis; it may also be a strong predictor for future development of glaucoma and may be used as a valuable follow-up test in these cases.

• Higher rates of relative afferent pupillary defect detection are seen using infrared pupillometry in comparison to the swinging flashlight test or magnifier-assisted swinging flashlight test.

• Investigation of optic neuropathy may include blood tests (including inflammatory markers, serology and autoantibodies), electrodiagnostics and imaging (such as OCT and MRI).

• New imaging techniques are currently evaluating optic nerve structure and function, including possible pathological processes mediated by alteration in inflammation, blood flow and apoptosis.

• New treatment approaches in optic neuropathy are being investigated. These include neuroprotective strategies that aim to maintain neuronal function despite retinal ganglion cell loss. Gene replacement therapy is currently being investigated in Leber’s hereditary optic neuropathy. There are a range of cellular therapy approaches that aim to promote neuroprotection and neuroregeneration.

• Extrapolation of data acquired from animal experiments is often challenging owing to differences in the anatomy and biological behavior of the tissues between different species and also multifactorial pathogenic mechanisms of these neuropathies.

• Many of the animal models currently used reflect in part the disease described, reproducing the phenotype but not the pathophysiology. The validation of these models is necessary to develop new therapies for these disorders.