The Asia-Pacific Journal of Ophthalmology

  • Current Issue

    July/August 2018 - Volume 7 - Issue 4
    Special Issue on Controversies in Neuro-Ophthalmology
    pp: 215-279
    Guest Editors-in-Chief: Anthony Arnold, Prem Subramanian
    Guest Editors: Carmen Chan, Satoshi Kashii, Michael Lee, Janet Rucker, Patrick Yu-Wai-Man

Editorial

Controversies in Neuro-Ophthalmology: Where the Evidence Leads Us Subramanian, Prem S.; Arnold, Anthony C.
Historically, neuro-ophthalmologists were accused of “admiring” and not treating patients with various disorders of the optic nerve and central nervous system. Scientific and technological advances now allow for targeted management of neuromuscular disease, various forms of inflammatory and demyelinating optic neuropathies, and even nystagmus. New diagnostic tools permit more rapid and less invasive diagnosis of optic nerve abnormalities and systemic disease such as vasculitis. Research continues into cures for seemingly intractable problems like mitochondrial and relentlessly progressive optic neuropathies. With these advances come controversies, and in this issue of the Asia-Pacific Journal of Ophthalmology, experts tackle the promises and pitfalls in neuro-ophthalmic disease diagnosis and management.

Review Article

Steroid Treatment of Optic Neuropathies Stunkel, Leanne; Van Stavern, Gregory P.
The etiologies of optic neuropathy include inflammation, ischemia, toxic and metabolic injury, genetic disease, and trauma. There is little controversy over the practice of using steroids in the treatment of optic neuritis—it is well established that intravenous steroid treatment can speed visual recovery but does not alter final visual function. However, there is controversy surrounding the acceptable routes of administration, dosage, and course of treatment. Additionally, the typical patient with optic neuritis is young and otherwise healthy, and thus is likely to tolerate steroids well. In ischemic and traumatic causes of optic neuropathies, the initial injury is not inflammatory, but damage may be compounded by secondary injury due to resultant inflammation and swelling in the confined space of the optic canal. Steroids have been considered as a means of minimizing inflammation and swelling, and thus minimizing the secondary injury that results. However, the use of steroids in traumatic and ischemic optic neuropathies is highly controversial—the evidence for the efficacy of treatment with steroids is insufficient to show that there is significant benefit. Additionally, patients with these conditions are more likely to have comorbidities that make them vulnerable to significant adverse events with the use of steroids. In this article, we attempt to analyze the current state of the literature regarding the use of steroids in the treatment of optic neuropathies, specifically optic neuritis, nonarteritic anterior ischemic optic neuropathy, and traumatic optic neuropathy.
Neuromyelitis Optica: Review and Utility of Testing Aquaporin-4 Antibody in Typical Optic Neuritis Seay, Meagan; Rucker, Janet C.
Neuromyelitis optica (NMO) is an autoimmune, inflammatory demyelinating disorder often leading to severe vision impairment and disability. The discovery of a diagnostic biomarker, the aquaporin-4 antibody (AQP4-IgG), transformed the clinical diagnosis and treatment of NMO and broadened the spectrum of disease [NMO spectrum disorders (NMOSD)]. Though the antibody is highly sensitive and specific to NMOSD, routine testing in patients with typical optic neuritis is considered controversial. This article will provide a brief review of NMOSD and highlight the pros and cons of routine testing in typical optic neuritis.
Treatment of Nonarteritic Acute Central Retinal Artery Occlusion Sharma, Rahul A.; Dattilo, Michael; Newman, Nancy J.; Biousse, Valerie
Central retinal artery occlusion (CRAO) is an event most often caused by an embolus originating in the ipsilateral carotid artery, aortic arch, or heart. CRAO may result from partial or complete occlusion of the central retinal artery (CRA), which acts as the primary blood supply to the inner neurosensory retina, and typically results in profound vision loss and permanent visual disability. No consensus has emerged regarding the optimal treatment of CRAO. All proposed treatments are of questionable efficacy and many have uncertain risk profiles. In certain circumstances, thrombolysis may be attempted as a treatment option; however, the evidence to support broad use of thrombolytics in the treatment of acute CRAO remains elusive. It is known that the risk factors that predispose to other cardiovascular and cerebrovascular events are often present in CRAO. Accordingly, identification of patients at highest risk of stroke and secondary prevention of ischemic events remains the primary focus of management. This review offers a summary of the clinical presentation, diagnosis, and prognosis of CRAO, with an emphasis on treatment options.
Leber Hereditary Optic Neuropathy—Light at the End of the Tunnel? Kim, Ungsoo Samuel; Jurkute, Neringa; Yu-Wai-Man, Patrick
Leber hereditary optic neuropathy (LHON) is an important cause of mitochondrial blindness. The majority of patients harbor one of three mitochondrial DNA (mtDNA) point mutations, m.3460G>A, m.11778G>A, and m.14484T>C, which all affect complex I subunits of the mitochondrial respiratory chain. The loss of retinal ganglion cells in LHON is thought to arise from a combination of impaired mitochondrial oxidative phosphorylation resulting in decreased adenosine triphosphate (ATP) production and increased levels of reactive oxygen species. Treatment options for LHON remain limited, but major advances in mitochondrial neuroprotection, gene therapy, and the prevention of transmission of pathogenic mtDNA mutations will hopefully translate into tangible benefits for patients affected by this condition and their families.
Neuroprotection in Optic Neuropathy Levin, Leonard A.
Almost all optic neuropathies are untreatable, motivating the search for new therapies that address the final common pathway of optic nerve disease, retinal ganglion cell loss. These neuroprotective strategies have been primarily studied in glaucoma, the most common optic neuropathy, but increasing also tested at the laboratory and animal model level in nonglaucomatous optic neuropathies. More recently, several clinical trials, most of which are randomized, have begun to examine whether neuroprotection is efficacious in human optic nerve disease. Many of these trials are reviewed, along with the critical issues in the major areas of optic neuropathy, particularly the site of injury, the mechanism of axonal damage, and disease-specific features relevant to neuroprotection studies.
Updates and Controversies in the Management of Acute Optic Neuritis Meltzer, Ethan; Prasad, Sashank
Optic neuritis remains a common diagnosis with controversial management. Although typical optic neuritis is often associated with “good” recovery of visual acuity, patients are often left with persistent impairments of contrast sensitivity, color vision, and visual field. These permanent visual deficits correlate with structural injury to the anterior visual pathway and are closely linked to visual quality of life. High dose corticosteroids are commonly used for patients with acute optic neuritis. However, even several decades after the initial clinical trials, there remains significant controversy regarding the efficacy and utility of this treatment. There is a need for more effective treatments, and many new immunomodulatory and neuroprotective agents have been investigated recently. Atypical optic neuritis, such as that seen with neuromyelitis optica spectrum disorder, often requires more aggressive initial treatment. Thus, it is important for clinicians to have a framework for rapid diagnosis and triage of patients who present with typical or atypical optic neuritis. Lastly, optic neuritis is associated with an elevated long-term risk of developing multiple sclerosis. Some patients may benefit from initiation of medications targeting multiple sclerosis at the time of initial presentation of optic neuritis. Appropriate identification and treatment of patients at highest risk of developing multiple sclerosis may help impact their disease course, while limiting exposure to potential adverse effects in patients who are at lower risk and do not require disease-modifying treatment.
Treatment of Ocular Myasthenia Gravis Cornblath, Wayne T.
Myasthenia gravis is a relatively common neuromuscular disorder, with ocular myasthenia gravis being a subset defined as myasthenia gravis limited to the orbicularis, levator, and extraocular muscles. Patients with ocular myasthenia gravis can have disabling diplopia or functional blindness from ptosis and in most cases treatment is required. Like generalized myasthenia gravis, there are a variety of treatments available that include pyridostigmine, immunosuppression, intravenous immunoglobulin, plasmapheresis, thymectomy, lid crutches, ptosis surgery, and extraocular muscle surgery. Unfortunately, there is limited data on the use of individual treatments in ocular myasthenia gravis and no data comparing treatments. Using a combination of available data on treatment of generalized myasthenia gravis, data on treatment of ocular myasthenia gravis, best practices, and clinical experience we will provide a rational framework for treatment of ocular myasthenia gravis.
Use of Noninvasive Imaging in Giant Cell Arteritis Halbach, Caroline; McClelland, Collin M.; Chen, John; Li, Suellen; Lee, Michael S.
Giant cell arteritis (GCA) requires a prompt diagnosis to avoid significant morbidity among the elderly. An accurate diagnosis is also paramount given the side effect profile of long-term corticosteroid treatment. Temporal artery biopsy (TAB) has long remained the gold standard for the diagnosis of GCA but requires an invasive procedure that is not without risk. This article discusses the argument for and against the use of noninvasive imaging including ultrasound, magnetic resonance imaging, and positron emission tomography scanning for the diagnosis of GCA. It also provides a suggested diagnostic algorithm for when to consider noninvasive imaging versus TAB.
The Role of Optical Coherence Tomography in the Acute Management of Neuro-Ophthalmic Diseases Chan, Noel C.Y.; Chan, Carmen K.M.
Optical coherence tomography (OCT) can provide highspeed and high-resolution images of the anatomical structures of the optic nerve head and macula. However, in neuro-ophthalmic conditions that present acutely, structural changes lag functional deficits, and the role of OCT in the acute setting has been challenged. This review aims to summarize the recent literature and evidence supporting the use of OCT in the acute management of some common neuro-ophthalmic scenarios, including the differential diagnosis of optic disc swelling, and in patients with suspected papilledema, optic neuritis, ischemic optic neuropathies, and Leber hereditary optic neuropathy. The limitations of OCT are also discussed.
The Role of Optical Coherence Tomography in Differentiating Optic Disc Drusen from Optic Disc Edema Costello, Fiona; Malmqvist, Lasse; Hamann, Steffen
An elevated optic nerve head can be an ominous sign, sometimes signifying an underlying basis for raised intracranial pressure. Alternatively, patients may harbor a different mechanism for this optic nerve head appearance, including optic disc drusen (ODD), which does not confer any life-threatening implications. It is important to refine
the approach to distinguishing ODD from papilledema because this is a relatively common, and important, conundrum encountered in clinical practice. Optical coherence tomography (OCT) is a noninvasive, readily accessible, and cost-effective ocular imaging technique that can improve the diagnostic accuracy for detecting ODD; or, instead, increase the index of suspicion for papilledema, thus prompting additional investigations
needed to identify (or exclude) potential causes of raised intracranial pressure. In this review, we will discuss the value of OCT in the diagnostic approach to cases of mild optic disc elevation, with acknowledgment of the potential pearls and pitfalls of this imaging technology. In particular, we will emphasize the helpful role OCT can play in differentiating cases of ODD from mild papilledema in the context of idiopathic intracranial hypertension (IIH).
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