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Handb Clin Neurol 2021 ;178:79-96

UCL Institute of Ophthalmology, University College London, London, United Kingdom; Department of Electrophysiology, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. Electronic address:

This chapter reviews common applications of visual electrophysiology relevant to neuro-ophthalmology practice. The use of standard tests and extended protocols are described including the cortical visual evoked potential and pattern and full-field electroretinogram (PERG; ERG) methods, the latter including the photopic negative response. Abnormalities of these recordings are rarely specific but provide valuable diagnostic guidance and an objective measure of visual pathway function, difficult or impossible to infer by other methods. Read More

Am J Ophthalmol Case Rep 2020 Dec 16;20:100932. Epub 2020 Sep 16.

Roski Eye Institute, University of Southern California, Los Angeles, CA, 90033, USA.

Purpose: To report a rare case of reversible vision loss from tacrolimus-associated toxic optic neuropathy.

Observations: A 30-year-old man with cystic fibrosis requiring bilateral lung transplantation developed painless, bilateral, gradual onset central vision loss with dyschromatopsia two years after starting tacrolimus. Visual fields revealed bilateral cecocentral scotomas. Read More

Nutrients 2020 Aug 31;12(9). Epub 2020 Aug 31.

Ophthalmology Unit, S. Orsola-Malpighi University Hospital, University of Bologna, 40138 Bologna, Italy.

Nutritional optic neuropathy is a cause of bilateral, symmetrical, and progressive visual impairment with loss of central visual acuity and contrast sensitivity, dyschromatopsia, and a central or centrocecal scotoma. The clinical features are not pathognomonic, since hereditary and toxic forms share similar signs and symptoms. It is becoming increasingly common due to the widespread of bariatric surgery and strict vegetarian or vegan diets, so even the scientific interest has recently increased. Read More

Optom Vis Sci 2020 Jul;97(7):477-481

Department of Ophthalmology, Consorcio Hospital General Universitario of Valencia, Valencia, Spain.

Significance: Nutritional and toxic optic neuropathies are rare disorders characterized by visual impairment due to optic nerve damage by a toxin, usually with coexisting nutritional deficiencies. Its pathophysiology is still unclear, and multiple mechanisms implicated act synergistically to bring about this condition. The decline in its incidence and its confusing clinical appearance make diagnosing nutritional and toxic optic neuropathies challenging. Read More

J Neuroophthalmol 2020 09;40(3):423-427

Departments of Ophthalmology and Vision Sciences (PF, EM), and Medical Imaging (LA-S), Faculty of Medicine, University of Toronto, Toronto, Canada; Department of Biomedical Physics (GM), Ryerson University, Toronto, Canada; Department of Laboratory Medicine (DH), University of Toronto, Toronto, Canada.

A 70 year-old man presented with insidiously progressing central visual acuity loss in both eyes over several years. Objectively the only abnormality identified on the exam was questionable granularity in the fovea in each eye. Extensive work up which included neuro-imaging, screening blood work for toxic and nutritional causes of optic neuropathy as well as electroretinogram and fluorescein angiography to rule out subtle maculopathy was all unrevealing. Read More

Continuum (Minneap Minn) 2019 Oct;25(5):1265-1288

Purpose Of Review: The diagnosis of visual loss from toxic-metabolic and hereditary optic neuropathies may be delayed in some cases because of a failure to elicit important information in the clinical history or to recognize typical examination findings. An understanding of the features specific to each type of toxic-metabolic and hereditary optic neuropathy, and of the underlying mechanism of insult to the optic nerve, could lead to earlier recognition, diagnosis, and treatment (when available).

Recent Findings: Understanding of the role of mitochondria in toxic-metabolic and hereditary optic neuropathies is growing, particularly regarding the mechanism of insult of certain agents (medications and toxins) and of vitamin B12 deficiency. Read More

Neuropediatrics 2019 12 22;50(6):341-345. Epub 2019 Jul 22.

ENT Unit, Department of Otorhinolaryngology, University of Catania, Italy.

Optic neuropathy consists of several etiological events. The primary etiologies of its acute form include optic neuritis, ischemic optic neuropathy, inflammatory (nondemyelinating) disorders, and trauma. Its subacute and chronic forms are most often linked to compressive, toxic, nutritional, or hereditary-genetic causes. Read More

Curr Treat Options Neurol 2019 Feb 7;21(1). Epub 2019 Feb 7.

Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK.

Purpose Of Review: Nutritional optic neuropathy is a potential cause of severe visual loss; however, appropriate and timely management can result in excellent visual outcomes. The purpose of this review is to outline our current understanding of the treatment and outcomes for nutritional optic neuropathy.

Recent Findings: Current understanding of nutritional optic neuropathy has been greatly aided by some well-reported and investigated epidemics of the condition, most notably the Cuban epidemic optic neuropathy of the early 1990s. Read More

Exp Eye Res 2019 01 24;178:255-262. Epub 2018 Aug 24.

Laboratory for Nutrition and Vision Research, USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington St, Boston, MA, 02111, USA. Electronic address:

Laboratory and epidemiological data indicate that high blood sugar levels and/or consuming high glycemia diets are linked to multiple age-related diseases, including age-related macular degeneration, cataract, Parkinson's disease, Alzheimer's disease, diabetic retinopathy, and, apparently glaucoma. High concentrations of blood sugar and perturbations of the systems that regulate blood sugar lead to the accumulation of advanced-glycation end products (AGEs). AGEs are toxic compounds that are formed from the combination of sugars and their metabolites with biomolecules in a non-enzymatic biochemical reaction called glycation. Read More

MEDICC Rev 2018 Apr;20(2):27-31

Neurology and Neurosurgery Institute, Havana, Cuba.

From 1991 to 1993, an epidemic of optic and peripheral neuropathy-the largest of the century-broke out in Cuba, affecting more than 50,000 people. Initially the main clinical features were decreased visual acuity, central and cecocentral scotomas, impaired color vision and absence of the papillomacular bundle. Later, peripheral and mixed optic-peripheral forms began to appear. Read More

Medicine (Baltimore) 2017 Dec;96(50):e9200

Department of Infectology, National Institute of Pediatrics Department of Ophtalmology, National Institute of Pediatrics Laboratory of Pharmacology, National Institute of Pediatrics, and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.

Background: Toxic optic neuropathies are alterations of the optic nerve and can be caused by environmental, pharmacological, or nutritional agents.

Case: It is about a 7-year-old male patient, a native of the State of Mexico, Mexico who was diagnosed with cervical mycobacterial lymphadenitis that required management with linezolid.

Observations: After 7 months of treatment, visual acuity of the left eye decreased and was accompanied by headache. Read More

Ir J Med Sci 2017 Aug 30;186(3):565-570. Epub 2016 Dec 30.

Mater Misericordiae University Hospital, Eccles Street, Dublin, 7, Ireland.

Background: Optic neuropathy is a disorder characterised by dysfunction or destruction of the optic nerve tissues. Acquired causes include interruption in the blood supply, nutritional deficiency, compression by a tumour or aneurysm, trauma, and toxic types (Ambizas and Patel In US Pharm 36(4):HS2-HS6, 1). Drug-induced optic neuropathy is of the toxic type and can be defined as a clinical syndrome characterised by papillomacular bundle damage, central, or cecocentral scotoma, and reduced colour vision (Ambizas and Patel In US Pharm 36(4):HS2-HS6, 2011; Sharma and Sharma In Indian J Ophthalmol 59(2):137-141, 2). Read More

Case Rep Neurol Med 2016 19;2016:5419432. Epub 2016 Jan 19.

Neurology Clinic, Dasman Diabetes Institute, P.O. Box 1180, 15462 Dasman, Kuwait; Al-Bahar Ophthalmology Center, Ibn Sina Hospital, P.O. Box 25427, 13115 Safat, Kuwait.

Optic neuritis is a common presentation of demyelinating disorders such as multiple sclerosis. It typically presents with acute painful monocular vision loss, whereas chronic optic neuropathy can be caused by compressive lesions along the anterior visual pathway, genetic, toxic, or nutritional causes. We report an unusual presentation mimicking optic neuritis, which was subsequently diagnosed as optic nerve sheath meningioma (ONSM). Read More

J Neuroophthalmol 2015 Sep;35(3):242-5

Department of Ophthalmology (LMCV, NFAS, AMDdS, RSdA, LAPAP, ARV, BICCJB, JPTF, DMA, JPPBdC), Central Lisbon Hospital Center, Lisbon, Portugal; Faculty of Medicine (LAPAP), Institute of Pharmacology and Neurosciences, University of Lisbon, Lisbon, Portugal; and Faculty of Medical Sciences (JPPBdC), New University of Lisbon, Lisbon, Portugal.

Objective: To analyze the retinal ganglion cell layer (RGL) by optical coherence tomography (OCT) in toxic and nutritional optic neuropathy and to correlate its thickness and volume with functional damage.

Methods: We conducted an observational cross-sectional study in healthy subjects and in patients with toxic optic neuropathy observed in the Neuro-Ophthalmology Department of Central Lisbon Hospital Center. Complete ophthalmologic examination, OCT (Heidelberg Spectralis), and automated static perimetry were performed. Read More

J Med Life 2014 Oct-Dec;7(4):472-6

"Carol Davila" University of Medicine and Pharmacy, Bucharest.

Part of the large group of nutritional and toxic optic neuropathies, tobacco-alcohol optic neuropathy is a disease often underdiagnosed or detected at a stage when the full recovery of vision is not possible. This article summarizes its signs and symptoms, describes the pathophysiological processes involved and provides the necessary information for diagnosis and treatment of the entity previously known as tobacco-alcohol amblyopia, reporting in the end, a challenging case along with its findings. Read More

Ann Afr Med 2015 Apr-Jun;14(2):109-13

Department of Ophthalmology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria.

Context: Optic atrophy is a clinical sign and not a disease. The etiology of optic atrophy is diverse, some of which may be life threatening.

Patients And Methods: A retrospective review of the medical records of all adult patients aged 16 years and above with nonglaucomatous optic atrophy at the eye clinic of the University of Benin Teaching Hospital over a 4-year period was conducted. Read More

Neurol India 2014 Nov-Dec;62(6):599-605

Department of Neurology, K. S. Hegde Medical Academy, Nitte University, Mangalore, Karnataka, India.

Visual loss consequent to anterior visual pathway involvement can occur in a variety of clinical settings. In a tropical country like India, apart from the usual suspects, nutritional, infective, and toxic amblyopia have to be considered in the differential diagnosis. The mode of onset (acute/chronic), unilateral versus bilateral involvement, accompanying occular pain or the lack of it, and pattern of visual loss are some of the pointers which help to differentiate optic neuropathy clinically. Read More

Acta Ophthalmol 2015 Aug 27;93(5):402-10. Epub 2014 Aug 27.

Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.

Toxic optic neuropathy (TON) is caused by the damage to the optic nerve through different toxins, including drugs, metals, organic solvents, methanol and carbon dioxide. A similar clinical picture may also be caused by nutritional deficits, including B vitamins, folic acid and proteins with sulphur-containing amino acids. This review summarizes the present knowledge on disease-causing factors, clinical presentation, diagnostics and treatment in TON. Read More

Continuum (Minneap Minn) 2014 Aug;20(4 Neuro-ophthalmology):877-906

Purpose Of Review: Toxic, nutritional, hereditary, traumatic, and neoplastic optic neuropathies result in significant disability due to visual dysfunction. Many of these conditions are treatable. Early diagnosis may allow for intervention to stabilize or improve vision and prevent unnecessary testing. Read More

Handb Clin Neurol 2014 ;121:1521-48

Department of Neurology, Weill Cornell Medical College, Methodist Neurological Institute, Houston, TX, USA. Electronic address:

A large number of causal agents produce spinal cord lesions in the tropics. Most etiologies found in temperate regions also occur in the tropics including trauma, herniated discs, tumors, epidural abscess, and congenital malformations. However, infectious and nutritional disorders occur with higher prevalence in tropical regions. Read More

J Neurol Sci 2013 Apr 7;327(1-2):41-5. Epub 2013 Mar 7.

Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, KS211, Boston, MA 02215, United States.

Introduction: Tobacco alcohol amblyopia is an outdated term for a rare condition characterized by visual impairment due to tobacco and alcohol abuse usually associated with nutritional deficiencies. The more accurate term used now is Nutritional Optic Neuropathy. The visual impairment generally presents as a centrocecal scotoma. Read More

Clin Neurol Neurosurg 2013 Aug 4;115(8):1389-93. Epub 2013 Feb 4.

Department of Clinical Neurophysiology, King's College Hospital, London, UK.

Background: The syndrome of subacute simultaneous peripheral neuropathy and bilateral optic neuropathy is known to occur in tropical countries, probably due to malnutrition or toxicity, but not often seen in developed countries. We report seven patients in London who were not malnourished or alcoholic, and in whom no clear cause was found.

Methods: We retrospectively reviewed the case notes and arranged some further investigations. Read More

Semin Ophthalmol 2010 Jul;25(4):112-22

Department of Neuro-ophthalmology, The Institute of Neurology and Neurosurgery, Havana, Cuba.

The similarities and differences between toxic/nutritional and hereditary optic neuropathy and the pathophysiologic mechanisms that they have in common are described. This is based on data from the epidemic suffered in Cuba in 1992, which affected the optic nerves of many individuals and the experience of the authors in dealing with various toxic optic neuropathies, as well as Leber's hereditary optic neuropathy. Read More

Eur J Radiol 2010 May 21;74(2):299-313. Epub 2010 Apr 21.

Head and Neck and Maxillofacial Radiology, Department of Radiology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH - 1211 Geneva 14, Switzerland.

This article provides an overview of the imaging findings of diseases affecting the optic nerve with special emphasis on clinical-radiological correlation and on the latest technical developments in MR imaging and CT. The review deals with congenital malformations, tumors, toxic/nutritional and degenerative entities, inflammatory and infectious diseases, compressive neuropathy, vascular conditions and trauma involving the optic nerve from its ocular segment to the chiasm. The implications of imaging findings on patient management and outcome and the importance of performing high-resolution tailored examinations adapted to the clinical situation are discussed. Read More

Acta Ophthalmol 2011 Aug 16;89(5):495-9. Epub 2010 Mar 16.

Department of Ophthalmology, Poznan City Hospital, Poland.

This article reviews the historical and current concepts of 'tobacco optic neuropathy' (TON) a rare disorder of optic nerve function related to the toxic effects of an unidentified constituent of tobacco. It is considered to be an entity distinct from that often described as 'tobacco-alcohol amblyopia', a disorder better described as a nutritional optic neuropathy. It is suggested that 'tobacco-alcohol amblyopia' is an inappropriate term, because the condition to which it refers is not an amblyopia, and there is little evidence to implicate a toxic effect of either tobacco or alcohol in the pathogenesis of that disorder. Read More

Drugs Today (Barc) 2007 Nov;43(11):827-36

Casey Eye Institute, Portland, Oregon, USA.

The term optic neuropathy is used to describe optic nerve damage caused by any of four main etiologies: ischemic, hereditary, nutritional and toxic. Ischemic and hereditary optic neuropathies produce profound and often irreversible vision loss. Proper diagnosis of nutritional or toxic optic neuropathies provides the opportunity for potential treatment and hope of restored visual function. Read More

Clin Ophthalmol 2007 Sep;1(3):233-46

Neuro-Ophthalmology Service, Department of Ophthalmology, Ibn Sina Hospital, PO Box 1262, Kuwait City, Kuwait.

Optic neuropathy is a frequent cause of vision loss encountered by ophthalmologist. The diagnosis is made on clinical grounds. The history often points to the possible etiology of the optic neuropathy. Read More

J Neurol Sci 2007 Nov 17;262(1-2):158-64. Epub 2007 Aug 17.

Department of Ophthalmology, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, 20, Rue Leblanc, 75015, Paris, France.

Nutritional deficiency may be the cause of a genuine optic neuropathy, sometimes associated with involvement of the peripheral nervous system. Nutritional optic neuropathies are usually bilateral, painless, chronic, insidious and slowly progressive. Most often, they present as a non-specific retrobulbar optic neuropathy. Read More