**Author details**

**Figure 4.** The pathways of apoptosis. Interference with any of these steps may prevent the apoptosis cascade.

also from ischemia if the optic disc does not receive enough oxygen even without AION. This damage is added to the damage caused by the mechanical effect of optic disc compression.

Patients with glaucoma suffer loss of axons of the ganglion cells as they pass the optic disc. Two theories explain the axonal loss. The first one is mechanical. According to this theory, the force caused by the IOP impedes axonal transport (flow) (micro-strangulation) and this may trigger axonal apoptosis [7]. The second theory is vascular. This means that the IOP impedes vascular supply to the optic disc. This causes a relative ischemia to the optic disc and triggers apoptosis. It is probable that both mechanisms coexist and the mechanical force may have a greater influence. Nonetheless, apoptosis, and not degeneration/necrosis, is the mechanism of axonal death in glaucoma. Apoptosis is programmed cell death, while necrosis is a different process involving extracellular components of inflammation. It consists of several pathways initiated be certain extracellular ligands such as programmed death ligand 1 (PD-L1), Fas ligand (FasL), tumor necrosis factor (TNF), nerve growth factor (NGF), growth factors, and others (**Figure 4**) [8, 9]. These molecules attach to receptors on the cell wall such as tropomyosin kinase receptor (TRK), tyrosine kinase receptor (RTK), receptor of apoptosis signal factor (Fas), and tissue necrosis factor receptor (TNFR) that trigger intracellular cascades that involve multiple pathways and molecules including the caspase cascade. These processes

**8.5. Continuation of the neuronal apoptosis**

30 Causes and Coping with Visual Impairment and Blindness

Shimon Rumelt\* and Schachar Schreiber

\*Address all correspondence to: shimonr@gmc.gov.il

Department of Ophthalmology, Galilee Medical Center, Nahariya and Faculty of Medicine, Bar Ilan University, Zefat, Israel

### **References**

[1] World Health Organization. Visual Impairment and Blindness. Fact Sheet No. 282. August 2014

**Chapter 3**

**Provisional chapter**

**Visual Loss in Neuro-Ophthalmology**

**Visual Loss in Neuro-Ophthalmology**

DOI: 10.5772/intechopen.80682

Optic neuropathy is damage to the optic nerve from any cause. Damage and death of these nerve cells lead to characteristic features of optic neuropathy. The main symptom is loss of vision (visual acuity and visual field damages), with colors appearing subtly washed out in the affected eye. The diagnosis is made on clinical examination. The history often points to the possible etiology of the optic neuropathy. In most of the cases, one eye is affected but it could be both. A rapid onset is typical of demyelinating, inflammatory, ischemic, and traumatic causes. A gradual course points to compressive, toxic/nutritional, and hereditary causes. The classic clinical signs of optic neuropathy are visual acuity and field defects, dyschromatopsia, and abnormal pupillary response. There are ancillary investigations that can support the diagnosis of optic neuropathy. Visual field testing, neuroimaging of the brain and orbit are essential in many optic neuropathies including demyelinating and compressive. In the last decade, increase of use new technology for optic neuropathies evaluation including multifocal visual evoked potentials and optic coherence tomography. Long standing of optic neuropathy is described by pale optic disk or optic atrophy, which means damage and death of these nerve cells or neurons. **Keywords:** optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy (NAION), arteritic anterior ischemic optic neuropathy (AION), traumatic

Accurate medical history is very important information, helping to evaluate the etiology of visual loss. Rapid onset is characteristic of optic neuritis, ischemic optic neuropathy, inflammatory (non-demyelinating), and traumatic optic neuropathy. On the other hand, gradual onset over months or even years is typical of compressive toxic/nutritional optic neuropathy. A history over years is seen in compressive and hereditary optic neuropathies. The

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.80682

Eitan Z. Rath

Eitan Z. Rath

**Abstract**

optic neuropathy

**1. Introduction**


#### **Visual Loss in Neuro-Ophthalmology Visual Loss in Neuro-Ophthalmology**

#### Eitan Z. Rath Eitan Z. Rath

**References**

August 2014

1999;**10**:474-482

2007;**35**:495-516

2000;**69**:217-245

2014;**23**:282-287

[1] World Health Organization. Visual Impairment and Blindness. Fact Sheet No. 282.

[2] Jorje J, Ramoa-Marques R, Lourenço S, et al. IOP variations in the sitting and supine

[3] Yoon D-Y. Effects of head elevation on intraocular pressure in healthy subjects: Raising

[4] Roy Chowdhury U, Fautch MP. Intracranial pressure and its relationship to glaucoma: Current understanding and future directions. Medical Hypothesis, Discovery and

[5] Berdahl JP, Allingham RR. Intracranial pressure and glaucoma. Current Opinion in

[6] Hayreh SS. Role of nocturnal arterial hypotension in the development of ocular manifestations of systemic arterial hypertension. Current Opinion in Ophthalmology.

[7] Quigly HA. Ganglion cell death in glaucoma: Pathology recapitulates ontogeny.

[8] Elmore S. Apoptosis: A Review of programmed cell death. Toxicologic Pathology.

[9] Strasser A, O'connor L, Dixit VM. Apoptosis signaling. Annual Review of Biochemistry.

[10] Lazzaro EC, Mallick A, Singh M, et al. The effect of positional changes on intraocular pressure during sleep in patients with and without glaucoma. Journal of Glaucoma.

Australian and New Zealand Journal of Ophthalmology. 1995;**23**:85-91

positions. Journal of Glaucoma. 2010;**19**:609-612

Innovation in Ophthalmology. 2015;**4**:71-78

Ophthalmology. 2010;**21**:106-111

32 Causes and Coping with Visual Impairment and Blindness

bed head vs. using multiple pillows. Eye. 2014;**28**:1328-1333

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.80682

#### **Abstract**

Optic neuropathy is damage to the optic nerve from any cause. Damage and death of these nerve cells lead to characteristic features of optic neuropathy. The main symptom is loss of vision (visual acuity and visual field damages), with colors appearing subtly washed out in the affected eye. The diagnosis is made on clinical examination. The history often points to the possible etiology of the optic neuropathy. In most of the cases, one eye is affected but it could be both. A rapid onset is typical of demyelinating, inflammatory, ischemic, and traumatic causes. A gradual course points to compressive, toxic/nutritional, and hereditary causes. The classic clinical signs of optic neuropathy are visual acuity and field defects, dyschromatopsia, and abnormal pupillary response. There are ancillary investigations that can support the diagnosis of optic neuropathy. Visual field testing, neuroimaging of the brain and orbit are essential in many optic neuropathies including demyelinating and compressive. In the last decade, increase of use new technology for optic neuropathies evaluation including multifocal visual evoked potentials and optic coherence tomography. Long standing of optic neuropathy is described by pale optic disk or optic atrophy, which means damage and death of these nerve cells or neurons.

DOI: 10.5772/intechopen.80682

**Keywords:** optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy (NAION), arteritic anterior ischemic optic neuropathy (AION), traumatic optic neuropathy

### **1. Introduction**

Accurate medical history is very important information, helping to evaluate the etiology of visual loss. Rapid onset is characteristic of optic neuritis, ischemic optic neuropathy, inflammatory (non-demyelinating), and traumatic optic neuropathy. On the other hand, gradual onset over months or even years is typical of compressive toxic/nutritional optic neuropathy. A history over years is seen in compressive and hereditary optic neuropathies. The

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ophthalmologist or neurologist can make the differential diagnosis according the symptoms, the age of onset, and the gender. Young age group (15–45 years) for optic neuritis women gender and pain on eye movement are more typical for optic neuritis versus. Elderly patients (older than 50 years), painless loss of vision without gender predisposition are typical for ischemic optic neuropathy. Additionally, in a young patient, history of neurological symptoms such as parenthesis, limb weakness, and ataxia is suggestive of demyelinating optic neuritis.

frequent in Caucasians, no gender predisposition, and mean age at onset in most studies is from 57 to 65 years. No clinically effective treatment exists because little is known about its pathophysiology, and there are only few histopathological studies of the acute condition.

Visual Loss in Neuro-Ophthalmology http://dx.doi.org/10.5772/intechopen.80682 35

NAION [1, 2] typically presents suddenly upon awakening the painless patient notes seeing poorly in one eye. Vision in that eye is obscured by a dark shadow, often involving just the upper or lower half of vision. On examination, the patient is found with visual acuity reduction from 20/25 down to hand movement only, relative afferent pupillary defect (RAPD), swollen disk (segmental or diffuse) with splinter hemorrhages (see **Figure 1**), absent of large cup, and contralateral disk is small and crowded in 20–40% of the patents [4]. In approximately 6 months following the infarct visual acuity improves by 3 or more lines of vision on the Snellen chart in 42.7% of patients. In addition, vision had worsened by 3 lines or more in 12.4% of patients; some clinicians use the term "progressive ischemic optic neuropathy". Second eye involvement occurs in approximately 20% of patients with NAION within 5 years. Furthermore, most cases of NAION involve the loss of an altitudinal hemifield (**Figure 2**) (either the upper or mostly lower half of the visual field, but not both), and visual acuity

**Figure 2** shows a few cases of NAION, which involve almost total loss of vision. The mechanism of injury for NAION is used to be controversial. Experts have come to a consensus that most cases involve two main risk factors. The first is a predisposition in the form of a type of optic disk shape named crowded disk [4, 5] or "disk at risk," where the cup/disk ratio is low (0.0–0.1), and secondly, cardiovascular risk factors as diabetes mellitus, hypertension, hypercholesterolemia, and coagulation deficits. Laboratory examinations at the presentation to differentiate between NAION and AAION include (erythrocyte sedimentation rate [ESR] that should be less than 40 mm/h) and C-reactive protein (CRP). It is advised to draw complete blood count and serum chemistry especially glucose, serum cholesterol and triglycerides, coagulophatic state, antitrombin III antiphospholipid antibody, and serum fibrinogen. Analysis of brain MRI suggests an increasing number of ischemic white matter lesions.

remains almost normal or slightly reduced.

**Figure 1.** Disk appearance in nonarteritic ischemic optic neuropathy.

In an elderly patient (more than 60 years mostly 70–80 years) with signs of severe optic neuropathy and the presence of preceding transient visual loss, temporal pain, jaw claudication, fatigue, fever, anemia, weight loss and myalgia, an arteritic ischemic optic neuropathy (AION) due to giant cell arteritis (GCA) should be suspected.

In children, a history of recent flu-like illness or vaccination days or weeks before vision loss points to a para-infectious or postvaccinia optic neuritis, respectively.

Transient visual obscurations, transient diplopia, and headache should raise the suspicion of increased intra-cranial pressure.

The use of any medications should be carefully noted, since some are either directly or indirectly toxic to the optic nerve. These include drugs as ethambutol, methanol, isoniazid, tobacco alcohol, and more. History of diabetes mellitus, systemic hypertension, hypercholesterolemia, coagulation deficit, and smoking is more common in patients with nonarteritic ischemic optic neuropathy (NAION). Patients who have history of malignancy may have infiltrative or para-neoplastic optic neuropathy. It is important to inquire into the patient's general health, eating, and social habits (drinking and smoking) in suspected nutritional optic neuropathy (complex B–vitamins). In addition, a detailed family history is inquired in diagnosing hereditary autosomal and mitochondrial optic neuropathies.

This chapter addresses the major diseases neuropathies accompanied by rapid visual loss: nonarteritic and arteritic optic neuropathy, traumatic optic neuropathy, and optic neuritis.
