Physics

Computed tomography (CT) uses X-ray beams to obtain tissue density values from which detailed cross-sectional images are formed by a computer. Tissue density is represented by a grey scale, white being maximum density (e.g. bone) and black being minimum density (e.g. air). Advanced CT scanners are able to acquire thinner slices leading to improved spatial resolution, together with faster examination times, without a proportionate increase in radiation dose. Images are acquired in an axial form and can be viewed in any plane using computer reconstruction. This multiplanar information can be an advantage over magnetic resonance (MR) with regard to anatomical detail. CT is widely available, easy to perform, relatively inexpensive and quick, but unlike MR exposes the patient to ionizing radiation.

Contrast enhancement

Iodinated contrast material improves sensitivity and specificity but is contraindicated in patients allergic to iodine and in those with renal failure. Contrast is not indicated in acute haemorrhage, bony injury or localization of foreign bodies because it may mask visualization of these high density structures.

Indications

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  Orbital trauma , for the detection of bony lesions such as fractures ( Fig. 19.1A ), blood, herniation of extraocular muscles into the maxillary sinus and surgical emphysema.

  
  

  
  

  
  

  

  
  

  
  

  CT scans. (A) Coronal image showing blow-out fractures of the left orbital floor and medial wall with orbital emphysema; (B) axial image showing bilateral enlargement of extraocular muscles and right proptosis; (C) axial image showing an acute parenchymal haematoma in the right temporal lobe; (D) axial image showing extensive subarachnoid blood in the basilar cisterns, and the Sylvian and interhemispheric fissures

  
  

  (Courtesy of N Sibtain – figs A, C and D; A Pearson – fig. B)

  
  
  
  
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  Evaluation of the extraocular muscles in thyroid eye disease ( Fig. 19.1B ); CT and MR (see below) have complementary advantages in the assessment of orbital disease.

  
  
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  Bony involvement of orbital tumours is better assessed using CT than MR.

  
  
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  Orbital cellulitis for assessment of intraorbital extension and subperiosteal abscess formation.

  
  
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  Detection of intraorbital calcification as in meningioma and retinoblastoma.

  
  
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  Detection of acute cerebral ( Fig. 19.1C ) or subarachnoid ( Fig. 19.1D ) haemorrhage , which is harder to visualize on MR within the first few hours of onset.

  
  
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  When MR is contraindicated (e.g. ferrous foreign body).

Physics

Magnetic resonance imaging (MRI) depends on the rearrangement of positively charged hydrogen nuclei (protons) when a tissue is exposed to a short electromagnetic pulse. When the pulse subsides, the nuclei return to their normal position, re-radiating some of the absorbed energy. Sensitive receivers pick up this electromagnetic echo. Unlike CT, it does not subject the patient to ionizing radiation. The signals are analyzed and displayed as a cross-sectional image that may be axial, coronal or sagittal.

Basic sequences

Weighting refers to two methods of measuring the relaxation times of the excited protons after the magnetic field has been switched off. Various body tissues have different relaxation times so that a given tissue may be T1- or T2-weighted (i.e. best visualized on that particular type of image). In practice, both types of scans are usually performed. It is easy to tell the difference between CT and MR images because bone appears white on CT but is not clearly demonstrated on MR.

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  T1-weighted images are generally optimal for viewing normal anatomy. Hypointense (dark) structures include cerebrospinal fluid (CSF) and vitreous. Hyperintense (bright) structures include fat, blood, contrast agents and melanin ( Figs 19.2A and C ).

  
  

  
  

  
  

  

  
  

  
  

  MR scans. (A) T1-weighted coronal image through the globe in which vitreous is hypointense (dark) and orbital fat is hyperintense (bright); (B) T2-weighted axial image in which vitreous and cerebrospinal fluid (CSF) are hyperintense; (C) T1-weighted midline sagittal image through the brain in which the CSF in the third ventricle is hypointense; (D) T2-weighted axial image through the brain in which the CSF in the lateral ventricles is hyperintense

  
  

  
  

  

  
  

  
  

  

  
  

  
  

  

  
  
  
  
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  T2-weighted images, in which water is shown as hyperintense, are useful for viewing pathological changes because oedematous tissue (e.g. inflammation) will display a brighter signal than normal surrounding tissue. CSF and vitreous are hyperintense as they have high water content. Blood vessels appear black on T2 imaging unless they are occluded ( Figs 19.2B and D ).

Image enhancement

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  Gadolinium contrast acquires magnetic moment when placed in an electromagnetic field. Administered intravenously, it remains intravascular unless there is a breakdown of the blood–brain barrier. It is only visualized on T1-weighted images, and enhancing lesions such as tumours and areas of inflammation will appear bright. Ideally MR is performed both before ( Fig. 19.3A ) and after ( Fig. 19.3B ) administration of gadolinium for most clinical indications. Special head or surface coils can also be used to improve spatial definition of the image. Adverse effects with gadolinium are uncommon and usually relatively innocuous.

  
  

  
  

  
  

  

  
  

  
  

  Enhancement techniques. (A) Pre-contrast sagittal T1-weighted image of a meningioma; (B) post-contrast image showing enhancement of the tumour; (C) coronal STIR image showing an intermediate signal intensity mass surrounding the left optic nerve consistent with an optic nerve sheath meningioma compared to STIR; (D) T1-weighted fat saturated coronal image of the same patient as (C) showing avid homogeneous enhancement of the meningioma; (E) coronal STIR image of right retrobulbar neuritis showing a high signal within the optic nerve with enlargement of the nerve sheath complex; (F) sagittal FLAIR image showing multiple periventricular plaques of demyelination

  
  

  (Courtesy of D Thomas – figs A and B; N Sibtain – figs C–F)

  
  

  
  

  

  
  

  
  

  

  
  

  
  

  

  
  

  
  

  

  
  

  
  

  

  
  
  
  
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  Fat-suppression techniques are useful for imaging the orbit because the bright signal of orbital fat on conventional T1-weighted imaging frequently obscures other orbital contents. Fat suppression eliminates this bright signal and better delineates normal structures (optic nerve and extraocular muscles) as well as tumours, inflammatory lesions and vascular malformations. The two types of fat-suppression sequence used for orbital imaging are:

  
  
  
  
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    T1 fat saturation used with gadolinium allows areas suspicious using other techniques to be enhanced, e.g. suppressing orbital fat signal to visualize optic nerve sheath lesions ( Figs 19.3C and D ).

    
    
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    STIR (short T1 inversion recovery) is the optimal sequence for detecting intrinsic lesions of the intraorbital optic nerve (e.g. optic neuritis – Fig. 19.3E ). STIR images have very low signal from fat but still have high signal from water.

  
  
  
  
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  FLAIR (fluid-attenuated inversion recovery) sequences suppress the bright CSF on T2-weighted images to allow better visualization of adjacent pathological tissue such as periventricular plaques of demyelination ( Fig. 19.3F ).

  
  
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  DWI/ADC (diffusion-weighted imaging and apparent diffusion coefficient). DWI measures aberrance in expected Brownian motion of free water, and is useful in acute ischaemic stroke to identify abnormalities at a very early stage – within minutes – and in distinguishing ischaemic damage reversible with treatment from irreversible damage such that intervention (e.g. with a thrombolytic agent) is unlikely to be of benefit.

  
  
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  FIESTA and CISS (fast imaging employing steady-state acquisition, and constructive interference in steady-state) are newer high-resolution sequences. In neuro-ophthalmology, a particular application may be the investigation of cranial nerve palsy.

Limitations

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  Bone appears black and is not directly imaged.

  
  
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  Recent haemorrhage is not detected, so MRI is inappropriate in patients with suspected acute intracranial bleeding.

  
  
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  It cannot be used in patients with magnetic foreign objects (e.g. cardiac pacemakers, intraocular foreign bodies and ferromagnetic aneurysm clips).

  
  
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  Substantial patient cooperation is required, including remaining motionless; it is poorly tolerated by claustrophobic patients as it involves lying in an enclosed space for many minutes.

Neuro-ophthalmic indications

MRI is the technique of choice for lesions of the intracranial visual pathways.

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  The optic nerve is best visualized on coronal STIR images in conjunction with coronal and axial T1 fat saturation post-gadolinium images. Axial T1 images are useful for displaying normal anatomy. MRI can detect lesions of the intraorbital part of the optic nerve (e.g. neuritis, glioma) as well as intracranial extension of optic nerve tumours.

  
  
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  Optic nerve sheath lesions (e.g. meningioma) are of similar signal intensity to the nerve on T1- and T2-weighted images but enhance avidly with gadolinium.

  
  
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  Sellar masses (e.g. pituitary tumours) are best visualized by T1-weighted contrast-enhanced studies. Coronal images optimally demonstrate the contents of the sella turcica as well as the suprasellar and parasellar regions and are usually supplemented by sagittal images.

  
  
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  Cavernous sinus pathology is best demonstrated on coronal images; contrast may be required.

  
  
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  Intracranial lesions of the visual pathways (e.g. inflammatory, demyelinating, neoplastic and vascular). MRI allows further characterization of these lesions as well as better anatomical localization.

Magnetic resonance angiography

Magnetic resonance angiography (MRA) is a non-invasive method of imaging the intra- and extracranial carotid and vertebrobasilar circulations ( Fig. 19.4A ) to demonstrate abnormalities such as stenosis, dissection, occlusion, arteriovenous malformations and aneurysms. The motion sensitivity of MR is utilized to visualize blood flow within vessels and does not require contrast. However, because of the reliance on active flow, thrombosed aneurysms may be missed and turbulent flow may lead to difficulties in interpretation. The technique has limited facility in the detection of very small aneurysms. MRA adds about 10 minutes to the standard MRI acquisition time.

Cerebral angiography. (A) Normal MRA of the external carotid and vertebral circulation; (B) MRI venogram, axial view, demonstrating narrowing of the left transverse sinus (arrow) in idiopathic intracranial hypertension; (C) CT angiogram shows a left posterior communicating aneurysm (arrows); (D) conventional catheter angiogram with subtraction shows an aneurysm arising from the internal carotid artery at its junction with the posterior communicating artery (arrow)

(Courtesy of N Sibtain – figs A and C; G Liu, N Volpe and S Galetta, from Neuro-Ophthalmology Diagnosis and Management , Saunders 2010 – fig. B; JD Trobe, from ‘Neuro-Ophthalmology’, in Rapid Diagnosis in Ophthalmology , Mosby 2008 – fig. D)

Magnetic resonance venography

Over recent years increasing attention has been paid to intracranial venous system pathology, particularly dural sinus occlusion and stenosis. Historically, the venous phase of conventional digital subtraction angiography (DSA) has been used for intracranial venous assessment, and still offers high sensitivity and specificity. However, both CT and MRI can be used to similar purpose and are relatively non-invasive and low-risk compared to DSA; technological advances have conferred greatly improved accuracy. Whilst CTV (see below) is generally faster and offers high spatial resolution, it entails a significant radiation dose and always requires contrast for image acquisition. Magnetic resonance venography (MRV) can be used with contrast or using non-contrast enhanced techniques, among other indications making it suitable for patients to whom contrast cannot be given. Substantial advances in MRV pulse sequences now allow excellent visualization of the venous system ( Fig. 19.4B ), and increasing reliance on MRV seems to be evident. However, local resource availability, experience and expertise are critical in determining the choice of technique.

Computed tomographic angiography

Computed tomographic angiography (CTA) has been emerging as the method of choice in the investigation of intracranial aneurysms ( Fig. 19.4C ). It enables acquisition of extremely thin slice images of the brain following intravenous contrast. Images of the vessels can be reconstructed in three dimensions and viewed from any direction, aiding the approach to treatment. The investigation is safe and quick and does not carry the 1% risk of stroke associated with conventional catheter angiography.

Computed tomographic venography

Computed tomographic venography (CTV) is a fast high-resolution technique in which patient motion artefact is of lesser importance than with MRV. CTV is believed to be at least as sensitive as MRV in the diagnosis of cerebral venous thrombosis; both techniques may provide complementary findings in difficult diagnostic situations. However, contrast is always required and a significant radiation dose is delivered. Visualization of skull base structures is limited by bony artefact relative to MRV. The technique is similar to that of CTA.

Conventional catheter angiography

Conventional intra-arterial catheter angiography is usually performed under local anaesthetic. A catheter is passed via the femoral artery into the internal carotid and vertebral arteries in the neck under fluoroscopic guidance. Following contrast injection, images are acquired in rapid succession. Digital subtraction results in images of the contrast-filled vessels with the exclusion of background structures such as bone ( Fig. 19.4D ). Until recently, this technique was the first-line investigation in the diagnosis of intra­cranial aneurysms but may now be reserved for cases where CTA is equivocal or negative.

General structure ( Figs 19.5A, B and C )

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  Afferent fibres. The optic nerve carries approximately 1.2 million afferent nerve fibres, each of which originates in a retinal ganglion cell. Most of these synapse in the lateral geniculate body, although some reach other centres, notably the pretectal nuclei in the midbrain. Nearly one-third of the fibres subserve the central 5° of the visual field. Within the optic nerve itself the nerve fibres are divided into about 600 bundles by fibrous septae derived from the pia mater.

  
  
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  Surrounding layers

  
  
  
  
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    The innermost layer is the delicate and vascular pia mater.

    
    
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    The outer sheath comprises the arachnoid mater and the tougher dura mater which is continuous with the sclera; optic nerve fenestration involves incision of this outer sheath. The subarachnoid space is continuous with the cerebral subarachnoid space and contains CSF.

  
  

Structure of the optic nerve. (A) Transverse section, P = pia, A = arachnoid, D = dura; (B) longitudinal section, LC = lamina cribrosa; arrow points to a fibrous septum; (C) surrounding sheaths and pial blood vessels; (D) clinical appearance of the normal optic disc

(Courtesy of Wilmer Eye Institute – figs A and B)

Anatomical subdivisions

The optic nerve is approximately 50 mm long from globe to chiasm. It can be subdivided into four segments:

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  Intraocular segment (optic nerve head) is the shortest, being 1 mm deep and approximately 1.5 mm in vertical diameter. The ophthalmoscopically visible portion is called the optic disc ( Fig. 19.5D ).

  
  
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  Intraorbital segment is 25–30 mm long and extends from the globe to the optic foramen at the orbital apex. Its diameter is 3–4 mm because of the addition of the myelin sheaths to the nerve fibres. At the orbital apex the nerve is surrounded by the tough fibrous annulus of Zinn, from which originate the four rectus muscles.

  
  
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  Intracanalicular segment traverses the optic canal and measures about 6 mm. Unlike the intraorbital portion, it is fixed to the canal, since the dura mater fuses with the periosteum.

  
  
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  Intracranial segment joins the chiasm and varies in length from 5 to 16 mm (average 10 mm). Long intracranial segments are particularly vulnerable to damage by adjacent lesions such as pituitary adenomas and aneurysms.

Introduction

Optic atrophy refers to the late stage changes that take place in the optic nerve resulting from axonal degeneration in the pathway between the retina and the lateral geniculate body, manifesting with disturbance in visual function and in the appearance of the optic nerve head. It can be classified in several ways, including by whether axonal death is initiated in the retina (anterograde) or more centrally (retrograde), and by cause. Optic ‘atrophy’ is not true atrophy, a term that strictly refers to involutional change secondary to lack of use. A classification according to ophthalmoscopic appearance is set out below.

Primary optic atrophy

Primary optic atrophy occurs without antecedent swelling of the optic nerve head. It may be caused by lesions affecting the visual pathways at any point from the retrolaminar portion of the optic nerve to the lateral geniculate body. Lesions anterior to the optic chiasm result in unilateral optic atrophy, whereas those involving the chiasm and optic tract will cause bilateral changes.

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  Signs

  
  
  
  
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    Flat white disc with clearly delineated margins ( Fig. 19.7A ).

    
    

    
    

    
    

    

    
    

    
    

    Optic atrophy. (A) Primary due to compression; (B) primary due to nutritional neuropathy – note predominantly temporal pallor; (C) secondary due to chronic papilloedema – note prominent Paton lines (see text); (D) consecutive due to vasculitis

    
    

    (Courtesy of P Gili – fig. C)

    
    

    
    

    

    
    

    
    

    

    
    

    
    

    

    
    
    
    
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    Reduction in the number of small blood vessels on the disc surface.

    
    
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    Attenuation of peripapillary blood vessels and thinning of the retinal nerve fibre layer (RNFL).

    
    
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    The atrophy may be diffuse or sectoral depending on the cause and level of the lesion. Temporal pallor of the optic nerve head may indicate atrophy of fibres of the papillomacular bundle, and is classically seen following demyelinating optic neuritis. Band atrophy is a similar phenomenon caused by involvement of the fibres entering the optic disc nasally and temporally; it occurs in lesions of the optic chiasm or tract and gives nasal as well as temporal pallor.

  
  
  
  
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  Important causes

  
  
  
  
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    Optic neuritis.

    
    
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    Compression by tumours and aneurysms.

    
    
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    Hereditary optic neuropathies.

    
    
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    Toxic and nutritional optic neuropathies; these may give temporal pallor, particularly in early/milder cases when the papillomacular fibres are preferentially affected ( Fig. 19.7B ).

    
    
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    Trauma.

  
  

Secondary optic atrophy

Secondary optic atrophy is preceded by long-standing swelling of the optic nerve head.

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  Signs vary according to the cause and its course.

  
  
  
  
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    Slightly or moderately raised white or greyish disc with poorly delineated margins due to gliosis ( Fig. 19.7C ).

    
    
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    Obscuration of the lamina cribrosa.

    
    
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    Reduction in the number of small blood vessels on the disc surface.

    
    
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    Peripapillary circumferential retinochoroidal folds, especially temporal to the disc (Paton lines – see Fig. 19.7C ), sheathing of arterioles and venous tortuosity may be present.

  
  
  
  
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  Causes include chronic papilloedema, anterior ischaemic optic neuropathy and papillitis. Intraocular inflammatory causes of marked disc swelling are sometimes considered to cause secondary rather than consecutive atrophy (see below).

Consecutive optic atrophy

Consecutive optic atrophy is caused by disease of the inner retina or its blood supply. The cause is usually obvious on fundus examination, e.g. extensive retinal photocoagulation, retinitis pigmentosa or prior central retinal artery occlusion. The disc appears waxy, with reasonably preserved architecture ( Fig. 19.7D ).

Glaucomatous optic atrophy

See Ch. 10 .

According to ophthalmoscopic appearance

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  Retrobulbar neuritis , in which the optic disc appears normal, at least initially, because the optic nerve head is not involved. It is the most common type in adults and is frequently associated with multiple sclerosis (MS).

  
  
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  Papillitis is characterized by hyperaemia and oedema of the optic disc, which may be associated with peripapillary flame-shaped haemorrhages ( Fig. 19.8 ). Cells may be seen in the posterior vitreous. Papillitis is the most common type of optic neuritis in children, but can also affect adults.

  
  

  
  

  
  

  

  
  

  
  

  Papillitis

  
  
  
  
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  Neuroretinitis is characterized by papillitis in association with inflammation of the retinal nerve fibre layer and a macular star figure (see below). It is the least common type and is only rarely a manifestation of demyelination.

According to aetiology

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  Demyelinating. This is by far the most common cause.

  
  
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  Parainfectious , following a viral infection or immunization.

  
  
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  Infectious. This may be sinus-related, or associated with conditions such as cat-scratch disease, syphilis, Lyme disease, cryptococcal meningitis and herpes zoster.

  
  
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  Non-infectious causes include sarcoidosis and systemic autoimmune diseases such as systemic lupus erythematosus, polyarteritis nodosa and other vasculitides.

Overview

Demyelination is a pathological process in which normally myelinated nerve fibres lose their insulating myelin layer. The myelin is phagocytosed by microglia and macrophages, subsequent to which astrocytes lay down fibrous tissue in plaques. Demyelinating disease disrupts nervous conduction within the white matter tracts of the brain, brainstem and spinal cord. Demyelinating conditions that may involve the visual system include the following:

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  Isolated optic neuritis with no clinical evidence of generalized demyelination, although in a high proportion of cases this subsequently develops.

  
  
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  Multiple sclerosis (MS), by far the most common demyelinating disease (see below).

  
  
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  Devic disease (neuromyelitis optica), a very rare disease that may occur at any age, characterized by bilateral optic neuritis and the subsequent development of transverse myelitis (demyelination of the spinal cord) within days or weeks.

  
  
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  Schilder disease , a very rare relentlessly progressive generalized disease with an onset prior to the age of 10 years and death within 1–2 years. Bilateral optic neuritis without subsequent improvement may occur.

Multiple sclerosis

Multiple sclerosis (MS) is an idiopathic demyelinating disease involving central nervous system white matter. It is more common in women than men.

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  Presentation is typically in the third–fourth decades, generally with relapsing/remitting demyelination that may switch later to an unremitting pattern, and less commonly with progressive disease from the outset.

  
  
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  Systemic features may include:

  
  
  
  
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    Spinal cord, e.g. weakness, stiffness, sphincter disturbance, sensory loss.

    
    
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    Brainstem, e.g. diplopia, nystagmus, dysarthria, dysphagia.

    
    
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    Cerebral, e.g. hemiparesis, hemianopia, dysphasia.

    
    
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    Psychological, e.g. intellectual decline, depression, euphoria.

    
    
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    Transient features, e.g. the Lhermitte sign (electrical sensation on neck flexion) and the Uhthoff phenomenon (sudden worsening of vision or other symptoms on exercise or increase in body temperature).

  
  
  
  
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  Ophthalmic features

  
  
  
  
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    Common. Optic neuritis (usually retrobulbar), internuclear ophthalmoplegia, nystagmus.

    
    
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    Uncommon. Skew deviation, ocular motor nerve palsies, hemianopia.

    
    
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    Rare. Intermediate uveitis and retinal periphlebitis.

  
  
  
  
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  Investigation

  
  
  
  
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    Lumbar puncture shows oligoclonal bands on protein electrophoresis of cerebrospinal fluid in 90–95%.

    
    
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    MRI almost always shows characteristic white matter lesions (plaques – Fig. 19.9 and see Fig. 19.3F ).

    
    

    
    

    
    

    

    
    

    
    

    Multiple sclerosis. T1-weighted axial MR image showing characteristic periventricular plaques

    
    
    
    
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    VEPs are abnormal (conduction delay and a reduction in amplitude) in up to 100% of patients with clinically definite MS.

  
  

Association between optic neuritis and multiple sclerosis

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  The overall 15-year risk of developing MS following an acute episode of optic neuritis is about 50%; with no lesions on MRI the risk is 25%, but over 70% in patients with one or more lesions on MRI; the presence of MRI lesions is therefore a very strong predictive factor.

  
  
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  A substantially lower risk of developing MS when there are no MRI lesions is conferred by the following factors, providing critical support in deciding whether to commence immunomodulatory MS-prophylactic treatment following an optic neuritis episode:

  
  
  
  
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    Male gender.

    
    
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    Absence of a viral syndrome preceding the optic neuritis.

    
    
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    Optic disc swelling, disc/peripapillary haemorrhages or macular exudates.

    
    
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    Vision reduced to no light perception.

    
    
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    Absence of periocular pain.

  
  
  
  
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  Optic neuritis is the presenting feature of MS in up to 30%.

  
  
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  Optic neuritis occurs at some point in 50% of patients with established MS.

Clinical features of demyelinating optic neuritis

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  Symptoms

  
  
  
  
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    Subacute monocular visual impairment.

    
    
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    Usual age range 20–50 years (mean around 30).

    
    
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    Some patients experience tiny white or coloured flashes or sparkles (phosphenes).

    
    
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    Discomfort or pain in or around the eye is present in over 90% and typically exacerbated by ocular movement; it may precede or accompany the visual loss and usually lasts a few days.

    
    
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    Frontal headache and tenderness of the globe may also be present.

  
  
  
  
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  Signs

  
  
  
  
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    Visual acuity (VA) is usually 6/18–6/60, but may rarely be worse.

    
    
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    Other signs of optic nerve dysfunction (see above), particularly impaired colour vision and a relative afferent pupillary defect.

    
    
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    The optic disc is normal in the majority of cases (retrobulbar neuritis); the remainder show papillitis (see Fig. 19.8 ).

    
    
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    Temporal disc pallor may be seen in the fellow eye (see Fig. 19.7B for similar appearance), indicative of previous optic neuritis.

  
  
  
  
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  Visual field defects ( Fig. 19.10 )

  
  
  
  
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    Diffuse depression of sensitivity in the entire central 30° is the most common.

    
    
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    Altitudinal/arcuate defects and focal central/centrocaecal scotomas are also frequent.

    
    
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    Focal defects are frequently accompanied by an element of superimposed generalized depression.

  
  

  
  

  
  

  

  
  

  
  

  Visual field defects in optic neuritis. (A) Central scotoma; (B) centrocaecal scotoma; (C) nerve fibre bundle; (D) altitudinal

  
  
  
  
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  Course. Vision worsens over several days to 3 weeks and then begins to improve. Initial recovery is fairly rapid and then slower over 6–12 months.

  
  
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  Prognosis

  
  
  
  
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    More than 90% of patients recover visual acuity to 6/9 or better.

    
    
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    Subtle parameters of visual function, such as colour vision, may remain abnormal.

    
    
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    A mild relative afferent pupillary defect may persist.

    
    
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    Temporal optic disc pallor or more marked optic atrophy may ensue.

    
    
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    About 10% develop chronic optic neuritis with slowly progressive or stepwise visual loss.

  
  

Treatment following demyelinating optic neuritis

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  Indications for steroid treatment. When visual acuity within the first week of onset is worse than 6/12, treatment may speed up recovery by 2–3 weeks and may delay the onset of clinical MS over the short term. This may be relevant in the patients with poor vision in the fellow eye or those with occupational requirements, but the limited benefit must be balanced against the risks of high-dose steroids. Therapy does not influence the eventual visual outcome and the great majority of patients do not require treatment.

  
  
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  Steroid regimen. Intravenous methylprednisolone sodium succinate 1 g daily for 3 days, followed by oral prednisolone (1 mg/kg daily) for 11 days, subsequently tapered over 3 days. Oral prednisolone may increase the risk of recurrence of optic neuritis if used without prior intravenous steroid.

  
  
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  Immunomodulatory treatment (IMT) reduces the risk of progression to clinical MS in some patients, but the risk versus benefit ratio has not yet been fully defined with the options available, which include interferon beta, teriflunomide and glatiramer. A decision should be individualized, based on risk profile – particularly the presence of brain lesions – and patient preference; most do not commence IMT until a second episode of clinical demyelination has occurred, though there may be an increasing tendency towards a lower threshold.

Sarcoidosis

Optic neuritis affects 1–5% of patients with neurosarcoid. It may occasionally be the presenting feature of sarcoidosis but usually develops during the course of established systemic disease. The optic nerve head may exhibit a lumpy appearance suggestive of granulomatous infiltration and there may be associated vitritis ( Fig. 19.11 ). The response to steroid therapy is often rapid, though vision may decline if treatment is tapered or stopped prematurely, and some patients require long-term low-dose therapy. Methotrexate may also be used as an adjunct to steroids or as monotherapy in steroid-intolerant patients.

Sarcoid granuloma of the optic nerve head with overlying vitreous haze

Autoimmune

Autoimmune optic nerve involvement may take the form of retrobulbar neuritis or anterior ischaemic optic neuropathy (see below). Some patients may also experience slowly progressive visual loss suggestive of compression. Treatment is with systemic steroids and other immunosuppressants.

Introduction

Neuroretinitis refers to the combination of optic neuritis and signs of retinal, usually macular, inflammation. Cat-scratch fever is responsible for 60% of cases. About 25% of cases are idiopathic (Leber idiopathic stellate neuroretinitis). Other notable causes include syphilis, Lyme disease, mumps and leptospirosis.

Diagnosis

• •
  

  Symptoms. Painless unilateral visual impairment, usually gradually worsening over about a week.

  
  
• •
  

  Signs

  
  
  
  
  • ○
    

    VA is impaired to a variable degree.

    
    
  • ○
    

    Signs of optic nerve dysfunction are usually mild or absent, as visual loss is largely due to macular involvement.

    
    
  • ○
    

    Papillitis associated with peripapillary and macular oedema ( Fig. 19.12A ).

    
    

    
    

    
    

    

    
    

    
    

    Progression of neuroretinitis. (A) Severe papillitis; (B) later stage in a different patient showing macular star

    
    

    (Courtesy of P Saine – fig. A; L Merin – fig. B)

    
    

    
    

    

    
    
    
    
  • ○
    

    A macular star ( Fig. 19.12B ) typically appears as disc swelling settles; the macular star resolves with a return to normal or near-normal visual acuity over 6–12 months.

    
    
  • ○
    

    Venous engorgement and splinter haemorrhages may be present in severe case.

    
    
  • ○
    

    Fellow eye involvement occasionally develops.

  
  
  
  
• •
  

  Optical coherence tomography (OCT) demonstrates sub- and intraretinal fluid to a variable extent.

  
  
• •
  

  Fluorescein angiography (FA) shows diffuse leakage from superficial disc vessels.

  
  
• •
  

  Blood tests may include serology for Bartonella and other causes according to clinical suspicion (see also Ch. 11 ).

Treatment

This is specific to the cause, and often consists of antibiotics. Recurrent idiopathic cases may require treatment with steroids and/or other immunosuppressants.

Introduction

Non-arteritic anterior ischaemic optic neuropathy (NAION) is caused by occlusion of the short posterior ciliary arteries resulting in partial or total infarction of the optic nerve head. Predispositions include structural crowding of the optic nerve head so that the physiological cup is either very small or absent, hypertension (very common), diabetes mellitus, hyperlipidaemia, collagen vascular disease, antiphospholipid antibody syndrome, hyperhomocysteinaemia, sudden hypotensive events, cataract surgery, sleep apnoea syndrome and erectile dysfunction. Patients are usually over the age of 50, but are typically younger than those who develop arteritic ION (see below).

Diagnosis

• •
  

  Symptoms

  
  
  
  
  • ○
    

    Sudden painless monocular visual loss; this is frequently discovered on awakening, suggesting a causative role for nocturnal hypotension.

  
  
  
  
• •
  

  Signs

  
  
  
  
  • ○
    

    VA is normal or only slightly reduced in about 30%. The remainder has moderate to severe impairment.

    
    
  • ○
    

    Visual field defects are typically inferior altitudinal but central, paracentral, quadrantic and arcuate defects may also be seen.

    
    
  • ○
    

    Dyschromatopsia is usually proportional to the level of visual impairment, in contrast to optic neuritis in which colour vision may be severely impaired when VA is reasonably good.

    
    
  • ○
    

    Diffuse or sectoral hyperaemic disc swelling, often associated with a few peripapillary splinter haemorrhages ( Fig. 19.13 ).

    
    

    
    

    
    

    

    
    

    
    

    Non-arteritic anterior ischaemic optic neuropathy

    
    
    
    
  • ○
    

    Disc swelling gradually resolves and pallor ensues 3–6 weeks after onset.

  
  
  
  
• •
  

  Investigation should include blood pressure, a fasting lipid profile and blood glucose. It is also very important to exclude occult giant cell arteritis (see below) with symptomatic enquiry and testing as appropriate. Atypical features may prompt special investigations, such as neuroimaging.

  
  
• •
  

  Prognosis. Improvement in vision is common although recurrence occurs in about 6%. About 50% of eyes achieve 6/9 or better, though 25% will only reach 6/60 or worse.

  
  
• •
  

  Fellow eye. Involvement of the fellow eye occurs in about 10% of patients after 2 years and 15% after 5 years. When the second eye becomes involved, optic atrophy in one eye and disc oedema in the other gives rise to the ‘pseudo-Foster Kennedy syndrome’.

Treatment

• •
  

  There is no definitive treatment.

  
  
• •
  

  Optic nerve fenestration has not been shown to be of benefit.

  
  
• •
  

  Some authorities advocate short-term systemic steroid treatment.

  
  
• •
  

  Any underlying systemic predispositions should be treated.

  
  
• •
  

  Although aspirin is effective in reducing systemic vascular events and is frequently prescribed in patients with NAION, it does not appear to reduce the risk of involvement of the fellow eye.

Diagnosis of giant cell arteritis

GCA is a granulomatous necrotizing arteritis ( Fig. 19.14A ) with a predilection for large and medium-size arteries, particularly the major aortic branches and the superficial temporal (STA), ophthalmic, posterior ciliary and proximal vertebral arteries. The severity and extent of involvement are associated with the quantity of elastic tissue in the media and adventitia and intracranial arteries are usually spared as they possess little elastic tissue. Smoking, low body mass index and early menopause may be independent risk factors. Patients are usually elderly (average 70 years) and the condition is extremely rare under the age of 50. Women are affected four times more commonly than men. The diagnosis of both GCA and PMR is essentially clinical; the American College of Rheumatology criteria may be helpful in diagnostic decision-making ( Table 19.2 ).

• •
  

  Symptoms

  
  
  
  
  • ○
    

    Scalp tenderness, first noticed when combing the hair, is common.

    
    
  • ○
    

    Headache, which may be localized to the frontal, occipital or temporal areas or be more generalized.

    
    
  • ○
    

    Jaw claudication (cramp-like pain on chewing), caused by ischaemia of the masseter muscles, is virtually pathognomonic.

    
    
  • ○
    

    Non-specific symptoms such as weight loss, fever, night sweats, malaise and depression are common.

    
    
  • ○
    

    Double vision may occur.

    
    
  • ○
    

    Arteritic anterior ischaemic optic neuropathy (see below).

  
  
  
  
• •
  

  Other features

  
  
  
  
  • ○
    

    Superficial temporal arteritis is characterized by thickened, tender, inflamed and nodular arteries ( Fig. 19.14B ), though the signs may be subtle.

    
    
  • ○
    

    Pulsation is initially present, but later ceases, a sign strongly suggestive of GCA, since a non-pulsatile superficial temporal artery is highly unusual in a normal individual.

    
    
  • ○
    

    Ocular motor palsies, including a pupil-involving third nerve palsy, can manifest.

    
    
  • ○
    

    Scalp gangrene may occur in very severe cases.

    
    
  • ○
    

    Rare complications include dissecting aneurysms, aortic incompetence, myocardial infarction, renal failure and brainstem stroke.

  
  
  
  
• •
  

  Investigation

  
  
  
  
  • ○
    

    Erythrocyte sedimentation rate (ESR) is often very high, with a level of >60 mm/hr, although in approximately 20% of patients it is normal, even low–normal.

    
    
  • ○
    

    C-reactive protein (CRP) is invariably raised and may be helpful when ESR is equivocal.

    
    
  • ○
    

    Full blood count: elevated platelets and normocytic normochromic anaemia are commonly present.

    
    
  • ○
    

    Liver function tests are abnormal in one-third.

    
    
  • ○
    

    Autoantibodies are normal.

    
    
  • ○
    

    Temporal artery biopsy (TAB) should be performed if GCA is suspected. Steroid treatment (see below) should never be withheld pending biopsy, which should ideally be performed within 3 days of commencing steroids. Systemic steroid administration of duration greater than 7–10 days may suppress histological evidence of active arteritis although this is not invariable. In patients with ocular involvement it is advisable to take the biopsy from the ipsilateral side. The ideal location is the temple because it lessens the risk of major nerve damage. At least 2.5 cm of artery should be collected and serial sections examined because of the phenomenon of ‘skip’ lesions in which inflamed segments of arterial wall are interspersed with histologically normal areas. A negative TAB should not prevent ongoing treatment in the presence of a convincing clinical picture of GA as 15% have normal histology; a contralateral biopsy may be positive in 5% following a negative initial biopsy.

    
    
  • ○
    

    Colour Doppler and duplex ultrasonography shows a hypoechoic halo around the superficial temporal artery lumen in around 75% due to oedema in the artery wall, and may be pathognomonic. There is some evidence that this provides a valid non-invasive alternative to TAB. Doppler imaging is also a useful aid to locating the artery for biopsy when it cannot be palpated.

    
    
  • ○
    

    Extracranial large vessel imaging. Aortic imaging with ultrasonography, MRA or positron emission tomography (PET) scanning may be used to exclude aortic aneurysm or dissection due to aortitis. Serial long-term imaging is increasingly being advocated to exclude these potentially life-threatening complications, the risk of which has now been demonstrated to be substantially increased in and following GCA.

    
    
  • ○
    

    Shoulder joint imaging. Recent work suggests that particular inflammatory features in the shoulder joints on MRI and ultrasonography may be useful diagnostically in PMR.

  
  

Giant cell arteritis. (A) Histology shows transmural granulomatous inflammation, disruption of the internal elastic lamina, proliferation of the intima and gross narrowing of the lumen; (B) the superficial temporal artery is often pulseless, nodular and thickened; (C) pale swollen disc in arteritic ischaemic optic neuropathy; (D) ischaemic optic neuropathy and cilioretinal artery occlusion

(Courtesy of J Harry and G Misson, from Clinical Ophthalmic Pathology , Butterworth-Heinemann 2002 – fig. A; S Farley, T Cole and L Rimmer – fig. B; SS Hayreh – figs C and D)

Treatment of giant cell arteritis without AAION

Treatment in the absence of visual symptoms is with oral prednisolone. An initial dose of 1 mg/kg/day is typical, the subsequent duration of treatment being governed by the response of symptoms and the level of the ESR or CRP; symptoms may recur without a corresponding rise in ESR or CRP and vice versa. Most patients need treatment for 1–2 years, although some may require indefinite maintenance therapy. Rapid tapering should generally not occur, with added caution when the dose is reduced to below about 10 mg a day. CRP may play an important role in monitoring disease activity, as the level seems to fall more rapidly than the ESR in response to treatment.

Arteritic anterior ischaemic optic neuropathy

Arteritic anterior ischaemic optic neuropathy (AAION) affects 30–50% of untreated patients with GCA, of whom one-third develop involvement of the fellow eye, usually within a week of the first. Posterior ischaemic optic neuropathy is much less common.

• •
  

  Symptoms

  
  
  
  
  • ○
    

    Sudden, profound unilateral visual loss not uncommonly preceded by transient visual obscurations (amaurosis fugax) and sometimes by double vision.

    
    
  • ○
    

    Periocular pain is common.

    
    
  • ○
    

    Other GCA symptoms are common; most cases of AAION occur within a few weeks of the onset of GCA, although at presentation about 20% do not have systemic symptoms.

    
    
  • ○
    

    Simultaneous bilateral involvement is rare but rapid involvement of the second eye, with resultant total blindness, should always be regarded as a substantial risk.

  
  
  
  
• •
  

  Signs

  
  
  
  
  • ○
    

    Severe visual loss is the rule, commonly to only perception of light or worse.

    
    
  • ○
    

    A strikingly pale ‘chalky white’ oedematous disc ( Fig. 19.14C ) is particularly suggestive of GCA.

    
    
  • ○
    

    Over 1–2 months, the swelling gradually resolves and severe optic atrophy ensues.

  
  
  
  
• •
  

  Prognosis is very poor. Visual loss is usually permanent, although, very rarely, prompt administration of systemic steroids may be associated with partial recovery.

  
  
• •
  

  Treatment is aimed at preventing blindness of the fellow eye, as visual loss in the index eye is unlikely to improve even with immediate treatment; the second eye may still become involved in 25% despite early steroid administration. The regimen is as follows:

  
  
  
  
  • ○
    

    Intravenous methylprednisolone, 500 mg to 1 g/day for 3 days followed by oral prednisolone 1–2 mg/kg/day. After 3 more days the oral dose is reduced to 50–60 mg (not less than 0.75 mg/kg) for 4 weeks or until symptom resolution and ESR/CRP normalization. A typical subsequent regimen consists of reducing the daily dose by 10 mg/day every 2 weeks until 20 mg/day is reached, with tapering afterwards titrated against ESR/CRP and symptoms, e.g. a 2.5 mg reduction every 2–4 weeks to 10 mg then a 1 mg reduction every 1–2 months.

    
    
  • ○
    

    Enteric-coated prednisolone may be appropriate, particularly in patients with a history of peptic ulceration.

    
    
  • ○
    

    Steroid treatment should be accompanied by bone and gastrointestinal protection, e.g. a weekly bisphosphonate, calcium/vitamin D supplementation and a proton pump inhibitor.

    
    
  • ○
    

    Monitoring should be performed by a physician with appropriate training and should look particularly for steroid-related complications. A full blood count, ESR/CRP, urea and electrolytes, random glucose and blood pressure should be checked at each visit. Every 1–2 years, a chest X-ray or more sophisticated imaging should be performed to exclude an aortic aneurysm and bone mineral density should be assessed.

    
    
  • ○
    

    Antiplatelet therapy, e.g. aspirin 600 mg stat then 100 mg/day should be commenced as this has been shown to reduce the risk of visual loss and stroke.

    
    
  • ○
    

    Any significant symptomatic relapse should be treated with an aggressive increase in steroid dose; intravenous methylprednisolone should be given if visual disturbance occurs.

    
    
  • ○
    

    Immunosuppressives such as methotrexate may be used as adjuncts in steroid-resistant cases or as steroid-sparing agents when extended treatment is required, though with caution as their benefit is considerably less proven than that of steroids.

    
    
  • ○
    

    Biological blockers have not been shown to have a definite protective effect.

  
  

Other manifestations

• •
  

  Cilioretinal artery occlusion may be combined with AAION ( Fig. 19.14D ).

  
  
• •
  

  Central retinal artery occlusion is often combined with occlusion of a posterior ciliary artery – with resultant choroidal hypoperfusion – as the two can arise from the ophthalmic artery by a common trunk.

  
  
• •
  

  Ocular ischaemic syndrome due to involvement of the ophthalmic artery is rare.

Introduction

Leber hereditary optic neuropathy (LHON) is a rare ganglion cell degeneration; the papillomacular bundle is particularly affected. The condition is caused by maternally inherited mitochondrial DNA point mutations, most frequently (50–90%) at nucleotide position 11778 (G to A) in the MT-ND4 gene. The condition typically affects males between the ages of 15 and 35 years, although in atypical cases the condition may affect females and present at any age between 10 and 60 years. The diagnosis of LHON should therefore be considered in any patient with bilateral optic neuropathy, irrespective of age.

Diagnosis

• •
  

  Symptoms. Typically acute or subacute severe painless unilateral (50%) loss of central vision. In initially unilateral cases, the fellow eye becomes similarly affected within weeks or months.

  
  
• •
  

  Signs during the acute stage are often subtle and easily overlooked, and in some patients the disc may be entirely normal.

  
  
  
  
  • ○
    

    Colour vision is likely to be subnormal.

    
    
  • ○
    

    There is often a relative afferent pupillary defect.

    
    
  • ○
    

    In typical cases there is disc hyperaemia with obscuration of the disc margins ( Fig. 19.15A ).

    
    

    
    

    
    

    

    
    

    
    

    Leber hereditary optic neuropathy. (A) Acute stage showing hyperaemic disc swelling with blurring of margins; (B) marked telangiectatic microangiopathy; (C) late – atrophic appearance

    
    

    
    

    

    
    

    
    

    

    
    
    
    
  • ○
    

    Dilated capillaries on the disc surface; these may extend onto adjacent retina (telangiectatic microangiopathy – Fig. 19.15B ).

    
    
  • ○
    

    Swelling of the peripapillary nerve fibre layer (pseudo-oedema).

    
    
  • ○
    

    Dilatation and tortuosity of posterior pole vasculature.

    
    
  • ○
    

    Subsequently, the vessels and pseudo-oedema regress, and severe optic atrophy supervenes ( Fig. 19.15C ), with nerve fibre layer dropout most pronounced in the papillomacular bundle.

    
    
  • ○
    

    Telangiectatic microangiopathy may be present in asymptomatic female relatives.

    
    
  • ○
    

    Surprisingly, the pupillary light reactions may remain fairly brisk.

  
  
  
  
• •
  

  LHON plus refers to rare variants with additional manifestations such as neuromuscular dysfunction.

  
  
• •
  

  Prognosis is poor, although some visual recovery may occur in a minority of cases even years later. Most patients suffer permanent bilateral visual loss with a final VA of 6/60 or less. The 11778 mutation carries the worst prognosis.

  
  
• •
  

  OCT. Patients show peripapillary retinal thinning; unaffected carriers frequently show variable thickening of the temporal retinal nerve fibre layer, perhaps due to compensatory mitochondrial accumulation.

  
  
• •
  

  Visual field defects usually consist of central or centrocaecal scotomas, with preserved peripheral vision.

  
  
• •
  

  FA shows no leakage from the disc or microangiopathic vessels.

  
  
• •
  

  Genetic testing to look for the three common causative mutations.

Treatment

• •
  

  Apart from symptomatic measures such as low vision aids, treatment is generally ineffective.

  
  
• •
  

  Various vitamins and co-factors, idobenone, creatine and others have been tried with anecdotal success, and subspecialist prescription of one or more of these may be worthwhile, particularly in early disease or prior to second eye involvement. Counterintuitively, the cyanocobalamin (but not the hydroxocobalamin) form of vitamin B ₁₂ has been reported to worsen outcomes.

  
  
• •
  

  Dietary deficiencies should be avoided, particularly of B ₁₂ .

  
  
• •
  

  Smoking and excessive alcohol consumption should be discouraged, theoretically in order to minimize mitochondrial stress.

  
  
• •
  

  Gene therapy is under active investigation.

Dominant optic atrophy (Kjer type optic atrophy, optic atrophy type 1)

• •
  

  Inheritance is autosomal dominant (AD); this is the most common hereditary optic neuropathy with an incidence of around 1 : 50 000; it is frequently due to a mutation in the OPA1 gene on chromosome, which causes mitochondrial dysfunction, but other genes can be responsible and X-linked and autosomal recessive (AR) forms have been reported. There is usually high penetrance but variable expressivity in the dominant forms.

  
  
• •
  

  Presentation is typically, though not always, in childhood with insidious visual loss. There is usually a family history, but the course may be variable even within the same family.

  
  
• •
  

  Optic atrophy may be subtle and temporal ( Fig. 19.16A ) or diffuse ( Fig. 19.16B ). There may be enlargement of the cup.

  
  

  
  

  
  

  

  
  

  
  

  Hereditary optic atrophy. (A) Bilateral temporal disc pallor; (B) bilateral diffuse pallor

  
  
  
  
• •
  

  Prognosis is variable (final VA 6/12–6/60) with considerable differences within and between families. Very slow progression over decades is typical.

  
  
• •
  

  Systemic abnormalities. Twenty per cent develop sensorineural hearing loss; other features are less common.

Behr syndrome

• •
  

  Inheritance is AR; heterozygotes may have mild features.

  
  
• •
  

  Presentation is in early childhood with reduced vision.

  
  
• •
  

  Optic atrophy is diffuse.

  
  
• •
  

  Prognosis is variable, with moderate to severe visual loss and nystagmus.

  
  
• •
  

  Systemic abnormalities include spastic gait, ataxia and mental handicap.

Wolfram syndrome

Wolfram syndrome is also referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness).

• •
  

  Inheritance. Three genetic forms are recognized, caused by a variety of mutations in WFS1, which gives Wolfram syndrome 1, CISD2 – Wolfram syndrome 2 – and probably a form caused by a mitochondrial DNA mutation, with inheritance being AR, AD or via the maternal mitochondrial line.

  
  
• •
  

  Presentation is usually between the ages of 5 and 21 years; diabetes mellitus is typically the first manifestation, followed by visual problems.

  
  
• •
  

  Optic atrophy is diffuse and severe and may be associated with disc cupping.

  
  
• •
  

  Prognosis is typically poor (final VA is <6/60).

  
  
• •
  

  Systemic abnormalities (apart from DIDMOAD) are highly variable, presumably in part due to genetic heterogeneity, and may include anosmia, ataxia, seizures, mental handicap, short stature, endocrine abnormalities and elevated CSF protein. Life expectancy is usually substantially reduced.

Introduction

Nutritional optic neuropathy (tobacco-alcohol amblyopia) is an apparently uncommon but likely underdiagnosed acquired optic neuropathy. The mechanism is thought to be deficient mitochondrial function, similar to that of the heritable optic neuropathies, and like these the papillomacular bundle is preferentially affected. In Western developed countries the condition typically affects individuals with high alcohol and tobacco consumption. Most patients have neglected their diet, and the features are most likely to be due principally to deficiency in the B-complex vitamins, particularly cyanocobalamin (B ₁₂ ) and thiamine (B ₁ ), but also riboflavin (B ₂ ), niacin (B ₃ ) and pyridoxine (B ₆ ). Copper, folic acid and protein deficiency may also be important, and direct toxic effects of alcohol and tobacco may also be significant. A strict vegan diet can also be causative, as can dietary deficiency in elderly patients. A similar clinical picture may be seen due to toxicity from medication or environmental (e.g. occupational) toxins. In under-resourced geographic regions, nutritional aetiological factors due to inadequate dietary intake predominate, and nutritional optic neuropathy can be epidemic. Pernicious anaemia sufferers may develop the condition due to reduced vitamin B ₁₂ absorption.

Diagnosis

The possibility of a range of causes, particularly alternative optic neuropathies and macular pathology, should be borne in mind.

• •
  

  Symptoms

  
  
  
  
  • ○
    

    The insidious onset of painless bilateral central blurring associated with abnormal colour vision.

    
    
  • ○
    

    Enquiry should be made about potentially causative medication (see Ch. 20 ), environmental toxin exposure and a vegan diet.

    
    
  • ○
    

    A family history of optic neuropathy should be excluded.

    
    
  • ○
    

    Peripheral neurological symptoms (sensory loss, gait disturbance) raise the suspicion of a peripheral neuropathy.

  
  
  
  
• •
  

  Signs

  
  
  
  
  • ○
    

    VA is very variably affected.

    
    
  • ○
    

    The discs at presentation are normal in most cases, but some patients show subtle pallor, often temporal, splinter-shaped haemorrhages on or around the disc, or minimal oedema.

    
    
  • ○
    

    The pupil reactions are often normal, but may respond weakly in more severe cases.

    
    
  • ○
    

    Other ocular and systemic features of nutritional deficiency should be sought (and investigations carried out accordingly), e.g. Korsakoff syndrome, Wernicke disease, pernicious anaemia; xerophthalmia and beriberi should be considered in developing nations.

  
  
  
  
• •
  

  Colour vision testing. A reduction in colour vision is disproportionate to the reduction in acuity. Red desaturation is likely to be present. Ishihara chart testing is a simple, moderately quantitative test that is widely available.

  
  
• •
  

  Visual field defects are bilateral, relatively symmetrical, centrocaecal scotomas. The margins of the defects are difficult to define with a white target but are more substantive with a red target.

  
  
• •
  

  OCT may show peripapillary retinal nerve fibre layer thickening and will help to exclude macular pathology.

  
  
• •
  

  Fundus autofluorescence (FAF) should be performed if available to exclude macular changes suggesting a cone or cone-rod dystrophy that may present with colour deficiency and central scotomata.

  
  
• •
  

  Prognosis is good in early cases provided patients comply with treatment although visual recovery may be slow; colour perception returns more slowly than measured acuity. In advanced cases there is likely to be a substantial permanent deficit, but it is highly unusual for complete loss of useful vision to occur, with preservation of peripheral field usual even in quite severe cases.

  
  
• •
  

  Blood tests. B ₁₂ (cobalamin) and folate (serum and red cell) and possibly other vitamin levels such as B ₁ (thiamine) and B ₂ , a full blood count and film (macrocytic anaemia) and serum protein levels. Some authorities advocate routine syphilis serology. Screening for specific toxins or for LHON (see above) mutations may be indicated. A high serum methylmalonate and/or homocysteine level may be an indicator of potentially functional B ₁₂ deficiency, even in the presence of a low-normal B ₁₂ .

  
  
• •
  

  VEP. The P100 amplitude is markedly reduced but with normal or near-normal latency.

  
  
• •
  

  MRI is commonly considered to rule out mimicking intracranial pathology, particularly with an atypical clinical picture (e.g. marked asymmetry, disc pallor but good vision).

Treatment

Consideration should be given to co-management with a general physician or neurologist. Compliance with treatment and review is commonly poor in tobacco-alcohol amblyopia.

• •
  

  Dietary revision with formal nutritional advice, incorporating increased fruit and leafy green vegetable intake.

  
  
• •
  

  Abstention from alcohol and tobacco ; reduction in consumption may be all that is practically possible.

  
  
• •
  

  Vitamins. A daily multivitamin preparation, plus thiamine (100 mg twice daily) and folate (1 mg daily). In someone who is both folate and B ₁₂ deficient, it is prudent to correct the B ₁₂ deficiency first to avoid precipitating subacute combined degeneration of the cord.

  
  
• •
  

  Intramuscular hydroxocobalamin (vitamin B ₁₂ ) injections. The use of injected B ₁₂ has become less common in recent years, as evidence shows that even in malabsorption states oral treatment may be as effective. Some work suggests that hydroxocobalamin injections improve vision in tobacco-alcohol amblyopia, including when smoking continues, perhaps by reversing cyanide toxicity; their use may therefore still be considered in severe or unresponsive cases, noting also that intramuscular treatment bypasses compliance failure. Regimens range from 1 mg weekly for 8 weeks to monthly for several months; injections every 3 months are typically continued for life.

  
  
• •
  

  Exposure to the identified agent should be discontinued immediately in cases due to medication or environmental toxicity.

Introduction

Papilloedema is swelling of the optic nerve head secondary to raised intracranial pressure (ICP). ‘Disc swelling’ and ‘disc oedema’ are non-specific terms that include papilloedema but also a disc swollen from other causes. All patients with papilloedema should be suspected of harbouring an intracranial mass. Not all patients with raised ICP will develop disc swelling. Causes of a swollen-appearing optic disc are given in Table 19.3 .

Cerebrospinal fluid

• •
  

  Circulation ( Fig. 19.17A )

  
  
  
  
  • ○
    

    Cerebrospinal fluid (CSF) is formed by the choroid plexus in the ventricles of the brain.

    
    
  • ○
    

    It leaves the lateral ventricles to enter the third ventricle through the foramina of Munro.

    
    
  • ○
    

    From the third ventricle, it flows through the Sylvian aqueduct to the fourth ventricle.

    
    
  • ○
    

    From the fourth ventricle, the CSF passes through the foramina of Luschka and Magendie to enter the subarachnoid space, flowing around the spinal cord and bathing the cerebral hemispheres.

    
    
  • ○
    

    Absorption is into the cerebral venous system through the arachnoid villi.

  
  

  
  

  
  

  

  
  

  
  

  (A) Circulation of cerebrospinal fluid; (B) causes of raised intracranial pressure – see text (FM = foramen magnum; LV = lateral ventricle; AQ = aqueduct of Sylvius)

  
  
  
  
• •
  

  Normal CSF pressure on lumbar puncture (not upright) is 10–18 cmH ₂ O in adults.

  
  
• •
  

  Causes of raised ICP ( Fig. 19.17B )

  
  
  
  
  • ○
    

    Idiopathic intracranial hypertension.

    
    
  • ○
    

    Obstruction of the ventricular system by congenital or acquired lesions.

    
    
  • ○
    

    Space-occupying intracranial lesions, including haemorrhage.

    
    
  • ○
    

    Impairment of CSF absorption due to meningitis, subarachnoid haemorrhage or trauma.

    
    
  • ○
    

    Cerebral venous sinus thrombosis.

    
    
  • ○
    

    Cerebral oedema from blunt head trauma.

    
    
  • ○
    

    Severe systemic hypertension.

    
    
  • ○
    

    Hypersecretion of CSF by a choroid plexus tumour (very rare).

  
  

Diagnosis of raised ICP

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  Headaches , which characteristically occur early in the morning and may wake the patient from sleep, although less commonly they can occur at any time of day. The pain may be generalized or localized, and may intensify with head movement, bending or coughing. They tend to get progressively worse over time. Very rarely, headache may be absent.

  
  
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  Nausea , often episodic and with associated projectile vomiting; may occur as an isolated feature or may precede the onset of headaches.

  
  
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  Deterioration of consciousness as severity increases, initially with drowsiness and somnolence. A dramatic deterioration in concscious level may be indicative of brainstem distortion and requires immediate attention.

  
  
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  Visual symptoms are commonly absent in mild or early raised ICP.

  
  
  
  
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    Transient visual obscurations lasting up to 30 seconds in one or both eyes are frequent in established papilloedema, and are sometimes precipitated by bending, coughing or the Valsalva manoeuvre; disc swelling due to other causes is usually associated with more persistent visual impairment.

    
    
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    Horizontal diplopia due to sixth nerve palsy caused by stretching of one or both abducens nerves over the petrous tip ( Fig. 19.18 ); this is a false localizing sign.

    
    

    
    

    
    

    

    
    

    
    

    Mechanism of sixth nerve palsy due to raised intracranial pressure

    
    
    
    
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    Vision is generally normal or minimally reduced. Significant reduction is a late feature in conjunction with secondary optic atrophy.

  
  
  
  
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  Neurological examination should be performed.

  
  
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  Investigations

  
  
  
  
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    B-scan ultrasonography can be used to aid in distinguishing between papilloedema and other causes of a swollen or apparently swollen (pseudopapilloedematous) optic disc with 80–90% sensitivity and specificity by measuring the external diameter of the optic nerve sheath (ONSD), which is substantially distended (5.0–5.7 mm or greater at 3.0 mm behind the globe – Fig. 19.19A ). The nerve must be scanned axially for the measurement to be accurate, and there is a degree of operator dependence. In contrast to spontaneous venous pulsation (SVP – see below), ONSD does not normalize with short-term ICP fluctuation. The ‘crescent sign’ ( Fig. 19.19B ) refers to an echolucent area in the anterior intraorbital nerve thought to represent increased separation of the nerve and its sheath. Lateral gaze (‘thirty degree test’) commonly leads to a 10% reduction in diameter on A-scan measurement in the presence of excess fluid ( Figs 19.19C and D ), but not if normal or if increased ONSD is due to infiltration. Fluid-related ONSD can also be caused by other pathology, such as inflammation and trauma.

    
    

    
    

    
    

    

    
    

    
    

    Ultrasonography in papilloedema. (A) Optic nerve sheath diameter of 7.1 mm, 3 mm posterior to the globe; (B) transverse B-scan showing crescent sign (arrowheads); (C) A-scan in primary position with retrobulbar nerve diameter of 4.8 mm; (D) in lateral gaze diameter reduces to 3.5 mm – positive 30° test

    
    

    (Courtesy of M Stone, from American Journal of Emergency Medicine 2009;27:376.e1–376.e2 – fig. A; L Lystad, B Hayden, A Singh, from Ultrasound Clinics 2008;3:257–66 – figs B–D)

    
    

    
    

    

    
    

    
    

    

    
    

    
    

    

    
    
    
    
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    MRI to exclude a space-occupying lesion and/or enlarged ventricles; MRI can also be used to measure ONSD (average normal diameter approximately 5.5 mm ± 1 mm on MRI).

    
    
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    In certain cases vascular imaging may be performed, such as venography to rule out cerebral venous sinus thrombosis.

    
    
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    Lumbar puncture (LP) must not be carried out until imaging has excluded a space-occupying lesion that might cause downwards herniation of the intracranial contents towards the LP-induced low-pressure area. Clotting abnormality, including therapeutic anticoagulation, is also a contraindication unless reversed prior to the LP.

  
  

Stages of papilloedema

Papilloedema is nearly always bilateral, but may be asymmetrical.

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  Early ( Fig. 19.20A )

  
  
  
  
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    Mild disc hyperaemia with preservation of the optic cup.

    
    
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    Indistinct peripapillary retinal nerve striations and disc margins.

    
    
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    SVP is absent in about 20% of normal individuals and may be difficult to identify even when present. An identifiable venous pulsation in at least one eye means that the ICP is normal at that point in time, bearing in mind that diurnal fluctuation can occur.

  
  

  
  

  
  

  

  
  

  
  

  Papilloedema. (A) Early; (B) acute established; (C) chronic; (D) atrophic – same eye as (C)

  
  

  
  

  

  
  

  
  

  

  
  

  
  

  

  
  
  
  
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  Established (acute – Fig. 19.20B )

  
  
  
  
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    Normal or reduced VA.

    
    
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    Severe disc hyperaemia, moderate elevation with indistinct margins and absence of the physiological cup.

    
    
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    Venous engorgement, peripapillary flame haemorrhages and frequently cotton wool spots.

    
    
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    As the swelling increases, the optic nerve head appears enlarged.

    
    
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    Circumferential retinal folds (Paton lines) may develop, especially temporally (see Fig. 19.7C ).

    
    
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    Macular fan: in younger patients small vesicles may form in the superficial retina, converging on the fovea in a fan shape with the apex at the fovea; this is not to be confused with a macular star, composed of exudates.

    
    
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    Enlarged blind spot.

  
  
  
  
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  Chronic ( Fig. 19.20C )

  
  
  
  
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    VA is variable and the visual fields begin to constrict.

    
    
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    Disc elevation; cotton wool spots and haemorrhages are characteristically no longer present.

    
    
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    Optociliary shunts (see Ch. 13 ) and drusen-like crystalline deposits (corpora amylacea) may be present on the disc surface.

  
  
  
  
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  Atrophic (secondary optic atrophy – Fig. 19.20D )

  
  
  
  
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    VA is severely impaired.

    
    
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    The optic discs are grey–white, slightly elevated, with few crossing blood vessels and indistinct margins.

  
  

Introduction

Idiopathic intracranial hypertension, previously known as benign intracranial hypertension or pseudotumour cerebri, is characterized by elevated ICP that by definition has no identifiable cause; obese young adult women are the most commonly affected group. Various medications including the contraceptive pill have been implicated (strictly ‘secondary intracranial hypertension’ if a cause is identified), as well as a range of conditions such as systemic lupus erythematosus, Lyme disease and sleep apnoea syndrome.

Diagnosis

• •
  

  Symptoms and signs are those of papilloedema, with headache in over 90%; pulsatile tinnitus may be experienced, and cranial nerve palsies and occasionally other symptoms may occur. The long-term visual prognosis is usually good, but up to a quarter will have a degree of permanent impairment.

  
  
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  Investigation is as for papilloedema: ONSD is increased and MRI may show slit-like ventricles and flattening of the pituitary gland (‘empty sella’ sign). MRV is usually carried out to exclude cerebral venous sinus thrombosis or stenosis. Additional investigation for an occult cause should be considered, especially in patients who do not fit the usual profile.

Treatment

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  Weight loss, including via bariatric surgery, can be very effective and formal dietary intervention is strongly recommended.

  
  
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  Other options include acetazolamide, furosemide, digoxin and analgesia, and in unresponsive cases optic nerve fenestration, lumboperitoneal shunting and transverse dural sinus stenting.

  
  
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  Steroids are controversial, but a short course is sometimes used in severe papilloedema.

  
  
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  Intravenous mannitol or a lumbar puncture are usually reserved for acute severe exacerbations.

  
  
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  The ophthalmologist’s role is usually confined to diagnosis and the monitoring of visual function with VA, colour vision and fields, and optic nerve appearance/photography.

Tilted disc

A tilted optic disc is a common anomaly, usually bilateral, describing an apparently oblique entry of the optic nerve into the globe. It is strongly associated with myopia and astigmatism. A suggested definition regards tilting as present when the ratio of the longest diameter of the disc to the shortest (ovality index) is greater than 1.3 ( Fig. 19.21A ), but this will not include many subjectively apparently tilted discs ( Fig. 19.21B ). A major implication of tilting is difficulty in excluding superimposed glaucomatous damage, as the temporal, particularly the inferotemporal, neuroretinal rim is frequently very thin.

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  Signs. Small, oval or D-shaped disc: the axis is most frequently directed inferonasally, but may be horizontal or nearly vertical.

  
  
  
  
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    The disc margin is indistinct where retinal nerve fibres are elevated.

    
    
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    Peripapillary chorioretinal thinning may be marked, and situs inversus may be present: the temporal vessels deviate nasally before turning temporally ( Fig. 19.21C ).

  
  
  
  
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  Perimetry may show superotemporal defects; these do not respect the vertical midline.

  
  
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  OCT may demonstrate sectoral peripapillary retinal nerve fibre layer thinning, but macular ganglion cell complex analysis is often – but not always – normal so may provide a more useful parameter for the exclusion of coexistent glaucomatous damage.

  
  
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  Complications (rare) include choroidal neovascularization and sensory macular detachment.

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