Ophthalmology: Sub-specialty – Neuro-ophthalmology

Pupil abnormalities

You must understand the pupil pathways and the innervation of the pupil.

Aims

  • Understand how to assess a patient with abnormal pupils.
  • Understand the causes of pupil abnormalities.
  • Understand the neuroanatomy of pupillary light reflexes.

Anatomy and physiology

Sympathetic innervation causes pupillary dilation via fibres from the cilio-spinal centre of Bulge via the superior cervical ganglion to the dilator papillae iris muscles (Figure 52.1).

Parasympathetic innervation leads to pupillary constriction via a circular muscle called the sphincter pupillae. The pathway of pupillary constriction begins at the Edinger–Westphal nucleus near the oculomotor nerve nucleus. The fibres enter the orbit with the third cranial nerve (CN III) fibres and synapse at the ciliary ganglion in the posterior
orbit, then go to the sphincter papillae muscle (Figures 52.2 and 52.3).

Pupil examination

When examining pupils, you need to check for:

  • symmetry
  • size
  • shape
  • light response
  • near response.

Afferent pupil defect and relative afferent pupillary defect

  • An afferent pupil defect (APD) results from damage to the visual pathway anywhere from the retinal ganglion cell layer to the lateral geniculate body, thus causing a reduction in the input (afferent) signal reaching the brainstem when a light is directed at the affected eye. Hence there is a similarly reduced output (efferent) signal reaching the
    pupil, which consequently constricts to a lesser extent than if it had received a full signal.
  • Because of the consensual light reflex, the unaffected pupil will also constrict to an equally lesser extent when the light is directed towards the damaged side.
  • Hence, if a light is directed at the better eye, both pupils will constrict fully and equally. If it is then immediately swung over (the ‘swinging flash light test’) and directed at the affected eye (e.g. an eye with an optic nerve lesion), both pupils will appear to dilate—a relative afferent pupillary defect (RAPD). In fact, what has happened here is that both pupils are constricting but to a lesser degree than when the light was directed at the normal eye, hence they only appear to dilate. When the light is swung back to the better eye, the pupils will constrict.

Fixed dilated pupil

  • If a pupil is dilated and doesn’t react to light or accommodation, it is important to examine eye movements and levator function in order to exclude a third nerve palsy. Note: a unilateral enlarged pupil caused by uncal herniation is a neurosurgical emergency.
  • Because of the superficial location of the pupillomotor fibres, a partial third nerve palsy can occur where only the pupil is involved. In such cases, a tumour or posterior communicating artery aneurysm (Figure 52.4) must be excluded.
  • A fixed dilated pupil can result from inadvertent or accidental contamination of the eye with cycloplegic agents such as atropine or cyclopentolate, hence the importance of a detailed history.
  • Previous trauma or surgery where there has been extensive damage to the sphincter pupillae can result in a fixed dilated pupil.
  • A fixed semidilated pupil in the presence of a hazy cornea, red eye and pain is seen in acute angle-closure glaucoma.

Small pupil (miosis) (Figure 52.5)

  • A small pupil in association with a very small amount of ptosis (no more than 2 mm—due to paralysis of Müller’s muscle) is known as Horner’s syndrome (Figure 52.6). This results from a lesion of the sympathetic chain anywhere from the hypothalmus to the eye.
  • On dimming the lights, the anisocoria will become more obvious as the affected pupil doesn’t dilate in the dark as well as its counterpart.
  • There may be other associated features such as elevation of the lower lid, which together with the ptosis gives the appearance of enophthalmos, reduced sweating on the ipsilateral side of the face and occasionally conjunctival hyperaemia.
  • Horner’s syndrome can be confirmed by putting 4% cocaine drops into each eye and observing the pupils 40 min later. The normal pupil will dilate, but the Horner’s pupil will not.
  • Causes of Horner’s syndrome include Pancoast’s tumour of the lung, thoracic aortic aneurysm, trauma, carotid artery dissection (usually accompanied by neck pain) and central nervous system disease. All patients should be investigated appropriately.
  • In congenital Horner’s syndrome, the iris on the affected side is a different colour—iris heterochromia.
  • Contamination of the eye with pilocarpine causes miosis.
  • Uveitis that has resulted in posterior synechiae can result in a small pupil.
  • Rarely, congenital microcoria can occur.

Light–near dissociation

In some cases, the pupil(s) will accommodate but not react to light. This dissociation of the light and near reflex can occur in various syndromes.

  • Dorsal midbrain or Parinaud’s syndrome. This may be due to a lesion (e.g. pinealoma or cranipharyngioma) compressing the pupillary light reflex fibres. The pupils may be large and eccentric. Associated features include the absence of an upgaze, upper lid retraction and convergence retraction nystagmus, characterized by rapid convergence movements and retraction of both eyes on attempted upgaze.
  • Neurosyphilis or Argyll Robertson pupils. These pupils are small and irregular, do not react to light but react briskly to near stimuli.
  • Holmes–Adie pupil (Figure 52.7). This is thought to result from a viral infection; the affected pupil is initially large and eventually may become miosed. There is no reaction to light, and the near reflex is intact but delayed and tonic (the patient should be asked to focus on a near target for at least 1 min before the pupils begin to constrict, and
    when the patient is then asked to relax his accommodation, the pupils are slow to dilate again). These patients may also have absent tendon reflexes. Both pupils may eventually become involved.
  • Patients with myotonic dystrophy may have light–near dissociation.
  • Patients with diabetes may develop a pupil neuropathy resulting in light–near dissociation.

Optic nerve disease

Optic nerve disease can be slow and insidious or more acute, and it represents a wide array of pathology, from Leber’s hereditary optic neuropathy (LHON) to multiple sclerosis, intracranial tumour and anterior ischaemic optic neuropathy (AION).

Aims

Know the causes of optic atrophy (pale disc) and swollen discs

Disc swelling

Unilateral disc swelling

Clinical features (Figure 53.1)
  • Visual acuity may be normal or reduced.
  • Reduced colour vision
  • Visual field defect: enlarged blind spot if there is significant swelling, and altitudinal defect if disc swelling is secondary to ischaemic optic neuropathy
  • Blurred disc margin ± splinter haemorrhages (Figure 53.2).
Aetiology
  • Vascular: for example, AION, central retinal vein or diabetic papillopathy
  • Inflammatory: ‘papillitis’, such as uveitis, sarcoidosis, viral, systemic lupus erythematosus or paranasal sinus disease
  • Demyelination: multiple sclerosis—disc swelling may become bilateral (Figure 53.2a and 53.2b). Disc(s) are swollen or normal in the acute phase, and they eventually become pale after recurrent attacks.
  • Hereditary: LHON—may become bilateral
  • Infiltrative: for example, lymphoma
  • Infective: for example, toxoplasmosis, herpes or Lyme disease.
Investigations
  • Visual field analysis
  • Full blood count (FBC), blood glucose, erythrocyte sedimentation rate (ESR), C-reactive protein, coagulation screen, infective screen (e.g. toxoplasmosis and Borelia titres), autoantibody screen
  • Blood is sent for analysis for Leber’s mutation if suspected.
  • Neuroimaging if demyelination or a compressive lesion is suspected. Magnetic resonance imaging (MRI) of the brain and optic nerves should be requested (Figure 53.2c).
  • Lumbar puncture if demyelination, neurosarcoidosis or lymphoma is suspected.

Bilateral disc swelling and papilloedema

Clinical features
  • Visual acuity may be normal or severely reduced.
  • Patients with papilloedema may complain of episodes of unilateral or bilateral transient visual loss lasting for a few seconds. These are transient visual obscurations (TVOs) and can be precipitated by changes in posture.
  • Colour vision is often reduced.
  • Enlarged blind spot if the swelling is significant; it will be normal in mild cases.
Aetiology
  • Raised intracranial pressure: space-occupying lesion, hydrocephalus, idiopathic intracranial hypertension (IIH)
  • Malignant hypertension
  • Diabetic papillopathy
  • Infiltrative papilloedema (Figure 53.3), such as lymphoma
  • Toxic, such as ethambutol.
Investigations
  • Blood pressure; Glucose, FBC and differential white cell count, U&E, creatinine and ESR; Neuroimaging; Lumbar puncture if the MRI is normal and IIH is suspected; Visual fields (to monitor blind spot).

Optic atrophy and neuropathy

Clinical features

  • VA is reduced but can be normal, depending on the degree of optic atrophy.
  • Relative afferent pupillary defect.
  • Disc pallor. In severe optic atrophy, the entire disc may be pale; in many cases, only part of the disc (e.g. the temporal part) will be affected, and subtle disc pallor will be missed if both discs are not compared.

Aetiology

  • Hereditary:
    ○ Autosomal dominant optic atrophy: Affected family members may vary considerably in abnormalities.
    ○ Autosomal recessive optic atrophy: poor visual acuity
    ○ LHON (Figure 53.4 and Table 53.1).
  • Retinal dystrophy:
    ○ Cone dystrophy: very poor acuity, markedly reduced colour vision, photophobia, central scotoma, nystagmus and typical ERG
    ○ Retinitis pigmentosa: typical retinal appearance, constricted visual fields and characteristic electroretinogram (ERG)
  • Vascular: central retinal artery occlusion.
  • Nutritional or toxic: vitamin B12 deficiency (gradual bilateral visual loss associated with pins and needles in hands and feet, poor diet, reduced colour vision and centrocaecal scotoma), tobacco–alcohol amblyopia or drugs (e.g. ethambutol or chloramphenicol).
  • Inflammatory: sarcoidosis, polyarteritis nodosa, contiguous sinus disease—more commonly present with disc swelling.
  • Demyelination: may have past history of typical attacks of optic neuritis, and may have other neurological symptoms. It is a common cause.
  • Compressive: optic nerve glioma or meningioma, orbital tumour or
    intracranial tumour.

Investigations

  • Formal visual field testing
  • Visual evoked response or potential (VER or VEP)
  • ERG
  • Relevant blood tests depending on clinical history (e.g. vitamin B12 and folate levels in a patient who is a vegan and has bilateral optic atrophy with glove and stocking paraesthesia)
  • Neuroimaging: MRI optic nerves and brain.

Cranial nerve palsies and eye movement disorders

Aim

Describe clinical features of third, fourth, fifth and seventh cranial nerve palsies, internuclear ophthalmoplegia (INO), gaze palsies and nystagmus. The neuroanatomy of these cranial nerves is shown in Figure 54.1.

Third nerve palsy

Symptoms

  • Double vision—horizontal and/or vertical
  • Droopy lid
  • Enlarged pupil
  • Headache. Note painful third nerve with pupil involvement— exclude a posterior communicating artery aneurysm as soon as possible.

Signs

  • Ptosis
  • Exotropia and hypotropia (globe appears down and out)
  • Fixed dilated pupil
  • Limitation of elevation, depression and adduction May present with any of these or a combination.

Aetiology

  • Ischaemic or vascular (usually pupil sparing due to the anatomy of the pupillomotor fibres, and referred to as a ‘medical third’): diabetes mellitus (DM), hypertension, vasculitis or migraine
  • Compressive lesion (pupil nearly always involved, and referred to as a ‘surgical third’): posterior communicating artery aneurysm or tumour
  • Trauma
  • Congenital third.

Fourth nerve palsy

Symptoms

Double vision—vertical.

Signs

  • Head tilt opposite to the side of the lesion.
  • Hypertropia on the affected side.
  • Limitation of eye movement down and to the right if left fourth nerve palsy, and vice versa.
  • Positive Bielchowsky’s sign, that is, the hypertropia on the affected side gets worse on tilting the head to the same side.

Aetiology

  • Trauma is the most common cause of fourth nerve palsy as this nerve has the longest intracranial course, is very slender and runs under the tentorial edge. Trauma may result in bilateral fourths.
  • Ischaemic or vascular: DM, hypertension or vasculitis
  • Compressive lesion (e.g. intracranial tumour)
  • Congenital.

Fifth nerve palsy

Corneal anaesthesia.

Sixth nerve palsy

Symptoms

Double vision—horizontal especially at distance.

Signs

  • Esotropia; it is worse for distance.
  • Limitation of abduction of the affected eye.

Aetiology

  • Vascular or ischaemic: DM, hypertension, or vasculitis
  • Invading intracranial or nasopharyngeal tumour
  • Trauma (e.g. fractured skull base).

Seventh nerve palsy

Symptoms

  • Inability to close eyelid (lagophthalmos) and facial weakness
  • Watery eye (due to weakness of orbicularis oculi)
  • Sore red eye (due to corneal exposure)
  • Blurred vision secondary to exposure keratitis
  • Drooling.

Signs

  • Ipsilateral facial muscle weakness, involving the frontalis in lower motor neurone lesions. The frontalis is spared in upper motor neurone lesions.
  • Lower lid ectropion secondary to orbicularis oculi weakness.
  • Corneal exposure may vary from superficial punctate erosions to corneal abrasion, and it must be treated urgently to prevent abscess formation and endophthalmitis.

Aetiology

  • Viral or idiopahtic, such as Bell’s palsy (usually improves spontaneously) or Ramsay–Hunt syndrome (herpes simplex infection)
  • Compressive lesion: intracranial tumour, such as acoustic neuroma (may have associated fifth, sixth and eighth nerve palsy) or parotid tumour
  • Vascular or ischaemic: DM, hypertension or vasculitis
  • Inflammation (e.g. sarcoidosis).

Internuclear ophthalmoplegia

Symptoms

  • Horizontal diplopia
  • Inability to coordinate eye movements.

Signs

  • Failure to adduct the ipsilateral eye
  • Abducting nystagmus of the contralateral eye.

Nystagmus

This is involuntary rhythmic to-and-fro oscillation of the eyes.

Symptoms

  • Congenital nystagmus is asymptomatic.
  • Acquired nystagmus may cause oscillopsia, a sensation of rapid movement or oscillation of the visual environment. Patients describe it as though looking at an old black-and-white film where everything flickers or wobbles; others notice only blurred vision, especially with gaze-evoked nystagmus.

Visual field defects

Aims

  • Understand the neuroanatomy of the various visual field defects (Figures 55.1 and 55.2).
  • Recognize the causes of different field defects.

Visual field defects

The most common visual field defects encountered in clinical practice include homonymous hemianopia, altitudinal field defect, bitemporal hemianopia, grossly constricted fields and enlarged blind spots.
Note obvious clues that will help you (e.g. a hemiparesis)—this patient is most likely to have an ipsilateral hemianopia as the result of a lesion in the contralateral cortex.

Optic nerve

A unilateral optic nerve lesion can result in various unilateral field defects depending on the nature of the lesion. The shape of field defect can give a clue to the diagnosis. For example:

  • Glaucomatous cupping can result in an arcuate scotoma of the superior (Figure 55.2, 1a) or inferior field (Figure 55.2, 1b).
  • Vitamin B12 deficiency can result in a centrocaecal scotoma (Figure 55.2, 1c).
  • Anterior ischaemic optic neuropathy (a swollen disc can be seen in the acute phase) and posterior ischaemic optic neuropathy (the disc will look normal in the acute phase) can result in an altitudinal field defect. This can be superior (Figure 55.2, 1d) or inferior (Figure 55.2, 1e), depending on which vessels are involved.
  • Complete severing of the optic nerve (e.g. as a result of trauma) will cause complete ipsilateral visual field loss.

Junction optic nerve with chiasm

Because of the arrangement of nerve fibres in the optic nerve and chiasm, a lesion pressing on the visual pathway at the junction of the intracranial optic nerve and the chiasm can produce a characteristic field defect (Figure 55.2, 2), known as a junctional scotoma. Such a field defect results because the lesion compresses both fibres from the
nasal fibres (serving the temporal visual field) of the ipsilateral optic nerve and the inferonasal fibres (superotemporal field) from the contralateral eye in Willebrand’s knee.

Chiasm

A lesion pressing on the optic chiasm, such as a pituitary tumour (Figure 55.3), will result in damage to the nasal fibres from both eyes as they cross the midline, and therefore results in a bitemporal hemianopia (Figure 55.2, 3). Early on, if the lesion is only minimally compressing the chiasm, the field defect will be very subtle and may be picked up only by using a red target (the individual will have red desaturation in the affected field—this is true for all subtle lesions).

Optic tract

A lesion of the optic tract involves the temporal fibres (nasal field) from the ipsilateral eye and the crossed nasal fibres (temporal field) from the contralateral eye. A lesion completely destroying, for example, the right optic tract will result in a complete left homonymous hemianopia. However, most optic tract lesions are partial, and because corresponding fibres from the nasal and retinal fields are not so close together in the tract, the homonymous hemianopia produced
is incongruous (i.e. the hemi-field defect from the right eye is not an identical shape to that of the left) (Figure 55.2, 4).

Meyer’s loop

A lesion of the optic radiation in the temporal lobe will affect Meyer’s loop, which contains fibres representing the inferior quadrant of the ipsilateral temporal retina, and the contralateral nasal retina. This results in a superior homonymous quadrantanopia, sometimes referred to as a ‘pie in the sky’ defect (Figure 55.2, 5).

Parietal lobe

A lesion in the parietal lobe may affect the fibres from the superior quadrants of the ipsilateral temporal and contralateral nasal retina, giving rise to an inferior homonymous quadrantanopia or a homonymous
hemianopia that is denser below than above (Figure 55.2, 6).

Optic radiation to occipital cortex

Any unilateral lesion affecting the more anterior portion of the occipital cortex will give rise to a homonymous hemianopia. Because of the close proximity of the cells representing the corresponding retinal points, the hemianopia will be congruous (Figure 55.2, 7), unlike the incongruous hemianopia seen with an optic tract lesion (the more
posterior the lesion, the more congruous the field defect). Because the macula has a large representation in the occipital cortex, and a dual blood supply, the central 5° of vision is maintained in an anterior cortical lesion—macular sparing (Figure 55.2, 8).

Macular fibres at occipital cortex

A posterior lesion affecting one side of the occipital cortex will result in a homonymous hemianopic scotomatous field defect (Figure 55.2, 9).

Retina

Retinal disease can grossly restrict the visual fields, as can advanced chronic open-angle glaucoma (Figure 55.2, 10).

Giant cell arteritis

Giant cell arteritis (GCA) is an ophthalmic and medical emergency.

Aims

  • Appreciate that ocular diagnosis of GCA can be lifesaving.
  • Be aware of GCA as a diagnosis, and investigate it appropriately.

GCA

  • GCA is a very important type of vasculitis manifesting in the eye. It is a disease that enables the student to appreciate how an ophthalmic diagnosis can be lifesaving. GCA is very commonly seen in eye casualty, and all physicians need to be able to manage it.
  • GCA predominantly affects medium and large-sized arteries, particularly the main branches of the aorta, the primary and secondary branches, and the superficial temporal, ophthalmic, posterior ciliary and vertebral arteries (Figure 56.1a).
  • GCA is between two and six times more common in women and is almost always seen in patients older than 50 (incidence is 15–25 per 100 000 per year in those over 50 years).

Pathology

  • GCA is characterized by granulomatous inflammation at the level of the internal elastic lamina, with an influx of macrophages, lymphocytes, fibroblasts and occasionally multinucleated giant cells (Figure 56.1b).
  • These manifest as ‘skip lesions’, and areas adjacent to these remain unaffected.
  • The inflammatory infiltrate and subsequent intimal hyperplasia can limit perfusion to the distal tissue, and ischaemia ensues.

Ophthalmic manifestations

  • Unilateral visual disturbance (transient or permanent) is due to central retinal artery occlusion or arteritic anterior ischaemic neuropathy (AAION).
  • Double vision is due to cranial nerve palsies.

Systemic associations

Polymyalgia rheumatica (PR) represents a systemic manifestation of the same underlying pathological process, causing distress by pain and morning stiffness in the neck, shoulder and pelvis. Ischaemic changes are not as readily seen as with GCA, and PR responds to low-dose steroids.

Clinical features

Symptoms

  • Neuro-ophthalmic:
    ○ headache and scalp tenderness (compromised superficial temporal artery)
    ○ hair loss and scalp ischaemia
    ○ diplopia
    ○ jaw claudication (ischaemia to the masseter)
  • Systemic:
    ○ myalgia
    ○ anorexia
    ○ weight loss

Signs

  • Point tenderness over the temporal artery.
  • White and swollen optic nerve head, cotton wool spots, haemorrhages, relative afferent pupil defect and visual field defects (AAION or vein occlusions).
  • Asymmetrical pulses and blood pressure readings (involvement of the subclavian artery).
  • Extreme cases will cause aortic dissection, transient ischemic attack or strokes.

Investigations and diagnosis

  • Acute phase response proteins (but may be normal)
    ○ a large American study has shown that in the absence of another cause, raised levels of both C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) are strong predictors of disease.
  • Thrombocytosis.
  • Liver function test.
  • Temporal artery biopsy (TAB) shows necrotizing vasculitis, but may be negative due to the nature of skip lesions.
  • Ultrasound shows up arterial wall oedema as hypo-echoic ‘halos’; but this investigation is more a research tool, rather than being used readily clinically.
  • Overall: if clinically suspicious and all results are negative, treat the patient for active disease.

Treatment

  • Usually visual loss cannot be halted in the involved eye, and treatment is geared to prevent contralaterally morbidity and indeed mortality. Oral glucocorticoids are the mainstay of treatment (initially
    prednisolone 1 mg/kg), and most patients are treated and weaned off over a year.
  • Unfortunately, there are multiple side effects associated with steroid use, including fluid retention, hypertension, hyperglycaemia, immune suppression, osteoporosis and psychoses. Hence, treating any inflammatory condition in the long run should involve steroid-sparing agents.
  • The evidence for steroid-sparing agents is fairly inconclusive. The most investigated agent is methotrexate, and one meta-analysis revealed that administrating a low dose late on in the disease reduces relapses. Poor results have been seen with all other agents, particularly infliximab.
  • Aspirin reduces the risk of CVA.