- Neuro-ophthalmological assessment
- Pupillary light reflex
- Swinging flashlight test
- Dazzle reflex
- Extraocular muscular control of eyeball position and movement
- Vestibular control of eyeball position and movement
- Somato-sensory innervation of the eyeball and eyelid
- Motor control of the eyelids
- Lacrimal gland function
- Sympathetic innervation to the eye and face
- Pharmacological evaluation of pupil function
- Electrophysiological evaluation of the visual system
The neuro-ophthalmological examination combines aspects of the neurological examination with components of the ophthalmic assessment and is an important element of both disciplines. Armed with a basic knowledge of the visual pathways and pupillary light reflex, performing the neuro-ophthalmological examination is simple, quick and requires no expensive or specialized equipment. From a neurological viewpoint, the visual system is both fascinating and unique, in that the retina and optic disc are the only components of the nervous system directly visible in the normal patient. Even in the absence of overt neuro-ophthalmological abnormalities, athorough evaluation of the eyes, including afundic examination, should always be performed in the neurological patient, as the underlying cause of neurological disease may be evident (). Conversely, a full neurological examination should be performed in any animal with neuro-ophthalmological abnormalities.
Terms that are commonly used in clinical neuro-ophthalmology are defined in Definitions of terms commonly used in clinical neuro-ophthalmology.
Definitions of terms commonly used in clinical neuro-ophthalmology
|Anisocoria||Pupils of unequal or asymmetrical size|
|Blepharospasm||Spasm of the orbicularis oculi muscle|
|Consensual PLR||Application of a light stimulus to one eye causing reflex constriction of the opposite pupil|
|Enophthalmos||Abnormal displacement or sinking of the eyeball into the orbit|
|Esotropia||Convergent strabismus: deviation of the visual axis of one or both eyes towards that of the opposite eye. Also called cross-eye|
|Exophthalmos||Abnormal displacement or protrusion of the eyeball out of the orbit|
|Exotropia||Divergent strabismus: deviation of the visual axis of one or both eyes away from that of the opposite eye. Also called wall eye|
|Miosis||Abnormal or excessive constriction of the pupil|
|Miotic||Drug or agent that causes pupillary constriction|
|Mydriasis||Abnormal or excessive dilation of the pupil|
|Mydriatic||Drug or agent that causes pupillary dilation|
|Nystagmus||Rhythmical, involuntary movements of the eyeball with either fast and slow phases (jerk nystagmus) or, less commonly, equal oscillations (pendular nystagmus)|
|Ophthalmoplegia||Paralysis of the eye muscles|
|Ophthalmoplegia interna||Paralysis of the iris and ciliary muscles|
|Ophthalmoplegia externa||Paralysis of the extraocular muscles|
|Pan-ophthalmoplegia||Paralysis of the iris, ciliary muscles and extraocular muscles. Also called total ophthalmoplegia|
|PLR||Pupillary light reflex. Also called the photomotor reflex|
|Ptosis||Abnormal or paralytic drooping of the upper eyelid|
|Strabismus||Abnormal deviation of the visual axis of the eye that the animal cannot overcome|
|Xeromycteria||Abnormal dryness of the nasal mucous membrane and planum|
Before performing a detailed neuro-ophthalmological examination, it is essential first to observe the animal from a distance ― the so-called ‘hands-off’ examination. This allows assessment of the patient’s interaction with its surroundings, giving an indication as to the level of consciousness, as well as allowing for evaluation of any localizing signs (e.g. circling, hypermetria or head tilt). Identifying animals with decreased levels of consciousness is important, as these animals may respond inappropriately to tests requiring conscious input, without there actually being a lesion within the pathway being tested.
Vision is supplied by cranial nerve (CN) II (optic). The optic nerve supplies conscious perception of vision as well as visual input into unconscious reflex pathways, including the pupillary light reflex (also termed the photomotor reflex) and dazzle reflex. As part of the ‘hands-off assessment, vision should be appraised by observing the animal interacting with and negotiating a strange environment (usually the consulting room) and navigating an obstacle course, and by performing the tracking response (evaluating whether the patient is able visually to follow moving but silent objects, such as a dropped piece of cotton wool).
The ‘hands-on’ assessment of vision includes the following.
- • Visual placing response. The patient is held under its chest and brought up towards a table edge, but without letting the thoracic limbs touch the table. The normal patient should see the table and attempt to place its thoracic limbs on the surface of the table
- • Menace response. This learned response may not be present in normal animals under 12 weeks of age. The test is performed by making a threatening movement towards each eye in turn while closing the other eye, without touching the patient (). The normal response is for the patient to blink, with or without aversion of the head. The motor innervation of the muscles responsible for the blink is via the facial nerve and this test therefore also assesses the integrity of the facial nerve (CN VII) and cortical awareness (). Furthermore, as the menace response is coordinated in the cerebellum, diffuse lesions of the cerebellum may result in ipsilateral loss of the menace response without loss of vision.
- • Pupillary light reflex (PLR). See below for details.
- • Swinging flashlight test. See below for details.
- • Dazzle reflex. See below for details.
- • Assessment of pupil size and symmetry. Check for anisocoria (unequal or asymmetrical pupils). This should include evaluation in both the light and the dark (further evaluation is detailed under the pupillary light reflex).
Pupillary light reflex
The pupillary light reflex is supplied by cranial nerve II (optic) and the parasympathetic portion of cranial nerve III (oculomotor). It evaluates the afferent visual pathways from the retina to just prior to the lateral geniculate nuclei in the thalamus (), while the efferent outflow is mediated via the parasympathetic portion of the oculomotor nerve (CN III). The pupillary light reflex is tested by shining a bright light into the pupil and assessing for constriction of the pupil (direct reflex). The opposite pupil should constrict at the same time (consensual reflex) but it is not necessary to assess the consensual reflex if the direct pupillary light reflex is intact in both eyes.
The normal direct pupillary light reflex response is initial pupillary constriction followed by slight dilation. The degree of dilation increases with decreasing brightness of light stimulation and with longer stimulation times; this is termed pupillary escape and is the consequence of light adaptation of photoreceptors. Besides the brightness of the light used, the resting sympathetic tone also determines the degree of pupillary constriction, which means that a common cause of apparent failure of the pupillary light reflex is using a light that is not bright enough in a nervous animal with high resting sympathetic tone. The pupillary light reflex requires fewer intact axons than conscious perception of vision and therefore in partial lesions of the proximal visual pathways the situation may exist where there is loss of vision but the pupillary light reflex is spared ().
Swinging flashlight test
The swinging flashlight test, a variation of the PLR, allows evaluation of both the direct and consensual PLRs. The test is performed by ‘swinging’ the light stimulus from one eye to the other. If both the direct and consensual PLRs are intact, as the light stimulus is swung from one eye to the other each pupil can be seen to be already constricted as the light stimulus is directed at it (consensual response) and continue to remain constricted for the duration of the direct stimulus (direct response). Because the pupil that is being directly stimulated tends to constrictto a slightly greater extentthan the contralateral pupil, slight further constriction may be evident as the light stimulus is directed at each eye.
The dazzle reflex (), supplied by cranial nerve II (optic) and cranial nerve VII (facial), is similar to the pupillary light reflex in that it does not evaluate the cortical aspects of the visual pathway. In contrast to the PLR, in which the efferent arm is mediated by the oculomotor nerve, in the dazzle reflex the efferent pathway is mediated via the facial nerve. The reflex is induced by flashing a very bright light into the eyes with the normal response being a rapid blink. Loss of the dazzle reflex implies a subcortical lesion. While cortical lesions causing blindness (with loss of the menace response) do not interrupt the dazzle reflex pathway, the dazzle reflex may be exaggerated in these patients through disinhibition as a result of loss of upper motor neuron innervation.
Extraocular muscular control of eyeball position and movement
The parasympathetic portion of the oculomotor nerve supplies the iris muscle for the pupillary light reflex as well as the ciliary muscle (). The oculomotor nerve (CN III) also supplies motor innervation to the extraocular muscles (including the dorsal, medial and ventral rectus muscles and the ventral oblique muscle of the eyeball) and the levator palpebra muscle of the upper eyelid. The trochlear nerve (CN IV) innervates the dorsal oblique muscle. The abducent nerve (CN VI) innervates the lateral rectus and retractor bulbi muscles.
The innervation to the extraocular muscles can be assessed individually but it is more usual to assess them together, as in most cases cranial nerve III is affected in isolation or all three nerves are affected together (producing external ophthalmoplegia). Assessing eyeball movement is achieved by:
- • Observing the eye movements as the patient looks around voluntarily and in response to induced movements (by holding the head fixed and creating a distraction on either side to see if the animal can appropriately fix the gaze on the visual stimulus in a bilaterally coordinated fashion)
- • Assessing the eyes for any asymmetry of the visual axis between the left and right eyes (strabismus or squint)
- • Evaluating the innervation to the retractor bulbi muscles (innervated by the abducent nerve) by observing for retraction of the globe during the corneal reflex (stimulated by touching the cornea ― sensation is mediated via the ophthalmic branch of the trigeminal nerve)
- • Retropulsion of eyeball to assess for presence of a retrobulbar mass.
The normal eye movements can be further evaluated by inducing physiological nystagmus (vestibulo-ocular reflex, which also evaluates cranial nerve VIII). The evaluation of physiological nystagmus is detailed below under vestibular control of eyeball position and movement. The absence of normal physiological nystagmus indicates a vestibular lesion, a lesion affecting the extraocular muscles or their innervation or a lesion affecting the connection between the two.
Vestibular control of eyeball position and movement
This is supplied by cranial nerve VIII (vestibulocochlear). There is a close association between the vestibular system and the innervation to the extraocular muscles that allows an animal to keep its gaze fixed on an object despite changes in the head position. When the head is moved from side to side or up and down at a steady rate without the gaze being fixed on a single object, a nystagmus is induced with the fast phase movements of the eyeball in the direction of the head movement. This nystagmus is termed physiological nystagmus or the vestibuloocular reflex. These normal vestibular eye movements are independent of vision and are normally still present in animals with acquired visual loss. Physiological nystagmus allows the gaze to jump from object to object and follow the object as the visual field moves past, instead of the visual input recording a constant blur of passing information. Physiological nystagmus should stop once the head movement stops. An exception to this is where the head movement continues for a prolonged period in the same direction and at a constant speed, such as being spun on a revolving chair ― in this situation the vestibular system has time to adapt, with the physiological nystagmus stopping during the constant movement but briefly restarting when the speed or direction of movement changes or is stopped.
In contrast to normal physiological nystagmus, lesions affecting vestibular input to the extraocular muscles may result in a static alteration in gaze direction (strabismus or squint) or involuntary eye movements (nystagmus) (as described later). The vestibular control of eyeball position and movement is therefore assessed by evaluating for strabismus, spontaneous nystagmus and the presence of normal physiological nystagmus. This should include elevating the animal’s head (with the ears level) and holding it briefly elevated to see if a strabismus can be induced, as well as altering the animal’s position (including turning it on its back) to assess for positional nystagmus. Other features of vestibular disease and associated cranial nerve deficits, including concurrent ipsilateral hearing deficits, facial nerve paresis, Homer’s syndrome and trigeminal nerve lesions, may be present (). In central (brainstem) lesions, the ascending proprioceptive and descending motor tracts to the limbs or the cerebellum may be affected.
Somato-sensory innervation of the eyeball and eyelid
The three branches of cranial nerve V (trigeminal) ― maxillary, mandibular and ophthalmic ― are responsible for sensory information from the entire face (), while the mandibular branch provides motor innervation to the masticatory muscles (masseter, temporal, pterygoids, rostral digastricus and mylohyoid). In addition, the ophthalmic and maxillary branches supply sensory information from the nasal mucosa.
The ophthalmic branch of the trigeminal nerve is assessed by performing the palpebral and corneal reflexes. The palpebral reflex is evaluated by touching the medial canthus of the eye and observing for the presence of a blink (mediated by cranial nerve VII, the facial nerve); the response to touching the lateral canthus is variable and probably innervated by the maxillary branch. The corneal reflex is evaluated by holding the eyelids open and lightly touching the cornea with a finger or cotton swab. The normal response to the corneal reflex is to retract the globe (mediated by cranial nerve VI, the abducent nerve) and prolapse the third eyelid. A more objective assessment of corneal sensation can be obtained by using a Cochet-Bonnet aesthesiometer (), but differences exist between breeds (with canine dolichocephalic breeds being more sensitive than brachycephalic breeds) and regions of the cornea (the centre being the most sensitive) (). The Cochet-Bonnet aesthesiometer consists of a retractable nylon filament that can be varied in length from 0 to 6 cm. The nylon filament is touched against the cornea to determine the minimum length at which no conscious response is present and this gives a measure of corneal sensation. The force exerted by the nylon filament when it touches the cornea is inversely proportional to its length (the longer the filament, the less rigid it is). Other non-contact corneal aesthesiometers are available, including gas puff devices.
Motor control of the eyelids
The motor innervation to the blink is supplied by cranial nerve VII, thefacial nerve, which additionally innervates the other muscles of facial expression, supplies parasympathetic innervation to (among other structures) the lacrimal gland and lateral nasal gland and sensation to the rostral two-thirds of the tongue and inner surface of the pinna. The parasympathetic innervation to the lacrimal gland splits from the facial nerve in the facial canal just prior to the close approximation between the facial nerve and the tympanic bulla.
Normal function of the facial nerve innervation to the orbicularis oculi muscles controlling the blink is assessed by:
- • Observing the animal for normal blinking
- • The menace response (described in the vision section)
- • The palpebral reflex (see above, under somatosensory innervation of the eyeball and eyelid).
Lacrimal gland function
This is supplied by cranial nerve V (trigeminal) (sensory) and the parasympathetic portion of cranial nerve VII (facial). Increased reflex tear production occurs in response to sensory stimuli (including direct corneal stimulation and exposure to cold and irritants) via the ophthalmic branch of the trigeminal nerve. Trigeminal lesions will not usually affect basal tear production but reflex tear production in response to corneal, conjunctival or nasal stimulation is lost. The lacrimal gland is innervated by the parasympathetic portion of the facial nerve, a branch of which also innervates the lateral nasal gland, a serous secreting gland that functions to keep the nose moist. The normal function of the facial nerve innervation to the lacrimal gland is assessed by performing a Schirmer tear test and examining the ipsilateral nostril for dryness.
Sympathetic innervation to the eye and face
The pathway consists of first, second and third order neurons, with the first order neurons originating in the hypothalamus and rostral mid-brain and travelling down the tectotegmental spinal tract. The synapses with the second order neurons occur in the lateral horn of the spinal cord grey matter at the level of T1 to T3 spinal cord segments. The second order axons then leave the spinal cord with the T1 to T3 nerve roots. The brachial plexus innervating the thoracic limb is made up of contributions from nerve roots C6 to T1 (and sometimes T2) (); part of the sympathetic supply leaving the spinal cord is therefore closely associated with the innervation to the thoracic limb.
The sympathetic axons separate from the T1 to T3 nerve roots as the ramus communicans and form the thoracic sympathetic trunk. The sympathetic trunk courses cranially in close apposition to the descending vagus nerve, together forming the vagosympathetic trunk within the carotid sheath. The sympathetic axons course rostrally through the caudal cervical ganglion, synapsing in the cranial cervical ganglion, adjacent to the tympanic bulla. From here the third order sympathetic axons pass through the middle ear and enter the cranial cavity with the glossopharyngeal nerve, then pass close to the cavernous sinus with the carotid artery, before leaving the cranial cavity via the orbital fissure in close approximation to the ophthalmic branch of the trigeminal nerve. The sympathetic supply to the eye and face innervates smooth muscle in the iris (dilatormuscle), orbit, upper and lower eyelids (Muller’s muscle), third eyelid and walls of blood vessels of the head. The effect is to contribute to the control of pupil and palpebral fissure size and maintain smooth muscle tone within the orbit (affecting eyeball position and third eyelid protrusion).
Pharmacological evaluation of pupil function
Pharmacological testing may be useful in ascertaining the site of lesions affecting the efferent arm of the pupillary light reflex and the sympathetic supply to the eye (Homer’s syndrome). However, pharmacological testing is not an exact science and the times to a response should be used only as a guide to the site of the lesion. There are differences in opinion on the utility of this form of testing and, in particular, on the concentrations of drugs used. Pharmacological testing should always be performed on both eyes, using the normal eye as a comparison, and it is important to apply the same dose of a drug to each eye. The basis of the tests lies in the development of denervation hypersensitivity (). Pharmacological testing of the sympathetic nervous system is discussed in more detail under Homer’s syndrome in disorders of pupil size and function. Lesions affecting the efferent arm of the pupillary light reflex (parasympathetic lesions producing mydriasis) can be localized further by application of direct and indirect parasympathomimetics.
- • Differentiation between pre ― and post-ganglionic lesions (ciliary ganglion) can be achieved by the topical administration of an indirect-acting parasympathomimetic (0.5% physostigmine drops). This drug inhibits cholinesterase, thereby increasing the concentration of acetylcholine at the neuromuscular junction. If the post-ganglionic neuron is preserved, it apparently releases low levels of acetylcholine continuously, the local concentration of which is increased by application of physostigmine. Iris constriction occurs 40-60 minutes before the control eye in pre-ganglionic lesions, due to denervation hypersensitivity. However, in post-ganglionic lesions, physostigmine has no effect. If neither pupil responds, the test is considered a false negative and must be repeated.
- • The use of a direct-acting parasympathomimetic (1% pilocarpine drops) may allow differentiation between pre ― and post-ganglionic lesions. Iris constriction occurs more rapidly in the affected eye than in the contralateral normal eye in post-ganglionic lesions, due to denervation hypersensitivity. Many people believe that concentrations of pilocarpine of 1% or greater will produce iris constriction, no matter what the neurological status, and therefore recommend the use of 0.05-0.1% pilocarpine (dilute the solution with saline) for differential detection of denervation hypersensitivity in post-ganglionic lesions. In practice this test is often non-specific, with a more rapid response indicating only that the lesion is neurological, rather than specifying the site. For example, this test can be used to differentiate mydriasis due to iris disease or pharmacological blockade from atropine or atropine-like substances, both of which are unresponsive to pilocarpine, from neurological disease ().
Electrophysiological evaluation of the visual system
Electrophysiological evaluation of the visual system largely comprises electroretinography (ERG) and the less commonly performed visual evoked response (VER, also termed visual evoked potential).
The ERG is a test of retinal function, assessing both the rod and cone photoreceptors. It is useful for the identification of those cases of blindness due to retinal disease where the retina appears normal on ophthalmic examination (e.g. sudden acquired retinal degeneration). The ERG can be performed under general anaesthesia, or under sedation in a cooperative patient. A corneal contact-lens electrode is used to record retinal voltage changes that occur in response to a defined flash of light or repeated flashes of light. The ERG response is expressed as a waveform, with the most common recording type having a- and b-waves. The waveform of the ERG and in particular the amplitude and latency of the a- and b-waves are measured when evaluating the ERG ()
Visual evoked potentials
Visual evoked potentials (VEPs) are the recordings of occipital cortex potentials, arising in response to brief flashes of light, using scalp recording electrodes and signal averaging techniques. The VEP waveform assesses the function of the central retinal region and post-retinal structures, including the optic nerve, optic tracts and visual cortex. The VEP is largely a research procedure and its use in clinical neuro-ophthalmology is limited.
To simplify the approach to the neuro-ophthalmology patient, the presenting clinical signs can be subdivided into a number of categories, with the most clinically significant being those where vision and/or the pupillary light reflex are impaired:
• Decreased vision with no pupillary light reflex deficits
• Disorders of pupil size and function
• Disorders of the third eyelid
As discussed previously, an occasional consideration is that the pupillary light reflex requires fewer intact axons than conscious perception of vision and therefore in lesions that do not completely interrupt the proximal visual pathways vision is impaired but the pupillary light reflex is spared.
Disorders of the third eyelid
Protrusion of the third eyelid may occur passively following a loss of sympathetic tone to the orbit (Homer’s syndrome and systemic illness), in conditions causing enophthalmos and secondary to retrobulbar masses. Intermittent, brief protrusion of the third eyelid may occur in tetanus ().
Haw’s syndrome in young cats
Haw’s syndrome is bilateral protrusion of the third eyelid of unknown cause and occurs in young cats in the absence of other systemic and ophthalmic abnormalities. It has been suggested to occur in dogs and in particular the Golden Retriever (). The condition may develop following a history of diarrhoea and generally persists for some time before gradually resolving. Although treatment is usually not necessary, either topical 1-2% epinephrine or 10% phenylephrine to abolish the third eyelid protrusion (by stimulating smooth muscle contraction), or 1 % atropine to dilate the pupil, has been suggested if the third eyelid protrusion is severe enough to cause visual impairment ().