Background: Neuro-ophthalmic disorders, although still uncommon, are being reported more often in horses. Cases can present with a wide range of clinical signs, from chronic, non-healing corneal ulcers to behavioural changes due to visual impairment. Achieving the correct diagnosis is not always easy. Using a systematic approach to examine horses with suspected neuro-ophthalmic disorders will help the clinician to achieve a neuroanatomic diagnosis and a list of differential diagnoses. The diagnostic tests are always planned based on this list of differentials and the treatment is targeted to the final or most likely diagnosis. Understanding the neuro-ophthalmic anatomy is mandatory to achieve the correct neurolocalisation and plan the appropriate diagnostic modalities.
Aim of the article: This article reviews the most important neuro-ophthalmic pathways to interpret the clinical signs and underlying causes seen in this field.
Statistics from Altmetric.com
Roser Tetas Pont qualified from Universitat Autònoma de Barcelona, Spain in 2006. She is currently a lecturer in ophthalmology at the Royal Veterinary College, London.
Elsa Beltran qualified from CEU Cardinal Herrera University in Valencia, Spain in 2002. She is currently a senior lecturer in neurology and neurosurgery at the Royal Veterinary College, London.
Key learning outcomes
After reading this article, you should understand:
The variety of clinical signs associated with neuro-ophthalmic disorders;
A structured diagnostic approach to blindness, anisocoria, strabismus and abnormal facial movement or sensation;
The importance of performing and the technique used for a fundus examination;
The anatomy involved in the different neuro-ophthalmic diagnostic tests;
The tools needed for a complete neuro-ophthalmic examination in the horse.
In the current veterinary literature, reports of horses affected with neuro-ophthalmological disorders are infrequent (Davis and others 2002, Mitchell and others 2006, Barnet and others 2008, Hepworth and others 2014, Howe and others 2014, Beltran and others 2015, Sano and others 2017); however, over the past few years, mainly due to the availability of advanced imaging and further understanding of the different diseases, the number of published articles is rising (D’Août and others 2015, Gonçalves and others 2015, Manso-Diaz and others 2015, Ledbetter and Van Hatten 2017). Several neuro-ophthalmic disorders are well recognised within the equine veterinary population, such as Horner’s syndrome (dysfunction of the sympathetic innervation to the eye) or facial paralysis; however, other more subtle deficits are frequently misdiagnosed or not detected until the disease is more advanced. We have found that some horses that are referred to us have neuro-ophthalmic disorders that have been underdiagnosed in first-opinion equine practice.
Clinical signs of neuro-ophthalmic disorders
Before interpreting the dysfunction of the neuro-ophthalmic pathways it is important to understand the pathway’s normal function, and readers are referred to DeLahunta and others (2015a).
Clinical signs presented by a horse with neuro-ophthalmic disorders include:
Decreased or absent vision,
Neurogenic keratoconjunctivitis sicca,
Facial paresis/paralysis with secondary neuroparalytic keratopathy,
The initial clinical approach to a horse presenting with any of the above mentioned clinical signs should include:
An evaluation of the signalment,
An evaluation of the horse’s history,
Tests for neuro-ophthalmic examination:
We recommend that clinicians familiarise themselves with these neuro-ophthalmic tests; for example, by routinely performing them in cases without the specific need. This method will increase the clinician’s sensitivity to subtle deficits, as well as imprinting the required protocol to diagnose these cases.
Fundus examination by direct ophthalmoscopy
One of the first steps when presented with a horse that displays neuro-ophthalmic signs is to carefully examine the ocular fundus by direct ophthalmoscopy (Fig 1) (Webb and Cullen 2013). When examining the fundus a protocol must be used to ensure the assessment of relevant structures. The clinician should always examine the optic disc (optic nerve head), retinal vasculature, tapetal/non-tapetal junction, tapetal/non-tapetal fundus and peripheral retina (Webb and Cullen 2013). When using a direct ophthalmoscope, the clinician must practice a full body manoeuvre to ensure the assessment of the most peripheral parts. Pharmacological dilation is not necessary when assessing the fundus with a direct ophthalmoscope (Featherstone and Heinrich 2013). However, performing this technique in a space where the environmental light can be dimmed will facilitate examination by promoting pupillary dilation.
Assessing vision in horses is subjective (Dwyer 2017). Vision requires a clear visual axis (ie, clear path of light through the cornea, anterior chamber, lens and vitreous), as well as a functional retina, optic nerve, optic chiasm (around 80 per cent of the optic nerve fibres cross over at this level), contralateral optic tract, contralateral lateral geniculate nucleus, contralateral optic radiations and contralateral visual cortex (occipital cortex) (Fig 2) (Webb and Cullen 2013, de Lahunta and others 2015a). Detecting a visual deficit is often easier in acute cases, since horses with chronic vision loss can develop adaptive strategies to cope with decreased vision; frequently, owners of blind horses describe some adaptive mechanisms, such as them relying on other companions for guidance, adopting an abnormal head position or head movement while assessing their surroundings.
Menace response is a more accurate test for vision. For a positive menace response an intact visual pathway (ie, retina to occipital cortex) is required (Fig 2), an intact motor pathway of the eyelids (ie, facial nerve nuclei to the orbicularis oculi muscle), and intact communicating neurons between both pathways (Webb and Cullen 2013, de Lahunta and others 2015a). To elicit a menace response a threatening gesture is made towards the eye, and it is observed with a subsequent blink. It is important to avoid touching the eyelashes and vibrissae that surround the eye or creating excessive air currents as these can trigger the palpebral or corneal reflex, and therefore a false-positive menace response. Menace response should be undertaken in both medial and lateral visual fields, by directing the hand from in front of the muzzle towards the medial part of the cornea (medial visual field) and from in front of the ear towards the lateral part of the cornea (lateral visual field) (Webb and Cullen 2013, de Lahunta and others 2015a). It is important to note that the threatening movement of the hand in front of one eye will elicit a blink in both eyes in the absence of other neurological deficits (de Lahunta and others 2015a). This may not always be observed by the clinician while on the side of the horse, but an assistant or the client themselves can assess the blink on the contralateral eye.
If the menace response is decreased or absent, the facial nerve needs to be evaluated by the palpebral reflex, because facial nerve deficits may result in reduced or absent menace response without visual impairment. Furthermore, it is also worth mentioning that menace response is a conscious and learned response; therefore, new-born foals will not develop menace response until they are one- to two-weeks-old (de Lahunta and others 2015a). Moreover, horses that are stressed, obtunded or disorientated may not respond appropriately to the menace response, without necessarily being affected by a lesion in the menace response pathway (Beltran and others 2017).
Decreased or absent vision and subsequent reduced or absent menace response is not rare. A complete ophthalmic examination is indicated in these cases to rule out the presence of any ocular opacity or abnormality in the ocular fundus (Webb and Cullen 2013). The orbit also needs to be assessed in cases with an absent menace response. The orbit is anatomically closely related to several structures of the head commonly affected with pathology in horses, such as the head sinuses (Hartley and Grundon 2017, Ledbetter and Van Hatten 2017). Neoplasia or inflammation within the sinuses can involve the orbit and the optic nerve, causing blindness and exophthalmos (Fig 3) (Davis and others 2002, Barnet and others 2008, Hartley and Grundon 2017, Sano and others 2017). Assessing the facial and ocular symmetry, percussing the periorbital sinuses, and testing for reduced airflow from the ipsilateral nostril are mandatory diagnostic steps in cases with unilateral blindness without globe abnormalities (Fig 4) (Hartley and Grundon 2017).
A rough assessment of vision can be made with a maze test (obstacle course). This test subjectively assesses the horse’s navigation in an unknown surrounding, with the aim of eliciting deficits in a particular visual field. A series of obstacles (such as overturned buckets) are laid out and then the horse is loosely led across the path to determine its response and movement. Towels and hoods can be used as blindfolds to assess vision in each eye (Fig 5). Maze testing should be performed in both good and dim light conditions to demonstrate specific photoreceptor disorders (Dwyer 2017).
A dazzle reflex (photic blink reflex) is induced by flashing a strong light into the eye, causing a blink. Assessing the dazzle reflex will test the first part of the visual pathway only (from the retina to the optic tract). At the level of the optic tract, the fibres involved with the dazzle reflex abandon the ones responsible for vision to reach the facial nucleus and induce a blink (Webb and Cullen 2013, de Lahunta and others 2015a). The blink will be bilateral. It is important to note that a positive dazzle reflex does not imply vision, since the higher parts of the visual pathway are not assessed with this test (Fig 2). Moreover, eyes with severe intraocular opacities, such as mature cataracts, can present an intact dazzle reflex but have completely impaired vision (McMullen and Gilger 2017). We recommend not using this reflex on its own to neurolocalise as the exact anatomical pathways have not been fully elucidated.
Assessing facial musculature movement and facial sensation
Movement of the ears, muzzle and facial musculature (including eyelids) are mediated by the facial nerve and its branches (Webb and Cullen 2013, de Lahunta and others 2015b). Moreover, the facial nerve carries parasympathetic innervation to the lacrimal gland as well as sensory information of the inner ear (de Lahunta and others 2015b). There are several tests that assess the integrity of the motor fibres of the facial nerve. As discussed above, the menace response and dazzle reflex test the motor component of the facial nerve and the orbicularis oculi muscle.
When assessing the palpebral reflex both canthi of the eye are gently touched to stimulate the sensory innervation of the eyelid skin (branches of the trigeminal nerve) and elicit a blink (Fig 6). It is important to stimulate both canthi since the sensory innervation differs in the medial canthus (ophthalmic branch of the trigeminal nerve) versus the lateral canthus (maxillary branch of the trigeminal nerve). Threatening movements are avoided so as not to stimulate a menace response instead of facial sensation (Webb and Cullen 2013, de Lahunta and others 2015b).
Branches of the facial nerve are often located superficially under the skin and some can be blocked at several points to reduce regional muscular movement; for example, the auriculopalpebral nerve block commonly performed to facilitate ophthalmic examination in horses (Stoppini and Gilger 2017).
Trauma to the facial nerve is quite common (de Lahunta and others 2015b). Traumas to the base of the ear or around the zygomatic arch are often associated with reduced or absent eyelid movement (Fig 7). Trauma will rarely affect the non-motor branches of the facial nerve, but neurogenic keratoconjunctivitis sicca can occur secondary to parasympathetic denervation of the lacrimal gland (de Lahunta and others 2015b). It is important to note that the integrity of the eyelids and tear film are paramount for a good ocular surface health. Horses affected with chronic facial paralysis will develop corneal exposure (lagophthalmos), with subsequent corneal drying and ulcerative keratitis (Fig 8). Ulcers secondary to facial paralysis (neuroparalytic ulcers) have a poor prognosis (de Lahunta and others 2015b). In these cases, placement of permanent or temporary tarsorrhaphies may be indicated to prolong vision and globe retention (Hartley and Grundon 2017). Unfortunately, most horses with persistent severe facial nerve deficits end up requiring enucleation.
Corneal reflex and nasal sensation
The cornea and the nasal mucosa are innervated by sensory endings of the trigeminal nerve (ophthalmic branch) (Fig 9). When assessing the corneal reflex the lateral corneal quadrant is gently contacted to stimulate the sensory innervation of the cornea (ophthalmic branch of the trigeminal nerve) to elicit a blink (facial nerve) and the globe retraction with subsequent third eyelid protrusion (abducens nerve) (Fig 10) (Featherstone and Heinrich 2013). This test must be performed before application of topical anaesthesia and care needs to be taken to avoid stimulating a menace response. To assess nasal sensation the nasal mucosa is gently touched, which will induce a head movement if the sensation is intact (Webb and Cullen 2013, de Lahunta and others 2015b).
Assessing both a corneal reflex and nasal sensation are particularly important in cases of suspected middle cranial fossa syndrome. The ophthalmic branch of the trigeminal nerve reaches the orbit via the orbital fissure with several other cranial nerves (oculomotor nerve, trochlear nerve, abducens nerve, sympathetic innervation to the eye). Lesions at the level of the orbital fissure or middle cranial fossa can present with absent/reduced corneal and nasal sensation, as well as internal and external ophthalmoplegia/ophthalmoparesis (Webb and Cullen 2013, de Lahunta and others 2015b).
Assessing pupil size and movement
Within the iris there are two differentiated groups of muscles that control the pupil size and movement: the sphincter muscle and the dilator muscle. Sympathetic innervation to the iris mediates mydriasis by inducing constriction of the dilator muscle and relaxation of the sphincter muscle. On the other hand, iris parasympathetic innervation mediates miosis by inducing constriction of the sphincter muscle and relaxation of the dilator muscle (Gum and MacKay 2013, de Lahunta and others 2015c). There are two important tests when assessing the pupil size and movement: evaluation of the pupil size at rest and PLR.
Observation of the pupil size at rest
Assessing the pupil size at rest can help to establish if there is anisocoria (different size pupils). To perform this test, the clinician applies a light source that can be dimmed (ie, direct ophthalmoscope or an ocular transilluminator). The clinician should be positioned six to eight feet in front of the horse with the light source close to their eyes. The light is directed towards the centre of the horse’s head, subsequently both pupils will be highlighted by the tapetal reflection (Stoppini and Gilger 2017). Both pupils should have the same size and shape (oval horizontal in the horse) (Fig 11). It is important to assess the resting pupil size in both environmental light and dim room light conditions. This will be very helpful when determining which pupil has an abnormal size in cases of anisocoria (Fig 12).
A normally functioning pupil will dilate in the dark. If anisocoria is due to an abnormally large pupil (unilateral left mydriasis, Fig 12), the normal pupil will dilate in the dark, while the abnormal pupil will stay the same size. Subsequently, the anisocoria will become less obvious in the dark than in light conditions. On the other hand, if the abnormal pupil is the small one then in the dark the normal pupil will dilate, while the abnormal pupil will remain smaller. In this case, the anisocoria will become more obvious in the dark than in light conditions (Featherstone and Heinrich 2013).
Pupillary light reflex
Assessing the pupil reaction to light is also an important neuro-ophthalmic test. The PLR tests the first part of the visual pathway only (from the retina to the contralateral optic tract) but does not test vision. At the level of the contralateral optic tract, the fibres involved with the PLR abandon the ones responsible for vision and cross over to reach the parasympathetic nucleus of the oculomotor nerve. From this point, parasympathetic fibres of the oculomotor nerve (as preganglionic fibres) reach the ciliary ganglion via the orbital fissure. From the ciliary ganglion, the short ciliary nerves (as postganglionic fibres) innervate the iris sphincter muscle causing miosis (Webb and Cullen 2013, de Lahunta and others 2015c) (Fig 13). In the absence of disease, when illuminating one eye both pupils will constrict due to crossing of fibres (around 80 per cent of the optic nerve fibres) both at the level of the optic chiasm and later on when reaching the nuclei of both oculomotor nerves. Miosis will be stronger in the illuminated eye (direct PLR) than in the contralateral eye (indirect or consensual PLR). This terminology can be confusing so we recommend that clinicians note what happens in each eye separately when light is directed into it (de Lahunta and others 2015c). Assessing the PLR can confirm which one of the pupils is abnormal in cases of anisocoria.
When anisocoria is diagnosed, it is the clinician’s responsibility to determine which one of the pupils is the abnormal one. When the presence of unilateral miosis or mydriasis in the affected horse has been determined, a differential diagnosis is made based on the signalment, history, systemic assessment, and other neurological and ophthalmic findings.
The list of underlying causes of unilateral mydriasis is long, but it is vital to determine if there is an afferent problem (retina, optic nerve, optic chiasm or contralateral optic tract), or an efferent problem of the pupil (oculomotor nerve/ciliary ganglion or short ciliary nerve) (Webb and Cullen 2013, de Lahunta and others 2015c). Horses with optic neuropathies, for example related to local invasion of periorbital masses (Figs 3, 4), can present with a dilated pupil with absent direct PLR, absent dazzle reflex, absent menace response and absent PLR to the contralateral eye when this eye is being illuminated (de Lahunta and others 2015c). On the other hand, horses can also develop oculomotor neuropathy secondary to masses or inflammation at the level of the orbital fissure or middle cranial fossa (de Lahunta and others 2015c). These present clinically with a dilated unresponsive pupil with normal vision (positive menace response, absent direct PLR when the affected pupil is tested, and absent indirect PLR when the contralateral eye is tested).
Anisocoria secondary to unilateral miosis in horses with ocular disease is commonly reported, since miosis is often associated with uveitis (Gilger and Hollingsworth 2017). As discussed above, it is mandatory that all horses with a neuro-ophthalmic disorder receive a full ophthalmic examination to rule out the presence of an underlying ocular condition. Horner’s syndrome is relatively common in horses and can present with a miotic pupil (Webb and Cullen 2013, de Lahunta and others 2015c).
Assessing eyeball position and movement
Direct observation and vestibulo-ocular reflex
Direct observation and vestibulo-ocular reflex (VOR) are used to assess eyeball position and movement.
Globe movement and its position within the orbit are governed by the coordination of the cranial nerves that innervate the extraocular muscles (trochlear and abducens nerve and the motor component of the oculomotor nerve), as well as the vestibular system (including the vestibulocochlear nerve). Nystagmus can be grossly divided into physiological and pathological (Webb and Cullen 2013, de Lahunta and others 2015d). Direct observation of any spontaneous eye movement can elicit the suspicion of pathological nystagmus (Stoppini and Gilger 2013, de Lahunta and others 2015d). The most common cause of pathological nystagmus is vestibular disease (de Lahunta and others 2015d).
Assessing the VOR tests the presence of a physiological nystagmus. To perform this test, the horse’s face is moved horizontally sideways and the involuntary eye movement is assessed. The slow phase of the nystagmus will be in the opposite direction to the head movement and the high-velocity reorientation phase towards the direction of the head movement (Webb and Cullen 2013, de Lahunta and others 2015d). An absent or reduced VOR may be indicative of a lesion in the extraocular muscles, oculomotor, trochlear, abducens or vestibulocochlear nerve. Horses with vestibular dysfunction will exhibit other signs of vestibular dysfunction (ie, head tilt, vestibular ataxia). It is important to note that horses with visual impairment or blindness will present an intact VOR since the visual pathway is not involved in this reflex (de Lahunta and others 2015d). However, active visual experience is required during early and adult life to develop and maintain a normal VOR.
Strabismus is an abnormal position of the eyeball relative to the orbit and there are two main types of strabismus: vestibular strabismus (ie, a positional strabismus which is seen with vestibular dysfunction, when the head and neck move dorsal or ventral due to loss of antigravity tone) and neuromuscular strabismus (fixed strabismus). The neuromuscular strabismus is seen as a deviated position of the eyeball relative to the orbit regardless of head position. Neuromuscular strabismus can be due to loss of innervation of the extraocular muscles or myopathy of the extraocular muscles and can be caused by orbital or intracranial disorders (congenital, inflammatory, infectious, neoplastic and traumatic processes) (Webb and Cullen 2013, de Lahunta and others 2015d).
Neuro-ophthalmic disease can present with a wide variation of clinical signs in horses. Understanding the neurological pathways as well as how to perform the relevant tests will facilitate the clinical approach to achieving a correct neuro-localisation and subsequent differential diagnostic list. Following a systematic examination protocol and assessing each cranial nerve with different tests will increase the clinician’s sensitivity to subtle signs of neuro-ophthalmic disorders.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.