Keratoconjunctivitis sicca in dogs

Keratoconjunctivitis sicca (KCS), or dry eye, is an ocular condition commonly diagnosed in dogs, and less commonly in other species. KCS results most often from an inadequate quantity of tears or a deficient quality of tears. Tears are produced by the lacrimal or tear gland, and the gland of the third eyelid. Tears are needed to provide lubrication and nutrition to the cornea, as well as remove debris and/or infectious agents from the eye (Haeussler and Korb, 2018).

The aim of this article is to provide detailed information on contributing factors and treatment options. A glossary containing ophthalmology terms is provided (Table 1).

Causes

There are several known causes of KCS in dogs, including: immune-mediated, congenital, metabolic, infectious, drug-induced, neurogenic, radiation, iatrogenic, and idiopathic (Dodi, 2015).

• Immune-mediated: immune-mediated diseases that damage the aqueous tear producing glands. This is the most common cause of KCS and is poorly understood. The body's immune system attacks the cells that produce a portion of the tear film resulting in decreased production. This is thought to be an inherited disorder (Hunter and Ward, 2019).
• Congenital: congenital alacrima observed in the Yorkshire Terrier, Bedlington Terrier, English Cocker Spaniel, and Cavalier King Charles Spaniel (Dodi, 2015).
• Metabolic: hypothyroidism, hyperthyroidism and diabetes mellitus. As many as 20% of dogs with hypothyroidism have also been reported to have KCS (Gelatt, 2005). Established ocular manifestations of canine diabetes mellitus include cataracts, corneal endothelial cell loss, endothelial cell pleomorphism and polymegathism, decreased corneal sensitivity, and increased susceptibility to KCS (Foote et al, 2019). One study showed a significant reduction in tear production in animals with diabetes mellitus, hypothyroidism and hyperadrenocorticism (Williams et al, 2019).
• Infectious: canine distemper virus affects the lacrimal glands and glands of the third eyelid and may result in temporary or permanent dysfunction. KCS has also been associated with Leishmania spp. infection and with chronic viral or bacterial conjunctivitis with fibrosis of the glands or their ducts. Feline herpesvirus may induce KCS through fibrosis of the lacrimal gland ductules (Maggs et al, 2012).
• Drug-induced: KCS in dogs has been associated with the non-steroidal anti-inflammatory drug (NSAID) etodolac, as well as with many sulpha derivatives. Temporary reduction in tear production may also be caused by general anaesthesia and topical or systemic atropine (Maggs et al, 2012).
• Neurogenic: disease of the central nervous system is occasionally seen after traumatic proptosis or after a neurologic disease that interrupts the nerves of the tear gland. Patients may often have a dry nose the same side as the dry eye (petMD, 2019).
• Radiation: in some patients that have undergone radiation therapy there can be damage to the lacrimal glands, but luckily it is a less common cause of KCS in dogs (Dodi, 2015).
• Iatrogenic: KCS commonly occurs after removal of a prolapsed gland of the third eyelid, but the median time for this occurrence is 4.5 years after the operation. It may also be seen in patients in which the facial nerve is disrupted (e.g. ear canal ablation) (Maggs et al, 2012).
• Idiopathic: an underlying cause is unknown.

Clinical signs and diagnostics

Clinical signs of KCS depend on the severity of the condition. Recurrent conjunctivitis with a mucopurulent discharge and dull, lacklustre cornea are usual. Progression leads to conjunctival thickening, corneal vascularisation and pigmentation and sometimes severe ulceration (Turner, 2005). The patient may be rubbing at the eye(s), holding the eye(s) completely shut or have some degree of blepharospasm (Figure 1).

KCS can be diagnosed by the use of a Schirmer tear test (STT) (Figure 2). The STT should always be the first test carried out during an ophthalmic examination to ensure that no excessive tearing has been caused by manipulation of ocular structures, which may then lead to a false result. Readings of less than 10 mm wetting in a minute confirm KCS, while readings of 10–15 mm are suspicious in dogs (Turner, 2005). Normal tear production in dogs is >15 mm/minute.

It may not be possible to perform an accurate STT at the time of examination. It could be that the patient has developed ulcer/s due to a severely dry cornea, in which case there may be excessive epiphora and the result would be inaccurate. It could also be that the patient is aggressive (temperament or due to pain) and will not allow the test to be performed. In each situation the patient history, clinical signs and potential causes should be considered.

Factors influencing KCS

Breed

Breed prevalence of immune-mediated KCS has been determined by clinical research carried out in the UK and in the USA. Breeds at increase risk include: Cavalier King Charles Spaniels, English Bulldogs, Lhasa Apsos, Shih Tzus, West Highland White Terriers, Pugs, Bloodhounds, American Cocker Spaniels, English Cocker Spaniels and English Springer Spaniels, Pekingeses, Boston Terriers, Miniature Schnauzers, and Samoyeds (Dodi, 2015).

Conformation

Brachycephalic breeds in particular show various conformational abnormalities of the eye including exophthalmos (abnormal protrusion of the eyes), macropalpebral fissure (an excessively wide opening of the eyelids compared with the size of the eye) and lagophthalmia (inability to close the eyelids completely) (Godfrey and Godfrey, 2019). These conformational abnormalities mean that the tear film is unable to cover the full surface of the eye, leading to insufficient lubrication and potentially harmful particles that have made their way onto the corneal surface not being washed away.

Age

Tear production decreases with age in normal dogs; KCS is, in fact, more frequent in older animals than in younger ones (Dodi, 2015).

Sedation and anaesthesia

It is well known that tranquillisers, sedatives, opioids, and general anaesthetic drugs affect tear production and intraocular pressure in dogs. Although the decrease in tear production due to sedation or anaesthesia is transient, it may lead to clinical disorders, such as corneal erosions and ulcers, which affect vision and cause discomfort (Leonardi et al, 2019).

In one study 39 dogs had a Schirmer tear test pre-anaesthetic and all measured normal; they also had an ophthalmic examination which did not reveal anything abnormal. Following anaesthesia there was a statistically significant reduction in tear production, which returned to normal values 2 hours postanaesthesia, regardless of the duration of the operation (Komnenou et al, 2013).

Another study by Volk et al showed an intramuscular premedication of methadone and acepromazine resulted in a decrease in tear production in dogs before elective general anaesthesia (Volk et al, 2018).

Treatment

Once KCS has been diagnosed or suspected it is important to start treatment promptly and it will need to be continued lifelong. Failure to diagnose and treat KCS will result in the condition progressing and causing severe corneal opacities and later blindness (Herrera, 2005).

Treatment can be medical or surgical, and sometimes both. Medical management aims to stimulate tear production (with topical cyclosporin) and supplement tears with a variety of lubricants. Topical antibiotics and anti-inflammatory agents might also be required (Turner, 2005).

It is important to determine the patient's temperament at this stage as medical management may not be an option for the owner if the dog will not tolerate eye drops; in this case surgical options should be instantly explored.

Prior to administering medications, it is important to clean away the discharge from each eye to avoid crusting and to ensure the medication reaches the ocular surface. Sterile saline can be used or owners can be instructed to use cooled down boiled water on some cosmetic cotton pads at home to gently clean the eyes as necessary. A different cotton pad should be used for each eye so that if bacteria are present in one eye, they are not transferred to the other.

Cyclosporin ointment (Optimmune, MSD Animal Health) treats the underlying auto-immune disease that causes dry eye, as well as the symptoms, by stimulating the tear glands to resume some tear production, halting the immune destruction of these glands and reducing inflammation of the eyes (Msd-animal-health.co.nz, 2018). Cyclosporin can be a little difficult to administer as it is an oily ointment rather than a drop, and so owners often benefit from being shown how to administer it before being sent home with the treatment.

If tear production still has not increased, 1% or 2% cyclosporin every 8 hours or topical tacrolimus every 12 hours should be considered (Maggs et al, 2012). Tacrolimus ointment is another topically applied immunomodulatory agent that has become more widely used, however it is off-licence in the UK so should be used for cases that do not respond to cyclosporin (Lewin, 2014). Preliminary results on a small study carried out by Hendrix et al, support tacrolimus ophthalmic solution as potentially successful in increasing tear production in dogs non-responsive to treatment with cyclosporin A (Hendrix et al, 2011).

It can take up to 8 weeks for either tacrolimus or cyclosporin to increase tear production (Kuonen Cavens, 2018). Treatment efficacy is best evaluated by a decrease in the clinical signs of blepharospasm, conjunctival hyperaemia, mucoid ocular discharge, corneal scarring, and corneal ulceration (Kuonen Cavens, 2018). Use of cyclosporin A appears to be safe in patients with corneal ulceration (Gelatt, 2005).

Pilocarpine can also be an effective tear stimulant in cases of neurogenic KCS, provided some functional lacrimal tissue is present. It can be used topically (however has undesired side effects (such as pain, redness and stinging of the eyes) or, more commonly, orally in the food twice daily. Dose rates are empirical and depend on the response in each individual (Turner, 2005), and will be determined by the veterinary surgeon.

Oral pilocarpine 1–2% eye drops must be mixed with the food with the following initial dose: 1 drop/10 kg body-weight for every 12 hours (Dodi, 2015). The dose can then be gradually increased until unwanted side effects are observed. Side effects of oral pilocarpine can be diarrhoea, drooling, vomiting, or drop in heart rate. For this reason if the dog's weight is <5 kg it is recommended to use only 1% pilocarpine (Dodi, 2015).

Topical lubricants are used in treatment of KCS, often in combination with cyclosporin. These artificial tears moisten and lubricate the dry ocular surfaces, and many different types exist. Gel combinations containing carbomer 980 (Viscotears, CIBA vision; GelTears, Chauvin) are longer lasting and require 4–6 times daily application (Turner, 2005) (Figure 3).

For dogs that do not respond to medical therapy there are surgical options for KCS including a parotid duct transposition, buccal mucosal grafting and episcleral cyclosporin implantation (Kuonen Cavens, 2018).

It is also worth considering eye lid surgery in brachycephalic patients, to help improve their abnormal conformation. Medial canthoplasty surgery means reducing the eyelid length and palpebral fissure (aperture between the eyelids) by removing some of the eyelid in the corner next to the nose (Royal Veterinary College, n.d). This will help ensure the eyelids are able to cover the whole of the globe and allow tears to lubricate the eye better.

Cyclosporin implants

For those patients that will not allow administration of topical medications, cyclosporin implants are an excellent alternative.

Ocular sustained-release medication devices or implants have many advantages over more traditional methods of drug administration to the eye. These advantages include delivery of constant therapeutic levels of drug directly to the site of action, bypassing some of the blood-ocular barriers, and eliminating the need to rely on owners (Gilger, 2017).

Most commonly these devices are used in horses. A study showed that episcleral cyclosporin implants in dogs were safe, and it produced lacrimal gland drug levels 1–2 log units higher than those reported with a variety of topical cyclosporin formulations (Gilger et al, 2014). The episcleral implant is placed into a subconjunctival pocket, and fibrous encapsulation adequately secures the implant to the episclera (Gelatt et al, 2014) (Figure 4). The patient will need to be under general anaesthetic for this procedure. Implants usually require replacing after around 3 years, in the author's experience. For this reason it is important the patient returns to the veterinary practice to be examined and a repeat STT performed.

A pilot study by Barachetti et al (involving 15 dogs) suggested that the cyclosporin implants were well tolerated and efficacious in dogs with KCS responsive to topical cyclosporin A as well as dogs with poor response to topical therapy. Over the follow-up period, complications or signs of toxicity associated with implants or cyclosporin A were not observed (Barachetti et al, 2015). The suggested dose in the study was 12 mg of cyclosporin contained in implants that were 1.9 cm long, 2 mm wide and 1 mm thick (Maggs et al, 2017).

Conclusion

KCS can progress to be a very uncomfortable and painful condition for patients and it is important to carry out a STT as part of the ophthalmic examination. There are various causes of KCS and factors influencing its development, however the most commonly seen cause in canine patient is immune-mediated. Depending on the cause, it may be necessary to explore options that will aid in reducing dry eyes, such as medial canthoplasty in brachycephalic dogs. Treatment for KCS should start as soon as possible and any secondary problems such as ulcers and infections should be treated immediately. There are various treatment options available and cyclosporin implants can be beneficial, especially if the patient is aggressive or difficult to medicate.

KEY POINTS

• There are several known causes of keratoconjunctivitis sicca (KCS) in dogs, including immune-mediated, congenital, metabolic, infectious, drug-induced, neurogenic, radiation, iatrogenic and idiopathic.
• Clinical signs depend on the severity of the condition. Recurrent conjunctivitis with a mucopurulent discharge and dull, lacklustre cornea are usual.
• The Schirmer tear test should always be the first test carried out during an ophthalmic examination to ensure that no excessive tearing has been caused by manipulation of ocular structures, which may then lead to a false result.
• Treatment can be medical or surgical, and sometimes both. Medical management aims to stimulate tear production and supplement tears.
• For those patients that will not allow administration of topical medications, cyclosporin implants are an excellent alternative.