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Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Shih Tzu Shih Tzu

Keratoconjunctivitis Sicca

Related terms: “dry eye”; Canine Immune-mediated Lacrimal Syndrome (CILS).

Outline: Keratoconjunctivitis sicca (dry-eye) is caused by insufficient tear production following disease of the tear glands. Inadequate lubrication of the surface of the eyes leads to painful abrasion and damage of their delicate tissues. The disease, which affects both eyes, typically starts before 4 years of age and is life-long and progressive. Unless it can be successfully treated (which is difficult), it can lead to ulceration and blindness.


Summary of Information

(for more information click on the links below)

1. Brief description

Keratoconjunctivitis sicca (KCS) is the result of insufficient tear production (Crispin 2002, Herring 2004). The surface of the eye needs to be constantly bathed in tears. Without this, the eyes become dry, inflamed and diseased, resulting in the signs of KCS.

KCS or a “dry eye” can be initiated by a number of things. The common breed-associated KCS being discussed in this document is an immune –mediated disease leading to progressive destruction of the lacrimal and nictitans glands which produce the aqueous (water) part of tears (Renwick 1996, Herring 2004).

The cause of this immune-mediated KCS in dogs is currently not understood. Shih tzus are predisposed to this type of KCS (Kaswan & Salisbury 1990, Renwick 1996, Crispin 2002, Herring 2004, Sanchez et al 2007). The disease is invariably bilateral ie occurs in both eyes, though it may start earlier in one eye than the other (Renwick 1996).

Often the first sign of KCS is conjunctivitis (inflammation of the conjunctiva), showing as redness; the conjunctiva is the thin layer of tissue that makes up the outer surface layer of the eyeball (Renwick 1996). Other signs include a pusy, sticky discharge from the eye. If the discharge is thick and a yellow/ green colour it suggests the presence of secondary bacterial infection. In affected animals, the cornea - the transparent front part of the eye - instead of looking shiny, has a lack-lustre, uneven appearance and may show various signs of damage including vascularisation (blood vessels invading its surface) and pigmentation (the surface becomes pigmented rather than transparent). Corneal epithelialisation and thickening give the eye a grey appearance and scarring may be seen (Renwick 1996). These signs tend to be associated with a more chronic disease process. Blepharospasm (increased blinking and holding the eye closed) can be associated with this condition and indicates discomfort.

Ulceration of the cornea can occur but generally less often in chronic forms of the disease, that are persistent and long lasting, than in the acute form - which is severe, with rapid onset (Renwick 1996). It is always associated with pain. These ulcers often deepen rapidly and sometimes rupture (Renwick 1996) which can lead to loss of the eye (Herring 2004). Both chronic and acute forms lead to severe scarring of the corneas and permanent blindness unless the disease process is controlled with veterinary treatment.

Shih tzus with KCS tend to show the ulcerative pattern of disease. In one study, 72% of affected Shih tzus showed evidence of past or current corneal ulceration (Sanchez et al 2007). Some hypothesise that the Shih tzu breed tends to show ulcerative KCS as opposed to more chronic corneal changes because of its brachycephalic head shape and more prominent eyes (Sanchez et al 2007, Moore as cited in Purina Proclub 2010).

Life-long medicinal treatment is usually necessary.

2. Intensity of welfare impact

Without treatment, KCS leads to complete blindness in affected animals. It also causes pain that may be mild in some affected dogs but is severe in others. Shih tzus are prone to the more acute ulcerative form of KCS and frequently suffer from eye ulcers that are particularly painful (Renwick 1996). These ulcers may rupture, leading to loss of the eye.

The regular veterinary and owner interventions needed to control this condition may cause significant stress in some individuals.

3. Duration of welfare impact

KCS frequently develops in young Shih tzus, most often before they are four years of age (Sandez et al 2007) and is a life-long progressive condition (Renwick 1996).

4. Number of animals affected

We are unaware of any published epidemiological studies on the prevalence of the disease but it has been suggested that the prevalence in the USA is about 1% (Purina proclub 2010). In a study by Sanchez et al (2007) in the UK, 5% of 229 cases of KCS were in Shi tzus. It may be more prevalent in males than females (Sanchez et al 2007).

5. Diagnosis

Keratoconjunctivitis sicca would be suspected if the clinical signs, described above, eg of red, inflamed eyes, are seen in the presenting animal. Definitive diagnosis is made using the Schirmer 1 tear test (Crispin 2002, Herring 2004), which measures rate of tear production. Other tests may be necessary to rule out concurrent eye diseases, some of which are also prevalent within Shi tzus.

6. Genetics

The genetics of canine KCS have not been elucidated but the fact that certain breeds, including the Shih tzu, are predisposed to the condition very strongly suggests that there is a genetic cause.

7. How do you know if an animal is a carrier or likely to become affected?

Currently it is not known if there are carriers (animals that can pass on the disease without developing it themselves) and there is no test available for detecting them. Before purchasing a dog, their eyes should be thoroughly examined and only those dogs with healthy eyes, and whose parents and grandparents were also free of any eye disease should be bought, so as to avoid the risk of perpetuating such conditions. 

8. Methods and prospects for elimination of the problem

We are unaware of any selective breeding programmes aimed at decreasing the prevalence of the condition in this breed. Affected individuals should not be bred from (http://www.upei.ca/~cidd/intro.htm). Ideally, animals to be used for breeding should have an annual veterinary examination for KCS prior to mating. Those with affected parents, grandparents or siblings should be considered at high risk of carrying a significant genetic burden for the disease and should not be used for breeding. However, because of the prevalence of this and other hereditary eye conditions in the breed, it may be difficult to find breeding animals with ancestry complete free of all these conditions.

Progress in understanding the genetic basis of the disease is likely to be helpful for its elimination.


For further details about this condition, please click on the following:
(these link to items down this page)


1. Clinical and pathological effects

Keratoconjunctivitis sicca (KCS) is a disease of the eye that is the result of insufficient tear production (Crispin 2002, Herring 2004). The surface of the eye needs to be constantly bathed in tears, which clean and lubricate it. Without this, the eyes become dry, inflamed and diseased which results in the signs of KCS. The disease may be exacerbated by concurrent abnormalities in the some of the secretions that are found in tears (Crispin 2002).

Tears are produced by tiny glands that surround the eye. The tear film these glands produce covers the whole surface of the eye, including the cornea (the clear front of the eye), parts of the sclera (the whites of the eye), both sides of the third eyelid (an extra eyelid found in dogs and other animals which is located in the inner corner of the eye socket) and the conjunctiva (the tissue which lines the inside of the eyelids). The ‘film’ is comprised of three constituent layers: an outer oily layer, a middle aqueous layer, and an inner mucin layer (Renwick 1996, Crispin 2002). In KCS it is a deficiency of the aqueous layer which causes the eye disease (Renwick 1996, Crispin 2002).

The fluid of the aqueous layer is produced by the lacrimal gland which is sited in the dorsolateral edge (towards the top and outer side) of the eye socket, and by the accessory lacrimal glands and the nictitans gland under the third eyelid (Crispin 2002). The fluid of this layer provides lubrication and protection to the cornea and conjunctiva, and nutrition to the cornea (Crispin 2002). The cornea is an unusual tissue in that it is avascular – it doesn’t have a blood supply. It depends on tears to supply its outer layers with the necessary oxygen, immune protection and nutrients to remain healthy. In a healthy eye the aqueous layer is transparent.

Keratoconjunctivitis Sicca figure 1 

Figure 1. The Lacrimal and nictitans glands are responsible for producing the fluid film covering the eye, which is vital for supplying it with nutrients, lubrication and protection as the cornea does not have a blood supply. In keratoconjunctivitis sicca the function of these glands is disrupted, therefore compromising the health of the eye. (Image courtesy of DM McCurnin, Clinical Textbook for Veterinary Technicians, 2010, Elsevier/ Saunders. We are grateful to DM Curnin and to Elsevier for permission to reproduce this figure).

Keratoconjunctivitis sicca or a “dry eye” can be initiated by a number of things. The common breed-associated KCS described here is an immune –mediated disease which causes progressive destruction of the lacrimal and nictitans glands leading to decreased aqueous tear production (Renwick 1996, Herring 2004).

The cause of immune-mediated KCS in dogs is currently not understood. Some disturbance of the immune system results in it attacking and destroying tissue in the lacrimal and nictitans glands. In KCS, the damage seems to be restricted to these glands only. Shih tzus are predisposed to this type of KCS (Renwick 1996, Crispin 2002, Herring 2004, Sanchez et al 2007). Immune-mediated KCS is bilateral i.e. it occurs in both eyes, although it may start earlier in one eye than in the other (Renwick 1996) and it is the probably the commonest form of KCS (Kaswan et al 1984, 1985). (Other forms of KCS and  dry eye are caused by a failure of the lacrimal and nictitans glands to develop properly (Aguirre and others 1971); systemic infections such as distemper (Martin & Kaswan 1985) and leishmaniasis; radiation therapy (Roberts et al 1987, Jamieson et al 1991); trauma to the head and eye (Sansom and Barnett 1985); side-effects of certain drugs such as sulphonamide antibiotics; ageing; metabolic diseases such as diabetes mellitus and hypothyroidism (under active thyroid gland) (Cullen et al 2005, Crispin 2002); untreated prolapse of the third eyelid (nictitans) gland (Morgan et al 1993); surgical removal of the third eyelid gland (Moore et al 2001, Saito et al 2001); or deficits in the innervation of the tear producing glands (Kern & Hollis 1987)).

In many breeds of dog KCS is insidious: starting with subtle signs but progressing to advanced disease, and without treatment commonly to complete blindness (Renwick 1996). Often the first sign of the disease is conjunctivitis (inflammation of the conjunctiva) with associated redness of the eye (Renwick 1996). Other signs include a pusy, sticky discharge from the eye. If the discharge is thick with a yellow/ green colour this suggests the presence of secondary bacterial infection. In affected animals, the cornea, instead of looking shiny, has a lack-lustre uneven appearance and may show various signs of damage including vascularisation (blood vessels invading its surface) and pigmentation (the surface becomes pigmented rather than transparent). Corneal epithelisation and thickening give the eye a grey appearance and scarring may occur (Renwick 1996). These signs tend to be associated with a more chronic disease process. Blepharospasm (excessive blinking or holding the eye closed) and photophobia (sensitivity to light) can be associated with this condition, both indicate discomfort.

Keratoconjunctivitis Sicca figure 2   Keratoconjunctivitis Sicca figure 3

                      Figure 2                                                         Figure 3

Figures 2 and 3 show advanced cases of keratoconjunctivitis sicca. The dull appearance of the cornea in Figure 3 is characteristic of the condition, and the pusy discharge in both images is characteristic of the condition.

(Images property of Susan Jacobi at www.vision4pets.com, to whom we are grateful for permission to reproduce them here).

Ulceration of the cornea can occur but generally less often in chronic forms of the disease, that are persistent and long lasting, than in the acute form - which is severe with rapid onset (Renwick 1996). It is always associated with pain. Ulcers often deepen rapidly in the acute condition, sometimes causing the eyeball to rupture (Renwick 1996), leading to loss of the eye (Herring 2004). Both chronic and acute forms lead to severe scarring of the corneas and permanent blindness unless the disease process can be successfully controlled.

Keratoconjunctivitis Sicca figure 4

Figure 4. In cases of rapid onset keratoconjunctivitis sicca, corneal ulcers (shown by the area that has taken up the green dye) may occur and these can lead to further disease complications issues if untreated. (Image property of Joel Mills).

Sanchez et al (2007) found that Shih tzus tended to show a more acute pattern of disease with ulcerative keratitis (inflammation of the cornea) than that typically seen in West Highland white terriers and English Cocker spaniels – two other breeds which are highly predisposed to the disease. Evidence of past or current ulceration was observed in 72% of cases of KCS in Shih tzus examined (Sanchez et al 2007). Some hypothesise that the high prevalence of ulcerative corneal changes seen in Shih tzus with KCS is related to their brachycephalic head shape and more exposed eyes (see also brachycephalic ocular disease in the shih tzu) (Sanchez et al 2007, Moore as cited in Purina Proclub 2010).

Herrera (2005) stated that KCS is often associated with skin disease as 70% of Shih tzus with KCS were also found to have atopic dermatitis (an allergic skin disease).

There is no cure for this progressive condition. Medical treatment of KCS involves the application of drugs to the eyes, for the following reasons:

  • To suppress the immune- mediated inflammation and prevent destruction of the lacrimal and nictitans glands. Drugs used include cyclosporine A and tacrolimus (Herring 2004, Berdoulay et al 2005).
  • To provide supportive treatments:  artificial tears to meet the deficit, antibiotics to clear up secondary bacterial infections, and, occasionally, corticosteroid drops (which may be beneficial providing no corneal ulcers are present (Herring 2004).

In cases in which the regular administration of medication is difficult or when there is poor response to these treatments, surgery can be performed to transpose the duct of the parotid salivary gland from the mouth to the eye with the aim of redirecting saliva to moisten the eye instead of tears. This surgery is not without its complications so is usually only used when medical treatment is failing (Herring 2004).

Medical treatment is invariably life-long. Regular nursing care is also required to remove the discharges and to monitor for signs of ulceration or other complications which might require rapid veterinary intervention (Herring 2004, Brooks & Williams 2010). Surgeries may be necessary to treat significant eye ulcerations. Despite such treatment, some dogs do not respond and become blind.

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2. Intensity of welfare impact

KCS is a progressive and life-long disease and, without treatment, it leads to blindness. It also causes pain which can be mild but is severe in some dogs, depending on the degree of deficiency in tear production and the nature and severity of the corneal disease. Regarding the chronic, non-ulcerative, form, “People with KCS say it feels like they have sand paper under their eyelids with every blink. Dogs show their discomfort by rubbing their eyes, squinting, and being sensitive to light” (http://www.upei.ca/~cidd/intro.htm).

Eye ulcers are particularly painful (Renwick 1996) and as Shih tzus are prone to the acute form of the disease, they frequently suffer from these. These ulcers may rupture leading to the loss of the eye.

The frequency of the treatments that need to be administered by vets or owners in these cases may cause significant stress to some of the affected animals.

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3. Duration of welfare impact

KCS tends to develop in young adult Shih tzus. Sanchez et al (2007) found two peak ages for disease development within the breed; these were between birth and two years of age and between two and four years of age, although animals of any age can be affected. KCS is a life-long condition.

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4. Number of animals affected

We are unaware of published epidemiological studies on the prevalence of KCS in Shih tzus but it has been suggested that in the USA, the prevalence is 1% (Purina proclub 2010). Sanchez et al (2007) found in a survey of KCS cases in the UK that 58% of cases involved only four breeds: the English Cocker spaniel, West Highland white terrier, Cavalier King Charles spaniel and the Shih tzu. Shih tzus represented 5% of the cases. Prevalence is likely to vary between different populations.

Sanchez et al (2007) suggested that the disease is more prevalent in males than females.

From data on estimates of total dog population in the UK and on the percentage of all micro-chip registered dogs that are Shih tzus (Lucy Asher 2011, personal communication), we estimate that the UK population size of this breed may be around 125,000. If the prevalence of KCS is 1% then the number of dogs affected in the UK may be about 1,250.

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5. Diagnosis

The clinical signs described above are suggestive of KCS but diagnosis can be confirmed using the Schirmer 1 tear test (Crispin 2002, Herring 2004). This involves measuring the amount of aqueous tears produced in 1 minute whilst the dog is conscious. This is done by placing one end of specifically designed test paper over the rim of the lower eyelid into the gap between cornea and conjunctiva. The column length of the fluid absorbed into the paper is then measured. In normal dogs the results are equal to or greater than 15mm, 10-15mm is considered borderline (Crispin 2002), less than 10mm is considered indicative and less than 5 mm is diagnostic of KCS (Renwick 1996). Rose Bengal dye can be used to stain and reveal the presence of dead and devitalised tissue indicating corneal deterioration. It is widely used in the diagnosis of KCS in humans (Crispin 2002).

Other eye diseases that Shih tzus are predisposed to include distichiasis and brachycephalic ocular disease, so a full ophthalmic examination should be given to all Shih tzus with signs of eye disease. It is not uncommon for more than one condition to be present at the same time in these dogs.

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6. Genetics

We are unaware of any studies of the genetics underlying this condition; however, as there are strong breed predispositions a genetic basis seems highly likely.

Studies have indicated that Shih tzus in the UK and USA are predisposed to immune-mediated KCS (Kaswan & Salisbury 1990, Renwick 1996, Crispin 2002, Herring 2004, Sanchez et al 2007).

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7. How do you know if an animal is a carrier or likely to become affected?

Currently it is not known if there are carriers (animals that can pass on the disease without developing it themselves) and there is no test available for detecting them. Before purchasing a dog, their eyes should be thoroughly examined and only those dogs with healthy eyes and whose parents and grandparents were also free of any eye disease should be bought, so as to avoid the risk of perpetuating such conditions.

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8. Methods and prospects for elimination of the problem

We are unaware of any selective breeding programmes aimed at decreasing the prevalence of this condition in the Shih tzu breed. In the USA, the Cavalier King Charles spaniel (another breed which is predisposed to acute onset, ulcerative KCS) Club recommends annual monitoring of all animals by a board-certified veterinary ophthalmologist and for breeding animals shortly before mating (http://www.cavalierhealth.org/dry_eye.htm). This seems wise advice also for Shih tzu owners and breeders.

Affected individuals should not be used for breeding (http://www.upei.ca/~cidd/intro.htm). Some may develop signs after breeding age. Those with affected parents, grandparents or siblings should be considered at high risk of carrying a high genetic burden for the disease and should not be used for breeding. However, because of the high prevalence of hereditary eye conditions in this breed finding animals from lines free of these conditions may be difficult.

Progress in understanding the genetic basis of the disease is likely to be helpful for its elimination.

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section and to Stephanie Kaufman for assistance in illustrating it.

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10. References

Aguirre GD, Rubin LF and Harvey CE (1971) Keratoconjunctivitis sicca in dogs. Journal of the American Veterinary Medical Association 158: 1566-1579

Berdoulay A, English RV and Nadelstein B (2005) Effect of topical 0.02% tacrolimus aqueous suspension on tear production in dogs with keratoconjunctivitis sicca. Veterinary Ophthalmology 8: 225-32

Brooks DE and Williams DL (2010) keratoconjunctivitis sicca. CD canis Vetstream. http://www.vetstream.com/canis/Content/Disease/dis00418. accessed 6.6.2011.

Crispin S (2002) The lacrimal system in Petersen-Jones S and Crispin S (eds) BSAVA Manual of Small Animal Ophthalmology 2nd Ed. BSAVA: Cheltenham, Glos, UK

Cullen CL, Ihle SL, Webb AA and McCarville C (2005) Keratoconjunctival effects of diabetes mellitus in dogs. Veterinary Ophthalmology 8: 215-225

Herrera D (2005) Canine keratoconjunctivitis sicca. Proceedings of 30th World Congress of WSAVA, 11th -14ht March 2005, Mexico City, Mexico. http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2005&PID=10925&O=Generic. Accessed 8/6/2011.

Herring I (2004) Keratoconjunctivitis sicca. Online VIN associate. http://www.vin.com/Members/Associate/Associate.plx?DiseaseId=506. Accessed 6/6/2011

Jamieson VE, Davidson MG, Nasisse MP and English RV (1991) Ocular complications following cobalt 60 radiotherapy of neoplasms in the canine head region. Journal of the American Animal Hospital Association 27: 51-55

Kaswan RL, Martin CL and Chapman WL (1984) Keratoconjunctivitis sicca: Histopathologic study of nictitating membrane and lacrimal glands from 28 dogs. American Journal of Veterinary Research 45(1): 112-118

Kaswan RL, Martin CL and Dawe DL (1985) Keratoconjunctivitis sicca: Immunological evaluation of 62 canine cases. American Journal of Veterinary Research 46: 376-383

Kaswan RL and Salisbury MA (1990) A new perspective on canine keratoconjunctivitis sicca. Treatment with ophthalmic cyclosporine. Veterinary Clinics of North America: Small Animal Practice 20: 583-613

Kern TJ and Hollis NE (1987) Facial neuropathy in dogs and cats: 95 cases (1975-1985). Journal of the American Veterinary Medical Association 191: 1604-1609

Martin CL and Kaswan R (1985) Distemper associated keratoconjunctivitis sicca. Journal of the American Animal Hospital Association 21: 355-359

Moore CP, McHigh JB, Thorne JG and Phillips T (2001) Effect of cyclosporine on conjunctival mucin in a canine keratoconjunctivitis sicca model. Investigative Ophthalmology and Visual Science 42: 653-659

Morgan RV, Duddy JM and McGlurg K (1993) Prolapse of the gland of the third eyelid in dogs: a retrospective study of 89 cases (1980-1990). Journal of the American Animal Hospital Association 29: 56-60

Purina ProClub (2010) Proactive breeders improve outcomes for dogs with ocular disease. Shih Tzu Update 4 (1): 1-2. http://www.shihtzu.org/improve_ocular_disease.pdf. Accessed 17.2.11

Renwick P (1996) Diagnosis and treatment of corneal diseases in dogs. In Practice 18: 315-328

Roberts SM, Lavach JD, Severin GA, Withrow SJ and Gillette EL (1987) Ophthalmic complications following megavoltage irradiation of the nasal and paranasal cavities in dogs. Journal of the American Veterinary Medical Association 190: 43-47

Saito A, Izumisawa Y, Yamashita K and Kotani T (2001) The effect of third eyelid gland removal on the ocular surface of dogs. Veterinary Ophthalmology 4: 13-16

Sanchez RF, Innocent G, Mould J and Billson FM (2007) Canine keratoconjunctivitis sicca: disease trends in a review of 229 cases. Journal of Small Animal Practice 48: 211–217

Sansom J and Barnett KC (1985) Keratoconjunctivitis sicca in the dog: a review of two hundred cases. Journal of Small Animal Practice 26: 121-131

http://www.cavalierhealth.org/dry_eye.htm

http://www.upei.ca/~cidd/intro.htm

© UFAW 2011


Credit for main photo above:

http://depositphotos.com/14607743/stock-photo-shih-tzu-dog.html  ©Depositphotos.com/chaoss