Download Topic 14: Keratoconjunctivitis sicca (“Dry eye”) Stephanie Shrader

Topic 14: Keratoconjunctivitis sicca (“Dry eye”)
Stephanie Shrader and John Robertson
Keratoconjunctivitis sicca (KCS) is a disease of the eyes, characterized by
inflammation of the cornea and conjunctiva, secondary to a deficiency in the
aqueous (watery) portion of the tear film (Cote, 2009). This leads to dry, irritated
eyes. It is more commonly known as dry eye or in veterinary terminology,
xerophthalmia. KCS is often seen in West Highland White Terriers, but is also
common in the Lhasa Apso, English Bulldog, American Cocker Spaniel, English
Springer Spaniel, Pekingese, Pug, Chinese Shar Pei, Yorkshire Terrier, Shih
Tzu, Miniature Schnauzer, German Shepherd, Doberman Pinscher, and Boston
Terrier. According to Cote, there is an increased predisposition reported for both
neutered male and female dogs, and for female West Highland White Terriers,
in particular. The current incidence of KCS across all dog breeds ranges between
1% and 2%, depending on which research article is referenced.
Understanding Tears
The tear film that covers the eyes is made up of three distinct layers (see
Figures 1 and 2 below). The outermost layer is made up of oils, which are
secreted by the Meibomian glands, located along the edge of the eyelid. This
lipid layer provides protection against evaporation and cohesive properties that
prevent tears from simply pouring out over the lower eyelid onto the face. The
middle layer is the aqueous layer, produced by the lacrimal glands. In the dog
there are two lacrimal glands; one is located just above and slightly lateral to the
eye, and the other is located medially by the third eyelid (also known as the
nictitating membrane). The aqueous layer contains mostly water, along with
important proteins and enzymes that help to maintain proper osmolarity and
protect against infection by viruses and bacteria. The innermost layer of the tear
film is the mucin layer. This hydrophilic layer is produced by tiny secretory cells in
the conjunctiva known as goblet cells. Being that this is the innermost layer, it is
what immediately bathes and protects the cornea.
Figure 1. Cross sectional view of the
composition of tears [Source:
http://www.optrex.co.uk/healthcare_professi
onals/refresh_your_knowledge_on_dry_eye
s.php]
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Figure 2: The location of the lacrimal (tear producing) apparatus in dogs. Source
http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/30101.htm
What causes keratoconjunctivitis sicca?
According to Kirk Gelatt (2005), a noted veterinary ophthalmologist, the failure of
tear production and corneal lubrication, due to lacrimal gland hyposecretion, may
result from a single disease process or a combination. The potential causes for
KCS, listed in the Clinical Veterinary Advisor (Cote. 2009), are presented below,
with in depth explanations for each.
Immune-mediated adenitis
Immune-mediated adenitis simply means that the body’s own immune
system is causing abnormal inflammation of a lymph node or gland; in this
case, the lacrimal gland. According to the Merck Veterinary Manual
(2009), this is thought to be the most common cause of KCS in dogs.
What triggers immune-mediated adenitis is currently not known.
Congenital acinar hypoplasia (congenital alacrima)
Alacrima (literally – no tears) refers to a variety of lacrimal secretory
disorders that are mostly congenital (genetic) in origin. This is an
autosomal recessive trait – a recessive allele carried on the non-sex
determining chromosomes. If two animals mate, each having the
recessive trait for alacrima, there is a 25% chance that the offspring will
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inherit the disorder. Breeding dogs with congenital disorders is
problematic - this continues the disease in future offspring. WHWT
breeders must appreciate this when selecting mating pairs so as not to
propagate this genetic problem. Most breeders will also monitor the
health of litters they have sold, in order to detect the emergence of this
problem in litters or breeding stock.
For potential buyers of WHWT from unknown sources, there is an old
Latin saying, “Caveat emptor” “Let the buyer beware”. Get the bitch’s and
sire’s history and health records before purchasing your new pet. Don’t
rely on a verbal assurance that the puppy is “pure bred”. Dealing with
well-established breeders will help prevent heartache and medical bills.
Drug and anesthesia induced KCS
Certain drugs/anesthetics can produce either temporary or permanent
KCS. Transient KCS is sometimes noted following anesthesia and surgery
but the exact relationship between anesthesia and KCS is unknown. It is
important for all veterinarians to provide a lubricating ointment or fluid to
protect eyes during surgery to prevent transient KCS.
Iatrogenic KCS
Iatrogenic means a medical problem may develop as a result of or
associated with a physician’s/veterinarian’s treatment. For example,
removal of the gland of the third eyelid (nictitans gland) to correct a
disease problem can increase the risk of a dog developing KCS, since
tear-production is associated partially with the nictitans. Years ago, a
condition known as “Cherry Eye” (inflammation and proliferation of
lymphoid tissue near the nictitans) was often treated by removal the gland
of the third eyelid. It was common to have chronically dry eyes after this
procedure. Today, the importance of this gland is understood, and instead
of removal, it is medically and surgically reduced if protrusion occurs.
Infectious diseases
The most common viral disease in dogs, canine distemper virus, is often
associated with KCS. Typical ophthalmic complications associated with
canine distemper virus infection include conjunctivitis, chorioretinitis
(retinal inflammation) and acute KCS (Gilger, 2009). Canine distemper
virus (CDV) is a highly contagious disease that is typically spread via
aerosolized respiratory secretions. In most cases, the virus first attacks
the respiratory system, and then spreads to the gastrointestinal and
nervous systems. When the virus colonizes sensitive glands of the eye,
including the cornea, this can lead to KCS. In this instance, KCS is caused
due the virus’ attack on lymphoid tissue (leading to immunosuppression)
and ocular epithelial cells.
Metabolic diseases/disorders
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Systemic metabolic diseases associated with the development of KCS
include hypothyroidism, diabetes mellitus, hyperadrenocorticism
(Cushing’s disease), atopy, and dysautonomia (Kaswan, et al, 1998).
Each of these diseases represents a chapter of its own, so it will suffice to
mention them in passing. Just be aware that KCS is a possible
complication in each of these diseases.
Neurologic
Parasympathetic innervation to the lacrimal glands is provided by cranial
nerve VII (facial nerve). Damage to this nerve, either due to disease or
trauma, can result in KCS by decreasing the amount of tear film produced.
One could also have loss of sensory innervation to the ocular surface if
there is damage to cranial nerve V (trigeminal nerve) (Gelatt, 2005). The
ophthalmic branch of the trigeminal nerve provides innervation to the
lacrimal gland, conjunctiva, and upper eyelids. Damage to this nerve,
either by disease or trauma, could result in KCS.
How is KCS diagnosed?
Dogs with KCS are often presented to the veterinarian because they have
red/irritated eyes, are pawing at their eyes because they itch and/or hurt, and
may have a thick ocular discharge that can range from off-white to green in color.
Upon physical examination, the doctor may also notice that the third eyelid is
protruded, that the cornea is no longer shiny in appearance, that there is corneal
keratitis (inflammation) present. In advanced cases of disease, corneal scarring
may lead to potential vision loss.
In order to differentiate KCS from other ocular disorders, the veterinarian will do a
comprehensive eye exam that will include a Schirmer tear test (STT), fluorescein
staining of the cornea, and evaluation of the intraocular pressures (to see if there
is glaucoma).
Schirmer tear test (see Figure 3 below)
The Schirmer tear test is designed to quantify the amount of tear film
produced by the eye. It is a painless procedure (but looks “yucky”).
The veterinarian will place a thin strip of paper (about an inch long and
quarter of an inch wide) just under the eyelid for one minute. This piece of
paper has a small scale on it. During this time period, the tear film will
“wick” up the paper. When the minute is over, the tear production can be
quantified, based on mm/min.
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Figure 3. The Schirmer tear test. Calibrated paper strips are placed
under the eyelid for a short period of time to quantify tear production.
Normal and abnormal values for canine tear production are found below
(these values can vary slightly depending on which text is referenced):
Normal: ≥ 15 mm/min
Early KCS: 11-14 mm/min
Mild/moderate KCS: 6-10 mm/min
Severe KCS: ≤ 5 mm/min
Application of fluorescein stain (see Figure 4 below)
Fluorescein is a bright yellow/orange stain that is used to detect corneal
ulceration. The veterinarian will place a few drops of the stain in the eye,
turn off the exam room lights, and use the ophthalmoscope to determine if
corneal ulcers are present. In dogs with KCS, it is not uncommon to also
find corneal ulceration because of the chronic irritation.
Figure 4: Photograph of the eye of a dog with a corneal ulcer (arrow) highlighted
by the application of fluorescein dye during ophthalmic examination. Source:
http://www.animal-eye-specialists.com/exam.htm
Examination of intraocular pressures
The veterinarian will assess the intraocular pressure of each eye by using
a handheld device known as a tonometer. It is a quick and painless
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method to determine whether the ocular disorder experienced by your dog
is something other than KCS (such as glaucoma). Typically three
measurements are obtained for each eye and averaged together. Normal
intraocular pressure for dogs is 15-25 mmHg. The image below is one
example of a handheld tonometer.
Treatment of KCS
There are various types of medical treatments that can be used to treat KCS in
dogs. Your veterinarian will select the type of therapy that is best for your
Westie’s situation. Common drugs used are listed below (Gelatt, 2005).
Topical antimicrobial agents:
Topical ophthalmic anti-bacterial drugs typically include a combination of
bacitracin, neomycin, polymyxin, dexamethasone, and/or hydrocortisone.
These medications are manufactured as ointments and solutions; your
veterinarian will determine which medication is best for your dog. Common
brand names include Terramycin and Neo Poly Bac.
Anti-inflammatory drugs
Topical corticosteroids can be used to decrease ocular inflammation and
pain associated with KCS. One of the common agents used today is
Cyclosporin A (CsA) (an immunosuppressive drug). The exact mechanism
of CsA’s action is unknown, but it appears to have immunomodulatory
(meaning an agent that modifies the immune response) and
lacrimostimulant effects (Beranek, 2006). Another immunomodulatory
agent used for treatment of KCS is Tacrolimus; a more recent medication
that belongs to a group of drugs called calcineuron inhibitors (Fourney,
2009). In simplistic terms, Tacrolimus blocks the proliferation of T
lymphocytes and cytotoxic cells (Forney), thereby decreasing the immune
response that may be an underlying cause of glandular inflammation and
decreased tear production.
Tear substitutes (lacrimomimetics)
Tear replacement solutions are typically a combination of ingredients that
replace one or more components of the tear film. There are many different
tear replacement medications and your veterinarian will prescribe one or
more to help control the signs associated with KCS. Many of these agents
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Gilger, BC, "Waltham - OSU Symposium." Veterinary Information Network (VIN) For Veterinarians, By Veterinarians. 12 Aug. 2009
<http://www.vin.com/VINDBPub/SearchPB/Proceedings/PR05000/PR00526.htm
>.
Kaswan R, Pappas Jr. C, Wall K, Hirsh SG. Survey of canine tear deficiency in
veterinary practice. In Sullivan et al. (eds): Lacrimal Gland, Tear Film, and Dry
Eye Syndromes 2. New York: Plenum Press, 1998. Pp. 931-939.
"Merck Veterinary Manual." The Merck Veterinary Manual. 20 July 2009
<http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/30107.htm>.
"Optrex Eye Care Advice: Healthcare professionals dry eye information." Optrex We understand the language of eyes. 20 July 2009
<http://www.optrex.co.uk/healthcare_professionals/refresh_your_knowledge_on_
dry_eyes.php>.
Additional Resources
American College of Veterinary Ophthalmologists (ACVO). http://www.acvo.com/
American Society of Veterinary Ophthalmology (ASVO). http://www.asvo.org/
Crispin, Sheila M. Notes on Veterinary Ophthalmology. Grand Rapids: Blackwell
Limited, 2005.
Grahn, Bruce H. Veterinary ophthalmology essentials. Philadelphia, Pa:
Butterworth-Heinemann, 2004.
Veterinary Information Network. http://www.vin.com
Veterinary Ophthalmology Services. http://vos-tn.com/index.php
http://www.vetmed.ucdavis.edu/courses/vet_eyes/default.html
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