Lacrimal disease can make you cry: What to do? (Proceedings)

Abnormalities of the lacrimal system are common and generally divided into those that affect the secretory system (e.g., dry eye) or the excretory system (e.g., blocked tear duct). The more common conditions are discussed.

Keratoconjunctivitis sicca (kcs) - dry eye

Keratoconjunctivitis sicca (KCS), or dry eye, is common in the dog and relatively uncommon in other domestic animals. It represents a quantitative tear abnormality with deficiency of aqueous tears. Clinical signs can include blepharospasm, mucoid to mucopurulent ocular discharge, conjunctival hyperemia, and varying degrees of corneal vessels, pigment, and scarring. Corneal ulcers can develop concurrent with KCS. In chronic or refractory cases, blindness is possible from severe corneal scarring or pigment, or progressive corneal ulceration. KCS is most often a disease of middle-aged or older dogs that develops gradually in one or both eyes, but it can occur acutely and in young dogs. Commonly affected (or predisposed) breeds include the Cavalier King Charles Spaniel, West Highland white terrier, Yorkshire terrier, American Cocker Spaniel, English bulldog, Shih Tzu and Lhasa apso, but any breed can be affected.

Schirmer's Tear Test-1 (STT-1) is most often used to confirm the diagnosis and is performed prior to application of diagnostic reagents to the eye. The STT-1 measures both reflex and basal tear production. Schirmer's Tear Test-2 is performed after topical anesthetic has been applied to the eye, and thus, measures primarily basal tear production. The STT-2 is of limited value for most veterinary patients. The normal STT-1 value is >15 mm of wetting after one minute for both dogs and cats. The significance of STT-1 values between 10-14 mm/minute should be interpreted with clinical signs, but values <10 mm/minute usually denote clinical KCS. Cats are an exception to this latter point. Low STT-1 values are common in cats with non-inflamed and otherwise normal eyes. Therefore, the difference in STT-1 values between the eyes may be more important for interpretation in cats than the absolute value. The STT-1 should be performed on any pet with an irritated eye, ocular discharge, or corneal disease of undetermined cause.

Canine KCS is most often due to immune-mediated disease directed against the orbital and nictitans lacrimal glands. Histopathology reveals lymphocytic-plasmacytic glandular infiltrates, and this is the basis for immunomodulating treatments. Other causes of KCS include lacrimal gland aplasia or hypoplasia, infection (e.g., distemper virus), neurogenic (e.g., trigeminal neuropathy), neuroparalytic (e.g., facial neuropathy), trauma, iatrogenic (e.g., nictitans gland excision), and drug-induced. Drugs with potential to reduce tear production include topical or systemic atropine, oral sulfonamides (e.g., azulfidine or sulfadiazine), etodolac (Etogesic), and certain glaucoma drugs (e.g., timolol). Conditions such as diabetes mellitus, hypothyroidism, and dehydration, may reduce tear production. Topical or general anesthesia will reduce tear production; pets under general anesthesia should have an artificial tear ointment applied to the eyes. Application of an antibiotic ointment during anesthesia is not advised because of greater potential for corneal toxicity and allergic reactions (especially in cats).

Effective dry eye treatment depends on an accurate assessment of the cause, correction of complicating factors (e.g., lagophthalmos), and owner compliance. Initial treatment usually requires a combination of tear stimulants and lubricants, topical antibiotic, and possibly topical steroid. Treatments are tapered or modified depending on patient response.

Lacrimomimetics are agents that imitate natural tears or tear components and are synonymous with artificial tears. Normal tears are trilaminar with lipid, aqueous, and mucin components, and each layer has a specific function. Artificial tear preparations are formulated to simulate one or more components of the tear film, and most are available over-the-counter as solutions, gels, or ointments. A combination of products can be helpful in severely affected patients, in part, because of different ocular retention times. Artificial tear solutions more closely resemble aqueous tears and are helpful for loosening ocular mucous and debris, but they have the shortest retention times. Gels and ointments have substantially longer contact times, thus providing justification for combination treatment. Mucinomimetic agents are those that simulate tear mucin. They tend to be viscous and consist of polymers such as carboxymethylcellulose (Celluvisc), hydroxypropyl methylcellulose (GenTeal Gel), carbomer (Lubrithal, Optixcare), and sodium hyaluronate (i-drop Vet PLUS, REMEND, AQuify, Blink Contacts). Artificial tear ointments usually combine petrolatum and mineral oil, and common OTC brands are Lacrilube, Refresh PM, Tears Naturale PM, etc. The ointments simulate tear lipid, have the longest retention times, and help to prevent evaporation of tears. Most artificial tear preparations are intended for repeated daily application and are well tolerated. However, pets can develop sensitivity to preservatives contained in these preparations, and preservative-free preparations (designated PF) are preferred in these instances. GenTeal gel has hydrogen peroxide as a preservative that is cleaved into water and oxygen immediately after application (the so-called disappearing preservative).

Lacrimostimulants (lacrimogenics, secretagogues) are agents that increase or stimulate natural tear production. Pilocarpine has historically been used for this purpose, and it may be of benefit in select cases unresponsive to newer treatments (i.e., cyclosporine or tacrolimus). Two percent pilocarpine ophthalmic solution at a dosage of 1 drop/20 pounds of body weight BID in the food is a good starting dose. The dosage is gradually increased until a response is observed or signs of toxicity develop. Toxic signs include salivation, bradycardia, vomiting, or diarrhea. Dilute topical pilocarpine solution may be used as an alternative to oral treatment, but accounts of its efficacy are primarily anecdotal. Pilocarpine applied topically may cause undesirable irritation and miosis. Concentrations of 0.125%-0.25% are recommended. Using a stock solution of 2%, these may be prepared as follows: 0.125% prepared by adding 1 ml of stock solution to 15 ml of artificial tears; 0.25% prepared by adding 2 ml stock solution to 14 ml artificial tears. Cyclosporine and tacrolimus are T-cell lymphocyte modulators that improve natural tear production by a combination of immunomodulation and direct lacrimal stimulation. Both drugs inhibit T-cell activation and lymphokine production by blocking calcineurin (a protein phosphatase), but their cellular receptors for this action are different. They are presently the most effective treatments for canine KCS, but similar drugs are under investigation (e.g., pimecrolimus). Cyclosporine is commercially available as a 0.2% ointment (Optimmune) but can be compounded in stronger concentrations as a 1% or 2% drop or ointment. Tacrolimus is usually compounded as a 0.02% or 0.03% drop or ointment. Either drug can be formulated in an oil or aqueous base. Aqueous-based formulations are easier for owners to apply and may be less irritating than oil-based preparations. Oil bases (e.g., corn oil, olive oil, etc.) have longer retention times that may enhance drug availability and efficacy, though comparative studies are lacking. Which drug to use depends on personal preference, prior treatment, and the severity of KCS. A stronger formulation is indicated for severe KCS or patients unresponsive to the 0.2% ointment. There is more data on cyclosporine than tacrolimus, but in one study, almost 50% of dogs that were unresponsive to cyclosporine improved after treatment with tacrolimus. The frequency of application for either drug is typically twice daily, but treatments can be increased to three times daily if response is inadequate. The potential for systemic toxicity of either drug after topical application appears low, though systemic absorption does occur. For some patients, many weeks or months of treatment may be required before improvement is noted, so patience and client education are important. Both drugs appear to improve patient comfort and reduce corneal inflammation, scarring, and pigment. In pets that do not respond with improved tear production, continued treatment with one or the other drug is still advised to prolong vision and comfort (perhaps even after parotid duct transposition surgery). Some ophthalmologists advocate combination treatment with cyclosporine and tacrolimus in patients that respond inadequately to either drug alone, but such treatment is controversial. There is no data to support or refute the efficacy of combination treatment. Combination treatment is more expensive and may increase the risk of systemic toxicity, but there is some rationale to support such treatment. Each drug binds to a different cellular receptor, and synergistic inhibitory action of T-cells has been demonstrated in vitro. Herpesvirus infection is usually implicated as the cause of feline KCS. The efficacy of these drugs in cats is unproven and may be contraindicated.

Natural tears have antibacterial properties, so it is not surprising that secondary bacterial infection is common with dry eye. Cyclosporine treatments have been shown to decrease ocular bacterial infection because of improved tear production. Topical antibiotic treatment is indicated in many KCS patients and in most with severe KCS. Empiric topical treatment with neo-poly-bac or erythromycin ointment is sufficient for most cases. Bacterial culture and susceptibility testing should be considered in pets where exudate and inflammation are profound. Antibiotic-resistant infection can develop in pets receiving long-term antimicrobial treatment; bacterial culture should also be considered for eyes with copious discharge after chronic antimicrobial treatment. The author prefers to use antibiotic ointment in most KCS patients for its combined antimicrobial and lubricant properties. A course of systemic antibiotics may be appropriate some KCS patients, since bacterial infection of the lacrimal gland is a potential cause of KCS. Oral cephalosporins are favored by many ophthalmologists, and sulfonamides should be avoided.

Judiciously applied topical corticosteroids are beneficial for many dry eye patients to reduce conjunctival and corneal inflammation and corneal vascular infiltrates. However, pets with KCS are at greater risk for corneal ulceration, and caution is advised, especially in pets with negligible tear production. Neo-poly-bac with hydrocortisone ointment is a good first choice because the steroid is relatively mild but sufficiently strong to be of benefit.

For initial KCS treatment, consider the following combination:

     1) Cyclosporine or tacrolimus on affected eye BID (drug concentration determined by severity)

     2) Antibiotic or antibiotic-steroid on affected eye BID-TID

     3) Artificial tear solution, gel, or ointment p.r.n. for lubrication

Tear production should be checked again in 2 weeks and periodically thereafter. Cyclosporine or tacrolimus treatments are modified depending on patient response (i.e., "go where the individual eye takes you"). In dogs with restoration of normal tear production (>15 mm/minute), it may eventually be possible to reduce cyclosporine or tacrolimus to once daily or every other day application and discontinue other topical treatments. Parotid duct transposition surgery should be considered for dogs that have not responded months of appropriate treatment.

Parotid duct transposition

Parotid duct transposition (PDT) surgery should be considered in dry eye patients unresponsive to treatment, which remain uncomfortable, or experience recurrent corneal ulcers. Saliva is similar enough in composition to tears to be an acceptable substitute. Both open and closed surgical techniques are described, and the reader is referred elsewhere for a detailed description of these procedures. A KCS patient with concurrent xerostomia will not benefit from PDT surgery, so saliva production should be assessed to determine suitability for surgery. A single application of 1% atropine solution (using a moistened cotton swab) to the oral mucosa and while observing the duct opening allows determination of optimal surgical candidates; saliva should be readily secreted. Note that systemically administered atropine will decrease both tear and saliva production. However, atropine applied directly to the oral mucosa stimulates salivation by virtue of its bitter taste. Possible complications of PDT surgery include mineral precipitates on the cornea and eyelids, chronic epiphora, facial dermatitis, and post-operative stenosis of the parotid duct. Mineral precipitates are the most common complication but can usually be managed with daily cleaning of the eyelids and periodic removal from the corneal surface with a cellulose surgical spear (e.g., 2-3 times annually). Topical 1.38% EDTA solution several times daily may be helpful in reducing deposits. Dietary management can also be helpful, and a diet low in mineral content (e.g., S/D) is advised for problem cases. Puppy chows are particularly high in mineral content and should be avoided.

Qualitative tear deficiency

Qualitative tear deficiencies occur with abnormalities of tear mucin or lipid. Mucin is important for anchoring tears to the cornea, lipid is necessary to prevent evaporation, and both are required for distribution of tears across the surface. Deficiency of either can result in conjunctivitis, and ulcerative or non-ulcerative keratitis in the absence of an obvious cause. Affected patients usually have normal Schirmer tear test values, and epiphora is evident in some cases. Qualitative deficiency should be considered in cats with non-healing corneal ulcers, especially those unresponsive to antiviral treatment. Tear film break-up time (TFBUT) is a noninvasive test that measures tear film stability and is helpful in diagnosis. Fluorescein stain is applied to the eye(s), the eyelids are closed for a moment, and when opened, the tear film is examined with magnification and a cobalt blue light. TFBUT is the time from when the eyelids are opened to the first evidence of tear evaporation. This appears as multiple dark spots or patches within the fluorescein-stained tear film that initially, appears as a smooth fluorescent layer across the corneal surface. Mean TFBUT in normal dogs and cats is 19.7 and 16.7 seconds, respectively (+/- 5 seconds). Eyes with qualitative tear deficiency usually have TFBUT <10 seconds, described as decreased or rapid TFBUT. Mucin deficiency may be more common than lipid deficiency. Topical cyclosporine has been shown to improve goblet cell function and mucin quality and is the primary treatment for mucin deficiency. Tacrolimus is presumably of similar benefit. Mucinomimetic tear preparations are beneficial but may not be required once a positive response is noted with cyclosporine or tacrolimus. When lipid deficiency is suspected, the eyelid margins and meibomian gland openings should be scrutinized for evidence of inflammation or swelling; anti-inflammatory and antimicrobial treatment should be administered as deemed necessary. Artificial tear ointments that soothe the corneal surface and reduce evaporation of tears are indicated for patients with suspected lipid deficiency.

Marginal blepharitis (meibomianitis or meibomitis)

This condition occurs primarily in dogs and is characterized by multifocal meibomian gland swellings along one or more eyelid margins. In some instances only one or two glands are affected, but it is not unusual for all four eyelid margins to be involved. There may drainage of exudate from the conjunctival or cutaneous eyelid surface. Examination of the marginal palpebral conjunctiva often reveals a glistening or cystic appearance to affected meibomian glands, yet lancing the gland usually results in minimal drainage. This condition should be distinguished from a chalazion that more often appears as solitary glandular swelling with minimal inflammation and little evidence of patient discomfort. If a chalazion is lanced, an abundance of tenacious, white, sebaceous secretion is usually expelled. The cause of meibomianitis is speculative. It is postulated to start with bacterial infection (e.g., Staphylococcus sp.), but chronic cases appear primarily immune-mediated. Bacterial culture of exudate from an affected gland is advised, but substantial growth is uncommon. Oral antibiotics are appropriate in initial treatment and pending culture results; cephalexin or doxycycline is preferred. Topical antibiotic/steroid ointment such as neo-poly-dex can be applied several times daily, but systemic steroids are usually required for severe cases. Azathioprine can be used in recurrent or refractory cases, and oral cyclosporine is helpful in some patients. Warm compresses may also be of benefit in initial treatment.

Obstructions of the nasolacrimal duct

Several conditions can result in a blocked nasolacrimal duct (or tear duct) and include imperforate lacrimal punctum, infection (i.e., dacryocystitis), obstruction with foreign material, scarring from prior infection (e.g., herpesvirus in cats), trauma, and compression from a lacrimal canalicular cyst (i.e., canaliculops), neoplasm, or bony malformation. Symptoms include serous to mucopurulent discharge, variable conjunctival hyperemia, minimal evidence of discomfort, and an otherwise normal globe. Mild to moderate swelling can be noted below the nasal canthus depending on the cause. Nasal discharge can be present if the obstruction is secondary to upper respiratory infection or a neoplasm. Fluorescein stain can be applied to the eyes and the nares examined shortly thereafter for the presence of stain (i.e., the Jones test). The presence of fluorescein at the nasal opening indicates the duct is patent. Stain should be applied to both eyes for comparison, and false negative results are possible. The definitive test to determine patency is to cannulate and flush the nasolacrimal duct. In dogs, this can be performed as an examination room procedure following application of topical anesthetic. However, cats often require sedation because the punctal openings are considerably smaller. Surgery may be required for patients where the duct(s) cannot be opened by attempts at flushing. Conditions such as imperforate lacrimal puncta are easily corrected. Chronic infection or foreign material within the duct is more difficult to resolve. For these cases, survey skull and contrast radiography (i.e., dacryocystorhinography) should be performed to confirm to location of the obstruction and possible cause. Corrective surgical procedures include dacryocystotomy (to remove material trapped in the lacrimal sac) and conjunctivorhinostomy (to create a new drainage pathway for tears).