Ocular Surface Disorders

The Preocular Tear Film

The preocular tear film consists of lipid, aqueous, and mucin components (Samuleson 2013). The most superficial layer is a lipid secreted by the meibomian glands that acts to slow or prevent evaporation of the aque­ous portion of the tear film.

Keratoconjunctivitis sicca

Keratoconjunctivitis sicca (KCS) is unfortu­nately an all too common ocular disease in the dog and it is generally a lifelong condition requiring chronic and diligent therapy and monitoring (Figure 4.4). The incidence of KCS in dogs is great with roughly 1% of the general population affected (Giuliano 2013). Quantitative or “classic” KCS is character­ized by a deficiency of the aqueous tear fluid which results in desiccation and inflamma­tion of the conjunctiva and cornea. Ocular pain and progressive corneal disease, with subsequent reduction in vision, occur.

The reduction or absence of lacrimal secretions may result from a single disease process or a combination of conditions affecting the lacrimal glands. The most common etiology is an immune-mediated inflammation of the lacrimal glands which results in dysfunction and impaired produc­tion of the aqueous fraction of tears (Giuliano 2013; Kaswan, Martin, and Dawe 1985; Hendrix et al.

Figure 4.4 Keratoconjunctivitis sicca in a West Highland White Terrier. Note the discoloration of the facial fur. This is common in many types of tear and ocular surface disorders. Also note the mucoid discharge present.

alterations (Giuliano 2013). Several breeds are disproportionately affected by acquired KCS, thus suggesting a genetic predisposi­tion (Table 4.1). The diagnosis of KCS is made on the basis of typical clinical signs and decreased Schirmer tear test (STT) results. In the clinical setting, STT I read­ings in dogs are generally interpreted as follows: ≥ 15 mm/min = normal production; 11-14 mm/min = early or subclinical KCS; 6-10 mm/min = moderate or mild KCS; and ≤ 5 mm/min = severe KCS (Table 4.2). Acute onset KCS is occasionally seen, wherein an eye becomes acutely and severely painful and usually exhibits axial corneal ulcera­tion (Figure 4.5). If not addressed promptly, these cases may develop suppurative inflammation which exacerbates the pro­gressive nature of the corneal disease with stromal malacia, descemetocele formation, and iris prolapse. Fortunately, in most cases, the onset of KCS is more gradual, with increasing severity over a period of several weeks (Giuliano 2013). These eyes initially present for redness and appear inflamed, with intermittent mucoid or mucopurulent discharge (Figure 4.6). As the severity and chronicity of the KCS increases, the ocular surface becomes lack­luster, the conjunctiva becomes progres­sively more hyperemic, and persistent tenacious mucopurulent ocular discharge develops. The keratitis, which progresses if left untreated, is usually characterized by exten­sive corneal vascularization and pigmentation (Figure 4.7 and Figure 4.8).

Treatment of quantitative dry eye has two primary goals: 1) stimulate the patient to pro­duce organic tears and 2) supplement the patient with topical lubricants (artificial tear preparations). Additionally, depending upon the presence and severity of other clinical signs, topical anti-inflammatory medications, usually corticosteroids, may be necessary to control initial or intermittent surface inflammation. Topical antibiotics maybe necessary to control secondary bacterial conjunctivitis. Dry eye is the foremost reason for bacterial conjunctivitis to develop. It is rare for primary bacterial con­junctivitis to occur in small animals without an antecedent condition. The use of a mucolytic agent may facilitate administration of other topical medications and may make cleaning and removal of the mucoid discharge easier.

Since most cases of KCS are immune- mediated in origin, the most commonly employed tear stimulating drugs are the immunomodulating agents, cyclosporine (0.2-2.0%) and tacrolimus (0.02-1.0%), both of which work by targeting T-helper cells and decreasing the inflammatory response

Table 4.1 Breed predisposition to chronic ocular disease.

within the lacrimal glands (Giuliano 2013; Kaswan, Martin, and Dawe 1985; Hendrix et al.

Table 4.2 Interpretation of STT I values and treatment recommendations.

Figure 4.5 A deep stromal corneal ulcer that has resulted from dry eye.

Figure 4.6 Mild to moderate KCS with early corneal changes and mucoid discharge.

KCS, wherein the innervation to the lacrimal glands is disrupted (Giuliano 2013). If the KCS has developed due to a neurogenic insult, the addition of pilocarpine may be helpful to supplement the absent neuro­transmitter and stimulate aqueous tear pro­duction from the glands. It may be given orally (1-2 drops of the 2% topical prepara­tion per 10 kg body weight PO in the food q12h, increasing in one drop intervals if no improvement is noted until clinical signs of hypersalivation, vomiting, or diarrhea occur; or a dilute preparation (0.1%) given topically q12h).

Figure 4.7 Keratitis in a Shih Tzu secondary to moderate dry eye. Note the corneal vascularization and superficial pigmentation.

Figure 4.8 Severe KCS with extensive corneal pigmentation and fibrosis in a Chinese Crested Dog.

If the KCS fails to respond to medical ther­apy, surgical options exist. Parotid duct transposition wherein the salivary duct is repositioned into the ventral conjunctival fornix will supply the ocular surface with lubrication, however, it may be associated with undesirable consequences such as excessive “epiphora,” facial dermatitis and mineral accumulation on the cornea or eye­lids (Giuliano 2013). It can dramatically improve patient comfort, however. Recently, the use of buccal mucosal grafts has been advocated to improve patient comfort. In this procedure, a free graft of mucosa from the oral cavity is sutured into the conjunctival fornix. It is believed that the transplantation of glandular tissue from the mouth to the eye provides something in the way of additional lubrication, although the STT values remain unchanged.

Qualitative Tear Deficiencies (Qualitative Dry Eye)

If either the lipid produced by eyelid meibo­mian glands or the mucin produced by con­junctival goblet cells components of the tear film are absent or decreased in quantity, clinical signs of KCS will develop even if STT measurements are within the normal range (Giuliano 2013). This is known as qualitative dry eye. This condition most often occurs secondary to disruption or inflammation of the target tissues that pro­duce either the mucin or lipid fractions of the tears. Chronic conjunctivitis or chronic blepharitis or meibomianitis will result in a reduction of mucin and lipid, respectively. When the tear quality is impaired, aqueous tears will evaporate too quickly and will not be able to stay distributed evenly and ade­quately across the ocular surface, essentially creating a functional dry eye. The diagnosis is confirmed with either of the vital dyes, rose Bengal or Lissamine green, which localize to areas of the cornea where the mucin fraction is insufficient. Additionally, the tear film break-up time will help determine if the tear film is unstable and evaporating too quickly (Giuliano 2013). When fluorescein stain is applied to the ocular surface in high concentrations, it will saturate the tear film. After blinking to evenly distribute the dye, the patient's eye­lids are held open manually (to prevent blinking) and the time is counted in seconds until the homogenous green color on the ocular surface begins to develop dark splotches, indicating areas where the tear film has “broken up,” or become unstable and started to evaporate or dissipate. If this break up occurs before 10 seconds of elapsed time, the tear film is described as unstable and of poor quality.

Treatment is aimed at improving the qual­ity and amount of mucin and/or lipid and supplementing with artificial tears, essen­tially the same approach used in quantitative dry eye. Medical treatment with cyclosporine or tacrolimus will in most cases normalize or improve tear lipids and mucin and result in an improvement of clinical signs. Artificial tears will bridge the gap while tear quality is on the mend. Compounding the immu­nomodulators in an oily base will help with clinical signs. The addition of essential fatty acids to the diet is thought by some to be helpful in improving tear quality.

Conjunctivitis

Conjunctivitis can be a particularly frustrating condition when it becomes chronic. Conjunctival hyperemia, chemosis and dis­charge ranging in character from clear and serous to mucoid or mucopurulent are the most common clinical signs seen (Figures 4.9 and 4.10). With chronicity, the patient may develop conjunctival follicles which are semi­transparent, bubble-like aggregates of lym­phoid tissue, the result of chronic antigenic stimulation (Figure 4.11). The most common etiologies for chronic conjunctivitis in dogs are tear film abnormalities (see earlier discussion) and allergies. A thorough ocular examination with evaluation of the quantity and quality of the tear film is necessary to determine the etiology. Allergic conjunctivitis is a rule-out

Figure 4.9 Allergic conjunctivitis in a mixed breed dog. Note the conjunctival hyperemia and chemosis.

diagnosis that is made if the tear film is suffi­cient and there are no other signs or indications of ocular or systemic disease (Pena and Leiva 2008; Bistner 1994; Peiffer 1980; Lourenqo- Martins et al. 2011). Treatment of allergic con­junctivitis is best achieved with identification and removal of the offending antigen. If this is not possible, symptomatic treatment with the least amount of drug necessary to control clini­cal signs will be necessary. Topical corticoster­oids, cyclosporine, or antihistamines may be considered (Lourenqo-Martins et al. 2011). It may be challenging to find the right “cocktail” of empiric medications for some individual patients. Topical lubricants (artificial tears) may be helpful for short-term comfort.

Figure 4.10 Herpetic keratitis is a cat with profound conjunctival chemosis and hyperemia.

Figure 4.11 Chronic conjunctivitis in this Labrador Retriever has resulted in follicle formation.

Conjunctivitis in cats is most often initiated by an infectious agent. Feline her­pesvirus-1 (FHV-I) is the most common infectious agent responsible for conjunctivi­tis in cats (Peiffer 1980; Malik et al. 2009). Chlamydophila felis and mycoplasmal organisms are also implicated, but less often. When cats develop chronic conjunctivitis, it may be difficult to implicate FHV-1 because the classic respiratory signs associated with primary infections are usually absent. However, since the virus establishes itself and develops latency, it may contribute to active conjunctivitis and keratitis at any time, particularly during periods of stress. In some cats, the immune system will mount a response to the presence of viral antigen and cause ocular surface inflammation without the cytolytic contributions of viral replica­tion. Additionally, FHV-1 may initiate the development of KCS in cats, so clinical chronic conjunctivitis in cats may be due to a multitude of related problems (Giuliano 2013). The establishment of causation is dif­ficult to prove considering most cats have been exposed to FHV-1 and many become carriers and can shed virus without clinical signs. The presence of the virus detected via indirect fluorescent antibody staining or PCR will not necessarily be diagnostic (Sjodahl-Essen et al. 2008). Neither will con­junctival cytology be helpful in diagnosing FHV-1, however, it may be helpful for diag­nosing chlamydophilal (cytoplasmic inclu­sions), mycoplasmal (organisms seen), or eosinophilic conjunctivitis (eosinophils, mast cells), all of which may occur as con­current conditions or co-infections with FHV-1. Treatment can be very frustrating to both cats and their owners. Generally, if an infectious agent is suspected, a course of antimicrobial agents is recommended. If chlamydophilal or mycoplasmal organisms are present or suspected, a course of topical (oxytetracycline, chloramphenicol or eryth­romycin q6h for 2-3 weeks) and/or systemic tetracyclines or macrolides (doxycycline 5mg∕kg PO q12h or azithromycin 5mg∕kg PO q24h) may be helpful, but may not be effective at eliminating a carrier state. Herpetic keratoconjunctivitis is somewhat more difficult to control. The minimal amount of medical intervention should be employed. Often, particularly in mild cases, topical lubricants may be sufficient to help minimize discomfort until the flare-up sub­sides on its own. A short course of systemic non-steroidal therapy (meloxicam 0.1 mg/kg PO q24h or robenacoxib 1 mg/kg PO for 3 days) may be helpful initially as well. In severe or refractory cases, or those in which there is also corneal involvement, anti-viral therapy may be indicated. Antiviral therapy with topical agents will limit the extent of systemic side effects, but may be challenging due to the fact that effective drugs are not commercially available and must be pro­duced by a compounding pharmacy (cidofo- vir 0.5% q12h or idoxuridine 0.1% q4h) (Figure 4.12). If topical agents aren't success­ful in decreasing the severity of clinical signs or if there are systemic signs or dermatologic involvement, systemic antiviral may be used (famciclovir 10-90 mg/kg q24h) (Sjodahl- Essen et al. 2008). Antivirals are usually given until clinical signs resolve and then are discontinued, rather than tapered in frequency. A few cats require chronic admin­istration, rather than interval therapy during an active bout, and these cats should be monitored regularly with complete blood counts and serum chemistries to determine if any bone marrow or renal toxicity is developing.

Cats will also develop non-infectious con­junctivitis. Eosinophilic conjunctivitis, with or without keratitis, typically presents with the classic signs of conjunctivitis (hypere­mia, chemoisis, and discharge) but may also exhibit raised, irregular, or roughened lesions resembling granulation tissue in the bulbar, palpebral or nictitans conjunctiva or on the cornea (Allgower, Schaffer, and Stockhaus 2001) (Figure 4.13). Cytology of these lesions reveals the presence of eosino­phils and mast cells. Tear production may be decreased in these cats secondary to obstruction of lacrimal ductules by the

Figure 4.12 Severe herpetic Dlepharokeratoconjunctivitis in an eldery feline.

Figure 4.13 Eosinophilic keratoconjunctivitis conjunctivitis in a cat.

Figure 4.14 Lipogranulomatous conjunctivitis in a cat.

conjunctival swelling. Treatment is aimed at decreasing the inflammatory response and usually requires an extended course of treatment with a very slow taper of frequency. Lipogranulomatous conjunctivi­tis is an unusual form of conjunctivitis occurring in older cats as non-ulcerated white nodules in the palpebral conjunctiva (Kerlin and Dubielzig 1997) (Figure 4.14). Histopathology of the lesions describes macrophages and multinucleated giant cells filled with lipid. Surgical excision of the nodules may be curative, otherwise chronic therapy with corticosteroids is necessary to minimize the inflammation and improve patient comfort.