Conjunctiva

The conjunctiva is associated with many adnexal and bulbar diseases because of its exposure and close proximity to ocular structures. Thorough physical and ocular examinations should be performed on dogs with signs of conjunctival disease because some of these diseases can be an indication of systemic and/or severe ocular disease. The cause of conjunctival disease can often be determined solely on the basis of history and complete ophthalmic examination.

Functional Anatomy and Physiology

The conjunctiva, a mucous membrane, plays a role in tear dynamics, immunological protection of the eye, ocular movement, and corneal healing. The conjunctiva lines the inside of the eyelids, beginning at the eyelid margin and extending deep toward the orbit to create a fornix (conjunctival sac), at which it reverses direction and extends over the globe to the limbus. These three major areas are referred to as the palpebral conjunctiva, the fornix (i.e., “cul‐de‐sac”), and the bulbar conjunctiva, respectively. The palpebral conjunctiva is continuous with the epidermis of the eyelid, just as the bulbar conjunctiva is continuous with the corneal epithelium. Medially, the conjunctiva covers both the palpebral (outer) and bulbar (deep) surfaces of the nictitating membrane (NM).

Microscopic Anatomy

The conjunctiva is composed of nonkeratinized, stratified squamous epithelium and an underlying substantia propria. The substantia propria is divided into superficial and deep layers. The superficial layer contains many lymphoid nodules that are the major components of the conjunctiva‐associated lymphoid tissue (CALT). The purpose of CALT is to receive antigen and to present it to circulating mononuclear cells. The lymphatics that drain this area represent the only known lymphatic drainage of the canine eye. The deeper layer of the substantia propria is fibrous and contains the conjunctival vessels and nerves. M cells have been reported in the nictitans, but not in the remaining conjunctiva.

Goblet cells are also present in the epithelial layer of the conjunctiva. These cells produce a gel‐like mucin, which forms the deepest of the three layers of the preocular (i.e., precorneal) tear film and protects the ocular surface by trapping both debris and bacteria and by providing a medium for adherence of immunoglobulins (i.e., immunoglobulin A) and microbicidal lysozymes. For biopsy, the areas of highest goblet cell density in the dog are the lower nasal fornix, lower middle fornix, and lower nasal tarsal regions.

Vascular Supply and Innervation

The vascular supply of the conjunctiva is extensive. Branches of the dorsal and ventral palpebral and malar arteries, as well as terminal branches from the anterior ciliary arteries, provide the conjunctiva with its blood supply. Innervation is provided by branches of the long ciliary, zygomaticofacial, zygomaticotemporal, infratrochlear, and frontal nerves.

Normal Bacterial and Fungal Flora

Bacteria can be cultured from the conjunctival sac in 46–90% of normal dogs. Gram‐positive aerobes are the most commonly cultured, with Staphylococcus spp., Bacillus spp., Corynebacterium spp., and Streptococcus spp. predominating. Gram‐negative bacteria have been recovered from the conjunctival sac in 7–8% of normal dogs. Anaerobes are rarely isolated. While fungi are rare, the most commonly cultured are Cladosporium oxysporum, Curvularia lunata, and Malassezia pachydermatis. The normal conjunctival flora appears to vary with the season.

Conjunctival Cytology

Cytological examination of scrapings from normal conjunctiva reveals sheets of epithelial cells with large, round, homogeneous nuclei and abundant cytoplasm. Keratinized epithelial cells are uncommon. Bacteria are occasionally seen and leukocytes are rare. Cytological samples are easy to obtain from the dorsal and ventral conjunctiva. After administration of a topical anesthetic, a cytobrush, the blunt end of a scalpel blade, or even an impression using a membrane filter can be effective for obtaining cells. After infection, injury, or other insults, the conjunctival cytology changes (Table 8.1).

General Response to Disease

The conjunctiva responds to insult with a limited number of mechanisms. Chemosis, hyperemia, blepharospasm, and cellular exudation characterize acute conjunctivitis (Figure 8.1). The loose arrangement of the conjunctival stroma permits extensive edema to develop rapidly after trauma or exposure to allergens or toxins, and the vast blood supply as well as the lymphoid tissue allows acute development of hyperemia and a cellular response. Goblet cell proliferation occurs with keratoconjunctivitis sicca (KCS), chronic conjunctivitis, and vitamin A deficiency. Conjunctival flora is altered in dogs with various diseases. Bacteria are more likely to be isolated from the conjunctiva of dogs with ulcerative keratitis than from dogs with healthy eyes. Cytological and culture differences between the conjunctiva of dogs with atopic dermatitis and normal dogs found that affected dogs had significantly more bacteria, keratinized and nonkeratinized epithelial cells, eosinophils, and lymphocytes, and had more positive cultures regardless of clinical parameters.

Ocular redness, which can result from conjunctival hyperemia or episcleral congestion, occurs with many diseases, including abnormal eyelid conformation, abnormal cilia, allergic conjunctivitis, corneal disease, KCS, anterior uveitis, glaucoma, orbital disease, and toxic or septic shock. Conjunctival hyperemia should be differentiated from episcleral injection and ciliary flush, which occur with glaucoma and anterior uveitis. Generally, the conjunctival vessels are smaller in diameter, have a branching pattern, blanch quickly with topical application of 1–2% epinephrine, and are mobile. Episcleral vessels are larger in diameter, do not branch, do not blanch quickly with topical application of epinephrine, and are not mobile. While the vessels associated with ciliary flush form a branching network near the limbus, the vessels’ other characteristics are similar to those seen with episcleral vessels.

Infectious Conjunctivitis

Infectious conjunctivitis indicates the association with specific pathogens and is uncommon in the dog.

Bacterial Conjunctivitis

Primary bacterial conjunctivitis is an uncommon disease in the dog. In most cases, bacterial conjunctivitis develops secondary to eyelid abnormalities or KCS. Bacterial conjunctivitis is usually caused by Staphylococcus spp. and other Gram‐positive organisms. Cytological examination of conjunctival scrapings from dogs with bacterial conjunctivitis can help to confirm the diagnosis. Neutrophils with few mononuclear cells, many bacteria, and degenerating epithelial cells are present in acute infections (Figure 8.2). In chronic disease, neutrophils remain the predominant cell type, but there are many more mononuclear cells. Additionally, degenerate or keratinized epithelial cells are seen with the presence of bacteria being variable. Pending culture results, topical chloramphenicol, erythromycin or bacitracin, neomycin, and polymyxin B can be used for Gram‐positive bacteria conjunctivitis, and tobramycin, gentamicin, or topical bacitracin, neomycin, and polymyxin B can be used for bacterial conjunctivitis caused by Gram‐negative bacteria.

Viral Conjunctivitis

Viral conjunctivitis has been most commonly associated with canine distemper virus; however, a recent virological survey and other research added canine herpesvirus‐1 (CHV‐1). Of 30 dogs with clinical conjunctivitis, 5 were positive for CHV‐1 and 2 for canine adenovirus‐2. An outbreak of CHV‐1 in a closed colony of Beagles caused conjunctivitis and keratitis in all dogs, ulcers in 26% of dogs (punctate, dendritic, or geographic), and nonulcerative keratitis in 19% of dogs. All dogs tested were positive for CHV‐1 on PCR and virus isolation. The conjunctivitis began to decrease in severity over the following 15 days and returned to normal by day 35 (Figure 8.3). No dogs developed keratitis or signs of systemic disease. Ocular viral shedding was detected in all infected dogs between days 3 and 10 after infection. All infected dogs also developed CHV‐1 serum neutralizing antibody titers, beginning at 7 days after inoculation and peaking on day 21.

Recrudescent CHV‐1 disease has been induced in dogs with latent CHV‐1 infection by administration of an immunosuppressive dosage of prednisolone for seven days. Bilateral mild‐to‐moderate conjunctivitis, characterized by intermittent blepharospasm, conjunctival hyperemia, chemosis, and mucoid‐to‐mucopurulent ocular discharge or keratitis, was detected in 83% of dogs between days 3 and 18 after initiating the prednisolone.

Canine distemper virus is associated with conjunctivitis, chorioretinitis, KCS, and optic neuritis. Conjunctivitis generally occurs with the rhinitis and tracheobronchitis that accompanies the initial febrile episode; the neurological and ocular signs occur about a week later. A mucopurulent discharge is often present. Initially, mononuclear cells are seen on cytology. Later, the number of neutrophils increases, and plasma cells, goblet cells, and cellular debris are seen. Distemper viral antigens can be detected using direct immunofluorescence and PCR. Cytoplasmic inclusion bodies may be found in the conjunctival epithelial cells after six days of infection and are seen more frequently in cells acquired from the NM; however, these inclusions are scarce and infrequently seen.

Noninfectious Conjunctivitis

Allergic Conjunctivitis

Allergic conjunctivitis occurs frequently in the dog and is often a component of atopic dermatitis. Atopy is a type 1 hypersensitivity reaction. The common allergens are pollens, molds, and dust mites. Clinical signs include conjunctival hyperemia, chemosis, facial pruritis, periocular alopecia, and ocular discharge. With chronic antigenic stimulation, conjunctival lymphoid follicles develop. History, physical examination, and intradermal skin testing are used to make the diagnosis of atopy in the dog. Results of cytology and histopathology indicate eosinophils (even a single one) on cytological examinations of conjunctival scrapings are considered to be diagnostic for an allergic process; however, plasma cells and lymphocytes are more commonly seen with allergic responses in the dog.

Avoidance of the offending allergen, hyposensitization, and pharmacological modification of the clinical signs are the primary forms of treatment. Intermittent use of a topical ophthalmic hydrocortisone or dexamethasone may be necessary to relieve clinical signs. Topical antihistamines, such as naphazoline, and mast cell stabilizers may have some benefit, but studies on their efficacy in the dog have not been reported.

Intense chemosis and blepharedema may occur as an immediate‐type reaction mediated by histamine and immunoglobulin E after food absorption; drug administration; and envenomation by ant, bee, wasp, or hornet stings as well as spider bites (Figure 8.4). The chemosis is often bilateral, and the actual area of trauma (if caused by an insect) is rarely identified and may be distant from the eyes. These cases usually respond rapidly to intravenous or intramuscular short‐acting corticosteroids and an antihistamine with or without topical corticosteroid ophthalmic ointments.

Follicular Conjunctivitis

Follicular conjunctivitis develops secondary to chronic antigenic stimulation. There is no evidence to link follicle formation to a viral or bacterial cause. Semitransparent follicles form primarily on the bulbar surface of the NM, but they may also form elsewhere on the conjunctiva (Figure 8.5). The follicles on the bulbar surface of the NM that are present with this disease greatly outnumber those normally seen, and they can be significantly larger. Frequently, hyperemia of the conjunctiva and a mucoid ocular discharge are present concurrently. This condition occurs most frequently in dogs younger than 18 months of age. The diagnosis is made on the basis of characteristic clinical signs. Cytological results of conjunctival scrapings will confirm the diagnosis by revealing the lymphoid nature of the follicles. Most cases respond to treatment with saline irrigation and symptomatic use of ophthalmic dexamethasone administered three to four times daily.

Conjunctivitis Associated with Tear Deficiencies

KCS is a frequent cause of conjunctivitis in the dog, and it is the most common cause of secondary bacterial conjunctivitis. Thus, the Schirmer tear test (STT) should be performed on all dogs with conjunctivitis. Cytological examination of conjunctival scrapings from dogs with chronic KCS reveals increased mucus, goblet cells, and keratinization; cytology from dogs with acute KCS reveals bacteria, neutrophils, mucus, and debris. Treatment of KCS with cyclosporine has been shown to result in greater intraepithelial mucin quantities in vivo and to promote goblet cell differentiation in vitro. Treatment with cyclosporine, tacrolimus, or pimecrolimus decreases the conjunctival inflammation and mucous discharge associated with KCS.

Ligneous Conjunctivitis

Ligneous conjunctivitis is a rare disorder in dogs that results in thickened, hyperemic palpebral conjunctivae with proliferative, opaque membranes. It has been reported in four Doberman Pinschers, a Golden Retriever, and a Yorkshire Terrier. There are varying degrees of concurrent systemic illness. Histologically, the affected conjunctiva has a thick, amorphous, eosinophilic, hyaline‐like material in the substantia propria, with a moderate mononuclear infiltrate. Topical therapies have included corticosteroids, heparin, and cyclosporine or tacrolimus. Systemic treatment with prednisone, azathioprine, fresh frozen plasma, danazol, and diethylstilbestrol has been attempted but generally yields poor results.

Conjunctival Neoplasia

Melanomas, squamous cell carcinomas, angioendotheliomatosis, mast cell tumors, hemangiomas, hemangiosarcomas, angiokeratomas, papillomas, lymphosarcomas, histiocytomas, and transmissible venereal tumors all may affect the canine conjunctiva. The paucity of large studies and case reports, however, supports the clinical impression that conjunctival neoplasia occurs infrequently in the dog. Melanomas of the conjunctiva most commonly involve the NM, but they have also been reported to originate from the upper palpebral conjunctiva. These tumors tend to be malignant, and recurrences and metastasis are common. Combined excision and cryotherapy appear to be the most effective treatment.

Mast cell tumors can arise from the bulbar or palpebral conjunctiva or the NM. Some dogs may have a history of intermittent swelling and redness of the conjunctiva. These tumors are easily diagnosed via fine needle aspirate. Surgical excision is usually curative. Conjunctival mast cell tumors have a low risk of recurrence and are unlikely to metastasize regardless of tumor grade or having incomplete surgical margins. Squamous cell carcinoma of the perilimbal area is seen infrequently. These tumors are white to pink, elevated, and papillomatous. Conjunctival hemangiomas and hemangiosarcomas tend to occur at the nonpigmented, leading edge of the NM, and at the temporal bulbar conjunctiva. Hemangiosarcomas of the conjunctiva can encroach on the cornea, thereby causing corneal edema and vascularization. There is also a linear trend showing an increased risk of tumor development with increased UV exposure, and there is a statistically significant risk for conjunctival hemangiosarcoma development, compared to hemangioma, with increased UV levels. Resection appears to be curative in most cases, but recurrences are possible. Metastasis has not been confirmed.

Papillomatosis occurs on the palpebral and bulbar conjunctivae as well as the NM. The lesions are well demarcated, rough, and papillary or sessile (Figure 8.6). Histopathology shows various degrees of epithelial hyperplasia, acanthosis, hyperkeratosis with koilocytosis, and vascular and connective tissue cores. Some lesions are positive for gene fragments of canine oral papillomavirus DNA. While most lesions in young dogs regress spontaneously, excision is curative and may be necessary if the lesion is irritating.

Lymphosarcoma can infiltrate the conjunctiva causing thickening. Cytology of a conjunctival scraping may be diagnostic for lymphosarcoma, but in one known case of lymphosarcoma, a scraping revealed only reactive lymphoid hyperplasia. While conjunctival lymphosarcoma is usually considered to be associated with systemic lymphosarcoma, apparent ocular extranodal presentation has been reported with a T‐cell phenotype.

Canine lobular orbital adenomas can appear as a subconjunctival mass, eyelid swelling, or exophthalmos. The masses are either nodular or solid and extend into the orbit. These can be bilateral and commonly recur after excision. Histopathology reveals well‐differentiated, lobulated, glandular tissue resembling either lacrimal or zygomatic salivary gland with a mucoserous secretory pattern and a complete lack of ductular structures.

Non‐neoplastic Conjunctival Masses

Non‐neoplastic conjunctival masses can be inflammatory nodules, dermoids, displaced orbital fat, or cysts. Specific inflammatory diseases of the sclera, including episcleritis and scleritis, cause conjunctival hyperemia and swelling; they are described in the corneal Chapter 9.

Inflammatory Masses

Nodular granulomatous episclerokeratitis, fibrous histiocytoma, and recurrent proliferative keratoconjunctivitis are thought to represent very similar diseases, or even an identical disease syndrome. Collies appear to be predisposed, but the disease occurs in many breeds. This group of non‐neoplastic diseases primarily affecting the cornea, limbus, episclera, and nictitans often presents as a subconjunctival mass. Limbal masses infiltrate the corneal stroma causing vascularization and edema (Figure 8.7). Histopathologically, the lesions are primarily granulomatous with lymphocytes, plasma cells, histiocytes, fibroblasts, and reticulin formation. The lesions tend to recur when excised, but excision with adjunctive cryotherapy is reported to be a successful mode of therapy. Some lesions will respond to 1% ophthalmic prednisolone acetate with treatment initiated q.i.d. and very gradually tapered to the lowest effective dose. Additionally, azathioprine, with or without topical corticosteroids, can be used to induce resolution of the lesions. Dogs should be monitored for hepatotoxicity and myelosuppression every four to six weeks. Cryotherapy or intralesional triamcinolone at 4–12 mg per eye, with higher dosages for larger dogs, can also be used. Ocular nodular fasciitis, which may be a different disease syndrome, usually causes subconjunctival, scleral, corneal, nictitans, limbal, and eyelid masses. Histopathologically, fibroblasts and abundant reticulin formation are the primary changes, with lesser numbers of lymphocytes, plasma cells, and histiocytes. Excision of the lesions, even when incomplete, is curative.

Subconjunctival Fat Prolapse

Subconjunctival prolapse of orbital fat is seen as a nonpainful, movable light pink mass at the limbus. Cytological examination reveals multiple lipid droplets and few mononuclear cells. Surgical removal, while curative, should not be overzealous as enophthalmia can result. Onchocerciasis causes bean‐sized masses in the conjunctiva, nictitans, and sclera (Figure 8.9).

Cysts

Multiple causes of cyst formation in the conjunctiva have been described, but all occur only rarely in the dog. Conjunctival epithelial inclusion cysts, cystic neoplasms, parasitic cysts, lacrimal cysts (i.e., dacryops), orbital cysts with conjunctival fistula formation, and cysts of the lacrimal canaliculi can occur.

Conjunctival Hemorrhages

Conjunctival and subconjunctival hemorrhages occur commonly in the dog and most frequently result from trauma. When this condition is caused by trauma, no treatment is necessary if the remaining ophthalmic and physical examinations are normal (Figure 8.10). If there is no history or evidence of trauma, a coagulopathy or vasculitis must be considered as the possible cause. Specifically, conjunctival hemorrhage has been reported with angiostrongylosis and von Willebrand factor deficiency. No treatment is needed specifically for the conjunctival hemorrhages.

Foreign Bodies

Physical irritation caused by foreign bodies lodged within the conjunctiva or NM can cause a severe reaction, including blepharospasm, mucoid discharge, hyperemia, and corneal ulceration. Grass awns and other plant material are the most common culprits. Most foreign bodies can be removed with forceps after administration of a topical ophthalmic anesthetic.