The conjunctiva is a thin, transparent mucous membrane that covers the internal surface of the eyelids (palpebral conjunctiva), the external and internal parts of the third eyelid and the visible, anterior part of the bulb of the eye (bulbar conjunctiva). The conjunctiva is joined to and continues with the cornea at the limbus. The junction between the palpebral and bulbar conjunctiva is defined as the superior and inferior conjunctival fornix, respectively. The conjunctival sac is defined as the space delimited by the conjunctiva. The sac is strongly adherent to the eyeball at the limbus and in contact with the palpebral surface, while more posteriorly (conjunctival fornix) the contact is looser in order to enable freer movement of the eyelids and the eye itself.
From a histological point of view, the conjunctiva is formed of a superficial epithelial layer, consisting of several layers of cells containing numerous goblet cells, and a deeper stromal layer or substantia propria. In its turn the substantia propria is formed of a superficial glandular layer containing lymph follicles and glands and a deeper fibrous layer. The most external part of the superficial epithelium is constantly renewed by cells from the basal layer.
The blood supply is guaranteed by the palpebral, malar and temporal arteries, while the venous drainage is via the facial vein and the angular vein of the eye which empty into the orbital venous plexus and the superficial temporal vein. There are numerous anastomoses between the superficial and deep vessels at the limbus. The afferent sensory innervation is provided by the lachrymal, intratrochlear and anterior ciliary nerves.
The conjunctiva is rich in lymphatic tissue which can become organized into small follicular structures during inflammatory states. The lymphatic system from the lateral part of the conjunctiva drains into lymph nodes in the parotid region, while that from the medial region drains into the submandibular lymph nodes.
The purposes of the conjunctiva are to prevent the cornea from becoming dry, to facilitate movements of the eyelids and the eyeball, to produce the mucinous component of the tear film through its goblet cells and to provide a barrier against micro-organisms and foreign bodies.
Inflammation of the conjunctiva is the most frequent eye disorder in cats. It can be classified on the basis of its duration, the type of ocular discharge, the underlying cause and the clinical appearance. The disease can be localised to the bulbar part, the palpebral part or the lining of the third eyelid; very often, however, the conjunctivitis is generalised (Fig. 1).
AETIOLOGY
The causes of conjunctivitis in the cat include bacteria, viruses, fungi, parasites, immune-mediated factors and hypersensitivity, contact with chemical or toxic substances, abnormalities of the tear film, neoplasms and trauma of various types. The close anatomical contact of the conjunctiva with the palpebrae and the eyeball facilitate the extension of disorders of these structures to the conjunctiva itself.
Bacterial conjunctivitis
The incidence of bacterial forms of conjunctivitis is not particularly high in the cat, with conjunctival swabs being reported to be positive in 34% to 67% of clinically healthy cats. The bacteria isolated from cats include Staphylococcus albus, Staphylococcus aureus, Staphylococcus epidermidis, Mycoplasma spp., Bacillus spp., Chlamydia spp., Streptococcus alpha haemolyticus, Corynebacterium spp., Escherichia coli and Bordetella bronchiseptica.
Viral conjunctivitis
Herpesvirus, Calicivirus, Reovirus and Picornavirus are, in order, the most widely spread pathogenic agents responsible for viral conjunctivitis in cats.
Fungal conjunctivitis
The relevance of isolating fungi from cats is not yet completely clear, since there are studies showing that 40% of cats can be positive without having clinical signs. The most commonly isolated species include Aspergillus spp. (8%), Penicillium spp. and Cladosporium spp.
Parasitic conjunctivitis
In areas in which the nematode is widespread, adult Thelazia callipeda worms may be found, as may be larval forms of the Cuterebra fly. Although the cat does not seem to be a reservoir for Leishmania, in areas in which this parasite is endemic, cases of leishmaniasis have also been found in felines.
Conjunctivitis due to contact with chemical or toxic substances
The numerous chemical products that can accidently or deliberately come into contact with conjunctiva include both acid substances (sulphuric acid, sodium hypochlorite, hydrofluoric acid, acetic acid, chromic acid, hydrochloric acid) and alkaline ones (caustic soda, potash, magnesium hydroxide, calcium hydroxide, ammonium hydroxide, sodium hydroxide, potassium hydroxide)
Abnormalities of the tear film
Keratoconjunctivitis sicca may be the consequence of the direct action of a pathogen on the lachrymal gland or, much more probably, related to the mechanical action of inflamed and oedematous conjunctival tissue on the excretory ducts of the gland.
Traumatic conjunctivitis
The most common cause of traumatic conjunctivitis is undoubtedly fighting between animals. Other common causes are foreign bodies of vegetal origin (pieces of plants, blades of grass, woody fragments), animal origin (bits of nails), or of metal (gunshot). Foreign bodies are most commonly found in the inferior conjunctival fornix behind the nictitating membrane.
Mechanical contact
Possible problems are entropion, ectopic cilia, trichiasis (following eyelid agenesis) and distichiasis of the superior or inferior eyelid. Exophthalmos caused by orbital space-occupying lesions or lagophthalmos secondary to neurological problems can cause inflammation of the conjunctiva.
Physical agents
Air, wind and dust can all be responsible for inflammatory reactions.
Neoplasms
The types of intra-ocular neoplasms reported in cats are very malignant. They include melanoma, squamous cell carcinoma, haemangioma, haemangiosarcoma and lymphoma.
Other types of conjunctivitis
Eosinophilic conjunctivitis
The cause of this form of conjunctivitis is still unknown.
Lipogranulomatous conjunctivitis
The pathogenesis of this form of conjunctivitis probably involves damage to the Meibomian glands with a consequent inflammatory response due to contact between sebaceous material extruded from the ruptured gland and the conjunctival tissue. It has been suggested that the cause of this damage could be ultraviolet radiation, while another hypothesis is that the lipids could originate from systemic hyperlipidaemia or contact with topically applied drugs.
Actinic conjunctivitis
A recognized predisposing cause of this form of conjunctivitis, in animals with little pigmentation, is exposure to solar radiation.
Allergic conjunctivitis
In the cat, as in other animal species, exposing the conjunctiva to antigens, by direct contact (for example, neomycin-based ointments), inhalation (pollens and dust) or ingestion (for example, food allergies) can give rise to an inflammatory response.
CLINICAL SIGNS AND SYMPTOMS
Independently of the underlying cause of the conjunctivitis, the clinical signs and symptoms of this condition are often the same. They may be present in one eye or both, depending on the aetiology. Nevertheless, as described below, there are some clinical conjunctival manifestations that are typical of particular ocular disorders.
Epiphora
An overflow of tears onto the face (epiphora) can be the consequence of afferent stimulation by the trigeminal nerve following any nociceptive or inflammatory stimulus. Since the excretory system is unable to drain the excess production of tears, these flow out of the eye at the medial canthus, leaving a brownish streak. Chronic epiphora may also be the consequence of stenosis or adhesions of the outflow tract occurring in particular infections (for example, Herpesvirus infection) (Fig. 2).
Conjunctival hyperaemia
Hyperaemia of the conjunctiva is the result of the local action of chemical mediators of inflammation on the conjunctival vessels. The response to the inflammatory stimulus causes what is commonly known as "pink eye". Since a pink eye can be a consequence of numerous ocular disorders, such as episcleritis, deep keratitis, uveitis, glaucoma, and orbital lesions, it is extremely important to evaluate the characteristics of the blood vessels in order to determine the depth of the inflammation and, thereby, the importance of the disorder present.
Ocular discharge
The characteristics of an ocular discharge can, in some cases, provide information on the possible cause of the discharge. A serous ocular discharge is common and usually indicates a minor inflammatory state (for example, an allergy). A mucous ocular discharge is the consequence of irritation of the muciparous cells of the conjunctiva and is manifested as sticky, grey, opaque matter, which tends to collect in particular at the medial canthus. The presence of greenish-yellow material, characteristic of a purulent discharge, implies septic complications (bacterial or fungal). A bloody discharge indicates the presence of particularly marked acute inflammation or conjunctival trauma. The ocular discharge often has mixed characteristics such that it may be both sero-mucosal and mucopurulent.
Chemosis
Conjunctival oedema or chemosis is manifested by thickening and formation of folds of the palpebral and bulbar mucosa due to the collection of the inflammatory transudate. Since the contact of the conjunctiva with the underlying tissues is very loose, the swelling can be very evident in some cases and often covers a large part of the corneal surface, in this way preventing inspection of both the fornix and the internal palpebral and bulbar parts of the cornea (Fig.
3).
Lymphoid follicles
These are structures normally present on the surface of the conjunctiva. When stimulated, particularly in the case of chronic inflammation, they can become hyperplastic taking on what is commonly called a “cobblestone” appearance. This phenomenon typically occurs in young animals and can be seen on the external surface of the third eyelid or, more frequently, on the bulbar part of this eyelid.
Pruritus and pain
These are manifested by the animal’s tendency to rub and harm itself or by photophobia and blepharospasm. When assessing these signs, care should be given to determining whether the cornea and intraocular and orbital structures are involved.
Haemorrhages or petechiae
These clinical signs can be noted in animals with systemic infectious diseases, following trauma or with blood dyscrasias (for example, thrombocytopenia, poisoning by oral anticoagulants) and generalised sepsis (Fig. 4).
Descriptions of some particular forms of conjunctivitis
In some forms of conjunctivitis the above described signs and symptoms are often associated with particular characteristics of the disease involved.
Herpetic conjunctivitis
This is an extremely widespread, often ubiquitous, form of conjunctivitis in which the affected animal shows upper respiratory tract and ocular signs. It affects predom
inantly young animals.The infected cat may sometimes remain symptomatic for very long periods or may become a chronic latent carrier. The marked tropism of feline Herpesvirus for both conjunctival and corneal epithelium leads to a predisposition to the development of erosive and ulcerative lesions on their surfaces. These lesions may be followed by the formation of persistent adhesions called symblepharon. Such adhesions may involve the corneal, palpebral, and bulbar surfaces and the surface of the third eyelid (Fig. 5).
As mentioned previously, involvement of the nasolachrymal drainage system can give rise to chronic epiphora due to obstruction of the lachrymal puncta and canaliculi. The infection often becomes persistent and recurrent in the same eye, leaving the contralateral one completely unaffected. The aetiological agent tends to localise to the trigeminal nerve and cornea in a chronic, latent form; in cases of particular stress or during treatment with immunosuppressant drugs, the virus can reactivate and cause a recurrence of the disease. In some cases the infection can lead to the development of keratoconjunctivitis sicca.
Conjunctivitisdue to Calicivirus
Besides causing lesions of the respiratory tract, oral cavity and joints, Calicivirus infection can, in cats, cause conjunctivitis. The pathogenicity of this disease is usually less than that of herpetic conjunctivitis and the condition tends to be self-limiting. Nevertheless, this infection, too, can become chronic, with the latent virus localised in the oro-pharynx.The aetiological agent of this form of conjunctivitis is an intracellular obligate. Gram-negative bacterium with marked tropism for mucous membranes.It predominantly affects the conju
nctiva, but can also cause gastrointestinal and respiratory problems. The infection often involves the conjunctiva in one eye and then, within a few days, affects the contralateral eye (Fig. 6). The cornea is very rarely involved in cats, unlike in other species. The conjunctivitis is almost always associated with symptoms of upper airway involvement, fever and regional lymphadenopathy. In some animals the disease may have a chronic evolution. There are documented cases of asymptomatic carriers and also of a latent phase, with the virus sheltering in the genital and gastrointestinal tracts.
Conjunctivitisdue to Mycoplasma
Mycoplasmainfection is an uncommon cause of conjunctivitis in felines and in order for this ocular manifestation of the infection to occur, there usually has to be concomitant stress. The conjunctivitis may initially appear in one eye and then affect the other eye within a few days. The condition is often self-limiting.
Eosinophilic conjunctivitis
The aetiology of this form of conjunctivitis is unknown; it may or may not be associated with a keratitis of the same nature. Eosinophilic conjunctivitis is manifested clinically by the presence of whitish, raised plaques with irregular borders attached to the conjunctival surface. The condition may be unilateral or bilateral (Fig. 7).
Lipogranulomatous conjunctivitis
This form of conjunctivitis is more usually bilateral and is characterized by the presence of single or multiple, small whitish nodules within the conjunctiva near the margin of the eyelid. The nodules are very often a source of annoyance to the animal. European breeds are affected more frequently and typically the condition occurs in old age (reported mean age: 11 years).
Neonatal conjunctivitis
Neonatal conjunctivitis, occurring in the very earliest perinatal period, before opening of the physiological ankyloblepharon, is an acute form of conjunctivitis with a mucopurulent discharge and marked conjunctival oedema. The eyelids often appear swollen because of the oedema, conjunctival inflammation and the underlying accumulation of exudate. Possible complications are corneal ulcers with their associated sequelae and the development of symblepharon. The most probable causes include Herpesvirus, Calicivirus, Chlamydia spp. and other opportunistic bacteria.
Squamous cell carcinoma
This ocular tumour is very invasive; it manifests as thickened areas, tending to be associated with erosions and ulcers, and also frequently involves the eyelid (Fig. 8).
DIAGNOSTIC INVESTIGATIONS
In cats it is sometimes extremely difficult to make a definitive aetiological diagnosis during the course of conjunctivitis and even sophisticated techniques, such as an immunofluorescence antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) analysis, are often of little help given that, in many studies, they have been shown to be positive also in clinically healthy animals.
The diagnostic investigations usually available are shown in Table 1.
Bacterial cultures, possibly with an antibiogram
Numerous investigations have found that culture studies are not very reliable for diagnostic purposes in conjunctivitis since pathogenic and non-pathogenic bacteria can frequently be isolated from asymptomatic animals.
Culture studies are, therefore, used above all in chronic forms of conjunctivitis and in cases resistant to prolonged treatment with antibiotics, even of different classes. The specimens for culture should be collected with previously moistened sterile swabs that should be placed immediately in the appropriate culture media. It should be remembered that some topical anaesthetics can inhibit bacterial growth and that, in order to avoid prevent secondary contamination, the specimens for culture should be taken before starting the clinical examination of the animal.
Conjunctival scrapes
A Kimura spatula or specific small brushes (for example, a cytobrush) can be used to collect the scrapings. Very useful information for diagnostic and therapeutic purposes can be gained from the cell morphology as well as from the presence or absence of bacteria (cocci or rods) and intracytoplasmic inclusion bodies.
Conjunctival biopsy
A conjunctival biopsy can be taken from co-operative subjects with the simple administration of a local anaesthetic (for example, oxybuprocaine) and the use of atraumatic tweezers with small, round-ended scissors for soft tissues. A small specimen (a few millimetres) taken in this way should be fixed on a piece of filter paper, to protect it from possible damage, and then introduced into a test-tube containing a preservative solution (for example, formalin).
Cytology of some conjunctival disorders
In cases of bacterial conjunctivitis, a smear can reveal numerous neutrophils and bacteria with often altered epithelial cells. In the acute forms there are usually few mononuclear cells, whereas these are more common in chronic forms.
Conjunctival scrapes taken from a subject with eosinophilic conjunctivitis show the presence of eosinophils and mast cells, while histological studies can identify eosinophils, lymphocytes, plasma cells, macrophages and mast cells.
Lipogranulomatous conjunctivitis is characterized by the presence of macrophages and giant multinucleated cells containing lipids. Some subjects may have an infiltrate containing lymphocytes, plasma cells and neutrophils.
Scrapings taken from an animal with herpetic conjunctivitis are non-specific, showing exclusively epithelial cells and numerous neutrophils.
In conjunctivitis due to Chlamydia the conjunctival scrapings can contain neutrophils, lymphocytes and the characteristic inclusion bodies in the cytoplasm of the conjunctival epithelial cells, while the scrapings from animals affected by Mycoplasma infections show polymorphonuclear cells and the causative micro-organisms, as coccoid bodies, associated with the conjunctival epithelial cells.
The cytological and histopathological findings in neoplastic conjunctivitis are extremely varied, depending on the malignancy present.
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Table 1. Diagnostic investigations.
TREATMENT
The treatment of conjunctivitis differs enormously depending on the underlying cause. It may be cause-specific or symptomatic, topical or systemic and, in some cases, vaccines can be used for prophylactic purposes.
Bacterial conjunctivitis may be treated locally with antibiotics (for example, tobramycin, quinolones, gentamicin, chloramphenicol). Lavage with bland disinfectant solutions based on diluted povidone-iodine and cleaning any accumulations of secretions in the palpebral area can be useful. The administration of systemic antibiotics is necessary only in the case of severe symptoms. In these cases the association of amoxicillin and clavulanic acid may be indicated, or cephalosporins, tetracycline or other antibiotics, depending on the veterinarian’s preference.
The treatment of eosinophilic conjunctivitis is based on the administration of topical corticosteroids (for example, dexamethasone, betamethasone) at tapered doses in order to keep the disease under control, inhibiting the clinical symptoms, with the smallest dose possible. This treatment may be combined with antibiotics (for example, tobramycin, quinolones, chloramphenicol, gentamicin). In some cases topical antiviral drugs (for example, idoxuridine, ganciclovir) are also used. Cyclosporine 0.2% may be administered locally and the condition can be helped by the use of artificial tears.
An alternative treatment is megestrol acetate per os at different doses depending on the usual practice of the veterinarian (Table 2). This drug does, however, have numerous adverse effects including the possible development of diabetes mellitus, gynaecomastia and adrenal gland suppression.
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Table 2. Possible therapeutic protocols for eosinophilic conjunctivitis and keratitis.
The treatment of lipogranulomatous conjunctivitis is surgical and consists of incision and curettage of the nodular lesions, together with topical administration of antibiotics and corticosteroids.
Herpetic conjunctivitis can be treated with topically applied antiviral drugs such as trifluridine, vidarabine, idoxuridine, cidofovir, acyclovir and ganciclovir. Unfortunately some of these active principles are not commercially available in many countries, but in some cases can be obtained in galenic preparations from specialised pharmacies. These topical drugs can be given together with systemic antiviral agents such as famciclovir (15-30 mg bid per os). The use of oral L-lysine (250-500 mg/die) or interferon – both systemically and topically – has also been recommended. Given the frequent concomitant presence of bacterial infections, the use of topical antibiotics, such as tobramycin, quinolones and chloramphenicol, has been suggested. The importance of vaccination in order to produce durable immunity is controversial.
Topical and systemic corticosteroids should always be avoided during the treatment of Herpesvirus infection as they could cause reactivation of latent virus.
Possible treatments for conjunctivitis due to Chlamydia are doxycycline (5 mg/kg for 3 weeks), erythromycin, azithromycin (5 mg/kg every 48-72 hours), rifampicin and fluoroquinolones. At a local level, the application of tetracycline, 4 times a day for 15 days, is recommended. Vaccination gives good protection against this disease.
The antibiotics of choice for the treatment of mycoplasmal conjunctivitis are tetracycline, chloramphenicol, gentamicin and erythromycin.
In the case of neonatal conjunctivitis, if the physiological ankyloblepharon is still present the eyelid must be opened surgically with a scalpel or cut with blunt-ended scissors. Careful cleaning of the mucopurulent ocular discharge associated with topical application of antibiotics and artificial tears may be curative if the disorder is tackled promptly.
The treatment of parasitic conjunctivitis is mechanical removal of the larvae, while spot-on imidacloprid can be used for prophylactic purposes.
In the case of contact with chemical agents, the speed of the intervention is fundamental. The eye involved must be washed repeatedly and for a long time with buffer solutions. The topical treatments used are antibiotics (for example, tobramycin, chloramphenicol, quinolones), collagenase inhibitors (for example, acetylcysteine), cycloplegics (atropine 1%) and artificial tears. The animal must also be given systemic antibiotics (for example, doxycycline) and non-steroidal anti-inflammatory drugs (for example, carprofen) or corticosteroids (for example, prednisone). It has been suggested that protecting the eye with a flap of the third eyelid could be useful in some cases.
Allergic conjunctivitis,if due to direct contact (dusts, allergens), can be helped by repeated rinsing with sterile saline solution. These forms of conjunctivitis can be treated with topical corticosteroids and, if the allergy is generalised, also with systemic corticosteroids. The therapeutic regimen should be limited to the lowest dose and frequency of administration necessary to keep the disease under control. Topical use of non-steroidal anti-inflammatory drugs, mast cell stabilisers (for example, sodium cromoglycate, olopatadine, lodoxamide) and antihistamines may also be useful in some cases to control symptoms.
In the case of conjunctivitis due to foreign bodies, these must obviously be removed and the conjunctival fornices carefully examined and irrigated abundantly with a disinfectant solution. It is, however, also necessary to determine whether the cornea is involved and to start topical antibiotic treatment. Topical antibiotic treatment is often sufficient to heal relatively small conjunctival wounds. In the case of severe conjunctival defects, the wound must be sutured with 7-8/0 calibre re-absorbable suture.
Follicular conjunctivitis is very common in young animals and usually does not require treatment unless there is a marked bacterial superinfection or tendency to rubbing and self-inflicted damage. Simple cleaning with bland solutions is often sufficient to keep the clinical symptoms in these individuals under control. In adult animals or in particularly complex situations, asportation of the follicles by surgery or scraping may be indicated, followed by local administration of corticosteroids and antibiotics.
For conjunctivitis due to mechanical causes (entropion, ectopic cilia, trichiasis, distichiasis), the defect present must be corrected surgically.
Conjunctivitis secondary to insufficient tears can be treated with a locally applied cyclosporine 0.2% unguent.
Conjunctival neoplasms must be removed with a wide excision margin given the invasiveness of these malignancies. Despite this, recurrences are extremely frequent and, unfortunately, necessitate orbital exenteration. Radiation therapy and cryosurgery can also be used to complement the traditional surgery.
Suggested readings
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- Bistner SI,Carlson JK,ShivelyJN et al. Ocular manifestations of feline herpesvirus infection. J Am Vet Med Assoc. 1971 Nov;159(10):1223-37.
- Read RA, Lucas J. Lipogranulomatous conjunctivitis: clinical findings from 21 eyes in 13 cats.Vet Ophthalmol. 2001 Jun;4(2):93-8.
- Allgoewer I, Schäffer EH, Stockhaus C, Vögtlin A. Feline eosinophilic conjunctivitis.
- Vet Ophthalmol. 2001 Mar;4(1):69-74.
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