The eyeball consists of three basic layers: the outer fibrous layer, consisting of the cornea and the sclera, the inner neuroectodermal layer, made up of the retina and optic nerve, and the intermediate vascular layer, which is composed of the uvea. The uveal tract is an ocular structure anatomically interposed between the scleral and retinal layers. It consists of the iris and ciliary body anteriorly, also called the anterior uvea, and the choroid or posterior uvea posteriorly. The uvea as a whole is responsible for the blood supply to the eye, but the parts making up the anterior portion also help to determine the amount of light entering the eyeball, participate in accommodation and produce the aqueous humor. The anterior uvea is also the site of the blood-aqueous barrier and plays a partial role in ocular refraction. All this explains why inflammation of the anterior uvea (anterior uveitis) is a clinical condition that can cause serious damage to the eye, even to the point of causing loss of vision.
SIGNS
The signs of anterior uveitis that may be found on clinical examination are extremely varied and appear to be independent of the cause of the uveitis. The signs may be found in one eye or both, and they do not necessarily occur concurrently.
Clinical signs that may present to a greater or lesser degree are photophobia and blepharospasm. Photophobia refers to discomfort in the eye induced by exposure to light, while blepharospasm is a disorder that is present regardless of exposure to light. In rare cases these clinical signs may not be particularly obvious. In some subjects, with a higher incidence in anterior uveitis than in posterior uveitis, pain occurs and is manifested by the subject’s tendency to rub the affected eye and, in some cases, by anorexia and depression. Eyelids are usually not affected, unless there is secondary involvement due to self-inflicted trauma or infectious diseases, such as leishmaniasis, or immune-mediated disorders such as the Vogt-Koyanagi-Harada syndrome.
Epiphora, an excessive increase in lachrymation, may be absent or moderate in forms of uveitis involving the posterior segment, and moderate or severe in cases of anterior uveitis. Pain and/or photophobia can cause secondary enophthalmos and then secondary prolapse of the third eyelid.
Conjunctival involvement is present and is manifested by severe hyperaemia. Ciliary flush, i.e. the involvement of the anterior ciliary vessels, may be associated with severe engorgement of the episcleral vessels. There can also be a mild swelling of the conjunctiva, called chemosis.
In the forms that affect the anterior segment, the cornea usually reacts to the inflammatory stimulus by becoming opaque due to stromal oedema; during the course of posterior uveitis, the cornea is only minimally affected by the inflammatory process.
Proteins and cells from the bloodstream may accumulate in the anterior chamber because of the breakdown of the blood-aqueousbarrier secondary to the inflammation. The resulting opacity of the aqueous humor is commonly called flare. The abnormal contents of the anterior chamber can include keratic precipitates (aggregates of inflammatory cells adhered to the corneal endothelium), hypopyon (organized pus) and hyphema (blood).
The iris may appear thickened, inflamed, and veiled due the presence of pre-iris fibro-vascular membranes resulting in rubeosis iridis. Synechiae, or anterior adherences (the iris attached to the cornea) or posterior adherences (iris adhered to the anterior capsule of the crystalline lens) may be seen, and the colour of the iris may be more pigmented, especially in the course of chronic uveitis or neoplastic forms (e.g. diffuse iris melanoma).
In subjects with anterior uveitis the diameter of the pupil is usually reduced (miosis), the pupil barely reacts to light stimulus and the reflex can be slow and incomplete. In chronic forms, the shape of the pupil may be irregular because of the presence of synechiae that cause dyscoria.
The intraocular pressure is usually reduced, except in cases in which there is glaucoma secondary to the inflammatory process, which results in increased pressure. The results of Schirmer's test are usually within the norm, but may be increased because of increased lachrymation associated with the inflammation. The fluorescein test gives normal results if the inflammatory phenomenon is not secondary or does not cause corneal ulcerative lesions. Subjects with anterior uveitis can have secondary vitreous involvement with opacity and haemorrhages (pars planitis and anterior vitritis). A cataract is a common consequence of uveitis or a triggering factor (phacolytic uveitis and phacoclastic uveitis) (Fig. 1).
AETIOLOGY
Numerous factors can cause uveitis. These factors have been classified as follows: infectious, immune-mediated, idiopathic, metabolic, toxic, traumatic, neoplastic and paraneoplastic.
In dogs, infectious/infestant anterior uveitis can be attributed to the following causes: viruses (Adenovirus, Paramyxovirus and Herpesvirus); bacteria (Brucella, Leptospira, Bartonella, Borrelia, spread from any septic foci in other regions); algae (protothecosis), fungi (aspergillosis, blastomycosis, candidiasis, cryptococcosis, coccidioidomycosis, histoplasmosis); parasites (migrant larvae of Angiostrongylus, Dirofilaria, Toxocara, Diptera); protozoa (Leishmania, Toxoplasma, Neospora; Trypanosoma); rickettsial infections and ehrlichiosis. The immune-mediated forms are represented by lens-induced uveitis (phacoclastic and phacolytic), uveo-dermatological syndrome or Vogt-Koyanagi-Harada disease, thrombocytopenia and vasculitis. Anterior uveitis may be idiopathic, due to trauma (sharp or blunt trauma and the presence of foreign bodies of various kinds), and secondary to other ocular diseases (keratitis, necrotising scleritis) and to many primary tumours (melanoma) and metastatic tumours (lymphosarcoma) of the anterior segment (Fig. 2).
In cats, the infectious/infesting causes of anterior uveitis are viruses: Coronavirus (infectious peritonitis virus), Feline leukaemia
virus, Feline immunodeficiency virus and Herpesvirus; and bacteria such as Bartonella and the tuberculosis mycobacterium, as well as all septic forms that can reach the anterior uvea metastatically from any other district. Theprotozoan forms, besides toxoplasmosis, include leishmaniasis, which has recently been recognized as a cause of anterior uveitis in this species. The fungal forms include aspergillosis, blastomycosis, candidiasis, cryptococcosis and histoplasmosis. The parasitic forms include Diptera, Toxocara and Cuterebra. As in dogs, anterior uveitis in cats may also be idiopathic, caused by trauma or be secondary to other eye diseases and to many primary neoplasms (diffuse iris melanoma, sarcoma) and metastatic cancers (lymphosarcoma) of the anterior segment. There are also some forms of vasculitis with an immune-mediated origin which may cause anterior uveitis in cats (Fig. 3).
Causes of anterior uveitis common to both species are the toxic forms, related to the topical administration of drugs, especially miotic agents such as pilocarpine, carbachol and prostaglandin derivatives. Radiation therapy near to the eye can cause secondary inflammation. In dogs, metabolic diseases, such as diabetes mellitus, may contribute to anterior uveitis and other associated causes include systemic hypertension, coagulopathies and hyperlipidaemia. In cats, systemic hypertension, and coagulopathies are causes of uveitis.
DIAGNOSIS
For a proper diagnosis, a complete ophthalmologic examination must be performed, in order to be able to make a differential diagnosis from other causes of red eye such as conjunctivitis, keratitis, and glaucoma. The examination should include careful observation of the individual anatomical ocular structures. The visual function of the animal must be tested by assessing the menace response, performing the cotton swab test, the visual placement test and the obstacle test. In the course of uveitis, vision may be normal, partially impaired or completely absent, depending on whether the uveitis is anterior or posterior and on any lesions caused by the inflammation. In general, anterior uveitis causes blindness less frequently than posterior uveitis, except in cases in which a massive inflammatory reaction causes opacity of the dioptric structures such as the cornea, aqueous humor and vitreous humor. Posterior uveitis, which involves extremely delicate structures (the choroid and the retina) that are essential for vision, is more often the cause of temporary or permanent blindness. It is, therefore, necessary to assess the presence of epiphora, photophobia, and blepharospasm, check the condition of the eyelids, the nictitating membrane, conjunctiva, cornea, anterior chamber and the iris, and carefully evaluate the diameter of the pupils and pupillary reflexes. The examination is completed by assessment of the vitreous humor and ocular fundus.
Additional tests which must be performed during the examination are the measurement of intraocular pressure, which usually turns out to be reduced, Schirmer's test, which is likely to show high values due to increased tear production, and the fluorescein test, which can be positive when there are ulcerative lesions of the cornea. Since uveitis is often a sign of a systemic disease, comprehensive laboratory tests on blood and urine samples are essential to identify any underlying cause. Ultrasonography and radiography will complete the range of instrumental investigations.
TREATMENT
Treatment is based on local and systemic administration of drugs and it may be causal and/or symptomatic. As far as concerns topical symptomatic treatment, it is essential to use mydriatics and cycloplegics such as atropine 1% and tropicamide, because the inflammation occurring during anterior uveitis causes miosis as a result of the spasm of the ciliary muscles. This leads to severe pain, which should be relieved to prevent the possibility of self-inflicted trauma. Cycloplegics must be used not only to produce mydriasis, which prevents the onset of synechiae (one of the most common complications in the course of anterior uveitis), but also to control pain.
In cases of particularly obvious pain, systemic analgesics can also be administered, such as butorphanol, morphine or tramadol. Topical corticosteroids, such as dexamethasone 0.1% or prednisolone 1%, in combination or not with antibiotics, may be used to reduce inflammation. Prednisone, a systemic corticosteroid, at a dose of 0.5-1 mg/kg/day is important for the control of inflammation in general and uveitis of immune-mediated origin in particular, in which case it is used at a higher dose. In these forms other immunosuppressive agents can also be given, such as azathioprine 0.5-1-2 mg/kg/day and cyclosporine 5 mg/kg/day. Non-steroidal anti-inflammatory drugs are frequently an alternative to corticosteroids. Piroxicam 0.5%, diclofenac 0.1%, flurbiprofen 0.03%, indomethacin 0.1% and ketorolac 0.5% can be used topically, whereas carprofen 4mg/kg/day, tolfenamic acid and flunixin meglumine are recommended for systemic use.
Systemic antibiotic treatment can be used against specific aetiological agents or as prophylaxis against secondary bacterial infections. The combination of amoxicillin and clavulanic acid, cephalosporins, or chloramphenicol can be used for this purpose. Causal treatment implies the use of antibiotics, parasiticides, antifungal medications or other drugs specific for the aetiology of the anterior uveitis. For example, the drugs most commonly used for targeted therapy are antimonials in combination with allopurinol to treat Leishmania and doxycycline to treat rickettsial infections.
Suggested readings
- Gwin RM. Anterior uveitis: diagnosis and treatment.Semin Vet Med Surg (Small Anim). 1988 Feb;3(1):33-9
- Peiffer RL Jr, Wilcock BP. Histopathologic study of uveitis in cats: 139 cases (1978-1988).
- J Am Vet Med Assoc. 1991 Jan 1;198(1):135-8.
- Wilcock BP, Peiffer RL Jr.The pathology of lens-induced uveitis in dogs.Vet Pathol. 1987 Nov;24(6):549-53.
- Massa KL, Gilger BC, Miller TL, Davidson MG. Causes of uveitis in dogs: 102 cases (1989-2000).Vet Ophthalmol.2002 Jun;5(2):93-8.
- Slatter D. Disease and surgery of the canine anterior uvea. In Slatter D, ed. Fundamentals of Veterinary Ophthalmology. 4rd ed. Philadelphia: Saunders WB, 2007: 812-858.
- Slatter D. Feline ophthalmology. In: Slatter D, ed. Fundamentals of Veterinary Ophthalmology. 4rd ed. Philadelphia: Saunders WB, 2007: 1117-1124.