VETcpd - Ophthalmology Peer Reviewed Understanding uveitis in the canine and feline eye Infl ammation within the eye can be a diffi cult condition to diagnose and treat. It often presents as a red eye and the key differential here is glaucoma, needing diametrically opposed treatment. The causes of feline uveitis are often infectious with viral diseases giving ocular infl ammation, while in the dog idiopathic immune-mediated disease, lens induced uveitis or conditions such as Vogt-Koyanagi-Harada-like syndrome are more commonly seen. Treatment involves anti-infl ammatory medication – topical or systemic, and pupil dilation with atropine which also reduces pain by countering ciliary muscle spasm.

Key words: uveitis, intraocular infl ammation, iritis, choroiditis, eye, atropine, steroid

Introduction uveal tissue play their part in giving the The classic tetrad of infl ammation is rubor, panoply of signs that make up the condi- color, dolor, tumor – redness, heat, pain tion uveitis. and swelling. While in the eye these may Immunology not appear quite in the same way as a boil Dr David L Williams MA It’s perhaps surprising that the immune on one’s nose or an infl amed appendix, cells of the uvea, the antigen presenting VetMD PhD CertVOphthal the principles are similar enough. Actu- cells that recognise that there is a foreign CertWEL FRCVS ally we have functio laesa, loss of function invader and the lymphocytes which as well which, in the eye, is all important. respond to that aberrant antigen, have David qualifi ed from Cambridge in For intraocular infl ammation is not only 1988, aiming to devote his professional their interaction nowhere near the eye but painful, it is sight threatening as well, thus rather in the spleen. life to veterinary ophthalmology. making it an important condition to diag- Having worked at the Animal Health nose rapidly and treat correctly. Redness is Perhaps you will remember back to the Trust and Royal Veterinary College, where we started and iridocyclitis – infl am- immunology lessons you had in your gaining his CertVOphthal and PhD, he mation of the iris and the ciliary body, is undergraduate days. If they were relatively returned to Cambridge, studied for his a classic cause of red eye. Another cause recent, you may have been told of the FRCVS, CertWEL and VetMD and now Th1 and Th2 arms of the immune system. teaches ophthalmology there as well as is glaucoma, already covered in VetCPD Even if like me, your preclinical lectures exotic animal medicine, animal welfare Journal (Williams 2015), but a condition and ethics. requiring the diametric opposite in the were before they had discovered this way of treatment to uveitis. Glaucoma has divergence of lymphocyte populations His latest foray into postnomials is a you will remember that T cells come from Masters in Education to improve his a dilated pupil which needs constricting teaching skills. while uveitis has a constricted pupil which the thymus and are involved in the cellular needs dilating. A correct diagnosis of the arm of the immune system while the B Fellow and Director of Studies, cells produce antibodies. The T cells then Veterinary Medicine and Pathology uveitic red eye is essential not only from divide themselves into T helper cells and T St John’s College, Cambridge CB2 1TP the perspective of the eye itself, but also with regard to systemic diseases which cytotoxic cells. T helper cells further split Associate Lecturer in Veterinary may result in uveitis such as generalised themselves into: Ophthalmology Department of Veterinary Medicine, Madingley Road, infections, infl ammations or even neoplas- • Th1 cells which secrete cytokine Cambridge CB3 0ES tic diseases. chemical messengers such as gamma Tel: 07939074682 interferon and interleukin 1 and 2. A bit of background They encourage cytotoxic T cells to E: [email protected] Anatomy kill any cells which might be infected www.davidlwilliams.org.uk The uvea comprises the iris, the ciliary by viruses. body and the choroid lying posterior • Th2 cells produce cytokines like to the retina (Figure 1). It consists of a interleukins 4 and 8 which encour- multitude of cell types. There is lymphoid age B cells to proliferate and turn into tissue, key in the infl ammatory processes antibody-producing plasma cells. in the eye. There are the muscles in the iris providing constriction of the pupil Put yourself, if you will, into the shoes and its dilation, and in the ciliary body of the controller of the ocular immune providing tension on the zonule of the system. Do you want your cytotoxic lens to facilitate accommodation. It con- lymphocytes to go in all guns blazing and tains pigmentary melanocytes and blood destroy cells left right and centre or would For Ophthalmology Referrals in vessels all held in a mesenchymal matrix. it be better to produce antibodies that your area: vetindex.co.uk/eyes All these diff erent cell types within the fl oat around in the aqueous and vitreous

Page 34 - VETcpd - Vol 3 - Issue 3 VETcpd - Ophthalmology humours and mop up any invading organ- isms? It’s a no-brainer isn’t it? And that is Cornea just what the spleen does. Limbus The camero-splenic axis is a primarily Th2 system. Antigen presenting cells which encounter a foreign antigen Sclera Iris migrate through the blood stream to the spleen and then interact with T lympho- cytes which are encouraged to become a Th2 lineage and travel back to the eye where they stimulate antibody production. There are in addition, other features of the Pars plicata eye that reduce the inflammatory response Lens within it. Cells in the anterior chamber produce transforming growth factor Ciliary body beta and this cytokine has an immune- suppressive effect. Additionally, all cells within the anterior chamber express a Pars plana molecule called Fas-L, the Fas ligand. When cells expressing Fas encounter these Fas-L molecules they quietly apoptose (commit cell suicide). And since lympho- cytes are Fas expressing most of them die before creating an inflammatory response, which would severely compromise the key function of the eye - sight.

Recognising anterior uveitis Choroid So what processes are going on in a case of uveitis? First lymphocyte proliferation in Retina the eye results in a swollen iris with loss of Optic disc the clear architecture of the crypts on its surface. This cell proliferation uses oxygen and the iris becomes somewhat ischae- mic, leading to formation of angiogenic cytokines such as vascular endothelial Optic nerve growth factor. This in turn leads to new blood vessel growth which can be seen on first glance as a change of colour of the iris – heterochromia iridis (Figure 2). Figure 1: The anatomy of the canine eye: The sclera posteriorly and the cornea anteriorly make up the outer coat of the eye. Inside that lies the uvea consisting of the iris anteriorly and the choroid posteriorly On a closer look this is seen to be a fine external to the retina. Between iris and the choroid lies the pas plicata giving rise to the zonule that holds peppering of new blood vessels with an the lens in place, the ciliary body that produces aqueous humour and then the pars plana over which inflammatory sheet over the iris (Figure the retina begins. All of these areas of the uvea can be involved in uveitis, with different appearances 3). This reddening of the iris is termed manifesting with varying areas inflamed. Note that the defect in the lens is an artefact of processing rubeosis iridis or preiridal fibrovascular membrane (PIFM). At the same time the lymphocytes are forming little lymphoid follicles in the iris (Figure 4). A bit more inflammation leads to cells - mostly lymphocytes but Figure 2: Heterochromia iridis in a cat with sometimes macrophages too - moving chronic uveitis out of the iris to float around the anterior chamber. This, together with fibrin which leaks out of the blood vessels as prosta- glandins, cause breakdown of the blood aqueous barrier, giving rise to what we call aqueous flare. If you shine a fine beam from a pen torch - or better still a Finhoff transilluminator - through a normal anterior chamber there should be black- Figure 3: The small new blood vessels causing Figure 4: Lymphoid follicles are seen as grey ness between the cornea and the iris. But rubeosis iridis (or PIFM) in uveitis areas in a cat with mild early uveitis

Full article available for purchase at www.vetcpd.co.uk/modules/ VETcpd - Vol 3 - Issue 3 - Page 35