Page 34 - VETcpd - Vol 3 - Issue 3

Dr David L Williams MA VetMD PhD CertVOphthal CertWEL FRCVS

David qualifi ed from Cambridge in 1988, aiming to devote his professional life to veterinary ophthalmology. Having worked at the Animal Health Trust and Royal Veterinary College, gaining his CertVOphthal and PhD, he returned to Cambridge, studied for his FRCVS, CertWEL and VetMD and now teaches ophthalmology there as well as exotic animal medicine, animal welfare and ethics.His latest foray into postnomials is a Masters in Education to improve his teaching skills.Fellow and Director of Studies, Veterinary Medicine and PathologySt John’s College, Cambridge CB2 1TPAssociate Lecturer in Veterinary Ophthalmology Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ESTel: 07939074682E: doctordlwilliams@aol.comwww.davidlwilliams.org.uk

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Understanding uveitis in the canine and feline eyeInfl 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

Peer ReviewedVETcpd - Ophthalmology

IntroductionThe classic tetrad of infl ammation is rubor, color, dolor, tumor – redness, heat, pain and swelling. While in the eye these may not appear quite in the same way as a boil on one’s nose or an infl amed appendix, the principles are similar enough. Actu-ally we have functio laesa, loss of function as well which, in the eye, is all important. For intraocular infl ammation is not only painful, it is sight threatening as well, thus making it an important condition to diag-nose rapidly and treat correctly. Redness is where we started and iridocyclitis – infl am-mation of the iris and the ciliary body, is a classic cause of red eye. Another cause is glaucoma, already covered in VetCPD Journal (Williams 2015), but a condition requiring the diametric opposite in the way of treatment to uveitis. Glaucoma has a dilated pupil which needs constricting while uveitis has a constricted pupil which needs dilating. A correct diagnosis of the uveitic red eye is essential not only from the perspective of the eye itself, but also with regard to systemic diseases which may result in uveitis such as generalised infections, infl ammations or even neoplas-tic diseases.

A bit of backgroundAnatomyThe uvea comprises the iris, the ciliary body and the choroid lying posterior to the retina (Figure 1). It consists of a multitude of cell types. There is lymphoid tissue, key in the infl ammatory processes in the eye. There are the muscles in the iris providing constriction of the pupil and its dilation, and in the ciliary body providing tension on the zonule of the lens to facilitate accommodation. It con-tains pigmentary melanocytes and blood vessels all held in a mesenchymal matrix. All these diff erent cell types within the

uveal tissue play their part in giving the panoply of signs that make up the condi-tion uveitis.

Immunology It’s perhaps surprising that the immune cells of the uvea, the antigen presenting cells that recognise that there is a foreign invader and the lymphocytes which respond to that aberrant antigen, have their interaction nowhere near the eye but rather in the spleen.

Perhaps you will remember back to the immunology lessons you had in your undergraduate days. If they were relatively recent, you may have been told of the Th1 and Th2 arms of the immune system. Even if like me, your preclinical lectures were before they had discovered this divergence of lymphocyte populations you will remember that T cells come from the thymus and are involved in the cellular arm of the immune system while the B cells produce antibodies. The T cells then divide themselves into T helper cells and T cytotoxic cells. T helper cells further split themselves into:

• Th1 cells which secrete cytokine chemical messengers such as gamma interferon and interleukin 1 and 2. They encourage cytotoxic T cells to kill any cells which might be infected by viruses.

• Th2 cells produce cytokines like interleukins 4 and 8 which encour-age B cells to proliferate and turn into antibody-producing plasma cells.

Put yourself, if you will, into the shoes of the controller of the ocular immune system. Do you want your cytotoxic lymphocytes to go in all guns blazing and destroy cells left right and centre or would it be better to produce antibodies that fl oat around in the aqueous and vitreous

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VETcpd - Ophthalmology

humours and mop up any invading organ-isms? It’s a no-brainer isn’t it? And that is just what the spleen does.

The camero-splenic axis is a primarily Th2 system. Antigen presenting cells which encounter a foreign antigen 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 eye that reduce the inflammatory response within it. Cells in the anterior chamber produce transforming growth factor beta and this cytokine has an immune-suppressive effect. Additionally, all cells within the anterior chamber express a 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 uveitisSo what processes are going on in a case of uveitis? First lymphocyte proliferation in the eye results in a swollen iris with loss of 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 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).

On a closer look this is seen to be a fine peppering of new blood vessels with an inflammatory sheet over the iris (Figure 3). This reddening of the iris is termed 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 sometimes macrophages too - moving 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-ness between the cornea and the iris. But

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 external to the retina. Between iris and the choroid lies the pas plicata giving rise to the zonule that holds the lens in place, the ciliary body that produces aqueous humour and then the pars plana over which the retina begins. All of these areas of the uvea can be involved in uveitis, with different appearances manifesting with varying areas inflamed. Note that the defect in the lens is an artefact of processing

Figure 2: Heterochromia iridis in a cat with chronic uveitis

Figure 3: The small new blood vessels causing rubeosis iridis (or PIFM) in uveitis

Figure 4: Lymphoid follicles are seen as grey areas in a cat with mild early uveitis

Pars plana

Optic disc

Optic nerve

Retina

Choroid

Ciliary body

Pars plicata

Iris

Limbus

Cornea

Sclera

Lens