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The eye and systemic disease

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01 February 2015, at 12:00am

Dr DAVID WILLIAMS believes it is always worthwhile examining the eye when faced with a systemic disease as many conditions have ocular signs which can aid in diagnosis and treatment

IT seems to have been Guillaume de Salluste Du Bartas, a 16th century Hugenot courtier and poet, who first penned the words “the eye is the window to the soul” though he was probably not a little influenced by Jesus who tells us in the sermon on the mount that the eye is the lamp of the body: “If your eyes are good then your whole body is good.”

As an ophthalmologist I would certainly agree there! But quite apart from the eye being a window to the soul, whatever that means, the eye can be a useful window on systemic disease in companion animals, the subject of this little offering.

It would be all too easy for this article to be merely a list of diseases and their ophthalmic manifestations – indeed such is given in Table 1, although this cannot hope to be a fully comprehensive treatment of the subject. Here really I want to ask a question to those of you interested in internal medicine and not primarily in ophthalmology: “Why look in the eye?”

Ophthalmoscopy isn’t necessarily the easiest of techniques to master and you could ask why someone who does not have the eye at the top of their priority list should bother examining it at each consultation. I would argue this should without doubt be the case.

Have you ever wanted to examine a vascular plexus in detail to evaluate hypertension, changes with hyperviscocity or whether vasculitis is present? Have you yearned to be able to open up an enlarged lymph node without taking a biopsy and see immediately what is going where an animal presents with a lymphadenopathy?

Have you wondered what it would be like if one could perform a momentary craniotomy and examine the brain of an animal with neurological disease but an owner without sufficient funds for an MRI scan? Then look in the eye!

The iris is the immunological heart of the eye. Inflammatory changes there, be they ever so mild, may well accompany systemic immunological and inflammatory diseases from those as widespread as lymphoma or as apparently localised as pyometritis and, as Figure 1 shows, they could be sitting there staring you in the face if you will look into the eye.

The vascular plexus comprised of the venules and arterioles of the fundus provides an unsurpassed view of vascular changes in hypertension, hyperviscocity syndromes, anaemia and coagulopathies as Figure 2 shows. And the optic nerve head is the only readily visible part of the central nervous system and optic neuritis or papilloedema may be useful indicators of intracranial disease from inflammation to neoplasia you will see in Figure 3.

For sure, not every case of these conditions will have ophthalmic manifestations, but for those that do, ocular examination is a real window not on the soul but on systemic disease in these animals.

Infectious disease

Systemic infectious disease can quite frequently result in ocular inflammatory signs, that is to say uveitis either involving the iris or the choroid.

Feline uveitis is often associated with viral disease, be it feline immunodeficiency virus, feline leukaemia virus or feline infectious peritonitis, although the exact mechanism by which these viral infections cause the ocular lesions is unclear.

Assessing whether there is specific intraocular immune response to the infectious agent is somewhat difficult, requiring antibody titres for both serum and aqueous humour.

A high ratio of these two figures, the Goldmann-Witmer co-efficient or C value, shows that antibody is being produced in the eye itself rather than merely leaking in from systemic production elsewhere.

The difficulty of taking an aqueous sample in an already inflamed eye means that this test is rarely performed – finding an elevated serum antibody titre in an animal with a uveitic eye is usually taken as sufficient evidence for an association.

The situation with canine adenoviral infection and blue eye related to corneal oedema is somewhat different: here it is antibody-antigen complexes which cause an immunological attack against corneal endothelial cells as part of a low-grade uveitis which leads to endothelial dysfunction and corneal oedema.

While unvaccinated and exposed puppies are still seen with this condition, the change in vaccine from one based on CAV-1 to CAV- 2 has prevented the condition seen commonly after vaccination in past decades.

Ocular manifestations of distemper include conjunctivitis and keratoconjunctivitis and also multifocal non-granulomatous chorioretinitis, although the low prevalence of the disease in the UK now means that these signs are very rarely seen.

When a student of mine went to work in Turkey, however, six out of seven cases of distemper she saw there had severe KCS (she will be presenting this as a clinical research abstract poster at BSAVA in April).

From a totally different perspective, feline herpesvirus can give severe conjunctivitis and keratitis as part of the upper respiratory manifestations of the disease or an ulcerative keratoconjunctivitis as a sign of recurrent disease in later life.

In this case the ocular signs are caused by the same sort of necrotic processes that result in severe nasal and oropharyngeal disease.

Here famciclovir (Famvir) given per os can be a useful antiviral agent with ocular and systemic ameliorative effects. There is limited published evidence on this drug but 1/8th or 1/4 of a 125mg tablet per day in kittens and adult cats respectively has shown good effects in our hands.

Bacterial disease either with a systemic condition such as Lyme’s disease caused by the spirochaete Borrelia burgdorferi or a more focal infection such as pyometritis, can both lead to uveitis, probably through breakdown of the blood aqueous barrier but maybe in the former case through presence of the organism in ocular tissue; the pathogenetic mechanism is as yet unclear.

Other bacterial causes of uveitis include brucellosis and leptospirosis as well as mycobacterial species, at least in the cat.

Parasitic and fungal disease

In a similar manner to infectious agents, several protozoal parasites and fungi can lead to intraocular inflammation. Toxoplasma gondii and Ehrlichia as well as a host of fungi from Cryptococcus to Histoplasmosis can give uveitis, most commonly involving the choroid and the serological diagnosis of the precise agent involved can be taking and costly.

Leishmaniosis particularly manifests as periocular alopecia with conjunctivitis, blepharitis, keratitis, secondary keratoconjunctivitis sicca and sometimes uveitis. Up to 80% of dogs with the disease can have ocular manifestations.

Rickettsial diseases have ocular manifestations through coagulopathic effects in canine cyclic thrombocytopaenia or the vasculitis seen in Rocky mountain spotted fever.

On occasion, nematodes such as Angiostrongylus can show themselves in the anterior segment of the eye while visceral larva migrans from Toxocara canis may be noted as areas of postinflammatory retinal degeneration.

We must not forget the rabbit as a species of growing importance in small animal practice. Dacryocystitis is seen associated with dental disease. The protozoan Encephalitozoan cuniculi causes cataract and lens induced uveitis which is best treated either with lens removal by phacoemulsification or with oral fenbendazole.

Hypertension

Cats with sudden blindness, dilated pupils and retinal detachment subsequent to hypertension are not uncommon.

Yet it is difficult to be sure what proportion of hypertensive cats have these ocular manifestations. Cases seen before blindness supervenes may have focal retinal detachment, vascular abnormalities such as “box-carring” where vessels are in turn engorged and constricted, and focal retinal haemorrhages.

Routine fundus examination of older cats and especially those with renal disease or hyperthyroidism will give advanced warning of hypertension and allow treatment with amlodipine.

Fewer hypertensive dogs seem to have ocular changes, although the smaller number of dogs seen with high blood pressure means that these abnormalities may be being missed, as we probably did with cats 20 years ago when hypertensive retinopathy was unheard of.

Other vascular disease

Another cause of retinal haemorrhage can be a systemic coagulopathy, be that warfarin toxicity,

thrombocytopaenia, haemorrhage associated with Angiostrongylus or another clotting disorder. These may also present as subconjunctival haemorrhages and merit a full coagulation work-up.

Hyperviscocity syndrome with diseases such as multiple myeloma can manifest as retinal detachment and haemorrhage, while polycythaemia, reactive or neoplastic, is demonstrated in the retinal vasculature by engorgement of the vessels. Lipaemia is seen as white retinal vessels and anaemia manifests as calibre reduction in retinal vessels and has been reported as causing retinal haemorrhage probably arising through hypoxic change to the vessel walls.

Metabolic, endocrine and neurological disease

Gangliosidoses, lipid storage disorders seen as inherited defects in several pedigree dog breeds, can be manifest as focal white corneal opacities or similar lesions in the retina.

Diabetes mellitus, hyperadrenocorticism and hypothyroidism can result in reduced tear production with corneal lipidosis also seen where circulating hyperlipidaemia occurs, especially in the latter disease.

The classic ocular sign seen with diabetes mellitus is that of a rapidly developing mature cataract in dogs. In fact, diabetic dogs examined ophthalmoscopically earlier in their disease have smaller cataracts characterised by vacuolar change in the lens.

This sudden presentation of a blinding mature cataract can be devastating for dogs and more so their owner. This occurs when there is sufficient glucose in the lens through diabetic hyperglycaemia to overwhelm the glucose-6-phosphatase enzyme which normally metabolises the sugar to carbon dioxide and water.

Once there is such a high level of intralenticular sugar, the enzyme aldose reductase converts it to the alcohol sorbitol. This has a profound osmotic effect, drawing water into the lens. We have shown that inhibiting this enzyme with a dietary supplement such as alpha lipoic acid prevents the formation of these cataracts for as long as the dog is taking the inhibitor daily. (I’ll be presenting this work as a clinical research abstract at 4.50pm on Friday at BSAVA so do come along and hear about it!)

Diabetic cats were previously thought not to develop cataracts, but we have shown that they do, although not with the dramatic complete lens opacities seen in dogs, so not needing prophylactic measures as do their canine counterparts.

With regard to neurological disease, animals with intracranial masses may present with papilloedema, while dogs with granulomatous meningioencephalitis can develop a blinding optic neuritis which resolves with anti-inflammatory treatment treating the more general neurological disease as well.

Neoplasia

Any neoplasm could metastasise to the eye, especially given the considerable vascular networks in the eye. Yet it is in lymphoma where ocular signs can be particularly important in diagnosing and staging disease.

Where iridal swelling is seen with neoplastic nodule formation or a less specific uveitis often with a pronounced hypopyon of neoplastic exuded lymphoblasts, the prognosis for the lymphoma significantly worsens – lymphoma with ocular involvement is classed as grade V disease.

Conclusion

In conclusion, it is always worthwhile examining the eye when confronted with a systemic disease. Many inflammatory, metabolic and neoplastic conditions have ocular signs which can aid in diagnosis and monitoring response to treatment by direct observation of immunological and vascular structures.