Chapter 15
Ocular Manifestations of Systemic Disease

When examining a patient for an ophthalmic problem, you must decide whether the lesions found represent purely ocular disease or are part of a generalized systemic problem. After defining the ocular problem, a physical examination is in order especially if the ocular findings are compatible with a systemic disease.

It was not my intention to include every systemic disease in which there are ocular signs; there is abundant literature on this subject (Adcock and Hibler; Aguirre, et al.; Buyukmihci, et al.; Campbell, et al.; Chavkin, et al.; Davidson, et al.; Dukes; Dukes and Lawler; Elkan and Zwart; Johnson, et al.; Keller and Lamarre; Martin, et al.; McDonald, et al.; Paulsen, et al.; Percy, et al.; Ramsey, et al.; Rebhun, et al.; Saunders, et al.; Stephan, et al.; Tate and Rubin). Nor will the diseases listed be described in detail. The purpose of this chapter is to provide highlights of some of the more common diseases. The descriptions for most of the diseases listed come primarily from observations of affected dogs and, sometimes, cats. The general pathological changes in the eyes caused by a particular disease, however, could apply to susceptible individuals of other species. In some cases there are species differences and I have tried to note these.

One way to understand ocular manifestations of systemic disease is to think about what the disease is doing elsewhere in the body, rather than trying to memorize the specific ocular signs. Most of the time, similar changes will occur in the eye.

May have severe, recurrent intraocular hemorrhage, especially retinal. Often, focal (bullous), or sometimes complete, retinal separation may occur. The retinal arterioles may be of various diameters (segmented appearance).

Aspergillosis (Mullaney, et al.)

The primary manifestation is a chorioretinitis. Retinal separation may occur as a result.

Blastomycosis (Buyukmihci; Buyukmihci and Moore)

Initially this begins as a mild granulomatous uveitis or uveoretinitis, but quickly becomes a panophthalmitis with retinal separation and glaucoma.

Problems arise when the dam becomes infected during gestation (especially between days 102 and 183). Abnormalities occur in the fetus and include cataract, focal and diffuse retinal degeneration, acute and chronic optic neuritis, retinal dysplasia, keratitis and microphthalmia.

Anterior uveitis, endophthalmitis and secondary glaucoma.

Hyphema is common. Granulomatous uveitis, retinitis and keratitis have been found in some individuals.

Cryptococcosis (Carlton, et al.)

Optic neuritis, granulomatous chorioretinitis and occasionally retinal separation may occur.

The most common ocular problem is cataract which will occur in virtually all untreated or poorly controlled canine patients . In humans and in some dogs, diabetic retinopathy (micro aneurysms and neovascularization into the vitreous with various sequelae), may occur and result in blindness. Affected cats generally do not develop cataracts.

Because glucose may enter the tears when it exceeds about 175-225 mg/dL in the blood, you often can make the diagnosis of diabetes mellitus by testing the tears. This can be done simply by using a Dextrostix® strip (Ames Co, Elkhart, IN): touch the conjunctiva with the tip until the tip is wet and read as per the directions on the container.

Adult worms occasionally have been found within the anterior chamber . This can cause keratitis and iritis.

Distemper (Fischer; Martin and Kaswan; Sarfaty, et al.)

Conjunctivitis of various degrees is present in almost all affected dogs. The lacrimal gland often is involved causing acute keratoconjunctivitis sicca. The most serious ocular lesions occur in the ocular posterior segment and include optic neuritis and retinitis or retinochoroiditis.

Infected dogs may have hyphema and conjunctival hemorrhage.

Inflammation of the temporal muscles leads to prominent exophthalmos along with eyelid and conjunctival edema in affected dogs.

When the acute disease is over, atrophy may occur and result in prominent enophthalmos.

Uveitis and glaucoma have been reported as sometimes occurring in the syndrome caused by this virus.

Feline infectious peritonitis

This may produce a pyogranulomatous uveitis with retinitis. The ocular lesions usually are seen in the non-effusive form of the disease rather than in the effusive form.

One of the most common ocular manifestations is bilateral iridocyclitis with fibrinous or hemorrhagic exudate into the anterior chamber . Other possibilities include thickening of the uveal tract by cellular infiltration, retinal hemorrhage and infiltration of the extraocular orbital tissue resulting in exophthalmos.

Corneal opacification and gray spots in the retina sometimes are found. These correspond to polysaccharide accumulation in the corneal endothelial cells and fibroblasts, and in the retinal ganglion cells, respectively.

Panuveitis, keratitis, cataract, retinal dysplasia and degeneration, retinoschisis and optic neuritis have been reported. Cats often get corneal ulceration (may be dendritic) and conjunctivitis. This can occur in adults or the young. Uveitis also has been reported. Diagnosis of herpesvirus as a cause of these conditions, however, may not be reliable (Maggs, et al.).

Granulomatous uveitis followed by panophthalmitis sometimes occurs.

Regardless of cause, increase in lipid or lipoprotein content in the blood will result in a pale pink appearance to the blood or serum. When this is observable in the retinal blood vessels, it is termed lipemia retinalis . A break in the vascular integrity in the anterior uvea may lead to escape of lipid into the anterior chamber giving the aqueous a milky appearance . Neither of these conditions is abnormal per se.

When there is hyperviscosity of the blood, regardless of the cause, there sometimes are changes in the ocular fundus. Congestion and tortuosity of retinal blood vessels, retinal hemorrhage and retinal separation can occur.

An anterior uveitis with corneal endothelial damage may occur during recovery from natural infection with street virus or following vaccination with modified live virus . Although this occurs more commonly with natural infection, vaccination has reduced the incidence of natural infection so that most cases are seen following vaccination.

This does not occur frequently enough to warrant discontinuing the vaccination of dogs against hepatitis.

Pathogenesis: First there is a viremia during which virus localizes within corneal endothelium and iris. Iridocyclitis occurs, but often resolves spontaneously without becoming obvious.

If virus remains in the iris and cornea, local antibody production may occur. This antibody reacts with cell-associated viral antigen to produce a hypersensitivity reaction which leads to necrosis and disruption of cells with concomitant inflammation. The corneal endothelial damage leads to corneal edema.

Clinical signs: Usually only one eye is involved. Signs begin in 7 to 28 days after vaccination, but usually by 14 days. The signs are typical of iridocyclitis (miosis, ciliary flush, hypotony, aqueous flare). However, corneal edema is considerably more severe than in the usual case of iridocyclitis and is the reason the disease often is referred to as 'blue eye.'

Treatment and course: Without treatment the course usually is 3-4 weeks. Research has shown that just the use of atropine drops topically may be as effective as the use of any other medication. Atropine provides iridocycloplegia to reduce the pain associated with iridocyclospasm, and mydriasis to reduce the probability of synechiae in the visual axis.

The use of steroids is not encouraged.

Comments: Most cases will spontaneously resolve without permanent damage, but may take several weeks (or sometimes months).

In a few dogs, the inflammation may be severe enough to cause complications which may lead to glaucoma (chamber angle obstruction or closure). For some unknown reason Afghan hounds are more prone to develop glaucoma as a result of this disease than are other breeds. If a patient develops glaucoma, treatment should be instituted immediately.

You may want to delay vaccinating against canine hepatitis until the individual is over six months old because this reduces the incidence of the disease (the patient still should be vaccinated against canine distemper as usual).

Postvaccination reactions usually occur only with the first injection if they are going to occur. Therefore, vaccination boosters are not necessarily contraindicated in a dog who previously had a reaction.

Canine adenovirus type 1 is the virus responsible for the ocular sensitivity and resulting inflammation. This is the virus from which the usual canine hepatitis vaccine is made. Norden Laboratories has developed a canine hepatitis vaccine using canine adenovirus type 2 which reportedly is as effective immunologically, but supposedly does not produce the harmful ocular (and other) effects seen with type 1. It would seem type 2 would be the vaccine of choice. There have been, however, some instances of vaccine reaction with type 2.

Endophthalmitis is the principal ocular abnormality produced by this parasite. Affected patients almost invariably are from Greece or the Middle East region.

This is described in the section on equine recurrent uveitis.

Often produces keratoconjunctivitis which is striking. The resulting corneal edema and thickening may obscure other changes that may be present including iridocyclitis, and retinitis and optic neuritis (the lesions are primarily vascular in both). For some reason, the choroid usually is spared.

Virtually any systemic neoplasm can metastasize to the eye. Some are more prone to do so than others and include lymphosarcoma, transmissible venereal sarcoma (in dogs) and mammary adenocarcinoma. The ocular signs seen depend upon the location of the metastasis and the amount of damage being produced.

This is described in the section on equine recurrent uveitis.

Retinal hemorrhage and separation, along with optic neuritis, have been associated with acute and subacute pancreatitis.

Granulomatous chorioretinitis with retinal separation has been reported. Bloody diarrhea is commonly seen.

Keratoconjunctivitis, iritis, retinal vasculitis, ganglion cell degeneration and optic neuritis may occur. Usually the systemic involvement is not survivable.

Retinal hemorrhage is not uncommon with uremia, and is a sign that death may be imminent. Renal disease may result in hypertension with accompanying signs as mentioned previously.

Septicemia from any cause may produce a variety of ocular inflammatory diseases, especially uveitis. Septic emboli sometimes may be seen lodged in retinal blood vessels.

Migrating larvae sometimes reach the eye and die there. This produces a granulomatous inflammation involving especially the choroid and retina.

Retinochoroiditis is the most prominent lesion produced . Iridocyclitis, optic neuritis and myositis of the extraocular muscles also are seen.