Introduction

Visceral leishmaniasis is a parasitic infection caused by protozoa of the Leishmania donovani species complex and is transmitted by sand flies. It is a disease of human beings and animals. Dogs are considered the main reservoir. The disease has a worldwide distribution. Leishmania infantum is the causative agent of the Old World canine leishmaniasis. The disease has been reported around the Mediterranean Basin, Southern Europe, West, East and North Africa, the Middle East, India and China. Leishmania chagazi, considered now as synonymous with L. infantum is responsible for the disease in the New World (South America). More and more foci are reported outside the conventional endemic areas and recently canine leishmaniasis (CanL) was identified in North America. Clinical features of the disease vary widely. It is very important for clinicians to know and recognise early ocular manifestations of leishmaniasis not only to avoid the development of irreversible lesions leading to blindness but also to initiate systemic anti-leishmanial treatment. Ocular lesions can appear independently from systemic signs, or can be combined with, before or after anti-leishmanial therapy. Any ocular tissue or adnexa can be involved, but blepharitis, conjunctivitis, keratitis and anterior uveitis are the most frequent lesions.

Diagnosis

The diagnosis of ocular manifestations of CanL is based on clinical findings, parasitological techniques, serological tests and more recently using molecular methods.

Clinical signs

 Eyelids. Periocular alopecia with desquamation is a characteristic feature of the disease .A differential diagnosis should be made with the same type of lesion caused by demodex. Sometimes these two causes are seen together. Pemphigus is another cause to be considered in differential diagnosis. In rare cases, multiple granulomas can be observed on eyelids margins. These granulomas contain a great density of parasites. They are considered as typical signs of the infection and could represent the site of vector bites.

 Conjunctiva, Sclera and Nictitating Membrane. Conjunctival hyperemia is a common finding in ocular leishmaniasis. Classical conjunctival alteration is chemosis. Sometimes the very prominent conjunctival thickening precedes an anterior uveitis. Deep inflammation reaches the scleral layer. Multifocal pink granulomas can appear on nictitating membrane margins or at the limbus. In these cases, a differential diagnosis with nodular episclerokeratitis, using cytology and parasite visualisation, should be considered.

 Cornea. Corneal involvement is rarely seen independently. More often concurrent inflammation of the conjunctiva (kerato-conjunctivitis) or anterior uvea (kerato- uveitis) are present. Keratitis can be superficial with epithelial erosions, ulcers, neovascularization and eventually pigmentation (not to be confused with the so called "German Shepherd chronic superficial keratitis"). Large limbal conjunctival granulomas can extend to the cornea. Interstitial keratitis is characterized by focal opacities (edema or inflammatory cells infiltrate).Deep keratitis with vessel growth and endothelial alterations is secondary to anterior uveitis.

 Anterior uvea. In our series, in an endemic area, 70% of cases of anterior uveitis in dogs are caused by CanL. In a previous cytological study, we demonstrated that in most of the cases, there is a predilection for anterior segment inflammation. Granulomatous or plastic types of anterior uveitis can be seen but anterior chamber exudation is not a frequent tendency of CanL. It is in CanL that anterior uveitis is often associated with very low antibody titres and response to anti-leishmanial therapy is very poor.

 Posterior segment. In our series, only 9% of CanL ocular signs involve the posterior segment. In case of anterior segment loss of transparency, Ultrasound or ERG can be useful to evaluate the posterior segment situation. Hyalitis, chorioretinitis, papillitis, mall retinal hemorrhages and retinal detachment have been seen. Frequently, chorioretinal abnormalities appear to be secondary to an other organ involvement (e.g., renal insufficiency).

 Infrequent signs. They include: corneal dystrophies, exophthalmos, strabismus. In endemic areas, when they are observed, CanL should be considered as a possible cause. Large haemorrhages (in anterior chamber or vitreous) are not found in CanL.

 Complications. The most severe complication is glaucoma secondary to anterior uveitis.(the cause of 10% of the cases of blindness in our survey ).At present, all treatments are ineffective. The other observed complications are KCS, corneal pigmentation, iris atrophy, cataract, retinal detachment, panophthalmitis and phtisis bulbi.

Parasitological techniques

Leishmania amastigote can be observed from lymph nodes, bone marrow smears or from ocular tissue. The sensitivity of the technique is low except for smears from granulomas which always reveal a large number of parasites. Cultures and inoculation take too long for practical purposes.

Serological tests

The Indirect Immunofluorescent Antibody Test (IFAT) and Enzyme Linked Immunosorbent Assay (ELISA) are techniques used worldwide. The Direct Agglutination Test is also a good tool under field conditions. If available, the Western Blot technique is more sensitive and suitable for diagnosis of ocular forms.

Molecular techniques

If serological techniques are able to demonstrate a previous contact with the organism, Polymerase Chain Reaction (PCR) is able to detect, by amplification, a very small quantity of leishmania DNA in tissues. In a recent comparative study on the results of IFAT, Western Blot and PCR it was noted that , in an endemic area, 38% of dogs with an ocular inflammation are IFAT seronegative but PCR and Western blot positive and that 68 % of asymptomatic and IFAT negative dogs are Western blot positive and 59% PCR positive.

Treatment

As a rule, ocular inflammation must be treated aggressively to avoid complications. Adnexal signs respond well to anti-leishmanial therapy. This is not always the case for deeper inflammation. Priority however should be given to control ocular inflammation. Topical and subconjunctival corticosteroids are used to treat keratoconjunctivitis but intra-ocular inflammation requires the use of systemic anti-inflammatory drugs.

When uveitis is diagnosed, the classical treatment for anterior uveitis should be applied namely: Atropine, topical and subconjunctival corticosteroids (SAIDS). Intra-ocular inflammation requires the use of systemic anti inflammatory drugs. It is advisable to begin with injections of Non Steroidal Anti Inflammatory Drugs (NSAIDS). These are administered as a long term therapy. If not effective enough, a low dose corticosteroid (prednisolone: 0,16 mg/kg) is added to NSAIDS. If the uveitis is still unresponsive, a systemic cyclosporine (10-5 mg/kg) treatment should be initiated. Topical use of cyclosporine is ineffective against intra-ocular leishmanial inflammation. The goal is to control inflammation before synechiae occur.

Personal protocols

Leishmanial Ocular Inflammation Treatment

 Ocular inflammation alone: Dog seronegative or low antibody titer:

 Systemic Allopurinol

 Systemic NSAIDS

 Local anti inflammatory treatment

 Ocular inflammation + other organs involvement :Dog seropositive

 Systemic Allopurinol+ Methylglucamine

 Systemic NSAIDS

 Local anti inflammatory treatment

Uveitis Treatment. Personal protocol

 Local treatment:

 Atropine

 Corticosteroids drops

 Corticosteroids subconjunctival injection (watch out for post injection granulomas)

 Systemic Anti inflammatory Treatment:

 NSAIDS (see Text on "uveitis")

 NSAIDS + SAIDS

 Cyclosporine