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Original Article Equine recurrent uveitis: A clinical manifestation of leptospirosis L. Frellstedt Marion DuPont Scott Equine Medical Center, Virginia-Maryland Regional College of Veterinary Medicine, 17690 Old Waterford Road, PO Box 1938, Leesburg, Virginia 20177, USA.

Keywords: horse; Leptospira spp., leptospirosis; equine recurrent uveitis

Summary appear to be involved in the aetiology of ERU predisposing certain breeds (Appaloosas, some Warmbloods) and even Leptospirosis is a zoonosis of worldwide distribution some individuals of these breeds with certain coat and affecting domestic animals, wildlife and man. The colour patterns. A recent report showed that MHC class I bacterial disease is caused by pathogenic Leptospira haplotype-A9 is associated with ERU in German spp., which are transmitted from reservoir hosts to Warmblood horses (Deeg et al. 2004a). The equine MHC is accidental hosts. Horses are accidental hosts and can also believed to explain the susceptibility to ERU of become susceptible to leptospiral infections. Widespread Appaloosas (Dwyer and Gilger 2005), which are more exposure to leptospires exists and is significantly more frequently and often more severely affected than other common than clinical disease. breeds (Dwyer et al. 1995). ERU most commonly manifests Leptospirosis can have different clinical manifestations as anterior uveitis but posterior uveitis and panuveitis are including abortion, still birth, systemic disease with hepatic also seen depending on the main location of the or renal dysfunction, and equine recurrent uveitis (ERU). intraocular inflammation. The differences in the clinical ERU is the most frequently encountered clinical appearance of ERU may also indicate that there are manifestation and this article will focus on the review of different diseases or initiating factors involved. This review leptospira-associated ERU. will focus on the relationship between ERU and Equine recurrent uveitis is the most common cause of leptospirosis. vision impairment and blindness in horses. The Leptospirosis is a zoonosis of ubiquitous distribution pathogenesis of leptospira-associated ERU involves direct affecting domestic animals, wildlife and man. It is a bacterial bacterial effects and immune-mediated responses. disease caused by infection with pathogenic Leptospira Clinical signs vary between the acute and chronic phases spp. Due to the nonspecific nature of clinical signs of the disease and progress over time. The diagnosis of attributable to the disease, leptospirosis may occur more leptospira-associated ERU can be difficult and usually frequently than is actually diagnosed (Hogan et al. 1996). requires a combination of diagnostic tests. Medical and Leptospirosis was first recognised and reported in man surgical treatments have been described with varying by Adolf Weil in 1886 (Weil 1886). In 1915, the aetiology of outcomes. The prognosis for sight is usually poor, although the disease was demonstrated independently by core vitrectomy may improve the outcome. Avoidance of researchers in Japan and Germany (Kobayashi 2001; leptospiral exposure of horses is the only reliable Levett 2001). Subsequently, leptospirosis was recognised in prevention of leptospira-associated disease. dogs and livestock (Alston and Broom 1958). Naturally occurring leptospirosis in horses was first reported in Russia Introduction (Lubashenko and Novikova 1947). Equine recurrent uveitis and abortion are the most common clinical manifestations Equine recurrent uveitis (ERU) is a major ophthalmic disease of leptospirosis in horses, although renal and hepatic and the most common cause of blindness in horses. Uveitis diseases have also been reported. can be induced by many infectious (bacterial, viral, protozoal or parasitic) and noninfectious (trauma, Aetiology neoplasia, immune-mediated) disease processes. Recurrent episodes usually result from dysregulated Leptospires are the smallest spirochete bacteria (0.1 µm in immune responses within the eye. Genetic factors also width x 6–30 µm in length). The organisms are flexible, EVE 08-122 Frellstedt_Layout 1 15/09/2009 12:43 Page 3

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tightly coiled, unicellular bacteria with pointed ends, Icterohaemorrhagiae) that transmit the bacteria to which are bent into distinctive hooks. Stimson first accidental hosts, which are not typical carriers of the described the causative organism in 1907 (Stimson 1907). disease but can become susceptible to leptospiral Due to its appearance with hooked ends and the infection. The organisms multiply in the kidneys of the resemblance to a question mark the organism was adapted hosts and are shed in the urine. The organism is named Spirochaeta interrogans. Leptospires are motile, believed to be transmitted through direct contact with Gram-negative bacteria that are difficult to stain. Like all blood, urine, placental fluids and tissues of affected spirochetes, they have a typical double membrane animals or indirect contact via contaminated water or structure consisting of a cytoplasmic membrane and feed. Leptospires enter the accidental host through peptidoglycan cell wall that are closely associated and mucous membranes or skin abrasions (Thiermann 1984; surrounded by an outer membrane. As in other Gram- Timoney et al. 1988). negative bacteria, lipopolysaccharide molecules and Horses are accidental hosts and usually become lipoproteins (outer membrane proteins [OMPs]) are exposed to Leptospira spp. when they consume associated with the outer membrane. Leptospiral contaminated groundwater that contains urine shed from lipopolysaccharides are similar in their composition to a host-adapted species. Leptospires then penetrate those of other Gram-negative bacteria but have much mucous membranes and abraded skin, and rapidly gain lower endotoxic activity (Haake 2000). The access to the vascular space. This is followed by lipopolysaccharides are highly immunogenic and bacteraemia, which persists for about 8 days and is responsible for serovar specificity. An inverse relationship characterised by high fevers (39–41°C) 7–9 days after the between expression of transmembrane OMPs and initial exposure (Morter et al. 1964, 1969). The second virulence was demonstrated in serovar Grippotyphosa phase is known as the immune phase and is characterised (Haake et al. 1991). by the disappearance of the organism from the Two separate systems of classification are used for bloodstream and appearance of antibodies (Levett 2001). organisms within the genus Leptospira (Levett 2001; Hines Leptospiral antibodies are first detectable in serum 2007). The traditional phenotypic classification based on 4–8 days after exposure (Morter et al. 1964, 1969) and may serotyping has been widely used and groups leptospires be maintained for at least 7 years (Roberts 1958; Swart into 2 species, the pathogenic species Leptospira et al. 1982). Most of the complications of leptospirosis are interrogans and the nonpathogenic, saprophytic species associated with localisation of leptospires within immune Leptospira biflexa (Levett 2001; Hines 2007). Within each privileged sites such as the placenta, renal tubules, and species, serovars are organised into serogroups based on anterior and posterior chambers of the eyes during the shared antigenicity. Over 200 serovars of L. interrogans are immune phase. Infected horses may shed pathogenic recognised and organised into 23 serogroups. L. biflexa leptospires in the urine for up to 4–5 months (Morter et al. contains 60 serovars organised into 28 serogroups. 1964; Bernard et al. 1993). The second system of classification is a genotypic The most common isolates associated with equine classification based on DNA homology that has been disease are species within the Leptospira interrogans developed in recent years (Levett 2001; Hines 2007). The serogroup Pomona in North and South America (Hall and genotypic classification does not correspond to the Bryans 1954; Roberts 1969; Sillerud et al. 1987; Divers et al. serological classification. The reclassification of leptospires 1992; Giles et al. 1993; Poonacha et al. 1993; Dwyer et al. based on their genotype is taxonomically correct but not 1995; Hogan et al. 1996; Frazer 1999; Faber et al. 2000), and clinically useful. Many diagnostic laboratories have species within Leptospira kirchneri serovar Grippotyphosa retained the serological classification of pathogenic in Europe (Ellis et al. 1983; Wollanke et al. 2001). In North leptospires until simpler molecular identification methods America, Leptospira interrogans serogroup Pomona become available. serovar Kennewicki also referred to as Leptospira Leptospirosis is thought to be the most widespread interrogans serovar Kennewicki is the most common zoonosis in the world (Sperber and Schleupner 1989). The leptospiral isolate (Thiermann et al. 1985; Donahue and disease appears to be endemic in certain geographical Williams 2000). areas due to favourable environmental conditions, which Leptospira interrogans serovar Kennewicki is believed include a mild climate and high precipitation (tropical to be transmitted by skunks (Carpio et al. 1977; Ellis 1999), climate). High periods of precipitation increase the although it is also hypothesised that horses maintain and exposure to leptospires by releasing the leptospires from transmit Leptospira interrogans serovar Kennewicki among the soil and bringing them to the surface in standing water themselves (J.M. Donahue and J.F. Timoney, personal or even floods. Other risk factors that predispose horses to communication 2007). This leads to the assumption that infection with leptospires are a high population density Leptospira interrogans serovar Kennewicki is not always and an increased exposure to wildlife and rodents pathogenic and will be easily eliminated from the body in (Barwick et al. 1997). healthy animals, but will cause an infection in stressed or Leptospires rely on reservoir hosts (i.e. raccoons for immunosuppressed animals (J.M. Donahue, personal serovar Grippotyphosa, rats and mice for serovar communication 2007). EVE 08-122 Frellstedt_Layout 1 15/09/2009 12:43 Page 4

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Seroprevalence Equine recurrent uveitis

Serological surveys to assess prevalence of antibody to Equine recurrent uveitis, also known as periodic leptospiral organisms have been performed in horses. These ophthalmia or moon blindness, is an inflammatory disease studies confirm that there is widespread exposure to of all parts of the uvea that can affect one or both eyes. leptospira worldwide and that exposure is significantly more ERU is the most common cause for impaired vision and common than clinical disease. Seroprevalence in horses blindness in horses with a prevalence of 7.6–8.3% varies from 1–95% depending on the geographic location (Errington 1941; Szemes and Gerhard 2000). The recurrent and the serovars examined (Cole and Pursell 1973; Smith episodes of acute uveitis are separated by quiescent et al. 1976; Carpio et al. 1977; Hathaway et al. 1981; Slatter periods of variable duration (Cook and Harling 1983). and Hawkins 1982; Swart et al. 1982; Egan and Yearsley Each attack is associated with progression of irreversible 1986; Kitson-Piggot and Prescott 1987; Lees and Gale 1994; ocular pathology. The extent of damage depends on the Rocha et al. 2004). Titres to the following serovars are most severity and duration of the acute uveitic attack, and common: Icterohemorrhagica, Bratislava, Pomona and the promptness and effectiveness of therapy (Fruhauf Grippotyphosa (Cole and Pursell 1973; Smith et al. 1976; et al. 1998). Carpio et al. 1977; Slatter and Hawkins 1982; Swart et al. A correlation between chronic uveitis and leptospiral 1982; Egan and Yearsley 1986; Kitson-Piggot and Prescott infection was initially suggested by Rimpau (1947). Several 1987; Schoenberg et al. 1987; Lees and Gale 1994). The high studies have demonstrated the presence of high titres of seroprevalence of serovar Bratislava without presence of leptospiral agglutinins in the blood of horses suffering from disease in multiple studies in Europe and Canada leads to recurrent uveitis (Halliwell et al. 1985; Dwyer et al. 1995; the assumption that horses are maintenance hosts for this Brem et al. 1998, 1999; Faber et al. 2000; Wollanke et al. specific serovar in the described areas. 2001; Hartskeel et al. 2004). The presence of antibodies against leptospires in Clinical findings ocular fluids from horses with ERU has been consistently described in 70–94% of affected eyes examined in Leptospirosis can have different clinical manifestations in Germany (Halliwell et al. 1985; Brem et al. 1998, 1999; horses. Abortions, still birth, systemic disease with hepatic or Wollanke et al. 2001; Hartskeel et al. 2004; Brandes et al. renal dysfunction, and ERU are most commonly reported. 2007) but in only 25% of affected eyes in a recent study in Leptospira spp. have been reported as a significant the southeastern USA (Gilger et al. 2008). Researchers cause of abortion, still birth, perinatal death and have also isolated leptospiral organisms from ocular fluids placentitis in horses in Kentucky, Northern Ireland and in up to 75% of horses suffering from ERU (Brem et al. 1998, England (Donahue and Williams 2000). In Kentucky it has 1999; Faber et al. 2000; Wollanke et al. 2001; Wollanke been recognised to be the third most common bacterial 2002; Hartskeel et al. 2004; Brandes et al. 2007). Faber and cause of abortion (Giles et al. 1993) with a reported Brandes confirmed leptospiral DNA by use of PCR in 70% of prevalence of 2.5–4.4% (Donahue et al. 1991, 1992, 1995). eyes examined from horses with ERU in the western USA A higher prevalence of 40% was identified in Ireland (Ellis (Faber et al. 2000) and 100% of eyes examined from horses et al. 1983). The most common isolate were leptospires in with ERU in Germany (Brandes et al. 2007). These results the serogroup Pomona, identified as serovar Kennewicki suggest that there are differences in disease prevalence (Donahue et al. 1991, 1992, 1995). Serovar Grippotyphosa and its association with leptospirosis between different is less commonly reported. geographic regions. It appears that leptospirosis is an Systemic disease due to leptospirosis occurs important factor in the aetiogenesis of ERU in central infrequently in the equine population. Reports of Europe. In European studies, serovar Grippotyphosa (Brem leptospirosis in adult horses have possible association with et al. 1998, 1999; Wollanke et al. 2001; Wollanke 2002; fever, anorexia, and lethargy (Hall and Bryans 1954; Hartskeel et al. 2004; Brandes et al. 2007) is the most Halliwell et al. 1985) as well as icterus and hepatic commonly identified isolate in cases of ERU, whereas dysfunction (Roberts et al. 1952; Hathaway et al. 1981; serovar Pomona predominates in North America (Halliwell Swan et al. 1981). Acute renal failure associated with et al. 1985). leptospirosis has been documented in several publications Uveitis typically occurs months to years after naturally (Divers et al. 1992; Hogan et al. 1996; Frazer 1999). Acute acquired (Roberts et al. 1952) or experimentally induced leptospirosis causing renal disease in horses is a rare but (Morter et al. 1969; Williams et al. 1971) systemic serious condition that requires immediate veterinary leptospiral infection. Affected horses develop circulating attention. The lack of pathognomonic clinical signs makes antibodies against L. interrogans. The titre of these an immediate diagnosis difficult. With early and aggressive antibodies tends to rise during a flare-up of the lesion and treatment these cases have a good outcome. drops while the lesion is in remission. Anti-leptospiral Equine recurrent uveitis is the most frequently antibodies have been detected in tears and aqueous encountered clinical manifestation and this article will humour at the time corneal opacity develops (Parma focus on the review of ERU associated with leptospirosis. et al. 1987) and bind to the equine cornea and lens in EVE 08-122 Frellstedt_Layout 1 15/09/2009 12:43 Page 5

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vivo, activating complement (Parma et al. 1992). The uveitis (Deeg 2008; Deeg et al. 2002b, 2004b, 2006b, 2008) immunogenic lipoproteins LruA and LruB of pathogenic although only IRBP and cRALBP induced recurrent uveitis Leptospira spp. have been identified in uveitic eyes and in horses (Deeg et al. 2002b, 2006b). In conclusion, ERU is cross-react with equine ocular tissue (Verma et al. 2005). It probably caused by an autoaggressive T cell reaction was suggested that these lipoproteins play a significant against retinal proteins, which leads to subsequent role in the pathogenesis of ERU (Verma et al. 2005). destruction of intraocular structures and uveitic relapses Wollanke et al. (2001) showed that antibody titres in mediated by shifting immune reactions to auto-antigens vitreous samples were 4 times higher than in serum (Deeg 2008). Leptospiral antigens may contribute samples and concluded that intraocular infection with by cross-reacting with ocular auto-antigens and L. interrogans is the principal stimulus for local antibody modulate the immune response of the eye (Dwyer and production in the eye (Wollanke et al. 2001). The immune Gilger 2005). component of recurrent uveitis appears to be directly induced and maintained by persistent leptospiral Clinical signs of ERU infection of the eye (Wollanke et al. 2001). In contrast to these findings, a recent study in the USA In the acute phase of uveitis blepharospasm, identified no leptospiral DNA in aqueous and vitreous photophobia, lacrimation, chemosis, miosis, hypotonia humour from horses with ERU (Gilger et al. 2008). There was oculi, iritis and aqueous flare can be observed. Within also no significant difference in seroprevalence for 48–72 h these changes may progress to increased Leptospira spp. between normal horses and horses with aqueous flare, hypopyon, corneal oedema, corneal ERU. Gilger et al. (2008) hypothesised that bacterial vascularisation, conjunctival and circumcorneal infections, such as leptospirosis, may help initiate ERU in congestion, and vitreal haze. Visual disturbances may horses, but leptospiral organisms may not have a direct become evident. Chronic clinical signs are sequelae of effect on the pathogenesis of the recurrent disease in the acute lesions and include anterior and posterior some geographic areas, such as the southeastern USA. synechiae, cloudy vitreous, pigmented opacities on the This study supported the theory that recurrent episodes of anterior lens capsule, cataract formation, altered iris color, inflammation in horses with ERU are a result of an immune- iris atrophy, atrophy of corpora nigra, chorioretinal mediated response. scarring, retinal detachment, lens luxation, glaucoma and The pathogenesis of the immune response in ERU is still phthisis bulbi (Cook and Harling 1983; Sillerud et al. 1987). poorly understood although our knowledge has been Blindness is caused by cataract formation, glaucoma or significantly improved in the past decade. To this point it retinal detachment. is unclear whether one mechanism or a combination of multiple mechanisms lead to the recurrent episodes of Diagnosis of leptospiral involvement in ERU inflammation in ERU. Recurrent attacks may result from the incorporation of infectious agents or antigens into the The microscopic agglutination test (MAT) is the reference vitreous or uveal tract, from the deposition of antibody- method for serological diagnosis of leptospirosis. Reliance antigen complexes in the uveal tract and/or from the on the use of serology as a means of establishing a reactivation of persistent T lymphocytes (Dwyer and diagnosis is uncertain, and opinions differ as to what Gilger 2005). T lymphocytes are the predominant cell type constitutes a significant leptospiral titre (Faber et al. 2000). in eyes of horses with ERU (Gilger et al. 1999; Deeg et al. A positive serological reaction does not necessarily 2002a). Their reactivation occurs by ocular or systemic re- indicate current or recent infection because titres may exposure to the original antigen or by exposure to a self- persist for many years after infection (Roberts 1958; Swart protein that is similar to the original antigen (Dwyer and et al. 1982). To aid in confirming a chronic leptospiral Gilger 2005). The constant presence of the antigen in infection as a cause of ERU, aqueous and vitreous humour tissues causes chronic and relapsing disease, which is are important samples (Brem et al. 1998; Hartskeel et al. characteristic of a delayed-type hypersensitivity (DTH) 2004). Antibody titres can be determined in ocular fluids reaction (Gilger et al. 1999). Inciting antigens and epitope by use of MAT and are more reliable than antibody titres spreading are required to induce a pathological immune in the serum. Direct culture of ocular fluids is available to response (Dwyer and Gilger 2005). Inciting antigens may isolate leptospiral organisms, although the rate of isolation be microbial antigens originating from ocular or systemic is low since leptospires require special media and are infection or autoantigens to the horse’s own ocular tissue difficult to grow. It has been demonstrated that PCR (Dwyer and Gilger 2005). Recently, retinal auto-antigens analysis for leptospiral DNA in ocular fluids is a sensitive (S-antigen [S-Ag], interphotoreceptor retinoid-binding tool for the detection of leptospiral DNA in equine protein [IRBP], cellular retinaldehyde-binding protein recurrent uveitis (Faber et al. 2000; Brandes et al. 2007). [cRALBP], malate dehydrogenase [MDH]) have been The combined use of the Goldmann-Witmer coefficient identified in intraocular fluids of horses with ERU (Deeg (GWC) and PCR analysis has been suggested to be the et al. 2001, 2006a,b). Their pathological relevance has most sensitive method to determine the role of bacteria in been proven by their capability of inducing experimental uveitis (Gilger et al. 2008). The GWC for each leptospiral EVE 08-122 Frellstedt_Layout 1 15/09/2009 12:43 Page 6

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serovar is calculated by dividing the aqueous humour reduce the incidence and severity of uveitic attacks leptospiral antibody titre value by the serum leptospiral (Winterburg and Gerhards 1997; Fruhauf et al. 1998). antibody titre value. Vitreous replacement has proven to be a good method of conserving the globe in advanced cases although vision Treatment of ERU could not be conserved in all treated eyes due to cataract formation (Winterburg and Gerhards 1997; Current medical treatment for ERU consists of a Fruhauf et al. 1998). The procedure appears to be most combination of anti-inflammatory agents and mydriatic successful for treatment of posterior uveitis, although it has cycloplegics to decrease pain and inflammation, minimise been reported that eyes with anterior uveitis are treated as chronic changes, and prolong vision. Topical atropine is successfully as eyes with posterior uveitis (Wollanke 2002). the most commonly used mydriatic cycloplegic. It is given Studies from Germany concerning core vitrectomy have to effect and continued as required to ensure pupil reported higher success rates than American studies dilation. Horses should be monitored closely while (Brooks 2001); these findings implicate a geographic receiving atropine since it can cause gastrointestinal stasis difference in the aetiology of ERU and make careful case and abdominal pain. Topical corticosteroids and selection very important. nonsteroidal anti-inflammatory drugs (NSAIDs) are used to The value of systemic or local antibiotics in the decrease inflammation. Prednisolone acetate and treatment of suspected leptospiral-induced ERU remains dexamethasone have excellent ocular penetration. The unclear (Hines 2007). However, since persistent infection of most commonly given topical NSAID is flurbiprofen; the eye with leptospires is present in some horses with ERU, however, diclofenac sodium can also be administered. antibiotic therapy is recommended. Doxycycline has Topical NSAIDs, unlike topical corticosteroids, do not been reported for treatment of leptospira-associated potentiate the risk of infection but do delay healing of uveitis although its efficacy and mode of action are corneal ulcers by slowing corneal neovascularisation unknown. Intravitreal injections of gentamicin have been (Dwyer and Gilger 2005). Systemic anti-inflammatory described to minimise recurrent episodes of uveitis (Hines therapy is the most potent therapy for management of 2007). Fluoroquinolones are bactericidal antibiotics with a ERU. Medications used include flunixin meglumine, relatively low MIC (<0.2 mg/l) against Leptospira (Murray phenylbutazone, aspirin, dexamethasone and and Hospenthal 2004). Enrofloxacin has good in vitro prednisolone, with flunixin meglumine being the preferred antimicrobial susceptibility against Leptospira strains anti-inflammatory for the eye. Systemic corticosteroids are isolated from animal clinical cases (Kim et al. 2006). Divers usually required for management of more severe cases. et al. (2008) showed that intravenously administered Systemic treatment should be tapered off over a period of enrofloxacin has good ocular penetration and reaches time to decrease the risk of recurrence of uveitis by concentrations in the aqueous humour fluid within 1 h after allowing for the slow return of endogenous ACTH and i.v. administration that are above the reported MIC for corticosteroid function. The subconjunctival injection of Leptospira. These new data suggest that enrofloxacin is an triamcinolone has also been described for treatment of excellent choice of antimicrobial treatment for cases of severe cases. leptospira-associated uveitis. Two new therapies have been promoted recently. Rohrbach et al. (2005) investigated the effect of a Both therapies are invasive, expensive and require vaccine containing 6 serovars of Leptospira (serovars specialised skill and equipment (Rohrbach et al. 2005). Bratislava, Canicola, Hardjo, Icterohemorragica, A suprachoroidal cyclosporine implant has been Pomona and L. kirchneri serovar Grippotyphosa) for promoted to significantly decrease uveitis flare-ups and treatment of horses with ERU. The vaccine increased the blindness. This implant should only be placed during time to recurrence but failed to slow the progression of quiescent periods when acute inflammation has resolved. ERU. These data do not support the use of vaccination Cyclosporine A, through its ability to block IL-2 against leptospirosis as adjunctive therapy for horses transcription, leading to impaired proliferation of with uveitis. activated T helper and T cytotoxic cells among other immunological effects, is an ideal drug to prevent Prognosis of ERU reactivation of ocular inflammation (Gilger et al. 2006). There is also evidence that cyclosporine A has Prognosis of ERU with medical treatment is poor because bacteriostatic effects on leptospires that may contribute of the recurrent nature of the disease and the progressive to uveitis (Gilger et al. 2006). Cyclosporine A is delivered globe destruction which typically leads to blindness. via a sustained-release drug device that is placed deep to Vitrectomy may be a good method to preserve the globe the sclera adjacent to the suprachoroidal space of the and eliminate recurrence of ERU in carefully selected eye. The implant requires 30–45 days to reach adequate cases. The prognosis for sight may be better with surgical ocular levels of cyclosporine A. treatment as long as no ocular inflammatory changes are Core vitrectomy and replacement with a saline present and post operative cataract formation can be solution containing gentamicin has been reported to minimised. EVE 08-122 Frellstedt_Layout 1 15/09/2009 12:43 Page 7

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Prevention Deeg, C.A., Kaspers, B., Gerhards, H., Thurau, S.R., Wollanke, B. and Wildner, G. (2001) Immune responses to retinal autoantigens and peptides in equine recurrent uveitis. Invest. Ophthalmol. Vis. Sci. 42, The only measures for prevention of leptospirosis are basic 393-398. precautions including the early identification and isolation Deeg, C.A., Hauck, S.M., Amann, B., Pompetzki, D., Altmann, F., Raith, of infected animals, rodent and wildlife control on farms, A., Schmalzl, T., Stangassinger, M. and Ueffing, M. (2008) Equine reducing the exposure to standing water sources, and recurrent uveitis--a spontaneous horse model of uveitis. Ophthalmic Res. 40, 151-153. feeding horses off the ground. Currently no vaccines Divers, T.J., Byars, T.D. and Shin, S.J. (1992) Renal dysfunction associated against leptospirosis are approved for use in horses. with infection of Leptospira interrogans in a horse. J. Am. vet. med. Ass. 201, 1391-1392. 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