Leptospirosis is a zoonotic infectious disease caused by Gram-negative bacteria of the genus Leptospira, a type of spirochete. It is also known as Weil disease. It is the most common zoonotic disease worldwide, with an estimated 500,000 high-risk cases occurring annually. Mortality can reach up to 30% [1, 5].
The infection rate is about 10 times higher in tropical and subtropical regions compared to temperate regions. In Japan, sporadic cases occur nationwide. In urban areas, infection can occur through sewer work or contact with rat feces and urine. Imported cases, where infection occurs during overseas travel and symptoms develop domestically, are also increasing.
Leptospiral uveitis is common among agricultural workers. It is most frequently seen in young to middle-aged men.
Systemic symptoms are diverse and are broadly divided into the following two stages.
Acute phase (anicteric phase)
Fever: Onset with sudden high fever.
Muscle pain and joint pain: Accompanied by cold-like symptoms.
Conjunctival hyperemia: Also observed in the anicteric phase.
Others: Headache, nausea, loss of appetite, abdominal pain, etc. Mild cases resolve spontaneously.
Late phase (icteric phase/Weil's disease)
Weil’s triad: Accompanied by hemorrhage, jaundice, and renal impairment (proteinuria).
Renal involvement: Interstitial nephritis, uremia, oliguria.
Meningitis: Meningeal irritation symptoms (headache) are observed.
Others: Severe systemic symptoms such as psychosis, confusion, and delirium.
In typical cases, recovery often occurs without sequelae.
Leptospirosis presents a wide range of clinical manifestations from mild to severe. Weil’s disease is its severe form, referring to the late icteric phase with hemorrhage, jaundice, and renal impairment.
Ocular symptoms usually develop 6 months after systemic infection. However, the onset can range from 2 weeks to several years.
Ocular findings in leptospirosis differ between the acute phase and the late immune phase.
Ocular findings may be unilateral or bilateral.
Leptospira bacteria are carried by wild animals such as rodents, as well as livestock and pets. The bacteria are excreted in urine, so infection occurs through contact with water or soil contaminated by urine.
The main routes of infection are as follows:
The main risk factors are as follows.
Serological tests play a central role in the definitive diagnosis of leptospirosis.
The following should be considered in the ophthalmologic differential diagnosis of leptospiral uveitis.
| Differential Diagnosis | Key Points for Differentiation |
|---|---|
| Fuchs heterochromic iridocyclitis | Presence of acute perilimbal injection, flare, and anterior chamber inflammation |
| Toxoplasmosis | Presence of inflammatory lesions in the choroid and retina |
| Acute retinal necrosis | Presence of inflammatory lesions in the choroid and retina |
Furthermore, differentiation from the following diseases is also important.
In leptospiral uveitis, choroidal thickening and exudative retinal detachment are not observed. In Harada disease, these appear from the early stage, which is an important differentiating point.
Treatment of leptospirosis depends on the severity of the disease.
The mainstays are fluid management and control of pain and fever.
Systemic antimicrobial therapy is necessary.
Generally, treatment is given for about 3 weeks with penicillin, azithromycin, doxycycline, etc.
The main treatments for ocular findings are as follows.
Because ocular uveitis is a delayed lesion caused by an immune reaction, the mainstay of ophthalmic treatment is steroids and mydriatics. However, if systemic infection is active, systemic administration of antibiotics is also combined.
The pathogenesis of ocular symptoms in leptospirosis is thought to involve both the host immune response and bacterial toxins.
The following changes within the eye have been reported.
These findings suggest that endotoxin may be a trigger for leptospiral uveitis [3].
Ocular findings appear 1 to 6 months after infection. Acute conjunctival hyperemia is directly related to bacteremia. In contrast, uveitis in the late immune phase is due to an immune reaction and not direct ocular tissue damage by the bacteria.
The absence of typical chorioretinal lesions suggests that the pathology is not direct infection of the choroid but primarily an immune reaction in the anterior chamber and vitreous cavity.
Ocular uveitis is thought to be a delayed reaction due to the host immune response, not direct damage by the bacteria. Elevated cytokines in the aqueous humor and involvement of endotoxins have been suggested. For details, see the “Pathophysiology” section.
There is currently no widely available human vaccine. Vaccination in animals is effective for infection prevention, but application to humans is still under research.
Current preventive measures include avoiding exposure to contaminated environments, prophylactic administration of antibiotics (doxycycline) to high-risk individuals, and vaccination of animals. Prophylactic antibiotic use before travel to endemic areas may also be considered.
Regarding the elucidation of the pathogenesis of leptospiral uveitis, research is ongoing on cytokine profiles in the aqueous humor and the role of endotoxins. These findings may lead to the development of more targeted therapies.
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Rathinam SR, Rathnam S, Selvaraj S, Dean D, Nozik RA, Namperumalsamy P. Uveitis associated with an epidemic outbreak of leptospirosis. Am J Ophthalmol. 1997;124(1):71-79. PMID: 9222235
Priya CG, Rathinam SR, Muthukkaruppan V. Evidence for endotoxin as a causative factor for leptospiral uveitis in humans. Invest Ophthalmol Vis Sci. 2008;49(12):5419-5424. PMID: 18658094
Shukla D, Rathinam SR, Cunningham ET Jr. Leptospiral uveitis in the developing world. Int Ophthalmol Clin. 2010;50(2):113-124. PMID: 20375866
Arrieta-Bechara CE, Carrascal-Maldonado AY. Ocular leptospirosis: a review of current state of art of a neglected disease. Rom J Ophthalmol. 2022;66(4):282-288. PMID: 36589326
