Ophthalmological Features of Leptospirosis
Leptospirosis (Weil disease) is a gram-negative, water-borne, spirochete that is part of the Leptospira genus within the Leptospiraceae family. This tropical disease is the most common zoonotic illness worldwide. The majority of cases present with the acute (anicteric) phase consisting of self-limiting clinical manifestations including sudden fever, myalgia, headache, scleral icterus, chemosis, nausea, anorexia, and abdominal pain. Weil disease is the late icteric phase following severe systemic manifestations including interstitial nephritis, uremia, oliguria, kidney lesions, vascular injury, meningitis, jaundice, psychosis, confusion, and delirium. Both anterior and posterior segment ophthalmic manifestations can occur in Leptospirosis and this Eyewiki emphasizes these ocular findings.
Modes of Transmission
The primary mode of human transmission is direct or indirect contact with infected animals (e.g. cattle, pigs, horses, racoons, porcupines, domesticated dogs) or their body fluids (especially urine) via water or soil contamination.
Leptospirosis is the most common zoonotic illness globally with an estimated 500,000 high-risk cases per year and 30% mortality rate. The incidence of infection is 10 times higher in tropical and subtropical climates as opposed to temporal climates. In addition, leptospiral uveitis is most prevalent in young to middle-aged men, likely from their higher involvement in agricultural work.
The etiology of ocular features of leptospirosis has been postulated as a host immune response and/or toxin production. Specifically, the presence of serovar-specific lipopolysaccharide (LPS) with an increase of Interleukin-6 (IL-6), IL-8, IL-10, IL-12p70, and tumor necrosis factor (TNF) cytokines and selective neutrophil infiltration in aqueous humor is indicative of endotoxin as a possible causative factor for leptospiral uveitis.
Since there is no widely available human vaccine, preventative measures include avoiding potential sources of infection (contaminated water or food), antimicrobial prophylaxis (doxycycline) in individuals at high risk of exposure, and vaccination of animals.
Ocular findings in the leptospiremic acute phase of the illness include sub-conjunctival hemorrhage, scleral icterus, circum-corneal congestion without conjunctival discharge, conjunctival suffusion, and chemosis. Ophthalmic findings of the late immune phase (Weil disease) of infection include nongranulomatous uveitis, interstitial keratitis, conjunctival suffusion, cranial nerve palsies (third, fourth, sixth, or seventh cranial nerves) retinal vasculitis and hemorrhages, and optic neuropathy.
Unilateral or bilateral uveitis (anterior or diffuse and acute or recurrent) generally develops 6 months after a systemic infection, although presentation can range from 2 weeks to a few years, with clinical signs of iridocyclitis, iritis, hypopyon, vitreous inflammatory reaction, cataract, retinal vasculitis, and papillitis. Anterior uveitis is typically mild and self-limiting while panuveitis can be severe and relapsing.
Involvement of the optic nerve can manifest through papillitis, optic neuritis, neuroretinitis, and optic disc hyperemia (found in 3%-64% of case presentations). Disc leakage on fluorescein angiography and a delayed response on visual-evoked potential testing can reveal the presence of optic neuropathy in leptospirosis. Inflammation of peripapillary retinal layers and the optic nerve can result in a macular star seen in neuroretinitis. Finally, field abnormalities or color vision defect may be manifestations of a retrobulbar optic neuropathy or optic neuritis in leptospirosis.
The microscopic agglutination test (MAT) is the gold standard and most common diagnostic test for leptospirosis. Other diagnostic testing includes other serological-based assays (i.e. enzyme linked immune-sorbent assay (ELISA), solid phase assay, and indirect hemagglutination assay), direct diagnostic methods (histochemical staining, immunostaining, and dark field or phase contrast microscopy) nested polymerase chain. reaction (PCR), and culture methods.
Uveitis, keratitis, hypopyon, cranial nerve palsies, retinal vasculitis, optic neuropathy
Sub-conjunctival hemorrhage, scleral icterus, circum-corneal conjunctival congestion, chemosis, conjunctival suffusion
The following list includes the different diagnoses that should be taken into consideration for leptospirosis.
- Dengue Fever
- Hantavirus pulmonary syndrome
- Hepatitis A
- Enterovirus infections
- Kawasaki disease
- Typhoid fever
- Q fever
- Primary HIV
- Other hemorrhagic fevers
Ocular Differential Diagnosis
Idiopathic uveitis and ocular manifestations associated with ankylosing spondylitis, tuberculosis, syphilis, leprosy, sarcoidosis, and borreliosis might be considered on the differential for the ocular findings of leptospirosis. Bechet syndrome and human leukocyte antigen B27 (HLA-B27) uveitis can result in similar presentations (e.g., uveitis with hypopyon and/or arthralgia).
Leptospiral uveitis should also be differentiated from Fuchs heterochromic iridocyclitis, toxoplasmosis, acute retinal necrosis, sarcoidosis, and endogenous endophthalmitis. The acute circumferential corneal congestion, flare, and inflammatory reaction of the anterior chamber seen on slit lamp examination can help differentiate leptospiral uveitis from Fuchs heterochromic iridocyclitis. The absence of choroidal and retinal inflammatory lesions can be used to differentiate leptospiral uveitis from toxoplasmosis, acute retinal necrosis, and sarcoidosis. Leptospiral uveitis with disc edema should be differentiated from sympathetic ophthalmia and Vogt-Koyanagi-Harada (VKH) syndrome by the identification of absent choroidal thickening or exudative retinal detachment. Furthermore, optic disc edema seen in leptospiral uveitis may be differentiated from multiple sclerosis, sarcoidosis, and pars planitis via absence of magnetic resonance imaging (MRI) findings and central nervous system (CNS) involvement, absence of bilateral granulomatous uveitis, and absence of snow banking, respectively. Finally, retinal vasculitis with leptospiral uveitis should be differentiated from Eales’ disease, sarcoidosis, and Behcet syndrome.
General management of leptospirosis depends on disease severity. Mild cases can be managed through administration of fluids with pain and fever control. Alternatively, treatment for severe illness includes systemic antibiotic therapy (ceftriaxone, doxycycline, amoxycillin, or penicillin early in the disease course or intravenous ampicillin or penicillin in severe systemic cases), administration to the ICU, and mechanical ventilation for patients with respiratory involvement. Diuretics and inotropic agents should also be considered in some severe cases.
Mainstay treatment for ocular findings include use of topical, periocular, or systemic corticosteroids and mydriatics.
The prognosis of the ocular findings of leptospirosis, including leptospiral uveitis, is generally good with timely treatment and correct diagnosis. Although vitreous opacities may be seen months after the patient regains 6/6 visual acuity. In cases of severe inflammation, steroid induced glaucoma and cataract (seen in 14% of patients with sero-positive leptospiral uveitis) can result. Although complete recovery of vision is associated with anti-glaucoma treatment and cataract removal with intraocular lens implantation.
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Kahloun R, Abroug N, Ksiaa I, Mahmoud A, Zeghidi H, Zaouali S, Khairallah M. Infectious optic neuropathies: a clinical update. Eye Brain 2015;7:59-81.
- ↑ 2.0 2.1 2.2 2.3 2.4 Wang S, Gallagher M, Dunn N. Leptospirosis. Treasure Island (FL): StatPearls Publishing 2021. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK441858/
- ↑ 3.0 3.1 3.2 3.3 Samrot A, Tan Chuan S, Bhavya K, Sahithya C, Chandrasekaran S, Palanisamy R, Robinson E, Subbiah S, Mok P. Leptrospiral Infection, Pathogenesis and Its Diagnosis-A Review. Pathogens 2021;10:145.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Verma A, Stevenson B. Leptospiral Uveitis-There is More to It Than Meets the Eye! Zoonoses and Public Health 2012;59(s2):132-141.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Rathinam S. Ocular manifestations of leptospirosis. Journal of Postgraduate Medicine 2005;51(3):189-194.
- ↑ Priya C, Rathinam S, Muthukkaruppan V. Evidence for endotoxin as a causative factor for leptospiral uveitis in humans. Invest Ophthalmol Vis Sci 2008;49(12):5419-24.
- ↑ Gonçalves-de Albuquerque, C, Burth P, Silva A, Younes-Ibrahim M, Castro-Faria-Neto H, Castro-Faria M. Leptospira and Inflammation. Mediators Inflamm 2012;2012:317950.
- ↑ Day N. Measles: Leptospirosis: Treatment and prevention. UpToDate 2020. Available from: https://www.uptodate.com/contents/leptospirosis-treatment-and-prevention#H8
- ↑ Khurana S, Gupta P, Ram J. Bilateral conjunctival suffusion-An ocular manifestation of leptospirosis. Indian Journal of Ophthalmology 2020;68(9):1971.