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  • Uveitis

    Ocular inflammation can occur in patients with documented Lyme disease and has been reported to involve any part of the eye. Uveitis is uncommon, but case reports and small series demonstrate a wide variety of presentations including iridocyclitis, vitritis, multifocal choroiditis, exudative retinal detachment and panophthalmitis. Although Lyme disease is the most commonly reported tick-borne infection in the United States and Europe, there are unresolved issues related to its diagnosis and management. For early Lyme disease, therapy is clear, but for both late-stage disease and presumed chronic Lyme disease, therapeutic approaches are not as well defined. This article offers a rational approach to treating Lyme disease patients.

    Lyme disease basics

    Lyme disease is a systemic tick-borne illness with protean manifestations, including dermatologic, rheumatologic, neurologic and cardiac abnormalities.1 While Borrelia burgdorferi causes Lyme disease, it is now known that there are several genospecies included in the group called Borrelia burgdorferi sensu lato. Different species with differing surface proteins may have different pathogenicity and genetic heterogeneity that may affect the clinical presentation.

    Borrelia burgdorferi sensu lato includes nine genospecies in Europe and Asia and three in North America. Three genospecies cause the majority of cases of Lyme borreliosis: Borrelia burgdorferi sensu stricto, Borrelia andersonii and Borrelia bissetti. Borrelia burgdorferi sensu stricto is the only species known to cause Lyme disease in humans in North America.1,2

    Borrelia are transmitted to humans through a bite from an infected Ixodes tick-Ixodes scapularis and Ixodes pacificus in the United States and Ixodes ricinus in Europe. Both adult and nymph forms of the tick can cause human infection. Since nymphs feed in spring and summer and adults in autumn, there is seasonal variation in patterns of the disease. Nymph forms have been found on many species, including mice, shrews, squirrels, voles and deer, and adults on white-tailed deer. The percentage of Ixodes ticks infected with Borrelia burgdorferi even in an endemic area may be as low as 20 to 30 percent. Transmission to humans requires attachment of the tick for 48 to 72 hours.3 Since the same ticks that transmit Borrelia burgdorferi may also be infected with Anaplasma phagocytophilium, which causes human granulocytic anaplasmosis, and Babesia microti, which causes babesiosis, coinfection with these organisms is possible.4

    Once a person is bitten by an infected tick, the typical skin lesion, erythema migrans, a ring-like erythematous reaction of at least 5 cm, develops in about 50 percent of patients. Systemic symptoms of malaise, fatigue, fever, headache, myalgias and lymphadenopathy may also develop. About 45 percent of patients with erythema migrans have spirochetemia, with 60 percent of untreated patients developing monoarticular or oligoarticular arthritis, 10 percent neurologic abnormalities and 5 percent cardiac complications.5

    Ocular symptoms

    Lyme disease has been divided into three stages: early localized, early disseminated and late disseminated.4 Ocular involvement has been reported during all stages of Lyme disease. During early Lyme disease, within the first weeks of infection, a nonspecific self limited follicular conjunctivitis has been described as occurring in about 10 percent of patients.5 Photophobia has been reported during this stage, as has periorbital edema.

    During early disseminated and late disseminated  Lyme disease, keratitis, iridocyclitis, vitritis, multifocal choroiditis, exudative retinal detachment and panophthalmitis have all been reported.6-9 The reported cases of keratitis seen in Lyme disease patients, described as nummular stromal opacities without overlying epithelial involvement, are not believed to be infectious and respond to topical corticosteroids. Neuro-ophthalmic manifestations include optic neuritis, disc edema and oculomotor palsy.10,11

    With no pathognomonic form of ocular inflammation in Lyme disease, multiple strains of Borrelia and the possibility of coinfection with other tick-borne zoonoses, the diagnosis of ocular inflammation caused by Lyme disease requires a systematic approach. Ophthalmologists should be suspicious of Lyme disease in patients with any form of intraocular inflammation if the individual was at risk of having been exposed to the disease due to having lived or travelled in a Lyme-endemic area.

    Laboratory testing

    Laboratory criteria for the diagnosis of Lyme disease consist of the isolation of B. burgdorferi from clinical specimens or positive Immunoglobulin M (IgM) or Immunoglobulin G (IgG) antibodies to B. burgdorferi in serum. IgM becomes positive after two weeks and peaks at two months. IgG and IgM response may persist for months to years.12 A two-tiered approach with confirmation of enzyme immunoassay or immunofluoresence antibody positivity followed by a positive Western blot is recommended.1 A patient with documented erythema migrans does not require laboratory testing to confirm the diagnosis.5

    Clinical course and treatment

    Erythema migrans resolves spontaneously within four weeks without treatment. Early antibiotic treatment is highly effective at preventing late manifestations of Lyme disease. Intraocular inflammation, a late finding, may occur in patients who have not received early systemic antibiotics.

    Antibiotics should be started immediately, without waiting for laboratory confirmation, in patients with erythema migrans. Effective antibiotics are listed in Table 1.5 For patients with disseminated Lyme disease, recommended therapy is 2 g ceftriaxone delivered intravenously daily for 14 to 21 days or 200 mg of doxycycline taken orally twice a day for 10 to 20 days. These treatments are equally effective.4

    Robert Weinberg
    Table 1. Antibiotics used for treating early Lyme disease.

    Chronic Lyme disease, also known as post-treatment Lyme disease syndrome, occurs in fewer than 5 percent of patients with early-stage disease treated with appropriate antibiotics. There is no evidence that it is caused by persistent bacterial infection that requires additional courses of antibiotics.13 The possibility that some patients are coinfected with other tick-borne and untreated zoonoses must be considered.14

    There is no specific therapeutic regimen for patients with ocular involvement and a history of Lyme disease. A patient with intraocular inflammation and a documented history of erythema migrans who has never received appropriate systemic antibiotics should be managed differently than a patient with intraocular inflammation who is at risk for Lyme disease, due to having lived or traveled in a Lyme-endemic area, and has received a course of systemic antibiotics for documented early Lyme disease. In the former case, treatment with appropriate anti-inflammatory medication only seems reasonable. In the latter case, anti-inflammatory medication combined with systemic antibiotics is indicated. With no controlled studies to support either approach, the ophthalmologist's therapeutic regimen must be based on what is known about the systemic disease.

    Because of the effectiveness of therapy at eliminating infection in early Lyme disease patients, the wide variation in clinical presentation, the possibility of different clinical manifestations that may be caused by infection with differing strains of B. burgdorferi and the fact that positive Lyme serology may persist despite appropriate treatment, the ophthalmologist must adopt a rational approach to treating Lyme disease patients.


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    Author Disclosure

    Dr. Weinberg states that he has no financial relationship with the manufacturer of any product discussed in this article or with the manufacturer of any competing product.