Brucellosis is a systemic zoonotic infection caused by bacteria of the genus Brucella (Brucella spp.). Brucella are facultative intracellular gram-negative coccobacilli that survive and multiply within macrophages, and human disease is mainly caused by four species: B. melitensis, B. abortus, B. suis, and B. canis.
The routes of infection are as follows.
It is endemic in the Mediterranean basin, the Middle East, Central and South Asia, Latin America, and parts of Africa.
Ocular involvement is rare but can threaten vision. According to reports, ocular symptoms are observed in approximately 3–26% of patients with systemic brucellosis. Sungur et al. reported ocular symptoms in 21% of 132 confirmed brucellosis patients, with anterior uveitis (41%) and choroiditis (32%) being the most common 1). In a large 26-year study in Peru by Rolando et al., 3.4% of 1551 cases had ocular symptoms, with posterior uveitis (35%) and panuveitis (32%) being frequent 1).
In a meta-analysis of 27 studies involving 159 cases by Evlice et al., the pooled prevalence of ocular symptoms was 52.2%, and conjunctivitis was 17.6%. Patients with systemic infection symptoms accounted for 27.7%, and only 37.1% recovered vision after treatment 1).
Ocular symptoms can occur at any stage of the systemic disease. They may appear in the acute phase or progress insidiously during chronic infection. Rarely, ocular symptoms may precede systemic symptoms.
Although reports vary, ocular symptoms are observed in approximately 3–26% of patients with systemic brucellosis. Uveitis is the most common, accounting for nearly half of all ocular symptoms 1).
The subjective symptoms of ocular brucellosis are nonspecific and share many similarities with other eye diseases.
Ocular symptoms often appear in the chronic phase of systemic infection, and early detection is rare1).
Ocular brucellosis presents with a variety of clinical findings and is classified by anatomical site.
Anterior Segment
Anterior uveitis: One of the most common ocular symptoms. It can be granulomatous or non-granulomatous, presenting with anterior chamber cells, flare, keratic precipitates, posterior synechiae, and hypopyon.
Conjunctivitis and episcleritis: Mild hyperemia, tearing, and discomfort. Most cases are self-limited and accompany acute systemic symptoms.
Corneal lesions: Coin-shaped keratitis (subepithelial infiltrates) or interstitial keratitis may occur.
Posterior Segment
Chorioretinitis: Multifocal lesions with vitritis. May be complicated by cystoid macular edema (CME) or serous retinal detachment.
Retinal vasculitis: Presents with vascular sheathing, hemorrhages, and cotton-wool spots; occlusive vasculitis can cause ischemia and neovascularization.
Endophthalmitis: Rare but most severe. Presents with hypopyon and dense vitritis, with poor prognosis.
Neuro-ophthalmology
Optic neuritis: Presents with decreased visual acuity, color vision abnormalities, and visual field defects. Often associated with neurobrucellosis.
Papilledema: Secondary to meningitis or increased intracranial pressure.
Cranial nerve palsy: Abducens nerve palsy presents as horizontal diplopia.
The approximate frequency of each symptom is shown below.
| Ocular symptom | Frequency |
|---|---|
| Anterior uveitis | 20–40% |
| Posterior/panuveitis | 15–30% |
| Optic neuritis/optic neuropathy | 3–8% |
Brucella infects humans through exposure to contaminated animals or animal products. After being taken up by macrophages, the bacteria inhibit phagolysosome fusion to evade intracellular killing and reach multiple organs including the eye via hematogenous dissemination (see “Pathophysiology” section).
Risk factors for ocular symptoms include:
Farmers, veterinarians, slaughterhouse workers, and others with occupational livestock contact are at high risk for brucellosis itself. Ocular involvement is more likely with delayed diagnosis of systemic infection, inappropriate treatment, chronic or recurrent course, and immunodeficiency.
Ocular symptoms of brucellosis are nonspecific and mimic other infectious and inflammatory diseases, so an integrated assessment of systemic epidemiological background and ocular findings is essential.
Obtain exposure history (consumption of unpasteurized dairy products, contact with livestock, residence in endemic areas) and check for uveitis, retinitis, vasculitis, vitritis, and optic disc edema.
The main diagnostic methods are shown below.
| Test Method | Main Use | Remarks |
|---|---|---|
| Rose Bengal test | Rapid screening | High sensitivity but slightly low specificity |
| Agglutination test (Wright method) | Confirmation of systemic infection | Positive at 1:160 or higher |
| Culture (blood, bone marrow) | Definitive diagnosis | Low sensitivity but gold standard |
Serological tests (Rose Bengal test, agglutination test, Coombs test, ELISA) confirm systemic infection. Culture is the gold standard for definitive diagnosis, but due to long culture periods and high biosafety requirements, it may be omitted when serology provides a clear diagnosis1).
In the case by Wei et al., diagnosis was made with positive Rose Bengal test and agglutination test 1:100++, and other etiologies were excluded by negative tuberculin test, syphilis test (FTA-ABS), rheumatoid factor, antinuclear antibody, and toxoplasma antibody1).
Cerebrospinal fluid examination is essential when neuro-ophthalmic signs are present.
As screening tests for uveitis, in addition to complete blood count, CRP, and ESR, pathogen-related tests such as syphilis serology and QuantiFERON-Tb are performed to proceed with differential diagnosis.
Ocular brucellosis requires differentiation from the following diseases.
The mainstay of treatment is appropriate systemic combination antibiotic therapy. Control of systemic infection is essential for resolution of ocular inflammation and prevention of recurrence.
The WHO-recommended standard regimen is a combination of doxycycline and rifampicin for at least 6 weeks, or rifampicin replaced by streptomycin for the first 2–3 weeks1).
Triple therapy is recommended for complicated cases.
A treatment duration of 3 months or longer is recommended1).
Systematic reviews and network meta-analyses have shown that triple therapy is superior to dual therapy, monotherapy has a high failure rate, and treatment lasting 6 weeks or longer is significantly more effective than shorter treatment1).
In addition to systemic antimicrobial therapy, address ocular inflammation and its complications.
In the case reported by Wei et al., in addition to triple therapy for 3 months, indomethacin eye drops and tobramycin/dexamethasone eye drops were used for 1 month. Symptoms improved after 2 weeks of treatment, visual acuity recovered to 1.0 in both eyes at 2 months, and no recurrence was observed after 1 year1).
There are reports that early treatment with a combination of antimicrobial therapy and local treatment can lead to resolution of inflammation and recovery of visual acuity within about two months1). However, posterior uveitis and panuveitis tend to have a poor prognosis, with one report indicating that visual acuity recovery is only 37.1% even after treatment1).
There are multiple mechanisms by which Brucella bacteria spread to the eye.
After being phagocytosed by macrophages, Brucella avoids intracellular killing by inhibiting phagolysosome fusion. It proliferates intracellularly, inducing granulomatous inflammation and establishing chronic infection.
Hematogenous dissemination allows the bacteria to reach multiple organs, including the eyes. The ocular pathology involves a combination of the following four mechanisms.
The contributions of direct microbial invasion and immune dysregulation vary by case, resulting in diverse ocular manifestations. This leads to clinical similarities with other diseases such as tuberculosis, syphilis, sarcoidosis, and Behçet’s disease.
Metagenomic next-generation sequencing (mNGS) is a technology that enables unbiased, high-throughput analysis of all microbial DNA/RNA in intraocular fluids (aqueous humor and vitreous humor), allowing rapid pathogen identification 1). In ocular infections caused by intracellular bacteria such as brucellosis, which are difficult to identify by conventional culture, mNGS may contribute to improved diagnostic accuracy.
Zhu et al. reported that mNGS testing of vitreous humor from patients with endophthalmitis enabled rapid detection of pathogens that could not be identified by conventional methods 1).
In the future, clarification of the clinical spectrum through multicenter prospective studies and establishment of evidence-based treatment guidelines are expected 1).
