Ocular Manifestations of Brucellosis
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Introduction
Brucellosis is a systemic zoonotic infection caused by Brucella species, which are small, facultative intracellular Gram-negative coccobacilli capable of surviving and replicating within macrophages.[1] Human disease results most commonly from B. melitensis, B. abortus, B. suis, and B. canis, typically transmitted through ingestion of unpasteurized dairy products, contact with infected animals, or inhalation of aerosols in laboratory or occupational settings. The infection remains endemic in the Mediterranean basin, Middle East, Central and South Asia, Latin America, and parts of Africa.[1]
Ocular involvement is uncommon but potentially vision-threatening. Across published series, ocular manifestations occur in approximately 3–26% of patients with systemic brucellosis. Ocular disease may arise during acute infection, evolve during chronic or relapsing disease, or rarely precede systemic symptoms entirely.[2] Because the spectrum ranges widely—from mild conjunctivitis to severe panuveitis, chorioretinitis, optic neuritis, or endophthalmitis—prompt recognition and interdisciplinary management are essential to preserving vision.[2] This article reviews the mechanisms of ocular involvement, epidemiology, clinical spectrum, diagnostic evaluation, and treatment considerations.
Etiology and Pathogenesis Relevant to the Eye
Brucellosis develops following human exposure to animals or animal products contaminated with Brucella organisms. Transmission occurs through unpasteurized dairy, undercooked meat, direct inoculation via skin or mucosa, and inhalation of infectious aerosols. High-risk groups include farmers, veterinarians, abattoir workers, and laboratory personnel.[3]
Once in the host, Brucella organisms are phagocytosed by macrophages but avoid intracellular killing by inhibiting phagolysosomal fusion, promoting granulomatous inflammation, and establishing chronic infection. Hematogenous dissemination permits involvement of multiple organs, including the eye. Ocular pathology reflects several mechanisms:[4]
- Direct infection of ocular tissues: Organisms reach the uveal tract, retina, or optic nerve, causing localized inflammation.[4]
- Immune-mediated injury: Delayed-type hypersensitivity, immune complex deposition, and granulomatous inflammation contribute to keratitis, uveitis, choroiditis, and some forms of optic neuropathy.[4]
- Vasculitis and vascular compromise: Brucella-associated vasculitis leads to retinal vascular sheathing, occlusion, ischemic retinitis, and occasionally papilledema due to cerebral involvement.[4]
- CNS-related mechanisms: In neurobrucellosis, meningeal inflammation, demyelination, and elevated intracranial pressure contribute to optic neuritis, papilledema, and cranial nerve palsies.[4]
- The relative contribution of direct microbial invasion and immune dysregulation results in a diverse range of ocular presentations, often mimicking other infectious or autoimmune diseases.[4]
Epidemiology of Ocular Brucellosis
The reported prevalence of ocular involvement varies significantly depending on geographic location, exposure patterns, and diagnostic criteria.[5] Across large series, ocular findings occur in approximately 3.4–26% of patients with systemic brucellosis. Uveitis is the most frequently reported manifestation, often accounting for half of all ocular presentations. Conjunctivitis, episcleritis, posterior segment inflammation, and neuro-ophthalmic complications appear less commonly but may lead to significant visual morbidity when diagnosis is delayed.[5]
Adults constitute the majority of cases, but pediatric patients may show a different profile, including a comparatively higher rate of optic nerve involvement and neurobrucellosis. Males may predominate in endemic regions due to occupational exposure, although distribution varies by setting.[6] Risk factors for ocular involvement include chronic or relapsing systemic disease, delayed diagnosis, inadequate antimicrobial therapy, high organism load, and confirmed neurobrucellosis. Immunosuppressed patients may have more severe presentations.[6]
Ocular manifestations can arise at any stage of systemic disease. They may present concurrently with acute brucellosis, develop insidiously during chronic infection, or appear after partial resolution of systemic symptoms.[7] A subset of patients presents initially with ocular inflammation—most often uveitis or optic neuritis—prompting evaluation that ultimately reveals underlying brucellosis.[8]
| Ocular Manifestation | Approximate Frequency (Across Series) | Notes |
|---|---|---|
| Conjunctivitis / episcleritis | 10–20% | Often mild; may accompany acute systemic symptoms. |
| Anterior uveitis | 20–40% | Granulomatous or non-granulomatous; may present with hypopyon. |
| Intermediate / posterior uveitis | 15–30% | Includes vitritis, choroiditis, retinitis, and vasculitis. |
| Panuveitis | 5–15% | More common in chronic disease; higher risk of complications. |
| Retinal vasculitis / retinitis | 5–15% | May resemble infectious or autoimmune vasculitides. |
| Optic neuritis / optic neuropathy | 3–8% | Often associated with neurobrucellosis; poorer visual prognosis. |
| Papilledema | <5% | Typically secondary to meningitis or increased intracranial pressure. |
| Endophthalmitis | <1–2% | Rare but severe; may require vitrectomy and aggressive therapy. |
Classification of Ocular Manifestations
Ocular brucellosis encompasses a wide range of clinical findings that reflect both direct microbial invasion and immune-mediated inflammation. Because presentations can mimic tuberculosis, sarcoidosis, syphilis, viral uveitis, and autoimmune vasculitides, an anatomical classification provides a practical framework for diagnosis.[9] Brucellosis may involve the ocular adnexa, anterior segment, intermediate uveal tract, posterior segment, or the optic nerve and CNS pathways. Uveitis—particularly posterior or panuveitic disease—is the most commonly reported clinically significant manifestation, whereas neuro-ophthalmic involvement and endophthalmitis are rare but carry the poorest visual prognosis. Brucellosis may involve:[9]
Table 1. Anatomical Classification of Ocular Manifestations
| Category | Representative Manifestations | Clinical Notes |
|---|---|---|
| Ocular adnexa and surface | Conjunctivitis, episcleritis, scleritis, dacryoadenitis | Typically milder disease; scleritis may mimic autoimmune etiologies. |
| Cornea and anterior segment | Nummular or interstitial keratitis, keratoconjunctivitis, anterior uveitis, hypopyon | Anterior uveitis is common; keratitis is less frequent but distinctive. |
| Intermediate and posterior segment | Vitritis, intermediate uveitis, choroiditis, chorioretinitis, retinitis, vasculitis | Often associated with chronic or undertreated systemic infection. |
| Panuveitis | Combined anterior and posterior inflammation | Aggressive course; higher risk of complications. |
| Neuro-ophthalmic involvement | Optic neuritis, papilledema, cranial nerve palsies | Usually due to neurobrucellosis; poor prognosis. |
| Severe intraocular complications | Endophthalmitis, cystoid macular edema, secondary glaucoma | Rare but vision-threatening. |
Ocular Adnexal and Anterior Segment Manifestations
Ocular adnexal and anterior segment manifestations may appear during any stage of systemic brucellosis. Although often less severe than posterior disease, these findings may represent early clinical clues in patients with relevant epidemiologic exposures.[10]
- Conjunctivitis, episcleritis, and scleritis: Conjunctivitis typically presents with mild hyperemia, tearing, and surface discomfort. Episcleritis produces sectoral redness and tenderness, while scleritis results in deeper pain and diffuse or nodular scleral inflammation. Scleritis may mimic autoimmune etiologies; necrotizing disease is rare but indicates severe inflammation.[10]
- Dacryoadenitis and lacrimal system involvement: Dacryoadenitis presents with unilateral eyelid swelling, lacrimal gland tenderness, and tearing. Involvement of the lacrimal drainage apparatus may cause epiphora or predispose to secondary infections.[10]
- Corneal involvement: Nummular keratitis manifests as bilateral or unilateral subepithelial infiltrates resembling viral or immune-mediated keratitis. Interstitial keratitis may cause stromal haze and photophobia. Corneal ulceration is uncommon and generally occurs in severe anterior segment inflammation or delayed therapy.[10]
- Anterior uveitis: Anterior uveitis is one of the most common ocular manifestations. It may be granulomatous or nongranulomatous and presents with anterior chamber cells, flare, keratic precipitates, synechiae, and occasionally hypopyon. Symptoms include pain, photophobia, and blurred vision. Chronic or recurrent inflammation can result in cataract and secondary glaucoma.[10]
Table 2. Key Anterior Segment Manifestations
| Manifestation | Typical Presentation | Clinical Relevance |
|---|---|---|
| Conjunctivitis | Mild redness, tearing, irritation | Often self-limited; may accompany systemic brucellosis. |
| Scleritis | Deep pain, nodular or diffuse injection | Must distinguish from autoimmune scleritis; may be severe. |
| Nummular/interstitial keratitis | Subepithelial infiltrates, stromal haze | May mimic viral keratitis; requires systemic therapy. |
| Anterior uveitis | Cells/flare, KPs, synechiae, hypopyon | May lead to cataract or secondary glaucoma if untreated. |
Intermediate, Posterior, and Panuveitis
Posterior and panuveitic disease represent the most vision-threatening ocular manifestations of brucellosis. These forms of inflammation often correlate with delayed systemic diagnosis, undertreated infection, or chronic disease.[11]
- Intermediate uveitis: Intermediate uveitis is characterized by vitreous cells, snowballs, and peripheral vascular changes. Patients experience floaters and blurred vision, with minimal anterior segment inflammation. It may remain isolated or progress to posterior uveitis or panuveitis.[11]
- Posterior uveitis: Posterior involvement includes choroiditis, chorioretinitis, retinitis, and retinal vasculitis. Chorioretinal lesions may be multifocal and associated with vitritis. Retinal vasculitis may produce vascular sheathing, hemorrhages, cotton-wool spots, and ischemia. Severe vasculitis may cause retinal vascular occlusions, macular ischemia, or serous detachment. Retinitis can resemble viral or autoimmune etiologies.[11]
- Choroiditis and chorioretinitis: Lesions may be solitary or multifocal. Complications include cystoid macular edema and serous retinal detachment. OCT and angiography may be necessary when visualization is limited by vitritis.[11]
- Panuveitis: Panuveitis reflects inflammation across the anterior chamber, vitreous, retina, and choroid. It is more common in chronic or relapsing disease and carries increased risk of cataract, glaucoma, macular edema, and optic nerve damage.[11]
- Endophthalmitis: Endophthalmitis is rare but severe, presenting with rapid vision loss, hypopyon, and dense vitritis. Management requires systemic antibiotics and often vitrectomy. Prognosis is guarded.[11]
Table 3. Posterior Segment Manifestations and Associated Risks
| Manifestation | Clinical Features | Potential Complications |
|---|---|---|
| Retinitis | White lesions, hemorrhages, cotton-wool spots | Risk of macular involvement, ischemia. |
| Retinal vasculitis | Sheathing, leakage, occlusion | BRAO/BVO, macular ischemia, neovascularization. |
| Choroiditis / chorioretinitis | Multifocal lesions, vitritis | CME, serous retinal detachment. |
| Panuveitis | Pan-ocular inflammation | Cataract, glaucoma, CME, tractional changes. |
| Endophthalmitis | Hypopyon, dense vitritis | Poor prognosis; often requires vitrectomy. |
Neuro-Ophthalmic Manifestations
Neuro-ophthalmic involvement reflects extension of infection or inflammation to the meninges, optic nerve, or intracranial vasculature. Optic neuritis presents with reduced visual acuity, impaired color vision, and visual field defects; the optic disc may appear swollen or later become pale depending on disease stage.[12] Papilledema arises in the setting of increased intracranial pressure, most often associated with meningitis or meningoencephalitis, and typically presents with headache or transient visual obscurations. Cranial nerve palsies, especially abducens nerve dysfunction, manifest as binocular diplopia and result from meningeal inflammation or raised intracranial pressure. Rare cortical or optic tract involvement may lead to homonymous field defects with corresponding MRI abnormalities.[12]
Table 1. Neuro-Ophthalmic Findings and Key Clinical Indicators
| Manifestation | Clinical Indicators | When to Suspect |
|---|---|---|
| Optic neuritis | Visual loss, dyschromatopsia, field defects | Neurobrucellosis or unexplained optic neuropathy in endemic settings |
| Papilledema | Disc edema with preserved visual acuity early | Headache or suspected meningitis |
| CN VI palsy | Horizontal diplopia, abduction deficit | Elevated ICP or meningeal irritation |
| Cortical involvement | Homonymous field loss | CNS lesions on MRI |
Diagnostic Evaluation
Diagnosis requires correlation of systemic risk factors with ocular findings and confirmatory laboratory testing. Exposure history should include unpasteurized dairy ingestion, livestock contact, or residence in endemic regions.[13] Ocular examination focuses on identifying uveitis, retinitis, vasculitis, disc edema, or vitritis. Serologic testing (Wright agglutination, Coombs, or ELISA) establishes systemic infection, while cultures—although less sensitive—offer definitive confirmation. CSF examination is essential when neuro-ophthalmic signs are present.[13]
Imaging complements clinical assessment. OCT characterizes macular edema or serous detachments; fluorescein angiography delineates vasculitis and chorioretinal involvement; B-scan assists with media opacity. MRI of the brain and orbits is reserved for suspected neurobrucellosis or optic neuropathy.[13]
Table 2. Diagnostic Modalities and Principal Utility
| Modality | Primary Utility |
|---|---|
| Serologic testing | Confirms systemic brucellosis |
| Culture (blood or marrow) | Definitive identification when positive |
| CSF analysis | Required for neurobrucellosis evaluation |
| OCT | Defines macular involvement |
| FA/ICG angiography | Identifies retinal/choroidal inflammation and leakage |
| MRI brain/orbits | Detects optic nerve or meningeal involvement |
Management
Management centers on adequate systemic antimicrobial therapy, which is essential for resolving ocular inflammation and preventing relapse. Standard regimens combine doxycycline with rifampin for at least six weeks, with aminoglycosides added for severe or complicated cases. Neurobrucellosis and recurrent disease typically require prolonged treatment.[14]
Ocular therapy addresses inflammation and its sequelae. Topical corticosteroids and cycloplegics are used for anterior uveitis, while systemic corticosteroids may be considered for posterior uveitis or optic neuropathies once antimicrobial therapy is initiated. Macular edema or persistent vitritis may require adjunctive periocular or intravitreal corticosteroids in selected cases. Pars plana vitrectomy is reserved for complications such as non-clearing vitritis, retinal detachment, or endophthalmitis.[14]
Multidisciplinary coordination with infectious disease and neurology optimizes outcomes, especially in neuro-ophthalmic presentations. Close follow-up is critical due to the potential for delayed complications or recurrence.[14]
Differential Diagnosis
Because ocular brucellosis imitates numerous infectious and inflammatory diseases, the differential diagnosis must remain broad until systemic and serologic evaluation clarifies the etiology. Tuberculosis is frequently considered due to overlapping presentations of granulomatous uveitis, choroiditis, and retinal vasculitis. Syphilis can produce posterior uveitis, neuro-ophthalmic findings, and vasculitis indistinguishable from brucellosis without serologic testing. [15] Viral retinitides (HSV, VZV, CMV) may mimic multifocal retinitis but often progress more rapidly and show characteristic necrosis patterns. Sarcoidosis and Behçet disease may present with panuveitis or occlusive vasculitis; however, these typically lack the systemic infection profile of brucellosis. Endogenous bacterial endophthalmitis should be considered in cases of severe vitritis or hypopyon, especially in patients with systemic risk factors.[15]
Table 3. Key Distinguishing Features in the Differential Diagnosis
| Condition | Distinguishing Features |
|---|---|
| Tuberculosis | Positive IGRA or chest imaging; chronic granulomatous uveitis |
| Syphilis | Positive treponemal tests; wide range of uveitis patterns |
| Viral retinitis | Rapid progression, necrosis, marked retinal whitening |
| Sarcoidosis | Noncaseating granulomas; bilateral hilar lymphadenopathy |
| Behçet disease | Recurrent oral/genital ulcers; occlusive vasculitis |
| Endogenous bacterial endophthalmitis | Severe vitritis with systemic bacteremia or sepsis |
Complications
Complications arise primarily from prolonged inflammation, delayed treatment, or severe posterior segment involvement. Cystoid macular edema is among the most common causes of persistent visual decline and may require adjunctive local therapy once infection control is established. Retinal vascular occlusions, particularly in occlusive vasculitis, can lead to macular ischemia or neovascular complications. Chronic uveitis predisposes patients to cataract formation and secondary glaucoma, which may persist even after systemic infection resolves. Optic neuropathy, whether inflammatory or ischemic, leads to irreversible visual field loss in advanced cases.[16] Endophthalmitis represents the most severe complication, often resulting in profound vision loss despite aggressive management. Long-term follow-up is essential to monitor for relapse, structural damage, or secondary ocular disease.[16]
Prognosis
Visual prognosis in ocular brucellosis varies widely and depends on the severity and chronicity of intraocular inflammation, the promptness of therapy, and the presence of complications such as macular edema or optic neuropathy. Anterior uveitis typically responds well to antimicrobial therapy and has a favorable outcome when treated early. Posterior uveitis, retinal vasculitis, and panuveitis carry greater risk for permanent visual impairment due to macular ischemia, retinal atrophy, or optic nerve damage. Neuro-ophthalmic involvement portends a guarded prognosis, particularly when optic nerve injury is extensive or when diagnosis is delayed. Recurrence is possible, especially when systemic therapy is inadequate or prematurely discontinued, emphasizing the need for follow-up afte[2]
Special Considerations, Prevention, and Long-Term Follow-Up
Certain patient groups require additional attention when evaluating and managing ocular brucellosis. Children may present with more frequent neuro-ophthalmic manifestations, including optic neuritis or papilledema, and are at greater risk of elevated intracranial pressure due to their susceptibility to neurobrucellosis.[12] Pregnant patients pose a therapeutic challenge because standard antimicrobial agents such as doxycycline and certain aminoglycosides are contraindicated; rifampin-based regimens may be required. Immunocompromised individuals can exhibit atypical or aggressive posterior inflammation and are more prone to relapse without extended antimicrobial courses.[12]
Prevention is primarily achieved through control of systemic brucellosis. Public health measures include pasteurization of dairy products, screening of livestock, occupational protection for high-risk workers, and improved diagnostic access in endemic regions. For patients diagnosed with ocular brucellosis, early initiation of appropriate antimicrobial therapy remains the most effective strategy to reduce the risk of complications and recurrent inflammation. Educating patients about the importance of treatment adherence and completion of the full therapeutic course is essential to prevent relapse, which is a recognized contributor to chronic ocular morbidity.[17]
Long-term follow-up is recommended even after clinical improvement. Posterior uveitis and neuro-ophthalmic disease may evolve over weeks or months, and structural complications such as macular edema, optic nerve damage, cataract, or secondary glaucoma may appear late in the disease course. Regular monitoring with visual acuity testing, intraocular pressure measurement, and OCT is particularly valuable in patients with macular involvement.[17] Those with a history of neurobrucellosis require periodic neurologic assessment and may benefit from repeat imaging if symptoms recur.[17]
References
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- ↑ 1.0 1.1 Hayoun MA, Muco E, Shorman M. Brucellosis. [Updated 2023 Apr 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441831/
- ↑ 2.0 2.1 2.2 Rolando I, Olarte L, Vilchez G, Lluncor M, Otero L, Paris M, Carrillo C, Gotuzzo E. Ocular manifestations associated with brucellosis: a 26-year experience in Peru. Clin Infect Dis. 2008 May 1;46(9):1338-45. doi: 10.1086/529442. PMID: 18419433.
- ↑ Qureshi KA, Parvez A, Fahmy NA, Abdel Hady BH, Kumar S, Ganguly A, Atiya A, Elhassan GO, Alfadly SO, Parkkila S, Aspatwar A. Brucellosis: epidemiology, pathogenesis, diagnosis and treatment-a comprehensive review. Ann Med. 2023;55(2):2295398. doi: 10.1080/07853890.2023.2295398. Epub 2024 Jan 2. PMID: 38165919; PMCID: PMC10769134.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Huy TXN, Nguyen TT, Kim H, Reyes AWB, Kim S. Brucella Phagocytosis Mediated by Pathogen-Host Interactions and Their Intracellular Survival. Microorganisms. 2022 Oct 11;10(10):2003. doi: 10.3390/microorganisms10102003. PMID: 36296279; PMCID: PMC9610446.
- ↑ 5.0 5.1 El Jammal T, Loria O, Jamilloux Y, Gerfaud-Valentin M, Kodjikian L, Sève P. Uveitis as an Open Window to Systemic Inflammatory Diseases. J Clin Med. 2021 Jan 14;10(2):281. doi: 10.3390/jcm10020281. PMID: 33466638; PMCID: PMC7828680.
- ↑ 6.0 6.1 Marques R, Martins C, Machado I, Monteiro JP, Campos N, Calhau P. Unilateral optic neuritis as a presentation of neurobrucellosis. Pediatr Rep. 2011 Jun 16;3(2):e11. doi: 10.4081/pr.2011.e11. PMID: 21772948; PMCID: PMC3133493.
- ↑ Evlice O, Çeviker SA, Filik A, Ağın A. Ocular Involvement of Brucellosis: A Pooled Analysis Study. Ocul Immunol Inflamm. 2023 Oct;31(8):1677-1686. doi: 10.1080/09273948.2022.2164727. Epub 2023 Jan 13. PMID: 36638336
- ↑ Evlice O, Çeviker SA, Filik A, Ağın A. Ocular Involvement of Brucellosis: A Pooled Analysis Study. Ocul Immunol Inflamm. 2023 Oct;31(8):1677-1686. doi: 10.1080/09273948.2022.2164727. Epub 2023 Jan 13. PMID: 36638336.
- ↑ 9.0 9.1 Ghasemi Barghi R, Meraat H, Pahlevan AA. A review on ophthalmic manifestations of brucellosis and reporting a case of ophthalmic brucellosis. Iran Red Crescent Med J. 2011 May;13(5):352-3. Epub 2011 May 1. PMID: 22737494; PMCID: PMC3371975.
- ↑ 10.0 10.1 10.2 10.3 10.4 Ma C, Li H, Lu S, Li X, Wang S, Wang W. Ocular Lesions in Brucella Infection: A Review of the Literature. Infect Drug Resist. 2022 Dec 22;15:7601-7617. doi: 10.2147/IDR.S394497. PMID: 36579126; PMCID: PMC9791996.
- ↑ 11.0 11.1 11.2 11.3 11.4 11.5 AlMutairi N, AlRubaie K, Asharari KS, Albalawi HB. Unusual bilateral panuveitis uveitis with brucellosis. Saudi J Ophthalmol. 2022 Feb 18;35(2):143-145. doi: 10.4103/1319-4534.337852. PMID: 35391805; PMCID: PMC8982952.
- ↑ 12.0 12.1 12.2 12.3 Uygun GG, Balci SY, Tireli H. Neurobrucellosis Manifesting as an Altitudinal Visual Field Defect. J Coll Physicians Surg Pak. 2022 Dec;32(12):SS154-SS156. doi: 10.29271/jcpsp.2022.Supp0.SS154. PMID: 36597323.
- ↑ 13.0 13.1 13.2 Aroch I, Ofri R, Sutton GA. Ocular Manifestations of Systemic Diseases. Slatter's Fundamentals of Veterinary Ophthalmology. 2008:374–418. doi: 10.1016/B978-072160561-6.50021-6. Epub 2009 Jun 5. PMCID: PMC7150115.
- ↑ 14.0 14.1 14.2 Alavi SM, Alavi L. Treatment of brucellosis: a systematic review of studies in recent twenty years. Caspian J Intern Med. 2013 Spring;4(2):636-41. PMID: 24009951; PMCID: PMC3755828.
- ↑ 15.0 15.1 Konana VK, Babu K. Current concepts in the diagnosis of ocular tuberculosis: A narrative review. Taiwan J Ophthalmol. 2025 Jun 10;15(2):203-211. doi: 10.4103/tjo.TJO-D-24-00115. PMID: 40584192; PMCID: PMC12204663.
- ↑ 16.0 16.1 Rotsos TG, Moschos MM. Cystoid macular edema. Clin Ophthalmol. 2008 Dec;2(4):919-30. doi: 10.2147/opth.s4033. PMID: 19668445; PMCID: PMC2699812.
- ↑ 17.0 17.1 17.2 Mohammadi Z, Dehghani A, Ghanbari HO, Akhlaghi MR, Nasrollahi K, Salam H. Ocular manifestations in a child with systemic brucellosis. J Res Med Sci. 2014 Jul;19(7):677-9. PMID: 25364370; PMCID: PMC4214029.
