Clinicians traditionally recognize cat scratch disease as the classic cause of neuroretinitis with macular star formation. However, recent evidence reveals a broader spectrum of ocular disease. A multi-centre study demonstrates that Bartonella-associated uveitis presents with varied anatomical manifestations across tertiary clinics. Notably, atypical phenotypes occurred just as frequently as classical neuroretinitis. Therefore, ophthalmologists must expand diagnostic suspicion beyond traditional paradigms when evaluating posterior uveitis.

Spectrum of Clinical Presentations in Bartonella-Associated Uveitis

Historically, ophthalmologists have linked intraocular Bartonella infections primarily with optic disc edema accompanied by macular exudation. Nevertheless, this multi-centre investigation demonstrates that classic neuroretinitis represents only 50.0% of confirmed cases. Specifically, researchers evaluated seventy eyes of fifty-three patients presenting across tertiary uveitis centres. They discovered that posterior uveitis was the most frequent anatomical classification, occurring in 57.1% of eyes. Meanwhile, panuveitis developed in 30.0% of cases, demonstrating that inflammation frequently affects multiple intraocular compartments. Furthermore, visual acuity varied widely at presentation. The median presenting best-corrected visual acuity was 20/50, but recorded values ranged from 20/20 to 20/400. Thus, physicians should not expect mild visual impairment in every patient. In addition, bilateral disease occurred in a notable subset of individuals, which initially suggested autoimmune panuveitis. Consequently, these findings prove that ocular bartonellosis generates extensive anatomical disruption rather than simple focal neuroretinitis. As a result, clinicians should suspect this pathogen in various severe posterior inflammatory conditions, ensuring timely antimicrobial intervention.

Frequency and Diversity of Non-Neuroretinitis Phenotypes

Importantly, the multi-centre study established that non-classical ocular phenotypes represent half of all presentations. Although neuroretinitis occurred in 35 eyes, non-neuroretinitis manifestations proved remarkably common across the cohort. For instance, optic neuritis without macular stars appeared in 34.3% of evaluated eyes. Furthermore, multifocal retinitis presented in 30.0% of cases as discrete retinal infiltrates. In addition, isolated papillitis affected 24.3% of eyes, which frequently mimics idiopathic intracranial hypertension. Retinal vascular occlusions developed in 18.6% of eyes, leading to localized retinal ischemia and hemorrhages. Notably, clinicians observed multifocal choroiditis in 11.4% of patients. Because these presentations deviate from classical descriptions, clinicians often suspect non-infectious autoimmune conditions. Consequently, many patients risk receiving inappropriate high-dose systemic immunosuppressive therapy without antimicrobial protection. Therefore, ophthalmologists must appreciate that Bartonella causes diverse retinal vascular and neurosensory pathology. Understanding this phenotypic diversity ensures earlier diagnostic testing and prevents irreversible visual morbidity in tertiary uveitis practice.

Diagnostic Challenges and Multimodal Imaging Modalities

Accurate clinical identification of atypical phenotypes requires structured multimodal ophthalmic imaging and confirmatory laboratory evaluation. Fundus fluorescein angiography plays an indispensable diagnostic role by identifying active optic disc leakage, retinal vasculitis, and capillary non-perfusion. In addition, optical coherence tomography visualizes subretinal fluid, retinal thickening, and early intraretinal lipid deposits before macular stars form. Similarly, indocyanine green angiography detects distinct hypocyanescent choroidal spots in eyes with concurrent choroiditis. However, imaging findings alone cannot differentiate bartonellosis from tuberculosis, syphilis, or sarcoidosis. Therefore, clinicians must obtain definitive serological confirmation using indirect immunofluorescence assays. High IgM antibody titers or a fourfold rise in convalescent IgG titers confirm active infection. Nevertheless, clinical diagnosis remains difficult because patients often lack systemic signs, such as fever or regional lymphadenopathy. Moreover, many individuals do not recall prior kitten scratches. Consequently, physicians practicing in endemic areas must maintain rigorous exposure histories and order Bartonella serologies when encountering atypical retinal inflammatory lesions.

Pathophysiological Mechanisms Behind Ocular Inflammation

Investigating the microbiological pathophysiology clarifies why Bartonella triggers varied intraocular presentations. Bartonella henselae is a fastidious, Gram-negative facultative intracellular bacterium that exhibits marked tropism for vascular endothelial cells and erythrocytes. After vector transmission or animal scratch inoculation, the organism enters bloodstream circulation. Subsequently, the bacterium invades endothelial cells and stimulates pro-angiogenic cascades alongside localized microvascular thrombosis. This profound endothelial injury explains why patients develop branch retinal vein or artery occlusions during active infection. Furthermore, direct invasion of the optic nerve head provokes intense vascular permeability, causing peripapillary fluid leakage. Consequently, lipid-rich exudates track into the outer plexiform layer, producing the classic stellate macular star. In contrast, when cell-mediated immune responses or direct bacterial seeding predominate in retinal tissues, multifocal retinitis or isolated papillitis develops instead. As a result, patients present with non-neuroretinitis phenotypes rather than typical neuroretinitis. Therefore, the balance between direct angioproliferative bacterial activity and host inflammatory response determines the clinical phenotype.

Therapeutic Approaches and Clinical Management Strategies

Prompt initiation of targeted antimicrobial therapy remains vital to preserve vision in posterior segment disease. Although systemic cat scratch disease in immunocompetent individuals often resolves spontaneously, intraocular involvement requires active medical management. In particular, oral doxycycline represents the preferred first-line antimicrobial agent because it demonstrates superior intraocular and central nervous system penetration. Clinicians typically prescribe doxycycline at 100 mg twice daily for four to six weeks. Additionally, specialists frequently co-prescribe oral rifampicin at 300 mg twice daily to achieve synergistic intracellular eradication. For pediatric patients or pregnant individuals, azithromycin or trimethoprim-sulfamethoxazole offers a safe, effective therapeutic alternative. Furthermore, clinicians can add oral corticosteroids to suppress severe optic disc edema, macular exudation, and retinal vasculitis. However, physicians must never administer systemic corticosteroids without concurrent bactericidal coverage. Doing so induces rapid bacterial proliferation and extensive retinal necrosis. Finally, serialized optical coherence tomography and visual field testing ensure complete resolution of inflammation and safeguard long-term visual acuity.

What are the most common non-neuroretinitis manifestations of Bartonella infection?

Beyond classical neuroretinitis, Bartonella infection frequently causes optic neuritis, multifocal retinitis, and isolated papillitis. In addition, patients regularly develop retinal vascular occlusions and multifocal choroiditis. These atypical phenotypes can occur independently without the traditional macular star pattern. Consequently, clinicians must recognize that intraocular bartonellosis presents across a diverse continuum of posterior segment inflammation, requiring high clinical suspicion whenever evaluating unexplained chorioretinal lesions or vascular events.

How do clinicians confirm the diagnosis of ocular Bartonella infection?

Clinicians confirm ocular Bartonella through targeted serological testing alongside comprehensive multimodal imaging. Serum indirect immunofluorescence or enzyme-linked immunosorbent assays detect diagnostic IgM and IgG titers. A significantly elevated IgM titer or a fourfold rise in convalescent IgG titers confirms recent infection. Additionally, fluorescein angiography and optical coherence tomography identify focal retinitis, disc hyperfluorescence, and neurosensory detachments, helping physicians differentiate bartonellosis from other infectious or autoimmune uveitic etiologies.

Why must corticosteroids be combined with antibiotics in Bartonella uveitis?

Corticosteroids potently reduce intraocular inflammation, macular edema, and optic disc swelling, which significantly accelerates visual recovery. However, Bartonella is an active bacterial infection. Administering corticosteroids alone without bactericidal coverage suppresses host immune defense and promotes unchecked microbial proliferation. Therefore, physicians must always initiate targeted antibiotics, such as doxycycline or rifampicin, before or concurrently with oral corticosteroids to treat the infection safely and prevent irreversible visual morbidity.

Disclaimer: This content is for informational and educational purposes only and should not be considered medical advice. Always consult a qualified healthcare professional regarding any medical condition or treatment. Refer to the latest local and national guidelines for clinical practice.

References

1. Samalia PD et al. Beyond Neuroretinitis: A Multi-Centre Study of Bartonella-Associated Uveitis. Ocul Immunol Inflamm. 2026 Sep 23. doi: 10.1080/09273948.2026.2735417. PMID: 42773980.
2. Cirone D, Mandarà E, De Simone L, Pellegrini F, Cimino L. Ophthalmic manifestations of cat scratch disease. Ann Eye Sci. 2021;6:14.
3. Kalogeropoulos D, Koumpoulis I, Mentis A, et al. Bartonella henselae- and quintana-associated uveitis: a case series and approach of a potentially severe disease with a broad spectrum of ocular manifestations. Int Ophthalmol. 2020;40(3):711-721.