Skip to main content

Central retinal vein occlusion associated with Bartonella henselae infection

Abstract

Purpose

To report the clinical features and treatment course of a case of central retinal vein occlusion (CRVO) as the initial sign of ocular Bartonella henselae (B. henselae) infection.

Observation

A 36-year-old male was evaluated for unilateral vision loss. He denied prodromal symptoms but reported prior exposure to fleas. Best corrected visual acuity (BCVA) was 20/400 in the left eye. Clinical examination revealed a CRVO with atypical features including significant peripapillary exudates and peripheral vascular sheathing. Laboratory testing revealed elevated B. henselae IgG titers (1:512) with no abnormalities on hypercoagulability testing. The patient was treated with doxycycline and aflibercept with an excellent clinical response and improvement in BCVA to 20/25 in the left eye two months later.

Conclusion

CRVO is a rare but sight-threatening complication of ocular bartonellosis and can be the presenting sign of infection, even in the absence of cat exposure or prodromal symptoms.

Introduction

Bartonella henselae (B. henselae) is a gram-negative, intracellular bacteria that is the causative agent of cat-scratch disease (CSD). Transmission of B. henselae typically occurs through cat scratches, bites, or wound contamination with over 90% of CSD cases reporting a history of exposure to cats; however, direct human exposure to the cat flea (Ctenocephalides felis) or its feces has also been implicated in disease pathogenesis [1,2,3]. The clinical presentation of CSD is variable and ranges from mild self-limited disease to atypical cases that include ocular findings [4].

Ocular bartonellosis is uncommon and occurs in 5–10% of patients [5]. While the most common ocular manifestation is Parinaud’s oculoglandular syndrome, other reported findings include vascular and inflammatory changes such as retinal vascular occlusions, neuroretinitis, vitritis, retinitis, retinal vasculitis, serous retinal detachments, and choroiditis [6, 7]. The prevalence of retinal vascular occlusions in ocular bartonellosis is variable, with one review article reporting a rate of 4–23% [8]. The majority of vascular occlusions involve a branch artery or vein, with central retinal vein occlusion (CRVO) due to B. henselae infection being exceedingly rare (two reported adult cases) and associated with broader, severe ischemic ocular disease [9, 10]. We report a unique case of a 36-year-old patient with no exposure to cats or prodromal illness who presented with a CRVO as the only clinical sign, with subsequent serologic testing revealing B. henselae infection. The patient had excellent visual recovery with oral doxycycline and anti-vascular endothelial growth factor (anti-VEGF) therapy.

Case report

A 36-year-old Ethiopian male presented with a 10-day history of acute, painless vision loss in the left eye (OS). A review of systems was negative. His past medical history was notable for hiatal hernia related gastric ulcers; there was no history of vascular risk factors apart from prior tobacco use. The patient denied exposure to cats but lived on farmland where fleas were reportedly endemic. On evaluation, his best corrected visual acuities (BCVA) were 20/20 in his right eye (OD) and 20/400 in the left eye (OS). A 1 + relative afferent pupillary defect OS was present. Anterior segment exam was notable for trace pigmented cell in the anterior chamber OS. Fundus examination of the left eye revealed trace pigmented anterior vitreous cell with no haze, optic disc edema, macular edema with exudates in the nasal macula, scattered cotton wool spots, mildly increased venular engorgement with peripheral vascular sheathing, and diffuse intraretinal hemorrhages in the macula and all four quadrants of the periphery (Fig. 1B). Optical coherence tomography (OCT) of the macula showed subretinal fluid with cystoid macular edema (CME) OS (Fig. 1D). Fluorescein angiography revealed leakage of the disc and macula with peripheral capillary ischemia and diffuse vessel leakage consistent with a predominant phlebitis OS (Fig. 2B, D). The findings were consistent with an ischemic central retinal vein occlusion OS. Clinical exam and multimodal imaging in the right eye were unremarkable (Figs. 1 A, C and 2 A, C).

Fig. 1
figure 1

Wide-field color fundus photos demonstrating normal findings in the right eye (A), and optic disc edema, macular edema with peripapillary exudates, venous engorgement with vascular sheathing in nasal periphery, and diffuse hemorrhages consistent with a central retinal vein occlusion in the left eye (B). Optical coherence tomography shows no abnormalities in the right eye (C), and prominent subretinal and cystic intraretinal fluid with inner retinal thickening nasally in the left eye (D)

Fig. 2
figure 2

Wide-field fluorescein angiography shows no retinal vascular leakage in the right eye (AC). In the left eye there is peripheral ischemia seen in early and late frames with disc leakage, macular leakage, and diffuse, large vessel, vascular leakage predominantly affecting the venules (BD)

Given the patient’s young age and lack of vascular risk factors, a laboratory workup was performed to identify potential underlying precipitating factors such as coagulation disorders, infection, or inflammatory diseases. The blood pressure was 132/84, hemoglobin A1c was 5.0%, and no dyslipidemia was noted on lipid panel testing. An extensive hypercoagulable workup was unrevealing including normal homocysteine levels, protein C/S levels, antithrombin III activity, anti-cardiolipin levels, and absence of anti-proteinase-3 and anti-myeloperoxidase antibodies. No prothrombin 20210 or factor V leiden mutation was detected. Infectious workup revealed positive Bartonella henselae IgG with elevated titers of 1:512 on immunofluorescence assay testing (Mayo Clinic Laboratories, Rochester, MN). IgM antibodies were negative. Syphilis total antibody testing, quantiFERON-TB Gold, and HIV 1/2 testing were all negative. Toxoplasma gondii IgG antibodies were mildly positive (84 International Units/mL) while no IgM antibodies were detected.

The patient was diagnosed with a CRVO in the setting of Bartonella henselae infection based on high B. henselae IgG titers, atypical presentation including the observed inflammatory findings, and the absence of co-existent risk factors. The patient was started on doxycycline 100 mg PO BID and treated with monthly aflibercept injections for the CME. Initiation of oral steroids was deferred given the patient’s concurrent gastric ulcers.

Repeat examination two months after completing a 4-week course of doxycycline and receiving two aflibercept injections showed improvement in the left eye with a BCVA of 20/25 with resolution of pigmented anterior chamber cell and stable trace pigmented vitreous cell. Multimodal imaging of the left eye revealed improvement of the retinal hemorrhages with resolution of optic disc edema and vascular sheathing (Fig. 3A). Repeat OCT of the macula showed resolution of subretinal fluid and cystoid macular edema with residual focal ellipsoid zone irregularities (Fig. 3B). On fluorescein angiography there was resolution of disc and macular leakage along with resolved vascular leakage; there was improved but persistent peripheral ischemia (Fig. 3C, D). Repeat B. henselae titers revealed lower IgG titers (1:256) and negative IgM titers.

Fig. 3
figure 3

Repeat evaluation 2-months after presentation and treatment initiation shows resolution of optic disc edema and improvement of retinal hemorrhages (A). Optical coherence tomography shows resolution of subretinal and intraretinal fluid with residual focal ellipsoid zone irregularities (B). There is near resolution of leakage on fluorescein angiogram with persistent but improved peripheral ischemia during mid-phase (C) and late frames (D)

Discussion

We report a rare case of CRVO associated with B. henselae infection confirmed by serological testing. Our patient lacked the preceding contact to cats but did have exposure to arthropod vectors such as fleas. The CRVO was suspected to be inflammatory in etiology given the patient’s young age, absence of vascular and hypercoagulable risk factors, and clinical features such as vascular sheathing, severe phlebitis on fluorescein angiogram, and prominent peripapillary exudates. There was an excellent clinical response to anti-VEGF agents and oral doxycycline.

The clinical presentation of B. henselae infection can involve multiple organ systems. Systemic findings seen in typical CSD can include transient papules or pustules at the inoculation site followed by regional lymphadenopathy with or without fever [11]. Other findings are broad and can range from constitutional symptoms such as malaise, nausea, vomiting and anorexia to organic specific findings such as hepatomegaly, splenomegaly, endocarditis, hemolytic anemia, thrombocytopenic purpura, glomerulonephritis, and osteomyelitis [5, 11]. Immunocompromised patients are at risk of bacillary angiomatosis, altered mental status and dementia [5].

Ocular manifestations of B. henselae infection are varied and can affect numerous ocular structures. While Parinaud’s oculoglandular syndrome with fever, granulomatous conjunctivitis, and regional lymphadenopathy is the most common ocular finding, posterior segment manifestations including neuroretinitis, retinochoroiditis, retinitis, macular hole, serous retinal detachments, vitritis, vasculitis, papillitis, retinal bacillary angiomatosis, subretinal vascular masses, uveitis, and retinal vascular occlusions have been reported in the literature [2, 6, 7]. Bilateral ocular involvement has been described in 17–24% of patients; 58% of ocular bartonellosis patients reported fever and 77% had malaise and/or weakness in one retrospective study by Habot-Wilner and colleagues [5, 6].

Reported literature cites branch retinal vascular occlusions as the most common variant of vascular occlusion in ocular bartonellosis and may be the presenting sign of disease [6, 8]. In a 20-year retrospective study, 8/107 (7%) of eyes had a retinal vascular occlusion; four eyes had a branched retinal artery occlusion (BRAO), three had branched retinal vein occlusion (BRVO), and one patient had a combined BRAO and BRVO. In one case, the BRVO was the only manifestation of CSD [6]. A case series from Greece of 14 eyes of eight patients with ocular bartonellosis noted one 36-year-old patient with a BRVO and periphlebitis on fluorescein angiography and an IgG titer of 1:32. Treatment with rifampin and azithromycin lead to an improvement in visual acuity and macular edema [11]. Eiger-Moscovich et al. showed six, young, otherwise healthy patients with a BRAO due to B. henselae infection. Four patients had an exposure to cats, while one patient had a history of flea bites and another with no exposure identified; all patients had a single highly elevated IgG or IgM titer for B. henselae [12]. A study of 35 eyes with ocular bartonellosis with posterior segment findings reported a retinal vascular occlusion in 14% of eyes, with four patients having a BRAO and one patient with a BRVO. On imaging the point of occlusion was closely associated with a focus of chorioretinal inflammation [7]. Several theories have been postulated for the association of B. henselae infection and retinal vascular occlusion. B. henselae has a propensity to invade vascular endothelium and is thought to induce vascular occlusion either through a direct obliterative vasculitis from the organisms themselves or via vascular endothelial damage resulting in thrombogenesis and vaso-occlusion. An intense, focal, inflammatory response may also result in a mechanical obstruction. Optic disc swelling leading to vascular compression has also been implicated [6, 7, 9, 12].

Cases involving CRVO are much more limited. Only two cases of CRVO associated with B. henselae infection in adults and one possible case in a child have been reported with 2 of the three cases reporting a history of cat exposure [9, 10, 13]. Both adult patients initially presented with classic ocular signs of B. henselae infection and subsequently developed CRVO along with broader, severe, ocular ischemic disease in the absence of treatment. Ghadiali et al. reported a patient who initially presented with optic neuritis, peripapillary hemorrhage and macular star formation with initially negative Bartonella serologies. Repeat evaluation revealed elevated B. henselae IgG titers (1:256) with the subsequent exam showing development of central retinal vein occlusion, concurrent choroidal ischemia and ischemic retinopathy that improved without treatment [9]. Gray and colleagues described a patient who presented with optic disc edema in the setting of illness and cervical and preauricular lymphadenopathy 4 weeks prior. The patient subsequently developed an exudative macular star and reported being previously scratched by a kitten, B. henselae IgG titers were elevated (1:128). The patient was non-compliant with antibiotic therapy and developed a combined central retinal artery occlusion and CRVO with neovascular glaucoma [9, 10].

The mainstay of laboratory diagnosis of CSD is serological testing, however local seroprevalence can make interpretation challenging as healthy persons may have low titers of B. henselae [6]. Seroprevalence rates differ amongst countries, with seropositivity seen in up to 32.38% in Eastern China, 13.7% in Brazil, 5% in New Zealand, and 10.3% in vulnerable populations in the United States and Europe [14,15,16]. IgG titers greater or equal to 1:256 on serologic testing confirms presence of CSD, and to our knowledge this is the first reported case of B. henselae associated CRVO with titers above this threshold, suggesting an active or recent infection [14, 17, 18]. While the presence of IgM antibodies is also useful to detect acute infection, its utility is limited by variable or limited sensitivities [14]. Our case adds to the scarce literature showing that not only is CRVO an exceedingly rare manifestation of ocular bartonellosis, but as in our patient it can be the presenting clinical finding, be associated with acute or recent infection, occur in the absence of cat exposure or broader ocular ischemic disease, and have excellent visual recovery with prompt treatment.

A CRVO in an adult under 40 years-old warrants a thorough workup of inflammatory and infectious etiologies, including a careful history and inquire of risk factors for B. henselae [19]. Importantly, while prior exposure to cats and/or prodromal symptoms aids in diagnosis of ocular bartonellosis, they are not required to have the disease. Furthermore, the presence of a CRVO can mask or confound the ability to detect classic signs of ocular bartonellosis such as neuroretinitis due to overlapping features such as optic nerve and macular edema. Therefore, a low threshold for serological testing for B. henselae is warranted in this demographic in order to start prompt antibiotic therapy in addition to anti-VEGF agents to maximize visual recovery.

Availability of data and material

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

B. henselae :

Bartonella henselae

CSD:

Cat-scratch disease

anti-VEGF:

Anti-vascular endothelial growth factor

BCVA:

Best corrected visual acuity

OS:

Left eye

CRVO:

Central retinal vein occlusion

OD:

Right eye

OCT:

Optical coherence tomography

BRAO:

Branched retinal artery occlusion

BRVO:

Branched retinal vein occlusion

CME:

Cystoid macular edema

References

  1. Koehler JE, Glaser CA, Tappero JW (1994) Rochalimaea henselae Infection: A New Zoonosis With the Domestic Cat as Reservoir. JAMA 271(7):531–535. https://doi.org/10.1001/jama.1994.03510310061039.

    Article  CAS  PubMed  Google Scholar 

  2. Roe RH, Michael Jumper J, Fu AD, Johnson RN, Richard McDonald H, Cunningham ET (2008) Ocular Bartonella Infections. Int Ophthalmol Clin 48(3):93–105. https://doi.org/10.1097/IIO.0b013e31817d7697.

    Article  PubMed  Google Scholar 

  3. Chomel BB (2000) Cat-scratch disease. Rev Sci Tech 19(1):136–150. https://doi.org/10.20506/rst.19.1.1204.

    Article  CAS  PubMed  Google Scholar 

  4. Angelakis E, Raoult D (2014) Pathogenicity and treatment of Bartonella infections. Int J Antimicrob Agents 44(1):16–25. https://doi.org/10.1016/j.ijantimicag.2014.04.006.

    Article  CAS  PubMed  Google Scholar 

  5. Biancardi AL, Curi AL (2014) Cat-scratch disease. Ocul Immunol Inflamm 22(2):148–154. https://doi.org/10.3109/09273948.2013.833631.

    Article  PubMed  Google Scholar 

  6. Habot-Wilner Z, Trivizki O, Goldstein M et al (2018) Cat-scratch disease: ocular manifestations and treatment outcome. Acta Ophthalmol 96(4):e524–e532. https://doi.org/10.1111/aos.13684.

    Article  CAS  PubMed  Google Scholar 

  7. Solley WA, Martin DF, Newman NJ et al (1999) Cat scratch disease: posterior segment manifestations. Ophthalmology 106(8):1546–1553. https://doi.org/10.1016/s0161-6420(99)90452-9.

    Article  CAS  PubMed  Google Scholar 

  8. Amer R, Tugal-Tutkun I (2017) Ophthalmic manifestations of bartonella infection. Curr Opin Ophthalmol 28(6):607–612. https://doi.org/10.1097/icu.0000000000000419.

    Article  PubMed  Google Scholar 

  9. Ghadiali Q, Ghadiali LK, Yannuzzi LA (2020) BARTONELLA HENSELAE NEURORETINITIS ASSOCIATED WITH CENTRAL RETINAL VEIN OCCLUSION, CHOROIDAL ISCHEMIA, AND ISCHEMIC OPTIC NEUROPATHY. Retin Cases Brief Rep Winter 14(1):23–26. https://doi.org/10.1097/icb.0000000000000612.

    Article  Google Scholar 

  10. Gray AV, Michels KS, Lauer AK, Samples JR (2004) Bartonella henselae infection associated with neuroretinitis, central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss. Am J Ophthalmol 137(1):187–189. https://doi.org/10.1016/s0002-9394(03)00784-0.

    Article  PubMed  Google Scholar 

  11. Kalogeropoulos C, Koumpoulis I, Mentis A, Pappa C, Zafeiropoulos P, Aspiotis M (2011) Bartonella and intraocular inflammation: a series of cases and review of literature. Clin Ophthalmol 5:817–829. https://doi.org/10.2147/opth.S20157.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Eiger-Moscovich M, Amer R, Oray M, Tabbara KF, Tugal-Tutkun I, Kramer M (2016) Retinal artery occlusion due to Bartonella henselae infection: a case series. Acta Ophthalmol 94(5):e367–e370. https://doi.org/10.1111/aos.12932.

    Article  PubMed  Google Scholar 

  13. Taylor RH, Smith RA, Issa M (2002) Possible cat scratch disease causing neuroretinitis and CRVO in a child. Eye (Lond) 16(2):189–190. https://doi.org/10.1038/sj.eye.6700093.

    Article  CAS  PubMed  Google Scholar 

  14. Ksiaa I, Abroug N, Mahmoud A et al (2019) Update on Bartonella neuroretinitis. J Curr Ophthalmol 31(3):254–261. https://doi.org/10.1016/j.joco.2019.03.005.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zarkovic A, McMurray C, Deva N, Ghosh S, Whitley D, Guest S (2007) Seropositivity rates for Bartonella henselae, Toxocara canis and Toxoplasma gondii in New Zealand blood donors. Clin Exp Ophthalmol 35(2):131–134. https://doi.org/10.1111/j.1442-9071.2006.01406.x.

    Article  PubMed  Google Scholar 

  16. Leibler JH, Zakhour CM, Gadhoke P, Gaeta JM (2016) Zoonotic and Vector-Borne Infections Among Urban Homeless and Marginalized People in the United States and Europe, 1990–2014. Vector Borne Zoonotic Dis 16(7):435–444. https://doi.org/10.1089/vbz.2015.1863.

    Article  PubMed  Google Scholar 

  17. Bartonella Antibody Panel, IgG and IgM, Serum. Mayo Clinic Laboratories. Accessed 16 Jan , 2023, https://www.mayocliniclabs.com/api/sitecore/TestCatalog/DownloadTestCatalog?testId=81575.

  18. Boodman C, Wuerz T, Lagacé-Wiens P et al (2022) Serologic testing for Bartonella in Manitoba, Canada, 2010–2020: a retrospective case series. CMAJ Open Apr-Jun 10(2):E476-e482. https://doi.org/10.9778/cmajo.20210180.

    Article  Google Scholar 

  19. Călugăru D, Călugăru M (2016) Central retinal vein occlusion in a young adult Case report. Rom J Ophthalmol Apr-Jun 60(2):120–124.

    Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Open Access funding provided by the National Institutes of Health (NIH). The Authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this work was supported by the National Eye Institute Intramural Research Program and by the NIH Medical Research Scholars Program, a public–private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, the American Association for Dental Research, and the Colgate-Palmolive Company.

Author information

Authors and Affiliations

Authors

Contributions

All authors attest that they meet the current ICMJE authorship criteria for conception, design, acquisition, and analysis of this work. S.B., A.A., N.V.N., J.K.F., and S.K. wrote the main manuscript. S.B. and S.K prepared the figures. All authors reviewed the manuscript. The author(s) read and approved the final manuscript.

Authors’ information

Not applicable.

Corresponding author

Correspondence to Shilpa Kodati.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

The patient provided written informed consent for the use of patient information and images for the purposes of scientific publication.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bellur, S., Ali, A., Nguyen, N.V. et al. Central retinal vein occlusion associated with Bartonella henselae infection. J Ophthal Inflamm Infect 13, 14 (2023). https://doi.org/10.1186/s12348-023-00334-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12348-023-00334-5

Keywords

  • Central retinal vein occlusion
  • Macular edema
  • Vasculitis
  • Cat scratch disease
  • Ocular bartonellosis
  • Bartonella henselae