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 vascular endothelial growth factor (anti-VEGF) agents and oral doxycycline.
Ophthalmic findings of B. henselae infection are varied and can involve multiple 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 literature2,6,7.
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 disease6,8. 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 CSD6. 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 edema11. 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. henselae12. 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 inflammation7. 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 implicated6,7,9,12.
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 exposure9,10,13. 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 treatment9. 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 glaucoma9,10.
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 infection14–16. While the presence of IgM antibodies is also useful to detect acute infection, its utility is limited by variable or limited sensitivities14. 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. henselae17. 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.