The authors report an association between systemic Coxiella burnetii infection and neuroretinitis in two patients and describe a literature review, concluding that a possibility of Coxiella infection should be considered in cases of neuroretinitis of unknown origin.

From the *Department of Ophthalmology, F.C. Donders Institute, and the †Department of Virology, University Medical Center Utrecht, Utrecht, The Netherlands.

nounced in the right eye. An incomplete macula star was present in the right eye (Fig. 1A). Fluorescein angiography showed pathologic leakage in both optic disks with macular edema (Fig. 1, C and D). Results of uveitis screening (erythrocyte sedimentation rate, complete blood cell counts, serum angiotensin-converting enzyme levels, and HLA B27 status), serology (antibodies to Borrelia burgdorferi, Bartonella henselae, Rickettsieae, Treponema pallidum, and Toxoplasma gondii), and aqueous fluid examinations (polymerase chain reaction amplification for herpes simplex virus, varicella-zoster virus, and T. gondii)4 were within normal limits. Vitrectomy of the left eye was performed in May 1995 because of macular pucker. The patient had recurrent inflammatory activity in both eyes from 1994 to 2001 and received symptomatic treatment with topical and periocular corticosteroids. Serology for antibodies to Coxiella was performed using indirect immunofluorescence assay with Coxiella-expressing phase II antigens. The presence of bright fluorescent Coxiella microorganisms at a serum dilution of ⱖ1:10 was considered positive for IgM and IgG antibodies. In 2001, levels of IgM and IgG antibodies to C. burnetii in sera obtained in 1995 were positive (titers of 1:40 and 1:20, respectively). In 1999, IgM and IgG antibody titers were negative and 1:160, respectively. In 2001 and after, intraocular inflammation subsided, and visual acuity recovered to 16/20 in the right eye and 20/20 in the left eye. Fluorescein angiography documented only slight leakage in both optic disks and no macular edema. No antibiotic treatment was given.


euroretinitis is an (sub)acute inflammatory process affecting the optic nerve, which may result in permanent visual loss. Clinical characteristics include an afferent pupillary defect, optic nerve head swelling, and macular star exudates. The causes of neuroretinitis remain frequently undetermined, but the associations with infections have been regularly reported, including syphilis, borreliosis, bartonellosis, toxoplasmosis, tuberculosis, leptospirosis, and diverse viral infections.1 To our knowledge, only two cases of neuroretinitis have been attributed to infections due to Coxiella.2,3 In this report, we describe two patients with neuroretinitis and systemic Coxiella burnetii infection. Case Reports Case 1 A 52-year-old Moroccan woman was referred to our department in March 1994 with a 5-month history of redness and gradual loss of vision. Her medical history included no significant disease, and she received no medication. At examination, Snellen visual acuity was 20/20 in the right eye and 16/20 in the left eye. Both eyes had cells in the anterior chamber, posterior synechiae, and a few cells in the vitreous. In addition, swollen optic disks were present, which was more pro-

Case 2 In October 1996, a 34-year-old African woman consulted our department with pain and gradual loss of vision in her left eye for several months. She had no other complaints, and her previous medical history was not contributory. At examination, vision was 16/20 in the right eye and 6/20 in the left eye. Posterior synechiae and slight vitritis were found in the left eye. The optic disk of the right eye appeared normal, but a swollen optic disk was noted in the left eye. Fluorescein angiography showed slight leakage from the optic disk in the right eye and severe leakage from the optic disk and macular edema in the left eye. Results of uveitis screening were within the normal limits, and serologic examinations revealed

Reprint requests: Elsbeth S.M. Kerkhof, MD, F.C. Donders Institute, Department of Ophthalmology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands; e-mail: [email protected]







Fig. 1. Case 1. Fundus photograph showing edema of the optic nerve in both eyes and a macular star in the right eye (A and B). Fluorescence angiography documenting papillary leakage and macular edema in both eyes (C and D).

no evidence of infection with B. burgdorferi, B. henselae, Rickettsieae, T. pallidum, or T. gondii. A diagnosis of idiopathic neuroretinitis was made, and the patient was treated symptomatically with topical and periocular corticosteroids. From 1996 to 2001, recurrent activity of inflammation in the left eye was present. In 2000 and after, her right eye also exhibited visual loss (in 2001, visual acuity was reduced to 10/20 in the right eye and 5/20 in the left eye). In 2001, the possibility of infection due to Coxiella was considered, and a serum titer of IgG antibody was 1:160. The serum titer of IgG antibody to C. burnetii was 1:320 in a sample obtained in October 1996. Because of the persistent high serum titer of IgG antibody to C. burnetii and decreasing visual acuity, treatment with doxycycline (100 mg two times a day for 10 days) was initiated. Three months later, her vision almost completely recovered (20/20 in the right eye and 16/20 in the left eye). The intraocular inflammation did not recur during 9 months of follow-up.

Discussion Q fever (“query fever”) is a zoonosis caused by C. burnetii, a member of Rickettsieae with a worldwide distribution. Q fever was first described in 1935 as a febrile illness in abattoir workers in Australia.5 The main reservoirs are cattle, sheep, goats, ticks, and cats. Infection can be spread via bites but primarily via inhalation. In humans, the infection causes Q fever, the clinical course of which is often nonspecific and self-limiting. The incidence of Q fever in Western Europe has been reported to be low.2 Systemic infec-

tion with Coxiella is characterized by influenza-like symptoms, atypical pneumonia, hepatitis, endocarditis, and, rarely, involvement of the central nervous system.6 However, many patients have atypical symptoms or none at all. In general, the prognosis of patients with neuroretinitis caused by C. burnetii is good, although relapse can occur.3 Due to the frequent subclinical course, which may mimic a viral illness, the disease frequently remains undiagnosed. Our two patients had no systemic symptoms of Q fever. Ocular manifestations associated with infection due to Coxiella are similar to those of other rickettsial diseases and include sore red eyes with conjunctival papillae, chemosis, and petechiae. Furthermore, iritis, venous engorgement, arteriolar occlusion, macular exudates, and optic nerve edema might be present.7,8 Techniques for the confirmation of the diagnosis of intraocular infection caused by Coxiella are not yet available. Developments of polymerase chain reaction analysis for Coxiella have made it possible to demonstrate the presence of limited amounts of microorganisms; however, to our knowledge, there is no experience with the diagnosis of intraocular infection due to Coxiella.9 Furthermore, the pathogenesis of infection caused by Coxiella is not known, and it is question-



able whether the bacteria invade the intraocular space or whether neuroretinitis is an autoimmune epiphenomenon. Concerning the pathogenesis of neuroretinitis in Q fever, two hypotheses have been put forward: either a direct effect of the microorganism on nerve fibers or an indirect effect on the nerve fibers through vasculitis.10 In neuroretinitis, evidence of the presence of intraocular bacteria is scarce. In cases of cat-scratch disease, borreliosis, and syphilis, an association with neuroretinitis is generally based on serologic findings. In addition, our second patient responded dramatically to antibiotic treatment, as is known for C. burnetii infection. Finally, in all cases in the literature that we reviewed, neuroretinitis caused by Coxiella gave rise to bilateral optic disk abnormalities, as observed in our patients.2,11–13 In conclusion, systemic infection due to Coxiella may be associated with neuroretinitis and may respond to treatment with antibiotics. The possibility of infection caused by Coxiella should be considered in patients with neuroretinitis of unknown origin. Key words: Coxiella burnetii, neuroretinitis, uveitis, inflammation. References 1.

Ray S, Gragoudas E. Neuroretinitis. Int Ophthalmol Clin 2001;41:83–102.





6. 7. 8.

9. 10. 11. 12. 13.

Schuil J, Richardus JH, Baarsma GS, Schaap GJ. Q fever as a possible cause of bilateral optic neuritis. Br J Ophthalmol 1985;69:580–583. Shaked Y, Samra Y. Q fever meningoencephalitis associated with bilateral abducens nerve paralysis, bilateral optic neuritis and abnormal cerebrospinal fluid findings. Infection 1989; 17:394–395. Boerde JHVC, Bruinenberg M, Rothova A, et al. Serologic and polymerase chain reaction analysis of infections uveitis. Am J Ophthalmol 1996;121:650–658. Derrick EH. “Q” fever, new fever entity: clinical features, diagnosis and laboratory investigation. Med J Aust 1973;2: 281–299. Spelman DW. Q fever: a study of 111 consecutive cases. Med J Aust 1982;1:547–548, 551, 553. Smith TW, Burton TC. The retinal manifestations of Rocky Mountain spotted fever. Am J Ophthalmol 1977;84:259–262. Duffey RJ, Hammer ME. The ocular manifestations of Rocky Mountain spotted fever. Ann Ophthalmol 1987;19:301–303, 306. Maurin M, Raoult D. Q fever. Clin Microbiol Rev 1999;12: 518–553. Pedriel G, Michel A, Guyard M, Hoe¨ll J. Les manifestations oculaires de la fie`vre. Ann Ocul (Paris) 1961;194:957–970. Catros A, Hoell J. Nevrite optique axiale bilaterale a fievre Q. Bull Soc Ophtalmol Fr 1960;60:325–330. Deller M, Streiff E. Nevrite retrobulbaire et fievre Q. Bull Mem Soc Fr Ophtalmol 1956;69:309–314. Siegert R, Simrock W, Stroeder U. Uber einen epidemische Ausbruch von Q Feber in einem Krankenhaus. Z Tropenmed Parasitol 1950;2:1–40.

Coxiella burnetii infection, a potential cause of neuroretinitis-two case reports and literature review.

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