Chlamydia pneumoniae Seropositivity and the Risk of Nonarteritic Ischemic Optic Neuropathy Martin Weger, MD, 1 Anton Haas, MD, 1 Olaf Stanger, MD, 2 Yosuf El-Shabrawi, MD, 1 Werner Temmel, MD, 1 Richard Maier, MD, 1 Andrea Berghold, PhD, 3 Eva-Maria Haller-Schober, PhD 1 Objective: To determine whether IgG antibodies to Chlamydia pneumoniae are associated with nonarteritic ischemic optic neuropathy (NAION). Design: Retrospective case-control study. Participants: The study cohort consisted of 71 consecutive patients with NAION and 71 controls matched for age and gender. Main Outcome Measures: Serum immunoglobulin G (IgG) antibody titers to Chlamydia pneumoniae. Results: Patients with NAION had significantly higher IgG antibody titers to C. pneumoniae compared with control subjects (IgG titer 1:128: 29 patients versus 15 controls, P = 0.017). The odds ratio for patients with an IgG titer 1:128 was 2.56 (95% confidence interval [CI], 1.2–5.5). Adjustment for arterial hypertension, diabetes mellitus, and myocardial infarction resulted in an odds ratio of 3.48 (95% CI, 1.3–9.6). Conclusions: Our results suggest that elevated titers of IgG antibodies to C. pneumoniae are associated with NAION. Ophthalmology 2002;109:749 –752 © 2002 by the American Academy of Ophthalmology. Nonarteritic ischemic optic neuropathy (NAION) is a vi- sion-threatening disease, commonly affecting patients older than 50 years. 1 Insufficient blood flow in the short ciliary arteries is known to cause infarction of the optic nerve head. Arterial hypertension, diabetes mellitus, arterial sclerosis, hyperhomocystinemia, and smoking have been identified as some of the risk factors. 2–4 Not all cases of NAION can be completely explained by the known risk factors. Hence, identification of other as yet unknown risk factors is impor- tant. A possible novel risk factor for NAION might be infec- tion with Chlamydia pneumoniae. C. pneumoniae is a gram- negative bacterium that causes respiratory tract infections. 5 Most infections are asymptomatic, and approximately 50% of the general population show seroconversion to C. pneu- moniae positivity by the age of 50 years. 6 In 1988, Saikku et al 7 were the first to report an associ- ation between recent myocardial infarction and elevated immunoglobulin G (IgG) antibody titers to C. pneumoniae. Since then, numerous seroepidemiologic studies have sug- gested that infection with C. pneumoniae is a risk factor for atherosclerosis, myocardial infarction, and stroke. 8 –11 In addition, in histopathologic studies this obligate intracellu- lar bacterium was frequently found in atherosclerotic le- sions but rarely in normal vessels. 12,13 Evidence from animal experiments demonstrating induc- tion and progression of atherosclerotic lesions after inocu- lation with C. pneumoniae also strongly supports the hy- pothesis that infection with this bacterium plays an important role in atherogenesis. 14 Summarizing the results of the aforementioned studies indicating an important role of C. pneumoniae in athero- sclerosis and associated diseases prompted us to investigate the role of C. pneumoniae in NAION. Materials and Methods We studied 71 consecutive patients with NAION who met the inclusion criteria, and 71 controls matched for age and gender. All participants were seen at our department between January 1996 and June 2000 and gave written informed consent before enroll- ment. The study was approved by the Ethics Committee of the Karl-Franzens University, Graz, Austria. Criteria for diagnosis of NAION included sudden visual loss, optic disc edema followed by optic atrophy, relative afferent pupillary defect, and visual field defects consistent with ischemic optic neuropathy. Exclusion criteria for all subjects were an eryth- rocyte sedimentation rate greater than 40 mm/hour, a history of jaw claudication, headache of recent onset, scalp tenderness, fever, myalgias, anorexia, and weight loss. Subjects with malignancy, current respiratory tract infection, history of chronic obstructive pulmonary disease, vasculitis, and intake of corticosteroids or immunosuppressive medication were excluded from the study. According to the exclusion criteria, another 13 patients with NAION, who were also seen at our department, were excluded Originally received: June 14, 2001. Accepted: September 11, 2001. Manuscript no. 210410. 1 Department of Ophthalmology, Karl-Franzens University, Graz, Austria. 2 Atherothrombosis Research Group, Department of Cardiac Surgery, Karl-Franzens University, Graz, Austria. 3 Institute for Medical Informatics, Statistics and Documentation, Karl- Franzens University, Graz, Austria. Reprint requests to Martin Weger, MD, Department of Ophthalmology, Auenbruggerplatz 4, 8036 Graz, Austria; e-mail: martin.weger@ kfunigraz.ac.at. 749 © 2002 by the American Academy of Ophthalmology ISSN 0161-6420/02/$–see front matter Published by Elsevier Science Inc. PII S0161-6420(01)01031-4