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• W2403946568 abstract "Weger et al (Ophthalmology 2002;109:749–52) found an increased rate of seropositivity for immunoglobulin G antibodies to Chlamydia pneumoniae in patients with nonarteritic anterior ischemic optic neuropathy (NAION). In their report, the authors discussed the development of atherosclerosis by C. pneumoniae-infected macrophage and endothelial cells. Because this was the only mechanism discussed that related to the development of NAION, it has the potential of leading one to believe that atherosclerosis plays a major role in NAION. However, studies to date indicate that atherosclerosis plays a minimal to no role in NAION.1Knox DL, Kerrison, Green WR. Histopathologic studies of ischemic optic neuropathy. Trans Am Ophthalmol Soc 2000;98;203–20; discussion 221–2Google Scholar, 2Knox D.L. Duke J.R. Slowly progressive ischemic optic neuropathy. A clinicopathologic case report.Trans Am Acad Ophthalmol Otolaryngol. 1971; 75: 1065-1068PubMed Google Scholar, 3Schatz N.J. Smith J.L. Non-tumor causes of the Foster-Kennedy syndrome.J Neurosurg. 1967; 27: 37-44Crossref PubMed Scopus (40) Google Scholar, 4Fry C.L. Carter J.E. Kanter M.C. et al.Anterior ischemic optic neuropathy is not associated with carotid artery atherosclerosis.Stroke. 1993; 24: 539-542Crossref PubMed Scopus (63) Google Scholar, 5Müller M. Wessel K. Mehdorn E. et al.Carotid artery disease in vascular ocular syndromes.J Clin Neuroophthalmol. 1993; 13: 175-180PubMed Google Scholar, 6Johnson L.N. Arnold A.C. Incidence of nonarteritic and arteritic anterior ischemic optic neuropathy. Population-based study in the State of Missouri and Los Angeles County, California.J Neuroophthalmol. 1994; 14: 38-44Crossref PubMed Google Scholar, 7Characteristics of patients with nonarteritic anterior ischemic optic neuropathy eligible for the Ischemic Optic Neuropathy Decompression Trial. Arch Ophthalmol 1996;114:1366–74Google Scholar, 8Botelho P.J. Johnson L.N. Arnold A.C. The effect of aspirin on the visual outcome of nonarteritic anterior ischemic optic neuropathy.Am J Ophthalmol. 1996; 121: 450-451Abstract Full Text PDF PubMed Scopus (82) Google Scholar, 9Beck R.W. Hayreh S.S. Podhajsky P.A. et al.Aspirin therapy in nonarteritic anterior ischemic optic neuropathy.Am J Ophthalmol. 1997; 123: 212-217Abstract Full Text PDF PubMed Scopus (148) Google Scholar Histopathologic studies of the vascular supply of the optic nerve and choroid, radiologic studies, and ultrasonographic studies of the internal carotid arteries have not shown atherosclerosis to be a primary causative factor of NAION.1Knox DL, Kerrison, Green WR. Histopathologic studies of ischemic optic neuropathy. Trans Am Ophthalmol Soc 2000;98;203–20; discussion 221–2Google Scholar, 2Knox D.L. Duke J.R. Slowly progressive ischemic optic neuropathy. A clinicopathologic case report.Trans Am Acad Ophthalmol Otolaryngol. 1971; 75: 1065-1068PubMed Google Scholar, 3Schatz N.J. Smith J.L. Non-tumor causes of the Foster-Kennedy syndrome.J Neurosurg. 1967; 27: 37-44Crossref PubMed Scopus (40) Google Scholar, 4Fry C.L. Carter J.E. Kanter M.C. et al.Anterior ischemic optic neuropathy is not associated with carotid artery atherosclerosis.Stroke. 1993; 24: 539-542Crossref PubMed Scopus (63) Google Scholar, 5Müller M. Wessel K. Mehdorn E. et al.Carotid artery disease in vascular ocular syndromes.J Clin Neuroophthalmol. 1993; 13: 175-180PubMed Google Scholar Further, if NAION is primarily the result of atherosclerosis, then racial or ethnic groups, such as African Americans, with a high prevalence and worse disease outcomes from diabetes mellitus and hypertension would be expected to have a higher incidence of NAION. Yet, NAION occurs rarely in black persons.6Johnson L.N. Arnold A.C. Incidence of nonarteritic and arteritic anterior ischemic optic neuropathy. Population-based study in the State of Missouri and Los Angeles County, California.J Neuroophthalmol. 1994; 14: 38-44Crossref PubMed Google Scholar, 7Characteristics of patients with nonarteritic anterior ischemic optic neuropathy eligible for the Ischemic Optic Neuropathy Decompression Trial. Arch Ophthalmol 1996;114:1366–74Google Scholar Last, aspirin does not prevent NAION or reduce the severity of visual loss in NAION, as it does in preventing and reducing mortality and morbidity for atherosclerotic cerebrovascular or cardiovascular diseases.8Botelho P.J. Johnson L.N. Arnold A.C. The effect of aspirin on the visual outcome of nonarteritic anterior ischemic optic neuropathy.Am J Ophthalmol. 1996; 121: 450-451Abstract Full Text PDF PubMed Scopus (82) Google Scholar, 9Beck R.W. Hayreh S.S. Podhajsky P.A. et al.Aspirin therapy in nonarteritic anterior ischemic optic neuropathy.Am J Ophthalmol. 1997; 123: 212-217Abstract Full Text PDF PubMed Scopus (148) Google Scholar These findings indicate that factors other than atherosclerosis contribute to the development of NAION. Similar to C. pneumoniae infection, we have shown that patients with a history of recurrent herpes labialis (oral fever blisters) have a three times increased risk of experiencing NAION.10Johnson L.N. Krohel G.B. Allen S.D. Mozayeni R. Recurrent herpes labialis as a potential risk factor for nonarteritic anterior ischemic optic neuropathy.J Natl Med Assoc. 1996; 88: 369-373PubMed Google Scholar Additionally, the herpes simplex virus has been implicated for years in the induction of atherosclerosis and vascular thrombosis.11Hajjar D.P. Warner-Lambert/Parke-Davis Award Lecture. Viral pathogenesis of atherosclerosis. Impact of molecular mimicry and viral genes.Am J Pathol. 1991; 139: 1195-1211PubMed Google Scholar But as indicated previously, atherosclerosis is not the culprit in NAION. How else may the authors relate herpes virus or C. pneumoniae infection with NAION? We would suggest that data from recent studies12Mojon D.S. Hedges 3rd, T.R. Ehrenberg B. et al.Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy.Arch Ophthalmol. 2002; 120: 601-605Crossref PubMed Scopus (184) Google Scholar, 13Hayreh S.S. Podhajsky P.A. Zimmerman B. Ipsilateral recurrence of nonarteritic anterior ischemic optic neuropathy.Am J Ophthalmol. 2001; 132: 734-742Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar, 14McGinty D. Beahm E. Stern N. et al.Nocturnal hypotension in older men with sleep-related breathing disorders.Chest. 1988; 94: 305-311Crossref PubMed Scopus (46) Google Scholar, 15Johnson L.N. Nonarteritic anterior ischemic optic neuropathy [letter].J Am Optom Assoc. 1998; 69: 422-423PubMed Google Scholar, 16Huang J. DeGraves F.J. Lenz S.D. et al.The quantity of nitric oxide released by macrophages regulates Chlamydia-induced disease.Proc Natl Acad Sci. 2002; 99: 3914-3919Crossref PubMed Scopus (51) Google Scholar, 17Benencia F. Courreges M.C. Nitric oxide and macrophage antiviral extrinsic activity.Immunology. 1999; 98: 363-370Crossref PubMed Scopus (35) Google Scholar, 18Vann V.R. Atherton S.S. Neural spread of herpes simplex virus after anterior chamber inoculation.Invest Ophthalmol Vis Sci. 1991; 32: 2462-2472PubMed Google Scholar, 19Paludan S.R. Ellermann-Eriksen S. Malmgaard L. Mogensen S.C. Inhibition of NO production in macrophages by IL-13 is counteracted by Herpes simplex virus infection through tumor necrosis factor-alpha-induced activation of NK-kappa B.Eur Cytokine Netw. 2000; 11: 275-282PubMed Google Scholar, 20Djeraba A. Musset E. Bernardet N. et al.Similar pattern of iNOS expression, NO production and cytokine response in genetic and vaccination-acquired resistance to Marek’s disease.Vet Immunol Immunopath. 2002; 85: 63-75Crossref PubMed Scopus (55) Google Scholar, 21Zagvazdin Y. Fitzgerald M.E. Reiner A. Role of muscarinic cholinergic transmission in Edinger-Westphal nucleus-induced choroidal vasodilation in pigeon.Exp Eye Res. 2000; 70: 315-327Crossref PubMed Scopus (25) Google Scholar, 22Fitzgerald M.E. Gamlin P.D. Zagvazdin Y. Reiner A. Central neural circuits for the light-mediated reflexive control of choroidal blood flow in the pigeon eye a laser Doppler study.Vis Neurosci. 1996; 13: 655-669Crossref PubMed Scopus (61) Google Scholar, 23Cuthbertson S. Zagvazdin Y.S. Kimble T.D. et al.Preganglionic endings from nucleus of Edinger-Westphal in pigeon ciliary ganglion contain neuronal nitric oxide synthase.Vis Neurosci. 1999; 16: 819-834Crossref PubMed Scopus (21) Google Scholar indicate: •Approximately 70% of patients with NAION have sleep apnea.•Patients with sleep apnea have significant increased risk of experiencing NAION (odds ratio, 11:2).•Some patients with NAION and patients with sleep apnea have recurrent episodes of nocturnal arterial diastolic hypotension.•The mean arterial pressure during periods of episodic nocturnal hypotension at times will fall to less than 60 mmHg (sometimes even less than 40 mmHg)—with 60 mmHg considered the limit of cerebral blood flow autoregulation.•Microstimulation of the neurovascular triangle (suprachiasmatic nucleus [SCN], the Edinger-Westphal nucleus [EWN], ciliary ganglion [CG]) results in a 300% to 700% increase in choroidal blood flow (at least in pigeons), without a corresponding increase in systemic blood flow. This increase in choroidal blood flow is mediated through the release of nitric oxide, a potent vasodilator, both at parasympathetic preganglionic nerve terminals, and from endothelial cells in the choroid and macrophages.•The suprachiasmatic nucleus is important in sleep–wake cycles (circadian rhythm) through the retino-hypothalamic pathway, and NAION occurs most often during sleep or shortly after awakening. Based on these findings, and as had been postulated in part by others, we suggest that patients with crowded optic nerve head (i.e., “disk at risk” with small cup-to-disc ratios) and baseline compression of vessels in the optic nerve head may experience episodic nocturnal diastolic arterial hypotension. This reduces the systemic mean arterial pressure to less than 60 mmHg, causing loss of blood flow autoregulation and local tissue hypoxia. We suspect this results in stimulation of the neurovascular triangle (SCN→EWN→CG), possibly by the retinohypothalamic pathway. As a result, nitric oxide is released either directly by the preganglionic parasympathetic nerve or by herpes virus, C. pneumonia-infected endothelial cells. Although this may promote increased blood flow to the choroid, we suspect that this may cause further reduction of blood flow to the optic nerve head, because available blood is shunted to the choroid. This produces a cycle of further hypoxia and ischemic edema, further compression of optic nerve head capillaries, then cell death either immediately or by apoptosis. Weger et al have provided very valuable information on the relationship of C. pneumoniae with NAION. However, we should look at other factors instead of atherosclerosis with NAION. (24Zagvazdin Y.S. Fitzgerald M.E. Sancesario G. Reiner A. Neural nitric oxide mediates Edinger-Westphal nucleus evoked increase in choroidal blood flow in the pigeon.Invest Ophthalmol Vis Sci. 1996; 37: 666-672PubMed Google Scholar) Author replyOphthalmologyVol. 110Issue 6Preview Full-Text PDF" @default.
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