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Hyperhomocysteinemia in bilateral anterior ischemic optic neuropathy after conventional coronary artery bypass graft: a case report
© The Author(s). 2018
Received: 22 February 2017
Accepted: 7 December 2017
Published: 17 January 2018
The incidence of anterior ischemic optic neuropathy after coronary artery bypass graft procedures ranges from 1.3 to 0.25%. The mechanisms of anterior ischemic optic neuropathy after cardiovascular procedures remain undefined but many systemic and related-to-surgery risk factors could underlie anterior ischemic optic neuropathy. In this case, we report a rare presentation of a bilateral anterior ischemic optic neuropathy after coronary artery bypass graft and speculate on the preoperative hyperhomocysteinemia as an independent risk factor for anterior ischemic optic neuropathy.
A 56-year-old white man, a tobacco smoker with type 2 diabetes and coronary artery disease, underwent a conventional coronary artery bypass graft with extracorporeal circulation. In spite of ongoing anti-aggregation, antithrombotic, and vasodilator therapy, 10 days after the surgery he complained of severe bilateral visual loss. Funduscopy and fluorescein angiography revealed a bilateral anterior ischemic optic neuropathy. Analysis of preoperative laboratory tests revealed hyperhomocysteinemia.
Hyperhomocysteinemia could increase the risk of ocular vascular damage and bilateral ocular involvement in patients who have undergone conventional coronary artery bypass graft.
Vision loss after non-ocular surgery is a rare event. Its incidence is 0.002% for all surgery treatments [1, 2]. The most common neuro-ophthalmologic causes of visual impairment after non-ocular surgery are the ischemic optic neuropathies (ION): anterior ION (AION) or posterior ION (PION). After coronary artery bypass graft (CABG) procedures the incidence of ION ranges from 0.11  to 0.06% [4, 5]. The incidence of AION after CABG procedures ranges from 1.3 to 0.25% [3, 6]. CABG is a vascular bypass implantation at the site of narrowing or blockage of coronary arteries. Healthy arteries or veins are grafted to the coronary arteries to allow the reperfusion of the ischemic area of the heart. During a conventional CABG (CCABG) procedure, extracorporeal circulation (ECC) is used. The mechanisms of visual loss after CCABG remain undefined but hypotension, anemia, and other factors could underlie the AION . Hyperhomocysteinemia, in addition to being an independent risk factor for vascular diseases and myocardial infarction , is a risk factor for AION [9, 10]. Weger et al. believe that determination of homocysteine level might have a diagnostic value in patients with AION . The homocysteine level could be routinely measured before CCABG procedure.
A 56-year-old white man, a tobacco smoker with type 2 diabetes and coronary artery disease, underwent cardiac revascularization. During CCABG, his internal mammary artery as arterial graft and double bypass with saphenous vein were used. He was under therapy with enoxaparin sodium 6000 I.U. anti-Xa activity (aXa) twice a day, acetylsalicylic acid 100 mg daily, prednisone 5 mg daily, and mild diuretic therapy. Ten days after cardiac surgery he complained of bilateral visual loss: best corrected visual acuity (BCVA) was 0.9 LogMAR in right eye (RE) and 1.0 LogMAR in left eye (LE). Afferent pupillary defect (APD) was revealed in his LE. In both eyes computerized perimetry showed an absolute and general reduction of the retinal sensitivity within 30 degrees around the fixation point.
In a review of 5.6 million patients from National Inpatient Sample the visual loss ratio after cardiac surgery was 8.64/10,000 . AION occurs most often after cardiac surgery . AION is the result of an insufficient blood flow provided by short posterior ciliary arteries to the retrolaminar portion of the optic nerve head.
In a previous study, 17 patients (0.06%) out of a total of 27,915 who underwent CABG had perioperative ION . Kalyani et al. found 11 patients (0.113%) with perioperative optic neuropathy out of 9701 surgical patients requiring cardiopulmonary bypass . In a case-control analysis of 126,666 surgical procedures the authors identified 17 patients (0.013%) with perioperative ION . Shapira et al. found the development of AION in 8 patients (1.3%) out of 602 consecutive cardiac surgery patients .
In CABG there are many correlated-to-surgery risk factors able to influence ocular blood flow causing AION: hypothermia induced during surgery could increase blood viscosity, leading to watershed infarction of the optic nerve  and lowering cerebral and ocular blood flow ; the activation of complement cascade with increase of C3a acts as a smooth-muscle spasmogen ; the long duration of the CABG procedure is associated with greater inflammation and higher levels of endogenous catecholamines that may act synergistically to produce vasoconstriction and ischemia in the posterior ciliary circulation [3, 4]; a lower postoperative hemoglobin value (≤8.5 g/dL) results in a reduction in oxygen-carrying capacity and subsequent ischemia ; a coronary angiogram within 48 hours of surgery acts as a risk factor by an unclear mechanism ; an arrhythmia could induce a reduction in cardiac output ; the large fluid infusion to support blood pressure  reduces oxygen-carrying capacity by hemodilution; the inotropic medications ; a blood loss associated or not with arterial hypotension causes activation of the sympathetic nervous system followed by vasoconstriction which induces choroidal and optic nerve ischemia ; and the use of vasoconstricting agents to correct intraoperative hypotension has also been suggested to promote optic nerve ischemia [15, 18, 19].
However, in a previous case-control analysis of 126,666 surgical procedures the authors concluded that perioperative ION can occur in the absence of any unusual or atypical fluctuations in many hemodynamic variables during the perioperative period . In that paper there was no difference between 17 patients with perioperative ION and 34 control patients in terms of preoperative variables like age, medical history, body mass index, mean arterial pressure, and hematocrit. We know that there are predisposing ocular risk factors of AION as preexisting “disc-at-risk” configuration, but the presence of this configuration cannot be determined in a swollen or atrophic optic disc, and a vascular disorder of the optic nerve was not noted in the clinical history of our patient.
Furthermore, there are many systemic, non-correlated-to-surgery risk factors of AION like high serum cholesterol, triglycerides, hyperlipidemia, hyperfibrinogenemia, prolonged tobacco smoking history, hypertension, anemia, and diabetes mellitus .
In our patient we found different systemic and non-correlated-to-surgery risk factors like hypertension, mild anemia, and diabetes which may reduce tolerance to hypotension of optic nerve blood flow during CABG procedure [21, 22]. Different authors [23–26] found postoperative anemia to be a predisposing cause for AION. Mansour et al. reported that severe anemia in patients undergoing CABG appears to be a risk factor for AION, especially in diabetics, and needs prompt correction to prevent or reverse ischemic ocular events . However, in our case the hematocrit and hemoglobin values were much higher than that reported in previous papers.
Furthermore, we found a moderate hyperhomocysteinemia probably correlated with our patient’s tobacco smoking history. Hyperhomocysteinemia is observed in approximately 5% of the general population and is associated with an increased risk of many disorders, including vascular and neurodegenerative diseases, autoimmune disorders, diabetes, renal diseases, neuropsychiatric disorders, and cancer . Hyperhomocysteinemia is an independent risk factor for atherosclerosis of the graft, one of the main limitations of long-term survival of patients who have undergone CABG . Furthermore, homocysteine is known as a risk factor for vascular eye pathologies . Hyperhomocysteinemia acting as an oxygen free radical causes dysfunction and necrosis of endothelial cells, and proliferation of smooth muscle cells with subsequent fibrosis and calcification of the vessel . On the other hand, high levels of homocysteine induce the formation of atheroma (atherosclerotic plaque) and the proliferation of smooth muscle cells resulting in endothelial damage and reduced elasticity of the vessel . Hyperhomocysteinemia also increases platelet adhesiveness and aggregation . We have to report that in this case the preoperative and postoperative antiplatelet and anticoagulant therapy did not avoid the optic nerve ischemia.
The CCABG procedure mentioned in this case report used an extracorporeal circulation with cardiopulmonary bypass which may lead to many postoperative complications like AION.
Several preoperative and intraoperative clinical conditions increase the risk of ocular complications like AION after CCABG procedure; so, preoperative hyperhomocysteinemia could increase the risk of ocular vascular damage and bilateral ocular involvement. We would like to conclude with the hypothesis that it would be worthwhile to investigate the potential benefit of treating preexisting hyperhomocysteinemia in patients undergoing CABG.
There is no financial support for this case report.
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AN conception and design, analysis and interpretation of data, and draft of the article. GS and AS acquisition of data, and analysis and interpretation of data. GA final approval of the version to be published. All authors read and approved the final manuscript.
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- Warner ME, Warner MA, Garrity JA, et al. The frequency of perioperative vision loss. Anesth Analg. 2001;93(6):1417–21.View ArticlePubMedGoogle Scholar
- Roth S, Thisted RA, Erickson JP, et al. Eye injuries after non-ocular surgery. A study of 60,965 anesthetics from 1988 to 1992. Anesthesiology. 1996;85(5):1020–7.View ArticlePubMedGoogle Scholar
- Shapira OM, Kimmel WA, Lindsey PS, Shahian DM. Anterior ischemic optic neuropathy after open heart operations. Ann Thorac Surg. 1996;61(2):660–6.View ArticlePubMedGoogle Scholar
- Nuttall GA, Garrity JA, Dearani JA, et al. Risk factors for ischemic optic neuropathy after cardiopulmonary bypass: a matched case/control study. Anesth Analg. 2001;93(6):1410–6.View ArticlePubMedGoogle Scholar
- Kalyani SD, Miller NR, Dong LM, et al. Incidence of and risk factors for perioperative optic neuropathy after cardiac surgery. Ann Thorac Surg. 2004;78:34–7.View ArticlePubMedGoogle Scholar
- Berg KT, Harrison AR, Lee MS. Perioperative visual loss in ocular and nonocular surgery. Clin Ophthalmol. 2010;4:531–46.PubMedPubMed CentralGoogle Scholar
- Johnson MW, Kincaid MC, Trobe JD. Bilateral retrobulbar optic nerve infarctions after blood loss and hypotension. A clinicopathologic case study. Ophthalmology. 1987;94(12):1577–84.View ArticlePubMedGoogle Scholar
- Verhoef P, Stampfer MJ, Buring JE, et al. Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol. 1996;143(9):845–59.View ArticlePubMedGoogle Scholar
- Manresa N, Mulero J, Zafrilla P. Homocysteine: Biosynthesis and Health Implications Hyperhomocysteinemia and Association of Eye Disease. 1st ed. New York: Nova Science Publishers; 2003.Google Scholar
- Pianka P, Almog Y, Man O, et al. Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion. Ophthalmology. 2000;107(8):1588–92.View ArticlePubMedGoogle Scholar
- Weger M, Stanger O, Deutschmann H, et al. Hyperhomocyst(e)inaemia, but not MTHFR C677T mutation, as a risk factor for non-arteritic ischaemic optic neuropathy. Br J Ophthalmol. 2001;85(7):803–6.View ArticlePubMedPubMed CentralGoogle Scholar
- Shen Y, Drum M, Roth S. The prevalence of perioperative visual loss in the United States: a 10-year study from 1996 to 2005 of spinal, orthopedic, cardiac, and general surgery. Anesth Analg. 2009;109(5):1534–45.View ArticlePubMedGoogle Scholar
- Connolly SE, Gordon KB, Horton JC. Salvage of vision after hypotension-induced ischemic optic neuropathy. Am J Ophthalmol. 1994;117(2):235–42.View ArticlePubMedGoogle Scholar
- Holy SE, Tsai JH, McAllister RK, Smith KH. Perioperative ischemic optic neuropathy: at a single institution. Anesthesiology. 2009;110(2):246–53.PubMedGoogle Scholar
- Sweeney PJ, Breuer AC, Selhorst JB, et al. Ischemic optic neuropathy: a complication of cardiopulmonary bypass surgery. Neurology. 1982;32(5):560–2.View ArticlePubMedGoogle Scholar
- Reuler JB. Hypothermia: pathophysiology, clinical settings, and management. Ann Intern Med. 1978;89(4):519–27.View ArticlePubMedGoogle Scholar
- Chenoweth DE, Cooper SW, Hugli TE, et al. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med. 1981;304(9):497–503.View ArticlePubMedGoogle Scholar
- Hayreh SS. Anterior ischemic optic neuropathy. VIII. Clinical features and pathogenesis of post-hemorrhagic amaurosis. Ophthalmology. 1987;94(11):1488–502.View ArticlePubMedGoogle Scholar
- Williams EL, Hart Jr WM, Tempelhoff R. Postoperative ischemic optic neuropathy. Anesth Analg. 1995;80(5):1018–29.PubMedGoogle Scholar
- Jacobson DM, Vierkant RA, Belongia EA. Nonarteritic anterior ischemic optic neuropathy. A case-control study of potential risk factors. Arch Ophthalmol. 1997;115:1403–7.View ArticlePubMedGoogle Scholar
- Haefliger IO, Meyer P, Flammer J, Luscher TF. The vascular endothelium as a regulator of the ocular circulation: a new concept in ophthalmology? Surv Ophthalmol. 1994;39(2):123–32.View ArticlePubMedGoogle Scholar
- Hayreh SS. Factors influencing blood flow in the optic nerve head. J Glaucoma. 1997;6(6):412–25.View ArticlePubMedGoogle Scholar
- Brown RH, Schauble JF, Miller NR. Anemia and hypotension as contributors to perioperative loss of vision. Anesthesiology. 1994;80:222–6.View ArticlePubMedGoogle Scholar
- Jaben SL, Glaser JS, Daily M. Ischemic optic neuropathy following general surgical procedures. J Clin Neuroophthalmol. 1983;3:239–44.View ArticlePubMedGoogle Scholar
- Moster ML. Visual loss after coronary artery bypass surgery. Surv Ophthalmol. 1998;42:453–7.View ArticlePubMedGoogle Scholar
- Jarrell III RL, Jones WL. Juxtapapillary nerve fiber layer infarction as a complication of coronary artery bypass surgery. J Am Optom Assoc. 1998;69:759–65.PubMedGoogle Scholar
- Mansour AM, Awwad ST, Najjar DM. Anterior ischaemic optic neuropathy after coronary artery bypass graft: the role of anaemia in diabetics. Eye (Lond). 2006;20(6):706–11.View ArticleGoogle Scholar
- Brustolin S, Giugliani R, Félix TM. Genetics of homocysteine metabolism and associated disorders. Braz J Med Biol Res. 2010;43:1–7.View ArticlePubMedGoogle Scholar
- Ambrost P, Barlatier A, Habib G, Gargon D. Hyperhomocysteinemia in heart transplanted recipients. Eur Heart J. 1994;15:1191–6.View ArticleGoogle Scholar
- Cattaneo M. Hyperhomocysteinemia, Atherosclerosis and Thrombosis. Thromb Haemost. 1999;81:165–76.PubMedGoogle Scholar
- Deutch D, Lewis RA. Intraocular pressure after cardiopulmonary bypass surgery. Am J Ophthalmol. 1989;107(1):18–22.View ArticlePubMedGoogle Scholar
- Larkin DF, Connolly P, Magner JB, et al. Intraocular pressure during cardiopulmonary bypass. Br J Ophthalmol. 1987;71(3):177–80.View ArticlePubMedPubMed CentralGoogle Scholar