Delayed Carbon Monoxide Optic Neuropathy

Carbon monoxide (CO) is a common cause of poisoning with significant effects on central nervous system. Visual loss, even severe, may thus be the final effect of CO poisoning, and prompt recognition and treatment are paramount to mitigate the toxic effects of CO on the visual system. We report a case of a 17-year-old girl with delayed bilateral optic neuropathy caused by CO poisoning and review the literature of the neuro-ophthalmological effects of this toxic gas. To our knowledge, this is the longest duration of isolated, delayed optic neuropathy after CO exposure to be reported in the English language, ophthalmic literature.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Delayed Carbon Monoxide Optic Neuropathy Daniele Brocca, MD, Francesco Pellegrini, MD, Alessandra Cuna, MD, Francesca Leonardi, MD, Andrew G. Lee, MD C arbon monoxide (CO) is a common cause of poisoning with significant effects on central nervous system. Visual loss, even severe, may thus be the final effect of CO poisoning, and prompt recognition and treatment are paramount to mitigate the toxic effects of CO on the visual system. We report a case of a 17-year-old girl with delayed bilateral optic neuropathy caused by CO poisoning and review the literature of the neuro-ophthalmological effects of this toxic gas. To our knowledge, this is the longest duration of isolated, delayed optic neuropathy after CO exposure to be reported in the English language, ophthalmic literature. CASE REPORT A 17-year-old girl presented complaining of visual loss for 3 months in both eyes. Medical history was negative, and she denied trauma or drug abuse. She felt otherwise well. Ten months before, the patient had carbon monoxide poisoning. The patient was involved in a house fire and had significant smoke exposure. She was admitted to the hospital and required high-flow oxygen supplementation. Initial laboratory studies revealed normal blood pH of 7.407 (normal, 7.35–7.45), pCO2 of 36.4 mm Hg (normal, 32–48 mm Hg), and pO2 of 93 (normal, 83–108). Carbon monoxide hemoglobin (COHb) levels were elevated at 15% (normal, 0.0–3.0), and oxygenated Hb was reduced at 82.7% (normal, 93%–98%), consistent with CO poisoning. On neuro-ophthalmologic examination best-corrected visual acuity was 20/50 in the right eye and 20/40 in the left eye. SlitOphthalmology Department (DB, AC, FL), “De Gironcoli” Hospital, Conegliano, AULSS 2 Marca Trevigiana, Italy; Ophthalmology Department (FP), “Santo Spirito” Hospital, Pescara, AUSL Pescara, Italy; Department of Ophthalmology (AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology (AGL), Neurology, and Neurosurgery, Houston Methodist Hospital and Weill Cornell Medicine, New York, New York; Departments of Ophthalmology (AGL), University of Texas Medical Branch (UTMB), Galveston, Texas and Baylor College of Medicine, Houston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas of Ophthalmology; and Department of Ophthalmology (AGL), Texas A and M College of Medicine, The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflict of interest. The patient gave her written informed consent for anonymously publication of images. Address correspondence to Daniele Brocca, MD, “De Gironcoli” Hospital, via Daniele Manin 110, 31015 Conegliano (TV), Italy; E-mail: [e-mail] e326 lamp examination was unremarkable, and intraocular pressure was 16 mm Hg in both eyes. Ophthalmoscopy showed mild temporal pallor of the optic nerves (ON) in both eyes (Fig. 1). Spectral-domain optical coherence tomography (OCT) of the optic nerves disclosed a diffuse bilateral thinning of the peripapillary retinal nerve fiber layer, especially in the temporal sectors consistent with papillomacular bundle dropout (Fig. 2). Macular OCT was normal in both eyes (Fig. 3). OCT of the ganglion cells layer and complex revealed a widespread thinning of the macular ganglion cell layers in both eyes (Fig. 4). Automated perimetry showed caecocentral scotoma in both eyes with breakout to the inferotemporal periphery (Fig. 5). MRI of the brain and orbit was unremarkable. Serum levels of vitamin B9 and B12 were normal, and genetic testing for dominant optic atrophy and Leber hereditary optic neuropathy were negative as well. DISCUSSION Carbon monoxide is a colorless, odorless, and tasteless but extremely dangerous and toxic gas. CO is produced by incomplete combustion of hydrocarbons, such as motor vehicle exhaust and combustion of heating units in industrial or home. CO poisoning is also a relatively common means of suicide attempt (e.g., starting an automobile in a closed garage) (1). CO has a binding affinity for hemoglobin (Hb) that is 210 times that of oxygen (O2). Exposure to CO will displace O2 from Hb and reduce oxygen carrying capacity of blood leading to ischemia. The diagnosis of CO poisoning is made on elevated serum measurements of COHb as seen in our case. CO shifts the hemoglobin–oxygen dissociation curve to the left, limiting the amount of oxygen released to tissues. Symptoms of CO poisoning can be difficult to diagnose because they range from nonspecific flu-like illness to severe neurologic impairment and even death. Headache is the most common presenting feature (84%) followed by dizziness (92%) and weakness (76%) (2). Neurologic symptoms range from memory loss and behavioral impairment to seizures and coma. Despite the clinical improvement and the recovery of consciousness after CO poisoning, some patients still develop signs and symptoms of a delayed encephalopathy within 2–60 days of “false recovery period.” This delayed encephalopathy effect of CO poisoning has a high morbidity and mortality (3). The visual dysfunction induced by Brocca et al: J Neuro-Ophthalmol 2022; 42: e326-e330 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Retinography shows mild temporal pallor of the optic disc OU. OU, both eyes. CO poisoning is common but variable, ranging from mild to serious visual function impairment including blindness (4). Likewise the prognosis can be good or poor depending on the quantity and duration of CO exposure, time to diagnosis, and effectiveness of treatment. CO poisoning causes tissue ischemia and hypoxia, and the central nervous system (CNS), including the optic nerve, is particularly sensitive to this type of biological insult. The proposed FIG. 2. OCT of the peripapillary retinal nerve fiber layer (pRNFL) showing a temporal reduction of the retinal fibers thickness in both eyes. OS, left eye; OD, right eye. Brocca et al: J Neuro-Ophthalmol 2022; 42: e326-e330 e327 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 3. Macular OCT of the right (A) and left (B) eye resulted within normal limits. FIG. 4. Ganglion cell analysis of the right eye (A) and left eye (B) shows a diffuse thinning of the ganglion cell layer (GCL+) and complex (GCL++). mechanisms of CO poisoning–related optic neuropathy include both anterior and posterior visual pathway disturbances (3): 1. Adenosine triphosphate–synthesis disorder with subsequent neurocyte edema and impairment to the visual center of the occipital lobe and visual radiation. 2. Initial vasospasm followed by vasodilation, interstitial edema, and retardation of axoplasmic flow. 3. Damage of vascular endothelial cells followed by increased platelet aggregation and adhesiveness, vasospasm, leukocyte aggregation, and other different cellular mechanisms resulting in local blood circulation disorders, such as microthrombosis. 4. Oxidative stress that may lead to the selective degeneration of small optic nerve fibers. Treatment of CO toxicity includes removing patient from the source of exposure and hyperbaric oxygen treatment (or 100% oxygen treatment). Oxygen treatment improves the content of tissue oxygen and reduces the concentration of COHb in the blood. Systemic FIG. 5. Standard 30-2 computerized perimetry of the left (B) and right (A) eyes showing caecocentral scotoma in both eyes with breakout to the inferotemporal periphery. e328 Brocca et al: J Neuro-Ophthalmol 2022; 42: e326-e330 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence TABLE 1. Cases reported in the literature of carbon monoxide optic neuropathy Author (year) Age(yrs) Sex Eyes BCVA at Presentation Time after CO Poisoning Brocca D et al (2020) Levine M et al (2016) Simmons IG et al (1998) 17 F OU — 10 months 5 M OU LP Acute 43 F OU 3–4 days 59 30 26 M M M OU OU 20/200 20/125 CF 20/66 — — Acute Acute 49 F OU — — 54 11 24 M M M OU OU OU — — — — — Acute Fepsey LC et al (1976) Bilchik RC et al (1971) Murray WZ et al (1926) Author (year) Presentation Systemic Association On and Fundus Findings Brocca D et al (2020) Levine M et al (2016) Visual loss — Temporal pallor — Decortical posturing Simmons IG et al (1998) Central visual loss — Unremarkable Vitreous haze, retinal hemorrhages, Roth spot Temporal pale disc Deficits long- and short-term memory Temporal pale disc — — Coma Coma and decerebrate posturing Weakness, nausea, vomiting, tinnitus, headaches Pale disc, cupping Peripapillary hemorrhages, venous engorgements Swollen discs, venous tortuosity, flame– shaped, and round retinal hemorrhages, cotton wool exudates, areas of retinal edema Hemorrhage and exudate Swollen discs, venous tortuosity, flame– shaped, and round retinal hemorrhages, cotton wool exudates, areas of retinal edema Swollen discs, venous tortuosity, nonpigmented chorioretinal scars, vitreous opacities Fepsey LC et al (1976) Bilchik RC et al (1971) Murray WZ et al (1926) — — — Syncope Syncope — — VF Defects BCVA Final Therapy Infero-temporal quadrantanopia — 20/50 20/40 20/30 20/40 High O2 Bilateral paracentral scotomas Central scotomas/peripheral constriction Centrocecal defect — 20/125 20/66 10 years (social reasons) Vit b12 — No reliquaries — Pure O2 — No reliquaries — — — No reliquaries No reliquaries — — — — — — — BCVA, best corrected visual acuity; CO, carbon monoxide; CF count fingers; LP light perception; ON, optic nerve; OU, both eyes; VF, visual field. hypoxia is thus reduced. Rapid relief of hypoxia can play a critical role in the repair of the retrochiasmatic visual radiation and center(s). However, some negative effects may persist even after treatment and may be related to the apoptotic effect that CO poisoning has on CNS. Interestingly, experimental evidence suggests that lowdose CO may paradoxically protect neuronal cells from apoptosis (5), whereas high-dose CO may induce apoptoBrocca et al: J Neuro-Ophthalmol 2022; 42: e326-e330 sis. Electrophysiology (6,7) studies show that there may be a common final pathway between CO and cyanide poisoning and that CO is able to cause a toxic optic neuropathy with a central/caecocentral scotoma and ophthalmoscopic and OCT evidence for papillomacular dropout as seen in our case. Between 2000 and 2009 in the United States, approximately 70,000 cases of CO poisoning were reported (8). e329 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence Both ischemic retinopathy and optic neuropathy have been reported in CO poisoning, including superficial flameshaped retinal hemorrhages, venous tortuosity and engorgement, cotton wool spots, bilateral swollen discs, optic atrophy, and retinal edema (9). Our patient was not examined in the acute phase however. In our review of the literature, we found 5 case reports and series of CO poisoning with eye and visual function involvement, totally 10 patients with a history of CO poisoning (Table 1). Among these, 6 patients showed clinical features of CO retinopathy or a mixed clinical picture of retinopathy and optic neuropathy. Three out of 9 patients displayed exclusively optic neuropathy signs, whereas the remaining 7 patients also showed a variable grade of neurological and systemic impairment ranging from weakness to coma. Murray et al in 1926 first described a case of a 24-year-old man with carbon monoxide poisoning. The patient showed bilateral papilledema, dilated retinal veins, retinal edema, and large vitreous opacity (10). Levin et al in 2016 found similar clinical features in a young male with acute CO intoxication. The authors speculated that these vitreous opacities were likely caused by dehemoglobinized red blood cells in the context of a vitreous hemorrhage (1). Moreover, Simmons et al in 1998 described 3 cases in whom CO poisoning caused an optic neuropathy leading to severe visual loss, optic disc changes such as pallor and cupping, and visual field scotomas. We speculate that CO exposure may affect the eye and the visual system in a bimodal way: an acute phase in which retinal edema, venous tortuosity and engorgement, and retinal hemorrhages are common features detectable if ophthalmoscopy is performed, and a chronic, delayed phase in which optic nerve atrophy and pallor develop with poor vision. Thus, we believe that our case represents a delayed CO optic neuropathy similar to the delayed CO encephalopathy cases reported in the literature. To our knowledge, this case experienced the longest delay from CO exposure to symptomatic visual loss to be reported in the Englishlanguage ophthalmic literature. Clinicians should be aware that CO poisoning has ophthalmic manifestations and that symptoms of visual loss may be delayed by weeks to months after CO exposure. CONCLUSIONS Carbon monoxide exposure may affect the eye leading to permanent visual loss. Two phases can be detected: e330 an acute “retinopathy” phase and a delayed chronic phase in which unspecific signs of optic neuropathy are predominant. Moreover, signs and symptoms of visual impartment may have a late presentation not only because of the chronic apoptotic effect of carbon monoxide on the CNS and retinal cells, but also because more immediate and life-threatening conditions, such as coma or brain edema, require prompt management with underestimation of ophthalmic involvement. METHODS OF LITERATURE SEARCH A Literature search on PubMed database was carried out looking for all relevant articles published in English between January 1920 and December 2020. The keywords used were “carbon monoxide poisoning”, “carbon monoxide retinopathy,” “carbon monoxide optic neuropathy.” Data extracted from each case included age, gender, presentation, visual field defects, visual surgical or medical therapy, and outcome. REFERENCES 1. Levin M, Hall JP, Guerami A. Vitreous hemorrhage from carbon monoxide retinopathy. Retin Cases Brief Rep. 2016;10:157– 159. 2. Prockop L, Chichkoca R. Carbon monoxide Intoxication: an updated review. J Neurol Sci. 2007;262:122–130. 3. Bi WK, Wang JL, Zhou XD, Li ZK, Jiang WW, Zhang SB, Zou Y, Bi MJ, Li Q. Clinical characteristics of visual dysfunction in carbon monoxide poisoning patients. J Ophthalmol. 2020;2020:1–8. 4. Karakurum B, Karatas M, Giray S, Tan M, Yildirim T. Partial recovery from cortical blindness following monoxide intoxication. Int J Neurosci. 2005;115:143–147. 5. Chen Z, Wang R, Wu J, Xia F, Sun Q, Xu J, Liu L. Low-dose carbon monoxide inhalation protects neuronal cells from apoptosis after optic nerve crush. Biochem Biophys Res Commun. 2016;469:809–815. 6. Oku H, Fukushima K, Miyata M, Wakakura M, Ishikawa S. Cyanide with vitamin B12 deficiency as the cause of experimental tobacco amblyopia. Nippon Ganka Gakkai Zasshi. 1991;95:158–164. 7. Simmons IG, Good PA. Carbon monoxide poisoning causes optic neuropathy. Eye (Lond). 1998;12:809–814. 8. Carbon Monoxide Exposures—United states, 2000-2009. Morbidity and Mortality Weekly Report; 2011;60:30. Available at: http://www.cdc.gov/co/deafault.htm. 9. Bilchik RC, Muller-Bergh HA, Freshman ME. Ischemic retinopathy due to carbon monoxide poisoning. Arch Ophthalmol. 1971;86:142–144. 10. Murray WZ. Amblyopia caused by inhalation of carbon monoxide gas. Minn Med. 1926;9:561–564. Brocca et al: J Neuro-Ophthalmol 2022; 42: e326-e330 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.