Optic Disc Cupping Due to Dolichoectatic Internal Carotid Artery Optic Nerve Compression

To determine whether significant compression of the optic nerve by the internal carotid artery (ICA) can produce an optic neuropathy with optic disc cupping that resembles glaucoma in patients without elevated intraocular pressure (IOP).

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Optic Disc Cupping Due to Dolichoectatic Internal Carotid Artery Optic Nerve Compression Jonathan A. Micieli, MD, Edward A. Margolin, MD C Background: To determine whether significant compression of the optic nerve by the internal carotid artery (ICA) can produce an optic neuropathy with optic disc cupping that resembles glaucoma in patients without elevated intraocular pressure (IOP). Methods: This was a retrospective case series of patients referred to neuro-ophthalmology for a possible nonglaucomatous optic neuropathy. Patients were included in the study if they had preserved visual acuity, optic discrelated visual field defects, optic nerve cupping, IOP less than 21 mm Hg, open angles, and unequivocal radiological compression of the ipsilateral optic nerve by an intracranial blood vessel. Results: Three patients were included with a mean age of 56.3 (range 29–82) years. Patient 1 was a 58-year-old man incidentally noted to have left optic nerve cupping on a routine examination. He had an inferior arcuate defect and the left prechiasmatic optic nerve was elevated and compressed by a tortuous left ICA. Patient 2 was a 29-year-old man with a normal-tension glaucoma (NTG) diagnosis for 7 years in the right eye treated with latanoprost. He had a superior greater than inferior arcuate defect and there was vascular compression of the optic nerve between the supraclinoid ICA and A1 segment of the anterior cerebral artery. Patient 3 was an 82-year-old woman with an NTG diagnosis for 10 years who had progression of her visual field defects despite low IOPs. MRI showed mass effect on the right optic nerve by a dolichoectatic right supraclinoid ICA. Conclusions: Significant compression of the optic nerve by a normal, tortuous, or dolichoectatic ICA may result in an optic neuropathy with optic disc cupping that resembles glaucoma. ranial nerves, including the optic nerves, are susceptible to neurovascular compression from dolichoectatic or otherwise normal intracranial blood vessels (1). This compression has been reported to affect both the anterior and retrochiasmal visual pathways with surgical decompression resulting in improved visual function in some cases (1– 4). In a case series of 18 patients with symptomatic compression of the optic nerve by the internal carotid artery (ICA), multiple patients surprisingly had preserved visual acuity, color vision, and nerve fiber bundle defects, resembling a glaucomatous optic neuropathy (2). Ogata et al (5) studied 54 Japanese patients with normal-tension glaucoma (NTG) and 52 age-matched controls and found that a significantly higher proportion of NTG patients had optic nerve compression by the ICA. A similar result was found in 16 Japanese NTG patients with NTG and 16 age-matched controls with elevated intraocular pressure (IOP) (6). However, these results were not reproduced in an American study of 20 NTG patients (7). In another study that reviewed 100 asymptomatic patients, 70% were reported to have unilateral or bilateral contact and 12% had bilateral compression of the optic nerve by the ICA (8). To lend additional evidence to this topic, we report a series of patients with an optic neuropathy that resembled glaucoma with unequivocal radiological compression of the optic nerve by the ICA. Journal of Neuro-Ophthalmology 2021;41:e560–e565 doi: 10.1097/WNO.0000000000001113 © 2020 by North American Neuro-Ophthalmology Society METHODS Department of Ophthalmology and Vision Sciences (JAM, EAM), University of Toronto, Toronto, Canada; Division of Neurology, Department of Medicine (JAM, EAM), University of Toronto, Toronto, Canada; and Kensington Vision and Research Centre (JAM), Toronto, Canada. The authors report no conflicts of interest. Address correspondence to Jonathan A. Micieli, MD, Kensington Vision and Research Centre, 340 College Street, Suite 501, Toronto, ON M5T 3A9, Canada; E-mail: [e-mail] e560 This study was approved by the Research Ethics Board at the University of Toronto. Patients referred to a tertiary neuroophthalmology practice between July 1, 2011, and July 1, 2019, were screened for inclusion in the study. All patients were seen by fellowship-trained neuro-ophthalmologists (J.A.M. or E.A.M.) and were specifically referred for a question regarding the diagnosis of glaucoma or another optic neuropathy. For inclusion in the study, patients must have had preserved visual acuity, preserved color vision measured by Ishihara color plates, an optic disc-related visual Micieli and Margolin: J Neuro-Ophthalmol 2021; 41: e560-e565 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution field defect consistent with glaucoma, cupping of the optic nerve without obvious pallor of the remaining neuroretinal rim, and an IOP less than 21 mm Hg on all clinical visits. In addition, the angles must have been open on gonioscopy (trabecular meshwork visible for at least 180°). All patients must have undergone MRI of the orbits and brain demonstrating unequivocal mass effect of any portion of the ICA or adjacent blood vessels on the optic nerve. MRI was performed at the discretion of the neuro-ophthalmologist, and no additional cause of optic neuropathy was felt to be more likely. Only patients with unilateral disease were included to avoid confounding factors. Clinical characteristics and clinical course were retrieved for analysis. RESULTS A total of 3 patients were included in the study (2 male and 1 female) with an average age of 56.3 (range 29–82) years. The right eye was affected in 2 patients and the left eye in one patient. Two patients were on topical eye drops at the time of diagnosis and the maximum IOP over their clinical course was not higher than 18 in any patient. Two patients had comorbidities of hypertension and one patient had dyslipidemia. The clinical presentation and course of each patient are described below. Patients Case 1 A 58-year-old black man was referred by an ophthalmologist after he was noted to have cupping in his right optic nerve on routine examination with an optometrist. He denied any visual symptoms and had no family history of glaucoma. The referring ophthalmologist documented an IOP of 12 in the right eye and 13 in the left eye with a cup-to-disc ratio of 0.3 in the right eye and 0.9 in the left eye. Neuroophthalmological assessment revealed a visual acuity of 20/ 20 in both eyes, a similar IOP of 12 in the right eye and 12 in the left eye, and cupping of the left optic nerve (cup-to-disc ratio of 0.9) without obvious pallor of the remaining neuroretinal rim. Optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) showed an average thickness of 105 mm in the right eye and 43 mm in the left eye (Fig. 1B). Humphrey visual field testing was normal in the right eye and showed an inferior arcuate defect with a mean deviation of 218.73 dB in the left eye (Fig. 1A). A workup for a left optic neuropathy was performed including an MRI of the orbits with contrast. A complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody, Venereal Disease Research Laboratory (VDRL), and angiotensin-converting enzyme (ACE) were normal. MRI of the orbits and brain revealed that the left prechiasmatic optic nerve and optic chiasm were elevated by a tortuous left ICA and appeared compressed between it and the anterior cerebral artery (Fig. 1C). Both arteries did not appear aneurysmal. The patient was observed and the optic neuropathy remained stable Micieli and Margolin: J Neuro-Ophthalmol 2021; 41: e560-e565 at 1-year follow-up. The IOP did not exceed 13 in the left eye at any follow-up appointment. Case 2 A 29-year-old black man was referred by a glaucoma specialist for a possible nonglaucomatous optic neuropathy. He was diagnosed with NTG 7 years prior in a different country during a routine eye examination. His IOP was 16 in the right eye and 17 in the left eye at this initial visit, and he was started on latanoprost nightly in both eyes. He moved to Canada and was seen by a glaucoma specialist where his IOP was 12 in both eyes on latanoprost and he had a cup-to-disc ratio of 0.8 in the right eye and 0.5 in the left eye without obvious pallor of the remaining neuroretinal rim. A neuro-ophthalmological assessment was arranged for further workup, given his atypical presentation at a young age and normal IOP. On examination, he had a visual acuity of 20/20 in both eyes, he saw 14/14 Ishihara color plates in both eyes, and had a right relative afferent pupillary defect. Angles were open on gonioscopy and dilated fundus examination revealed right optic disc cupping with a cup-to-disc ratio of 0.8 in the right eye and 0.5 in the left eye (Fig. 2C). OCT of the RNFL showed an average thickness of 58 mm in the right eye and 99 mm in the left eye (Fig. 2B). Humphrey visual field testing revealed a superior greater than inferior arcuate defect with a mean deviation of 212.58 dB in the right eye and was normal in the left eye (Fig. 2A). He underwent an MRI of the orbits and brain, and this showed vascular compression of the right optic nerve by the supraclinoid ICA and the A1 segment of the anterior cerebral artery (Fig. 2D). He continued treatment with latanoprost, and his visual field test and optic nerve appearance was stable 1 year later. Case 3 An 82-year-old black woman was referred by a glaucoma specialist to assess for a nonglaucomatous optic neuropathy. She had a medical history of hypertension, dyslipidemia, congestive heart failure, breast cancer 2 years before presentation treated with local resection, and a pulmonary embolism 3 years before. She underwent cataract extraction and intraocular lens placement in both eyes 1 year before presentation. Her medications included hydrochlorothiazide, irbesartan, warfarin, and atorvastatin. She was diagnosed with normal tension glaucoma on a routine examination 10 years before presentation, and her IOP before treatment was 16 in both eyes (central corneal thickness was 487 mm in each eye). She was found to have an inferior arcuate defect and cupping in the right optic nerve. She was started on latanoprost in both eyes before bed and monitored for progression. Her IOP did not exceed 12 at her regular follow-ups on treatment. However, despite normal IOP, her visual field defect progressed only in the right eye and she developed a superior arcuate defect in that eye. A neuro-ophthalmology consultation was arranged due to progression despite well-controlled IOP and treatment with timolol 0.5% twice per day in the right eye was started. e561 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Case 1. Humphrey 24-2 SITA-Fast visual field in the left eye demonstrating an inferior arcuate defect with mean deviation 218.73 dB (A). Optical coherence tomography of the retinal nerve fiber layer showing a reduced average thickness of 43 mm in the left eye (B). T2 coronal MRI of the orbits demonstrating the left prechiasmatic optic nerve (yellow arrow) and optic chiasm being elevated by a tortuous left internal carotid artery and compressed between it and the anterior cerebral artery (C). SITA, Swedish Interactive Threshold Algorithm. Neuro-ophthalmological assessment revealed a visual acuity of 20/20 in both eyes, normal color vision by Ishihara color plates, and a right relative afferent pupillary defect. Angles were open by gonioscopy, and IOP was 9 in the right eye and in the 10 left eye. Dilated fundus examination revealed cupping in the right optic nerve with a cup-to-disc ratio 0.9 in the right eye and 0.4 in the left eye (Fig. 3C). There was no obvious pallor of the remaining neuroretinal rim. OCT of the RNFL revealed an average thickness of 77 mm in the right eye and 99 mm in the left eye, and Humphrey visual field testing showed a superior and inferior arcuate defect in the right eye with a mean deviation of 214.33 dB (Figures A and B). She underwent an MRI of the orbits and brain that showed mass effect on the right optic nerve by a dolichoectatic right supraclinoid ICA (Fig. 3D). Additional workup revealed a normal complete blood count, ESR, CRP, VDRL, and ACE. The patient continued to follow with her glaucoma specialist and her visual field remained stable 1 year later. CONCLUSION Compression of the optic nerves by tumors, aneurysms, or normal blood vessels has been reported to cause an optic e562 neuropathy that resembles glaucoma (9–12). In this case series, we describe 3 patients who carried a diagnosis of NTG that had unequivocal and significant radiological compression of the affected optic nerve by a tortuous or dolichoectatic ICA. Each patient was referred to the neuro-ophthalmology service because there was doubt regarding the diagnosis of NTG or the patient had an unusual progression despite well-controlled IOPs. The radiological findings provided an explanation for the optic neuropathy, and no significant change in the visual function was noted over a follow-up period of one year in all these patients. Because optic atrophy and OCT RNFL thinning had developed in each patient, surgical risks were considered to outweigh the benefit. Similar to our cases, previous studies have found that vascular compression by the ICA may be influential in developing visual field defects in an optic neuropathy that resembles glaucoma (5,6). These studies demonstrated that a higher proportion of patients classified as NTG had radiological optic nerve compression compared to age-matched controls. An additional study also found that 20 patients with unexplained vision loss had a smaller distance between the optic nerve and the ipsilateral ICA, suggesting that the intimate relationship between these 2 structures may be Micieli and Margolin: J Neuro-Ophthalmol 2021; 41: e560-e565 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. Case 2. Humphrey 24-2 SITA-Fast visual field in the right eye demonstrating a superior greater than inferior arcuate defect with a mean deviation of 212.58 dB in the right eye (A). Optical coherence tomography of the retinal nerve fiber layer showing a reduced average thickness of 58 mm in the right eye (B). Optic disc photographs demonstrating cupping of the right optic nerve (C). T2 coronal MRI of the orbits demonstrating compression of the right optic nerve (yellow arrow) by the supraclinoid internal carotid artery and the A1 segment of the anterior cerebral artery. SITA, Swedish Interactive Threshold Algorithm (D). playing a role in causing an optic neuropathy (13). Jacobson reported that 21 of 24 affected eyes had optic disc pallor together with saucerlike excavation of the central and temporal papillary nerve fiber layer (2). Our cases differ from these patients in several ways. All 3 of our patients had normal color vision, whereas 12/18 patients in the Jacobson study had abnormal color vision with both sets of patients were evaluated with a similar 14-plate color assessment. All 3 of our patients had sparing of the central visual field, whereas 6/18 patients in the Jacobson series had central, paracentral, or cecocentral scotomas. One patient also had a bitemporal scotoma, which localizes to the optic chiasm and does not resemble glaucoma. Our 3 patients had 20/20 visual acuity, whereas only 6 patients had 20/20 or better vision in the Jacobson series with 2 of these patients having had abnormal color vision. Although Jacobson also excluded patients with elevated IOP, our patients all underwent gonioscopy to further exclude any possibility that intermittent IOP spikes from narrow angles may have contributed. Our case series provides additional evidence with OCT demonstrating how ICA compression may resemble glaucoma as vertical cupping was a feature in Case 3 Micieli and Margolin: J Neuro-Ophthalmol 2021; 41: e560-e565 (inferior RNFL quadrant ,1% of normal population and 11 o’clock RNFL clock hour ,5% of the normal population) and to a lesser extent in Case 2 (vertical RNFL clock hours were mainly affected). Case 1 also had relative sparing of the nasal RNFL quadrant. We also did not think pallor was a prominent feature of the optic disc evaluation, but this is a subjective sign that has high interobserver variability. All patients in the current study had some degree of an inferior arcuate defect and this may be a result of mechanical effect as the superior segment of the optic nerve is compressed against the above dural folds. Other potential mechanisms include chronic ischemia as regional perfusion is compromised by the local compression (2). It is unclear why some patients with optic nerve compression by the dolichoectatic vessels develop central visual loss and neuroretinal rim pallor and some manifest it as an optic neuropathy that resembles glaucoma with sparing of central acuity and optic nerve cupping. The relative contribution of compression vs ischemia may play a role. It is also possible that in cases of compressive optic neuropathy affecting central vision, the degree of compression by the dolichoectatic vessel is greater causing impairment of axons originating from e563 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 3. Case 3. Humphrey 24-2 SITA-Fast visual field in the right eye demonstrating a superior and inferior arcuate defect in the right eye with a mean deviation of 214.33 dB (A). Optical coherence tomography of the retinal nerve fiber layer showing a reduced average thickness of 77 mm in the right eye (B). Optic disc photographs demonstrating cupping of the right optic nerve without pallor (C). T2 coronal MRI of the orbits demonstrating mass effect on the right optic nerve by a dolichoectatic right supraclinoid internal carotid artery (D). SITA, Swedish Interactive Threshold Algorithm. papillomacular bundle. In cases of optic nerve cupping and sparing of central acuity, there may be less contact between the vessel and the optic nerve and it is the pulsating pressure of the vessel that is causing impairment of axons located on the periphery of the nerve thus sparing central axons. Moreover, compression of the optic nerve by the ICA may also reduce the threshold for glaucomatous damage at the lamina cribrosa and make otherwise healthy individuals more sensitive to normal IOP levels. It is worth noting that superior visual field defects are more common in glaucoma compared to inferior defects, which was the only defect present in Case 1 (14,15). The high prevalence of radiological optic nerve compression in the normal population makes it difficult to interpret radiological findings in isolation. Many patients with radiological compression of the optic nerve by incidentally found lesions such as meningiomas and pituitary adenomas maintain normal visual function and are followed for years without visual changes (16). Moreover, many individuals with elevated IOP also do not develop glaucomatous optic neuropathies, suggesting that genetic factors may influence whether the optic nerve bee564 comes compromised by various insults. Intrinsic characteristics of the compressing vessel may also play a role and variables such as calcifications, elasticity, and blood pressure may be important. Dolichoectasia of the intracranial blood vessels has been associated with vascular risk factors and these individuals may already have dysfunctional autoregulation (17). Further research into the mechanism of dolichoectasia may provide additional therapeutic options for these patients. We feel that it is unlikely that these 3 patients had NTG and unrelated ICA compression of the optic nerve because the severity of the optic nerve elevation and compression by an intracranial was much more than typically seen even in incidental cases. In each of the cases, the radiologist commented on the finding in the official report without additional prompting. The study was limited by the small sample size, but we included only selected cases with unequivocal clinical and radiological features to ensure that there were no confounding factors. The follow-up period was relatively short, given the chronic nature of glaucoma. Pallor of the remaining neuroretinal rim in cupped and excavated optic nerves may be difficult to determine and is Micieli and Margolin: J Neuro-Ophthalmol 2021; 41: e560-e565 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution open to subjective interpretation. However, the neuroophthalmologist in each case did not feel that pallor was a prominent feature of the optic disc examination. Improvement in visual function after surgical intervention would have provided additional evidence for causality, but no surgical intervention was pursued in each case given the associated neurosurgical risks. However, only unilateral cases were included and the benefit–risk ratio would likely change in bilateral, severe cases and with improvements in neurosurgical techniques in the future. In conclusion, compression of the optic nerves by tortuous, dolichoectatic, or otherwise normal ICAs are associated with the development of an optic neuropathy that may resemble glaucoma with optic disc cupping and sparing of central visual acuity. MRI can be considered in NTG patients that demonstrate an unusual clinical course or have atypical demographic characteristics. Although neurosurgical intervention is likely not practical in most cases, it may be considered in severe bilateral cases and as microinvasive neurosurgical approaches improve in the future. 3. 4. 5. 6. 7. 8. 9. 10. 11. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: J. A. Micieli and E. A. Margolin; b. Acquisition of data: J. A. Micieli and E. A. Margolin; c. Analysis and interpretation of data: J. A. Micieli and E. A. Margolin. Category 2: a. Drafting the manuscript: J. A. Micieli and E. A. Margolin; b. Revising it for intellectual content: J. A. Micieli and E. A. Margolin. Category 3: a. Final approval of the completed manuscript: J. A. Micieli and E. A. Margolin. 12. 13. 14. 15. REFERENCES 1. Purvin V, Kawasaki A, Zeldes S. Dolichoectatic arterial compression of the anterior visual pathways: neuro-ophthalmic features and clinical course. 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