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Optic nerve hypoplasia and internal carotid artery hypoplasia: a new association
CORRESPONDENCE Optic nerve hypoplasia and internal carotid artery hypoplasia: a new association Several associations have been described between optic nerve hypoplasia (ONH) and other central nervous system (CNS) disorders.1 However, the concurrence of ONH and internal carotid artery hypoplasia (ICAH) has not been previously reported. This fact has etiopathogenic implications as explained below. An asymptomatic 57-year-old female presented a right relative afferent pupillary defect without anisocoria. She had systemic hypertension and diabetes mellitus type II, which were well controlled with medical treatment. Otherwise her medical and family histories were noncontributory. Her best-corrected visual acuity was 20/20 OU. No palpebral ptosis, proptosis, or enophthalmos were observed. Extrinsic ocular motility, colour vision, and
anterior segment biomicroscopy were normal OU. Intraocular pressure was 16 mm Hg, and central corneal thickness was 500 microns bilaterally. Funduscopy demonstrated an abnormally small right optic nerve (ON) surrounded by a whitish peripapillary halo (“double ring” sign), which is characteristic of ONH, and no anomalies in her left ON (Fig. 1a). Automated perimetry revealed severe defects only in her right eye (Fig. 1b). Optical coherence tomography revealed pronounced diffuse thinning of the peripapillary retinal nerve fibre layer (Fig. 2a) and macular ganglion cell-inner plexiform layer thicknesses (Fig. 2b) in her right eye. The diurnal IOP curve was normal. Neurological examinations and laboratory tests (including screening of autoimmune/infectious diseases and hormone levels) did not show any abnormalities. Computed tomography (CT) revealed a narrowed right carotid
Fig. 1 — Neuro-ophthalmic examinations (I): Funduscopy and visual field test. Funduscopy of the optic nerves showing the “double ring” sign of the right nerve and normal left optic nerve (a). Automated perimetry of both eyes (b). Three-year visual field index (VFI) rate of progression of the right and left eye (c). The slight trend toward VFI improvement is attributed to the learning effect. CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
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Fig. 2 — Neuro-ophthalmic examinations (II): Optical coherence tomography (OCT). Peripapillary retinal nerve fibre layer OCT analysis of both eyes (a). Macular ganglion cell inner plexiform layer OCT analysis of both eyes (b).
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Correspondence canal (Fig. 3a). Magnetic resonance imaging (MRI) exhibited a small right intracranial ON (Fig. 3b) and the absence of a normal right internal carotid artery (ICA) in the supraclinoid segment with cluster collateral vessels instead (Fig. 3c). A filiform signal was recorded in all intracranial segments of the right ICA by magnetic resonance angiography (Fig. 3d, e). No other intracranial abnormalities were found. B-mode ultrasonography of supra-aortic trunks demonstrated a reduced diameter of the right ICA but symmetrical external carotid arteries (Fig. 3f). Ultrasound colour Doppler
imaging presented significantly reduced flow velocity in the right ICA (peak systolic velocity [PS], 34.19 cm/s; peak enddiastolic velocity [ED], 7.72 cm/s) compared with the left ICA (PS, 87.55 cm/s; ED, 30.19 cm/s) (Fig. 3g, h). Thus, the diagnosis of right ICAH was made. The right common carotid artery (CCA) was also found to be much smaller than the contralateral CCA (Fig. 4). A 3-year follow-up was carried out by means of neuroimaging and complete neuro-ophthalmic examinations, including automated perimetry, without deterioration (Fig. 1c).
Fig. 3 — Radiological and ultrasound examinations of the internal carotid arteries (ICA). Axial computed tomography of the skull base showing a small right carotid canal (white arrow) in comparison to left one (black arrow). This is a cardinal sign of carotid artery hypoplasia (a). Coronal magnetic resonance imaging of the head revealing asymmetry in optic nerve size and supporting the diagnosis of right optic nerve hypoplasia (b). Axial magnetic resonance imaging showing the absence of normal right ICA and cluster collateral vessels instead (white arrow) (c). Axial (d) and coronal (e) magnetic resonance angiography of the head demonstrating the asymmetry between right and left ICA territories. Transverse B-mode echographic supra-aortic trunk examination (both sides). Dotted white lines delineate the vascular lumina. Note the difference in size between right and left ICA (f). Ultrasound colour Doppler imaging exhibiting the difference of flow velocity between right (g) and left ICA (h). PS, peak systolic velocity; ED, peak end-diastolic velocity; ECA, external carotid artery. CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
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Fig. 4 — Ultrasound examinations of common carotid arteries. Longitudinal B-mode echographic supra-aortic trunk examination (both sides). The right common carotid artery (CCA) was also found to be much smaller than the left.
Unilateral ONH is a congenital disorder characterized by an underdevelopment of one of the ONs with marked intracranial asymmetry. Visual acuity ranges from 20/20 to amaurosis presenting variable visual field defects but the visual impairment is nonprogressive. A number of associations have been described. For example, septo-optic dysplasia (SOD) is a heterogeneous and inconstant combination of different CNS parenchymal malformations: ONH, pituitary hypoplasia (with hormonal deficiency), and midline malformations of the brain (absence of the septum pellucidum or thinning of the corpus callosum).1 The diagnosis of ONH is typically clinical, but the confirmation is more accurately established by MRI.1,2 Unilateral ICAH is a rare congenital disorder that causes a lack of blood flow from one side in the carotid system, which is mostly compensated by the Circle of Willis and other collateral vessels. Thus, unilateral ICAH is usually asymptomatic because the flow to intracranial vessels comes from contralateral ICA or even from vertebrobasilar system, if they are patent.3,4 However, ICAH induces a hemodynamic pressure increase in collateral arteries resulting in a higher prevalence of intracranial aneurysms in affected patients (24%–34%) compared with the normal population (2%–4%), so these patients require careful lifelong follow-up.5 Furthermore, the presence of unilateral ICAH is important in the study of cerebral ischemia. Indeed, emboli in one cerebral hemisphere may come from an atherosclerotic contralateral ICA. Otherwise, ICAH should be kept in mind when surgeries such as carotid endarterectomy or transsphenoidal pituitary surgery are planned.5 The diagnosis of ICAH is based on neuroimaging. A small carotid canal shown on CT is a definitive sign of this condition because the presence of ICA is obligatory for the development of the carotid canal in the temporal bone.3–5 A decrease in ipsilateral CCA size (Fig. 4) is another feature of congenital ICAH.3 The etiopathogenesis of ONH is still not well known. Several factors and mechanisms have been proposed.1,6 In the present case, the concurrence of ipsilateral ONH and ICAH highly suggests a causal relationship. Some arguments in favour of this consideration are as follows: (i) the ICA appears between day 24 and 28 of intrauterine development (and CCA even earlier),7 whereas the ON forms by the seventh week,8 so ICAH presumably
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occurred earlier than ONH; (ii) the arterial input to the ON is derived from the ICA, so an ICAH may have induced a secondary ONH9; and (iii) some evidence relates SOD etiology to a vascular disruption sequence during neuroembriogenesis.10–12 In conclusion, when ONH is found, neuroimaging should be performed to rule out other relevant entities such as ICAH. In addition, this unique case supports intrauterine restriction of blood supply as the origin of isolated ONH.
Disclosure The authors have no proprietary or commercial interest in any materials discussed in this article.
Jose Javier Garcia-Medina, *,†,‡ Monica del-Rio-Vellosillo, § Jesaran Fares-Valdivia, * Luis Alemañ-Romero, * Vicente Zanon-Moreno, ‡,║ Maria Dolores Pinazo-Duran ‡,║ *
General University Hospital Reina Sofia, Murcia, Spain; University of Murcia, Murcia, Spain; ‡Ophthalmic Research Unit “Santiago Grisolia,” Valencia, Spain; §University Hospital Virgen de la Arrixaca, Murcia, Spain; ||University of Valencia, Valencia, Spain. †
Correspondence to: Jose Javier Garcia-Medina, MD, PhD: [email protected] REFERENCES 1. Brodsky MC. Pediatric neuro-ophthalmology. 3rd ed. New York: Springer; 2016. 2. Lenhart PD, Desai NK, Bruce BB, Hutchinson AK, Lambert SR. The role of magnetic resonance imaging in diagnosing optic nerve hypoplasia. Am J Ophthalmol. 2014;158:1164-71. 3. Ide C, De Coene B, Mailleux P, Baudrez V, Ossemann M, Trigaux JP. Hypoplasia of the internal carotid artery: a noninvasive diagnosis. Eur Radiol. 2000;10:1865-70. 4. Taşar M, Yetişer S, Taşar A, Uğurel S, Gönül E, Sağlam M. Congenital absence or hypoplasia of the carotid artery: radioclinical issues. Am J Otolaryngol. 2004;25:339-49. 5. Nicoletti G, Sanguigni S, Bruno F, Tardi S, Malferrari G. Hypoplasia of the internal carotid artery: collateral circulation and ultrasonographic findings. A case report. J Ultrasound. 2009;12: 41-4.
Correspondence 6. Ryabets-Lienhard A, Stewart C, Borchert M, Geffner ME. The optic nerve hypoplasia spectrum: review of the literature and clinical guidelines. Adv Pediatr.. 2016;63:127-46. 7. Menshawi K, Mohr JP, Gutierrez J. A functional perspective on the embryology and anatomy of the cerebral blood supply. J Stroke. 2015;17:144-58. 8. Sadler TW. Langman’s medical embryology. 12th ed. Baltimore: Lippincott Williams & Wilkins; 2012. 9. Hayreh SS. Ischemic optic neuropathy. Prog Retin Eye Res. 2009;28: 34-62. 10. Lubinsky MS. Hypothesis: septo-optic dysplasia is a vascular disruption sequence. Am J Med Genet. 1997;69:235-6.
11. Riedl S, Vosahlo J, Battelino T, et al. Refining clinical phenotypes in septo-optic dysplasia based on MRI findings. Eur J Pediatr. 2008;167: 1269-76. 12. Atapattu N, Ainsworth J, Willshaw H, et al. Septo-optic dysplasia: antenatal risk factors and clinical features in a regional study. Horm Res Paediatr. 2012;78:81-7. Can J Ophthalmol 2017;]:]]]–]]] 0008-4182/16/$-see front matter & 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2017.05.006
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
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anterior segment biomicroscopy were normal OU. Intraocular pressure was 16 mm Hg, and central corneal thickness was 500 microns bilaterally. Funduscopy demonstrated an abnormally small right optic nerve (ON) surrounded by a whitish peripapillary halo (“double ring” sign), which is characteristic of ONH, and no anomalies in her left ON (Fig. 1a). Automated perimetry revealed severe defects only in her right eye (Fig. 1b). Optical coherence tomography revealed pronounced diffuse thinning of the peripapillary retinal nerve fibre layer (Fig. 2a) and macular ganglion cell-inner plexiform layer thicknesses (Fig. 2b) in her right eye. The diurnal IOP curve was normal. Neurological examinations and laboratory tests (including screening of autoimmune/infectious diseases and hormone levels) did not show any abnormalities. Computed tomography (CT) revealed a narrowed right carotid
Fig. 1 — Neuro-ophthalmic examinations (I): Funduscopy and visual field test. Funduscopy of the optic nerves showing the “double ring” sign of the right nerve and normal left optic nerve (a). Automated perimetry of both eyes (b). Three-year visual field index (VFI) rate of progression of the right and left eye (c). The slight trend toward VFI improvement is attributed to the learning effect. CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
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Correspondence
Fig. 2 — Neuro-ophthalmic examinations (II): Optical coherence tomography (OCT). Peripapillary retinal nerve fibre layer OCT analysis of both eyes (a). Macular ganglion cell inner plexiform layer OCT analysis of both eyes (b).
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Correspondence canal (Fig. 3a). Magnetic resonance imaging (MRI) exhibited a small right intracranial ON (Fig. 3b) and the absence of a normal right internal carotid artery (ICA) in the supraclinoid segment with cluster collateral vessels instead (Fig. 3c). A filiform signal was recorded in all intracranial segments of the right ICA by magnetic resonance angiography (Fig. 3d, e). No other intracranial abnormalities were found. B-mode ultrasonography of supra-aortic trunks demonstrated a reduced diameter of the right ICA but symmetrical external carotid arteries (Fig. 3f). Ultrasound colour Doppler
imaging presented significantly reduced flow velocity in the right ICA (peak systolic velocity [PS], 34.19 cm/s; peak enddiastolic velocity [ED], 7.72 cm/s) compared with the left ICA (PS, 87.55 cm/s; ED, 30.19 cm/s) (Fig. 3g, h). Thus, the diagnosis of right ICAH was made. The right common carotid artery (CCA) was also found to be much smaller than the contralateral CCA (Fig. 4). A 3-year follow-up was carried out by means of neuroimaging and complete neuro-ophthalmic examinations, including automated perimetry, without deterioration (Fig. 1c).
Fig. 3 — Radiological and ultrasound examinations of the internal carotid arteries (ICA). Axial computed tomography of the skull base showing a small right carotid canal (white arrow) in comparison to left one (black arrow). This is a cardinal sign of carotid artery hypoplasia (a). Coronal magnetic resonance imaging of the head revealing asymmetry in optic nerve size and supporting the diagnosis of right optic nerve hypoplasia (b). Axial magnetic resonance imaging showing the absence of normal right ICA and cluster collateral vessels instead (white arrow) (c). Axial (d) and coronal (e) magnetic resonance angiography of the head demonstrating the asymmetry between right and left ICA territories. Transverse B-mode echographic supra-aortic trunk examination (both sides). Dotted white lines delineate the vascular lumina. Note the difference in size between right and left ICA (f). Ultrasound colour Doppler imaging exhibiting the difference of flow velocity between right (g) and left ICA (h). PS, peak systolic velocity; ED, peak end-diastolic velocity; ECA, external carotid artery. CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
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Correspondence
Fig. 4 — Ultrasound examinations of common carotid arteries. Longitudinal B-mode echographic supra-aortic trunk examination (both sides). The right common carotid artery (CCA) was also found to be much smaller than the left.
Unilateral ONH is a congenital disorder characterized by an underdevelopment of one of the ONs with marked intracranial asymmetry. Visual acuity ranges from 20/20 to amaurosis presenting variable visual field defects but the visual impairment is nonprogressive. A number of associations have been described. For example, septo-optic dysplasia (SOD) is a heterogeneous and inconstant combination of different CNS parenchymal malformations: ONH, pituitary hypoplasia (with hormonal deficiency), and midline malformations of the brain (absence of the septum pellucidum or thinning of the corpus callosum).1 The diagnosis of ONH is typically clinical, but the confirmation is more accurately established by MRI.1,2 Unilateral ICAH is a rare congenital disorder that causes a lack of blood flow from one side in the carotid system, which is mostly compensated by the Circle of Willis and other collateral vessels. Thus, unilateral ICAH is usually asymptomatic because the flow to intracranial vessels comes from contralateral ICA or even from vertebrobasilar system, if they are patent.3,4 However, ICAH induces a hemodynamic pressure increase in collateral arteries resulting in a higher prevalence of intracranial aneurysms in affected patients (24%–34%) compared with the normal population (2%–4%), so these patients require careful lifelong follow-up.5 Furthermore, the presence of unilateral ICAH is important in the study of cerebral ischemia. Indeed, emboli in one cerebral hemisphere may come from an atherosclerotic contralateral ICA. Otherwise, ICAH should be kept in mind when surgeries such as carotid endarterectomy or transsphenoidal pituitary surgery are planned.5 The diagnosis of ICAH is based on neuroimaging. A small carotid canal shown on CT is a definitive sign of this condition because the presence of ICA is obligatory for the development of the carotid canal in the temporal bone.3–5 A decrease in ipsilateral CCA size (Fig. 4) is another feature of congenital ICAH.3 The etiopathogenesis of ONH is still not well known. Several factors and mechanisms have been proposed.1,6 In the present case, the concurrence of ipsilateral ONH and ICAH highly suggests a causal relationship. Some arguments in favour of this consideration are as follows: (i) the ICA appears between day 24 and 28 of intrauterine development (and CCA even earlier),7 whereas the ON forms by the seventh week,8 so ICAH presumably
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occurred earlier than ONH; (ii) the arterial input to the ON is derived from the ICA, so an ICAH may have induced a secondary ONH9; and (iii) some evidence relates SOD etiology to a vascular disruption sequence during neuroembriogenesis.10–12 In conclusion, when ONH is found, neuroimaging should be performed to rule out other relevant entities such as ICAH. In addition, this unique case supports intrauterine restriction of blood supply as the origin of isolated ONH.
Disclosure The authors have no proprietary or commercial interest in any materials discussed in this article.
Jose Javier Garcia-Medina, *,†,‡ Monica del-Rio-Vellosillo, § Jesaran Fares-Valdivia, * Luis Alemañ-Romero, * Vicente Zanon-Moreno, ‡,║ Maria Dolores Pinazo-Duran ‡,║ *
General University Hospital Reina Sofia, Murcia, Spain; University of Murcia, Murcia, Spain; ‡Ophthalmic Research Unit “Santiago Grisolia,” Valencia, Spain; §University Hospital Virgen de la Arrixaca, Murcia, Spain; ||University of Valencia, Valencia, Spain. †
Correspondence to: Jose Javier Garcia-Medina, MD, PhD: [email protected] REFERENCES 1. Brodsky MC. Pediatric neuro-ophthalmology. 3rd ed. New York: Springer; 2016. 2. Lenhart PD, Desai NK, Bruce BB, Hutchinson AK, Lambert SR. The role of magnetic resonance imaging in diagnosing optic nerve hypoplasia. Am J Ophthalmol. 2014;158:1164-71. 3. Ide C, De Coene B, Mailleux P, Baudrez V, Ossemann M, Trigaux JP. Hypoplasia of the internal carotid artery: a noninvasive diagnosis. Eur Radiol. 2000;10:1865-70. 4. Taşar M, Yetişer S, Taşar A, Uğurel S, Gönül E, Sağlam M. Congenital absence or hypoplasia of the carotid artery: radioclinical issues. Am J Otolaryngol. 2004;25:339-49. 5. Nicoletti G, Sanguigni S, Bruno F, Tardi S, Malferrari G. Hypoplasia of the internal carotid artery: collateral circulation and ultrasonographic findings. A case report. J Ultrasound. 2009;12: 41-4.
Correspondence 6. Ryabets-Lienhard A, Stewart C, Borchert M, Geffner ME. The optic nerve hypoplasia spectrum: review of the literature and clinical guidelines. Adv Pediatr.. 2016;63:127-46. 7. Menshawi K, Mohr JP, Gutierrez J. A functional perspective on the embryology and anatomy of the cerebral blood supply. J Stroke. 2015;17:144-58. 8. Sadler TW. Langman’s medical embryology. 12th ed. Baltimore: Lippincott Williams & Wilkins; 2012. 9. Hayreh SS. Ischemic optic neuropathy. Prog Retin Eye Res. 2009;28: 34-62. 10. Lubinsky MS. Hypothesis: septo-optic dysplasia is a vascular disruption sequence. Am J Med Genet. 1997;69:235-6.
11. Riedl S, Vosahlo J, Battelino T, et al. Refining clinical phenotypes in septo-optic dysplasia based on MRI findings. Eur J Pediatr. 2008;167: 1269-76. 12. Atapattu N, Ainsworth J, Willshaw H, et al. Septo-optic dysplasia: antenatal risk factors and clinical features in a regional study. Horm Res Paediatr. 2012;78:81-7. Can J Ophthalmol 2017;]:]]]–]]] 0008-4182/16/$-see front matter & 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2017.05.006
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
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