Optic Nerve Abnormalities in Morning Glory Disc Anomaly: An MRI Study

Background: The morning glory disc anomaly (MGDA) is a rare congenital malformation of the optic disc. The association with a significant enlargement of the optic nerve has been recently reported in a few cases, raising the question of potentially associated optic nerve gliomas. The objective was to report the anatomy of optic nerves on MRI in patients with MGDA. Methods: In this retrospective single-center study, files of patients with a clinical diagnosis of MGDA were identified through a rare disease database (CEMARA) and included. We reviewed every cerebral and orbital MRI available, performed between 2008 and 2018. Anatomy of the optic nerve from the optic disc to the chiasm was evaluated on MRI. Results: Nine patients were included. All presented unilateral MGDA. Age at first MRI was 0.6-62 years, median = 3.8 years. MRI showed posterior protrusion of the globe (staphyloma) centered by the optic disc in all cases (100%). Ipsilateral optic nerve abnormalities were found in all cases (100%). The optic nerve was found thinner than the contralateral one in its intraorbital, intracanalar, and intracranial portions in 1 case (11%); in 8 cases (89%), the thickness of the optic nerve was irregular and varied along its pathway: thick, normal, and/or thin. When gadolinium injection had been performed (3 cases), none exhibited gadolinium enhancement. When serial MRI scanning was available (4 cases), there was no evolution of the abnormalities. Conclusion: In patients with MGDA, optic nerve and chiasm abnormalities are the rule, with most often a unique pattern of irregular optic nerve thickness-hypertrophy and hypoplasia-from the orbit to the chiasm. Such pattern should be recognized and points to a developmental abnormality, rather than an optic nerve glioma.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Optic Nerve Abnormalities in Morning Glory Disc Anomaly: An MRI Study Diem-Trang Nguyen, MD, Nathalie Boddaert, MD, PhD, Dominique Bremond-Gignac, MD, PhD, Matthieu P. Robert, MD, PhD Background: The morning glory disc anomaly (MGDA) is a rare congenital malformation of the optic disc. The association with a significant enlargement of the optic nerve has been recently reported in a few cases, raising the question of potentially associated optic nerve gliomas. The objective was to report the anatomy of optic nerves on MRI in patients with MGDA. Methods: In this retrospective single-center study, files of patients with a clinical diagnosis of MGDA were identified through a rare disease database (CEMARA) and included. We reviewed every cerebral and orbital MRI available, performed between 2008 and 2018. Anatomy of the optic nerve from the optic disc to the chiasm was evaluated on MRI. Results: Nine patients were included. All presented unilateral MGDA. Age at first MRI was 0.6–62 years, median = 3.8 years. MRI showed posterior protrusion of the globe (staphyloma) centered by the optic disc in all cases (100%). Ipsilateral optic nerve abnormalities were found in all cases (100%). The optic nerve was found thinner than the contralateral one in its intraorbital, intracanalar, and intracranial portions in 1 case (11%); in 8 cases (89%), the thickness of the optic nerve was irregular and varied along its pathway: thick, normal, and/or thin. When gadolinium injection had been performed (3 cases), none exhibited gadolinium enhancement. When serial MRI scanning was available (4 cases), there was no evolution of the abnormalities. Conclusion: In patients with MGDA, optic nerve and chiasm abnormalities are the rule, with most often a unique pattern of irregular optic nerve thickness—hypertrophy and hypoplasia—from the orbit to the chiasm. Such pattern should be Ophthalmology Department (D-TN, DB-G, MPR), APHP, Necker Enfants Malades University Hospital, Paris, France; Paris Descartes University (D-TN, DB-G, MPR), Sorbonne Paris Cité, France; Necker Enfants Malades University Hospital Pediatric Radiology Department, (NB), APHP, Paris, France; INSERM U1000 (NB), Imagine Institute, Paris Descartes University, Paris, France; CNRS Unit FR33636 (DB-G), Paris Descartes University, Paris, France; and Borelli Center (MPR), UMR 9010, CNRS-SSA-ENS Paris Saclay—Paris University, France. The authors report no conflicts of interest. Address correspondence to Diem-Trang Nguyen, MD, Trousseau Hospital, 26 av du Dr Arnold Netter, 75012 Paris, France; E-mail: [e-mail] Nguyen et al: J Neuro-Ophthalmol 2022; 42: 199-202 recognized and points to a developmental abnormality, rather than an optic nerve glioma. Journal of Neuro-Ophthalmology 2022;42:199–202 doi: 10.1097/WNO.0000000000001412 © 2021 by North American Neuro-Ophthalmology Society T he morning glory disc anomaly (MGDA) is a rare congenital, nonhereditary malformation of the optic disc. Usually unilateral and sporadic, MGDA is diagnosed clinically through fundoscopy. It is characterized by a funnel-shaped posterior pole, including an enlarged and malformed optic disc, circumscribed by a peripapillary pigmented ring and sometimes contractile smooth muscle fibers, covered by the central glial tissue, whereas retinal vessels emerge from the periphery of the disk in a radial pattern. Kindler named the anomaly according to the clinical resemblance with the morning glory flower (1). Several ocular, cerebral, and vascular anomalies have been described associated with MGDA, notably ipsilateral cerebral vascular abnormalities considered as moyamoya (2,3). More recently, the association with a significant enlargement of the optic nerve has been reported in a few case reports, raising the question of potentially associated optic nerve gliomas (ONGs) (4–9). The aim of the study was to retrospectively report the anatomy of the optic nerve of patients with clinical MGDA, from the optic disc to the chiasm, by using available MRI. METHODS A retrospective study of all cases of MGDA seen in the ophthalmology department, Necker–Enfants Malades university Hospital, Paris, between 2008 and 2018, was conducted. Patients’ files were identified using a national reference database for rare diseases (CEMARA) (10). Patients with clinically diagnosed MGDA and MRI imaging available for analysis were included. Clinical criteria for 199 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Fundus images. A–C. 3 typical MGDA with a funnel-shaped posterior pole, including an enlarged and malformed optic disc, covered by the central glial tissue, circumscribed by a peripapillary pigmented ring and radial pattern of retinal vessels (case 1, 3 and 8). MGDA, morning glory disc anomaly. MGDA diagnosis were funnel-shaped excavation of an enlarged optic disc, presence of a central glial tuft, presence of a peripapillary chorioretinal pigmentation, and radial disposition of the retinal vessels (Fig. 1). The study adhered to the tenets of the Declaration of Helsinki. Clinical characteristics of the patients (age, sex, side of MGDA, and medical history), visual function, fundus descriptions, and images were reviewed. MRI had been initially performed to rule out evolutive vascular abnormalities potentially associated with MGDA, on a 1.5T MR scanner, with T1 and T2-weighted imaging, 3D T1 reconstruction MIP (maximum intensity projection), and optional sequences (flair, gadolinium). All MRI were reviewed by a specialized pediatric neuroradiologist (N.B.), assessing the presence/absence of a posterior protrusion of the globe (staphyloma) with funnel-shaped morphologic pattern of the optic disc; the shape of the optic disc in its intraorbital, intracanalar, and intracranial chiasmatic portions, and the presence/absence of an enhancement after gadolinium injection. RESULTS Of 21 patients in the CEMARA database, 10 were excluded because MRI was not available for review and 2 patients were excluded because fundus images did not fit all the clinical criteria of MGDA. Finally, 9 patients were included, 6 females and 3 males. All presented unilateral MGDA without dysmorphic systemic features. The median age at MGDA diagnosis was 14 months (6–36). The main sign having led to MGDA diagnosis was convergent strabismus. Three patients had signs of concomitant persistent fetal TABLE 1. Clinical characteristics of the patients and MRI aspects Age at Funnel- Tortuosity Optic Nerve Optic Nerve Optic Nerve in First Intracranial in in of the Reviewed Shaped Side Optic Disc Optic Intraorbital Intracanalar Portion— MRI of Associated Ocular Patient Chiasm Enhancement Portion Portion Nerve at MRI (years) Abnormalities NumberSexMGDA 1 2 3 M R F R F R 4 5 F R M L 6 F 7 M L 8 9 F F R L L Cataract 3.8 Retinal detachment 0.6 Strabismus and 4 persistent fetal vasculature 0 15 11.5 Strabismus, cataract, and retinal detachment 1.6 Persistent fetal vasculature and retinal detachment Strabismus, retinal 0.8 detachment, and persistent fetal vasculature Strabismus 0.7 Strabismus 62 Present Present Present Present Absent Absent Irregular Thin Thick Irregular Irregular Irregular Irregular Normal Thin No NA NA Present Present Absent Absent Thin Thin Irregular Thin Thick Thick NA NA Present Absent Thin Thin Thin NA Present Absent Irregular Thin Thin No Present Present Present Absent Thick Irregular Thick Irregular Normal Thick NA No MGDA, morning glory disc anomaly; M, male; F, female; L, left; R, right, NA, nonavailable. 200 Nguyen et al: J Neuro-Ophthalmol 2022; 42: 199-202 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. MRI imaging. Column A, Intraorbital features: axial T1 or T2-weighted images. Column B, Intracanalar features: axial MIP 3D T1 or flair-weighted images. Column C, Intracranial and chiasm features: coronal T1 or T2-weighted images. Line 1: case 6, right MGDA. Right staphyloma (A); the right optic nerve is thin in all its portions (A–C). Line 2: case 5, left MGDA. The left optic nerve is thin in its intraorbital (A) and intracanalar portions (B) and thick in its intracranial portion (C). Line 3: case 7, left MGDA. The left optic nerve is irregular in its intraorbital portion (A) and thin in its intracanalar (B) and intracranial portions (C). Line 4: case 1, right MGDA. Right staphyloma (A); the right optic nerve is moniliform and irregular in all its portions (A–C). Normal features on the contralateral side were documented in all cases. MGDA, morning glory disc anomaly. vasculature. In 4 patients, a retinal detachment had occurred during follow-up. Patients’ characteristics are displayed in Table 1. The median age at first MRI imaging was 3.8 years (0.6– 62 years). MRI showed staphyloma centered by the optic disc in all cases (100%). The optic nerve was thinner than the contralateral one in its intraorbital, intracanalar, and intracranial portions in 1 case (11%). In all other 8 cases (89%), the thickness of the optic nerve was irregular and considered moniliform, as it varied along its pathway: thick, normal, and/or thin (Fig. 2). The contralateral optic nerve and hemichiasm were always normal. In cases where a gadolinium injection had been realized (3 cases), no gadolinium enhancement was noticed. When serial MRI scanning was available (4 cases), there was no evolution of the optic nerve abnormalities, with a follow-up of 3.5 years (3–5). Detailed MRI findings are described in Table 1. CONCLUSIONS In previous studies, thickening of the intracranial part of the optic nerve and in the optic chiasm has been described (4–9). In this study with a larger number of patients, we report not only enlargement of the optic nerve/chiasm but also thinning of the optic nerve leading to irregularity of its caliber. These ipsilateral optic nerve thickness abnormalities were seen in all cases of MGDA. Such a pattern of irregular, moniliform Nguyen et al: J Neuro-Ophthalmol 2022; 42: 199-202 optic nerves is unique and could represent an MRI criterion of morning glory disc syndrome, useful in case of a doubtful optic disc appearance on fundus examination. MGDA is now considered a developmental abnormality, resulting from poor development of the lamina cribrosa and the posterior sclera and responsible for a posterior displacement of the sclera and developmental anomaly of the optic nerve (11). The nature of optic nerve thickening in MGDA being uncertain, some recent studies have hypothesized that it may result from ONGs, on the basis of their radiological characteristics (4–6). Optic nerve gliomas are low-grade tumors, usually pilocytic astrocytomas. Risk factors are associated with ONGs, such as neurofibromatosis type 1 (NF1) 210% to 70% of ONGs are associated with NF1 (12) and 8%– 31% of NF1 patients exhibit ONGs (13). In the absence of NF1, definite diagnosis relies on histopathology. In this series, none of the patients had any sign of NF1. On MRI, some characteristics were compatible with ONG features: irregular, tortuous optic nerves (12), with no gadolinium enhancement. During follow-up, however, no change in the thickness of the optic nerve was ever noticed. To date, no histopathologic study so far has ruled out the presence of glioma or optic nerve tumor associated with MGDA. The hypothesis of ONGs on the top of hypoplastic optic nerves, which could explain such MRI images, is yet 201 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution unlikely for 2 reasons: first, the stability over time of the optic nerve calibers; second, the extremely high rate of such abnormalities in association with MGDA, which would make MGDA the highest risk factor for ONGs. The limited number of patients and limited follow-up duration represent the major limitations of this retrospective study. In conclusion, in patients with MGDA, optic nerve and chiasm abnormalities are the rule, with most often a unique pattern of irregular optic nerve thickness—hypertrophy and hypoplasia—from the orbit to the chiasm. Such pattern should be recognized and points to a developmental abnormality, rather than an ONG. REFERENCES 1. Kindler P. Morning glory syndrome: unusual congenital optic disk anomaly. Am J Ophthalmol. 1970;69:376–384. 2. Lenhart PD, Lambert SR, Newman NJ, Biousse V, Atkinson DS Jr, TraboulsiKutchinson EIAK. Intracranial vascular anomalies in patients with morning glory disk anomaly. Am J Ophthalmol. 2006;142:644–650.e2. 3. Puvanachandra N, Heran MK, Lyons CJ. Morning glory disk anomaly with ipsilateral capillary hemangioma, agenesis of the internal carotid artery, and Horner syndrome: a variant of PHACES syndrome? Am Assoc Pediatr Ophthalmol Strabismus. 2008;12:528–530. 4. Doneda C, Pinelli L, Scaramuzzi M, Galli J, Fazzi E, Parazzini C, Righini A, Nucci P. Morning glory disc anomaly associated with 202 5. 6. 7. 8. 9. 10. 11. 12. 13. ipsilateral optic nerve and chiasm thickening: three cases and review of the literature. Neuropediatrics. 2017;48:463–466. Kinori M, Smiley NP, Zeid JL. Morning glory disc anomaly and ipsilateral sporadic optic pathway glioma. Am J Ophthalmol Case Rep. 2018;10:16–17. Thoma D, Nijs I, Demaerel P, Casteels I. Morning glory disc anomaly with an ipsilateral enlargement of the optic nerve pathway. Eur J Paediatr Neurol. 2017;21:787–791. Ceynowa DJ, Wickström R, Olsson M, Ek U, Eriksson U, Kristoffersen Wiberg M, Teär Fahnehjelm K. Morning glory disc anomaly in childhood—a population-based study. Acta Ophthalmol (Copenh). 2015;93:626–634. Bandopadhayay P, Dagi L, Robison N, Goumnerova L, Ullrich NJ. Morning glory disc anomaly in association with ipsilateral optic nerve glioma. Arch Ophthalmol Chic IL. 2012;130:1082– 1083. Ellika S, Robson CD, Heidary G, Paldino MJ. Morning glory disc anomaly: characteristic MR imaging findings. Am J Neuroradiol. 2013;34:2010–2014. Landais P, Messiaen C, Rath A, Le Mignot L, Dufour E, Ben Said M, Jais JP, Toubiana L, Baujat G, Bourdon-Lanoy E, Gérard-Blanluet M, Bodemer C, Salomon R, Aymé S, Le Merrer M, Verloes A; CEMARA task force. CEMARA an information system for rare diseases. Stud Health Technol Inform. 2010;160:481–485. Lee BJ, Traboulsi EI. Update on the morning glory disc anomaly. Ophthalmic Genet. 2008;29:47–52. Miller NR. Primary tumours of the optic nerve and its sheath. Eye. 2004;18:1026–1037. Listernick R, Louis DN, Packer RJ, Gutmann DH. Optic pathway gliomas in children with neurofibromatosis 1: consensus statement from the NF1 Optic Pathway Glioma Task Force. Ann Neurol. 1997;41:143–149. Nguyen et al: J Neuro-Ophthalmol 2022; 42: 199-202 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.