Eye (2004) 18, 1038–1048 & 2004 Nature Publishing Group All rights reserved 0950-222X/04 $30.00 www.nature.com/eye CAMBRIDGE OPHTHALMOLOGICAL SYMPOSIUM Congenital disorders GN Dutton of the optic nerve: excavations and hypoplasia Abstract Excavations of the optic disc The principal congenital abnormalities Optic disc coloboma of the optic disc that can significantly Definition impair visual function are excavation Optic disc coloboma (Figure 1) comprises a of the optic disc and optic nerve hypoplasia. clearly demarcated bowl-shaped excavation of The excavated optic disc abnormalities the optic disc, which is typically decentred and comprise optic disc coloboma, morning deeper inferiorly. glory syndrome, and peripapillary staphyloma. Optic nerve hypoplasia manifests as a small optic nerve, which Aetiology may or may not be accompanied by a Coloboma of the optic disc is thought to result peripapillary ring (the double ring sign). In from abnormal fusion of the two sides of the addition, the optic disc cupping, which proximal end of the optic cup.1 The condition occurs as a sequel to some cases of can occur in association with multiple periventricular leucomalacia, can arguably congenital abnormalities indicative of an insult be classified as a type of optic nerve to the developing foetus during the sixth week hypoplasia. All of these conditions can be of gestation.2 unilateral or bilateral and can impair visual Optic nerve coloboma may occur sporadically function mildly or severely. It is essential or be inherited with an autosomal dominant that children with poor vision due to inheritance.3 It has recently been shown to be any of these conditions are managed by associated with PAX2 gene mutations as part of Tennent Institute of treating refractive errors, giving occlusion the renal-coloboma syndrome.4–7 Expression of Ophthalmology therapy in selected cases, and optimising the PAX2 is restricted to cells of astrocytic lineage Gartnavel General Hospital conditions at home and at school Glasgow, UK both during retinal development and in in an attempt to ensure that impaired vision adulthood. Using immunohistochemistry, it has does not impede development or education. The Royal Hospital for Sick been found that adult retinal cells with the Children Eye (2004) 18, 1038–1048. Yorkhill doi:10.1038/sj.eye.6701545 Glasgow, UK Keywords: optic nerve; congenital; hypoplasia; Correspondence: coloboma GN Dutton Tennent Institute of Ophthalmology Gartnavel General Hospital Introduction Great Western Road Glasgow G12 0YN, UK Congenital anomalies of the optic disc are Tel: þ 44 141 211 2937 fortunately rare, and in many cases either Fax: þ 44 141 211 6290 unilateral or asymmetrical involvement E-mail: Sheena.MacKay@ means that functional vision is not significantly NorthGlasgow.Scot.NHS.UK impaired. However, children with poor vision due to these conditions are not Received: 4 September 2003 uncommonly seen in paediatric practice and Accepted: 4 September accurate diagnosis and good management are 2003 essential. Figure 1 Coloboma of the optic nerve head. Congenital disorders of the optic nerve GN Dutton 1039 antigenic phenotype present in mature perinatal retinochoroidal colobomas, rhegmatogenous detachment astrocytes are found only in the region surrounding the is probably not a recognised association.11 optic nerve head, and that astrocyte precursor cells Contrary to what is commonly taught, basal expressing PAX2 are found in a small region surrounding encephalocele is a rare association with optic nerve the optic nerve during early development. It has been coloboma11 (in contrast to the more common association argued that these findings suggest that coloboma with morning glory syndrome). formation may be associated with impaired astrocyte differentiation during development.8 Associations The association of optic nerve coloboma There is a wide range of associations. These have been with dysgenesis of the internal carotid reviewed by Brodsky11 and include the CHARGE artery and transphenoidal encephalocele association (coloboma, choanal atresia, congenital heart with hypopituitarism has led to the disease, and multiple other abnormalities), Walker– suggestion that the link between these malformations Warburg syndrome, Goltz focal dermal hypoplasia, is abnormal neural crest cell development.9 Aicardi syndrome, Goldenhar syndrome, and linear sebaceous naevus syndrome. More recently, associations Clinical features with Dandy Walker malformation22 and renal coloboma Unilateral and bilateral optic disc colobomata occur with syndrome (with a mutation of PAX2 transcription)4–7 similar frequencies.10 The coloboma occupies the lower have also been described. part of the optic nerve head. The neuro-retinal rim is absent inferiorly but is usually identifiable superiorly. In Treatment cases in which the adjacent inferior retina and choroid A trial of patching may result in improvement of vision 11 are deficient, microphthalmia may also be evident. in the child presenting early in life, and optimal Visual acuity is reduced to varying degrees. Careful refractive correction may be indicated. analysis of the photographic appearances of colobomata involving the optic nerve has shown that the only feature that relates to visual outcome is the degree of foveal Morning glory anomaly 12 involvement by the coloboma. The size of the Definition coloboma, the colour of the optic nerve, and the presence The morning glory optic disc (Figure 2) anomaly is a of subfoveal pigment change are not related to visual congenital optic disc dysplasia in which a conical outcome. Significant refractive error and anisometropia excavation of the posterior fundus includes the optic disc 12 are common. and is filled with glial tissue. The term reflects the Progressive optic nerve cupping and neural rim morphological similarity to the flower of the morning decrease have been documented in a patient with glory plant.23 bilateral autosomal dominant optic nerve colobomas with no evidence of raised intraocular pressure and remarkably, no progressive visual field loss.13 Circumferential intrascleral smooth muscle has been observed histologically14 and may account for the rare observation of spontaneous contractility of the colobomatous optic disc.15 Complications A small proportion of cases are associated with cysts arising from the optic nerve sheath, which communicate with the subarachnoid space.16 Rarely such cysts can enlarge and lead to compressive optic neuropathy.17 Peripapillary choroidal neovascularisation has been described in association with optic nerve coloboma.18 Retinal detachment is also a recognised complication, and remarkably, spontaneous re-attachment may occur.19–21 The source of the subretinal fluid is not known but could derive from fluid entering the retrobulbar space from surrounding orbital tissue, or from the Figure 2 Morning glory syndrome (reproduced with permis- choriocapillaris, or from CSF. In contrast to sion from the British Journal of Ophthalmic Photography). Eye Congenital disorders of the optic nerve GN Dutton 1040 Aetiology Associations and complications Morning glory syndrome is ostensibly a sporadic Morning glory syndrome tends to be an isolated condition but it has been described occurring in isolation condition and does not occur as part of a multisystem in a parent and child.24 disorder. It can however be associated with The pathogenesis of the condition is unknown.11 One transphenoidal encephalocele and hypopituitarism.30,31 hypothesis argues that the condition results from failure Patients with this condition tend to have a wide head and of closure of the foetal fissure and that it is a variant of hypertelorism associated with a flattened nasal bridge. optic nerve coloboma. Alternatively, a primary The encephalocele bulges into the nasopharynx where it mesenchymal abnormality has been postulated on the can obstruct respiration. Incorrect identification and basis of the glial tuft, the scleral and vascular management of this pathology as a nasal polyp has been abnormalities, and the finding of adipose and smooth reported to lead to a fatal outcome.32 muscle tissue around the terminal optic nerve. An Rhegmatogenous retinal detachment (which can now alternative argument is that the symmetrical excavation be successfully treated) can be associated with a break at of the optic nerve head, which characterises the disorder, the optic disc margin33 or within the optic disc cup,34 and is suggestive of dilation due to dysgenesis of the terminal may occur in about one-third of cases.11 Remarkably, optic stalk, which fails to close, leading to persistent optic nerve fenestration has been reported to lead to excavation of the optic nerve head. The central gliosis resolution of serous retinal detachment, suggesting that and the vascular pattern suggest primary neuro- the source of subretinal fluid can be CSF.35 Spontaneous ectodermal dysgenesis.10 resolution of retinal detachment has also been reported.36 Morning glory syndrome is more common in female Subretinal neovascularisation both under the population and (in the USA) occurs less commonly in peripapillary retina37 and under the fovea38 is a black people.10 recognised complication. Clinical features Treatment Morning glory syndrome is usually unilateral and is When the condition is first seen in young children, a trial characterised by a funnel-shaped, excavated optic disc of occlusion is warranted but should not be continued if (which may even include the macula) with central glial improvement in vision does not take