Current Eye Research, 2015; 40(4): 450–455 ! Informa Healthcare USA, Inc. ISSN: 0271-3683 print / 1460-2202 online DOI: 10.3109/02713683.2014.925931

SHORT COMMUNIC ATION

Systemic Abnormalities in Children with Congenital Optic Disc Excavations Francis Beby Department of Ophthalmology, Queen Fabiola Children’s University Hospital, Universite´ Libre de Bruxelles, Brussels, Belgium

ABSTRACT Purpose: Together with optic disc hypoplasia, excavated optic disc anomalies represent the most frequent congenital abnormality involving the optic nerve head. The purpose of the present study was to retrospectively review the results of a screening for extraocular abnormalities in children presenting with congenital optic disc excavations. Materials and methods: The medical records of 37 patients diagnosed with a unilateral or bilateral non glaucomatous optic disc excavation were retrospectively reviewed to analyze the result of the extra ocular evaluation and to report the associated ocular abnormalities. Results: An ocular abnormality was observed in conjunction with the excavated optic disc in 31% of the eyes. The systematic investigations revealed the presence of at least one extra-ocular disorder in 48% of the cases, and the optic disc excavation could be considered as syndromic in 30% of patients. The prevalence of extraocular malformations was significantly higher in infants presenting with associated ocular malformations or abnormal vision/development. Conclusions: The present study suggests that a systematic approach to search for any associated systemic abnormalities could be envisioned in patients presenting with congenital excavated optic discs, and particularly those presenting with abnormal vision, associated ocular defects or abnormal development. Keywords: Coloboma, congenital, microphthalmia, optic disc excavation, systemic anomalies

INTRODUCTION

recognizable (i.e. morning glory syndrome, optic pit), determining the exact signification of a congenital optic disc excavation may represent a challenge for the clinician. Moreover, the observation of a congenital excavated optic disc leads invariably the clinician to attempt to answer the following question: is the excavated optic disc occurring as part of a neurologic disease or polymalformative syndrome? There is to date little published data focusing on the causes of congenital optic disc excavations and potential associated systemic findings. The purpose of the present study was therefore to retrospectively review the results of a systematic screening for extraocular abnormalities in children presenting with unilateral or bilateral optic disc excavations.

Congenital malformations of the eye account for one of the most common causes of visual impairment in children.1 Together with optic disc hypoplasia, excavated optic disc anomalies represent the most frequent congenital abnormality involving the optic nerve head.2 Excavated optic disc anomalies include heterogeneous clinical malformations consisting in optic disc coloboma, morning glory disc anomaly, megalopapilla, optic pit, and papillorenal syndrome.2,3 In comparison to what is observed in adults, the optic nerve head is generally characterized in infants by a very minor excavation. Apart from some cases for which the anatomical presentation is characteristic and easily

Received 21 October 2013; revised 11 May 2014; accepted 11 May 2014; published online 9 June 2014 Correspondence: Francis Beby, Department of Ophthalmology, Queen Fabiola Children’s University Hospital, Universite´ Libre de Bruxelles, avenue de la Nive´ole 14, 1020 Brussels, Belgium. Tel: +32 4 77 83 22 16. E-mail: [email protected]

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Systemic Anomalies and Optic Disc Excavations

MATERIALS AND METHODS The retrospective study included 37 patients diagnosed or treated at the Edouard Herriot hospital, Lyon, France, over a 5 years period. The diagnosis of the congenital optic disc excavation was established on funduscopy by indirect ophthalmoscopy. The optic disc excavations included in the study were considered according to the following criteria: optic disc of normal size or enlarged, excavation contained within the optic disc, white and sharply delineated optic disc excavation, and cup-to-disc ratio estimation greater than or equal to 0.8. Rare cases corresponding to tilted optic disc or optic pit were not included in the study. As glaucomatous optic nerve excavations represent a particular entity for which the diagnosis can be made without systemic investigations, glaucomatous optic disc excavations were also excluded from the study. The general investigations included in most of the cases serologic screening for intrauterine infections, cardiology consultation with echocardiogram, audiology, renal ultrasonography, and neuroimaging study. For the patients who were diagnosed as having a polymalformative disorder, the investigations were completed by a genetic consultation with standard karyotype and comparative genomic hybridization.

RESULTS The study included 37 patients and 62 eyes with excavated optic disc. The eye fundus examination was performed for one of the following reasons: eye abnormality discovered by parents or pediatrician, abnormal visual function or nystagmus, ophthalmological examination recommended by pediatricians because of suspicion of abnormal development or mental retardation, or incidental finding during an ophthalmological assessment (Table 1). The mean age at the time of diagnosis was 1 year and 8 months. Females were affected in 54% of cases (20 of 37 patients) but the sex ratio difference was not statistically significant. The optic disc excavation was unilateral in 12 cases (32%) involving the right eye in 5 cases. In some cases, the suspected diagnosis for the optic disc excavation was an optic disc coloboma, because of a more pronounced excavation in the lower part of the optic disc and/or because of the presence of an iris or retinal coloboma affecting the contralateral eye. However, in most of the cases included in the study, it was not possible to identify with certainty a characteristic recognizable optic disc malformation. In 31% (19 of 62) of the affected eyes, another ocular defect was observed in conjunction with the excavated disk. Iris coloboma (10% of the eyes), microphthalmia (8%), and corneal or lens opacity (6%) were found to be the most common !

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associated ocular malformations. An ocular abnormality was registered in the fellow eye for 7 of the 12 patients with unilateral excavated optic disc. After the general evaluation, the excavated optic disc was found to be associated with at least one extraocular disorder in 48% (18 of 37) of the patients, and the optic nerve defect could be considered as syndromic in 30% of the patients (Table 1).

DISCUSSION Understanding the exact pathogenesis of an optic disc excavation in a child is challenging. The present report is focused on optic disc excavations diagnosed in children with normal intraocular pressure. Although glaucomatous cupping may also occur with normal intraocular pressure, normal tension glaucoma remains a diagnosis of exclusion, and other explanations need to be considered in priority. Congenital malformations of the optic nerve may present with large cup discs. These congenital defects include megalopapilla, morning glory disc, and optic disc coloboma. Megalopapilla is a congenital optic disc anomaly characterized by an abnormally large optic disc with high cup-disc ratio.4 Since the increased disc area is associated with a normal rim area and normal retinal nerve fiber layer, megalopapilla has been considered as a physiologic variant of normal optic disc papilla. However, visual acuity may be decreased in patients with megalopapilla,5 and the anomaly has also been reported in association with extraocular abnormalities.6,7 The morning glory disc anomaly consists of a funnel-shaped excavation that incorporates an enlarged optic disc with blood vessels emerging in a radial pattern.8 A white tuft of glial tissue is often observed in the central part of the optic cup, whereas the peripapillar retina is pigmented and elevated. The defect is usually unilateral and causes a visual impairment of variable degree. Morning glory disc anomaly has been reported in association with midline craniofacial defects, endocrine and central nervous system anomalies, and basal encephalocele.9– 11 Optic disc colobomas result from an incomplete closure of the embryonic fissure. The defect is characterized by a sharply, white, inferiorly decentered excavation of the optic disc. The optic disc is typically enlarged and the inferior neuroretinal rim is thin or absent. The optic disc coloboma may be associated with a coloboma involving the retina, the ciliary body, or the iris. The defect, which can be sporadic or inherited,12,13 has been associated with several polymalformative syndromes, including the Charge syndrome,14 renal coloboma syndrome,15 Aicardi syndrome,16 Solomon’s syndrome,17,18 or Noonan syndrome.19 Optic disc excavations may also be consecutive to optic nerve compression, intracranial hypertension,

M

F F M F

M

F

F

F

M F M M

M

M F

F

1

2 3 4 5

6

7

8

9

10 11 12 13

14

15 16

17

AVF

IF AD

IF

IF IF IF AD

AVF, N

EA

EA

AVF

AD IF IF AVF

EA, AVF

Circumstances leading to Patient Sex funduscopy

na

8 yr. 6 mo.

1 mo.

6 yr. 7 mo. 6 mo. 5 mo.

1 yr.

1 yr.

3 mo.

3 mo.

1 yr. 6 mo. 7 yr. 9 mo.

1 yr.

Age at diagnosis

Bil.

Bil. Bil.

Bil.

Bil. Bil. R Bil.

Bil.

L

L

L

Bil. R R L

R

odc

? odc

?

? odc odc ?

?

?

?

odc

odc ? ? odc

mgs

Eye(s) with Suspected optic disc diagnosis for excavation the excavation

na

R +1.50; L 2.75 (18 mo.) R +1.00; L +2.50 (1 yr.) na na

na

Refractive error, spherical equivalent in diopters (age at testing)

R LP; L 20/400

R 6/10; L 6/10 (8 yr.) R LP; L LP (6 mo.)

R 6/24; L 6/24 (2 yr.)

R 20/40; L 20/40 (6 yr.) R 20/100; L 20/100 (7 mo.) nm R LP; L LP (5 mo.)

R 20/200; L 20/100 (4 yr.)

R 7/10; L LP (6 yr.)

Present

np

present

Present np Present np

np

1.00 (6 yr.)

R nm; L

6.00 (12 yr.)

R +0.50; L +0.75 (8 yr.) nm

na

R 1.25; L na nm na

Absent

absent np

np

Absent np Present np



Solomon’s syndrome (epidermal nevus syndrome)

Hypospadias, intrauterine growth restriction –

Transetmoidal encephalocele, agenesis of the pituitary gland, cleft lip and palate. Charge syndrome – – –

Systemic abnormalities

– – Charge syndrome 1q duplication, cerebellar hypoplasia, corpus callosum agenesis, cryptorchidism, mandibular retrognathism Posterior embryotoxon, 6p25 deletion syndrome, anterior segment dysgenDandy-Walker malformaesis, corectopia, normal tion, cardiac defects, intraocular pressure prominent forehead, hypertelorism – – – Wolf-Hirschhorn syndrome, 4p16.3 deletion, hypertelorism, protruding eyes, mental retardation, seizures, deafness. L retinal detachment Renal coloboma syndrome, mutation in PAX2 gene.

mild L microphthalmia R iris coloboma – (R iris coloboma, R chorioretinal coloboma) L iris coloboma, (R chorioretinal coloboma) Bil. anterior segment dysgenesis with corneal opacities L mild microphthalmia, L microcornea, L dermoid cyst Bil. microphthalmia, Bil. lens opacities – L iris coloboma (L chorioretinal coloboma) Bil. ptosis

Bil. microphthalmia, Bil. microcornea

Relative afferent Associated ocular pupillary features (in brackets: contralateral eye) defect

R +10.00; L +10.00 (Bil. aphakia) Absent

R +2.25; L +4.00 (6 yr.)

R 20/200; L 20/400 (18 mo.) R +4.00; L +2.50 (18 mo.)

R 20/200; L LP (6 mo.)

R 20/200; L LP (18 mo.) na R 20/40; L 10/10 (7 yr.) BVA 20/400 (6 mo.)

R LP; L no LP (2 yr.)

Visual acuity estimation (age at testing)

TABLE 1 Ocular features and systemic abnormalities found among 37 patients presenting with congenital and non-glaucomatous optic disc excavation.

452 F. Beby

Current Eye Research

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F

M F M

M M

F

F M M F F

F M

M

M F

21

22 23 24

25 26

27

28 29 30 31 32

33 34

35

36 37

IF IF

AD, N

IF IF

N AD IF IF AD

AD

IF AD

IF EA AVF

IF

EA IF IF

7 mo. 5 yr.

na

3 yr. na

1 yr. na 19 mo. 1 yr. 2 mo.

1 yr.

1 mo. 1.5 mo.

2 yr. 4 mo. 4 mo.

8 yr.

17 mo. 8 mo. 1 yr.

Bil. Bil.

L

Bil. Bil.

Bil. Bil. Bil. Bil. Bil.

L

Bil. R

Bil. Bil. Bil.

Bil.

L Bil. Bil.

? ?

?

odc ?

? odc odc ? ?

odc

? ?

? odc ?

odc

odc ? ? 1.25; L

1.00 (11 yr.)

R nm; L

3.00 (6 yr.)

na R 4.00; L +1.00 (18 mo.)

na na nm

R

R +1.25; L 2.00 (17 mo.) R +0.75; L +0.50 (3 yr.) R +1.00; L +0.75 (3 yr.)

na R 6/10; L 8/10 (8 yr.)

BVA 20/400 (8 mo.)

BVA 20/100 (3 yr.) R 8/10; L 6/10 (4 yr.)

na R +0.25; L +0.75 (8 yr.)

nm

R 2.00; L 1.50 (3 yr.) R +1.00; L+1.50 (4 yr.)

R 20/200; L 20/200 (2 yr.) R 2.00; L 4;25 (2 yr.) na R +4.00; L +4.00 (18 mo.) na na R 20/100; L 20/100 (18 mo.) nm na na

R LP; L 20/100 (6 yr.)

na R LP; L 20/100 (18 mo.)

R 8/10; L 8/10 (5 yr.) na R LP; L LP (8 mo.)

R 9/10; L 8/10 (11 yr.)

R 20/100; L LP (17 mo.) R 5/10; L 3/10 (3 yr.) BVA 20/400 (3 yr.)

np np

np

Absent Absent

Absent Absent Absent np np

np

np Present

Absent np np

Absent

Present np np

– –

R optic nerve hypoplasia

– –

– R dermoid cyst, R corneal opacity L chorioretinal lacunae, (R microphthalmia, R persistent hyperplastic primary vitrous) – – – – –

– Bil. iris coloboma –



L iris coloboma – –

Periventricular leukomalacia Charge syndrome – – Intrauterine growth restriction, cerebellar hypoplasia, corpus callosum hypoplasia – Micropolygyria, mental retardation Agenesis of the septum pellucidum, septo-optic dysplasia – –

– – Pyruvate dehydrogenase deficiency Renal coloboma syndrome, mutation in PAX2 gene – – Microcephaly, cerebellar hypoplasia, mental retardation, deafness – Solomon’s syndrome (epidermal nevus syndrome) Aicardi syndrome, corpus callosum agenesis, infantile spasms.

M, Male; F, Female; yr., year(s); mo., month(s); EA, eye abnormality; AVF, abnormal visual function; N, nystagmus; AD, abnormal development or mental retardation; IF, incidental finding; mgs, morning glory syndrome; odc, optic disc coloboma; R, right; L, left; Bil., bilateral; LP, light perception; BVA, binocular visual acuity; na, not available; nm, not measurable; , absence; np, not performed.

F F F

18 19 20

Systemic Anomalies and Optic Disc Excavations 453

454 F. Beby or periventricular leukomalacia. Compressive optic neuropathy is characterized by progressive vision loss, visual field anomalies, dyschromatopsia, and relative afferent pupillary defect. The optic disc modifications include papilledema, optic disc pallor, increased cupping of the optic disc, or optic atrophy, depending on severity and duration of the compression. The compression may involve the intraorbital, intracanalicular, or intracranial segment of the optic nerve. A compression by enlarged extraocular muscles is a possible manifestation of dysthyroid orbitopathy. Other tumors such as optic nerve glioma, optic nerve sheath meningioma, rhabdomyosarcoma, or cavernous hemangiomas may also compress the optic nerve in the orbit. Depending on the location of the orbital tumor, clinical features may also include exophthalmos, limitation of ocular motility, choroidal striae, optociliary shunt vessels or venous stasis retinopathy. In children, it has been reported that orbital optic glioma can cause progressive enlargement of a previously normal-sized optic disc.20 Intracranial causes of compressive optic neuropathy include infectious disorders, aneurysms, and tumors such as gliomas, meningiomas, craniopharyngiomas, or pituitary adenomas. Approximately half of all patients diagnosed with optic pathway gliomas have neurofibromatosis.21 Although children with raised intracranial pressure typically have papilledema,22,23 intracranial hypertension also needs to be considered in a child with optic disc excavations and chronic headache,23 nausea and vomiting, deterioration of the vision, and visual field defects. Intracranial hypertension most commonly results from mass lesions, tension hydrocephalus, and pseudotumor cerebri.22 Increased intracranial pressure can also be due to medications, such as corticosteroids, tetracycline, cyclosporin, oral contraceptives, lithium, vitamin A, or growth hormone. Management for intracranial hypertension consists in a multidisciplinary approach and may involve medical treatment or surgical cerebrospinal fluid diversion procedure. Unfortunately, patients with excavated optic discs and intracranial hypertension are at risk for secondary optic atrophy and severe visual impairment.23 Periventricular leukomalacia, which is another cause of optic disc cupping in infants, represents the most common type of brain injury and the first cause of cerebral palsy in preterm infants.24,25 The disorder is characterized by multifocal areas of hypoxic-ischemic injuries found deep in the cortical white matter. The lesions are often symmetrical and occur adjacent to the lateral ventricles.26 Periventricular leukomalacia has been previously recognized as a possible cause of optic nerve hypoplasia and optic disc cupping.27 It has been previously reported that the disorder may cause a pseudoglaucomatous cupping

consisting in an abnormally large optic cup and a thin neuroretinal rim contained within a normalsized optic disc.28,29 It has been proposed that the optic disc cupping may be consecutive to a retrograde transsynaptic degeneration of retinogeniculate axons after the scleral canals had established normal diameter.28 The findings of the present study seem to be in line with published data on the incidence of systemic disorders encountered in patients with a well characterized developmental ocular defect. It has been reported that 30–73% of individuals with microphthalmia or anophthalmia have associated malformations,30,31 whereas systemic abnormalities have been found in 38 to 66% of the patients carrying a chorioretinal coloboma.32,33 According to this, extraocular assessment as well as multidisciplinary management are recommended for children with congenital eye defects consisting in optic nerve hypoplasia, microphthalmia, anophthalmia, or chorio-retinal coloboma.34,35 However, apart from these characteristic ocular malformations, some children may have optic nerve defects for which a definitive diagnosis is missing. This is precisely the case for some congenital and non-glaucomatous optic disc excavations. The present results could suggest that congenital excavated optic discs are associated with extraocular defects in almost half of the cases. However, it is important to take into account that such a study has an important limitation. In several cases, the optic disc excavation has been diagnosed on funduscopy because of abnormal vision or suspicion of an abnormal development. This point can be considered as a statistic bias that undoubtedly leads to an overestimation of the prevalence of the extraocular malformations in patients diagnosed with an optic disc excavation. Interestingly, the prevalence of extraocular abnormalities was only 22% of cases (4 of 18 patients) for the children who had an excavation found after incidental finding. This prevalence appears to be much lower than that observed for the children who present with either abnormal vision, ocular abnormality, or suspected abnormal development (73 %, 14 of 19 patients), and the difference between these two percentages can be considered as statistically significant (p50.01; ChiSquare test, one degree of freedom). Taken together, these results confirm that clinical observation of an excavated optic disc in a newborn or in an infant allows for the possibility of identifying systemic disorders or polymalformative syndromes, even in cases where the optic disc excavation was not suggestive of a characteristic developmental defect. In addition, these observations suggest that excavated optic discs with similar presentation can be associated with highly variable extraocular pathologies. Current Eye Research

Systemic Anomalies and Optic Disc Excavations

DECLARATION OF INTEREST The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.

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Systemic abnormalities in children with congenital optic disc excavations.

Together with optic disc hypoplasia, excavated optic disc anomalies represent the most frequent congenital abnormality involving the optic nerve head...
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