Acta Ophthalmologica 2015
Morning Glory Disc Anomaly in childhood – a population-based study Dylan J Ceynowa,1 Ronny Wickstro¨m,2 Monica Olsson,1,3 Ulla Ek,4 Urban Eriksson,1,5 Maria Kristoffersen Wiberg6,7 and Kristina Tea¨r Fahnehjelm1,8 1
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Neuropaediatric Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden 3 Department of Paediatric Ophthalmology and Strabismus, St. Erik Eye Hospital, Stockholm, Sweden 4 Department of Special Education, Stockholm University, Stockholm, Sweden 5 Department of Medical Retina, St. Erik Eye Hospital, Stockholm, Sweden 6 Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden 7 Department of Radiology, Karolinska University Hospital Huddinge, Stockholm, Sweden 8 Department of Paediatric Ophthalmology and Strabismus, St. Erik Eye Hospital, Karolinska University Hospital, Huddinge, Sweden 2
ABSTRACT. Purpose: To report prevalence, ocular characteristics and coexisting neurological, behavioural, somatic and neuroradiological abnormalities in children and adolescents with morning glory disc anomaly (MGDA). Methods: In a cross-sectional population-based study, 12 patients with MGDA, aged 2–20 years, were identified. All 12 agreed to ophthalmological assessments including visual functions, refraction, fundus photography, optical coherence tomography (OCT) and ocular motor score (OMS). Neurological examinations and behavioural/developmental screening were carried out. Data from previous or new neuroradiological investigations were collected. Results: The prevalence of MGDA was 2.6/100 000. MGDA was unilateral in 11/12 patients with a best-corrected visual acuity (BCVA) in the MGDA eye ranging from hand motion to 0.65 (median 0.06). Severe microphthalmus prevented unilaterality to be determined in one adolescent. All patients had a binocular BCVA of ≥0.5. OMS showed abnormalities in pupil response, vestibulo-ocular reflex, stereo visual acuity, strabismus and convergence. OCT revealed peripapillary or macular oedema in 5/8 patients and foveal aplasia in 3/8 patients. Three patients had extensive capillary hemangiomas, of which one had PHACES syndrome and one had additional cerebrovascular anomalies and corpus callosum agenesis. Neuroradiology showed craniovascular anomalies in two patients. Neurology was mostly normal. Behavioural/developmental screening showed attention deficit hyperactivity disorder in one patient. Conclusions: The prevalence data, previously not reported, of morning glory disc anomaly was 2.6/100 000. Coexisting retinal peripapillary or macular oedema was common, as were cerebral abnormalities and/or cutaneous vascular malformations. The associated findings may not be discovered through routine ophthalmological examination why OCT and neuroimaging are called for. Key words: malformation – morning glory – optic disc/nerve – retina
Acta Ophthalmol. 2015: 93: 626–634 ª 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
doi: 10.1111/aos.12778
626
Introduction The name morning glory was first coined by Kindler (1970); and describes a congenital excavated optic disc malformation resembling the morning glory flower (Kindler 1970). The prevalence of morning glory disc anomaly (MGDA) is unknown with the vast majority of cases reported to be unilateral and more common in females (Steinkuller 1980; Lee & Traboulsi 2008) (Table 1). MGDA is characterized by an enlarged optic disc with peripapillary pigmentations, a radiating pattern of retinal blood vessels and a central glial tuft (Brodsky 1994; Harasymowycz et al. 2005), resulting in a best-corrected visual acuity (BCVA) ranging between counting fingers and 0.1 (Brodsky 1994). Long-term complications include the risk of retinal detachment (Lee & Traboulsi 2008). The exact pathogenesis of MGDA remains unknown, but it has been related to poor development of the posterior sclera and lamina cribrosa during gestation (Lee & Traboulsi 2008). MGDA has been observed in Aicardi syndrome (Melbourne-Chambers et al. 2007), neurofibromatosis type 2 (Brodsky et al. 1999), Chiari malformation Type 1 (Razeghinejad & Masoumpour 2006), basal encephalocele (Lee & Traboulsi 2008) and the neurocutaneous disorder PHACES,
Acta Ophthalmologica 2015
Table 1. Comparison of previous MGDA studies including main patient characteristics.
Author(s) Harasymowycz et al. (2005) Cennamo et al. (2010) Fei et al. (2013) Steinkuller (one case and literature review) 1980
No. of patients
% female
21
48% (10/21)
2 (0.08–8)
19
74% (14/19)
12.6 (0.5–30)
32% (6/19, 3 bilateral)
19 21
42% (8/19) 67% (14/21)
2.05 (0.08–14) 4.1 (0.01–32)
47% (9/19, 3 bilateral) 57% (12/21)
which is an acronym for posterior fossa abnormalities, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities and sternal cleft and supraumbilical raphe syndrome (Kniestedt et al. 2004). Furthermore, MGDA has been observed together with other cerebrovascular anomalies, including Moyamoya disease (Lee & Traboulsi 2008). The prevalence of MGDA, visual characteristics and related somatic and neurological conditions and their severity among children are not fully known. As there is one single department of paediatric ophthalmology in Stockholm, this presents a unique opportunity for a multidisciplinary examination of these patients to increase knowledge on MGDA.
Methods Participants
The study was carried out at the department of paediatric ophthalmology at St. Erik Eye Hospital in Stockholm, covering a population of approximately 2.1 million individuals (Statistics Sweden 2013). The database was searched for patients diagnosed with optic nerve malformations (Q14.2, Q 14.8) yielding 12 patients with MGDA aged 2–19. Their families received letters inviting them to take part in the study, which all patients then consented to, and they were assessed at the department of paediatric ophthalmology from June 2013 to April 2014. Magnetic resonance imaging (MRI) of the eyes and brain was offered to patients who had not undergone neuroimaging previously. Prevalence data were calculated by means of Statistics Sweden’s online database (Statistics Sweden 2013). Ethical approval was obtained from the local
Mean Age at presentation (years)
% left side 48% (10/21, 1 bilateral)
ethical committee, and the study was carried out in accordance with the Tenets of the Declaration of Helsinki. Written consent was obtained from all parents or patients aged 15 years or older. Clinical ophthalmological assessment
Best-corrected visual acuity was classified in accordance with the World Health Organization (WHO) (World Health Organization 2009). Visual acuity categories hand motion (HM) and counting fingers (CF) were quantified following a definition developed by Lange et al. (2009) that is 0.0052 for HM and 0.010 for CF. Ocular alignment was assessed by means of the cover test, stereopsis and ocular motility. Refraction after cycloplegia was measured following one instillation of a mixture of cyclopentolate (0.85%) and phenylephrine (1.5%) both with the Topcon RM-8900 auto refractometer (Topcon Medical Systems, Inc., Oakland, NJ, USA) and manually with a Heine retinoscope (Herrsching, Germany). Refraction errors were defined as follows: myopia ≤ 0.5 D, hyperopia ≥ + 2.0 D, anisometropia ≥1.0 D and astigmatism ≥0.75 D (Gronlund et al. 2006). The anterior segment was examined by means of a Zeiss slit-lamp microscope (Oberkochen, Germany). Intra-ocular pressure (IOP) was measured with an Icare TA01i rebound tonometry apparatus (Vantaa, Finland). A Canon CR2 Digital Non-Mydriatic Retinal Camera (Canon, Tokyo, Japan) was used to obtain fundus photographs. The optic disc and the peripapillary retina were examined clinically and also using spectral domain optical coherence tomography (SD-OCT) by means of the 3D OCT-2000 Spectral Domain OCT (Topcon Medical Systems, Inc.).
Ocular motor score
Ocular motor function was assessed with static and dynamic tests by means of the ocular motor score (OMS) (Olsson et al. 2013). The static test covered head posture, position of eyelid, stereo acuity, pupil response and strabismus. The dynamic test included assessment of ductions and versions, fixation in primary position, fixation in eight gaze directions, saccades, smooth pursuit, convergence, fusional vergence, vestibulo-ocular reflex cancellation and optokinetic nystagmus. Outcome was scored and compared with age-grouped reference values (Olsson et al. 2013). Neuroradiological examinations
One specialist in neuroradiology evaluated all neuroradiological magnetic resonance imaging (MRI) and computed tomography (CT) scans of the brain and orbits available with regard to neuroanatomy and possible anomalies. Imaging from examinations carried out during the study, and examinations on record were re-evaluated. Physical examination neurological assessment
and
clinical
A general physical examination was performed, and the parents were asked questions about the children’s development and previous healthcare contacts. The neurological evaluation was performed by means of a modified Touwen infant neurological examination. The original Touwen consists of 58 items and was designed to discover minor neurological dysfunction (MND) in children (Touwen 1976). A shortened version with 16 selected items grouped into clusters was used with classifications based on the number of dysfunctional clusters. N indicated normal clusters, MND-1 one or two dysfunctional clusters and MND-2 more than two dysfunctional clusters (Fily et al. 2003). An adapted version of this test was used, adding posture during walking, biceps reflex and muscle tone in the elbows (Table 2). Assessment of general development and behaviour
General development and behaviour was screened by means of the Five To Fifteen (FTF) questionnaire, which the
627
Acta Ophthalmologica 2015
Table 2. Modified Touwen infant neurological examination based on an adaption by Fily et al. (2003). Cluster
Criteria for dysfunction
Dysfunctional muscle tone regulation Posture sitting Posture standing Posture walking Muscle tone of elbows Muscle tone of ankles Reflex abnormalities Biceps reflex Knee reflex Ankle jerk reflex Co-ordination and balance Finger–nose test Diadochokinesis Romberg Standing on one leg Walk along straight line Rarely occurring miscellaneous dysfunctions
Consistent mild deviations
Two signs of dysfunction
Age-inadequate performance in two tests
Evidence of mild cranial nerve palsy or excessive (for age) amount of associated movements.
Motor behaviour of face Motor behaviour of eyes
parents were asked to fill out prior to the clinical evaluation. The questionnaire is a tool for screening ADHD with or without comorbidities and contains 181 questions covering eight domains of adaption: motor skills, executive functions, perception, memory, language, learning, social skills and emotional–behavioural problems (Trillingsgaard et al. 2004). Each individual question was scored using 0 (does not apply), 1 (applies to some extent) or 2 (definitely applies). The sum for each domain was then divided by the number of items. Thus, a mean score between 0 and 2 could be derived from each domain. A psychologist evaluated the completed FTF according to its manual, and the score for each area was compared to the Swedish age-matched norms. A definite developmental problem was indicated by a score above the 90th percentile. Scores at or above the 98th percentile implied a major developmental problem. Statistical analyses
Frequency counts, mean, standard deviation, median, range and percentages were used for descriptive purposes. Fisher’s exact test was used for categorical data, and means in normally distributed variables were compared with one-sample t-test and paired t-test (tested for normality with
628
contacted/referred). Basic data on the patients are presented in Table 3. Best-corrected visual acuity
All visual and ocular characteristics are summarized in Table 4. The median BCVA in MGDA eyes was 0.063 ranging between hand motion to 0.65, while the fellow eyes had a BCVA median of 1.0 (0–1.3) with one patient having a microphthalmic completely blind fellow eye. Differences in BCVA between the MGDA eye and fellow eye were statistically significant (p = 0.006, Sign test). All 12 patients had a binocular BCVA better than 0.3 (median 1; range 0.5–1.3) and were therefore categorized as having no visual impairment according to WHO. BCVA is presented in Fig. 1. Retinoscopy and refraction after cycloplegia
Shapiro-Wilk’s test of normality). Variables not normally distributed were tested with the Sign test. A p-value of
Morning Glory Disc Anomaly in childhood – a population-based study Dylan J Ceynowa,1 Ronny Wickstro¨m,2 Monica Olsson,1,3 Ulla Ek,4 Urban Eriksson,1,5 Maria Kristoffersen Wiberg6,7 and Kristina Tea¨r Fahnehjelm1,8 1
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Neuropaediatric Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden 3 Department of Paediatric Ophthalmology and Strabismus, St. Erik Eye Hospital, Stockholm, Sweden 4 Department of Special Education, Stockholm University, Stockholm, Sweden 5 Department of Medical Retina, St. Erik Eye Hospital, Stockholm, Sweden 6 Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden 7 Department of Radiology, Karolinska University Hospital Huddinge, Stockholm, Sweden 8 Department of Paediatric Ophthalmology and Strabismus, St. Erik Eye Hospital, Karolinska University Hospital, Huddinge, Sweden 2
ABSTRACT. Purpose: To report prevalence, ocular characteristics and coexisting neurological, behavioural, somatic and neuroradiological abnormalities in children and adolescents with morning glory disc anomaly (MGDA). Methods: In a cross-sectional population-based study, 12 patients with MGDA, aged 2–20 years, were identified. All 12 agreed to ophthalmological assessments including visual functions, refraction, fundus photography, optical coherence tomography (OCT) and ocular motor score (OMS). Neurological examinations and behavioural/developmental screening were carried out. Data from previous or new neuroradiological investigations were collected. Results: The prevalence of MGDA was 2.6/100 000. MGDA was unilateral in 11/12 patients with a best-corrected visual acuity (BCVA) in the MGDA eye ranging from hand motion to 0.65 (median 0.06). Severe microphthalmus prevented unilaterality to be determined in one adolescent. All patients had a binocular BCVA of ≥0.5. OMS showed abnormalities in pupil response, vestibulo-ocular reflex, stereo visual acuity, strabismus and convergence. OCT revealed peripapillary or macular oedema in 5/8 patients and foveal aplasia in 3/8 patients. Three patients had extensive capillary hemangiomas, of which one had PHACES syndrome and one had additional cerebrovascular anomalies and corpus callosum agenesis. Neuroradiology showed craniovascular anomalies in two patients. Neurology was mostly normal. Behavioural/developmental screening showed attention deficit hyperactivity disorder in one patient. Conclusions: The prevalence data, previously not reported, of morning glory disc anomaly was 2.6/100 000. Coexisting retinal peripapillary or macular oedema was common, as were cerebral abnormalities and/or cutaneous vascular malformations. The associated findings may not be discovered through routine ophthalmological examination why OCT and neuroimaging are called for. Key words: malformation – morning glory – optic disc/nerve – retina
Acta Ophthalmol. 2015: 93: 626–634 ª 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
doi: 10.1111/aos.12778
626
Introduction The name morning glory was first coined by Kindler (1970); and describes a congenital excavated optic disc malformation resembling the morning glory flower (Kindler 1970). The prevalence of morning glory disc anomaly (MGDA) is unknown with the vast majority of cases reported to be unilateral and more common in females (Steinkuller 1980; Lee & Traboulsi 2008) (Table 1). MGDA is characterized by an enlarged optic disc with peripapillary pigmentations, a radiating pattern of retinal blood vessels and a central glial tuft (Brodsky 1994; Harasymowycz et al. 2005), resulting in a best-corrected visual acuity (BCVA) ranging between counting fingers and 0.1 (Brodsky 1994). Long-term complications include the risk of retinal detachment (Lee & Traboulsi 2008). The exact pathogenesis of MGDA remains unknown, but it has been related to poor development of the posterior sclera and lamina cribrosa during gestation (Lee & Traboulsi 2008). MGDA has been observed in Aicardi syndrome (Melbourne-Chambers et al. 2007), neurofibromatosis type 2 (Brodsky et al. 1999), Chiari malformation Type 1 (Razeghinejad & Masoumpour 2006), basal encephalocele (Lee & Traboulsi 2008) and the neurocutaneous disorder PHACES,
Acta Ophthalmologica 2015
Table 1. Comparison of previous MGDA studies including main patient characteristics.
Author(s) Harasymowycz et al. (2005) Cennamo et al. (2010) Fei et al. (2013) Steinkuller (one case and literature review) 1980
No. of patients
% female
21
48% (10/21)
2 (0.08–8)
19
74% (14/19)
12.6 (0.5–30)
32% (6/19, 3 bilateral)
19 21
42% (8/19) 67% (14/21)
2.05 (0.08–14) 4.1 (0.01–32)
47% (9/19, 3 bilateral) 57% (12/21)
which is an acronym for posterior fossa abnormalities, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities and sternal cleft and supraumbilical raphe syndrome (Kniestedt et al. 2004). Furthermore, MGDA has been observed together with other cerebrovascular anomalies, including Moyamoya disease (Lee & Traboulsi 2008). The prevalence of MGDA, visual characteristics and related somatic and neurological conditions and their severity among children are not fully known. As there is one single department of paediatric ophthalmology in Stockholm, this presents a unique opportunity for a multidisciplinary examination of these patients to increase knowledge on MGDA.
Methods Participants
The study was carried out at the department of paediatric ophthalmology at St. Erik Eye Hospital in Stockholm, covering a population of approximately 2.1 million individuals (Statistics Sweden 2013). The database was searched for patients diagnosed with optic nerve malformations (Q14.2, Q 14.8) yielding 12 patients with MGDA aged 2–19. Their families received letters inviting them to take part in the study, which all patients then consented to, and they were assessed at the department of paediatric ophthalmology from June 2013 to April 2014. Magnetic resonance imaging (MRI) of the eyes and brain was offered to patients who had not undergone neuroimaging previously. Prevalence data were calculated by means of Statistics Sweden’s online database (Statistics Sweden 2013). Ethical approval was obtained from the local
Mean Age at presentation (years)
% left side 48% (10/21, 1 bilateral)
ethical committee, and the study was carried out in accordance with the Tenets of the Declaration of Helsinki. Written consent was obtained from all parents or patients aged 15 years or older. Clinical ophthalmological assessment
Best-corrected visual acuity was classified in accordance with the World Health Organization (WHO) (World Health Organization 2009). Visual acuity categories hand motion (HM) and counting fingers (CF) were quantified following a definition developed by Lange et al. (2009) that is 0.0052 for HM and 0.010 for CF. Ocular alignment was assessed by means of the cover test, stereopsis and ocular motility. Refraction after cycloplegia was measured following one instillation of a mixture of cyclopentolate (0.85%) and phenylephrine (1.5%) both with the Topcon RM-8900 auto refractometer (Topcon Medical Systems, Inc., Oakland, NJ, USA) and manually with a Heine retinoscope (Herrsching, Germany). Refraction errors were defined as follows: myopia ≤ 0.5 D, hyperopia ≥ + 2.0 D, anisometropia ≥1.0 D and astigmatism ≥0.75 D (Gronlund et al. 2006). The anterior segment was examined by means of a Zeiss slit-lamp microscope (Oberkochen, Germany). Intra-ocular pressure (IOP) was measured with an Icare TA01i rebound tonometry apparatus (Vantaa, Finland). A Canon CR2 Digital Non-Mydriatic Retinal Camera (Canon, Tokyo, Japan) was used to obtain fundus photographs. The optic disc and the peripapillary retina were examined clinically and also using spectral domain optical coherence tomography (SD-OCT) by means of the 3D OCT-2000 Spectral Domain OCT (Topcon Medical Systems, Inc.).
Ocular motor score
Ocular motor function was assessed with static and dynamic tests by means of the ocular motor score (OMS) (Olsson et al. 2013). The static test covered head posture, position of eyelid, stereo acuity, pupil response and strabismus. The dynamic test included assessment of ductions and versions, fixation in primary position, fixation in eight gaze directions, saccades, smooth pursuit, convergence, fusional vergence, vestibulo-ocular reflex cancellation and optokinetic nystagmus. Outcome was scored and compared with age-grouped reference values (Olsson et al. 2013). Neuroradiological examinations
One specialist in neuroradiology evaluated all neuroradiological magnetic resonance imaging (MRI) and computed tomography (CT) scans of the brain and orbits available with regard to neuroanatomy and possible anomalies. Imaging from examinations carried out during the study, and examinations on record were re-evaluated. Physical examination neurological assessment
and
clinical
A general physical examination was performed, and the parents were asked questions about the children’s development and previous healthcare contacts. The neurological evaluation was performed by means of a modified Touwen infant neurological examination. The original Touwen consists of 58 items and was designed to discover minor neurological dysfunction (MND) in children (Touwen 1976). A shortened version with 16 selected items grouped into clusters was used with classifications based on the number of dysfunctional clusters. N indicated normal clusters, MND-1 one or two dysfunctional clusters and MND-2 more than two dysfunctional clusters (Fily et al. 2003). An adapted version of this test was used, adding posture during walking, biceps reflex and muscle tone in the elbows (Table 2). Assessment of general development and behaviour
General development and behaviour was screened by means of the Five To Fifteen (FTF) questionnaire, which the
627
Acta Ophthalmologica 2015
Table 2. Modified Touwen infant neurological examination based on an adaption by Fily et al. (2003). Cluster
Criteria for dysfunction
Dysfunctional muscle tone regulation Posture sitting Posture standing Posture walking Muscle tone of elbows Muscle tone of ankles Reflex abnormalities Biceps reflex Knee reflex Ankle jerk reflex Co-ordination and balance Finger–nose test Diadochokinesis Romberg Standing on one leg Walk along straight line Rarely occurring miscellaneous dysfunctions
Consistent mild deviations
Two signs of dysfunction
Age-inadequate performance in two tests
Evidence of mild cranial nerve palsy or excessive (for age) amount of associated movements.
Motor behaviour of face Motor behaviour of eyes
parents were asked to fill out prior to the clinical evaluation. The questionnaire is a tool for screening ADHD with or without comorbidities and contains 181 questions covering eight domains of adaption: motor skills, executive functions, perception, memory, language, learning, social skills and emotional–behavioural problems (Trillingsgaard et al. 2004). Each individual question was scored using 0 (does not apply), 1 (applies to some extent) or 2 (definitely applies). The sum for each domain was then divided by the number of items. Thus, a mean score between 0 and 2 could be derived from each domain. A psychologist evaluated the completed FTF according to its manual, and the score for each area was compared to the Swedish age-matched norms. A definite developmental problem was indicated by a score above the 90th percentile. Scores at or above the 98th percentile implied a major developmental problem. Statistical analyses
Frequency counts, mean, standard deviation, median, range and percentages were used for descriptive purposes. Fisher’s exact test was used for categorical data, and means in normally distributed variables were compared with one-sample t-test and paired t-test (tested for normality with
628
contacted/referred). Basic data on the patients are presented in Table 3. Best-corrected visual acuity
All visual and ocular characteristics are summarized in Table 4. The median BCVA in MGDA eyes was 0.063 ranging between hand motion to 0.65, while the fellow eyes had a BCVA median of 1.0 (0–1.3) with one patient having a microphthalmic completely blind fellow eye. Differences in BCVA between the MGDA eye and fellow eye were statistically significant (p = 0.006, Sign test). All 12 patients had a binocular BCVA better than 0.3 (median 1; range 0.5–1.3) and were therefore categorized as having no visual impairment according to WHO. BCVA is presented in Fig. 1. Retinoscopy and refraction after cycloplegia
Shapiro-Wilk’s test of normality). Variables not normally distributed were tested with the Sign test. A p-value of
