Acta Pædiatrica ISSN 0803-5253
REGULAR ARTICLE
Chorioretinal scars and visual deprivation are common in children with cochlear implants after congenital cytomegalovirus infection Kristina Te€ar Fahnehjelm ([email protected])1,2*, Monica Olsson1,2*, Cecilia Fahnehjelm3, Ilona Lewensohn-Fuchs4,5, Eva Karltorp6,7 1.Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden 2.Department of Paediatric Ophthalmology and Strabismus, St. Erik Eye Hospital, Karolinska University Hospital, Stockholm, Sweden 3.Karolinska Institutet, Stockholm, Sweden 4.Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden 5.Department of Clinical Microbiology, Karolinska University Hospital, Huddinge, Sweden 6.Department of Clintec, Karolinska Institutet, Stockholm, Sweden 7.Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden
Keywords Chorioretinal atrophy, Cochlear implants, Congenital cytomegalovirus infection, Ocular motility, Severe hearing impairment Correspondence K Te€ar Fahnehjelm, Department of Clinical Neuroscience, Karolinska Institutet and Dept. Ophthalmology Vrinnevi hospital, 60182 €ping, Sweden. Norrko Tel: +46708431641 | Fax: +46855620489 | Email: [email protected] *Current address: Ophthalmology Vrinnevi Hospital, Norrk€oping 60182, Sweden
Received 6 November 2014; revised 22 December 2014; accepted 25 February 2015. DOI:10.1111/apa.12988
ABSTRACT Aim: The aim of this study was to compare visual function and ocular characteristics in children with cochlear implants, due to severe hearing impairment caused by the congenital cytomegalovirus (CMV) infection, with control children fitted with cochlear implants due to connexin 26 mutations (Cx26), a genetic cause of hearing impairment. Methods: We carried out ophthalmological assessments, including visual acuity, ocular alignment, Ocular Motor Score, biomicroscopy and fundus photography, on 26 children with congenital CMV (median age 8.3 years, range 1.4–16.7) and 13 Cx26 controls (median age 5.6 years, range 1.7–12.5). Results: We found unilateral chorioretinal macular scars that reduced best-corrected visual acuity ≤0.3 in five (19%) of the children with congenital CMV, but in none of the children with Cx26 (p = 0.15). Ocular motility problems were more common among children with congenital CMV, but the difference was not significant (p = 0.20). The vestibulo-ocular reflex was more frequently pathological in children with congenital CMV (p = 0.011). Conclusion: Ocular complications with central chorioretinal scars and ocular motility disturbances were common in children treated with cochlear implants due to severe hearing impairment caused by the congenital CMV infection. Ophthalmological assessments are advisable in such children for early identification, intervention and follow-up.
INTRODUCTION Congenital cytomegalovirus (CMV) infection is one of the most common congenital viral infections and an important cause of nongenetic hearing impairment and neurodevelopmental problems (1,2). Birth prevalence has been reported to be from 0.5% to 1% (2–6). Transmission to the foetus most commonly occurs through maternal primary infection, but reactivation or reinfection can occur (2,3). The majority (87%) of the children are born asymptomatic, while approximately 13% present with petechiae, jaundice, hepatosplenomegaly, thrombocytopaenia, seizures, intracranial calcifications or ocular complications (2,6,7). In the past, neonatal hearing impairment was not considered a neonatal indicator, but this has changed with the introduction of neonatal hearing screening.
Approximately 0.5% of children with congenital CMV infection die. Long-term neurological sequelae occur in 17– 20% of those who survive and include hearing impairment, cerebral palsy, motor deficits and/or cognitive deficits (2,5,6,8,9). The hearing impairment can be unilaterally or bilaterally present at birth or its onset may be delayed and so not detected during neonatal hearing screening and/or
Key Notes
Abbreviations VOR, The vestibulo-ocular reflex.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 693–700
This study compared ocular complications in children fitted with cochlear implants after a congenital cytomegalovirus (CMV) infection and control children with a genetic cause of hearing impairment. Ocular complications with central chorioretinal scars and ocular motility disturbances were common in children with congenital CMV infection. Ophthalmological assessments are advisable in such children for early identification, intervention and followup.
693
Te€ar Fahnehjelm et al.
Chorioretinitis in congenital cytomegalovirus infection
develop progressively (10). Recently, extensive vestibular dysfunction and balance disturbances in children from the same cohort have been reported (11). Optic atrophy, chorioretinal scars, cerebral visual impairment, cataract and various optic nerve malformations have been reported in previous studies of children with congenital CMV infection (1,12–15). However, the extent and range of visual and ocular complications in children identified in universal screening is not fully known (6). In a large Swedish neonatal screening study, 60 children with congenital CMV infection were identified. No patient with ocular pathology was reported. However, ophthalmological examinations were performed in the children before the age of one, and no details regarding the assessments, results or difficulties in interpretation were presented (5). Congenital CMV infection is an important differential diagnosis for deaf-blindness or Usher syndrome in children with hearing impairment and/or balance disturbances. For this reason, knowledge about the characteristics of the ocular pathology linked to congenital CMV infection is important. The aims of the current study were to study visual functions and ocular characteristics, including motility and optic disc morphology, in a well-defined group of patients who had been fitted with cochlear implants due to congenital CMV infection and to compare these results with a group of children with hearing impairment due to Cx26 deficiency who had also received cochlear implants.
PATIENTS AND METHODS At the cochlear implant department at Karolinska University Hospital, Huddinge, Sweden, 224 children were fitted with cochlear implants from 2002 to 2012. The cause of the hearing impairment was unknown in 103 of these children, and 74 of 103 were tested regarding aetiology and regarding congenital CMV infection. If blood sample tests showed immunoglobulin G (IgG) against CMV, the dried blood spot cards were analysed for CMV deoxyribonucleic acid (DNA) to verify congenital infection. Congenital CMV infection was verified in 22 children, who were then invited to participate in the multidisciplinary study. All 22 children agreed to do so. In addition, nine teenagers earlier fitted with cochlear implants, and diagnosed with congenital CMV infection before screening started, were invited to take part and four of them agreed to do so. Thus, a total of 26 patients who had received cochlear surgery and had congenital CMV infection were included in this study (11). A group of 13 children with Cx26 mutations, all of whom had also received cochlear implants, were invited to serve as controls. These controls were selected due to the fact that Cx26 mutations are common causes of hearing impairment in early childhood, but not associated with other comorbidities. The children with Cx26 mutations were also tested for congenital CMV infection, but were negative. The controls were not matched, but of similar age (11). One eye problem that children with Cx26
694
mutations may risk is vascularising keratitis (16), but there have been no reports of any other specific ocular malformations (17). Each child was examined by the multidisciplinary team at one venue over the course of 1 day. The children were examined by a paediatrician, a neuropaediatrician, a speech and language pathologist, a physiotherapist and an otolaryngist. The results from the examinations and details regarding diagnoses, treatment, balance outcome, language and neurodevelopmental disabilities have previously been reported (11). Hearing impairment in the congenital CMV group was diagnosed at a mean age of 0.8 years. Cochlear implant surgery was performed at a mean age of 2.1 years, while bilateral cochlear implantations were completed at a mean age of 3.3 years. In the Cx26 group, hearing impairment was diagnosed at a mean age of 0.3 years, and cochlear implant surgery performed at a mean age of 1.6 years and 1.5 years of age, respectively (Table 2). Neonatal symptoms of congenital CMV infection were defined as jaundice, petechiae, hepatosplenomegaly and premature birth. These symptoms were present in six of the 26 children with congenital CMV infection, but in none of the children with Cx26 mutations. Hearing impairment was not defined as a neonatal symptom. Detailed clinical ophthalmological assessments were performed as part of the study in September 2012. In addition, the majority of the congenital CMV patients – 19 of the 26 – had previously been examined at the same department of paediatric ophthalmology, often by the author (KTF), on one to three occasions during childhood. The remaining seven patients lived outside the geographical area. All examinations performed as part of the study were adapted to the age of the patient and included grading acuity with preferential looking, best-corrected decimal visual acuity (BCVA) and ocular alignment. Refraction after cycloplegia was performed after a single instillation of a mixture of cyclopentolate (0.85%) and phenylephrine (1.5%), as was slit-lamp biomicroscopy and indirect ophthalmoscopy. The Ocular Motor Score test (18) was used to evaluate ocular motor functions, with zero being a normal score and 0.3–1.0 subnormal or pathological. Two different methods were used to measure the optic disc parameters. In the first, the optic disc to macula distance was measured with a ruler and divided by the mean diameter of the optic disc (19,20). A ratio of ≥3.0 normally suggests a hypoplastic optic disc. The second method involved the use of the semiautomated Retinal Size Tool method (21). The disc area, cup area and rim area values were compared to reference values. A small optic disc was defined as a disc area below 2 standard deviations (SD), corresponding to
REGULAR ARTICLE
Chorioretinal scars and visual deprivation are common in children with cochlear implants after congenital cytomegalovirus infection Kristina Te€ar Fahnehjelm ([email protected])1,2*, Monica Olsson1,2*, Cecilia Fahnehjelm3, Ilona Lewensohn-Fuchs4,5, Eva Karltorp6,7 1.Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden 2.Department of Paediatric Ophthalmology and Strabismus, St. Erik Eye Hospital, Karolinska University Hospital, Stockholm, Sweden 3.Karolinska Institutet, Stockholm, Sweden 4.Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden 5.Department of Clinical Microbiology, Karolinska University Hospital, Huddinge, Sweden 6.Department of Clintec, Karolinska Institutet, Stockholm, Sweden 7.Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden
Keywords Chorioretinal atrophy, Cochlear implants, Congenital cytomegalovirus infection, Ocular motility, Severe hearing impairment Correspondence K Te€ar Fahnehjelm, Department of Clinical Neuroscience, Karolinska Institutet and Dept. Ophthalmology Vrinnevi hospital, 60182 €ping, Sweden. Norrko Tel: +46708431641 | Fax: +46855620489 | Email: [email protected] *Current address: Ophthalmology Vrinnevi Hospital, Norrk€oping 60182, Sweden
Received 6 November 2014; revised 22 December 2014; accepted 25 February 2015. DOI:10.1111/apa.12988
ABSTRACT Aim: The aim of this study was to compare visual function and ocular characteristics in children with cochlear implants, due to severe hearing impairment caused by the congenital cytomegalovirus (CMV) infection, with control children fitted with cochlear implants due to connexin 26 mutations (Cx26), a genetic cause of hearing impairment. Methods: We carried out ophthalmological assessments, including visual acuity, ocular alignment, Ocular Motor Score, biomicroscopy and fundus photography, on 26 children with congenital CMV (median age 8.3 years, range 1.4–16.7) and 13 Cx26 controls (median age 5.6 years, range 1.7–12.5). Results: We found unilateral chorioretinal macular scars that reduced best-corrected visual acuity ≤0.3 in five (19%) of the children with congenital CMV, but in none of the children with Cx26 (p = 0.15). Ocular motility problems were more common among children with congenital CMV, but the difference was not significant (p = 0.20). The vestibulo-ocular reflex was more frequently pathological in children with congenital CMV (p = 0.011). Conclusion: Ocular complications with central chorioretinal scars and ocular motility disturbances were common in children treated with cochlear implants due to severe hearing impairment caused by the congenital CMV infection. Ophthalmological assessments are advisable in such children for early identification, intervention and follow-up.
INTRODUCTION Congenital cytomegalovirus (CMV) infection is one of the most common congenital viral infections and an important cause of nongenetic hearing impairment and neurodevelopmental problems (1,2). Birth prevalence has been reported to be from 0.5% to 1% (2–6). Transmission to the foetus most commonly occurs through maternal primary infection, but reactivation or reinfection can occur (2,3). The majority (87%) of the children are born asymptomatic, while approximately 13% present with petechiae, jaundice, hepatosplenomegaly, thrombocytopaenia, seizures, intracranial calcifications or ocular complications (2,6,7). In the past, neonatal hearing impairment was not considered a neonatal indicator, but this has changed with the introduction of neonatal hearing screening.
Approximately 0.5% of children with congenital CMV infection die. Long-term neurological sequelae occur in 17– 20% of those who survive and include hearing impairment, cerebral palsy, motor deficits and/or cognitive deficits (2,5,6,8,9). The hearing impairment can be unilaterally or bilaterally present at birth or its onset may be delayed and so not detected during neonatal hearing screening and/or
Key Notes
Abbreviations VOR, The vestibulo-ocular reflex.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 693–700
This study compared ocular complications in children fitted with cochlear implants after a congenital cytomegalovirus (CMV) infection and control children with a genetic cause of hearing impairment. Ocular complications with central chorioretinal scars and ocular motility disturbances were common in children with congenital CMV infection. Ophthalmological assessments are advisable in such children for early identification, intervention and followup.
693
Te€ar Fahnehjelm et al.
Chorioretinitis in congenital cytomegalovirus infection
develop progressively (10). Recently, extensive vestibular dysfunction and balance disturbances in children from the same cohort have been reported (11). Optic atrophy, chorioretinal scars, cerebral visual impairment, cataract and various optic nerve malformations have been reported in previous studies of children with congenital CMV infection (1,12–15). However, the extent and range of visual and ocular complications in children identified in universal screening is not fully known (6). In a large Swedish neonatal screening study, 60 children with congenital CMV infection were identified. No patient with ocular pathology was reported. However, ophthalmological examinations were performed in the children before the age of one, and no details regarding the assessments, results or difficulties in interpretation were presented (5). Congenital CMV infection is an important differential diagnosis for deaf-blindness or Usher syndrome in children with hearing impairment and/or balance disturbances. For this reason, knowledge about the characteristics of the ocular pathology linked to congenital CMV infection is important. The aims of the current study were to study visual functions and ocular characteristics, including motility and optic disc morphology, in a well-defined group of patients who had been fitted with cochlear implants due to congenital CMV infection and to compare these results with a group of children with hearing impairment due to Cx26 deficiency who had also received cochlear implants.
PATIENTS AND METHODS At the cochlear implant department at Karolinska University Hospital, Huddinge, Sweden, 224 children were fitted with cochlear implants from 2002 to 2012. The cause of the hearing impairment was unknown in 103 of these children, and 74 of 103 were tested regarding aetiology and regarding congenital CMV infection. If blood sample tests showed immunoglobulin G (IgG) against CMV, the dried blood spot cards were analysed for CMV deoxyribonucleic acid (DNA) to verify congenital infection. Congenital CMV infection was verified in 22 children, who were then invited to participate in the multidisciplinary study. All 22 children agreed to do so. In addition, nine teenagers earlier fitted with cochlear implants, and diagnosed with congenital CMV infection before screening started, were invited to take part and four of them agreed to do so. Thus, a total of 26 patients who had received cochlear surgery and had congenital CMV infection were included in this study (11). A group of 13 children with Cx26 mutations, all of whom had also received cochlear implants, were invited to serve as controls. These controls were selected due to the fact that Cx26 mutations are common causes of hearing impairment in early childhood, but not associated with other comorbidities. The children with Cx26 mutations were also tested for congenital CMV infection, but were negative. The controls were not matched, but of similar age (11). One eye problem that children with Cx26
694
mutations may risk is vascularising keratitis (16), but there have been no reports of any other specific ocular malformations (17). Each child was examined by the multidisciplinary team at one venue over the course of 1 day. The children were examined by a paediatrician, a neuropaediatrician, a speech and language pathologist, a physiotherapist and an otolaryngist. The results from the examinations and details regarding diagnoses, treatment, balance outcome, language and neurodevelopmental disabilities have previously been reported (11). Hearing impairment in the congenital CMV group was diagnosed at a mean age of 0.8 years. Cochlear implant surgery was performed at a mean age of 2.1 years, while bilateral cochlear implantations were completed at a mean age of 3.3 years. In the Cx26 group, hearing impairment was diagnosed at a mean age of 0.3 years, and cochlear implant surgery performed at a mean age of 1.6 years and 1.5 years of age, respectively (Table 2). Neonatal symptoms of congenital CMV infection were defined as jaundice, petechiae, hepatosplenomegaly and premature birth. These symptoms were present in six of the 26 children with congenital CMV infection, but in none of the children with Cx26 mutations. Hearing impairment was not defined as a neonatal symptom. Detailed clinical ophthalmological assessments were performed as part of the study in September 2012. In addition, the majority of the congenital CMV patients – 19 of the 26 – had previously been examined at the same department of paediatric ophthalmology, often by the author (KTF), on one to three occasions during childhood. The remaining seven patients lived outside the geographical area. All examinations performed as part of the study were adapted to the age of the patient and included grading acuity with preferential looking, best-corrected decimal visual acuity (BCVA) and ocular alignment. Refraction after cycloplegia was performed after a single instillation of a mixture of cyclopentolate (0.85%) and phenylephrine (1.5%), as was slit-lamp biomicroscopy and indirect ophthalmoscopy. The Ocular Motor Score test (18) was used to evaluate ocular motor functions, with zero being a normal score and 0.3–1.0 subnormal or pathological. Two different methods were used to measure the optic disc parameters. In the first, the optic disc to macula distance was measured with a ruler and divided by the mean diameter of the optic disc (19,20). A ratio of ≥3.0 normally suggests a hypoplastic optic disc. The second method involved the use of the semiautomated Retinal Size Tool method (21). The disc area, cup area and rim area values were compared to reference values. A small optic disc was defined as a disc area below 2 standard deviations (SD), corresponding to
