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AimsTo determine the ophthalmological outcome at 6.5 years of age in children treated for retinopathy of prematurity (ROP), and registered in the national Swedish National Register for ROP register.MethodsData on ROP, treatment and ophthalmological outcome were retrieved from the register. Visual acuity (VA), refractive errors and strabismus, together with visual impairment (VI) and any significant eye problem, defined as VA >0.5 logarithm of the minimal angle of resolution (logMAR) and/or strabismus and/or any refractive error were analysed. Risk factors such as sex, gestational age (GA), birth weight SD score, number of treatments and retreatments, postnatal age and postmenstrual age at first treatment were analysed.ResultsFollow-up data were available in 232 of 270 children born between 2007 and 2014 who had been treated for ROP. VI (VA >0.5 logMAR) was found in 32 (14%), strabismus in 82 (38%), refractive errors in 114 (52%) and significant eye problem in 143 (65%) children. Retreatment was a risk factor for VI and refractive errors. Male sex and neonatal brain lesion were risk factors for strabismus. An additional week of GA at birth reduced the risk for refractive errors, strabismus and significant eye problems.ConclusionThe results of the present study revealed a high number of eye problems in children treated for ROP, emphasising the need for long-term follow-up. Retreatment of ROP was a risk factor for VI, and emphasises the importance of an accurate first treatment for the long-term ophthalmological outcome.

Athanasia Skriapa-Manta,1,2 Mattias Nilsson,1 Jan Svoboda,3 Monica Olsson,1,2 Maria Nilsson,4 Kristina Teär Fahnehjelm1,2 1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 2Department of Paediatric Ophthalmology, Strabismus and Electrophysiology, St. Erik Eye Hospital, Stockholm, Sweden; 3Department of Paediatric Radiology, Karolinska University Hospital, Stockholm, Sweden; 4Unit of Optometry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenCorrespondence: Athanasia Skriapa-Manta, St Erik Eye Hospital, Eugeniavägen 12, Stockholm, 17164, Sweden, Tel +46 739 491 186, Email athanasia.skriapa-manta@ki.sePurpose: Optic nerve hypoplasia (ONH) is a common cause of visual impairment in children. Clinical complexity can cause diagnostic delay and difficulties predicting visual outcome. We evaluated whether optical coherence tomography (OCT) can improve the diagnosis and prediction of vision.Methods: Thirty-seven eyes with ONH from 12 girls and 8 boys, median age 10.5 years (range 2.8– 18.9 years), were included in this cross-sectional cohort study. The majority, 17/20, had bilateral ONH. Ophthalmological assessments included best corrected visual acuity (BCVA), fundus photography, measurement of the peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell complex (GCC), Bruch’s membrane opening (BMO) and visual fields. We compared OCT parameters with comparison data collected on 140 healthy individuals 5 to 25 years old. Pearson’s correlation coefficient was used to determine the correlation of OCT parameters and BCVA.Results: OCT demonstrated thinner mean pRNFL (p < 0.001) and mean GCC compared to the reference material (p < 0.001). BCVA displayed a strong or moderate correlation to pRNFL and to all sectors of the GCC except the inferotemporal. BCVA correlated strongly to Bruch’s membrane opening (BMO) (0.71, p < 0.001), and moderately to the Zeki ratio (− 0.52, p < 0.001). Multivariate analyses showed that BMO explained 48% of the variance in BCVA. Visual fields correlated strongly to pRNFL and GCC thickness. GCC thinning corresponded to visual field defects presence and location.Conclusion: OCT can facilitate the diagnosis of ONH. Parameters such as pRNFL, GCC and BMO can be predictors of visual acuity whereas GCC and pRNFL thinning can indicate location and severity of visual field defects.Keywords: optic nerve hypoplasia, OCT, ganglion cell complex, RNFL, visual fields, paediatric ophthalmology

To report ocular outcome, somatic co-morbidities, genetics, and quality of life in children born with anophthalmia (A) or microphthalmia (M).Thirty-five children (19 boys) with A/M underwent ophthalmological examinations and a review of medical records. Parents of 12/22 cases completed the Pediatric Quality of Life Inventory (PedsQL).Age at examination ranged from 7 months to 18 years (median 2.3 years). Ten cases were totally blind or had light perception. Isolated A/M occurred in 16/35 cases, while somatic, psychomotor, neuroradiological and/or genetic pathology occurred in 19/35 cases both in the bilateral (7/9) and in the unilateral group (12/26). Among 26 unilateral cases, 4/16 with one normal eye had associated problems compared to 9/10 if the contralateral eye was pathological (Somatic, psychomotor and/or neuroradiological pathologies were more common in bila-teral than unilateral cases, but the difference was not significant. There was decreased risk in unilateral cases with one normal eye. Genetic defects occurred in both unilateral and bilateral cases. Health-related quality of life was reduced.

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.

PURPOSE The aim of the study was to report prevalence, ocular outcome, neurological characteristics, cognitive and behavioural problems in children with optic disc coloboma (ODC). METHODS This was a population-based, cross-sectional study of 31 children between 2 and 18 years of age diagnosed with ODC. The children were part of a larger cohort of 184 children with congenital optic disc malformations. Clinical ophthalmological examinations, neurological assessments, behavioural and developmental screening were performed. RESULTS The prevalence of ODC was 8.9/100 000 children. Of the 31 patients, 18 had unilateral ODC (p = 0.21). The best-corrected visual acuity (BCVA) in the ODC eye ranged from blindness to 1.3 (median 0.3). BCVA was 0.82 in eyes with an isolated ODC (range 0.4-1.3) and 0.15 (range 0-0.5) in eyes with concurrent macular involvement (p

AIM This prospective study assessed the long-term ocular and visual outcomes of children with mucopolysaccharidoses type I Hurler syndrome (MPS IH) who were treated with haematopoietic stem cell transplants (HSCT). METHODS Clinical ophthalmological assessments were performed on eight patients at the St Erik Eye Hospital, Huddinge, Stockholm, Sweden, from 2001-2018: The median age at diagnosis and HSCT were 12.2 (range 5.0-16.4) and 16.7 (8.0-20.4) months. The last eye examination was at a median of 13.4 (6.3-19.0) years and follow-up lasted a median of 12.0 (5.0-17.4) years. RESULTS Poor visual acuity, poor night vision and, or, photophobia were reported by six children. The best corrected visual acuity at the last visit was a median of 0.4 and 0.5 in the right and left eye and had declined significantly in two patients. Corneal opacities had increased despite HSCT in five patients. High hyperopia, at a median of +6 Dioptres, occurred in all patients and stiff corneas in all four patients that were measured. The patients' corrected intraocular pressures were normal. Retinal degeneration was identified in two patients. CONCLUSION Despite HSCT, the long-term follow-up of patients with MPS IH showed reduced visual acuity due to corneal opacities or retinal degeneration.

AIM Optic nerve hypoplasia (ONH) is a congenital ocular malformation that has been associated with neurodevelopmental disorders, but the prevalence in unilateral disease and less severe visual impairment is unknown. We studied intellectual disability and autism spectrum disorders (ASDs) in patients with ONH. METHODS This was a population-based cross-sectional cohort study of 65 patients (33 female) with ONH below 20 years of age, living in Stockholm in December 2009, with data analysed in January 2016. Of these 35 were bilateral and 30 were unilateral. Neurodevelopmental disorders were diagnosed or confirmed by neurological assessments, the Five to Fifteen parent questionnaire and reviewing previous neuropsychological investigations or conducting neuropsychological tests. RESULTS Bilateral ONH patients had lower mean full scale intelligence quotient scores than unilateral patients (84.4 and 99.4, respectively, p = 0.049). We assessed intellectual disability in 55 eligible patients, and it was more common in patients with bilateral ONH (18 of 32, 56%) than unilateral ONH (two of 23, 9%, p < 0.001). ASDs were diagnosed in seven of 42 (17%) patients. CONCLUSION Children with bilateral ONH had a high risk of neurodevelopmental disorders, especially intellectual disability. The risk was lower in unilateral ONH, but the levels of neurodevelopmental disorders warrant screening of both groups.

Highlights • VEP recordings were abnormal in 17% of the patients median 6 years post hematopoietic stem cell transplantation in childhood. • Pathological VEPs were associated with decreased visual acuity. • Pathological VEPs were not linked to irradiation, chemotherapy or malignant diagnosis., Objective To study visual pathway pathology detected by visual evoked potentials (VEPs) in patients treated with hematopoietic stem cell transplantation (HSCT) in childhood and to determine the impact of adverse ocular findings, somatic diseases, and conditioning regimens on the VEP results. Methods Ophthalmological assessments including pattern VEPs were performed in 47 of 79 patients at a median age of 15 years (range 3–21 years) in median 6 years (1–17 years) after HSCT. Somatic data were extracted from medical records. Results Eight patients of 47 (17%) demonstrated pathological VEPs with prolonged latencies bilaterally (n = 3) or unilaterally (n = 5) at their latest VEP test at an age of 12–18 years. A subnormal visual acuity was present in 8/11 eyes with pathological VEPs: one eye had cataract, six eyes had cataract surgery where of two had developed secondary cataracts. One eye had residual retinopathy of prematurity. Pathological VEPs were associated with decreased visual acuity (p = 0.00019) but not linked to gender, malignant diagnosis or conditioning. Conclusion VEP recordings showed an association with decreased visual acuity but no relationship with irradiation or chemotherapy in the present study. Significance VEP recordings might be of clinical value for children with an unexplained subnormal visual acuity undergoing HSCT.

Aim: There have been few studies on long-term electroretinographic findings in patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). This study correlated long-term electroretinographic findings with age, metabolic control and clinical symptoms. Methods: We examined 12 Swedish patients with LCHADD. Visual acuity testing, fundus examinations, optical coherence tomography and electroretinography were performed. The results were correlated to age, the levels of 3-hydroxyacylcarnitine and acylcarnitine and clinical metabolic control. Results: Blindness or moderate visual impairment was found in two patients. Retinal pigmentation, atrophy and fibrosis were present in 11, seven and one of the patients, respectively, and optical coherence tomography showed retinal thinning in three of the six patients examined. Electroretinography was performed on 11 of the 12 patients. It was pathological, with reduced rod and cone responses, in five patients, subnormal in four and was related to poor clinical metabolic control and severe neonatal symptoms. Repeated electroretinographies revealed reduced function with increasing age. Conclusion: More than 80% of the LCHADD patients developed pathological or subnormal retinal function. This was more pronounced in patients with neonatal symptoms, but ameliorated by strict dietary treatment. Annual ophthalmological follow-ups, with electroretinography every second or third year, are recommended. (Less)

Optic nerve hypoplasia (ONH) is a congenital malformation with a reduced number of retinal ganglion cell axons in a thin optic nerve. It is a common cause of visual impairment in children and ONH is associated with neurodevelopmental disorders, pituitary hormone deficiencies, and brain malformations. In most cases, the aetiology is unknown, but both environmental factors and genetic causes have been described. This study aimed to identify genetic variants underlying ONH in a well-characterised cohort of individuals with ONH. We performed array comparative genomic hybridization and whole genome sequencing in 29 individuals with ONH. Rare variants were verified by Sanger sequencing and inheritance was assessed in parental samples. We identified 11 rare single nucleotide variants (SNVs) in ten individuals, including a homozygous variant in KIF7 (previously associated with Joubert syndrome), a heterozygous de novo variant in COL4A1 (previously described in an individual with porencephaly), and a homozygous variant in COL4A2. In addition, one individual harboured a heterozygous variant in OPA1 and a heterozygous variant in COL4A1, both were inherited and assessed as variants of unknown clinical significance. Finally, a heterozygous deletion of 341 kb involving exons 7-18 of SOX5 (associated with Lamb-Schaffer syndrome) was identified in one individual. The overall diagnostic yield of pathogenic or likely pathogenic variants in individuals with ONH using whole genome sequencing was 4/29 (14%). Our results show that there is a genetic heterogeneity in ONH and indicate that genetic causes of ONH are not rare. We conclude that genetic testing is valuable in a substantial proportion of the individuals with ONH, especially in cases with non-isolated ONH.

Ocular graft-versus-host disease (GVHD) occurs in more than half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity, which affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplant physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD, regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed in this review. Ocular GVHD has at least three biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have found several novel pathogenic mechanisms, including renin angiotensin system and endoplasmic reticulum stress signaling that can be targeted by therapeutic agents. Many studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. Efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important for all health professionals taking care of HCT recipients to have adequate knowledge of ocular GVHD for optimal care.

AIM This study examined the prevalence of neurological impairment and pituitary hormone deficiency (PHD) in patients with unilateral and bilateral optic nerve hypoplasia (ONH). METHODS A population-based cross-sectional cohort study of 65 patients (51% female) with ONH was conducted in Stockholm. Of these were 35 bilateral and 30 unilateral. The patients were below 20 years of age, living in Stockholm in December 2009 and found through database searching. The median age at the analysis of the results in January 2018 was 16.1 years (range 8.1-27.5 years). Neurological assessments and blood sampling were conducted, neuroradiology was reviewed and growth curves were analysed. Diagnoses of PHDs were based on clinical and biochemical evidence of hormone deficiency. RESULTS Neurological impairments were identified in 47% of the patients and impairments in gross and fine motor function were more prevalent in bilateral ONH (p

Non-graft-versus-host disease (GVHD) ocular complications are generally uncommon after hematopoietic cell transplantation (HCT) but can cause prolonged morbidity affecting activities of daily living and quality of life. Here we provide an expert review of non-GVHD ocular complications in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Complications discussed in this review include cataracts, glaucoma, ocular infections, ocular involvement with malignancy, ischemic microvascular retinopathy, central retinal vein occlusion, retinal hemorrhage, retinal detachment and ocular toxicities associated with medications. We summarize the incidence, risk factors, screening, prevention, and treatment of individual complications and generate evidence-based recommendations. Baseline ocular evaluation before HCT should be considered in all patients who undergo HCT. Follow-up evaluations should be considered according to clinical signs and symptoms and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplantation physicians and ophthalmologists should be knowledgeable about non-GVHD ocular complications and provide comprehensive collaborative team care.

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care. ispartof: Biol Blood Marrow Transplant vol:25 issue:2 pages:e46-e54 ispartof: location:United States status: published

In the original version of this article, author ‘Aisha Al-Khinji’ was incorrectly listed as ‘Aisha Ahmed’. This has now been corrected in both the PDF and HTML versions of the article to ‘Aisha Al-Khinji’.

The aim of the study was to study visual acuity, visual perceptual, and VMI skills in patients after HSCT in childhood. Tests of visual perceptual skills, VMI, and visual acuity were performed in 102 children/adolescents (age range 4.3-20.9 years). Mean time from HSCT to testing was 6.0 years (0.9-17.5 years). Visual acuity was median 1.0 decimal (range 0.16-1.6). Visual perceptual skills (memory, form constancy, visual sequential memory) and VMI were low compared to age-equivalent normative data with, respectively, 36%, 45%, 60%, and 46% of all patients performing below the 25 percentile. All patients performed significantly lower than the 50 percentile in the reference material in visual sequential memory, P < .001 (boys P < .001 and girls P < .05). All patients also performed significantly lower than the 50 percentile in VMI (P < .01) (boys P < .05). Pretransplant conditioning regimen did not affect outcome if the results were corrected for age at HSCT. Visual perceptual skill problems and VMI problems frequently occur in patients after HSCT in childhood. Age at HSCT and original diagnosis influence the outcome. Neuropsychological assessment including visual perception is recommended in children after HSCT.

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.

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.

Purpose: Fanconi anaemia (FA) is a multisystemic disorder with ocular implications. This study aims to describe visual function, ocular characteristics and visual processing skills in patients with FA after haematopoietic stem cell transplantation. Methods: Ten patients with FA, ages 8–17 years, underwent ophthalmological examinations, corneal, periocular and fundus photography, visual evoked potentials (VEPs), visual fields and ocular motor and visual processing information tests. Results: Best-corrected decimal visual acuity was ≥0.65 in all 20 eyes. Microcornea was present in 18 of 18 eyes, short axial lengths in six of six eyes, steep corneal curvatures in four of six eyes, ptosis in 14 of 16 eyes, short palpebral fissures in 15 of 16 eyes and hypotelorism in three of seven patients. Optic disc areas were smaller in patients with FA compared to controls (p = 0.0003 right, p = 0.0003 left eye). Visual fields were abnormal in 4 of 18 eyes, while VEP was abnormal in 1 of 20 eyes. Eight patients had ocular motor dysfunction, while nine of 10 patients showed delay in visual processing skills. Conclusion: Patients with FA can present with microcornea, microphthalmia, ptosis, steep corneal curvatures, small optic discs, ptosis and delay in visual processing skills. Detailed ophthalmological and visual processing skills assessments and developmental investigations are important to detect impairments and facilitate appropriate support.

Objective To describe visual outcomes after penetrating keratoplasty and deep anterior lamellar keratoplasty in patients with mucopolysaccharidoses. Methods This is a retrospective review of keratoplasty in consecutive patients from Brazil, England, Finland, Germany, Portugal, Sweden and the USA. All patients had corneal clouding due to mucopolysaccharidoses. Preoperative and postoperative visual outcome and ocular comorbidities were identified. Success was arbitrarily defined as any improvement in visual acuity or best-corrected visual acuity better than logarithm of the minimum angle of resolution 0.30 (20/40). Statistical analysis included only data from first operated eyes in the 16 patients who underwent bilateral keratoplasty. Results Forty-eight eyes from 32 patients with mucopolysaccharidoses I, IV or VI are reported. Mean follow-up was 70 months (range: 5–186). Penetrating keratoplasty was performed in 45 eyes and deep anterior lamellar keratoplasty in 3 eyes. At last follow-up, a successful visual outcome for penetrating keratoplasty in first operated/only operated eyes was found in 63%. Rejection episodes occurred in 23% of grafts; however, a clear graft was recorded at last follow-up in 94%. Ocular pathway comorbidities were identified in 63% of eyes transplanted. Conclusions Clear corneal grafts can be obtained for patients with corneal clouding due to mucopolysaccharidosis with improvement in visual acuity in the majority.

Purpose: Ocular motility disturbances are common in a number of neuropaediatric and neurometabolic disorders. Assessment of ocular motor function can be a source of information for diagnosis and follow-up of these patients. Aim: To evaluate a new clinical ocular motor function test: ocular motor score (OMS) and provide reference values in children and young adults without known ocular or neurological disorders. Material and Methods: A total of 233 children and young adults, 103 males and 130 females between the ages of 6 months and 19 years, were assessed according to a specific OMS protocol. They were divided into four different age groups: 0.5–3, 4–6, 7–10 and 11–19 years. The OMS protocol consists of 15 different subtests evaluating ocular motor function, and a total score of minimum 0 up to max 15 can be obtained: the minimum score, 0, is considered normal while 1 represents an abnormal function. Results: The median OMS in the whole reference group was 0.3 (range 0–4.8). The median OMS in the different age groups, starting with the youngest, was: 0.9 (range 0.3–4.8), 0.3 (range 0–3.4), 0.3 (range 0–2.3) and 0 (range 0–3.5), respectively. The youngest subjects, aged 0.5–3, showed a significantly higher total OMS compared with the other age groups (p

Purpose: High intraocular pressure (IOP) and glaucoma are often suspected in patients with mucopolysaccharidosis (MPS). To determine corneal hysteresis (CH) and IOP in children with mucopolysaccharidosis I-Hurler (MPS I-H) and MPS VI. Methods: Clinical measurements with ocular response analyzer (ORA). Results: In seven patients, five with MPS I-H treated with stem cell transplantation (SCT), and two with MPS VI, one treated with SCT and the other with enzyme therapy, the IOP was examined with ORA. Ocular response analyzer measurements were made at a median age of 8.7 years in the patients with MPS I-H and at a median age of 9.3 years in the patients with MPS VI. Earlier measurements had raised suspicion of high IOP in one patient. The ORA showed an increased CH and a falsely high IOP values in all 14 eyes. The recalculated IOPs were normal in all 14 eyes. Mild to severe corneal opacities were present in all 14 eyes. Optic disc areas, borders and cupping were clinically normal in the 12 of 14 eyes that were possible to examine. Severe corneal opacities hampered optic disc evaluation in the older patient with MPS VI. Three eyes in two patients had normal thickness of the retinal nerve fibre layer measured with scanning laser polarimetry with corneal compensation (GDx VCC). No patient was diagnosed or treated for glaucoma. Conclusion: The IOPs are often falsely high because of an increased resistance of the cornea and correlate to the extent of corneal clouding. In this small, cross-sectional study, it appears that corneal resistance is directly correlated with corneal clouding, although a longitudinal study that evaluates resistance as the cornea clears with treatment would provide more direct evidence that corneal deposits are directly related to resistance. A correct measured IOP can avoid unnecessary medical or surgical hypotensive treatment.

International audience; Ocular pathology is common in patients with mucopolysaccharidosis (MPS), an hereditary lysosomal storage disorder, where the eye as well as other tissues accumulate excessive amounts of glycosaminoglycans. Despite genetic and phenotypic heterogeneity within and between different types of MPS, the disease symptoms and clinical signs often manifest during the first six months of life with increasing head size, recurrent infections, umbilical hernia, growth retardation and skeletal problems. Typical ocular features include corneal clouding, ocular hypertension/glaucoma, retinal degeneration and optic nerve atrophy. Visual deterioration and sensitivity to light may substantially reduce the quality of life in MPS patients, particularly when left untreated. As an early intervention, haematopoietic stem cell transplantation and/or enzyme replacement therapy are likely to improve patients' symptoms and survival, as well as visual outcome. Thus, it is of utmost importance to ensure proper detection and accurate diagnosis of MPS at an early age. Fundamental herein is to increase awareness and knowledge among ophthalmologists of the ocular problems affecting MPS patients and to highlight potential diagnostic pitfalls and difficulties in patient care. This review provides insight into the prevalence and severity of ocular features in patients with MPS and gives guidance for early diagnosis and follow-up of MPS patients. MPS poses therapeutic challenges in ocular management, which places ophthalmologists next to paediatricians at the forefront of interventions to prevent long-term sequelae of this rare but serious disease.

The management of mucopolysaccharidosis (MPS) is focused on the multi-organ, sometimes life-threatening, clinical manifestations that occur over time. In the past, the limited, symptom-based treatment options led physicians to adopt a palliative approach towards individual disease-associated complications. The availability of systemic treatments such as haematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) has created a better prognosis for MPS patients, particularly when initiated early in life. As part of an integrated management approach, these therapies could be valuable in managing the ocular features that are present in many children with MPS. HSCT has been shown to stabilize or improve corneal clouding and optic nerve oedema for the majority of patients. Retinal degeneration, in contrast, seems not to be permanently arrested. ERT was more recently introduced and has therefore been less well examined than HSCT; with respect to ocular problems in MPS, the majority of reports indicate stabilization of corneal clouding or visual acuity. However, controversy remains about its effect on other ocular pathologies. Despite the lack of consistent ophthalmic improvement for all patients, both treatment modalities deserve consideration, because even reducing MPS-related eye disease progression is worthwhile.

Purpose: This study aimed to describe the Rarebit (RB) visual field and optic nerve size ⁄ morphology in patients treated with allogeneic stem-cell transplantation (SCT) in childhood, and to determine the impact of ocular status and conditioning regimens such as total body irradiation (TBI), chemotherapy and ⁄ or immunosuppressive drugs on the RB visual field. Methods: Ocular fundi were evaluated in 79 patients. Digital analyses regarding optic disc area (DA), rim area (RA) and cup area (CA) were performed in 45 of 49 patients. RB visual field testing was performed in 53 of 79 patients. The mean hit rate (MHR) was compared to corneal status, cataract, diagnosis and pre and post-SCT treatment. Two groups of healthy children and young adults (RB = 51, disc analysis = 49) were used as controls. Results: The SCT patients, examined at a median age of 15.4 years, had a significantly lower MHR [median 91% (range 45–99) right eye and 91% (range 41–91) left eye] compared to controls [median 96% (range 78–100) right eye]. SCT patients treated surgically for cataract and with intraocular lenses (IOLs) had a significantly lower MHR compared to other SCT patients. The MHR was also significantly influenced by type of conditioning. Patients conditioned with chemotherapy other than busulfan had significantly better MHR compared to those who had received single-dose TBI. SCT patients had a significantly larger CA and smaller RA than the controls. Conclusion: Patients treated with SCT in childhood have a significantly lower MHR than controls when examined with RB. Also, patients surgically treated for cataract and with IOL implantation had a significantly lower MHR.

Congenital cytomegalovirus (CMV) infection is asymptomatic in 90% of infected newborns but approximately 10-20% of these infants are at risk of developing sequelae later, mostly hearing deficit. The aims of the study were to investigate the prevalence of congenital CMV infection in a Swedish population of newborns and investigate the relative risk of hearing deficit in newborns with congenital CMV infection. The dried blood spot (DBS) samples of 6060 newborns in southern Stockholm during 12 months (October 2003-June 2004; August 2004-October 2004) were analysed for CMV DNA by TaqMan based real-time PCR. Hearing deficit was assessed by otoacoustic emission (OAE) within a newborn screening programme. 12 infants out of 6060 or 0.2% (95% CI 0.1-0.3%) had congenital CMV infection. One boy among the 12 infected infants had unilateral hearing loss, indicating that the risk of hearing loss is greatly increased (about 20 times) in CMV infected infants. No child developed ocular complications such as chorioretinopathy during 3 y of follow-up. Congenital CMV has an impact on child health but can easily be overlooked due to lack of signs in the neonatal period. Surveillance for congenital CMV is important in addition to programmes for prevention and treatment.

Purpose: To report the prevalence of dry-eye syndrome (DES) in children and young adults treated with allogeneic stem-cell transplantation (SCT) during childhood; to relate DES to conditioning regimes, including total body irradiation (TBI) and chemotherapy, and to immunosuppressive drugs and graft-versus-host disease (GVHD). Methods: This cross-sectional study included 60 children ⁄ young adults transplanted because of leukaemia, various haematological disorders and inborn errors of metabolism between 1986 and 2004, with a follow-up time of 7.0 years (median, range 2–18). Clinical assessments, performed at a median age of 15.6 years (range 5.5–23.5), included an inquiry form on dry-eye symptoms, corneal status including fluorescein staining, ‘break-up time’ (BUT) and Schirmer test. Results: A total of 37 of 60 patients had DES defined as presence of corneal epithelial lesions with a pathological BUT and ⁄ or Schirmer test. Twenty-nine had had staining

AIM The aim of this study was to study long-term visual outcome and cataract development in children and adolescents after hematopoietic stem cell transplantation (HSCT) in childhood. METHODS Best corrected visual acuity (BCVA), refraction and lens status were examined in a prospective study of 139 children and adolescents. RESULTS In total, 139 patients (58 female), median age 6.6 years at HSCT (range 0.4-17.5 years), were followed up for a median of 8.0 years (1-19.4 years). Median BCVA in the better eye was 1.0 decimal. Altogether 19 of 131 patients developed cataract requiring surgery, while 46 developed less prominent lens opacities and 66 had clear lenses at time of latest follow-up. Patients conditioned with total body irradiation had a higher risk of developing lens opacities or cataract (p < 0.0001) as did patients with malignant disease, irrespective of irradiation treatment (p < 0.0001). Cumulative analysis showed that 50% of all patients had developed lens opacities/cataract after 10.2 years. Patients who ultimately needed cataract surgery developed cataract earlier than others (p = 0.006). CONCLUSION Lens opacities or cataract were more common in children or adolescents with malignant disease and after conditioning with irradiation. Regular ophthalmological follow-up is important after HSCT for early intervention to avoid amblyopia.

Purpose: To present visual functions and ocular findings in four children with mucopolysaccharidosis I-Hurler (MPS I-H) treated early with stem cell transplantation (SCT). Methods: Clinical ophthalmological evaluations including visual evoked potentials (VEPs) were carried out. Results: Stem cell transplantation was performed before 20 months of age. Ocular follow-up lasted 1.3−5.6 years (median 4.1 years). Reductions in corneal opacities were observed in all four children post-SCT, but a slight cloudiness persisted. Decreased visual acuity and high hyperopia (median + 6.25 dioptres, range + 4.0 D to + 7.5 D spherical equivalents) were noted in all children. Hyperopia was initially undetected due to dull retinal reflexes and photophobia. Two children developed esotropia, one with amblyopia. Keratometry, performed in two children, demonstrated subnormal values with a mean of 39.33 D (range 37.62–41.00 D). Visual evoked potentials and intraocular pressures were normal. Neither cataract nor dry eye were detected during follow-up. Conclusions: Early SCT appears to be beneficial in reducing, but not eliminating, corneal opacities in children with MPS I-H. Subjects are at risk of developing high hyperopia and esotropia. Hyperopia might be caused by the storage of glucosaminoglucans that increase corneal rigidity, thereby straightening the curvature of the cornea and reducing refractive power. As early diagnosis and treatment are very important, paediatric ophthalmologists should remember to rule out MPS I-H in children with corneal opacities.

The objective of this study was to investigate clinical, biochemical, and genetic features in 7 probands (a total of 11 patients) with nicotine-amide adenine dinucleotide (NADH) dehydrogenase (complex I) deficiency. We screened the mitochondrial DNA for mutations and found pathogenic mutations in complex I genes (mitochondrial NADH dehydrogenase subunit (MTND) genes) in three probands. The 10191T〉C mutation in MTND3 and the 14487T〉C mutation in MTND6 were present in two probands with Leigh's-like and Leigh's syndrome, respectively. Four siblings with a syndrome consisting of encephalomyopathy with hearing impairment, optic nerve atrophy, and cardiac involvement had the 11778G〉A mutation in MTND4, previously associated with Leber hereditary optic neuropathy. These findings demonstrate that mutations in MTND genes are relatively frequent in patients with complex I deficiency. Biochemical measurements of respiratory chain function in muscle mitochondria showed that all patients had a moderate decrease of the mitochondrial adenosine triphosphate production rate. Interestingly, the complex I deficiency caused secondary metabolic alterations with decreased oxaloacetate-induced inhibition of succinate dehydrogenase (complex II) and excretion of Krebs cycle intermediates in the urine. Our results thus suggest that altered regulation of metabolism may play an important role in the pathogenesis of complex I deficiency. Ann Neurol 2005

Aim: To analyse pre- and neonatal data and ocular findings in children with visual impairment caused by posterior ocular malformations. Methods: Medical records were scrutinized, dried blood spot cards were analysed for virus DNA and ophthalmological assessments were performed in 28 children with optic nerve hypoplasia (ONH) and 10 with optic/chorio-retinal coloboma. Results: Prenatal exposure to possible teratogens was documented in 5/28, herpes simplex virus type 1 DNA was identified in the dried blood spot cards of 1/26 children and neonatal hypoglycaemia in 12/28 children with ONH. The time delay from ocular to endocrinological diagnosis and treatment was 3 years. Children with ONH and severe visual impairment had endocrinopathy more often (11/13) than ONH children with better visual functions (5/15). Prenatal exposure to teratogens or neonatal hypoglycaemia was not identified in any of the children with coloboma. Conclusion: Neonatal hypoglycaemia was common in children with ONH. Severe visual impairment predicted endocrinopathy. Analysis of dried blood spot cards could serve as an additional diagnostic tool in children with ocular malformations.

Purpose: To present four infants with optic nerve hypoplasia and cholestasis. Methods: All patients underwent detailed ophthalmological and hepatological assessment. Their endocrinological and neuroradiological examinations were re-evaluated. Results: All four infants presented with cholestasis and were subsequently found to have optic nerve hypoplasia. One child was blind according to the WHO definition and two had low vision. The fourth child had unilateral optic nerve hypoplasia and was too young to be assessed with optotypes. All four children had central nervous system and/or endocrine dysfunction. However, only one child had septo-optic dysplasia. The longterm outcome of liver disease seemed favourable in all children. Conclusion: Early assessment by a paediatric ophthalmologist as well as a multidisciplinary approach is of great importance in cholestatic infants.

Aim Although cytomegalovirus (CMV) is the most common congenital infection, existing research has not provided us with a full picture of how this can affect children in the future. The aim of this case–control study was to evaluate disabilities in a well-defined group of children with congenital cytomegalovirus (CMV) infection, who had been fitted with cochlear implants because of severe hearing impairment. Methods A multidisciplinary team assessed 26 children with congenital CMV infection for balance difficulties, neurodevelopmental disabilities and language and visual impairment. We also included a control group of 13 children with severe hearing impairment due to connexin 26 mutations. Results The majority of the children with congenital CMV infection (88%) displayed balance disturbances, including walking at a later age, but there were no cases in the control group. The CMV group also displayed frequent neurodevelopmental disabilities and feeding difficulties. Conclusion Congenital CMV infection affects the general development of the brain and gives rise to a complex pattern of difficulties. Identifying comorbid conditions is very important, as children with associated difficulties and disabilities need more support than children with just hearing impairment. Congenital CMV infection needs to be considered in children with hearing impairment and/or balance disturbance and/or neurodevelopmental disabilities.

Purpose: To describe a child with Muscle-Eye-Brain disease (MEB), one of three types of congenital muscular dystrophy associated with ocular abnormalities. Methods: Case report. Results: The child showed severe visual impairment due to progressive myopia and retinal degeneration, a pachygyria-type of migration disorder of the brain with a nodular cortical surface, i.e. cobblestone cortex, as well as muscular weakness and severe mental retardation. Conclusion: Ophthalmological assessments are important to help to diagnose and follow children with congenital muscular dystrophy.

Purpose: To prospectively study the incidence of structural and/or functional ophthalmological abnormalities in the offspring to an unselected population of women with epilepsy, subjected to a well controlled antiepileptic drug (AED) treatment during pregnancy. Methods: Forty-three children prenatally exposed to antiepileptic drugs and 47 controls were included. Blinded ophthalmological examinations including fundus photography were performed at a median age of 7 years and 4 months. Results: No major eye anomalies were found except in one child in the exposed group who had nystagmus and low vision. The visual acuity was lower in the eye with lowest acuity among the exposed children (p∞0.05). No other significant difference was found between the two groups. Conclusion: The results suggest that a well-controlled treatment with AEDs, preferably monotherapy, during pregnancy does not have any major adverse effects on the development of the eye and ophthalmological functions.

Vision loss in children may be of sudden onset or may be long standing but suddenly discovered. The neurologist must determine which children need urgent diagnostic neurologic or ophthalmic evaluation. Systematic assessment of visual acuity, eye movements, pupil response, visual fields, and optic nerve and fundus evaluation will enable the practitioner to refine the differential diagnosis and streamline evaluation and treatment. For parents, there are few conditions that are more anxiety provoking than the discovery that their child has poor vision in one or both eyes. Their concern is often in contrast to the child’s seeming indifference to the poor vision or wandering eye. There are also patients without any obvious visual loss where eye examinations may help diagnose neurologic damage, like retinal hemorrhages, suggestive, for example, for shaken baby syndrome. In this chapter, we will provide the clinician with a systematic approach to the child with apparent sudden onset of poor vision, strabismus, or abnormal pupil.

To report prevalence, ocular characteristics and coexisting behavioural problems in children and adolescents with optic nerve hypoplasia (ONH), which is a common cause of visual impairment in children in western countries, often associated with neurological or endocrinological problems and where autism has been reported in severe cases with blindness.This is a population-based cross-sectional study of patients20 years of age who had been diagnosed with ONH and lived in the county of Stockholm in December 2009. Ophthalmological assessments including fundus photographs with optic disc analyses were made. A questionnaire was used to screen for behaviour and development.The prevalence of ONH in all living children18 years of age in Stockholm was 17.3/100 000 with a prevalence of visual impairment (0.3) of 3.9/100 000. In total, 66 patients, median age 9.3 years (0.6-19.4), 36 with bilateral and 30 with unilateral ONH, were included in the current study; 53 were re-examined clinically, group A, and 13 agreed to retrospective analyses of existing medical records, group B. Analyses of the optic discs were made in fundus photographs from 53 patients comparing a semi-automated (Retinal Size Tool) and a manual method (Zeki). There was a strong curvilinear correlation (r(S) = -0.91 p 0.0001 for both eyes). Behavioural problems were more common (p 0.05) in bilateral ONH.Optic nerve hypoplasia is a common ocular malformation with a prevalence of 17.3/100 000 children and adolescents18 years of age in Stockholm. Unilateral ONH seems as common as bilateral.

Background/aims: To assess corneal refraction and axial length in children with mucopolysaccharidosis I-Hurler (MPS I-H), treated early with stem cell transplantation (SCT), in order to establish possible causes of hyperopia. Methods: Clinical ophthalmological follow-up included keratometry and measurements of axial length. Results: Five patients, with SCT performed before 23 months of age, were examined. Median age was 8.2 years (range 5.2–10.5). Best-corrected decimal visual acuity was ≥0.5 (≥20/40 Snellen fraction) in seven of 10 eyes. High hyperopia, ranging from +4.0 to +9.0 spherical equivalents, was noted in all 10 eyes. Mild to moderate corneal opacities occurred in all 10 eyes. Optic disc areas, borders and cuppings were normal in all 10 eyes. No patient had glaucoma. Keratometry could be performed in five patients and demonstrated low values in the group ranging from 38.24 to 41.56 Diopters (D) right eye to 38.24–41.94 D left eye, which was significantly lower than the age matching reference material (p

The aims of the present study were to investigate visual function, ocular motility and ocular characteristics in children and young adults with complex I deficiency.In a prospective study with longitudinal follow-up, the visual and ocular outcome in 13 patients with deficiency in complex I [nicotine-amide adenine dinucleotide (NADH) dehydrogenase] in the mitochondrial respiratory chain is presented. The patients were diagnosed during 1995-2007 and assessed during 1997-2009 at a median age of 12.8 years (range 3.1-23.4).Twelve of 13 patients had visual impairment and/or ocular pathology. Four of 10 patients who co-operated in visual assessment had a best corrected decimal visual acuity of ≤ 0.5 in one or both eyes. Cataract surgery was performed in one patient and another patient showed retinal pigmentations and ptosis. Eleven patients demonstrated ocular motility problems, mainly saccade deficiencies. Five patients had optic atrophy (OA), which was bilateral in four patients. In four siblings, the OA showed a similarity to Leber's Hereditary Optic Neuropathy. These patients also had the 11778 G → A mutation in mitochondrial DNA. Only one patient had normal visual acuity and ocular outcome including refraction and visual fields. Follow-up time was median 3.0 years (range 0-11).Visual impairment, ocular motility problems and OA are common in children and young adults with complex I deficiency and should prompt the paediatric ophthalmologist to consider mitochondrial disorders.

PURPOSE To present long-term ocular complications and electroretinographic (ERG) findings in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency - a life-threatening metabolic disease - and the relation to age at diagnosis, treatment and other clinical parameters. METHODS Ten children with LCHAD deficiency underwent repeated ophthalmological evaluations including ERG. RESULTS All 10 children developed chorioretinal pathology. Regardless of age at diagnosis, initiation of treatment and age at examination, inter-individual differences were present. Profound chorioretinal atrophy, severe visual impairment and progressive myopia had developed in two teenagers. Milder chorioretinopathy with or without subnormal visual acuity was present in all other children. ERG was pathological in seven children. The chorioretinopathy often started in the peripapillary or perimacular areas. In one patient, unilateral visual impairment was associated with fibrosis. CONCLUSION Early diagnosis and adequate therapy might delay but not prevent the progression of retinal complications. Late diagnosis with severe symptoms at diagnosis, neonatal hypoglycaemia and frequent decompensations may increase the progression rate of the chorioretinopathy. LCHAD deficiency, a potentially lethal disease, is sometimes difficult to diagnose. Unusual chorioretinal findings should alert the ophthalmologist to the long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, especially if there is a history of neonatal hypoglycaemia or failure to thrive.

Purpose: To report visual functions and prevalence of cataract after haematopoetic stem-cell transplantation (SCT) during childhood and to determine the impact of different conditioning regimes and other possible risk factors. Methods: Assessment of visual acuity (VA), slit-lamp biomicroscopy of the lenses and examination of the ocular fundii were performed in 79 subjects 2–18 years (median 7 years) after SCT. Results: Best-corrected decimal VA ‡ 0.5 was achieved in 152 ⁄ 158 eyes (96%). There was an increased risk of cataract after conditioning with singledose total body irradiation (s-TBI) or fractionated TBI (f-TBI) compared to busulfan or other chemotherapy ( P< 0.001) and an increased risk of developing cataract earlier if treated with s-TBI compared to f-TBI ( P< 0.01). The TBI mode did not affect the time to first surgical intervention. Apart from s-TBI and f-TBI, age was found to be an independent risk factor. Cataract also developed in patients prepared with chemotherapy but no patient required surgery. Neither treatment with steroids for 6 months or longer nor history of chronic graft versus host disease (GVHD) influenced cataract development. Conclusion: Conditioning with full dose f-TBI compared to s-TBI postpones but does not prevent cataract or cataract surgery while chemotherapy-based conditioning induces less severe cataracts, usually not requiring surgery. Corticosteroids or GVHD do not appear as risk factors.

To present four infants with optic nerve hypoplasia and cholestasis.All patients underwent detailed ophthalmological and hepatological assessment. Their endocrinological and neuroradiological examinations were re-evaluated.All four infants presented with cholestasis and were subsequently found to have optic nerve hypoplasia. One child was blind according to the WHO definition and two had low vision. The fourth child had unilateral optic nerve hypoplasia and was too young to be assessed with optotypes. All four children had central nervous system and/or endocrine dysfunction. However, only one child had septo-optic dysplasia. The longterm outcome of liver disease seemed favourable in all children.Early assessment by a paediatric ophthalmologist as well as a multidisciplinary approach is of great importance in cholestatic infants.