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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.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos da Percepção/etiologia , Transtornos Psicomotores/etiologia , Desempenho Psicomotor , Transtornos da Visão/etiologia , Acuidade Visual , Percepção Visual , Adolescente , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/psicologia , Humanos , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Transtornos da Percepção/diagnóstico , Transtornos Psicomotores/diagnóstico , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transtornos da Visão/diagnósticoRESUMO
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.
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Córnea/fisiopatologia , Transplante de Células-Tronco Hematopoéticas , Mucopolissacaridoses/complicações , Retina/fisiopatologia , Transtornos da Visão/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Mucopolissacaridoses/fisiopatologia , Mucopolissacaridoses/terapia , Estudos Prospectivos , Refração Ocular , Estrabismo , Acuidade Visual , Adulto JovemRESUMO
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.
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Catarata/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Catarata/diagnóstico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Adulto JovemRESUMO
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.
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Corioide/patologia , Cicatriz/epidemiologia , Infecções por Citomegalovirus/congênito , Perda Auditiva Neurossensorial/terapia , Retina/patologia , Transtornos da Visão/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Cicatriz/patologia , Implante Coclear , Implantes Cocleares , Conexina 26 , Conexinas , Feminino , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/patologia , Humanos , Lactente , Masculino , Transtornos da Visão/patologiaRESUMO
PURPOSE: The purpose of this study was to evaluate the optic disc and macula in a large cohort of patients with different severity of optic nerve hypoplasia (ONH) using high-resolution spectral domain optical coherence tomography (SD-OCT). METHODS: In total, 36 patients (52 ONH eyes and 17 fellow eyes in unilateral cases) and 45 healthy right eyes from 45 controls were evaluated. All patients underwent an examination to confirm the diagnosis. SD-OCT images of the disc and macula were obtained and analysed both quantitatively and qualitatively. RESULTS: OCT in ONH eyes demonstrated a shorter disc diameter (1061 ± 375 µm vs. 1751 ± 221 µm, p < 0.001), shallower mean cup depth (427 ± 171 µm vs. 551 ± 152 µm, p = 0.01), thinner ganglion cell complex (GCC) perifoveally (47.3 ± 13.0 µm, 60.8 ± 6.0 µm, p < 0.001) and reduced foveal depth (61 ± 36 µm, 119 ± 19 µm, p < 0.001) compared to control eyes. Qualitative analysis showed that 1/3rd of ONH eyes lacked signs of an optic cup, and 2/3rd had reduced or no sign of a foveal pit. Fellow eyes had shorter disc diameter (1446 ± 404 µm vs. 1751 ± 221 µm, p = 0.004) and reduced foveal depth (93 ± 27 µm vs. 119 ± 19 µm, p < 0.001) but similar GCC thickness (60.8 ± 7.1 µm vs. 60.8 ± 6.0 µm, p = 0.738) compared to controls. Disc diameter showed the best correlation with visual acuity in ONH eyes (ρ = 0.517, p < 0.001). CONCLUSION: ONH eyes have reduced GCC thickness and reduced or no foveal pit. Fellow eyes in presumed unilateral cases have a smaller disc diameter and reduced foveal depth compared to controls, suggesting the possibility of subclinical/mild disease. However, GCC thickness was normal. The correlation between structure and visual function is not always straightforward.
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PURPOSE: To report ocular outcome, somatic co-morbidities, genetics, and quality of life in children born with anophthalmia (A) or microphthalmia (M). METHODS: 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). RESULTS: 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 (p < .01). There was an increased risk for heart defects in children with psychomotor delay (p = .04). Pathogenic genetic abnormalities were identified in 10/24 cases. Neuroimaging demonstrated pathology in 14/20 cases with corpus callosum dysgenesis (6/20) being the most common. The median total PedsQL score of parent reports for ages 2-12 was 52.4 (range 22.6-100). CONCLUSIONS: 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.
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Anoftalmia , Microftalmia , Anoftalmia/epidemiologia , Anoftalmia/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Microftalmia/diagnóstico , Microftalmia/epidemiologia , Microftalmia/genética , Morbidade , Qualidade de VidaRESUMO
Purpose: 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.
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BACKGROUND: Fabry disease (FD) is an X-linked lysosomal disease, in which diagnosis is often established several years after onset of symptoms. Ocular manifestations can occur in childhood and be a clue to earlier diagnosis. The aim was to report ocular outcome and visual quality of life (QoL) in patients with FD. MATERIAL AND METHODS: FD-patients recruited from Karolinska University Hospital underwent ophthalmological examinations including best corrected visual acuity (BCVA), refraction, biomicroscopy, optical coherence tomography, keratometry, review of medical records and QoL Inventories. A total severity score (TSS), as estimated via Fabry Stabilization Index, was calculated. RESULTS: Twenty-six FD-patients (16 men) mean age 36.4 years (range 5.0-63.5 years) were included. BCVA was median 1.0 (range 0.5-1.6). Conjunctival blood vessel tortuosity occurred in 15/26 patients, chemosis in 2/26 patients, cornea verticillata in 23/26 patients, lens opacities in 19/26 patients, and tortuous or dilated retinal vessels in 20/25 patients. Group-wise comparisons of adult patients showed no differences regarding age, TSS, or ocular parameters. Overall, TSS was correlated to age (r = 0.53, p = 0.02). A linear regression model showed that age and sex explained 38% of the variance in TSS. Keratometry did not reveal corneal ectasia in any of the 12 patients examined. VFQ 25 in 15 patients showed a high median composite score, 93.6 (range: 78.1-100). CONCLUSIONS: BCVA in FD-patients was good despite corneal and lens pathology. Ocular variables did not show an association with TSS in adult patients. Corneal or lens opacities should also lead to a suspicion of FD in children.
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Catarata , Doenças da Túnica Conjuntiva , Doença de Fabry , Adulto , Masculino , Criança , Humanos , Pré-Escolar , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Doença de Fabry/complicações , Doença de Fabry/diagnóstico , Doença de Fabry/patologia , Qualidade de Vida , Doenças da Túnica Conjuntiva/diagnóstico , Catarata/patologia , Vasos Retinianos/patologiaRESUMO
Background: Bornholm eye disease (BED) is a rare X-linked cone dysfunction disorder with high myopia, amblyopia, and color vision defects.Materials and methods: Visual and ocular outcomes in a family where two of five siblings had molecularly confirmed BED are reported. Ophthalmological assessments included best-corrected visual acuity (BCVA), color vision test, and optical coherence tomography (OCT). Medical records, electroretinography (ERG), and genetic analyses were re-evaluated.Results: Two male siblings had confirmed BED with myopia and protanopia. The younger brother had high myopia, subnormal BCVA, and ocular fundi that showed tilted discs, crescent shaped peripapillary atrophy, and visible choroidal vessels. OCT confirmed retinal and choroidal atrophy. The older brother was lightly myopic with normal/subnormal BCVA and subtle findings in the fundi. Both brothers had abnormal ERG recordings with a decreased cone response. They also had a structurally intact OPN1LW/OPN1MW gene cluster. The OPN1LW gene was shown to carry a deleterious variant combination in exon 3 known to result in mis-splicing of opsin mRNA and acknowledged as LIAVA amino acid delineation (Leu153-Ile171-Ala174-Val178-Ala180), while the OPN1MW gene exon 3 showed a non-pathogenic variant combination (MVVVA). Another normal-sighted brother carried another wildtype variant combination (LVAIS) in exon 3 of the OPN1LW gene.Conclusions: The two affected brothers demonstrated a large variability in their phenotypes even though the genotypes were identical. They presented a disease-associated haplotype in exon 3 of OPN1LW that has been described as the molecular cause of BED.
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Ambliopia/genética , Defeitos da Visão Cromática/genética , Éxons/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Miopia Degenerativa/genética , Miopia/genética , Opsinas de Bastonetes/genética , Acuidade Visual/fisiologia , Adolescente , Ambliopia/diagnóstico , Ambliopia/fisiopatologia , Percepção de Cores/fisiologia , Testes de Percepção de Cores , Defeitos da Visão Cromática/diagnóstico , Defeitos da Visão Cromática/fisiopatologia , Eletrorretinografia , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Humanos , Masculino , Miopia/diagnóstico , Miopia/fisiopatologia , Miopia Degenerativa/diagnóstico , Miopia Degenerativa/fisiopatologia , Fenótipo , Retina/fisiopatologia , Perfil de Impacto da Doença , Tomografia de Coerência Óptica , Campos Visuais/fisiologia , Adulto JovemRESUMO
A randomised comparison was made between high and normal diuresis during the primary session of extracorporeal shock wave lithotripsy (SWL) for removal of ureteral stones. High diuresis was accomplished by pressure infusion of approximately 1 L of Ringer acetate solution together with 20 mg of furosemide during the 30-40 min treatment session (Group D). These patients also had a bladder catheter. Patients in Group 0 had a normal diuresis and no bladder catheter. The mean (SD) number of treatment sessions for the 65 patients in Group D were 1.26 (0.51) and for the 60 patients from Group 0 1.35 (0.84) [p > 0.10]. 51 (78%) and 46 (77%) patients in Group D and Group 0, respectively, required only one SWL session. Stones were located in the proximal, mid and distal ureter in 22, 9, and 29 of the patients in Group D and in 22, 5, and 38 in Group 0. No difference in treatment outcome was observed with regard to stone localisation. The stone treatment index (STI(GR)) calculated for Group D and Group 0 were 4.77 and 4.70, respectively. In conclusion there was no obvious advantage of using a forced diuresis during the primary SWL-session for treating patients with ureteral stones. Although a high diuresis and bladder catheter might be beneficial in certain complicated cases, in most situations it seems appropriate to omit this step.
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Diuréticos/uso terapêutico , Litotripsia , Cálculos Ureterais/terapia , Feminino , Humanos , Masculino , Indução de RemissãoRESUMO
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 < 0.0001). Nystagmus was observed more often in patients with bilateral ODC (9/13 versus 3/17, p = 0.004). Two patients had retinal detachment. Behavioural/psychological screening was performed in 21 patients with severe deficits identified in six cases. Intellectual disability was present in seven patients. Neurological dysfunction was diagnosed in 8/22 cases. All of the above children had already systemic diagnoses before the ODC diagnosis was made. CONCLUSIONS: ODC was the second most common optic disc malformation in this cohort after optic nerve hypoplasia. The children had a wide range of ocular comorbidity. An isolated ODC without macular involvement was not associated with profound vision loss. The ability of screening in the regular child care centres to diagnose extraocular comorbidities was very good and referral to a paediatrician appears redundant in cases of normal development.
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Coloboma/epidemiologia , Disco Óptico/anormalidades , Nervo Óptico/anormalidades , Vigilância da População , Acuidade Visual , Adolescente , Criança , Pré-Escolar , Coloboma/diagnóstico , Coloboma/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Morbidade/tendências , Disco Óptico/diagnóstico por imagem , Nervo Óptico/fisiopatologia , Prevalência , Estudos Retrospectivos , Suécia/epidemiologiaRESUMO
INTRODUCTION: This efficacy study investigated the effects of 1) Olympic-style weightlifting (OWL), 2) motorized strength and power training (MSPT), and 3) free weight strength and power training (FSPT) on muscle power. METHODS: Thirty-nine young athletes (20 ± 3 yr; ice hockey, volleyball, and badminton) were randomized into the three training groups. All groups participated in two to three sessions per week for 8 wk. The MSPT and FSPT groups trained using squats (two legs and single leg) with high force and high power, whereas the OWL group trained using clean and snatch exercises. MSPT was conducted as slow-speed isokinetic strength training and isotonic power training with augmented eccentric load, controlled by a computerized robotic engine system. FSPT used free weights. The training volume (sum of repetitions × kg) was similar between all three groups. Vertical jumping capabilities were assessed by countermovement jump (CMJ), squat jump (SJ), drop jump (DJ), and loaded CMJ (10-80 kg). Sprinting capacity was assessed in a 30-m sprint. Secondary variables were squat one-repetition maximum (1RM), body composition, quadriceps thickness, and architecture. RESULTS: OWL resulted in trivial improvements and inferior gains compared with FSPT and MSPT for CMJ, SJ, DJ, and 1RM. MSPT demonstrated small but robust effects on SJ, DJ, loaded CMJ, and 1RM (3%-13%). MSPT was superior to FSPT in improving 30-m sprint performance. FSPT and MSPT, but not OWL, demonstrated increased thickness in the vastus lateralis and rectus femoris (4%-7%). CONCLUSIONS: MSPT was time-efficient and equally or more effective than FSPT training in improving vertical jumping and sprinting performance. OWL was generally ineffective and inferior to the two other interventions.
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Força Muscular/fisiologia , Treinamento Resistido/métodos , Levantamento de Peso/fisiologia , Desempenho Atlético/fisiologia , Composição Corporal , Feminino , Humanos , Extremidade Inferior/fisiologia , Masculino , Exercício Pliométrico , Adulto JovemRESUMO
PURPOSE: Ocular motor score (OMS) is a new clinical test protocol for evaluating ocular motor functions in children and young adults. OMS is a set of 15 important and relevant non-invasive ocular motor function parameters derived from clinical practice. The aim of the study was to evaluate OMS according to intrarater and inter-rater agreement. METHODS: Forty children aged 4-10 years, 23 girls median age 6.5 (range 4.3-9.3) and 17 boys median age 5.8 (range 4.1-9.8) were included. The ocular motor functions were assessed and scored according to the OMS protocol. The examinations were videotaped. To obtain the intrarater agreement, the first author examined and scored the children twice, first in the clinic and 2 weeks later by watching the videotape. To obtain the inter-rater agreement, three other raters independently scored the ocular motor function of the children by watching the videotapes. RESULTS: The overall observed intrarater agreement was 88%, and the observed inter-rater agreement between the three raters was 80%. For none of the subtests was there an observed intrarater agreement lower than 65%. Three of the subtests had an observed inter-rater agreement of 65% or below. CONCLUSION: Overall there was high observed intra- and inter-rater agreement for the OMS test protocol. Subtests such as saccades and smooth pursuit were more difficult for raters to score similarly according the clinical OMS test protocol.
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Técnicas de Diagnóstico Oftalmológico , Transtornos da Motilidade Ocular/diagnóstico , Músculos Oculomotores/fisiologia , Criança , Pré-Escolar , Feminino , Fixação Ocular/fisiologia , Humanos , Masculino , Nistagmo Optocinético/fisiologia , Variações Dependentes do Observador , Transtornos da Motilidade Ocular/fisiopatologia , Reflexo Vestíbulo-Ocular/fisiologia , Reprodutibilidade dos Testes , Gravação em VídeoRESUMO
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.
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Anormalidades do Olho/epidemiologia , Disco Óptico/anormalidades , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Anormalidades do Olho/fisiopatologia , Feminino , Humanos , Pressão Intraocular , Masculino , Nistagmo Patológico/fisiopatologia , Nervo Oculomotor/fisiopatologia , Distúrbios Pupilares/fisiopatologia , Reflexo Vestíbulo-Ocular/fisiologia , Refração Ocular/fisiologia , Retinoscopia , Estrabismo/fisiopatologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Adulto JovemRESUMO
Mitochondrial DNA (mtDNA) polymerase γ (POLγ) harbours a 3'-5' exonuclease proofreading activity. Here we demonstrate that this activity is required for the creation of ligatable ends during mtDNA replication. Exonuclease-deficient POLγ fails to pause on reaching a downstream 5'-end. Instead, the enzyme continues to polymerize into double-stranded DNA, creating an unligatable 5'-flap. Disease-associated mutations can both increase and decrease exonuclease activity and consequently impair DNA ligation. In mice, inactivation of the exonuclease activity causes an increase in mtDNA mutations and premature ageing phenotypes. These mutator mice also contain high levels of truncated, linear fragments of mtDNA. We demonstrate that the formation of these fragments is due to impaired ligation, causing nicks near the origin of heavy-strand DNA replication. In the subsequent round of replication, the nicks lead to double-strand breaks and linear fragment formation.
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Replicação do DNA , DNA Mitocondrial/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo , Animais , Southern Blotting , DNA Polimerase gama , DNA Polimerase Dirigida por DNA/genética , Exodesoxirribonucleases/metabolismo , Humanos , Camundongos , Reação em Cadeia da Polimerase , Células Sf9 , SpodopteraRESUMO
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 < 0.001). CONCLUSION: This study provides reference values for the OMS test in a population aged 0.5-19 years. The test may be valuable as a screening tool for identification and follow-up of ocular motor dysfunction in children and young adults.
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Técnicas de Diagnóstico Oftalmológico , Movimentos Oculares/fisiologia , Músculos Oculomotores/fisiologia , Adolescente , Criança , Pré-Escolar , Convergência Ocular/fisiologia , Feminino , Fixação Ocular/fisiologia , Cabeça/anatomia & histologia , Humanos , Lactente , Masculino , Nistagmo Optocinético/fisiologia , Nistagmo Fisiológico/fisiologia , Postura/fisiologia , Pupila/fisiologia , Acompanhamento Ocular Uniforme/fisiologia , Valores de Referência , Reflexo Vestíbulo-Ocular/fisiologia , Movimentos Sacádicos , Adulto JovemRESUMO
The mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans in several tissues and organs. This accumulation results in an array of clinical manifestations and premature death in severe cases. Ocular problems are very common in children with MPS and may involve the cornea, sclera, trabecular meshwork, retina, optic nerve and also the posterior visual pathways. The aims of this study are to give an overview of ocular problems in MPS and to provide clinical guidelines for paediatric ophthalmologists for early diagnosis and management of ocular manifestations in children with MPS. Diagnostic problems may arise in children with severe corneal clouding, hampering visualization of the fundus. Intraocular pressures may be falsely high, even leading to suspicion and unnecessary pressure-lowering treatment. Simple interventions such as the use of prescription glasses or photochromatic glasses can considerably improve quality of life in children with MPS.
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Oftalmopatias/diagnóstico , Mucopolissacaridoses/diagnóstico , Guias de Prática Clínica como Assunto , Criança , Pré-Escolar , Técnicas de Diagnóstico Oftalmológico , Oftalmopatias/terapia , Óculos , Humanos , Lactente , Recém-Nascido , Mucopolissacaridoses/terapia , Qualidade de VidaRESUMO
PURPOSE: 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. MATERIAL AND METHODS: 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). RESULTS: 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 â 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). CONCLUSION: 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.
Assuntos
Doenças Mitocondriais/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Atrofia Óptica/diagnóstico , Transtornos da Visão/diagnóstico , Acuidade Visual/fisiologia , Adolescente , Criança , Pré-Escolar , Complexo I de Transporte de Elétrons/deficiência , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças Mitocondriais/fisiopatologia , Transtornos da Motilidade Ocular/fisiopatologia , Atrofia Óptica/fisiopatologia , Prevalência , Estudos Prospectivos , Transtornos da Visão/fisiopatologia , Campos Visuais/fisiologia , Adulto JovemRESUMO
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.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Disco Óptico/patologia , Doenças do Nervo Óptico/etiologia , Transtornos da Visão/etiologia , Campos Visuais , Adolescente , Antineoplásicos/administração & dosagem , Catarata/etiologia , Extração de Catarata , Criança , Síndromes do Olho Seco/etiologia , Feminino , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Imunossupressores/administração & dosagem , Implante de Lente Intraocular , Leucemia/terapia , Masculino , Doenças do Nervo Óptico/diagnóstico , Tonometria Ocular , Condicionamento Pré-Transplante , Transplante Homólogo , Transtornos da Visão/diagnóstico , Testes de Campo Visual , Irradiação Corporal Total , Adulto JovemRESUMO
The herpes simplex virus replicon consists of cis-acting sequences, oriS and oriL, and the origin binding protein (OBP) encoded by the UL9 gene. Here we identify essential structural features in the initiator protein OBP and the replicator sequence oriS, and we relate the appearance of these motifs to the evolutionary history of the alphaherpesvirus replicon. Our results reveal two conserved sequence elements in herpes simplex virus type 1, OBP; the RVKNL motif, common to and specific for all alphaherpesviruses, is required for DNA binding, and the WP XXXGAXXFXX L motif, found in a subset of alphaherpesviruses, is required for specific binding to the single strand DNA-binding protein ICP8. A 121-amino acid minimal DNA binding domain containing conserved residues is not soluble and does not bind DNA. Additional sequences present 220 amino acids upstream from the RVKNL motif are needed for solubility and function. We also examine the binding sites for OBP in origins of DNA replication and how they are arranged. NMR and DNA melting experiments demonstrate that origin sequences derived from many, but not all, alphaherpesviruses can adopt stable boxI/boxIII hairpin conformations. Our results reveal a stepwise evolutionary history of the herpes simplex virus replicon and suggest that replicon divergence contributed to the formation of major branches of the herpesvirus family.