Visual functions, ocular characteristics and visual quality of life in patients with homocystinuria.

BACKGROUND: Homocystinuria (HCU) is a rare metabolic disease that affects many organs, including the eyes. Aims: to assess visual functions, ocular characteristics, visual quality of life and time from the onset of ocular manifestations to HCU-diagnosis in patients with HCU. MATERIAL AND METHODS: Eighteen patients underwent ophthalmological examinations and visual quality of life questionnaires. RESULTS: Best corrected decimal visual acuity was median 1.0 (range amaurosis - 1.3) right eye and 1.0 (range amaurosis -1.3) left eye. Five patients presented with severe myopia as first HCU manifestation, duration to HCU diagnosis was mean 13.6 years (range 2-25). Two patients had suffered ectopia lentis as first HCU manifestation, HCU diagnosis was established mean 8.0 years (range 7-9) later. One patient had suffered both from thrombosis and ectopia lentis prior to diagnosis. Another four patients suffered thromboembolic events before diagnosis. Median VFQ-25 composite score was 93 (68-98). CONCLUSIONS: The prevalence of myopia, ectopia lentis and monocular blindness was high in HCU-patients, which was reflected in their visual quality of life. Diagnosis was often delayed after the first ocular manifestation, increasing the risk of other severe non-ocular complications.

Treatment for retinopathy of prematurity in Sweden 2008-2021: Reduced gestational age of treated infants and remaining differences in treatment type and recurrence rates between hospitals.

PURPOSE: This study aimed to investigate various aspects of treatment for retinopathy of prematurity (ROP) in Sweden over the past 14 years, nationally and at a hospital level. METHODS: Data on screening and treatment for ROP in infants born in Sweden from 2008 to 2021 were extracted from the national ROP register, SWEDROP. During this period, Swedish screening guidelines were reduced from gestational age (GA) < 32 weeks to <31 weeks in 2012 and to <30 weeks in 2020. RESULTS: Altogether, 10 959 infants were screened and 600 infants treated for ROP during the study period. Parallel to changed guidelines, the number of screened infants decreased (p < 0.000) and the incidence of ROP and frequency of treatment increased (p < 0.001), while both remained similar in infants with a GA below 30 weeks. Among treated infants, GA and BW were reduced over the years (p < 0.001). Laser treatment (85.2% of primary treatments) became less common and anti-VEGF injections (13.6%) became more common over time (p < 0.001). Altogether 16 eyes were treated with the encircling band and 13 with vitrectomy. The total frequency of retreatment (32.7% of treated eyes) remained similar over time but was more common after primary anti-VEGF injection (67.7%) than laser treatment (27.2%). There were differences between the seven university hospitals regarding type of treatment and number of retreatments (p < 0.001). CONCLUSION: The frequency of treatment and retreatment for ROP remained similar over time, but the type of treatment changed and anti-VEGF injections became more common. Differences between treating hospitals emphasize the importance of centralizing the most severe cases.

Ophthalmological outcome of 6.5 years children treated for retinopathy of prematurity: a Swedish register study.

AIMS: To 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. METHODS: Data 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. RESULTS: Follow-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. CONCLUSION: The 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.

Optical Coherence Tomography Can Predict Visual Acuity in Children with Optic Nerve Hypoplasia.

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.

Anophthalmia and microphthalmia in children: associated ocular, somatic and genetic morbidities and quality of life.

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.

Visual and ocular findings in a family with X-linked cone dysfunction and protanopia.

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.

Whole genome sequencing unveils genetic heterogeneity in optic nerve hypoplasia.

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.

High prevalence of pituitary hormone deficiency in both unilateral and bilateral optic nerve hypoplasia.

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 < 0.001). In addition, 9% had cerebral palsy and 14% had epilepsy. The prevalence of PHD was 29 and 19% had multiple PHD. CONCLUSION: Children with ONH had a high risk of neurological impairment, especially in bilateral disease. Both unilateral and bilateral ONH signified an increased prevalence of PHD and all these children should be endocrinologically followed up until completed puberty.

Optic Disc Coloboma in children - prevalence, clinical characteristics and associated morbidity.

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.

Children with mucopolysaccharidosis risk progressive visual dysfunction despite haematopoietic stem cell transplants.

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.

Children with optic nerve hypoplasia face a high risk of neurodevelopmental disorders.

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.

Outcomes of keratoplasty in the mucopolysaccharidoses: an international perspective.

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.

Cataract after allogeneic hematopoietic stem cell transplantation in childhood.

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.

Chorioretinal scars and visual deprivation are common in children with cochlear implants after congenital cytomegalovirus infection.

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.

Ocular Motor Score (OMS): a clinical tool to evaluating ocular motor functions in children. Intrarater and inter-rater agreement.

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.

Optic nerve hypoplasia in children and adolescents; prevalence, ocular characteristics and behavioural problems.

PURPOSE: 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. METHODS: This is a population-based cross-sectional study of patients <20 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. RESULTS: The prevalence of ONH in all living children <18 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. CONCLUSION: Optic nerve hypoplasia is a common ocular malformation with a prevalence of 17.3/100 000 children and adolescents <18 years of age in Stockholm. Unilateral ONH seems as common as bilateral.

Congenital CMV infection: prevalence in newborns and the impact on hearing deficit.

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.

Risk of visual impairment in children with congenital toxoplasmic retinochoroiditis.

PURPOSE: Reliable information is needed to counsel parents of children with congenital toxoplasmosis regarding the long-term risk of visual impairment resulting from ocular toxoplasmosis. DESIGN: Prospective cohort study of children with congenital toxoplasmosis identified by prenatal or neonatal screening. METHODS: After three years of age, ophthalmologists reported the site of retinochoroidal lesions and visual acuity and parents reported visual impairment. An ophthalmologist predicted the child's vision based on the last retinal diagram. Selection biases were minimized by prospective enrollment and data collection, high rates of follow-up, and exclusion of referred cases. RESULTS: Two hundred and eighty-one of 284 infected children who underwent ophthalmic examinations were followed up to a median age of 4.8 years. One in six children (49/281; 17%) had at least one retinochoroidal lesion, two-thirds of whom (32/49; 65%) had a lesion at the posterior pole. In children with retinochoroiditis who had visual acuity measured after 3 years of age, 94% (31/33) had normal vision in the best eye (6/12 Snellen or better), as did 91% of those with a posterior pole lesion (21/23). Analyses based on affected eyes showed that 42% (29/69) had a posterior pole lesion, of which just more than half (15/29, 52%) had normal vision, as did 84% (16/19) of eyes with a peripheral lesion alone. Vision predicted by the ophthalmologist was moderately sensitive (59%) but overestimated impairment associated with posterior pole lesions. Of 44 children with information on acuity, four (9%) had bilateral visual impairment worse than 6/12 Snellen. CONCLUSIONS: Severe bilateral impairment occurred in 9% of children with congenital toxoplasmic retinochoroiditis. Half the children with a posterior pole lesion and one in six of those with peripheral lesions alone were visually impaired in the affected eye.

Secondary metabolic effects in complex I deficiency.

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.