Viral shedding, and distribution of cytomegalovirus glycoprotein H (UL75), glycoprotein B (UL55), and glycoprotein N (UL73) genotypes in congenital cytomegalovirus infection.

BACKGROUND: Children with congenital CMV infection (cCMV) shed virus in urine and saliva for prolonged periods of time. Outcome of cCMV varies from asymptomatic infection with no sequelae in most cases, to severe longterm morbidity. The factors associated with asymptomatic cCMV are not well defined. We evaluated the viral shedding in a cohort of infants with cCMV identified on newborn screening. In addition, we describe the distribution of viral genotypes in our cohort of asymptomatic infants and previous cohorts of cCMV children in the literature. METHODS: Study population consisted of 40 children with cCMV identified in screening of 19,868 infants, a prevalence of 2/1000. The viral shedding was evaluated at 3 and 18 months of age by real-time CMV-PCR of saliva and plasma, and CMV culture of urine. CMV positive saliva samples were analyzed for genotypes for CMV envelope glycoproteins gB (UL55), and gH (UL75) by genotype specific real-time PCR, and gN (UL73) by cloning and sequencing RESULTS: At 3 months age 40/40 saliva and urine samples, and 19/40 plasma samples were positive for CMV. At 18 months age all urine samples tested (33/33), 9/37 of saliva samples, and 2/34 plasma samples were positive for CMV. The genotype distribution did not differ from the published data CONCLUSIONS: The urinary virus shedding is more persistent than salivary shedding in children with cCMV. The genotype distribution was similar to previous literature and does not explain the low disease burden of cCMV in our population.

The Burden of Congenital Cytomegalovirus Infection: A Prospective Cohort Study of 20 000 Infants in Finland.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most common congenital infection and causes significant morbidity. This study was undertaken to evaluate the benefits of screening newborns for cCMV and to understand the cCMV disease burden in Finland. METHODS: Infants born in Helsinki area hospitals were screened for CMV by testing their saliva with a real-time polymerase chain reaction assay. The CMV-positive infants and matched controls were monitored to determine their neurodevelopmental, audiological, and ophthalmological outcomes at 18 months of age. Griffiths Mental Development Scales, otoacoustic emission and sound field audiometry, and ophthalmologic examination were performed. RESULTS: Of the 19868 infants screened, 40 had confirmed cCMV infection (prevalence, 2 in 1000 [95% confidence interval, 1.4-2.6 in 1000]). Four (10%) infants had symptomatic cCMV. Griffiths general quotients did not differ significantly between the CMV-positive (mean, 101.0) and control (mean, 101.6) infants (P = .557), nor did quotients for any of the Griffiths subscales (locomotion, personal-social, hearing and language, eye and hand, performance) (P = .173-.721). Four of 54 CMV-positive ears and 6 of 80 CMV-negative ears failed otoacoustic emission testing (P = 1.000). The mean minimal response levels over the frequencies 500 Hz to 4 kHz in the sound field audiometry did not differ between CMV-positive (mean, 34.31-dB hearing level) and control (mean, 32.73-dB hearing level) infants (P = .338). No CMV-related ophthalmologic findings were observed. CONCLUSIONS: The prevalence of cCMV was low, and outcomes at 18 months of age did not differ between the infected infants and healthy control infants. With such a low burden in Finland, universal newborn screening for cCMV seems unwarranted.

Identification of OAF and PVRL1 as candidate genes for an ocular anomaly characterized by Peters anomaly type 2 and ectopia lentis.

Keratolenticular dysgenesis (KLD) and ectopia lentis are congenital eye defects. The aim of this study is the identification of molecular genetic alterations responsible for those ocular anomalies with neurologic impairment in an individual with a de novo balanced chromosome translocation t(11;18)(q23.3;q11.2)dn. Disruption of OAF, the human orthologue of the Drosophila oaf, by the 11q23.3 breakpoint results in reduced expression of this transcriptional regulator. Furthermore, four most likely nonfunctional chimeric transcripts comprising up to OAF exon 3, derived from the der(11) allele, have also been identified. This locus has been implicated by publicly available genome-wide association data in corneal disease and corneal topography. The expression of the poliovirus receptor-related 1(PVRL1) or nectin cell adhesion molecule 1 (NECTIN1), a paralogue of nectin cell adhesion molecule 3 (PVRL3) associated with congenital ocular defects, situated 500 kb upstream from 11q23.3 breakpoint, is increased. The 18q11.2 breakpoint is localized between cutaneous T-cell lymphoma-associated antigen 1(CTAGE1) and retinoblastoma binding protein 8 (RBBP8) genes. Genomic imbalance that could contribute to the observed phenotype was excluded. Analysis of gene expression datasets throughout normal murine ocular lens embryogenesis suggests that OAF expression is significantly enriched in the lens from early stages of development through adulthood, whereas PVRL1 is lens-enriched until E12.5 and then down-regulated. This contrasts with the observation that the proposita's lymphoblastoid cell lines exhibit low OAF and high PVRL1 expression as compared to control, which offers further support that the alterations described above are most likely responsible for the clinical phenotype. Finally, gene interaction topology data for PVRL1 also agree with our proposal that disruption of OAF by the translocation breakpoint and misregulation of PVRL1 due to a position effect contribute to the observed ocular and neurological phenotype.

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.

[Treatment of hemangiomas]. / Hemangioomien hoito.

Hemangioma is the most common benign tumor in infancy. Over 90% of hemangiomas require no treatment, but there is a need to recognize those that may require even quick measures to secure vital functions or normal development of organs. Propranolol has established itself as the first-line treatment. Pulsed dye laser has proven effective in the treatment of ulcerated hemangiomas. Corticosteroid therapy is applied only rarely, but surgical treatment or angiography and embolization therapy associated with it may sometimes be indicated.

Anterior segment optical coherence tomography in congenital corneal opacities.

PURPOSE: To evaluate the clinical usefulness of anterior segment (AS) optical coherence tomography (OCT) in diagnosis and follow-up of children with congenital corneal opacities. DESIGN: Noncomparative case series. PARTICIPANTS: Seven consecutive patients with bilateral congenital corneal opacity between 2 days and 2.5 years of age. METHODS: In addition to basic outpatient examination, eyes were imaged using AS OCT. Anterior segment structures and corneal thicknesses were evaluated from the images. Three children also underwent evaluation under anesthesia, including measurement of corneal thickness with ultrasound pachymetry. MAIN OUTCOME MEASURES: Evaluation of the type and severity of the congenital corneal opacity based on the findings in AS OCT. RESULTS: Thirteen of the 14 eyes could be imaged using AS OCT. The youngest patient studied was only 2 days old. Three distinct phenotypes were found based on the AS OCT findings. Three patients with iridocorneal adhesions were deduced to have type 1 Peters' anomaly, and 2 patients with lenticulocorneal adhesions were deduced to have type 2 Peters' anomaly. The 2 youngest patients had complete corneal opacity with features of corneal staphyloma and marked changes in the AS structures during the first months of life. CONCLUSIONS: Anterior segment OCT was a valuable method in the diagnosis and follow-up of patients with congenital corneal opacities. As a fast and noncontact technique, it was applicable even for neonates. It allowed early characterization of the type and the extent of the AS disorder. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Refined staging for chorioretinopathy in long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency.

OBJECTIVE: Neonatal screening and earlier diagnosis have improved the prognosis of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency, which causes a need to refine the staging of the pigmentary chorioretinopathy and thus improve monitoring and comparability of patients under dietary therapy. METHODS: Seven children with LCHAD deficiency caused by homozygous G1528C mutation attended sequential fundus photography for stage 2 chorioretinopathy in 1997­2006. After arranging 21 pairs of fund us photographs according to the severity of the fundus changes,the images best representing 3 different grades of pigmentary deposits (P1­P3) and retinal pigment epithelial(RPE) atrophy (A1­A3) were chosen as reference photographs.To evaluate the substaging, 29 pairs of photographs were graded according to the reference photographs. RESULTS: In the assessment of pigmentary deposits, the 3 ophthalmologists agreed in 41% and differed by a single substage in 45% of instances (combined weighted ĸ statistic was 0.38, indicating moderate agreement). In pairwise comparisons,the weighted ĸ statistic ranged from 0.31 to 0.56 (agreement, 71­81%). In the assessment of RPE atrophy, all 3 raters agreed in 17% and 2 raters in 70% of instances (combined ĸ statistic 0.018, indicating poor agreement). DISCUSSION: Despite variation in imaging techniques and limitations in the visual assessment of fundus photographs, the agreement obtained in grading the pigmentary deposits was comparable to that reported for photographic grading of retinopathy of prematurity. We recommend photographic documentation and substaging based on reference photographs in the follow-up of LCHAD retinopathy. The refined staging allows a more detailed assessment on the progression of the retinopathy and optimization of the therapeutic protocols in individual patients and between centres using different therapeutic protocols.

Clinical guidelines for diagnosing and managing ocular manifestations in children with mucopolysaccharidosis.

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.

Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis.

OBJECTIVE: To evaluate the efficacy of anti-tumour necrosis factor (anti-TNF) treatment in juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: 24 patients with uveitis taking etanercept and 21 taking infliximab were studied. The endpoint ophthalmological evaluation was at 24 months or at the termination of the first biological agent. The ocular inflammatory activity was graded on the basis of the number of anterior chamber cells. RESULTS: Of the 45 patients, uveitis improved in 14 (31%), no change was observed in 14 (31%) and the activity of uveitis increased in 17 (38%). Inflammatory activity improved more frequently (p=0.047) in the patients taking infliximab than in those taking etanercept. The number of uveitis flares/year was higher (p=0.015) in the patients taking etanercept (mean 1.4, range 0-3.2) than in those taking infliximab (mean 0.7, range 0-2). Uveitis developed for the first time while taking anti-TNF treatment in five patients-4 taking etanercept (2.2/100 patient-years) and 1 taking infliximab (1.1/100 patient-years). CONCLUSIONS: During anti-TNF treatment, the ophthalmological condition improved in one-third of the patients with uveitis. In chronic anterior uveitis, associated with refractory JIA, infliximab may be more effective than etanercept.

Orbital abscess caused by Fusobacterium necrophorum.

We report the case of previously healthy boy with orbital abscess secondary to sinusitis. Fusobacterium necrophorum and Streptococcus anginosus was cultured both from the maxillary sinus and the orbital abscess. After surgical drainage and intravenous antibiotic treatment the boy recovered without complications.

Human picornavirus and coronavirus RNA in nasopharynx of children without concurrent respiratory symptoms.

The prevalence of human rhino-, entero-, and coronaviruses was investigated by RT-PCR in nasopharyngeal aspirates from 107 children without concurrent respiratory symptoms. The children were admitted to the hospital for elective surgery. The parents filled a questionnaire about the occurrence of respiratory symptoms four weeks before and two weeks after the surgery. The rate of viral detection was 45% in children with related past or recent respiratory infection whereas 20% of the samples taken from children without any related past or recent respiratory infections were positive for picornavirus RNA, P = 0.008. Thirty-one (29%) of the nasopharyngeal aspirates were positive for viral RNA, 18% for rhinovirus, and 11% for enterovirus RNA. Coronavirus RNA was not found in any of the children. Fifty-five percent of the children with virus-positive samples had an infection-related diagnosis. In addition, 81% of the children with virus-positive samples had had previously respiratory symptoms or there were concurrent respiratory symptoms in other family members. Only four of the 31 virus-positive samples were from children without infection-related diagnosis or recent past (or immediate future) respiratory symptoms.