Manoj V. Parulekar

Septo-Optic Dysplasia: Antenatal Risk Factors and Clinical Features in a Regional Study

Background: Septo-optic dysplasia (SOD) is a disorder with postulated environmental and genetic aetiology. This study delineates clinical features and potential perinatal environmental factors along with epidemiology in SOD children. Methods: Assessment of patients with SOD triad features in the UK West Midlands region. Results: Of 227 patients identified between 1998 and 2009 with 1 or more feature of the triad, 55 had midline defects, 149 had optic nerve hypoplasia and 132 had hypopituitarism. Eighty-eight children (52% males; incidence 8.3/100,000 live births) had SOD defined as 2 out of 3 features and 21 (24%) had all 3. Sixty-one percent had anterior pituitary deficiency and 21.5% had diabetes insipidus. Median maternal/paternal ages in SOD were 21 and 23.5 years, compared to UK means of 29.3 and 32.4 years (p < 0.001). First trimester bleeding was markedly increased at 12/48 (25%) compared to 0.07% in the UK (p < 0.001). Ethnicity showed a non-significant higher prevalence in Afro-Caribbean and mixed race groups, and significantly lower prevalence (p = 0.004) in South Asian groups compared to West Midland and Birmingham city data: 8% versus 2.5 and 6.7%, 9% versus 1.8 and 3.2% and 3% versus 8.4 and 21%, respectively. Conclusions: SOD is associated with younger maternal and paternal age, primigravida births and ethnic differences. Increased first trimester bleeding may indicate that SOD is a vascular disruption sequence.

Relationship of infantile periocular hemangioma depth to growth and regression pattern.

PURPOSE Most infantile periocular hemangiomas undergo rapid growth in the first year of life, followed by gradual resolution over years. Treatment is indicated if vision is compromised and is usually continued through the growth phase. The objective of this study was to determine which clinical characteristics might aid in the prediction of growth and/or regression patterns of periocular hemangiomas. METHODS Retrospective review of medical records and photographs of children with periocular hemangiomas presenting to a UK pediatric eye unit over a 7-year period. Age at presentation, growth pattern, size, location, amblyopia, and refractive status were documented. RESULTS Forty-two infants with periocular hemangiomas were evaluated between 2000 and 2007, with a mean follow-up of 24 months (range, 6 months to 5 years). One-third (n=14, 33%) of the hemangiomas were superficial (strawberry nevi); one-third were subcutaneous (n=13, 31%), and the remainder were mixed (n=8, 19%) and orbital (n=7, 17%). There was a marked difference between the growth patterns of superficial (strawberry nevi) and deeper hemangiomas (orbital and subcutaneous), with a more prolonged period of growth noted in the deeper hemangiomas. CONCLUSIONS Periocular hemangiomas with a deep component tend to have a later onset and prolonged period of growth compared to strawberry nevi. Clinically evident depth of the hemangioma appears to be a valuable predictor of rapidity of resolution. This finding may be useful in assessing prognosis and planning treatment of infantile periocular hemangiomas.

Craniosynostosis with Ectopia Lentis and a Homozygous 20-base Deletion in ADAMTSL4

Craniosynostosis with ectopia lentis has been described five times since 1950 with unknown inheritance and variable phenotype. The patient was diagnosed with right coronal synostosis at age 10 weeks requiring surgery, and bilateral ectopia lentis with high myopia at 10 months. No other family member was affected. There is no known consanguinity within the family. Genetic screening ruled out FBN1, TGFBR2, and the known craniosynostosis hotspots (FGFR2 exon 8 and exon 10 and FGFR3 exon 6) as the cause. A homozygous deletion in exon 6 of ADAMTSL4 (c.767_786del 20) that has been shown to cause isolated ectopia lentis was found. The mutation results in a premature termination codon (p.Gln256ProfsX38). The proband’s mother, father and one sibling are heterozygous carriers of the mutation. This is the first detailed report of a possible genetic determinant of craniosynostosis with ectopia lentis. Although this mutation causes isolated ectopia lentis, this may be evidence of pleiotropic effects of ADAMTSL4 and may represent an overlapping syndrome with a causative mutation in ADAMTSL4. These findings need to be confirmed in further cases with craniosynostosis and ectopia lentis.

Metabolite profiling in retinoblastoma identifies novel clinicopathological subgroups

Background:Tumour classification, based on histopathology or molecular pathology, is of value to predict tumour behaviour and to select appropriate treatment. In retinoblastoma, pathology information is not available at diagnosis and only exists for enucleated tumours. Alternative methods of tumour classification, using noninvasive techniques such as magnetic resonance spectroscopy, are urgently required to guide treatment decisions at the time of diagnosis.Methods:High-resolution magic-angle spinning magnetic resonance spectroscopy (HR-MAS MRS) was undertaken on enucleated retinoblastomas. Principal component analysis and cluster analysis of the HR-MAS MRS data was used to identify tumour subgroups. Individual metabolite concentrations were determined and were correlated with histopathological risk factors for each group.Results:Multivariate analysis identified three metabolic subgroups of retinoblastoma, with the most discriminatory metabolites being taurine, hypotaurine, total-choline and creatine. Metabolite concentrations correlated with specific histopathological features: taurine was correlated with differentiation, total-choline and phosphocholine with retrolaminar optic nerve invasion, and total lipids with necrosis.Conclusions:We have demonstrated that a metabolite-based classification of retinoblastoma can be obtained using ex vivo magnetic resonance spectroscopy, and that the subgroups identified correlate with histopathological features. This result justifies future studies to validate the clinical relevance of these subgroups and highlights the potential of in vivo MRS as a noninvasive diagnostic tool for retinoblastoma patient stratification.

Long‐term retinoblastoma follow‐up with or without general anaesthesia

Children with treated retinoblastoma undergo frequent examinations to monitor for recurrent or new tumours. Examinations under anaesthesia allow a more complete examination in younger children, however they are stressful for the family, subject the child to medical risk and consume resources. The risk of recurrent or new tumours declines with age and it is common practice to examine older children without general anaesthesia. There are no studies on the safety and cost effectiveness of this practice, or guidelines on when examination without anaesthesia (EWA) can be safely commenced.Background Children with treated retinoblastoma undergo frequent examinations to monitor for recurrent or new tumours. Examinations under anaesthesia allow a more complete examination in younger children, however they are stressful for the family, subject the child to medical risk and consume resources. The risk of recurrent or new tumours declines with age and it is common practice to examine older children without general anaesthesia. There are no studies on the safety and cost effectiveness of this practice, or guidelines on when examination without anaesthesia (EWA) can be safely commenced. Procedure Retrospective case note review of 128 sequential patients treated for retinoblastoma in a national referral centre over 10 years. Results Following exclusions, 113 eyes of 84 children were analysed. The mean age at diagnosis was 20 months (range birth to 71 months). There were 55 unilateral and 29 bilateral cases. The mean follow-up was 77.7 months (range 12–178 months). EWA was commenced at a mean age of 53 months (range 12–98 months). The age of conversion to EWA was largely dependent on child cooperation and disease activity. Tumour activity was detected on EWA in one child at the age of 86 months, 9 months after the last active treatment and treated successfully. Conclusions Examination without general anaesthesia does not appear to expose children to an increased risk of undetected tumour growth. This study highlights the important factors to be considered when deciding a safe time to commence EWA. Pediatr Blood Cancer 2014;61:260–264.

Molecular testing prognostic of low risk in epithelioid uveal melanoma in a child

Aims To characterise a histologically unusual paediatric uveal melanoma by gene expression and karyotypic profiling and assess prognosis. Methods The tumour was studied by histopathology, karyotype analysis, single nucleotide polymorphism and gene expression profile analysis for correlation with clinical outcome. Results The tumour had predominantly epithelioid histology. Karyotype analysis showed none of the poor prognosis features normally associated with uveal melanoma. single nucleotide polymorphism analysis revealed no imbalance at chromosome 3. Gene expression profiling indicated low risk disease. Conclusions We report a child remaining relapse-free 6 years after diagnosis of a very rare uveal melanoma, with poor prognosis epithelioid histology, but gene expression profiling that accurately predicted low risk disease.

Coats disease in a 3-week-old boy.

Coats disease is a rare, idiopathic retinal vasculopathy that predominantly affects males in the first decade of life. We report the case of a 3-week-old boy who presented with atypical rapidly progressing disease suggestive of Coats exudative vasculopathy. The eye developed retinal fibrosis and phthisis bulbi within 4 weeks. Retinoblastoma could not be ruled out, although histopathology after enucleation revealed no retinoblastoma. To our knowledge, this is the youngest case of Coats disease to be reported in the literature. This case highlights the wide variation in the clinical presentation of Coats disease and the difficulty in differentiating it from diffuse infiltrative retinoblastoma.

Ectopic lens material in an otherwise healthy 5-week-old infant

PurposeTo report the unusual finding of ectopic lens material in an otherwise healthy 5-week-old infant.MethodsCase report and literature review.ResultsAn asymptomatic 5-week-old female infant was found to have unilateral ectopic lens material in the retrolental space of the left eye associated with a posterior capsular defect.ConclusionThe abnormality is likely embryological in origin, and the established progression for similar conditions means long-term monitoring is required to ensure the best possible visual outcome.

How to use…the direct ophthalmoscope

Ophthalmoscopy and red reflex examination are core medical skills required to identify sight-threatening and life-threatening disease. We discuss the predictive utility and limitations of findings with an ophthalmoscope and tips as to how to optimise these. We outline important considerations in three clinical scenarios: an abnormal red reflex, an abnormal optic disc and retinal haemorrhages in the context of child protection concerns.