Anisohypermetropia as a sign of unilateral glaucoma in the pediatric population.

Childhood glaucoma poses a diagnostic and therapeutic challenge to ophthalmologists. Difficulty in examination and limitations on ability to perform structural and functional testing of optic nerve make diagnosis and verification of glaucoma control difficult in children. It is well known that an excessive loss of hyperopia is a useful sign in alerting the examining ophthalmologist to the possible diagnosis of glaucoma. We present an interesting case of juvenile onset glaucoma presenting with anisohypermetropic amblyopia in one eye and normal vision in the fellow eye that has glaucoma. It is an unusual case as the left eye with abnormal vision from hypermetropic amblyopia, though by itself requiring treatment, was a red herring for a potentially blinding condition in the fellow eye with normal vision and lower and less amblyogenic hyperopia on examination. We believe that glaucomatous enlargement of the right eye resulted in significant loss of hyperopia in that eye and in turn contributed to anisohypermetropic amblyopia in the left eye. To the best of our knowledge, this is the first reported case of juvenile onset glaucoma presenting with anisohypermetropic amblyopia in one eye and normal vision in the fellow eye that has glaucoma.

Mutation spectrum of RB1 mutations in retinoblastoma cases from Singapore with implications for genetic management and counselling.

Retinoblastoma (RB) is a rare childhood malignant disorder caused by the biallelic inactivation of RB1 gene. Early diagnosis and identification of carriers of heritable RB1 mutations can improve disease outcome and management. In this study, mutational analysis was conducted on fifty-nine matched tumor and peripheral blood samples from 18 bilateral and 41 unilateral unrelated RB cases by a combinatorial approach of Multiplex Ligation-dependent Probe Amplification (MLPA) assay, deletion screening, direct sequencing, copy number gene dosage analysis and methylation assays. Screening of both blood and tumor samples yielded a mutation detection rate of 94.9% (56/59) while only 42.4% (25/59) of mutations were detected if blood samples alone were analyzed. Biallelic mutations were observed in 43/59 (72.9%) of tumors screened. There were 3 cases (5.1%) in which no mutations could be detected and germline mutations were detected in 19.5% (8/41) of unilateral cases. A total of 61 point mutations were identified, of which 10 were novel. There was a high incidence of previously reported recurrent mutations, occurring at 38.98% (23/59) of all cases. Of interest were three cases of mosaic RB1 mutations detected in the blood from patients with unilateral retinoblastoma. Additionally, two germline mutations previously reported to be associated with low-penetrance phenotypes: missense-c.1981C>T and splice variant-c.607+1G>T, were observed in a bilateral and a unilateral proband, respectively. These findings have implications for genetic counselling and risk prediction for the affected families. This is the first published report on the spectrum of mutations in RB patients from Singapore and shows that further improved mutation screening strategies are required in order to provide a definitive molecular diagnosis for every case of RB. Our findings also underscore the importance of genetic testing in supporting individualized disease management plans for patients and asymptomatic family members carrying low-penetrance, germline mosaicism or heritable unilateral mutational phenotypes.

Post-operative strabismus control and motor alignment for basic intermittent exotropia.

AIM: To assess strabismus control and motor ocular alignment for basic exotropia surgery at 5y follow-up. METHODS: The medical records of 80 consecutive patients aged less than 17 years of age, who underwent surgery for basic exotropia by a single surgeon between years 2000 to 2009 and completed a minimum of 5y follow-up post-operatively were reviewed. Pre- and post-operative characteristics were documented at 1wk, 6mo, 1, 3 and 5y follow-up. Subjects at 5-year follow-up were assigned to the success group if they had a post-operative angle of deviation within 10 prism diopters of exotropia or within 5 prism diopters of esotropia for distance on prism cover test, and had moderate to good strabismus control. The remaining subjects were assigned to the failure group. RESULTS: Post-operative surgical success at one week was 75%, which decreased to 41% at 5y follow-up. The success group was noted to have more patching pre-operatively (P=0.003). The duration of patching a day (P=0.020) and total duration of patching pre-operatively (P=0.030) was higher in the success group. Surgical success at 1y (P=0.004) and 3y (P=0.002) were associated with higher surgical success at 5y follow-up. CONCLUSION: Post-operative motor alignment and strabismus control for basic exotropia surgery at 1y and beyond is associated with higher exotropia surgery success at 5-year follow-up. There is an association between pre-operative patching and 5-year surgical success of basic intermittent exotropia surgery.

Periocular capillary hemangioma: management practices in recent years.

PURPOSE: To present a case series on the management options for capillary hemangiomas involving the eyelid and orbit. METHODS: This is a retrospective chart review of clinically diagnosed capillary hemangioma cases involving the periocular region treated at two local eye institutions. The patients' demographics and clinical presentation - including visual acuity, refractive error, periorbital and orbital examinations, and ultrasound and magnetic resonance imaging findings - were reviewed. The clinical progression, modalities of treatment, and treatment outcomes were studied. RESULTS: Sixteen cases of capillary hemangiomas involving the eyelid and orbit were studied. The mean age at consultation was 9.6 months (range: 1 month-72 months). The majority were females (75%), with 50% presenting as upper-eyelid hemangiomas and the remaining as lower-eyelid (38%) and glabellar (12%) lesions. Combined superficial and deep involvement was common (64%). Cases whose lesions were located at the upper eyelid or superior orbit led to amblyopia (25%). Fifty-six percent of cases (9/16) were managed conservatively, and 44% (7/16) underwent treatment with either single-agent (n = 4) or combined treatments (n = 3). CONCLUSION: Close monitoring of visual development and prompt institution of amblyopia therapy for children with periocular capillary hemangiomas generally preserve vision. Extensive lesions that affect the visual axis require local and systemic treatments, alone or in combination, in order to reduce the size and impact of lesions on the eyeball, to reduce induced refractive error and visual occlusion, and to prevent the development of amblyopia, in order to achieve good visual outcomes.

Risk factors for strabismus and amblyopia in young Singapore Chinese children.

PURPOSE: To determine the risk factors for strabismus and amblyopia in young Singapore Chinese children. METHODS: A total of 3009 children were recruited for the population-based cross-sectional Strabismus, Amblyopia and Refractive Error in Singaporean Preschoolers Study (STARS). Strabismus was defined as any tropia identified on cover test. Visual acuity was measured in children aged 30-72 months with a logMAR chart where possible and the Sheridan-Gardiner test if not. Amblyopia was defined based on visual acuity and refractive error or presence of strabismus or past/present visual axis obstruction. Parents completed questionnaires on family, prenatal and birth histories. RESULTS: Our study showed that 24 children aged 6-72 months (1.2%) had strabismus (20 with exotropia), and 20 children aged 30-72 months (0.8%) were amblyopic. After multivariate analysis, strabismus was associated with astigmatism ≥1.00 diopter (D; p = 0.03), amblyopia (p = 0.003), a sibling with strabismus (p < 0.001), and families with lower parental education (p = 0.04). In addition to strabismus, amblyopia was associated with anisometropia ≥1.00 D (p < 0.001) and astigmatism ≥1.00 D (p < 0.001). No association was noted between either strabismus or amblyopia and prematurity, maternal age or smoking. CONCLUSION: This study highlights the importance of family history in strabismus, and the close associations between refractive error and strabismus with amblyopia. These factors play a more important role in young Singapore Chinese children.

Clinical profile, management, and outcome of retinoblastoma in singapore.

PURPOSE: To analyze the clinical manifestations and treatment outcomes for patients with retinoblastoma in Singapore from 1997 to 2010. METHODS: Medical records of 51 patients (67 eyes) diagnosed as having retinoblastoma were analyzed. Data on laterality, genetics, presentation, disease severity, treatment, and prognosis were collected. RESULTS: The mean age of presentation was 25.7 ± 19.9 months. Sixteen (31.4%) of the patients had bilateral disease, of whom 2 had an associated pineal tumor. Leukocoria was the most common sign. Two had metastasis at diagnosis. Only 3 patients (5.9%) had a family history. Using the International Intraocular Retinoblastoma Classification, 6.0% were Group A, 6.0% were Group B, 3.0% were Group C, 38.8% were Group D, and 49.2% were Group E. Chemotherapy and focal therapy were administered for 4 of 35 (12.9%) patients with unilateral retinoblastoma (50% had successful globe preservation) and 13 of 16 (81.3%) patients with bilateral retinoblastoma (42.3% had successful globe preservation). Overall, globe preservation was achieved in 100% of Groups A, B, and C, and 23.1% of Group D cases. The 5-year survival rate overall, for unilateral retinoblastoma, and for bilateral retinoblastoma was 91%, 97%, and 76% respectively. CONCLUSION: The overall 5-year survival rate is comparable to international data in most developed countries. However, most patients presented with advanced disease, making the rate of globe preservation lower than in some developed countries. Better education of the public and healthcare professionals may increase awareness and enable early detection of the disease.

Characteristics of divergence excess type intermittent exotropia in Asian children.

BACKGROUND: Exotropia is twice as common as esotropia in Asian children, with divergence excess intermittent exotropia contributing more than one half of exotropia cases. In this study, distance-near relationships and ratios of accommodative convergence to accommodation (AC/A) are compared using different measurement methods in Asian children with divergence excess intermittent exotropia. METHODS: Children with intermittent exotropia and a distance deviation exceeding the near by at least 10(Δ) were consecutively recruited. After prism cover test measurements at 6 m and 33 cm, AC/A ratios were calculated using the heterophoria method and the gradient method with -2.0 D and +3.0 D lenses at 6 m and 33 cm, respectively. AC/A ratios were recalculated after 1 hour of monocular patching. RESULTS: A total of 42 children (mean age, 6.9 years; range, 3-16 years) were included. The mean difference between distance and near deviation was 22(Δ) before occlusion and 14(Δ) after (P < 0.001). Approximately one third had a distance-near difference <10(Δ) after occlusion. With the heterophoria method, 100% of patients had high AC/A ratios before occlusion, with 71% continuing to have high AC/A ratios after. With the gradient method, 52% of patients had high AC/A ratios before occlusion, with 68% of this subgroup continuing to have high AC/A ratios after. CONCLUSIONS: Pseudo-divergence excess was found in one third of the subjects. More children were diagnosed with high AC/A ratios using the heterophoria method than with the gradient method. Without monocular occlusion, approximately one third of the children with normal AC/A ratios may be mistaken to have high AC/A ratios when measured with either method. Identification of high AC/A ratio exotropic patients is critical due to the risk of developing consecutive esotropia at near after strabismus surgery.

Unilateral retinoblastoma in an eye with Peters anomaly.

Retinoblastoma and Peters anomaly are presumably unrelated ocular conditions, although other congenital ocular anomalies have been described in association with retinoblastoma. We report the case of a neonate who presented with unilateral retinoblastoma and Peters anomaly. Retinoblastoma arises from a deregulation of cellular events secondary to inactivation of both RB1 gene alleles, whereas Peters anomaly has been linked to eye-development genes and chromosomal anomalies. A second locus for retinoblastoma, RBL2, which encodes the p130 protein, has been shown to contribute to retinoblastoma oncogenesis. Coincidentally, p130 also plays a role in corneal cell differentiation. Although the association of retinoblastoma and Peters anomaly in this patient may be coincidental, it raises the question of whether the RBL2 mutation contributed to both conditions.

Prevalence of amblyopia and strabismus in young singaporean chinese children.

PURPOSE. To determine the prevalence of amblyopia and strabismus in young Singaporean Chinese children. METHODS. Enrolled in the study were 3009 Singaporean children, aged 6 to 72 months. All underwent complete eye examinations and cycloplegic refraction. Visual acuity (VA) was measured with a logMAR chart when possible and the Sheridan-Gardner test when not. Strabismus was defined as any manifest tropia. Unilateral amblyopia was defined as a 2-line difference between eyes with VA < 20/30 in the worse eye and with coexisting anisometropia (> or =1.00 D for hyperopia, > or =3.00 D for myopia, and > or =1.50 D for astigmatism), strabismus, or past or present visual axis obstruction. Bilateral amblyopia was defined as VA in both eyes <20/40 (in children 48-72 months) and <20/50 (<48 months), with coexisting hyperopia > or =4.00 D, myopia < or = -6.00 D, and astigmatism > or =2.50 D, or past or present visual axis obstruction. RESULTS. The amblyopia prevalence in children aged 30 to 72 months was 1.19% (95% confidence interval [CI], 0.73-1.83) with no age (P = 0.37) or sex (P = 0.22) differences. Unilateral amblyopia (0.83%) was twice as frequent as bilateral amblyopia (0.36%). The most frequent causes of amblyopia were refractive error (85%) and strabismus (15%); anisometropic astigmatism >1.50 D (42%) and isometropic astigmatism >2.50 D (29%) were frequent refractive errors. The prevalence of strabismus in children aged 6 to 72 months was 0.80% (95% CI, 0.51-1.19), with no sex (P = 0.52) or age (P = 0.08) effects. The exotropia-esotropia ratio was 7:1, with most exotropia being intermittent (63%). Of children with amblyopia, 15.0% had strabismus, whereas 12.5% of children with strabismus had amblyopia. CONCLUSIONS. The prevalence of amblyopia was similar, whereas the prevalence of strabismus was lower than in other populations.

Orbital cellulitis in children-medical treatment versus surgical management.

INTRODUCTION: Ophthalmologists differ in their threshold for surgical management in paediatric patients with orbital cellulitis. We studied the management choices and outcome of children admitted with this disorder. MATERIAL AND METHODS: A retrospective review was performed on patients with orbital cellulitis admitted between January 2001 and December 2004 to a tertiary paediatric referral centre in Singapore. The patients were studied for age, associated systemic disease, medical treatment, drainage procedure undertaken, organism isolated and outcome. Statistical methods were applied for comparing medical treatment with surgical treatment with respect to recovery time, recurrence, and time between the presentation of patient and initiation of treatment. RESULTS: Twenty patients were studied. Average age was 5.5 years. 5/20 (25%) had a preceding history of upper respiratory tract infection. From CT findings, we came to know that 3/20 (15%) were due to isolated ethmoiditis, 5/20 (25%) had obstruction of the osteomeatal complex of the paranasal sinuses, 2/10 (10%) had intracranial abscesses due to frontal sinusitis. 4/20 (20%) had all 4 ipsilateral paranasal sinuses infected. 2/20 (10%) had preseptal cellulitis with posterior extension into the orbit. 2/20 (10%) had orbital cellulitis related to dacryoadenitis and 2/20 (10%) had pansinusitis with orbital soft tissue stranding. 13/20 (65%) had orbital and /or endoscopic drainage. The remainder of the patients had good immediate response to sole medical treatment and did not require surgery. The most commonly isolated organism was Staphylococcus aureus 5/20 (25%). All patients recovered within a mean of 9.6 days with no complications or functional deficit. CONCLUSIONS: Paediatric orbital cellulitis can be treated conservatively or with surgical drainage. Indications for surgery include pansinusitis, large abscesses with significant mass effect, concurrent intracranial involvement, poor response to initial medical treatment and the presence of an orbital abscess and gas. Sole medical treatment worked well in children with no orbital abscess, small or medial abscesses as they tend to have a single organism infection. This is also of particular significance in young children below the age of one where endoscopic surgery can be technically difficult. Intracranial involvement occurred in association with frontal sinusitis and affected patients had the longest duration of hospitalization.

High incidence of allelic loss at 16q12.2 region spanning RBL2/p130 gene in retinoblastoma.

Retinoblastoma (Rb) is the most common intra-ocular tumor that manifests in early childhood. It is initiated by the inactivation of RB1/p105 gene, a prototype tumor suppressor gene. However, observed recurrent chromosomal aberrations accompanying RB1/p105 mutations suggest the involvement of additional mutational events. Chromosome 16q is one of the loci with recurrent losses which are likely to contain tumor suppressor genes. In this study, allelic loss was demonstrated at a second locus for retinoblastoma, RBL2/p130 on 16q12.2. Using intragenic single nucleotide polymorphisms (SNPs) (rs1074182 and rs10748) and flanking extragenic microsatellite markers (D16S411 and D16S408), 40 retinoblastoma tumor samples were analyzed. Loss of heterozygosity (LOH) of these markers was found in 11 (57.9%) out of 19 informative tumors at the RBL2/p130 gene locus and while a total of 15 (78.9%) tumors showed LOH in at least one marker. Deletions extending more than 13 cM across the pericentromeric region of 16q12.1-q13 were inferred from four tumors. Microsatellite instability was observed in two other tumors at the flanking markers. No mutations were found in RBL2/p130 exons 19-22 coding for the protein domain critical for biological activity. This is the first evidence of LOH within RBL2/p130 gene in retinoblastoma. The high frequency of allelic loss provides further evidence on the implication of this gene in retinoblastoma development and/or progression.

Atropine for the treatment of childhood myopia.

PURPOSE: To evaluate the efficacy and safety of topical atropine, a nonselective muscarinic antagonist, in slowing the progression of myopia and ocular axial elongation in Asian children. DESIGN: Parallel-group, placebo-controlled, randomized, double-masked study. PARTICIPANTS: Four hundred children aged 6 to 12 years with refractive error of spherical equivalent -1.00 to -6.00 diopters (D) and astigmatism of -1.50 D or less. INTERVENTION: Participants were assigned with equal probability to receive either 1% atropine or vehicle eye drops once nightly for 2 years. Only 1 eye of each subject was chosen through randomization for treatment. MAIN OUTCOME MEASURES: The main efficacy outcome measures were change in spherical equivalent refraction as measured by cycloplegic autorefraction and change in ocular axial length as measured by ultrasonography. The primary safety outcome measure was the occurrence of adverse events. RESULTS: Three hundred forty-six (86.5%) children completed the 2-year study. After 2 years, the mean progression of myopia and of axial elongation in the placebo-treated control eyes was -1.20+/-0.69 D and 0.38+/-0.38 mm, respectively. In the atropine-treated eyes, myopia progression was only -0.28+/-0.92 D, whereas the axial length remained essentially unchanged compared with baseline (-0.02+/-0.35 mm). The differences in myopia progression and axial elongation between the 2 groups were -0.92 D (95% confidence interval, -1.10 to -0.77 D; P<0.001) and 0.40 mm (95% confidence interval, 0.35-0.45 mm; P<0.001), respectively. No serious adverse events related to atropine were reported. CONCLUSIONS: Topical atropine was well tolerated and effective in slowing the progression of low and moderate myopia and ocular axial elongation in Asian children.

Morning glory disc anomaly, midline cranial defects and abnormal carotid circulation: an association worth looking for.

We report on a 4-year-old boy who presented to the ophthalmology department for assessment of convergent strabismus. Ophthalmic examination showed a left morning glory optic disc anomaly and retinal detachment. Plain films obtained for investigation of short stature prior to ophthalmic examination revealed delayed bone age. Ophthalmological findings prompted CT and MRI imaging and angiographic investigations. Midline cranial defects and abnormal carotid circulation were identified. These findings may be associated with morning glory optic disc anomaly, and their association is often under-recognized. It is important that clinicians and radiologists be aware of this spectrum of disorders, as the vascular abnormalities may predispose the patient to transient ischemic attacks and strokes. Growth delay may result from hypopituitarism.