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Background The use of chemotherapy to manage newly diagnosed low grade glioma (LGG) was first introduced in the 1980s. One randomised trial has studied two- versus four-drug regimens with a duration of 12 months of treatment after resection. Methods Within the European comprehensive treatment strategy for childhood LGG, the International Society of Paediatric Oncology–Low Grade Glioma (SIOP LGG) Committee launched a randomised trial involving 118 institutions and 11 countries to investigate the addition of etoposide (100 mg/m2, days 1, 2 & 3) to a four-course induction of vincristine (1.5 mg/m2 × 10 wkly) and carboplatin (550 mg/m2 q 3 weekly) as part of 18-month continuing treatment programme. Patients were recruited after imaging diagnosis, resection or biopsy with progressive disease/symptoms. Some 497 newly diagnosed patients (M/F 231/266; median age 4.26 years (interquartile range (IQR) 2.02–7.06)) were randomised to receive vincristine carboplatin (VC) (n = 249) or VC plus etoposide (VCE) during induction (n = 248), stratified by age and tumour site. Findings No differences between the two arms were found in term of survival and radiological response. Response and non-progression rates at 24 weeks for VC and VCE, were 46% versus 41%, and 93% versus 91% respectively; 5-year Progression-Free Survival (PFS) and Overall Survival (OS) were 46% (StDev 3.5) versus 45% (StDev 3.5) and 89% (StDev 2.1) versus 89% (StDev 2.1) respectively. Age and diencephalic syndrome are adverse clinical risk factors for PFS and OS. 5-year OS for patients in early progression at week 24 were 46% (StDev 13.8) and 49% (StDev 16.5) in the two arms, respectively. Interpretation The addition of etoposide to VC did not improve PFS or OS. High non-progression rates at 24 weeks justify retaining VC as standard first-line therapy. Infants with diencephalic syndrome and early progression need new treatments to be tested. Future trials should use neurological/visual and toxicity outcomes and be designed to discriminate between the impact on disease outcomes of ‘duration of therapy’ and ‘age at stopping therapy’., Highlights • A randomised trial in the commonest brain tumour type in children – low grade glioma. • Tumour response assessment at 6 months identifies those at greatest risk of subsequent progression and death. • Intensifying induction treatment with etoposide does not improve progression-free survival. • International consortium successfully recruits from 11 European countries in a childhood brain tumour. • Carboplatin hypersensitivity is reduced by coadministration of etoposide.

Corneal clouding or opacification is a prominent feature of mucopolysaccharidosis (MPS), particularly in MPS I and VI. In patients with marked corneal clouding and visual impairment, penetrating keratoplasty may be considered to improve the patient's vision, functional capacity and quality of life. In MPS, glycosaminoglycans mainly accumulate in the corneal stroma and not in Descemet's membrane or the endothelium, therefore deep anterior lamellar keratoplasty (DALK) may be preferred in these patients over penetrating keratoplasty. Although there are only limited data on the use of DALK in MPS (I and VI) patients, the results are generally favourable. Nonetheless, when deciding on whether to perform keratoplasty in patients with MPS, the risk of general anaesthesia due to potential concomitant cardio-pulmonary problems and cervical spine instability, the potential presence of other ocular manifestations that also impair vision (e.g. glaucoma, retinal degeneration and optic atrophy) and/or complications such as allograft rejection and the risk of re-opacification of the graft, all need to be taken into consideration. Limbal stem cell transplantation, which can be combined with keratoplasty, also holds potential promise in the treatment of these complex cases. A review of the indications, local and systemic risks, techniques of lamellar and penetrating keratoplasty, and the potential of limbal stem cell transplantation is provided in the context of corneal opacity in MPS.

An 8-year-old boy with recurrent acute bleeding of lymphangioma of the left orbit is described. D-dimer levels increased as the size of the mass became stable, showing the effect of fibrinolysis within the hemorrhagic mass after clotting. D-dimer levels confirmed the possible use of conservative management of this lymphangioma. [J Pediatr Ophthalmol Strabismus 2010;47:174–177.]

Congenital aniridia frequently causes severe visual impairment that is usually evident early in life. A precocious management of ocular complications is essential to prevent or limit low vision in these children. For planning rehabilitation treatment a complete opthalmological examination includes a careful visual assessment, using tests appropriate for the child’s age and ability to cooperate. Measurement of visual acuity is challenging in children, especially in infants or in patients with mental retardation (WAGR or Gillespie Syndrome). In such patients visual acuity can be evaluated with preferential looking test (Teller Acuity Cards). Starting from the 3 years of age, visual acuity can be evaluated with ETDRS charts. Management of children with aniridia and low vision is problematic: glare, reduced distance vision, reduced near vision due to foveal hypoplasia, fatigue, accommodation spasms, blurry vision, difficulty in distinguishing colors, anomalous head posture (compensatory positioning), nystagmus and the absence of stereopsis. The aim of rehabilitation is to improve visual performance though the correction of refractive errors, specific strategies and low vision aids, to reduce or relieve symptoms (glare, photophobia), and to promote learning, communication and daily living safety skills, and to foster social and scholastic participation and the child’s development and overall well-being.

Visual electrophysiological techniques represent excellent means for assessing retinal, optic pathways and visual cortex function. Electroretinograms, visual evoked potentials, and clinical records of 17 patients with mucopolysaccharidosis registered in the neurophysiological database of our institution were reviewed retrospectively. Ten patients were on enzyme replacement therapy, 2 underwent bone marrow transplantation, one also keratoplasty. Changes in the electroretinogram pointed to the diagnosis of retinal dystrophy type rod-cone in 8 patients. In patients in whom severe corneal clouding precluded fundus oculi inspection and at an early stage before typical fundus appearance diagnosis was possible only using the electroretinogram. Visual evoked potentials were useful to confirm the loss of visual function in patients difficult to test clinically. The authors suggest the use of electroretinogram and visual evoked potentials primarily as research tools to describe the natural history and ophthalmologic outcome in mucopolysaccharidoses, although they may have clinical utility in very selected cases.

Purpose To study causal links between the visual, cognitive, and psychomotor outcomes of premature babies who are small for gestational age (SGA). Methods A cohort study of 17 SGA cases and 34 controls who were appropriate for gestational age (AGA) was carried out. The cases were all premature babies without any other pathology. All subjects underwent a visual, mental, and psychomotor evaluation at 1 year of age. Results Of the SGA cases, 41% had a “below normal” visual acuity versus 17.7% of the AGA controls. At 1 year of age the SGA babies showed an odds ratio of 18.73 for low visual acuity, 9.09 for low mental performance, and no significant risk for a decreased psychomotor performance. Conclusions In this small cohort of premature infants, the SGA babies were more prone to developing low visual performance and abnormal cognitive development.

Purpose To report our experience using the RetCam II to evaluate retinal pathology and morphology in children who did not cooperate for standard examination and to follow them by monitoring changes and development of the diseases Methods We reviewed charts of 107 consecutive uncooperative children with fundus abnormalities that were photographed using the RetCam as a routine part of patient care.Since 2004 detailed diagnostic examination with use of RetCam II was performed in children with ocular tumors, vitreo-retinal dysplasia, hereditary retinal dystrophies, ROP, congenital abnormalities of optic disc, retinal haemorrhages in shaking injury, neuroretinitis. All eyes were dilated with 1% tropicamide. 0.4% oxibuprocaine drops were used prior image acquisition. A blefarostat was used to keep the eye lids wide apart during the examination.The children were directed to lie supine, under sedation. Results The authors report cases series: 7 cases of Ret Cam imaging (2 siblings with gyrate atrophy of the choroid and retina after reduction of plasma ornithine with diet; 1 Pedler’s coloboma with overlay of the peripapillary retina,2 cases with retinal haemorrhages in shaking injury in the acute phase and until the bleeding reabsorption,1 infant with early onset autosomal dominant hereditary rod-cone dystrophy , 1 optic nerve glioma extending to the retina, 1 case with chorioretinal dysplasia in systemic disease. Conclusion In this study analysis of RetCam digital images allowed to evaluate objectively, to determine exactly the areas of the disease, and to estimate changes and worsening.In our cases series the wide-field digital ophthalmic camera provided a new tool for the evaluation and precise documentation in paediatric retinal disease.

Purpose To study the relationship between the location of orbital and palpebral(eyelid)hemangiomas and ocular problems in children and the interventions needed to prevent or reduce the severity of visual impairment. Methods This study included 12 cases (10 female and 1 male;age range:1 day to 5 months old at first evaluation;mean age 2,5 months)of eyelid and/or orbit hemangiomas gathered over a 6 year period (2005-2011).Ultrasonography and magnetic resonance imaging(MRI)identified these lesions to be:palpebral in 2 cases, palpebral and orbital involvement in 9 cases.Pediatric and ophthalmological evaluation(orthoptic examination,visual acuity determination with Teller Acuity Cards,refractometry and fundus opthalmoscopy)were performed in all cases. Results The mean follow-up was 36 months (range 11-63 months) Treatments for infants and children with hemangiomas obstructing the visual axis included oral steroid administration(9 cases);in 1 case a surgical treatment was associated.4 cases developed amblyopia and 1 case strabismus.Treatment of early amblyopia through selective patching part-time patch occlusion of the uninvolved eye and early prescription of astigmatism correction was performed.10 children achieved normal vision at last evaluation. Conclusion In our study 10 patients treated for visual impairment and available for long-term follow-up showed an excellent functional outcome with no residual amblyopia.In most cases,early intervention to address hemangioma-related visual disturbances can lead to a good functional outcome. Intervention typically involves medical debulking of the hemangioma(using oral steroids)combined with the treatment of early amblyopia through selective patching and/or optical correction with refractive lenses.

Purpose To evaluate the ocular findings and the visual outcome in a group of patients with mucopolysaccaridoses(MPS) followed and treated with new therapeutic options. Methods 18 pazients with MPS (9 males and 9 females) were examinated: 3 cases with MPS type I, 4 with MPS type II,7 with MPS type III, 1 with MPS type IV and 3 with MPS type VI. The patients underwent an ophthalmological assessment with : visual acuity (with Teller Acuity Cards, Lea Symbols o letter chart, depending on patient age or degree of cohoperation), slit-lamp examination, fundus ophthalmoscopy, intraocular pressure, refractometry, electroretinography and eye echography. Results The mean follow-up was 48 months (ranged from 3 to 190 months).The mean age at first ophtalmologic evaluation was 6,9 years ( ranged from 1 to 20 years). 8 case presented progressive corneal clouding, 5 case retinal pigmentary degeneration, and 1 papilledema. Visual acuity worsened severely in 3 cases with MPS type I: 1 case from 10/10 to 5/10, 1 case from 5/10 to 1/10; in another case visual acuity decreased to 1/20 and underwent to corneal transplantation with good visual outcome (RE 5/10 and LE 7/10). The other cases showed slightly reduction of visual function. 3 patients had ocular hypertension and were treated with hypotensive eye drops. 8 patients underwent enzyme replacement therapy. Conclusion The mucopolysaccaridoses(MPS) are rare systemic disorders caused by accumulation of glycosaminoglycans. Ophthalmological manifestations are frequent in MPS, particularly in MPS I, II and VI, characterized by corneal clouding, retinal distrophy and blindness.Regular ophthalmic monitoring to determine disease progression and management of complications are necessary as a part of multidisciplinary approach.

Purpose To study long-term outcome of SBS on visual and cognitive functions. Methods Case series of 10 children (7 M, 3 F) with confirmed SBS has been examined and followed-up. All chldren underwent a fundus evaluation by indirect ophtalmoscopy and wide-field digital ophtalmic camera (RetCam II) in the acute phase and until retinal hemorrhage resorption. The assessment was repeated at follow-up combined with ocular motility evaluation, visual field (BEFIE test), visual acuity by preferential looking tecnique (teller acuity cards), refractometry, cognitive-behavioural evaluations (Griffiths scales, Child Behaviour Check List), and family stress measurement (Parenting Stress Index). Results Mean age at acute episode of SBS: 6 months (range 2-20). Mean age at last follow-up evaluation: 27.6 months (range 4.5-41). At last follow-up evaluation: 1 out of 6 had a decreased visual acuity (cortical visual impairment), 3 out of 6 had mild-severe visual field deficits, 3 out of 6 has strabismus. None of the cases showed significant refractive errors. Due to age or severity of impairment and delay in global development, in any of the cases we were able to perform a recognition acuity test by symbols or E-charts. Cognitive and behavioural assessment demonstrated global delay and impaiments in speech/language development and attention problems. Conclusion SBS is characterized by severe long-term sequelae both in visual and cognitive function. Several visual impairments are observed, mainly related to cortial injury of visuo-spatial area. Although follow-up is difficult due to family history, there is strong indication for global assessment until scholar age where other impairments are demonstrated.

Purpose: Describe the long term follow-up of children affected by congenital achromatopsia (CA). CA is a rare recessive inherited vision disorder (1:50000) and includes two clinical categories: complete CA and incomplete CA. Methods: Fourteen children (9 M, 5 F) were followed-up and a rehabilitation individual program was carried out. The assessment included: far and near visual acuity (Teller, Lea Symbols, Snellen Charts),refraction, color vision (Farnsworth, Ishihara, Montessori), contrast sensitivity, visual field, slit lamp examination, fundus ophthalmoscopy, electrophysiologic tests (photopic, scotopic and flicker ERG and VEPs) and genetic examination. Results: Early onset of nystagmus, low vision and photophobia are first clinical manifestations of CA. The differential diagnosis includes Leber Amaurosis, and congenital nystagmus and albinism. Visual acuity in our patients is around 1/10 and it is worse for near. Refractive errors showed a distribution toward hyperopia (50%) and emmetropia (35%). Macular hypoplasia is present in all cases and electrophysiology showed a reduced or absent photopic ERG, while scotopic system appears normal. Conclusions: Due to abnormal or totally absent cone function, which lead to macular hypoplasia, CA shows reduced visual acuity, absent/severely impaired color vision, nystagmus and photophobia. Low vision aids such as telescopic systems and magnification devices along with OCR/ICR software were prescribed after a carefully evaluation. Spectral filters were early prescribed to reduce photophobia and improve vision. The molecular analysis may confirm the diagnosis and give genetic couseling to the family. An early detection of CA is underlined by the importance to carry out a complete and precocious rehabilitative approach.

We evaluated the visual outcome of a cohort of children with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG) treated according to standardized therapeutic guidelines. The study population consisted of all consecutive patients with NF1 and OPG referred to a specialized pediatric neuro-oncology program between 1994 and 2004. Treatment was instituted only in cases of progressive disease or clinical deterioration. Treatment modalities were chemotherapy (based on vincristine/carboplatin) for children younger than 5 years and radiotherapy for all others. Ten boys and 10 girls (seven with a positive family history) entered the trial (median age at diagnosis of OPG, 29 months). At a median follow-up time of 78 months, seven patients had been treated with chemotherapy only, four with radiotherapy, and four with chemotherapy plus radiotherapy. Five patients were observed only. Currently, 18 are alive and two have died. Eight patients were treated for progressive visual loss in the face of stable disease, five for tumor volume increase without visual deterioration, and two for symptomatic tumor volume increase. At referral, six children had a visual acuity (VA) of < 30% in both eyes; eight children had 100% VA bilaterally. At referral, the visual field (VF) could be assessed in three children: One had VF loss in both eyes, one had VF loss in one eye, and one had normal VF. At last follow-up, eight children had VA < 20% in both eyes; only two children had 100% VA in both eyes. Among 11 children who had some visual function, three had VF loss in one eye and three in both eyes, and five had an intact VF. Contrast and color sensitivity were abnormal in seven and six patients, respectively. Thirteen children fell into the WHO hypovision category. In summary, among the 15 children treated, one had a definitive and two a mild improvement in VA. In conclusion, the visual outcome of this selected cohort of NF1 patients with OPG is unsatisfactory. A critical reappraisal of the therapeutic strategy adopted is needed.

A girl with HIV infection acquired at birth by blood transfusion, was admitted at the age of 10 years for diplopia, vomiting, headache and papilledema. CT scan was negative. A lumbar puncture revealed clear CSF, protein 0.40 g/l, glucose 2 mmol/l, 5 mononuclear cells/mm3. The Indian ink preparation and the latex agglutination antigen test were positive for Cryptococcus n. Treatment with amphotericin B and flucytosine was started. After 10 days, since the in vitro susceptibility testing of the isolates showed resistence to both drugs, fluconazolo (400 mg/day) was started. Acetazolamide, furosemide and spironolactone were then added to the antifungal therapy for the persistence of severe intracranial hypertension. Diuretics were maintained for 10 weeks. The patient returned to school two and half months after the admission to the hospital. After 19 months, she is doing well and she is on maintenance of fluconazole (200 mg/day). We hypothesized that the increased intracranial pressure would be due to an impaired CSF reabsorption probably as a consequence of a direct cryptococcal infiltration of the villi.