Systolic hypertension as side effect of topical low dose atropine drops.

Purpose: To present a case of increased systemic hypertension and pupil dilation related to low dose atropine eyedrops. Observations: A thirteen-year-old male with progressive myopia received atropine 0.05% ophthalmic drops to slow down myopia progression. He exhibited systemic systolic hypertension, photophobia, and bilateral nonreactive mydriasis. The atropine drops were discontinued, and his blood pressure and pupillary function normalized. Conclusions and importance: This case demonstrates sensitivity to low dose atropine with increased systemic blood pressure and pupillary dilation.

Glaucoma-Related Adverse Events at 10 Years in the Infant Aphakia Treatment Study: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Glaucoma-related adverse events constitute serious complications of cataract removal in infancy, yet long-term data on incidence and visual outcome remain lacking. Objective: To identify and characterize incident cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of 10.5 years and to determine whether these diagnoses are associated with optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) assessment. Design, Setting, and Participants: Analysis of a multicenter randomized clinical trial of 114 infants with unilateral congenital cataract who were aged 1 to 6 months at surgery. Data on long-term glaucoma-related status and outcomes were collected when children were 10.5 years old (July 14, 2015, to July 12, 2019) and analyzed from March 30, 2019, to August 6, 2019. Interventions: Participants were randomized at cataract surgery to either primary intraocular lens (IOL), or aphakia (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis. Main Outcomes and Measures: Development of glaucoma and glaucoma + glaucoma suspect in operated-on eyes up to age 10.5 years, plus intraocular pressure, axial length, RNFL (by optical coherence tomography), and ONH photographs. Results: In Kaplan-Meier analysis, for all study eyes combined (n = 114), risk of glaucoma after cataract removal rose from 9% (95% CI, 5%-16%) at 1 year, to 17% (95% CI, 11%-25%) at 5 years, to 22% (95% CI, 16%-31%) at 10 years. The risk of glaucoma plus glaucoma suspect diagnosis after cataract removal rose from 12% (95% CI, 7%-20%) at 1 year, to 31% (95% CI, 24%-41%) at 5 years, to 40% (95% CI, 32%-50%) at 10 years. Risk of glaucoma and glaucoma plus glaucoma suspect diagnosis at 10 years was not significantly different between treatment groups. Eyes with glaucoma (compared with eyes with glaucoma suspect or neither) had longer axial length but relatively preserved RNFL and similar ONH appearance and visual acuity at age 10 years. Conclusions and Relevance: Risk of glaucoma-related adverse events continues to increase with longer follow-up of children following unilateral cataract removal in infancy and is not associated with primary IOL implantation. Development of glaucoma (or glaucoma suspect) after removal of unilateral congenital cataract was not associated with worse visual acuity outcomes at 10 years. Trial Registration: ClinicalTrials.gov Identifier: NCT00212134.

Outcomes of Bilateral Cataract Surgery in Infants 7 to 24 Months of Age Using the Toddler Aphakia and Pseudophakia Treatment Study Registry.

PURPOSE: To evaluate outcomes of bilateral cataract surgery in children aged 7 to 24 months and compare rates of adverse events (AEs) with other Toddler Aphakia and Pseudophakia Study (TAPS) registry outcomes. DESIGN: Retrospective clinical study at 10 Infant Aphakia Treatment Study (IATS) sites. Statistical analyses comparing this cohort with previously reported TAPS registry cohorts. PARTICIPANTS: Children enrolled in the TAPS registry between 2004 and 2010. METHODS: Children underwent bilateral cataract surgery with or without intraocular lens (IOL) placement at age 7 to 24 months with 5 years of postsurgical follow-up. MAIN OUTCOME MEASURES: Visual acuity (VA), occurrence of strabismus, AEs, and reoperations. RESULTS: A total of 40 children (76 eyes) who underwent bilateral cataract surgery with primary posterior capsulectomy were identified with a median age at cataract surgery of 11 months (7-23); 68% received a primary IOL. Recurrent visual axis opacification (VAO) occurred in 7.5% and was associated only with the use of an IOL (odds ratio, 6.10; P = 0.005). Glaucoma suspect (GS) was diagnosed in 2.5%, but no child developed glaucoma. In this bilateral cohort, AEs (8/40, 20%), including glaucoma or GS and VAO, and reoperations occurred in a similar proportion to that of the published unilateral TAPS cohort. When analyzed with children aged 1 to 7 months at bilateral surgery, the incidence of AEs and glaucoma or GS correlated strongly with age at surgery (P = 0.011/0.004) and glaucoma correlated with microcornea (P = 0.040) but not with IOL insertion (P = 0.15). CONCLUSIONS: Follow-up to age 5 years after bilateral cataract surgery in children aged 7 to 24 months reveals a low rate of VAO and very rare glaucoma or GS diagnosis compared with infants with cataracts operated at < 7 months of age despite primary IOL implantation in most children in the group aged 7 to 24 months. The use of an IOL increases the risk of VAO irrespective of age at surgery.

Safety and efficacy data supporting U.S. FDA approval of intracameral phenylephrine and ketorolac 1.0%/0.3% for pediatric cataract surgery: clinical safety and pupil and pain management.

PURPOSE: To assess the safety of phenylephrine and ketorolac (PE/K) 1.0%/0.3% compared with phenylephrine (PE) 1.0% in children aged 0 to 3 years undergoing cataract surgery. The effect of PE/K to PE on intraoperative pupil diameter and postoperative pain were also compared. SETTING: Multicenter study in the United States. DESIGN: Randomized double-masked phase 3 clinical trial. METHODS: This study was powered to assess safety only. Depending on randomization, 4 mL of PE/K 1.0%/0.3% or PE 1.0% was injected into the surgical irrigation solution. Safety endpoints were assessed up to 90 days postoperatively. From surgical videos, a masked central reader measured the change in pupil diameter from immediately prior to incision to wound closure. Postoperative pain was measured using Alder Hey Triage Pain Score at 3 hours, 6 hours, 9 hours, and 24 hours following wound closure and recorded by parent/caregiver. RESULTS: Seventy-two patients received masked intervention. There were no notable changes in vital signs or ophthalmological complications in either group. Mean change in pupil diameter was similar between PE/K 1.0%/0.3% and PE 1.0% (mean difference in area under the curve -0.071; P = .599). Postoperative ocular pain scores and overall mean scores were lower in PE/K group at all individual time points, and differences in overall mean scores were statistically significant at 6 and 24 hours (P = .029 and 0.021, respectively). CONCLUSIONS: PE/K 1.0%/0.3% was safe for use in children and maintained mydriasis during cataract surgery. Postoperative pain levels were lower in the PE/K 1.0%/0.3% group.

Outcomes of Bilateral Cataracts Removed in Infants 1 to 7 Months of Age Using the Toddler Aphakia and Pseudophakia Treatment Study Registry.

PURPOSE: To evaluate outcomes of bilateral cataract surgery in infants 1 to 7 months of age performed by Infant Aphakia Treatment Study (IATS) investigators during IATS recruitment and to compare them with IATS unilateral outcomes. DESIGN: Retrospective case series review at 10 IATS sites. PARTICIPANTS: The Toddler Aphakia and Pseudophakia Study (TAPS) is a registry of children treated by surgeons who participated in the IATS. METHODS: Children underwent bilateral cataract surgery with or without intraocular lens (IOL) placement during IATS enrollment years 2004 through 2010. MAIN OUTCOME MEASURES: Visual acuity (VA), strabismus, adverse events (AEs), and reoperations. RESULTS: One hundred seventy-eight eyes (96 children) were identified with a median age of 2.5 months (range, 1-7 months) at the time of cataract surgery. Forty-two eyes (24%) received primary IOL implantation. Median VA of the better-seeing eye at final study visit closest to 5 years of age with optotype VA testing was 0.35 logarithm of the minimum angle of resolution (logMAR; optotype equivalent, 20/45; range, 0.00-1.18 logMAR) in both aphakic and pseudophakic children. Corrected VA was excellent (<20/40) in 29% of better-seeing eyes, 15% of worse-seeing eyes. One percent showed poor acuity (≥20/200) in the better-seeing eye, 12% in the worse-seeing eye. Younger age at surgery and smaller (<9.5 mm) corneal diameter at surgery conferred an increased risk for glaucoma or glaucoma suspect designation (younger age: odds ratio [OR], 1.44; P = 0.037; and smaller cornea: OR, 3.95; P = 0.045). Adverse events also were associated with these 2 variables on multivariate analysis (younger age: OR, 1.36; P = 0.023; and smaller cornea: OR, 4.78; P = 0.057). Visual axis opacification was more common in pseudophakic (32%) than aphakic (8%) eyes (P = 0.009). Unplanned intraocular reoperation occurred in 28% of first enrolled eyes (including glaucoma surgery in 10%). CONCLUSIONS: Visual acuity after bilateral cataract surgery in infants younger than 7 months is good, despite frequent systemic and ocular comorbidities. Although aphakia management did not affect VA outcome or AE incidence, IOL placement increased the risk of visual axis opacification. Adverse events and glaucoma correlated with a younger age at surgery and glaucoma correlated with the presence of microcornea.

Sudden-onset trochlear nerve palsy: clinical characteristics and treatment implications.

PURPOSE: To identify clinical characteristics, etiologies, and treatment implications of sudden-onset, acquired cases of superior oblique palsy. METHODS: The medical records of patients diagnosed with trochlear nerve palsy between January 2010 and January 2018 were reviewed retrospectively to identify cases of acquired trochlear nerve palsy with a specific date of onset of acute symptoms or specific causative incident. Patients with congenital palsies or an uncertain date of onset, history of other strabismus, concomitant oculomotor or abducens nerve palsies, or history of strabismus surgery were excluded. RESULTS: Of 214 patients with superior oblique palsy, 23 had sudden-onset, acquired palsies. There were 14 cases of unilateral palsy and 9 cases of bilateral palsy. Patients with unilateral palsy presented with vertical diplopia, while those with bilateral palsy complained of either torsional (4/9 patients) or vertical (5/9 patients) diplopia. The most common etiologies were severe trauma associated with traumatic brain injury, followed by central nervous system neoplasm and stroke. Fifteen patients underwent surgical intervention, 3 of whom required more than one surgery. CONCLUSIONS: Patients with acute superior oblique palsy invariably complain of vertical and/or torsional diplopia. Neuroimaging should be considered in cases of acquired superior oblique palsy without a known traumatic cause. Bilateral cases of acquired superior oblique palsy are more challenging to manage surgically because of symptomatic torsional diplopia.

Outcomes of Unilateral Cataracts in Infants and Toddlers 7 to 24 Months of Age: Toddler Aphakia and Pseudophakia Study (TAPS).

PURPOSE: To evaluate outcomes of unilateral cataract surgery in children 7 to 24 months of age. DESIGN: Retrospective case series at 10 Infant Aphakia Treatment Study (IATS) sites. PARTICIPANTS: The Toddler Aphakia and Pseudophakia Study is a registry of children treated by surgeons who participated in the IATS. METHODS: Children underwent unilateral cataract surgery with or without intraocular lens (IOL) placement during the IATS enrollment years of 2004 and 2010. MAIN OUTCOME MEASURES: Intraoperative complications, adverse events (AEs), visual acuity, and strabismus. RESULTS: Fifty-six children were included with a mean postoperative follow-up of 47.6 months. Median age at cataract surgery was 13.9 months (range, 7.2-22.9). Ninety-two percent received a primary IOL. Intraoperative complications occurred in 4 patients (7%). At 5 years of age, visual acuity of treated eyes was very good (≥20/40) in 11% and poor (≤20/200) in 44%. Adverse events were identified in 24%, with a 4% incidence of glaucoma suspect. An additional unplanned intraocular surgery occurred in 14% of children. Neither AEs nor intraocular reoperations were more common for children with surgery at 7 to 12 months of age than for those who underwent surgery at 13 to 24 months of age (AE rate, 21% vs. 25% [P = 0.60]; reoperation rate, 13% vs. 16% [P = 1.00]). CONCLUSIONS: Although most children underwent IOL implantation concurrent with unilateral cataract removal, the incidence of complications, reoperations, and glaucoma was low when surgery was performed between 7 and 24 months of age and compared favorably with same-site IATS data for infants undergoing surgery before 7 months of age. Our study showed that IOL implantation is relatively safe in children older than 6 months and younger than 2 years.

Immediate Postoperative Alignment Measurements as a Predictor of Alignment Stability in Fixed Suture Strabismus Surgery.

PURPOSE: To evaluate the use of immediate postoperative alignment measurements as a predictor of future alignment stability in fixed suture strabismus surgery. METHODS: Forty-seven patients were prospectively evaluated after undergoing horizontal or vertical rectus muscle surgery using a fixed suture technique. Alignment measurements were taken approximately 1 hour, 1 to 3 weeks, and 2 to 3 months postoperatively. A Spearman correlation coefficient was used to compare measurements from the immediate postoperative period to the 2- to 3-month postoperative period. Patients with dissociated strabismus, only oblique muscle surgery, or poor vision in one or both eyes precluding precise alternate cover test were excluded. RESULTS: Mean age of all patients was 46.7 years (range: 12 to 86 years). Twenty-two patients underwent surgery for exotropia: 19 for esotropia and 6 for hypertropia. Mean alignment for all surgeries was 2 prism diopters (PD) undercorrection in the immediate postoperative period, which was similar to the mean of 4.6 PD undercorrection at 2 to 3 months postoperatively. However, the Spearman correlation between the immediate postoperative and 2- to 3-month postoperative measurements was 0.18 for all surgeries, 0.03 for exotropia, 0.56 for esotropia, and 0.40 for hypertropia. The overall success rate, defined as 8 PD or less of horizontal deviation and 4 PD or less of vertical deviation, was 77% at 2 to 3 months postoperatively. CONCLUSIONS: The relationship between immediate postoperative alignment and future alignment stability in fixed suture strabismus surgery has not been previously defined. The current study demonstrated that although the surgical success rate was reasonably good, poor correlation occurred between the alignment immediately postoperatively and 2 to 3 months postoperatively. [J Pediatr Ophthalmol Strabismus. 2018;55(4):240-244.].

Long-term efficacy of endoscopic cyclophotocoagulation in the management of glaucoma following cataract surgery in children.

PURPOSE: To report the long-term efficacy of endoscopic cyclophotocoagulation (ECP) in pediatric glaucoma following cataract surgery (GFCS). METHODS: ECP was performed on 35 eyes of 25 patients <16 years of age with GFCS. Patients were followed for a minimum of 2 years. Treatment failure was defined as consecutive postoperative intraocular pressure (IOP) of >24 mm Hg, alternative glaucoma procedure following ECP, or occurrence of visually significant complications. Analysis was performed to estimate risk factors for failure. RESULTS: A total of 27 aphakic and 8 pseudophakic eyes were included. Pretreatment IOP averaged 33.9 ± 7.9 mm Hg. Final IOP after a mean follow-up period of 7.2 years was 18.9 ± 8.8 mm Hg (P < 0.001). The success rate was 54% (19/35 eyes). The failure rate was not increased in pseudophakic patients relative to aphakic patients. Patients with single ECP demonstrated preserved visual acuity from baseline to final follow-up. CONCLUSIONS: In this patient cohort, with average follow-up period of 7.2 years, ECP was useful in the treatment of pediatric GFCS.

Peters anomaly in PHACE syndrome.

PHACE syndrome is a rare neurocutaneous disorder, with a complex pathogenesis. It presents with a large facial hemangioma associated with anomalies of the posterior fossa of the brain, arterial anomalies, cardiac anomalies, coarctation of the aorta, and eye anomalies. Ocular abnormalities are rare. We report the first published case of an infant with PHACE syndrome and Peters anomaly.

An international survey of classification and treatment choices for group D retinoblastoma.

AIM: To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. METHODS: An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism. RESULTS: The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children's Hospital of Los Angeles (CHLA) version, 33% used the Children's Oncology Group (COG) version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were: Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were: Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center (P<0.0001). CONCLUSION: Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.

Anisometropia at Age 5 Years After Unilateral Intraocular Lens Implantation During Infancy in the Infant Aphakia Treatment Study.

PURPOSE: To report the prevalence of anisometropia at age 5 years after unilateral intraocular lens (IOL) implantation in infants. DESIGN: Prospective randomized clinical trial. METHODS: Fifty-seven infants in the Infant Aphakia Treatment Study (IATS) with a unilateral cataract were randomized to IOL implantation with an initial targeted postoperative refractive error of either +8 diopters (D) (infants 28 to <48 days of age) or +6 D (infants 48-210 days of age). Anisometropia was calculated at age 5 years. Six patients were excluded from the analyses. RESULTS: Median age at cataract surgery was 2.2 months (interquartile range [IQR], 1.2, 3.5 months). The mean age at the age 5 years follow-up visit was 5.0 ± 0.1 years (range, 4.9-5.4 years). The median refractive error at the age 5 years visit of the treated eyes was -2.25 D (IQR -5.13, +0.88 D) and of the fellow eyes +1.50 D (IQR +0.88, +2.25). Median anisometropia was -3.50 D (IQR -8.25, -0.88 D); range -19.63 to +2.75 D. Patients with glaucoma in the treated eye (n = 9) had greater anisometropia (glaucoma, median -8.25 D; IQR -11.38, -5.25 D vs no glaucoma median -2.75; IQR -6.38, -0.75 D; P = .005). CONCLUSIONS: The majority of pseudophakic eyes had significant anisometropia at age 5 years. Anisometropia was greater in patients that developed glaucoma. Variability in eye growth and myopic shift continue to make refractive outcomes challenging for IOL implantation during infancy.

Myopic Shift 5 Years after Intraocular Lens Implantation in the Infant Aphakia Treatment Study.

PURPOSE: To report the myopic shift at 5 years of age after cataract surgery with intraocular lens (IOL) implantation for infants enrolled in the Infant Aphakia Treatment Study (IATS). METHODS: Refractions were performed at 1 month and every 3 months postoperatively until age 4 years and then at ages 4.25, 4.5, and 5 years. The change in refraction over time was estimated by linear mixed model analysis. RESULTS: Intraocular lens implantation was completed in 56 eyes; 43 were analyzed (median age, 2.4 months; range, 1.0-6.8 months). Exclusions included 11 patients with glaucoma, 1 patient with Stickler syndrome, and 1 patient with an IOL exchange at 8 months postoperatively. The mean rate of change in a myopic direction from 1 month after cataract surgery to age 1.5 years was 0.35 diopters (D)/month (95% confidence interval [CI], 0.29-0.40 D/month); after age 1.5 years, the mean rate of change in a myopic direction was 0.97 D/year (95% CI, 0.66-1.28 D/year). The mean refractive change was 8.97 D (95% CI, 7.25-10.68 D) at age 5 years for children 1 month of age at surgery and 7.22 D (95% CI, 5.54-8.91 D) for children 6 months of age at surgery. The mean refractive error at age 5 years was -2.53 D (95% CI, -4.05 to -1.02). CONCLUSIONS: After IOL implantation during infancy, the rate of myopic shift occurs most rapidly during the first 1.5 years of life. Myopic shift varies substantially among patients. If the goal is emmetropia at age 5 years, then the immediate postoperative hypermetropic targets should be +10.5 D at 4 to 6 weeks and +8.50 D from 7 weeks to 6 months. However, even using these targets, it is likely that many children will require additional refractive correction given the high variability of refractive outcomes.

Comparison of the rate of refractive growth in aphakic eyes versus pseudophakic eyes in the Infant Aphakia Treatment Study.

PURPOSE: To compare the rate of refractive growth (RRG) between aphakic eyes and pseudophakic eyes in the Infant Aphakia Treatment Study (IATS). SETTING: Twelve clinical sites across the United States. DESIGN: Randomized clinical trial. METHODS: Patients randomized to unilateral cataract extraction with contact lens correction versus intraocular lens (IOL) implantation in the IATS had their rate of refractive growth (RRG3) calculated based on the change in refraction from the 1-month postoperative examination to age 5 years. The RRG3 is a logarithmic formula designed to calculate the RRG in children. Two-group t tests were used to compare the mean refractive growth between the contact lens group and IOL group and outcomes based on age at surgery and visual acuity. RESULTS: Longitudinal refractive data were studied for 108 of 114 patients enrolled in the IATS (contact lens group, n = 54; IOL group, n = 54). The mean RRG3 was similar in the contact lens group (-18.0 diopter [D] ± 11.0 [SD]) and the IOL group (-19.0 ± 9.0 D) (P = .49). The RRG3 value was not correlated with age at cataract surgery, glaucoma status, or visual outcome in the IOL group. In the aphakia group, only visual outcome was correlated with refractive growth (P = .01). CONCLUSIONS: Infants' eyes had a similar rate of refractive growth after unilateral cataract surgery whether or not an IOL was implanted. A worse visual outcome was associated with a higher RRG in aphakic, but not pseudophakic, eyes. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

A pilot randomized clinical trial of intermittent occlusion therapy liquid crystal glasses versus traditional patching for treatment of moderate unilateral amblyopia.

PURPOSE: To compare the effectiveness of intermittent occlusion therapy (IO therapy) using liquid crystal glasses and continuous occlusion therapy using traditional adhesive patches for treating amblyopia. METHODS: Children 3-8 years of age with previously untreated, moderate, unilateral amblyopia (visual acuity of 20/40 to 20/100 in the amblyopic eye) were enrolled in this randomized controlled trial. Amblyopia was associated with strabismus, anisometropia, or both. All subjects had worn any optimal refractive correction for at least 12 weeks without improvement. Subjects were randomized into two treatment groups: a 4-hour IO therapy group with liquid crystal glasses (Amblyz), set at 30-second opaque/transparent intervals (occluded 50% of wear time), and a 2-hour continuous patching group (occluded 100% of wear time). For each patient, visual acuity was measured using ATS-HOTV before and after 12 weeks of treatment. RESULTS: Data from 34 patients were available for analysis. Amblyopic eye visual acuity improvement from baseline was 0.15 ± 0.12 logMAR (95% CI, 0.09-0.15) in the IO therapy group (n = 19) and 0.15 ± 0.11 logMAR (95% CI, 0.1-0.15) in the patching group (n = 15). In both groups improvement was significant, but the difference between groups was not (P = 0.73). No adverse effects were reported. CONCLUSIONS: In this pilot study, IO therapy with liquid crystal glasses is not inferior to adhesive patching and is a promising alternative treatment for children 3-8 years of age with moderate amblyopia.

Use of the Delphi process in paediatric cataract management.

PURPOSE: To identify areas of consensus and disagreement in the management of paediatric cataract using a modified Delphi approach among individuals recognised for publishing in this field. DESIGN: A modified Delphi method. PARTICIPANTS: International paediatric cataract experts with a publishing record in paediatric cataract management. METHODS: The process consisted of three rounds of anonymous electronic questionnaires followed by a face-to-face meeting, followed by a fourth anonymous electronic questionnaire. The executive committee created questions to be used for the electronic questionnaires. Questions were designed to have unit-based, multiple choice or true-false answers. The questionnaire included issues related to the preoperative, intraoperative and postoperative management of paediatric cataract. MAIN OUTCOME MEASURE: Consensus based on 85% of panellists being in agreement for electronic questionnaires or 80% for the face-to-face meeting, and near consensus based on 70%. RESULTS: Sixteen of 22 invited paediatric cataract surgeons agreed to participate. We arrived at consensus or near consensus for 85/108 (78.7%) questions and non-consensus for the remaining 23 (21.3%) questions. CONCLUSIONS: Those questions where consensus was not reached highlight areas of either poor evidence or contradicting evidence, and may help investigators identify possible research questions.

High-sensitivity sequencing reveals multi-organ somatic mosaicism causing DICER1 syndrome.

BACKGROUND: Somatic mosaicism is being increasingly recognised as an important cause of non-Mendelian presentations of hereditary syndromes. A previous whole-exome sequencing study using DNA derived from peripheral blood identified mosaic mutations in DICER1 in two children with overgrowth and developmental delay as well as more typical phenotypes of germline DICER1 mutation. However, very-low-frequency mosaicism is difficult to detect, and thus, causal mutations can go unnoticed. Highly sensitive, cost-effective approaches are needed to molecularly diagnose these persons. We studied four children with multiple primary tumours known to be associated with the DICER1 syndrome, but in whom germline DICER1 mutations were not detected by conventional mutation detection techniques. METHODS AND RESULTS: We observed the same missense mutation within the DICER1 RNase IIIb domain in multiple tumours from different sites in each patient, raising suspicion of somatic mosaicism. We implemented three different targeted-capture technologies, including the novel HaloPlex(HS) (Agilent Technologies), followed by deep sequencing, and confirmed that the identified mutations are mosaic in origin in three patients, detectable in 0.24-31% of sequencing reads in constitutional DNA. The mosaic origin of patient 4's mutation remains to be unequivocally established. We also discovered likely pathogenic second somatic mutations or loss of heterozygosity (LOH) in tumours from all four patients. CONCLUSIONS: Mosaic DICER1 mutations are an important cause of the DICER1 syndrome in patients with severe phenotypes and often appear to be accompanied by second somatic truncating mutations or LOH in the associated tumours. Furthermore, the molecular barcode-containing HaloPlex(HS) provides the sensitivity required for detection of such low-level mosaic mutations and could have general applicability.