Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

OBJECTIVE: To develop Canadian recommendations for the screening, monitoring, and treatment of uveitis associated with juvenile idiopathic arthritis (JIA). METHODS: Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach. A working group of 14 pediatric rheumatologists, 6 ophthalmologists, 2 methodologists, and 3 caregiver/patient representatives reviewed recent American College of Rheumatology (ACR)/Arthritis Foundation (AF) recommendations and worked in pairs to develop evidence-to-decision (EtD) tables. A survey to assess agreement and recommendations requiring group discussion was completed. EtD tables were presented, discussed, and voted upon at a virtual meeting, to produce the final recommendations. A health equity framework was applied to all aspects of the adolopment process including the EtD tables, survey responses, and virtual meeting discussion. RESULTS: The survey identified that 7 of the 19 recommendations required rigorous discussion. Seventy-five percent of working group members attended the virtual meeting to discuss controversial topics as they pertained to the Canadian environment, including timing to first eye exam, frequency of screening, escalation criteria for systemic and biologic therapy, and the role of nonbiologic therapies. Equity issues related to access to care and advanced therapeutics across Canadian provinces and territories were highlighted. Following the virtual meeting, 5 recommendations were adapted, 2 recommendations were removed, and 1 was developed de novo. CONCLUSION: Recommendations for JIA-associated uveitis were adapted to the Canadian context by a working group of pediatric rheumatologists, ophthalmologists with expertise in the management of uveitis, and parent/patient input, taking into consideration cost, equity, and access.

Trametinib therapy for children with neurofibromatosis type 1 and life-threatening plexiform neurofibroma or treatment-refractory low-grade glioma.

PURPOSE: To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. METHODS: We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. RESULTS: Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. CONCLUSION: Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.

Guide de pratique clinique fondé sur des données probantes pour l'examen périodique de la vue chez les enfants de 0 à 5 ans au Canada.

CONTEXTE: Étant donné que les maladies oculaires avant l'âge de 5 ans sont courantes, une certaine forme de dépistage des troubles de la vision devrait être effectuée chez les enfants avant qu'ils ne fréquentent l'école primaire. Cependant, l'absence de recommandations nationales cohérentes crée de la confusion chez les patients, les professionnels des soins oculovisuels et les gouvernements. MéTHODES: L'objectif de ce document est de fournir des recommandations quant aux types d'examens oculaires à pratiquer chez les enfants en bonne santé de 0 à 5 ans ainsi que sur le moment et la périodicité de tels examens. Une recension des écrits a produit 403 articles. Un comité d'experts multidisciplinaire (composé de deux optométristes, d'un ophtalmologiste effectuant des examens complets de la vue, d'un ophtalmologiste pratiquant en pédiatrie, d'un médecin de famille et d'un pédiatre) a établi de façon indépendante les articles jugés essentiels à la question clinique. Les articles se prêtant à un classement [n = 16] ont ensuite été soumis à une évaluation critique indépendante par un groupe externe, lequel a fourni un profil « GRADE ¼ des articles à utiliser et leur a attribué une cote. RECOMMANDATIONS: En plus du dépistage de routine effectué par les professionnels de première ligne, un examen complet de la vue mené par un professionnel possédant l'expertise nécessaire à la détection des facteurs de risque de l'amblyopie (comme un ophtalmologiste ou un optométriste) est requis durant la petite enfance. Les conclusions confirment l'importance de la détection précoce de l'amblyopie avant 36 mois et au plus tard 48 mois par le dépistage assorti d'au moins un examen complet de la vue avant l'âge de 5 ans. CONCLUSIONS: Le dépistage de la vue effectué chez les bébés et les enfants par les fournisseurs de soins de première ligne au cours des consultations de routine et des vaccinations périodiques est un élément essentiel de la détection des maladies oculaires. Toutefois, le potentiel de détection précoce est limité et un examen oculovisuel complet est également recommandé avant que l'enfant n'entre à l'école. Si l'amblyopie, le strabisme ou une autre pathologie oculaire est détecté ou soupçonné, et que le problème dépasse le champ de compétences du professionnel qui examine le patient, celui-ci peut être dirigé vers le spécialiste approprié, ce qui permet d'amorcer le traitement en temps opportun.

Evidence-based clinical practice guidelines for the periodic eye examination in children aged 0-5 years in Canada.

BACKGROUND: As eye disease before age 5 years is common, some form of vision screening should be performed on children before attending primary school. However, the lack of consistent national recommendations creates confusion for patients, eye care professionals, and governments alike. METHODS: The objective of this document is to provide guidance on the recommended timing, intervals, and types of ocular assessments for healthy children aged 0-5 years. A literature search yielded 403 articles. A multidisciplinary expert committee (comprising 2 optometrists, a comprehensive ophthalmologist, a pediatric ophthalmologist, a family physician, and a pediatrician) independently determined those articles deemed to be key to the clinical question. Articles that were gradable (n = 16) were then submitted for independent critical appraisal by an external review group, which provided a Grading of Recommendations Assessment, Development and Evaluation profile of the reviewed articles to use for assigning a grade of evidence. RECOMMENDATIONS: In addition to routine screening by a primary health care professional, a comprehensive eye examination by an individual with the expertise to detect risk factors for amblyopia-such as an ophthalmologist or optometrist-is required in early childhood. The findings support the importance of early detection of amblyopia before 36 months and no later than 48 months of age via screening with at least 1 comprehensive eye examination before age 5 years. CONCLUSIONS: Vision screening performed by primary health care providers during routine well-baby/child visits and scheduled vaccinations is an essential part of the detection of ocular disease. However, this early detection potential is limited, and a full oculovisual assessment is also recommended before the child entering the school system. If amblyopia, strabismus, or other eye pathology is detected or suspected that is beyond the scope of the eye care professional examining the patient, a referral to the appropriate specialist can be made, allowing treatment to be initiated in a timely fashion.

Evaluation of ophthalmology clerkships across teaching sites at the University of British Columbia.

OBJECTIVE: Clerkship at the University of British Columbia (UBC) Medical School encompasses a variety of models: traditional rotation-based clerkship; distributed rotation-based clerkship at sites across the province; and a longitudinal integrated community clerkship. The purpose of this study was to: (i) Evaluate the undergraduate ophthalmology clerkship experience at UBC to compare outcomes and experiences across the various sites and models; and (ii) Apply educational theories to evaluation outcomes in order to improve curriculum design for clerkship programs. DESIGN: Cross-sectional evaluation of the ophthalmology clerkship program at UBC. METHODS: Using a logic model, we identified inputs, activities, and outputs of the ophthalmology clerkship experience at each site at UBC. Site directors and administrators were contacted for information regarding program curriculum and delivery, and outcomes were described using written exam and clinical assessment scores as well as student and instructor feedback (questionnaires with narrative responses). RESULTS: Site directors and administrators from all clerkship sites participated in the study. Clerkship experiences across all sites (rotation-based and integrated community clerkship) were found to be unique in contexts and clinical activities. There were no significant differences noted between outcomes in the rotation-based sites. CONCLUSION: Clerkship experiences can be delivered in various contexts and through varied clinical settings, yet provide an equivalent student learning experience. As longitudinal and distributed clerkship models gain traction in medical education around the world, there are lessons for undergraduate medical education both in ophthalmology and in other areas.

Severe retinopathy of prematurity predicts delayed white matter maturation and poorer neurodevelopment.

OBJECTIVE: To determine whether severe retinopathy of prematurity (ROP) is associated with (1) abnormal white matter maturation and (2) neurodevelopmental outcomes at 18 months' corrected age (CA) compared with neonates without severe ROP. DESIGN: We conducted a prospective longitudinal cohort of extremely preterm neonates born 24-28 weeks' gestational age recruited between 2006 and 2013 with brain MRIs obtained both early in life and at term-equivalent age. Severe ROP was defined as ROP treated with retinal laser photocoagulation. Using diffusion tensor imaging and tract-based spatial statistics (TBSS), white matter maturation was assessed by mean fractional anisotropy (FA) in seven predefined regions of interest. Neurodevelopmental outcomes were assessed with Bayley Scales of Infant and Toddler Development-III (Bayley-III) composite scores at 18 months' CA. Subjects were compared using Fisher's exact, Kruskal-Wallis and generalised estimating equations. SETTING: Families were recruited from the neonatal intensive care unit at BC Women's Hospital. PATIENTS: Of 98 extremely preterm neonates (median: 26.0 weeks) assessed locally for ROP, 19 (19%) had severe ROP and 83 (85%) were assessed at 18 months' CA. RESULTS: Severe ROP was associated with lower FA in the posterior white matter, and with decreased measures of brain maturation in the optic radiations, posterior limb of the internal capsule (PLIC) and external capsule on TBSS. Bayley-III cognitive and motor scores were lower in infants with severe ROP. CONCLUSIONS: Severe ROP is associated with maturational delay in the optic radiations, PLIC, external capsule and posterior white matter, housing the primary visual and motor pathways, and is associated with poorer cognitive and motor outcomes at 18 months' CA.

Painful Acute Corneal Ulceration and Anterior Stromal Keratitis in an Adolescent With Reactive Arthritis.

Reactive arthritis is occasionally associated with conjunctivitis and uveitis, but rarely keratitis. The authors describe a patient with paracentral anterior stromal keratitis with overlying epithelial erosion and multiple satellite subepithelial infiltrates. The initial appearance and the severe pain were suggestive of an infectious process. Recovery was rapid following introduction of topical steroid, with features suggesting an immune process in the recovery phase. The authors suggest that a history of arthritis and/or recent enteritis should be sought in the work-up of an atypical keratitis with or without epithelial defect. [J Pediatr Ophthalmol Strabismus. 2016;53:e61-e63.].

Prenatal versus Postnatal Screening for Familial Retinoblastoma.

PURPOSE: To compare overall outcomes of conventional postnatal screening of familial retinoblastoma and prenatal RB1 mutation identification followed by planned early-term delivery. DESIGN: Retrospective, observational study. PARTICIPANTS: Twenty children with familial retinoblastoma born between 1996 and 2014 and examined within 1 week of birth. METHODS: Cohort 1 included spontaneously delivered neonates examined within 1 week of birth and confirmed postnatal to carry their family's RB1 mutant allele. Cohort 2 included infants identified by amniocentesis to carry their family's RB1 mutant allele, and therefore scheduled for early-term delivery (36-38 weeks' gestation). Treatment for retinoblastoma was performed at the Hospital for Sick Children, Toronto, Canada. MAIN OUTCOME MEASURES: Age at first tumor in each eye, eye stage, treatments given, ocular salvage, treatment success (defined as avoidance of enucleation, external-beam irradiation, or both), visual outcome, number of anesthetics, pregnancy or delivery complications, and estimated treatment burden. RESULTS: Vision-threatening tumors were present at birth in 4 of 8 infants in cohort 1 and in 3 of 12 infants in cohort 2. Eventually, all infants demonstrated tumors in both eyes. At the first treatment, 1 of 8 infants in cohort 1 had eyes in stage cT1a/cT1a or cT1a/cT0 (smallest and least vision-threatening tumors), compared with 8 of 12 infants in cohort 2 (P = 0.02). Null RB1 germline alleles induced earlier tumors than low-penetrance alleles (P = 0.03). Treatment success was achieved in 3 of 8 children in cohort 1 compared with 11 of 12 children in cohort 2 (P = 0.002). Acceptable vision (better than 0.2 decimal) was achieved for 8 of 16 eyes in cohort 1 compared with 21 of 24 eyes in cohort 2 (P = 0.014). Useful vision (better than 0.1, legal blindness) was achieved for 8 of 9 children in cohort 1 compared with 12 of 12 children in cohort 2. There were no complications related to early-term delivery. Median follow-up was 5.6 years, cohort 1 and 5.8 years, cohort 2. CONCLUSIONS: When a parent had retinoblastoma, prenatal molecular diagnosis with early-term delivery increased the likelihood of infants born with no detectable tumors, better vision outcomes, and less invasive therapy. Prenatal molecular diagnosis facilitates anticipatory planning for both the child and family.

A variant of unknown significance in the GLA gene causing diagnostic uncertainty in a young female with isolated hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is genetically heterogeneous, and largely caused by mutations in genes encoding sarcomere proteins. However, GLA mutations causing Fabry disease, an X-linked lysosomal storage disorder, may also present with isolated HCM. As HCM genetic testing panels are increasingly being used clinically, variants of unknown significance (VUS) are encountered, leading to challenges in interpretation. We present an illustrative case: a 10-year-old girl with isolated HCM who, on testing with a HCM multi-gene panel, was found to carry a maternally inherited p.W24R variant in GLA. Attempts to evaluate the significance of this variant, by direct biochemical testing of patient specimens, gave inconclusive results. Subsequent in vitro protein expression studies suggested that the variant is unlikely to be pathogenic. This case highlights diagnostic dilemmas that can be provoked by VUS in general, and specifically raises a question whether GLA sequencing should be included in first-line diagnostic testing for female children with isolated hypertrophic cardiomyopathy.

Ophthalmic complications of otitis media in children.

PURPOSE: To evaluate the outcome of ophthalmic complications in children with otitis media. METHODS: The records of children with ophthalmic complications arising from otitis media who presented to the British Columbia Children's Hospital between August 2006 and March 2008 were reviewed retrospectively. RESULTS: Of 1,400 patients presenting to the emergency department for otitis media during the study period, 7 with ophthalmic complications were identified (age range, 1-11 years). All patients had abducens nerve palsy on presentation. Other notable ophthalmic complications included papilledema, Horner syndrome, and proptosis. Extracranial and intracranial complications included mastoiditis, petrositis, parapharyngeal abscess, hydrocephalus, epidural abscess, and cerebral venous thrombosis, including cavernous sinus thrombosis in 2. Of the 7 patients, 6 were treated with surgery, including myringotomy and tube placement (6 patients) and mastoidectomy (3 patients). All patients were initially anticoagulated and received intravenous antibiotics. Satisfactory final visual outcomes and stereopsis ranging from 40 to 100 seconds were achieved in all patients. CONCLUSIONS: Ophthalmic complications of otitis media in children are likely to include abducens palsy. All patients in our series required anticoagulation and intravenous antibiotics. Most required otolaryngologic surgery, but none required strabismus surgery, and all patients had satisfactory visual and ocular motility outcomes.

The effect of changing oxygen saturation protocols on the incidence of laser treatment for retinopathy of prematurity.

OBJECTIVE: To compare the incidence of retinopathy of prematurity (ROP) requiring laser treatment among infants with birth weights of ≤ 1250 g before and after the implementation of a new oxygen saturation protocol in the neonatal intensive care unit of British Columbia Children's Hospital. DESIGN: Retrospective, comparative review of medical records. PARTICIPANTS: Premature infants with birth weights of ≤ 1250 g who were screened for retinopathy of prematurity from November 2003 to October 2005 and February 2006 to January 2008 (269 patients). METHODS: The hospital's ROP database was reviewed, and the patients were divided into 2 groups. The preprotocol group (November 2003-October 2005) consisted of patients who were screened before the new oxygen monitoring protocol was instituted and the postprotocol group (February 2006-January 2008) consisted of patients screened after its implementation. RESULTS: A total of 141 patients were in the preprotocol group and 128 patients in the postprotocol group. The mean birth weight and gestational age of the 2 groups were comparable (p = 0.81, 0.71, respectively). There was a 30% reduction in the incidence of laser treatment in the postprotocol group (preprotocol group = 22/141 [15.6%] vs postprotocol group = 13/128 [10.2%]; p = 0.19). CONCLUSIONS: We observed a decrease in the rate of severe ROP requiring laser treatment after the implementation of the new oxygen monitoring protocol. While not statistically significant, this is consistent with what has been found at other centres.

Therapy resistant neonatal seizures, linear vesicular rash, and unusually early neuroradiological changes: incontinentia pigmenti: a case report, literature review and insight into pathogenesis.

CASE PRESENTATION: A substance abusing G2P1 mother spontaneously delivered at term an appropriate for gestational age girl. Neonatal seizures appeared at 21 hours and empiric anticonvulsive and antimicrobial treatment was started. At 25 hours, first vesicles appeared. While routine evaluations remained normal, a head CT revealed multifocal ischemic injuries, and a later MRI showed multifocal petechiae and diffusion abnormalities in the corticospinal tracts. The clinical diagnosis of incontinentia pigmenti (stage 1) was secured by histopathology. Follow-up at 13 months showed global developmental delay. DISCUSSION: We discuss the unusually early bilateral, fronto-occipital corticomedullar ischemias (CT day 3). On the MR imaging (day 7) extensive symmetric cerebral corticomedullar destruction and diffusion sequences with corticospinal tracts abnormalities are seen, which then evolve (day 26) to extensive symmetric cerebral destruction. We review the literature, genetics, suspected pathophysiology and possible neonatal manifestation. CONCLUSION: Incontinentia pigmenti is rare and, therefore, diagnosis is frequently delayed. Nevertheless, in the setting of therapy refractory seizures, excluded infections, and linear vesicular rash, a high index of suspicion is needed. This is the first report of simultaneous corticomedullar involvement as early as the third day of life.

Superfetation as a cause of growth discordance in a multiple pregnancy.

A triplet pregnancy is described, in which the diagnosis of in utero growth restriction is questioned after postnatal suspicion of superfetation, by using neurosonography and ophthalmic examination to aid gestational age assessment.

Vitrectomy for dense vitreous hemorrhage in infancy.

PURPOSE: To report clinical data, including etiology and visual outcome, in newborns requiring vitrectomy for dense vitreous hemorrhage. METHODS: In this retrospective case series, we surveyed subscribers to the American Association for Pediatric Ophthalmology and Strabismus ListServe regarding patients under their care. RESULTS: A total of 28 eyes of 21 patients were included. Most common etiologies were thrombocytopenia, shaken baby syndrome, and birth trauma. In 9 cases (12 eyes), the vitreous hemorrhage was idiopathic. Mean time between diagnosis and surgery was 1.4 months. Complications included strabismus, cataract, glaucoma, high myopia, and retinal detachment. Recognition visual acuities were available for 8 eyes: 20/25 (2 eyes), 20/30, 20/40 (2 eyes), 20/60 (2 eyes), and 20/100. One eye had no light perception. CONCLUSIONS: The etiologies encountered in our patients were similar to those reported previously. Visual outcomes were much worse in cases with retinal complications. Other patients had better visual outcomes. Despite potential surgical and postoperative complications, this series demonstrates favorable visual outcomes can be achieved following early vitrectomy in this setting.