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The purpose of this article is to determine the cause of Leber congenital amaurosis (LCA) in Chuuk state, Federated States of Micronesia (FSM). In this prospective observational case series, five patients with early-onset vision loss were examined in Chuuk state, FSM, during an ocular genetics visit to study the elevated incidence of microphthalmia. Because of their low vision these patients were incorrectly assumed to have microphthalmia. A complete ophthalmological exam established a clinical diagnosis of LCA. Candidate gene exons were sequenced with a targeted retinal dystrophy panel. Five subjects in three related families were diagnosed with LCA. All five were from Tonoas Island, within the Chuuk Lagoon, with ages ranging from 6 months to 16 years. DNA sequencing of affected individuals revealed a homozygous CRB1 NM_201253.3:c.3134del pathogenic variant, which was heterozygous in their parents. CRB1 genotypes were confirmed by a PCR restriction assay. We report identification of a founder pathogenic variant in CRB1 responsible for autosomal recessive LCA in this isolated community. This discovery will lead to appropriate recurrence risk counseling.

ImportanceFamilial exudative vitreoretinopathy (FEVR) is a nonsyndromic autosomal dominant retinal disorder commonly caused by variants in the FZD4 gene. This study investigates the potential role beyond ocular abnormalities for FZD4 gene variants in patients with FEVR.ObjectiveTo evaluate the role of FZD4 in symptoms beyond those associated with FEVR through a patient with biallelic variants in FZD4.Design, Setting, and ParticipantsThis case series included the DNA testing and phenotyping of 1 patient proband and her parents, combined with signaling assays, to determine the association of patient-derived compound heterozygous variants on FZD4 signaling and biologic function.Main Outcomes and MeasuresFZD4 genes were tested using next-generation sequencing and Sanger sequencing. Cell-based assays measured the effect of the variants on FZD4 signaling.ResultsThe proband presented with absent red reflexes from complete tractional retinal detachments diagnosed at 3 days of age and failed the newborn screening hearing test. Auditory brainstem response at 6 months of age showed bilateral mild to moderate high-frequency sensorineural hearing loss. The patient manifested developmental delays in speech and walking. Intravenous fluorescein angiography (IVFA) of the patient’s parents detected stage 1 FEVR. Genetic testing revealed 2 FZD4 variants in the patient, each variant found in 1 parent. Signaling assays confirmed that the presence of both variants was associated with significantly worse signaling activity compared with the heterozygous state.Conclusions and RelevanceResults of this case series suggest that extraocular syndromic FEVR was associated with FZD4 variants. The decrease in FZD4 signaling owing to the biallelic nature of the disease resulted in hearing deficits, developmental delays, and a more severe retinal phenotype.

Introduction: There is an increasing need for occupational therapists with the skills to provide low vision services, however, there is a lack of standardized training of low vision occupational therapy services. The purpose of this study is to design and evaluate a course for occupational therapy students to improve their skills and knowledge about ophthalmology and low vision. Methods: A multifaceted, 15-week curriculum using didactic learning, clinical experience, and reflective writing was created to instruct second-year occupational therapy students in ophthalmology and low vision. Participants included 19 occupational therapy students from Thomas Jefferson University. Each trainee participated in the course modules and then submitted their course evaluations and reflective writings for review. Participants evaluated their satisfaction with the course using a Likert-scale and open-ended comments. Reflective writing from each participant was reviewed by occupational therapy faculty authors (AB, AL). Results: Nineteen students participated in the course, with 19 (100%) of participants reporting being “satisfied” or “highly satisfied” with the course. Analysis of the reflective writings revealed three main themes: the impact of eye-related medical conditions on daily life, insight into the provider-patient interaction and relationship, and the potential role of the occupational therapist on the vision team as an agent to maximize patient adjustment and function. Discussion: This collaborative, multimodal interprofessional educational model can assist in training and sensitizing occupational therapy students in the areas of ophthalmology and low vision. Implications for Practitioners: This report provides a model for medical educators to utilize in the training of occupational therapy students.

Refractive surgery has been performed under general anesthesia on pediatric and neurobehaviorally challenged adults without reported loss of vision or serious complications. Persistent epithelial defect (PED) is a rare complication of photorefractive keratectomy (PRK) in the general refractive surgery population. We report a case of PED following PRK under general anesthesia for high myopia in a man with autism and ocular history of juvenile open-angle glaucoma and dry eye syndrome.

The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.

BackgroundAxenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition.MethodsGenetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses.Results128 individuals with causative variants inPITX2orFOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma forFOXC1-related ARS. Systemic anomalies were seen in all individuals withPITX2-related ARS and the majority of those withFOXC1-related ARS.PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum.FOXC1-related ARS exhibited characteristic hearing loss and congenital heart defects as well as previously unrecognised phenotypes of dental enamel hypoplasia and/or crowding, a range of skeletal and joint anomalies, hypotonia/early delay and feeding disorders with structural oesophageal anomalies in some. Brain imaging revealed highly penetrant white matter hyperintensities, colpocephaly/ventriculomegaly and frequent arachnoid cysts. The expanded phenotype ofFOXC1-related ARS identified here was found to fully overlap features of De Hauwere syndrome. The results were used to generate gene-specific management plans for the two types of ARS.ConclusionSince clinical features of ARS vary significantly based on the affected gene, it is critical that families are provided with a gene-specific diagnosis,PITX2-related ARS orFOXC1-related ARS. De Hauwere syndrome is proposed to be a FOXC1opathy.

Objective To assess the impact of eyeglass administration after a vision-screening program on standardized testing scores in school-aged children. Design Retrospective study of children who participated in a vision-screening program that provided free eyeglasses where indicated. Participants Students in kindergarten through grade 5 in a large urban school district in North America. Methods Children in kindergarten through grade 3 were administered the Developmental Reading Assessment (DRA), and children in grades 3 through 5 were administered the Pennsylvania System of School Assessment (PSSA). Classroom teachers completed eyeglass adherence questionnaires. Results A total of 4523 children participated in the vision-screening program. Eyeglasses were worn most of the time (>75%) by 67.4% of the children and never or rarely worn ( Conclusions In some children, wearing eyeglasses was associated with maintenance in standardized reading scores. High adherence to wearing eyeglasses suggests that children perceive a benefit, perhaps beyond that which these standardized test results were able to document.

Neurosurgical procedures may occur prior to eye examination in children with suspected abusive head trauma and raise questions by child abuse physicians and ophthalmologists regarding the contribution of neurosurgery to retinal hemorrhage found postoperatively. The purpose of this study was to determine the prevalence and patterns of retinal hemorrhage attributable to neurosurgical intervention in children.We conducted a retrospective cohort study of children undergoing neurosurgery who had postoperative ophthalmoscopy. Some children were also examined preoperatively. Primary outcome measures were the prevalence and patterns of retinal hemorrhage attributable to neurosurgical intervention. Medical records were reviewed to identify confounding coexistent diseases.Among 267 children undergoing 289 neurosurgical procedures, there were no cases in which children had post-procedural retinal hemorrhage that could be attributed to neurosurgery. Retinal hemorrhage was seen in 32 (12%) cases, but in every case they were either already present on preoperative examination (13 cases) or matched the pattern of a coexistent known cause of retinal hemorrhage, including head trauma with unambiguous history and/or nonocular signs (13), hydrocephalus-related increased intracranial pressure with papilledema-associated peripapillary retinal hemorrhage (5), and retinopathy of prematurity ridge-associated retinal hemorrhage (1). No retinal hemorrhage could be attributed only to neurosurgery.Although children undergoing child abuse evaluations may have intracranial hemorrhage requiring neurosurgery that occurs before a dilated retinal examination can be performed, our data suggest that neurosurgery independently is unlikely to produce retinal hemorrhage and therefore is not a significant confounding factor in the interpretation of retinal hemorrhage patterns in child abuse evaluations.

International audience; Cyclic nucleotide-gated channel β1 (CNGB1) encodes the 240-kDa β subunit of the rod photoreceptor cyclic nucleotide-gated ion channel. Disease-causing sequence variants in CNGB1 lead to autosomal recessive rod-cone dystrophy/retinitis pigmentosa (RP). We herein present a comprehensive review and analysis of all previously reported CNGB1 sequence variants, and add 22 novel variants, thereby enlarging the spectrum to 84 variants in total, including 24 missense variants (two of which may also affect splicing), 21 nonsense, 19 splicing defects (7 at noncanonical positions), 10 small deletions, 1 small insertion, 1 small insertion-deletion, 7 small duplications, and 1 gross deletion. According to the American College of Medical Genetics and Genomics classification criteria, 59 variants were considered pathogenic or likely pathogenic and 25 were variants of uncertain significance. In addition, we provide further phenotypic data from 34 CNGB1-related RP cases, which, overall, are in line with previous findings suggesting that this form of RP has long-term retention of useful central vision despite the early onset of night blindness, which is valuable for patient counseling, but also has implications for it being considered a priority target for gene therapy trials.

Gillespie syndrome (GLSP) is characterized by bilateral symmetric partial aplasia of the iris presenting as a fixed and large pupil, cerebellar hypoplasia with ataxia, congenital hypotonia, and varying levels of intellectual disability. GLSP is caused by either biallelic or heterozygous, dominant-negative, pathogenic variants in ITPR1. Here, we present a 5-year-old male with GLSP who was found to have a heterozygous, de novo intronic variant in ITPR1 (NM_001168272.1:c.5935-17G > A) through genome sequencing (GS). Sanger sequencing of cDNA from this individual's fibroblasts showed the retention of 15 nucleotides from intron 45, which is predicted to cause an in-frame insertion of five amino acids near the C-terminal transmembrane domain of ITPR1. In addition, qPCR and cDNA sequencing demonstrated reduced expression of both ITPR1 alleles in fibroblasts when compared to parental samples. Given the close proximity of the predicted in-frame amino acid insertion to the site of previously described heterozygous, de novo, dominant-negative, pathogenic variants in GLSP, we predict that this variant also has a dominant-negative effect on ITPR1 channel function. Overall, this is the first report of a de novo intronic variant causing GLSP, which emphasizes the utility of GS and cDNA studies for diagnosing patients with a clinical presentation of GLSP and negative clinical exome sequencing.

Craniosynostosis has a varied clinical spectrum, ranging from isolated single suture involvement to multisutural fusions. Syndromic and nonsyndromic patients require orchestrated and multidisciplinary care from birth to adulthood. Advances in our understanding of craniosynostosis over the last quarter-century have resulted in more systematic management of the problems associated with the syndromic and nonsyndromic forms of this condition. This review provides an update on the genetic basis of, management of strabismus and oculoplastic manifestations in, and visual surveillance of patients with craniosynostosis.

Background Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by multisystem abnormalities, including distinct ophthalmologic findings. In recent years, advances in molecular genetics have begun to provide new insight into the characterization of these clinical features and the genetic basis of the syndrome. Materials and methods We included 37 articles that were identified through an electronic search in PubMed and through the reference lists of previously conducted reviews. Studies of 30 or more patients were used to report frequencies of common and less common findings. Genotype-phenotype studies were used to provide additional information when available. Results Ocular anomalies are present in most patients with CdLS. Common findings include long eyelashes, synophrys, hirsutism of the eyebrows, peripapillary pigment ring, and myopia. Less common findings include hyperopia, ptosis, blepharitis, short palpebral fissure length, down-slanting palpebral fissures, mild microcornea, strabismus, nystagmus, and optic nerve abnormalities. Conclusions This review provides a comprehensive summary of the ophthalmologic findings in CdLS. Mutations in certain genes may be associated with specific ocular abnormalities, although future genotype studies are needed to further characterize these relationships.

To examine the incidence of uveitis in children prescribed prostaglandin analogs (PGAs) for glaucoma.In this dual-center cohort study, the medical records of consecutive patients18 years old treated with a PGA between January 1, 2012, and December 31, 2018, were reviewed retrospectively. Patients with all forms of glaucoma, including those with a prior history of uveitis, were included. Patients who had been on a PGA prior to their first recorded visit were excluded. Patient charts were reviewed for new or recurrent uveitis during the first year of PGA therapy.A total of 103 children (147 eyes) were included, with a total PGA exposure of 1,352 child-months. Ninety-eight children (142 eyes) tolerated the PGA without an episode of uveitis. Five patients with a documented prior history of uveitis experienced a unilateral episode of uveitis. A review of their medical records identified prescribed or unscheduled decrease in topical steroids or immunosuppressive medication as the most likely cause of uveitis recurrence.This study provides further evidence that PGAs are unlikely to induce uveitis in children being treated for glaucoma and suggests that this may also be true in those with a history of uveitis. We are unable to evaluate whether PGAs make recurrence more likely or the tapering of steroids more difficult.

Objective Optic nerve aplasia (ONA) is a rare ocular anomaly. We report ophthalmologic, systemic, and genetic findings in ONA. Methods Patients were identified through an International Pediatric Ophthalmology listserv and from the practice of the senior author. Participating Listserv physicians completed a data collection sheet. Children of all ages were included. Neuroimaging findings were also recorded. Results Nine cases of ONA are reported. Patients' ages ranged from 10 days to 2 years (median 9 months). Seven cases were bilateral. All patients had absence of the optic nerve and retinal vessels in the affected eye or eyes. Ophthalmologic findings included glaucoma, microcornea, persistent pupillary membrane, iris coloboma, aniridia, retinal dysplasia, retinal atrophy, chorioretinal coloboma, and persistent fetal vasculature. Systemic findings included facial dysmorphism, cardiac, genitourinary, skeletal, and developmental defects. A BCOR mutation was found in one patient. One patient had rudimentary optic nerves and chiasm on imaging. Conclusion ONA is a unilateral or bilateral condition that may be associated with anomalies of the anterior or posterior segment with or without systemic findings. Rudimentary optic nerve on neuroimaging in one case suggests that ONA is on the continuum of optic nerve hypoplasia.

Three patients with facial port wine birthmarks were randomly assigned to receive treatment with topical timolol or the placebo. Three masked observers evaluated photographs of the patients, noting improvement in patients who were treated with timolol and two controls. The photographic technique was not standardized. This pilot study suggests topical timolol warrants further evaluation for port wine birthmarks. [ J Pediatr Ophthalmol Strabismus . 2021;58(2):e1–e4.]

Background Epilepsy in typical Sturge-Weber syndrome (SWS) is common, and many questions remain regarding the treatment outcomes. We analyzed a large multicenter database with focus on neurological drug treatment in different demographic and SWS characteristic groups. Methods A total of 268 patients with brain involvement and a history of seizures were selected from a research data registry generated from a multicenter cross-sectional questionnaire. We examined associations between medication use and binary variables such as sex, ethnicity, and brain, skin, and eye involvement laterality. We analyzed group differences in mean number of antiseizure medications and age at diagnosis, enrollment, and seizure onset and examined differences in median SWS neurological scores in groups of interest. Results The most frequently used medications were levetiracetam (48.1%), low-dose aspirin (44.8%), oxcarbazepine (39.9%), and phenobarbital (14.9%). Lamotrigine was more frequently used in adults than in children (P = 0.001). History of neurosurgery was associated with no current antiseizure medication use (P = 0.001), whereas bilateral brain involvement and family history of seizures were associated with using a higher number of antiseizure medications (P = 0.002, P = 0.027, respectively). Subjects with bilateral brain involvement and early seizure onset were associated with using a higher number of antiseizure medications (P = 0.002) and phenobarbital use (0.003). Conclusions Levetiracetam, low-dose aspirin, and oxcarbazepine were the most frequently used medications. More severely affected patients were frequently on a greater number of antiseizure medications. Surgery for epilepsy was associated with the ability to discontinue antiseizure medication. Longitudinal studies are needed to further investigate medication use in patients with SWS.

To describe the natural history, management, and visual outcome in children with congenital primary aphakia (CPA).This is a multicenter retrospective consecutive case series from five academic centers in England and North America.A total of 27 eyes of 14 patients were included (male:female, 1.7:1). Thirteen patients had bilateral CPA, and 1 patient had unilateral CPA. Mean age at diagnosis was 18 months (median, 21; range, 0.5-144). Of 11 patients who underwent genetic testing, 9 had FOXE3 pathogenic variants. In all patients, visual acuity at presentation was not better than fixing and following light. Typical findings included silvery appearance of the cornea with vascularization (96%), glaucoma (81%), iridocorneal adhesions (74%), optic nerve coloboma (55%), abnormal vitreous (33%), retinal detachment (30%), and aniridia with hypoplasia of ciliary body (19%). Surgical interventions in select patients included penetrating keratoplasty (PKP), glaucoma drainage device implantation, and cyclophotocoagulation (CPC).Eyes with corneal ectasia and a silvery appearance of the cornea with vascularization should alert the physician to the possibility of CPA. Glaucoma causes globe enlargement and may increase the risk of corneal perforation, but glaucoma is often refractory to medical treatment, and the threshold for surgical treatment should be low. PKP outcomes are very poor.

PURPOSE We previously reported costs and outcomes of the Children's Eye Care Adherence Program (CECAP1), a social worker intervention designed to improve adherence to eye care for underserved children in urban Philadelphia. Using cost findings from CECAP1, we revised the intervention to reduce costs. The aim of this study was to evaluate costs and effectiveness of the revised intervention (CECAP2). DESIGN Retrospective cohort study. METHODS Records of children needing ophthalmic follow-up after 2 community-based vision screening programs were reviewed. We modified CECAP1 to prioritize children more likely to visit, decreased phone calls and scheduling attempts, better documented children already followed by other doctors, and constricted our geographic catchment area for better accessibility. Cost was calculated using time spent executing CECAP2 by our salaried social worker. Effectiveness was defined as the percentage of patients completing at least 1 follow-up visit within the recommended time frame. RESULTS Of 462 children referred to CECAP2 from our in-school and on-campus screening programs, 242 (52.4%) completed subsequent recommended eye examinations, a proportion identical to our prior report (52.3%). Social worker time per patient was 0.8 hours; a significant reduction from the previous 2.6 hours (P < .01). Cost per patient was $32.73; a significant reduction compared to the previous $77.20 (P < .01). CONCLUSIONS Programmatic changes to reduce social worker intervention time and target potential patients by likelihood to attend along with constriction of the catchment area led to reduced costs by more than 50%, without impairing CECAP effectiveness.

Background Retinal hemorrhages (RH) are a common manifestation of abusive head trauma (AHT) resulting from acceleration-deceleration injury with or without blunt impact. Evaluation of a child with RH requires careful consideration of these differential diagnoses. The extent to which coagulopathy alone can cause RH would be useful to understand as coagulopathy may accompany AHT. Objective In this systematic review, we sought to identify whether coagulopathies have been reported with RH similar to those of AHT. Methods We performed a literature search for ocular manifestations of bleeding disorders in children less than 18 years old. We included clotting factor deficiencies, vitamin K deficiency, platelet function abnormalities, thrombocytopenia, disseminated intravascular coagulation (DIC), and trauma induced coagulopathy (TIC). We included only pediatric reports of intraocular bleeding or documented eye examinations that indicated no hemorrhages. We then re-examined cases for ocular and systemic findings that could potentially mimic abuse. Results Our initial search yielded 816 results. Sixty-one articles met our inclusion criteria. Of these, there were 32 children within the AHT age range (less than 5 years old) who had RH and concomitant coagulopathy. Only 5 cases might potentially be confused for abuse. Of these, no classic characteristics of RH from abuse such as retinoschisis or retinal folds were found. Systemic features were inconsistent with AHT. Conclusions The presence of coagulopathy alone does not rule out the possibility that the child has been abused. Coagulopathy alone has not been reported as an etiology of RH that are consistent with AHT, especially when other findings are present.

Background Rebound tonometry (RBT) can be used to measure intraocular pressure (IOP) in children unable to tolerate measurement with applanation tonometry (AT) while awake. RBT readings are often 2–3 mm Hg higher than AT. We have experienced children with a repeatedly higher difference between RBT and AT measurements (≥6 mm Hg). The purpose of this study was to identify demographic and ocular characteristics that contribute to this artifactuous discrepancy. Methods The medical records of pediatric patients with IOP measured by RBT followed by AT within 6 months without intervening surgery or change in medical management were retrospectively reviewed to identify potential predictors of greater difference between RBT and AT readings. Results A total of 123 eyes of 65 patients were included. In patients with normal IOP (≤24 mm Hg), 18.5% had a ≥6 mm Hg difference between RBT and AT, with RBT being higher. Risk factors for this included presence of persistent fetal vasculature (PFV), increased corneal diameter, and higher initial RBT value (>20). In patients with elevated IOP (>24 mm Hg), 77% had ≥6 mm Hg difference, with larger corneal diameter being the sole predictor. Eyes were less likely to have significant RBT-AT difference if there was corneal opacity or iris abnormalities in eyes with elevated IOP (>24 mm Hg). Conclusions In some children, RBT readings are ≥ 6 mm Hg higher than AT readings. Caution should be taken when interpreting RBT values in patients with PFV, increased corneal diameter, and higher initial RBT values.

Ocular Genetics at Wills Eye Hospital sees a wide range of rare disorders for accurate diagnosis. To demonstrate how focused consultation and genetic testing results in precise diagnoses, we investigated false diagnosis rates for patients referred with a diagnosis of Stargardt disease. This is a retrospective review of patients over a 3 year period referred to our Ocular Genetics clinic for possible Stargardt disease, or already holding a diagnosis of Stargardt disease. Results of diagnostic and genetic testing were compared to standard definition of Stargardt. Of 40 patients, 14 (35%) had been misdiagnosed. Four had non-Stargardt phenotype of which three had ABCA4 pathogenic variants with phenotypes inconsistent with Stargardt disease. Two of those with pathogenic ABCA4 variants were related. Nine had pathogenic variants in other different genes with overlapping features of Stargardt disease. One had Thioridazine maculopathy. Our study highlights the essential role of the subspecialty field of ocular genetics in obtaining accurate diagnoses for the delivery of correct counseling and interventional trial eligibility assessment.

Objective To assess ocular diagnoses and follow-up patterns of children referred for a comprehensive eye examination after a school-based vision screening program. Design Retrospective chart review. Participants Students in grades K–5 from the School District of Philadelphia public schools screened by The Wills Eye Vision Screening Program for Children between January 2014 and June 2015. Methods Children with subnormal best-corrected visual acuity or other ocular conditions were referred to the Wills Eye pediatric ophthalmology service. A social worker assisted parents/guardians of referred children in scheduling an appointment and navigating insurance/payment issues. Measured outcomes included demographic information, ocular diagnoses, treatments, and follow-up patterns. Results Of 10 726 children screened, 509 (5%) were referred for a follow-up eye examination. Of these 509 children, only 127 (25%) completed a referral eye examination with parental consent. Most children (58%) were diagnosed with more than one eye condition, including refractive error (76%), amblyopia (43%), strabismus (16%), and anisometropia (13%). Other conditions included macular hypoplasia, ptosis, and other congenital anomalies. Conclusions This program discovered and addressed potentially vision-threatening conditions in underserved children susceptible to amblyopia by offering social worker services and financial support to enable referred children to complete an eye examination. Contact by the social worker required consent. Obtaining such consent proved to be a barrier to connecting children with the recommended consultation.

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning., Cornelia de Lange syndrome is a genetic disorder affecting multiple organ systems that exhibits great phenotypic heterogeneity. This Consensus Statement summarizes recommendations for the diagnosis and management of patients with Cornelia de Lange syndrome.

The Childhood Glaucoma Research Network (CGRN) has created a new classification system for childhood glaucoma that has become the first International Consensus Classification. The purpose of this review is to present this classification system and share its use to date.The diagnoses of the classification system include glaucoma and glaucoma suspect. The primary glaucomas include: primary congenital glaucoma and juvenile open-angle glaucoma. The secondary glaucomas include: glaucoma following cataract surgery, glaucoma associated with nonacquired systemic disease or syndrome, glaucoma associated with nonacquired ocular anomalies, and glaucoma associated with acquired conditions. This system reached consensus agreement at the Ninth World Glaucoma Association Consensus, which has been adopted by the American Board of Ophthalmology, and has been implemented in outcomes research, incidence studies, and review articles. The new Robison D. Harley, MD CGRN International Pediatric Glaucoma Registry uses this classification system as a shared language, allowing international clinicians and researchers to collaborate and make large-scale investigations of this otherwise rare disease possible.The diagnoses in this system are assigned by following a logical and systematically approachable path. The ability to easily adopt and implement the system lends itself to international research.

Pigmentary retinal dystrophy and macular dystrophy have been previously reported in Heimler syndrome due to mutations in PEX1. Here we reported the ocular manifestations in Heimler syndrome due to mutations in PEX6.Medical records were reviewed to identify patient demographics, ophthalmic and systemic findings, and results of diagnostic testing including whole genome sequencing.Patient 1 is 12-year-old boy with a novel mutation c.275TG (p.Val92Gly) and known mutation c.1802GA (p.Arg601Gln) in PEX6. Patient 2 is a 7-year-old girl with the same known c.1802GA (p.Arg601Gln) mutation and another novel missense mutation c.296GT (p.Arg99Leu). Both patients exhibited a pigmentary retinopathy. Visual acuity in patient 1 was 20/80 and 20/25 following treatment of intraretinal cystoid spaces with carbonic anhydrase inhibitors, while patient 2 had visual acuity of 20/20 in both eyes without intraretinal cysts. Fundus autofluorescence showed a multitude of hyperfluorescent deposits in the paramacular area of both eyes. OCTs revealed significant depletion of photoreceptors in both patients and macular intraretinal cystoid spaces in one patient. Full field electroretinograms showed normal or abnormal photopic but normal scotopic responses. Multifocal electroretinograms were abnormal.Heimler syndrome due to biallelic PEX6 mutations demonstrates a macular dystrophy with characteristic fundus autofluorescence and may be complicated by intraretinal cystoid spaces.

We report the case of a 12-year-old girl diagnosed with Nicolaides-Baraitser syndrome with novel ocular features. Diagnosis was based on clinical features, including developmental delay, sparse hair, and craniofacial features along with de novo mutation in SMARCA2. Eye findings included bilateral glaucoma, cataracts, and degenerative vitreoretinopathy. Given the absence of an associated recognizable disorder and the low prevalence of these ocular findings in the general population, we suggest that these ocular features may not be chance association.

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel β 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNGβ1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene augmentation using adeno-associated virus vectors robustly sustained the rescue of rod function and preserved retinal structure in the dog model. Together, our results reveal an early loss of rod function in CNGB1-deficient patients and a wide window for therapeutic intervention. Moreover, the identification of potential biomarkers of outcome measures, availability of relevant animal models, and robust functional rescue from gene augmentation therapy support future work to move CNGB1-RP therapies toward clinical trials.