Publications by authors named "Alex V Levin"

197 Publications

A review on clotting disorders and retinal hemorrhages: Can they mimic abuse?

Child Abuse Negl 2021 Aug 25;118:105070. Epub 2021 May 25.

Thomas Jefferson University, Philadelphia, PA, USA; Department of Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, Philadelphia, PA, USA. Electronic address:

Background: The characteristic findings of abusive head trauma (AHT) include retinal hemorrhages (RH). RH have many etiologies in childhood, which should be considered in the differential diagnosis of possible child abuse. The relationship between RH and thrombophilia in children is not well established.

Objective: In this literature review, we sought to assess whether retinal findings in pediatric patients with thrombophilia could mimic those of AHT.

Methods: A literature search was performed to identify all cases of thrombophilia in children less than 18 years old with ocular manifestations. Disorders of thrombophilia including protein C and S deficiency, factor V Leiden (FVL), prothrombin variant, MTHFR mutation, hyperhomocysteinemia, elevated factor VIII, and elevated lipoprotein (a) were considered. All cases of pediatric thrombophilia with retinal examination or intraocular bleeding were included. If provided, descriptions of the RH were reviewed.

Results: Our initial search yielded 514 results. Forty-three articles met our inclusion criteria. We identified 3 children with RH within the AHT usual age range (<5 years old), ages 5 weeks and 7 weeks old, in the setting of thrombophilia. One child had ocular findings that could potentially mimic abuse. No other indicators of abuse were present in this case.

Conclusions: Based on previous reports, thrombophilia alone has not been shown to clearly mimic abusive head trauma. In reported cases of thrombophilia with RH, the clinical picture and ophthalmic findings are usually distinct from abuse.
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http://dx.doi.org/10.1016/j.chiabu.2021.105070DOI Listing
August 2021

Comprehensive phenotypic and functional analysis of dominant and recessive FOXE3 alleles in ocular developmental disorders.

Hum Mol Genet 2021 May 27. Epub 2021 May 27.

Department of Pediatrics and Children's Research Institute at the Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI 53226, USA.

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.
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http://dx.doi.org/10.1093/hmg/ddab142DOI Listing
May 2021

A novel de novo intronic variant in ITPR1 causes Gillespie syndrome.

Am J Med Genet A 2021 Aug 5;185(8):2315-2324. Epub 2021 May 5.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

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.
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http://dx.doi.org/10.1002/ajmg.a.62232DOI Listing
August 2021

Falsely high rebound tonometry.

J AAPOS 2021 Apr 24;25(2):97.e1-97.e5. Epub 2021 Apr 24.

Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, Philadelphia, Pennsylvania; Department of Ophthalmology, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jaapos.2020.11.017DOI Listing
April 2021

Persistent epithelial defect after photorefractive keratectomy in a patient with autism.

J AAPOS 2021 Apr 22. Epub 2021 Apr 22.

Department of Pediatric Ophthalmology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jaapos.2021.01.002DOI Listing
April 2021

Optic Nerve Aplasia.

J Neuroophthalmol 2021 Apr 14. Epub 2021 Apr 14.

Philadelphia College of Osteopathic Medicine (BDS), Philadelphia, Pennsylvania; Pediatric Ophthalmology and Ocular Genetics (BDS, SHY), Wills Eye Hospital, Philadelphia, Pennsylvania; Pediatric Ophthalmology (BEG), Helen DeVos Children's Hospital, Grand Rapids, Michigan; The Rotterdam Eye Hospital (JTHNF), Rotterdam, the Netherlands; Cullen Eye Institute (LSB), Baylor College of Medicine, Houston, Texas; Department of Pediatric Ophthalmology (MB), LV Prasad Eye Institute, Hyderabad, India; Ophthalmology Unit (SG), Ricardo Gutiérrez Children Hospital, Buenos Aires, Argentina; Cataract and Laser Institute of Southern Oregon PC (TR), Medford, Oregon; Flaum Eye Institute and Golisano Children's Hospital (AVL), University of Rochester, New York, New York.

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.
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http://dx.doi.org/10.1097/WNO.0000000000001246DOI Listing
April 2021

Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome.

Pediatr Neurol 2021 Jun 5;119:3-10. Epub 2021 Mar 5.

Department of Neurology, Hugo Moser Kennedy Krieger Research Institute, Baltimore, Maryland; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pediatrics, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address:

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.
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http://dx.doi.org/10.1016/j.pediatrneurol.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162684PMC
June 2021

Resident immune cells of the avascular lens: Mediators of the injury and fibrotic response of the lens.

FASEB J 2021 04;35(4):e21341

Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.

Tissues typically harbor subpopulations of resident immune cells that function as rapid responders to injury and whose activation leads to induction of an adaptive immune response, playing important roles in repair and protection. Since the lens is an avascular tissue, it was presumed that it was absent of resident immune cells. Our studies now show that resident immune cells are a shared feature of the human, mouse, and chicken lens epithelium. These resident immune cells function as immediate responders to injury and rapidly populate the wound edge following mock cataract surgery to function as leader cells. Many of these resident immune cells also express MHCII providing them with antigen presenting ability to engage an adaptive immune response. We provide evidence that during development immune cells migrate on the ciliary zonules and localize among the equatorial epithelial cells of the lens adjacent to where the ciliary zonules associate with the lens capsule. These findings suggest that the vasculature-rich ciliary body is a source of lens resident immune cells. We identified a major role for these cells as rapid responders to wounding, quickly populating each wound were they can function as leaders of lens tissue repair. Our findings also show that lens resident immune cells are progenitors of myofibroblasts, which characteristically appear in response to lens cataract surgery injury, and therefore, are likely agents of lens pathologies to impair vision like fibrosis.
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http://dx.doi.org/10.1096/fj.202002200RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200928PMC
April 2021

Treatment of Port Wine Birthmarks in Sturge-Weber Syndrome Using Topical Timolol.

J Pediatr Ophthalmol Strabismus 2020 Feb 22;58:e1-e4. Epub 2020 Feb 22.

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 Strabimus. 2021;58:e1-e4.].
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http://dx.doi.org/10.3928/01913913-20201202-01DOI Listing
February 2020

Reducing the Costs of an Eye Care Adherence Program for Underserved Children Referred Through Inner-City Vision Screenings.

Am J Ophthalmol 2021 07 11;227:18-24. Epub 2021 Feb 11.

Pediatric Ophthalmology and Ocular Genetics, Flaum Eye Institute, University of Rochester, Rochester New York, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ajo.2021.02.012DOI Listing
July 2021

Stargardt misdiagnosis: How ocular genetics helps.

Am J Med Genet A 2021 03 24;185(3):814-819. Epub 2020 Dec 24.

Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.

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.
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http://dx.doi.org/10.1002/ajmg.a.62045DOI Listing
March 2021

Early Experience with Netarsudil in Pediatric Patients: A Retrospective Case Series.

Ophthalmol Glaucoma 2021 Mar-Apr;4(2):232-234. Epub 2020 Oct 14.

Glaucoma Service, Wills Eye Hospital, Philadelphia, Pennsylvania. Electronic address:

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http://dx.doi.org/10.1016/j.ogla.2020.10.005DOI Listing
October 2020

Referral outcomes from a vision screening program for school-aged children.

Can J Ophthalmol 2021 02 6;56(1):43-48. Epub 2020 Aug 6.

From the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA; Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, Philadelphia, PA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jcjo.2020.07.009DOI Listing
February 2021

Impact of eyeglasses on academic performance in primary school children.

Can J Ophthalmol 2020 02 13;55(1):52-57. Epub 2019 Sep 13.

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA; Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, Philadelphia, PA. Electronic address:

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 (<25%) by 18.6% of children. DRA results were available for 2226 children. When eyeglasses were prescribed and worn, initially high reading performances (DRA level 3) were less likely to decline (odds ratio [OR] = 4.36, p < 0.001). Improvement was not observed for children who initially scored DRA level 1 or 2 (OR = 0.29, p < 0.001 and OR = 1.00, p = 0.986, respectively). PSSA reading results were available for 847 children. When eyeglasses were prescribed and worn, Asian children were more likely to score higher PSSA reading levels (OR = 2.53, p = 0.004). This trend was also observed in black and Hispanic children without reaching statistical significance (OR = 1.70, p = 0.061; OR = 2.67, p = 0.067, respectively).

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.
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http://dx.doi.org/10.1016/j.jcjo.2019.07.011DOI Listing
February 2020

Optical Coherence Tomography in Knobloch Syndrome.

Ophthalmic Surg Lasers Imaging Retina 2019 08;50(8):e203-e210

Background And Objective: Knobloch syndrome is a genetic disorder defined by occipital defect, high myopia, and vitreoretinal degeneration. The authors studied retinal changes in patients with Knobloch syndrome using optical coherence tomography (OCT).

Patients And Methods: The authors report patients with Knobloch syndrome who received OCT testing during their care from 2011 to 2016. Diagnosis was based on high myopia, characteristic fundus, and occipital scalp or skull abnormalities with/without featureless irides and/or ectopia lentis. When available, diagnosis was confirmed by the detection of COL18A1 mutations.

Results: The authors studied eight eyes from five patients. Two eyes were excluded due to chronic retinal detachment. OCT findings included epiretinal membrane, peripapillary vitreoretinal traction with retinoschisis, absent or rudimentary foveal pits, mean macular thickness of 113.4 μm, poor lamination, retinal pigment epithelium (RPE) atrophy, photoreceptor depletion, and mean choroidal thickness of 168.5 μm with enlarged choroidal vessels.

Conclusion: OCT findings in Knobloch syndrome include abnormal vitreoretinal traction, poor foveal differentiation, poor retinal lamination, retinal thinning, RPE attenuation, myopic choroidal thinning, and pachychoroid. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e203-e210.].
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http://dx.doi.org/10.3928/23258160-20190806-13DOI Listing
August 2019

Association of Preoperative Disclosure of Resident Roles With Informed Consent for Cataract Surgery in a Teaching Program.

JAMA Ophthalmol 2019 Sep;137(9):1045-1051

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania.

Importance: Cataract surgery is the most commonly performed intraocular surgery. Academic centers have mandates to train the next surgeon generation, but resident roles are often hidden in the consent process.

Objective: To investigate associations of full preoperative disclosure of the resident role with patient consent rates and subjective experience of the consent process.

Design, Setting, And Participants: Full scripted disclosure of residents' roles in cataract surgery was delivered by the attending surgeon. Qualitative analysis was conducted from recorded interviews of patients postoperatively regarding consent process experience and choice of whether to allow resident participation. Associations were sought regarding demographic characteristics and consent rates. Patients were recruited though a private community office. Surgery was performed at a single hospital where resident training was routinely conducted. The study included systemically well patients older than 18 years with surgical cataract. They had no previous eye surgery, English fluency, and ability to engage in informed consent decision-making and postsurgery interview. Patients were ineligible if they had monocular cataracts, required additional simultaneous procedures, had history of ocular trauma, or had cataracts that were surgically technically challenging beyond the usual resident skill level.

Interventions: Eligible patients received an informed consent conversation by the attending physician in accordance with a script describing projected resident involvement in their cataract surgery. Postoperatively, patients were interviewed and responses were analyzed with a quantitative and thematic qualitative approach.

Main Outcomes And Measures: Consent rates to resident participation and qualitative experience of full disclosure process.

Results: Ninety-six patients participated. Participants were between ages 50 and 88 years, 53 were men (55.2%), and 75 were white (85.2%). A total of 54 of 96 participants (56.3%; 95% CI, 45.7%-66.4%) agreed to resident involvement. There were no associations between baseline characteristics and consent to resident involvement identified with any confidence, including race/ethnicity (60% [45 of 75] in white patients vs 30.8% [4 of 13] in nonwhite patients; difference, 29.2%; 95% CI, -0.7% to 57.3%; Fisher exact P = .07). Thematically, those who agreed to resident involvement listed trust in the attending surgeon, contributing to education, and supervision as contributing factors. Patients who declined stated fear and perceived risk as reasons.

Conclusions And Relevance: Our results suggest 45.7% to 66.4% of community private practice patients would consent to resident surgery. Consent rates were not associated with demographic factors. Because residents are less often offered the opportunity to do surgery on private practice patients vs academic center patients, this may represent a resource for resident education.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.1919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659148PMC
September 2019

Survey of practice patterns for the management of ophthalmic genetic disorders among AAPOS members: report by the AAPOS Genetic Eye Disease Task Force.

J AAPOS 2019 08 21;23(4):226-228.e1. Epub 2019 Jun 21.

Pediatric Ophthalmology and Strabismus, Center for Genetic Eye Diseases, Cole Eye Institute, Cleveland, Ohio; Center for Graduate Medical Education, Education Institute, Cleveland Clinic, Cleveland, Ohio.

To better understand AAPOS member pediatric ophthalmologists' knowledge and needs regarding genetic eye disorders, the AAPOS Genetic Eye Disease Task Force developed a 16-question survey that was circulated to national and international AAPOS members. Responses to questions on practice patterns, baseline knowledge, and educational interests regarding patients with suspected ophthalmic genetic disorders were collected. A majority of respondents (93%) evaluate patients with suspected genetic disorders. Knowledge gaps were present in heritability of certain conditions, genetic testing strategies, and referral to clinical trials. Most respondents expressed interest in further education in these areas. A model for care is proposed as a first step in the education process.
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http://dx.doi.org/10.1016/j.jaapos.2019.04.005DOI Listing
August 2019

Central Corneal Thickness in Childhood Cataract.

Cornea 2019 Aug;38(8):1003-1005

Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA.

Purpose: We explored elevated central corneal thickness (CCT) in children with cataracts as possibly reflecting preexisting corneal malformation related to specific cataract morphology.

Methods: All children consecutively seen during the study periods who had cataracts and corneal pachymetry as part of their routine care were enrolled at academic centers in large cities of Canada and the United States. Study data collected included age, sex, CCT, and cataract morphology. Differences among cataract morphology groups with respect to mean CCT measurements were evaluated and compared with a historical control thickness of 558 μm.

Results: A total of 96 children were enrolled in this study. The average subject age was 5.1 years, and 55 children (57%) were female. The mean CCT value for all subjects was 566.1 μm. There was little evidence to conclude that the cataract morphology groups differed from each other (P = 0.65) or from controls with respect to CCT.

Conclusions: In children, CCT is likely independent of cataract morphology. This implies that factors other than preoperative malformation are more likely related to elevated CCT observed in children with aphakia and pseudophakia.
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http://dx.doi.org/10.1097/ICO.0000000000001970DOI Listing
August 2019

Ocular hypotony: A comprehensive review.

Surv Ophthalmol 2019 Sep - Oct;64(5):619-638. Epub 2019 Apr 25.

Wills Eye Hospital, Philadelphia, Pennsylvania, USA; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address:

Ocular hypotony is an infrequent, yet potentially vision-threatening, entity. The list of differential causes is extensive, involving any condition that may compromise aqueous humor dynamics or the integrity of the globe and sometimes following medical treatments or procedures. Depending on the cause and the clinical impact, treatment options aim to correct the underlying pathology and to reestablish anatomical integrity, as well as visual function. We review the pathophysiology, clinical presentation, different causes, and associated therapeutic options of ocular hypotony.
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http://dx.doi.org/10.1016/j.survophthal.2019.04.006DOI Listing
December 2019

An update of ophthalmic management in craniosynostosis.

J AAPOS 2019 04 27;23(2):66-76. Epub 2019 Mar 27.

Wills Eye Institute, Philadelphia, Pennsylvania. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jaapos.2018.10.016DOI Listing
April 2019

Physical and Family History Variables Associated With Neurological and Cognitive Development in Sturge-Weber Syndrome.

Pediatr Neurol 2019 07 20;96:30-36. Epub 2018 Dec 20.

Department of Neurology, Kennedy Krieger Institute, Baltimore, Maryland; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: Sturge-Weber syndrome (SWS) is caused by a somatic mutation in GNAQ leading to capillary venous malformations in the brain presenting with various neurological, ophthalmic, and cognitive symptoms of variable severity. This clinical variability makes accurate prognosis difficult. We hypothesized that the greater extent of physical factors (extent of skin, eye, and brain involvement), presence of possible genetic factors (gender and family history), and age of seizure onset may be associated with greater symptom severity and need for surgery in patients with SWS.

Methods: The questionnaire was collected from 277 participants (age: two months to 66 years) with SWS brain involvement at seven US sites.

Results: Bilateral brain involvement was associated with both learning disorder and intellectual disability, whereas port-wine birthmark extent was associated with epilepsy and an increased likelihood of glaucoma surgery. Subjects with family history of vascular birthmarks were also more likely to report symptomatic strokes, and family history of seizures was associated with earlier seizure onset. Learning disorder, intellectual disability, strokelike episodes, symptomatic stroke, hemiparesis, visual field deficit, and brain surgery were all significantly associated with earlier onset of seizures.

Conclusion: The extent of brain and skin involvement in SWS, as well as the age of seizure onset, affect prognosis. Other genetic factors, particularly variants involved in vascular development and epilepsy, may also contribute to neurological prognosis, and further study is needed.
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http://dx.doi.org/10.1016/j.pediatrneurol.2018.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288445PMC
July 2019

Ophthalmologic findings in the Cornelia de Lange syndrome.

Ophthalmic Genet 2019 02 15;40(1):1-6. Epub 2019 Feb 15.

a Sidney Kimmel Medical College , Thomas Jefferson University , Philadelphia , Pennsylvania , USA.

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.
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http://dx.doi.org/10.1080/13816810.2019.1571617DOI Listing
February 2019

Glaucoma and degenerative vitreoretinopathy in a girl with Nicolaides-Baraitser syndrome.

J AAPOS 2019 06 29;23(3):169-171. Epub 2019 Jan 29.

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, Philadelphia, Pennsylvania. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jaapos.2018.12.002DOI Listing
June 2019

Retinal Findings in Young Children With Increased Intracranial Pressure From Nontraumatic Causes.

Pediatrics 2019 02 10;143(2). Epub 2019 Jan 10.

Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania;

Objectives: Increased intracranial pressure (ICP) has been suggested in legal settings as an alternative cause of retinal hemorrhages (RHs) in young children who may have sustained abusive head trauma. We assessed the prevalence and characteristics of RHs in children with increased ICP.

Methods: We conducted a prospective, multicenter study of children <4 years old with newly diagnosed increased ICP as determined by using direct measurement and/or clinical criteria. Infants who were premature, neonates, and suspected survivors of abusive head trauma were excluded on the basis of nonocular findings. Fundus examinations were performed; extent, number, and type of RH in each of 4 distinct retinal zones were recorded.

Results: Fifty-six children (27 boys) were studied (mean age 15.4 months; range 1-43 months). All of the children had elevated ICP that required intervention. One child had papilledema. No child (0%; 95% confidence interval: 0%-6.4%) or eye (0%; 95% confidence interval: 0%-3.3%) was found to have an RH. Causes of increased ICP included hydrocephalus, intraventricular hemorrhage, congenital malformations, malfunctioning shunts, and the presence of intracranial space-occupying lesions.

Conclusions: Although acute increased ICP can present in children with a pattern of peripapillary superficial RHs in the presence of papilledema, our study supports the conclusion that RHs rarely occur in the absence of optic disc swelling and do not present beyond the peripapillary area in the entities we have studied.
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http://dx.doi.org/10.1542/peds.2018-1182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361344PMC
February 2019

Traumatic macular retinoschisis in infants and children.

J AAPOS 2018 12 28;22(6):433-437.e2. Epub 2018 Oct 28.

Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, Philadelphia, Pennsylvania. Electronic address:

Purpose: To provide detailed description of pediatric traumatic retinoschisis.

Methods: The medical records of children with either abusive head trauma and traumatic macular retinoschisis seen at a single center from 1993 to 2006 were reviewed retrospectively. Clinical details were extracted from the record and photographic documentation. Evaluation regarding abuse excluded ophthalmology findings to avoid circular reasoning.

Results: Of 134 patients with suspected abusive head trauma, 31 had retinoschisis. Mean age was 9 months. Of the 31, 22 (71%) offered a history of injury, and 9 (29%) were found unresponsive without history of injury; 6 were reportedly shaken. All patients had seizures, vomiting, and/or altered responsiveness. All had subdural hemorrhage, with cerebral edema in 17 (55%). In 10 (32%), there were findings of blunt force head injuries; in 4 of these there was no impact history. Retinal hemorrhages were present in all cases. Agreement between sidedness of retinoschisis and subdural hemorrhage was poor. Eleven patients had retinal folds, 3 of which had a hemorrhagic edge to the schisis. Nine patients had extracranial manifestations of abuse. Multidisciplinary team adjudications were as follows: of the 31 cases, 18 were suspicious for abuse, 11 were indeterminate, and 2 were possibly accounted for by accidental severe crush injury. Three children died, and 11 suffered neurological sequelae.

Conclusions: Traumatic retinoschisis in children is highly associated with subdural hemorrhage, neurologic symptoms, and poor outcomes. Even with a conservative approach to opinion formulation, traumatic retinoschisis was associated with likely abuse.
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http://dx.doi.org/10.1016/j.jaapos.2018.08.007DOI Listing
December 2018

Ophthalmic manifestations associated with RARB mutations.

Clin Dysmorphol 2019 Jan;28(1):46-49

Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital.

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http://dx.doi.org/10.1097/MCD.0000000000000246DOI Listing
January 2019

Ocular manifestations of Emanuel syndrome.

Am J Med Genet A 2018 09 4;176(9):1964-1967. Epub 2018 Sep 4.

Wills Eye Hospital, Philadelphia, Pennsylvania.

Emanuel syndrome is caused by a supernumerary der(22)t(11;22) and typically manifests with intellectual disability and craniofacial dysmorphism. Ocular abnormalities have infrequently been described. We report a 36-year-old man with severe intellectual disability, aphasia, and facial dysmorphism, with high myopia and juvenile open angle glaucoma (JOAG). Microarray analysis results included 47,XY,+der(22)t(11;22)(q23;q11.2), and a 269 kb deletion of 7q31.33(125,898,014-126,166,829). Two candidate genes were identified as possible etiologies for the ocular pathologies in our patient: a MFRP duplication on chromosome 11, which may play a role in high myopia and dysregulation of emmetropization, and a GRM8 deletion on chromosome 7, which may cause glutamate-induced excitotoxicity and therefore have a role in the development of JOAG, unrelated to the Emanuel syndrome genotype. We provide the first detailed description these ocular abnormalities in a patient with Emmanuel syndrome.
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http://dx.doi.org/10.1002/ajmg.a.40361DOI Listing
September 2018

New classification system for pediatric glaucoma: implications for clinical care and a research registry.

Curr Opin Ophthalmol 2018 Sep;29(5):385-394

Sidney Kimmel Medical College at Thomas Jefferson University.

Purpose Of Review: 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.

Recent Findings: 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.

Summary: 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.
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http://dx.doi.org/10.1097/ICU.0000000000000516DOI Listing
September 2018

PATHOLOGY OF PERIMACULAR FOLDS DUE TO VITREORETINAL TRACTION IN ABUSIVE HEAD TRAUMA.

Retina 2019 Nov;39(11):2141-2148

Pediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, Philadelphia, Pennsylvania.

Purpose: To demonstrate vitreoretinal traction as a mechanism for perimacular folds in abusive head trauma.

Methods: We performed gross and histopathologic examination of eyes of children with suspected abusive head trauma and identified those with typical perimacular folds. Information was collected regarding the incident that led to the child's death and systemic manifestations noted at autopsy. Eyes were prepared in a fashion that allowed for demonstration of the vitreoretinal interface.

Results: Ten eyes of five patients (2-13 months) were examined. All patients had systemic manifestations of abusive trauma including intracranial injury. All cases provided evidence of vitreoretinal traction producing perimacular folds. Condensed vitreous was seen attached to the apices of the retinal folds, and the detached internal limiting membrane comprising the inner surfaces of the schisis cavity. Four cases showed severe bilateral multilayered symmetric retinal hemorrhages extending to the ora serrata. All cases showed optic nerve sheath subdural hemorrhage and subarachnoid hemorrhage. Orbital hemorrhage was unilateral in two cases and bilateral in three cases. Four cases showed orbital fat hemorrhage. One case showed extraocular muscle sheath and cranial nerve sheath hemorrhage. Two cases showed juxtapapillary intrascleral hemorrhage.

Conclusion: Vitreoretinal traction is the likely mechanism of perimacular folds in abusive head trauma.
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http://dx.doi.org/10.1097/IAE.0000000000002273DOI Listing
November 2019

The Eye Examination in the Evaluation of Child Abuse.

Pediatrics 2018 08;142(2)

Child abuse can cause injury to any part of the eye. The most common manifestations are retinal hemorrhages (RHs) in infants and young children with abusive head trauma (AHT). Although RHs are an important indicator of possible AHT, they are also found in other conditions. Distinguishing the number, type, location, and pattern of RHs is important in evaluating a differential diagnosis. Eye trauma can be seen in cases of physical abuse or AHT and may prompt referral for ophthalmologic assessment. Physicians have a responsibility to consider abuse in the differential diagnosis of pediatric eye trauma. Identification and documentation of inflicted ocular trauma requires a thorough examination by an ophthalmologist, including indirect ophthalmoscopy, most optimally through a dilated pupil, especially for the evaluation of possible RHs. An eye examination is helpful in detecting abnormalities that can help identify a medical or traumatic etiology for previously well young children who experience unexpected and unexplained mental status changes with no obvious cause, children with head trauma that results in significant intracranial hemorrhage and brain injury, and children with unexplained death.
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http://dx.doi.org/10.1542/peds.2018-1411DOI Listing
August 2018
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