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

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.

Measurement of the intraocular pressure (IOP) is central to the diagnosis and management of pediatric glaucoma. An examination under anesthesia is often necessary in pediatric patients. Different agents used for sedation or general anesthesia have varied effects on IOP. Hemodynamic factors, methods of airway management, tonometry technique, and body positioning can all affect IOP measurements. The most accurate technique is one that reflects the awake IOP. We review factors affecting IOP measurements in the pediatric population and provide recommendations on the most accurate means to measure IOP under anesthesia based on the present literature.

Heterozygous mutation in the PACS1 (phosphofurin acidic cluster sorting proteins 1) gene is a known cause of developmental delay, multiple congenital anomalies, dysmorphism, and ocular abnormalities. We present the case of an affected 10-year-old girl, conceived by assisted reproductive technology, who has ocular coloboma and findings characteristic of PACS1 mutation.

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.

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 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.

Alström syndrome is a multi-system recessive disorder caused by mutations in ALMS1 gene. The aim of this study was to characterize morphological retinal changes in Alström patients using spectral-domain optical coherence tomography.We studied volunteer patients attending the conference of Alström Syndrome International, a support group for affected families, using hand-held spectral-domain optical coherence tomography (SD-OCT) in an office setting. Patients had a clinical dilated retinal examination. Past medical records were reviewed.Twenty-two Alström patients (mean age 17 years, range 2-38 years, 12 males) were studied. OCT imaging demonstrated that central macular OCT changes are often mild during the first decade of life and gradually progress, demonstrating disruption of normal retinal architecture, and progressive loss of photoreceptors and retinal pigment epithelium. Other changes found included hyperreflectivities in all retinal layers, severe retinal wrinkling, optic nerve drusen, and vitreoretinal separation. Vision correlated with severity of OCT macular changes (r = 0.89, p = 0.002).This study reports on OCT findings in a large group of patients with Alström syndrome. We document a panretinal gradual progression of retinal changes, which are often mild during the first years of life. Previously unreported observations include intraretinal opacities, optic nerve drusen, and foveal contour abnormalities. Morphological retinal changes demonstrated by SD-OCT may help in understanding the pathophysiology of the disease and defining strategies for treatment such as gene therapy.

When Abusive Head Trauma (AHT) is suspected in a child, a dilated eye examination by an ophthalmologist is an essential part of the medical workup, as the presence and pattern of retinal hemorrhages can have a high positive predictive rate for abusive head injury. This article proposes to review the clinical presentation, pathophysiology, natural history, sequelae, and differential diagnosis of retinal hemorrhages and other ocular lesions associated with AHT.

Sturge-Weber syndrome (SWS) is a vascular neurocutaneous disorder that results from a somatic mosaic mutation in GNAQ, which is also responsible for isolated port-wine birthmarks. Infants with SWS are born with a cutaneous capillary malformation (port-wine birthmark) of the forehead or upper eyelid which can signal an increased risk of brain and/or eye involvement prior to the onset of specific symptoms. This symptom-free interval represents a time when a targeted intervention could help to minimize the neurological and ophthalmologic manifestations of the disorder. This paper summarizes a 2015 SWS workshop in Bethesda, Maryland that was sponsored by the National Institutes of Health. Meeting attendees included a diverse group of clinical and translational researchers with a goal of establishing research priorities for the next few years. The initial portion of the meeting included a thorough review of the recent genetic discovery and what is known of the pathogenesis of SWS. Breakout sessions related to neurology, dermatology, and ophthalmology aimed to establish SWS research priorities in each field. Key priorities for future development include the need for clinical consensus guidelines, further work to develop a clinical trial network, improvement of tissue banking for research purposes, and the need for multiple animal and cell culture models of SWS.

Introduction: The etiologies of congenital and developmental cataracts are diverse. Most are not syndromic and have no identifiable cause, thus creating a diagnostic dilemma. We investigated the utility of chromosomal microarray in identifying the etiology of isolated childhood cataracts. Methods: Patients with congenital or developmental cataracts without other associated abnormalities received a single-nucleotide polymorphism (SNP) microarray. copy number variations (CNV) and regions of homozygosity (ROH) were compared with previous literature reports and analyzed for candidate genes to assess pathogenicity. Results: We enrolled 37 patients. The mean age of the patient population was 10.98 years old. Nineteen patients (51.4%) had bilateral cataract. Positive family history was found in 11 patients (29.7%). Eighteen patients (48.7%) had a variant on microarray: 10 (27%) with CNV, 5 (13.5%) with ROH, and 3 patients (8.1%) with both CNV and homozygosity. In five patients (13.5%), we found a potentially causative cataract gene within an ROH. Discussion: There is a high rate of notable findings among the CNV and ROH detected. Three patients were homozygous in a region known to have a cataract gene suggesting a possible autosomal recessive disease. In those with CNV, segregation would help to affirm the pathogenicity of these regions and may lead to the identification of new genes. Conclusion: SNP microarray had a surprisingly high rate of notable findings in patients with isolated cataract and may reveal the opportunities for genetic counseling, lead to discovering new cataract genes and identify additional affected genes that could lead to other clinical abnormalities.

Cutaneous horns uncommonly involve the periocular region. Involvement of the ocular surface is particularly rare. The authors present a patient who underwent a perinatal buccal mucosal graft for corneal perforation due to congenital corneal ectasia, most likely resulting from Peters anomaly. She developed a giant ocular horn 10 years later.

There are no clear guidelines addressing whether a duty exists in a research-subject relationship to report child maltreatment and endangerment unveiled in research studies involving normal children. Researchers may have concerns about taking personal and professional risks by reporting suspected injury particularly if the researcher is not adequately trained in the area of abuse. Researchers may have concerns regarding the risk-benefit ratio of reporting, thresholds for reporting, and their own certainty about the information received. Researcher reporting may also be in conflict with ongoing child abuse interventions that are not known to the researcher. Research involving children and child endangerment relies upon children responding accurately to sensitive questions regarding abuse. If not, then data may be inaccurate or incomplete. There may also be obligations to forewarn parents/guardians that such information is being collected and what implications this may have in terms of reporting, intervention and protection.

In this chapter, we discuss informed consent, assent, and deception. In child abuse research, several unique scenarios exist relating to obtaining informed consent. First, for a child subject whose parents may be suspected of abuse, it can be argued that they are not able to act in the child’s best interest and thus not able to provide consent. Second, a child who is a ward of the state/crown has substitute parents/foster parents with limited decision-making power. Lastly, situations may exist where information needs to be obtained from a third party (such as a school or daycare) as part of a research study. Each of these situations raises questions relating to informed consent. Assent of a child subject also introduces challenges in the context of child abuse research. How to obtain assent from an abused child and how much information is necessary are subjects of much debate. Finally, there are circumstances where the disclosure of the purpose of a research study to a potential subject could influence the participation and/or actions of that subject in the study. This concept of ‘non-disclosure’ is separate and distinct from ‘deception’ in that deception involves the process of misleading a subject.

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.]

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.

To demonstrate vitreoretinal traction as a mechanism for perimacular folds in abusive head trauma.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.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.Vitreoretinal traction is the likely mechanism of perimacular folds in abusive head trauma.

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.

Background: Alagille syndrome is an autosomal dominant disorder characterized by neonatal cholestasis, characteristic facies, and cardiac abnormalities. Ocular abnormalities include posterior embryotoxon, mosaic pattern of iris stromal hypoplasia, microcornea, optic disc drusen, and pigmentary retinopathy. We present the second report of ocular pathology in two cases of Alagille syndrome. Methods: Gross and histologic preparations of four eyes of two patients. Results: Posterior embryotoxon is seen in both cases, with iris processes extending to the embryotoxon in case 1. Case 1 exhibited distinctly abnormal iris stroma with a prominent cleft separating the anterior and posterior stroma. Lacy vacuolization of the iris pigment epithelium was seen in case 2. Conclusions: Alagille syndrome is primarily a hepatic disorder but presents with several distinct ocular pathologic features, most specifically posterior embryotoxon. This and the unusual iris stroma may be caused by improper migration of neural crest cells due to mutation in the Jagged 1 gene that causes Alagille syndrome. Patients with Alagille syndrome rarely present to ocular autopsy. Pathology findings may help us better understand the pathophysiology of the ocular abnormalities in this disorder.

Purpose: The Philadelphia Eagle Eye Mobile (EEM) provides optometric vision care to children who fail a vision screening performed by nurses at schools in low-income areas. Methods: Data for children seen on the EEM between 2006 and 2008 for whom school nurse feedback was available regarding glasses wear at 1-, 4-, and 12-month intervals served as the study population. Optometric findings and glasses prescriptions at initial examination were recorded in the EEM database. The ophthalmic records for children referred for pediatric ophthalmology consultation at our institution were reviewed and those who did not attend were counted. Results: A random subset of 689 students at 28 different schools at which follow-up forms were distributed to the school nurses regarding glasses wear was studied. This represents 10.8% of 6,365 children screened at 131 public schools visited by the EEM during that period. False-positive rates of school nurse screening averaged 16.11% (0% to 44%) for 689 children from 28 schools. Glasses compliance was 71% at 12 months and correlated to higher prescriptions. Only 53% of children attended their pediatric ophthalmology referral. Conclusions: Nurse training to reduce false-positive screening and strategies to improve attendance at arranged pediatric ophthalmologist consultations are recommended. The EEM effectively gets glasses to students where needed and use rates are satisfactory. [ J Pediatr Ophthalmol Strabismus. 2015;52(2):98–105.]

Axenfeld–Rieger spectrum (ARS) includes the anterior segment abnormalities posterior embryotoxon, irido-corneal adhesions, corectopia, and other abnormalities of pupil size and shape. Glaucoma occurs in approximately 50% of affected children. It is often caused by mutations of FOXC1 or PITX2. Timing of expression and dosage of these transcription factors appear to be very critical in the development of the anterior segment. We report on one child with a deletion and another with a duplication involving 6p25, causing an anirdia-like phenotype. Classic anirdia is a pan-ophthalmic disorder caused by heterozygous mutations involving the paired homeobox gene PAX6 at 11p13. It is often associated with optic nerve hypoplasia, foveal hypoplasia, corneal pannus, nystagmus, and cataract. Microdeletion of 11p13 may be associated with life threatening Wilms tumor. Distinguishing these two syndromes has critical implications for prognosis and treatment. We demonstrate how chromosomal microarray can be instrumental in differentiating these phenotypes. © 2015 Wiley Periodicals, Inc.

Cystoid macular edema (CME) and non-leaking intraretinal cystoid spaces (ICS) have different pathophysiologic mechanisms.We report a patient with retinitis pigmentosa (RP) with ICS due to a mutation in the male germ cell-associated kinase (MAK) gene.A 41-year-old Ashkenazi Jewish male was referred for abnormal visual field revealed by regular optometric examination. His visual acuity was 20/20 in each eye. Dilated examination revealed typical finding of RP. Optical coherence tomography showed cystoid changes in each fovea. Photoreceptors were also degenerated. Intravenous fluorescein angiography showed no leakage. Genetic testing identified a homozygous mutation in the MAK gene: a 353-bp Alu insertion (K429insAlu).Mak regulates microtubule stability via phosphorylating RP1. Abnormal Mak may impact retinal photoreceptor ciliary length and subcompartmentalization. Mak is required for the survival of photoreceptors in mice. ICS has been reported in other ciliopathies. We report the first case of ICS due to mutation in MAK.

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.