Automated syndrome diagnosis by three-dimensional facial imaging.

PURPOSE: Deep phenotyping is an emerging trend in precision medicine for genetic disease. The shape of the face is affected in 30-40% of known genetic syndromes. Here, we determine whether syndromes can be diagnosed from 3D images of human faces. METHODS: We analyzed variation in three-dimensional (3D) facial images of 7057 subjects: 3327 with 396 different syndromes, 727 of their relatives, and 3003 unrelated, unaffected subjects. We developed and tested machine learning and parametric approaches to automated syndrome diagnosis using 3D facial images. RESULTS: Unrelated, unaffected subjects were correctly classified with 96% accuracy. Considering both syndromic and unrelated, unaffected subjects together, balanced accuracy was 73% and mean sensitivity 49%. Excluding unrelated, unaffected subjects substantially improved both balanced accuracy (78.1%) and sensitivity (56.9%) of syndrome diagnosis. The best predictors of classification accuracy were phenotypic severity and facial distinctiveness of syndromes. Surprisingly, unaffected relatives of syndromic subjects were frequently classified as syndromic, often to the syndrome of their affected relative. CONCLUSION: Deep phenotyping by quantitative 3D facial imaging has considerable potential to facilitate syndrome diagnosis. Furthermore, 3D facial imaging of "unaffected" relatives may identify unrecognized cases or may reveal novel examples of semidominant inheritance.

Acute corneal injury in rabbits following nitrogen mustard ocular exposure.

Sulfur mustard (SM), a potent vesicating chemical warfare agent, and its analog nitrogen mustard (NM), are both strong bi-functional alkylating agents. Eyes, skin, and the respiratory system are the main targets of SM and NM exposure; however, ocular tissue is most sensitive, resulting in severe ocular injury. The mechanism of ocular injury from vesicating agents' exposure is not completely understood. To understand the injury mechanism from exposure to vesicating agents, NM has been previously employed in our toxicity studies on primary human corneal epithelial cells and ex vivo rabbit cornea organ culture model. In the current study, corneal toxicity from NM ocular exposure (1%) was analyzed for up to 28 days post-exposure in New Zealand White male rabbits to develop an acute corneal injury model. NM exposure led to conjunctival and eyelid swelling within a few hours after exposure, in addition to significant corneal opacity and ulceration. An increase in total corneal thickness and epithelial degradation was observed starting at day 3 post-NM exposure, which was maximal at day 14 post-exposure and did not resolve until 28 days post-exposure. There was an NM-induced increase in the number of blood vessels and inflammatory cells, and a decrease in keratocytes in the corneal stroma. NM exposure resulted in increased expression levels of cyclooxygenase-2, Interleukin-8, vascular endothelial growth factor and Matrix Metalloproteinase 9 indicating their involvement in NM-induced corneal injury. These clinical, biological, and molecular markers could be useful for the evaluation of acute corneal injury and to screen for therapies against NM- and SM-induced ocular injury.

Non-organic Vision Loss in the Afghanistan and Iraq Conflicts.

Non-organic visual loss (NOVL), defined as a decrease in visual acuity or field without an identifiable organic cause, can be challenging to diagnose, especially in patients whose NOVL is superimposed on some component of true organic pathology. Exposure to combat puts soldiers at risk of emotional distress and physical trauma, which can contribute to the development of NOVL with conversion disorder or malingering. This case series describes six patients with NOVL who sustained ocular or non-ocular injuries while serving in combat operations in Iraq and Afghanistan, and highlights diagnostic pearls and components of inter-disciplinary management in the unique military context.

Clinical progression of ocular injury following arsenical vesicant lewisite exposure.

Ocular injury by lewisite (LEW), a potential chemical warfare and terrorist agent, results in edema of eyelids, inflammation, massive corneal necrosis and blindness. To enable screening of effective therapeutics to treat ocular injury from LEW, useful clinically-relevant endpoints are essential. Hence, we designed an efficient exposure system capable of exposing up to six New-Zealand white rabbits at one time, and assessed LEW vapor-induced progression of clinical ocular lesions mainly in the cornea. The right eye of each rabbit was exposed to LEW (0.2 mg/L) vapor for 2.5, 5.0, 7.5 and 10.0 min and clinical progression of injury was observed for 28 days post-exposure (dose-response study), or exposed to same LEW dose for 2.5 and 7.5 min and clinical progression of injury was observed for up to 56 days post-exposure (time-response study); left eye served as an unexposed control. Increasing LEW exposure caused corneal opacity within 6 h post-exposure, which increased up to 3 days, slightly reduced thereafter till 3 weeks, and again increased thereafter. LEW-induced corneal ulceration peaked at 1 day post-exposure and its increase thereafter was observed in phases. LEW exposure induced neovascularization starting at 7 days which peaked at 22-35 days post-exposure, and remained persistent thereafter. In addition, LEW exposure caused corneal thickness, iris redness, and redness and swelling of the conjunctiva. Together, these findings provide clinical sequelae of ocular injury following LEW exposure and for the first time establish clinically-relevant quantitative endpoints, to enable the further identification of histopathological and molecular events involved in LEW-induced ocular injury.

Retinal hemorrhage after cardiopulmonary resuscitation with chest compressions.

Retinal hemorrhages in children in the absence of risk factors are regarded to be pathognomonic of shaken baby syndrome or other nonaccidental injuries. The physician must decide whether the retinal hemorrhages in children without risk factors are due to abuse or cardiopulmonary resuscitation with chest compression (CPR-CC). The objective of this study was to determine if CPR-CC can lead to retinal hemorrhages in children. Twenty-two patients who received in-hospital CPR-CC between February 15, 1990, and June 15, 1990, were enrolled. Pediatric ophthalmology fellows carried a code beeper and responded to calls for cardiopulmonary arrest situations. At the scene of CPR-CC, an indirect funduscopic examination was conducted for presence of retinal hemorrhages in the posterior pole. Follow-up examinations were performed at 24 and 72 hours. Of the 22 patients, 6 (27%) had retinal hemorrhages at the time of CPR-CC. Of these 6 patients, 5 had risk factors for retinal hemorrhages. The sixth patient had no risk factors and may have represented the only true case of retinal hemorrhages due to CPR-CC. Retinal hemorrhages are uncommon findings after CPR-CC. Retinal hemorrhages that are found after CPR-CC usually occur in the presence of other risk factors for hemorrhage with a mild hemorrhagic retinopathy in the posterior pole.

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries.

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100nmol) exposure of the corneas for 2h (cultured for 24h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2h and every 4h thereafter, for 24h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100µg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline+dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants.

A rare case of an isolated PAX6 mutation, aniridia, and Wilms tumor.

Introduction: Wilms tumor (WT) is the most common renal malignancy of children and can be seen in WAGR syndrome (WT, aniridia, genitourinary anomalies, and intellectual disability). WAGR results from a contiguous gene deletion within the 11p13 region, encompassing the WT1 gene, often responsible for WT development, and the PAX6 gene, responsible for aniridia. Aniridia, a pan-ocular disease resulting from iris hypoplasia, is thought to increase the risk for WT development if their genetic alteration spans both the WT1 and the PAX6 genes on 11p13.Case Description: We describe a unique case of a patient with aniridia secondary to a heterozygous PAX6 nonsense mutation who developed WT despite no additional identifiable germline genetic drivers for this disease.Discussion: Isolated mutations in PAX6 previously have not been associated with increased risk of WT development case raises the question of if surveillance for WT should be continued in patients with aniridia with an isolated PAX6 mutation identified.

Clinical Utility of Electroretinograms for Evaluating Vigabatrin Toxicity in Children.

PURPOSE: To determine changes in the clinical treatment of pediatric patients taking vigabatrin for seizure control in response to results of electroretinogram (ERG) performed for retinal toxicity screening. METHODS: The authors retrospectively reviewed the medical records of patients who received ERGs at Children's Hospital of Colorado from 2009 to 2012. Age, indication for ERG, ERG data, and clinical management of vigabatrin were extracted from the records. ERGs were interpreted according to LKC Technologies normative values. A physician trained in ERG analysis interpreted each ERG. RESULTS: One hundred seventy ERGs were performed during the study period, and 147 ERGs were available for analysis. Every patient received general anesthesia for the procedure. Thirty-three ERGs were performed in 29 patients specifically as screening for retinal toxicity due to vigabatrin use, and 30 were available for analysis. Within this cohort, only 2 ERGs were normal (6.6%), and 28 were abnormal (93.3%). In patients who received abnormal results, 1 patient discontinued vigabatrin in response to the screening. CONCLUSIONS: In this study cohort, clinical management generally did not change in response to an abnormal screening result. Given the need for general anesthesia in the pediatric population receiving ERG testing, and minimal change in clinical decision-making in the face of abnormal results, ERG screening for retinal toxicity due to vigabatrin in the pediatric cohort should be reconsidered. [J Pediatr Ophthalmol Strabismus. 2021;58(3):174-179.].

Pathophysiology and inflammatory biomarkers of sulfur mustard-induced corneal injury in rabbits.

Sulfur mustard (SM) is a cytotoxic, vesicating, chemical warfare agent, first used in 1917; corneas are particularly vulnerable to SM exposure. They may develop inflammation, ulceration, neovascularization (NV), impaired vision, and partial/complete blindness depending upon the concentration of SM, exposure duration, and bio-physiological conditions of the eyes. Comprehensive in vivo studies have established ocular structural alterations, opacity, NV, and inflammation upon short durations (<4 min) of SM exposure. In this study, detailed analyses of histopathological alterations in corneal structure, keratocytes, inflammatory cells, blood vessels, and expressions of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), and cytokines were performed in New Zealand white rabbits, in a time-dependent manner till 28 days, post longer durations (5 and 7 min) of ocular SM exposure to establish quantifiable endpoints of injury and healing. Results indicated that SM exposure led to duration-dependent increases in corneal thickness, opacity, ulceration, epithelial-stromal separation, and epithelial degradation. Significant increases in NV, keratocyte death, blood vessels, and inflammatory markers (COX-2, MMP-9, VEGF, and interleukin-8) were also observed for both exposure durations compared to the controls. Collectively, these findings would benefit in temporal delineation of mechanisms underlying SM-induced corneal toxicity and provide models for testing therapeutic interventions.

Incidental detection of bilateral corectopia by photo screening leads to the diagnosis of multiple sclerosis. A case report.

PURPOSE: To describe a case of an incidental finding of bilateral corectopia detected by photo screening which ultimately led to the diagnosis of multiple sclerosis. METHODS: Case presentation and literature review. RESULTS: Corectopia may be congenital or acquired. Midbrain corectopia is commonly caused by infarction and demyelinating disease can cause autonomic pupil abnormalities resulting in corectopia. CONCLUSION: A careful history and ocular examinatin can aid in determining the etiology of corectopia. Additional genetics or neurologic consultation may be necessary to diagnosis systemic disease.

Comparison of a Novel Trainer to a Traditional Swine Model for Training Providers in Lateral Canthotomy and Cantholysis.

RESEARCH OBJECTIVE: Military personnel are at greater risks of head and facial traumas and permanent blindness from orbital compartment syndrome in modern warfare. Rapid treatment must be implemented with a low-risk surgical remedy: lateral canthotomy and cantholysis (LCC). Traditional training of LCC is primarily performed using an animal tissue trainer (ATT); however, limitations to these types of trainers exist. Therefore, our research objectives were focused on highlighting the effectiveness, benefits, and vision-saving potential of learning LCC on a synthetic trainer. METHODS: Participants included 22 second-year medical students and 6 healthcare professionals. A pre-quiz assessed baseline knowledge. Next, an experienced ophthalmologist provided an overview and instruction. Subjects were randomized to either the synthetic trainer or the ATT and then switched to the other model for comparison. After performing LCC procedures on both models, a post-quiz and survey were administered. RESULTS: Participants found the synthetic trainer easier to use than the ATT model (p < 0.01). There was no statistically significant preference (p = 0.23), or preference of practical eye anatomy (p = 0.26) between the trainers. Post-quiz results demonstrated an overall improvement from pre-quiz scores for participants (p < 0.001). CONCLUSIONS: The synthetic trainer is comparable to the traditional swine model for training LCC procedures, and should be considered as a future training platform.

The effect of amniotic membrane grafting on healing and wound strength after strabismus surgery in a rabbit model.

BACKGROUND: Amniotic membrane grafts (AMGs) are used, with mixed results, as a platform for ocular healing and to reduce pathologic scarring. This study evaluated wound tensile strength and histopathologic changes after strabismus surgery with AMGs in 20 New Zealand white rabbits. METHODS: All subjects underwent 4 mm inferior rectus hang-back recessions to both eyes. The right eyes served as controls. Ten left eyes (group 1) received processed dehydrated amniotic membrane allografts (Ambiodry2, IOP Inc, Costa Mesa, CA) and ten left eyes (group 2) received cryopreserved human amniotic membrane allografts (AmnioGraft, Bio-Tissue, Miami, FL) between the sclera and muscle insertion and between the muscle and repositioned conjunctiva. At postoperative month 1, tensile strengths of the muscle-globe and conjunctiva-globe attachments were measured, and histopathologic analysis of each eye was performed. RESULTS: In group 1 the mean tensile strength of the muscle-globe attachments was 441.4 ± 274.4 g; of the conjunctiva-globe attachments, 640.3 ± 266.4 g. In the control eyes, the comparable values were 365.8 ± 199.8 g and 595.2 ± 315.3 g, respectively (P = 0.19, P = 0.13). In group 2 the mean tensile strengths were 456 ± 297.5 g and 608.2 ± 306.7 g, compared with control values of 352.7 ± 114.8 g and 583.8 ± 347.1 g (P = 0.43, P = 0.45). CONCLUSIONS: There was no significant change in tensile strength of the muscle insertion using AMGs. In a rabbit model, AMGs do not reduce inflammation or improve scar formation 1 month after strabismus surgery.

Optimizing Tactical Medical Performance: The Effect of Light Hue on Vision Testing.

BACKGROUND: Red and blue are the historical tactical lighting hues of choice to ensure light discipline and to preserve dark adaptation. As yet, no scientifically ideal hue for use in Special Operations medicine has been identified. We propose red/green polychromatic light as a superior choice that preserves visual function for tactical medical tasks in austere settings. METHODS: Thirty participants were enrolled in this institutional review board-approved study. Participants completed four vision tasks in low-light settings under various lighting conditions. The Pelli-Robson Near Contrast Sensitivity test (PR), tumbling E visual acuity test, Farnsworth D-15 color-vision test (FD15), and pseudoisochromatic plate (PiP) testing was performed under white, green, or red light illumination and also red/green and red/green/yellow lights. PR and tumbling E tests were performed using blue and blue/red lights. RESULTS: The test results for each light were compared against a white-light standard. Contrast sensitivity as measured by PR testing showed no statistical difference when white light was used compared with red/green or red/green/yellow light, and the differences between red, green, blue, and blue/red all were statistically different from when white light was used. When measuring visual acuity, blue light was the only color for which there was a statistically significant decrease in visual acuity in comparison with white. There was no reduction in visual acuity with any other lights compared with white. Performance on FD15 testing with all single-hue and multihue lights was significantly worse than with white light for measuring color-vision perception. Color discrimination as measured by PiP testing showed red and green light was significantly worse than with white light, whereas test results when green/red and green/red/yellow lights were used were not statistically different from white. CONCLUSION: Red/Green/yellow and red/green were superior light sources and performance results only were worse than white light on FD15 testing.

Guidelines for postmortem protocol for ocular investigation of sudden unexplained infant death and suspected physical child abuse.

Postmortem examination is a cornerstone in identifying the cause of unexplained sudden death in children. Even in cases of suspected or known abuse, an autopsy may help characterize the nature of the abuse, which is particularly important in the forensic autopsy of children in the first 3 to 4 years of life when inflicted neurotrauma is most common. Forensic examinations are vital in cases that might otherwise be diagnosed as sudden infant death syndrome. The ocular autopsy in particular may demonstrate findings that were not appreciated on antemortem clinical examination. This protocol for postmortem examination of the eyes and orbits was developed to promote more consistent documentation of findings, improved clinical and forensic decision making, and more replicable and coherent research outcomes.

Combat ophthalmology. When there isn't an assigned ophthalmologist.

The National Guard has extensive capabilities that are impossible to attain in active duty units, largely because its citizen Soldiers bring their civilian expertise in addition to their military occupational specialties. While deploying to Afghanistan as the flight surgeon for a forward deployed Special Forces (SF) battalion, this Colorado Army National Guardsman also provided basic ophthalmology care in theater in the absence of an assigned ophthalmologist. The SF Battalion Preventive Medicine (PM) NCO was also an experienced eye technician in civilian life. Emergency eye surgery was provided for allied, coalition and host nationals in accordance with the Rules of Engagement. Elective eye surgery was an excellent method to build rapport and trust in keeping with the Special Forces "winning the hearts and minds" philosophy.

Atropine Eye Drops: A Proposed Field Expedient Substitute in the Absence of Atropine Autoinjectors.

Nerve agents are a threat to military and civilian health. The antidote, atropine sulfate, is delivered by autoinjector, which is a limited resource. We propose the use of 1% atropine ophthalmic solution (supplied commercially in 5mL or 15 mL bottles) via oral, ocular, and intranasal administration as an expedient substitute in austere environments.

Histopathological and Molecular Changes in the Rabbit Cornea From Arsenical Vesicant Lewisite Exposure.

Lewisite (LEW), a potent arsenical vesicating chemical warfare agent, poses a continuous risk of accidental exposure in addition to its feared use as a terrorist weapon. Ocular tissue is exquisitely sensitive to LEW and exposure can cause devastating corneal lesions. However, detailed pathogenesis of corneal injury and related mechanisms from LEW exposure that could help identify targeted therapies are not available. Using an established consistent and efficient exposure system, we evaluated the pathophysiology of the corneal injury in New Zealand white rabbits following LEW vapor exposure (at 0.2 mg/L dose) for 2.5 and 7.5 min, for up to 28 day post-exposure. LEW led to an increase in total corneal thickness starting at day 1 post-exposure and epithelial degradation starting at day 3 post-exposure, with maximal effect at day 7 postexposure followed by recovery at later time points. LEW also led to an increase in the number of blood vessels and inflammatory cells but a decrease in keratocytes with optimal effects at day 7 postexposure. A significant increase in epithelial-stromal separation was observed at days 7 and 14 post 7.5 min LEW exposure. LEW also caused an increase in the expression levels of cyclooxygenase-2, IL-8, vascular endothelial growth factor, and matrix metalloproteinase-9 at all the study time points indicating their involvement in LEW-induced inflammation, vesication, and neovascularization. The outcomes here provide valuable LEW-induced corneal injury endpoints at both lower and higher exposure durations in a relevant model system, which will be helpful to identify and screen therapies against LEW-induced corneal injury.

Validation of WINROP for detecting retinopathy of prematurity in a North American cohort of preterm infants.

BACKGROUND: WINROP (weight, insulin-like growth factor 1, neonatal, retinopathy of prematurity) is a web-based retinopathy of prematurity (ROP) risk algorithm that uses postnatal weight gain as a surrogate of insulin-like growth factor-1 (IGF-1) to predict the risk of severe ROP in premature infants. The purpose of this study was to validate the web-based algorithm WINROP in detecting severe (type 1 or type 2) ROP in a North American cohort of infants. METHODS: The records of consecutive infants who underwent ROP examinations between 2008 and 2011 were reviewed retrospectively. Infants were classified into categories of "alarm" (at risk for developing severe ROP) and "no alarm" (minimal risk for severe ROP). RESULTS: A total of 483 were included. Alarm occurred in 241 neonates (50%), with the median time from birth to alarm of 2 weeks. WINROP had a sensitivity of 81.8% (95% CI, 67.3%-91.8%) and specificity of 53.3% (95% CI, 48.5%-58.0%) for identifying infants with severe ROP. Eight of the 44 infants with severe ROP were not detected (5 with type 1 and 3 with type 2). Of these 8 infants, 7 (88%) had birth weight in excess of the 70th pecentile. With additional weight data entry, sensitivity of WINROP rose to 88.6%. CONCLUSIONS: Very preterm infants (gestational age of ≤27 weeks) with relatively high birth weight for gestational age may not be detected by WINROP as high risk for developing severe ROP.

A symptom survey and quality of life questionnaire for nasolacrimal duct obstruction in children.

PURPOSE: To develop and validate a new parental questionnaire addressing symptoms and health-related quality of life (HRQL) in childhood nasolacrimal duct obstruction (NLDO). DESIGN: Cross-sectional study. PARTICIPANTS: Children ages 6 to younger than 48 months with and without clinical signs of NLDO. METHODS: A new questionnaire was developed using semistructured interviews with parents of children with NLDO and through discussions with expert clinicians. Questionnaires were completed by parents of children with and without NLDO. Cronbach's alpha was calculated as a measure of internal-consistency reliability. Factor analysis was used to evaluate a priori subscales: symptoms and HRQL. Discriminant construct validity was assessed by comparing questionnaire scores between children with and without NLDO and between affected and unaffected eyes of children with unilateral NLDO. Instrument responsiveness was determined by comparing presurgical and postsurgical intervention scores in a subset of NLDO patients who underwent surgical treatment. MAIN OUTCOME MEASURE: The NLDO questionnaire score. RESULTS: Eighty-seven children were enrolled, 56 with and 31 without NLDO. All but 2 questions on the questionnaire showed a good distribution of responses, a high correlation with the rest of the questionnaire, and excellent discrimination between patients with and without NLDO. Cronbach's alpha values were good for the overall questionnaire (0.95), and for 2 predetermined subscales: symptoms (0.95) and HRQL (0.85). On a 0 to 4 scale, NLDO patients had worse scores compared with non-NLDO patients for both symptoms (mean difference, 2.1; 95% confidence interval [CI], 1.9-2.3) and HRQL (mean difference, 1.2; 95% CI, 0.9-1.5) subscales. The NLDO patients had worse scores before intervention compared with after intervention for both the symptoms (mean difference, 2.2; 95% CI, 1.6-2.9) and HRQL (mean difference, 1.4; 95% CI, 0.8-2.1) subscales. Finally, NLDO patients had worse symptom scores for affected eyes compared with unaffected eyes (mean difference, 2.3; 95% CI, 1.9-2.6). CONCLUSIONS: This novel NLDO questionnaire is useful in quantifying parental perception of symptoms and HRQL in childhood NLDO. The questionnaire may have a role in future clinical studies of NLDO.

Postmortem orbital findings in shaken baby syndrome.

PURPOSE: To compare postmortem orbital findings in pediatric accidental head injury to Shaken Baby Syndrome (SBS). DESIGN: Retrospective study. SETTING: Institutional. STUDY POPULATION: Thirty-six patients underwent postmortem modified exenteration with sectioning of the orbital contents; 18 victims of SBS and 18 cases of fatal accidental head trauma. OBSERVATION PROCEDURE: In all cases of children who died from accidental head trauma, the orbital tissues were separated to expose the optic nerve sheath. Patients with gross evidence of hemorrhage within the sheath were included. All cases of SBS were included. After accidental head injury, exenteration was performed only if optic nerve sheath hemorrhage was suspected on gross examination. All children younger than 18 years old with head injury as primary cause of death were included. SBS is defined as having at least two of the following: (1) typical abnormal findings on neuroimaging, (2) typical skeletal injury, (3) retinal hemorrhages, (4) history of abusive shaking with or without blunt head trauma, or (5) an inadequate history to explain the observed injuries. MAIN OUTCOME MEASURE: Presence or absence of orbital hemorrhage. RESULTS: Orbital tissue injury is more common in SBS than accidental head trauma without orbital fracture. In addition, optic nerve sheath and optic nerve intradural hemorrhage are also significantly more common in SBS (P < .0001). CONCLUSIONS: Our study reports new evidence of injury to orbital tissues in SBS and supports the concept that these finding are due to unique acceleration-deceleration forces of this type of abusive head injury.