Performance of the Spot Vision Screener in children with Down syndrome and other special needs.

BACKGROUND: Amblyopia is a common cause of monocular vision impairment and disproportionally affects developmentally delayed children. Photoscreeners have been suggested as a method to detect amblyopia risk factors (ARFs) in children with developmental disabilities who may not be amenable to traditional vision screening methods. The Spot Vision Screener is a commonly used photoscreener for detecting ARF and has shown excellent sensitivity and accuracy in the general pediatric population. The purpose of this study was to evaluate its accuracy in children with Down syndrome and other special needs. METHODS: Children with various disabilities or delays were recruited from outpatient clinics at the Children's Hospital of Colorado. Participants had their photograph taken with Spot before and after pupil dilation and cycloplegia. Images were compared to results of a comprehensive clinical eye examination. RESULTS: A total of 100 children participated in the study. Images could not be obtained in 12 children; 5 children did not attend their clinical examination. The overall sensitivity of Spot was 90%, with a positive predictive value of 80% in undilated subjects. The area under the receiver operator curve (AUROC) was 0.68 (95% CI, 0.57-0.79), which did not differ significantly from the AUROC after dilation/cycloplegia (0.68; 95% CI, 0.54-0.81). CONCLUSIONS: The Spot Vision Screener could be used by primary care clinics and vision screening programs with a high sensitivity to determine which patients with Down syndrome and special needs should be referred for clinical examination.

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.

Socioeconomics of retinopathy of prematurity screening and treatment in the United States.

BACKGROUND: Retinopathy of prematurity (ROP) screening, an integral part of pediatric ophthalmology, can be time consuming and resource intensive. The purpose of this study was to evaluate the economic landscape of ROP screening and treatment among pediatric ophthalmologists in the United States. METHODS: An online survey was distributed to US pediatric ophthalmologists through a pediatric ophthalmology email listserv. Survey results were compiled, and responses were deidentified and analyzed, with particular focus on factors affecting financial compensation. RESULTS: A total of 97 responses were collected. Almost half of respondents worked in private practice settings. Over 80% of respondents had a formal contract to perform ROP care, but only 26% enlisted the assistance of an attorney to negotiate their contract. Just over half of respondents believed themselves adequately compensated for their services. Respondents that had retained an attorney for contractual negotiations were more likely to have a higher mean annual compensation rate ($126,545 ± $145,133 vs $70,214 ± $50,671; P = 0.05). Physicians who believed themselves adequately compensated were more likely to be in academic practice settings (78% academic vs 55% combo/other vs 24% private; P < 0.001) and were more likely to have contracts to perform ROP care (68% with contracts vs 15% without; P = 0.001). Average annual compensation was $82,968 ± $84,132, approximately $24,000 higher than reported in 2013. CONCLUSIONS: More pediatric ophthalmologists among our respondents obtained contracts for their services, and compensation rates have increased since 2013. Nevertheless, concerns regarding under-compensation and time commitment persist, raising concerns about the long-term sustainability of current models for providing ROP services.

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.].

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.

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.

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.

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.

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.

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.

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.

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.

Lipogranulomatous subconjunctival nodules: a novel presentation in Blau syndrome.

Blau syndrome is an early-onset granulomatous disease known to affect the skin, joints, and eyes. We report a child with diffuse rash, arthritis, and subconjunctival nodules. Biopsy of the bulbar conjunctiva revealed noncaseating lipogranulomas that lead to a diagnosis of Blau syndrome. To our knowledge, noncaseating lipogranulomas of the conjunctiva have not been reported previously as a presenting finding in Blau syndrome. Although uveitis is the classic manifestation, it is important to broaden the awareness of other ocular signs, as these variations can aid in diagnosis.

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.

Case Report of an Anthrax Presentation Relevant to Special Operations Medicine.

Special Operations Forces (SOF) medical personnel function worldwide in environments where endemic anthrax (caused by Bacillus anthracis infection) may present in one of three forms: cutaneous, pulmonary, or gastrointestinal. This report presents a rare periocular anthrax case from Haiti to emphasize the need for heightened diagnostic suspicion of unusual lesions likely to be encountered in SOF theaters.

Colorado retinopathy of prematurity model: a multi-institutional validation study.

PURPOSE: The Colorado retinopathy of prematurity (ROP) prediction model (CO-ROP), developed using a cohort of infants from Colorado, calls for ROP examination of infants meeting all of the following criteria: gestational age of ≤30 weeks, birth weight of ≤1500 g, and a net weight gain of ≤650 g between birth and 4 weeks of age. The purpose of this study was to perform an external validation to assess the sensitivity and specificity of the CO-ROP model in a larger cohort of babies screened for ROP from four academic institutions in the United States. METHODS: The medical records of neonates screened for ROP according current national guidelines was conducted at 4 US academic centers were retrospectively reviewed. Sensitivity, specificity, and respective 95% confidence intervals in detecting ROP using CO-ROP were calculated for type 1, type 2, and any grade of ROP. RESULTS: A total of 858 cases were included. The CO-ROP algorithm had a sensitivity of 98.1% (95% CI, 93.3%-99.8%) for type 1 ROP, 95.6% (95% CI 78.0-99.9%) for type 2 ROP, and 95.0% (95% CI, 93.1-97.4%) for all grades of ROP. The CO-ROP model would have reduced the total number of infants screened by 23.9% compared to current 2013 screening guidelines. CONCLUSIONS: CO-ROP demonstrated high sensitivity in predicting ROP and would have greatly reduced the number of infants needing examination.

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.

The Colorado-retinopathy of prematurity model (CO-ROP): postnatal weight gain screening algorithm.

PURPOSE: To describe a novel retinopathy of prematurity (ROP) screening model incorporating birth weight, gestational age, and postnatal weight gain that maintains sensitivity but improves specificity in detecting all grades of ROP compared to current 2013 screening guidelines. METHODS: The medical records of 499 neonates from a single tertiary referral center who met the 2013 screening guidelines for ROP were retrospectively reviewed. Weekly weights were analyzed using standard logistic regression to determine the age at which the weekly net weight gain best predicted the development of ROP, which was designated as the postnatal weight gain criterion. The 2013 birth weight and gestational age criteria were included in an "and" fashion to form the CO-ROP model. Sensitivities and specificities in detecting high grade (type 1 and 2) and all grades of ROP were calculated. RESULTS: The CO-ROP model screens infants with a gestational age at birth of ≤30 weeks and birth weight of ≤1500 g and net weight gain of ≤650 g between birth and 1 month of age. In our cohort, CO-ROP had a sensitivity of 100% (95% CI, 92.1%-100.0%) for high-grade (type 1 and 2) ROP and 96.4% (95% CI, 92.3%-98.7%) for all grades of ROP. It would reduce the number of infants screened by 23.7% compared to 2013 guidelines. Calibrating the model to detect only high-grade ROP would result in a 45.9% reduction in the total number of infants screened. CONCLUSIONS: CO-ROP is a simple model that maintains a statistically similar sensitivity in detecting all grades of ROP while significantly reducing the total number of required ROP screenings compared to 2013 guidelines. The study had a small sample size but shows promise for future research and clinical efforts.