Diagnostic yield of workups ordered by pediatric ophthalmologists for bilateral pediatric cataracts at a tertiary pediatric hospital in the United States.

BACKGROUND: Children with unexplained bilateral cataracts routinely undergo testing for genetic, infectious, and metabolic etiologies. We evaluated the diagnostic yield of various tests ordered by pediatric ophthalmologists to evaluate bilateral cataracts in children at a single institution. METHODS: We retrospectively identified all children with bilateral unexplained cataracts who underwent cataract surgery by a pediatric ophthalmologist at Children's Hospital Colorado from 2006 to 2022. We reviewed the results of genetic, infectious, and metabolic testing ordered by pediatric ophthalmologists to evaluate the cataracts in these children. RESULTS: A total of 43 children met inclusion criteria. Of these, 34 (79%) had genetic testing, 34 (79%) had infectious disease testing, 33 (77%) had galactosemia testing, and 17 (40%) had urine-reducing substances testing performed during their cataract evaluation. Of the genetic tests ordered, 17 (50%) revealed a pathogenic mutation associated with cataracts. Twenty-three (68%) patients were IgG-positive for a TORCH infection, but no child was found to be positive on confirmatory testing. Of the galactosemia and URS tests ordered, 3 tests (9%) and 1 (6%) test were initially found to be abnormal, respectively, but confirmatory testing and clinical judgment ruled out metabolic disease in each case. CONCLUSIONS: Genetic testing should be strongly considered in all cases of unexplained bilateral pediatric cataracts. Metabolic and infectious testing is best considered only after consultation with the child's pediatrician, guided by the patient's clinical context and the availability of genetic testing.

Prevalence of cerebrotendinous xanthomatosis among patients diagnosed with early-onset idiopathic bilateral cataracts: final analysis.

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1, a gene involved in bile acid synthesis. Impaired function in this gene leads to accumulation of plasma cholestanol (PC) in various tissues, often in early childhood, resulting in such clinical signs as infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration. The current study aimed to identify cases of CTX in a population of patients with a greater CTX prevalence than the general population, to facilitate early diagnosis. Patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years were enrolled. Genetic testing of patients with elevated PC and urinary bile alcohol (UBA) levels was used to confirm CTX diagnosis and determine CTX prevalence. Of 426 patients who completed the study, 26 met genetic testing criteria (PC ≥ 0.4 mg/dL and positive UBA test), and 4 were confirmed to have CTX. Prevalence was found to be 0.9% in enrolled patients, and 15.4% in patients who met the criteria for genetic testing.

Ophthalmic manifestations of ruptured arachnoid cysts in children.

BACKGROUND: Intracranial arachnoid cysts are relatively common in the pediatric population. Rarely, they rupture, leading to acute subdural fluid collections, which can cause a sudden increase in intracranial pressure. The purpose of this study was to characterize ophthalmic sequelae in a large cohort of these patients. METHODS: The medical records of all children treated for ruptured arachnoid cysts who presented at a single tertiary pediatric hospital for initial assessment between 2009 and 2021 were reviewed retrospectively. RESULTS: Of 35 children treated for ruptured arachnoid cysts during the study period, 30 received ophthalmological examination. Papilledema was found in 57% of these children, abducens palsy in 20%, and retinal hemorrhages in 10%. Of the 30 children, 22 were seen in outpatient follow-up, of whom 5 had a best-corrected visual acuity of 20/40 or worse in one or both eyes at most recent follow-up. Cranial nerve palsies resolved in all cases without strabismus surgery. CONCLUSIONS: Given high rates of papilledema, cranial nerve palsies, and vision loss, all children with ruptured arachnoid cysts should be evaluated by pediatric ophthalmologists.

Ganciclovir-resistant cytomegalovirus retinitis in a 4-month-old infant.

We present a case of ganciclovir-resistant cytomegalovirus retinitis (CMV) in a 4-month-old boy with congenital CMV infection. This case highlights the potential utility of a combination of intermittent viral load monitoring and retinal examinations in cases of congenital CMV with retinitis.

Physician burnout in ophthalmology: U.S. survey.

PURPOSE: To determine the prevalence of physician burnout among ophthalmologists in the United States and identify associated risks. SETTING: All practice types within the United States. DESIGN: Cross-sectional study. METHODS: A survey was distributed through email listservs to several national ophthalmology societies. Participants completed a modified Mini Z Burnout Survey, a 10-item questionnaire measured in 5-point Likert scales, followed by demographic questions. The Mini Z Burnout survey assessed 3 main outcomes: stress, burnout, and work satisfaction. The percentage of subgroups experiencing burnout were presented and comparisons made with odds ratios from logistic regression modeling. RESULTS: Of the 592 ophthalmologists responding to the survey, 37.8% (224) self-reported symptoms of burnout with a low of 30.8% (12/39) for vitreoretinal specialists to a high of 45.4% (30/66) for uveitis specialists. Most of those reporting burnout were categorized as mild (65.2% [146/224]), followed by moderate (29.5% [66/224]) and severe (5.4% [12/224]). Women had almost twice the odds of reporting burnout (odds ratio [OR] = 1.9 [95% CI: 1.3-2.7]; P = .0005). Physicians employed in academic (OR = 2.0 [95% CI: 1.2-3.2]; P = 0.007) and hospital facilities (OR = 2.4 [95% CI: 1.3-4.6]; P = .008) reported higher rates of burnout compared with those in large private groups. Burnout was associated with self-reported low work control, insufficient time for documentation, and misalignment with departmental leaders (P < .0001). CONCLUSIONS: Ophthalmologists exhibited a high degree of self-reported burnout in the U.S. This study highlights sex, employment autonomy, and practice type as major factors associated with burnout.

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.].

Trends in Retinopathy of Prematurity over 12 Years in a Colorado Cohort.

PURPOSE: To determine trends in retinopathy of prematurity (ROP) in a Colorado cohort between 2006 and 2017 and compare trends in risk factors between our cohort and statewide data. METHODS: A retrospective cohort study was conducted by the use of records from two registry databases: 1) an academic center's ROP registry, and 2) vital statistics birth data from the Colorado Department of Public Health and Environment (CDPHE). ROP was categorized as severe (type 1 or type 2), low grade (not type 1 or type 2), or no ROP. Other variables included in the analyses were gestational age and birth weight at delivery, and infant mortality. Trends over time were evaluated for both registry databases using generalized linear models. RESULTS: In our ROP registry cohort of 1,267 eligible infants, 134 (10.6%) developed severe ROP and 279 (22%) developed low-grade ROP. We found no overall trend in severe ROP rates (p = .23), and a decreasing trend in rates of low-grade ROP (p < .01) over the study period. Trends in gestational age, birth weight, and mortality rates remained stable during the study period in both the ROP registry and the CDPHE cohorts. CONCLUSION: The rate of severe ROP in our ROP registry cohort did not change over time. There was evidence of a decreasing trend in low grade ROP during the 12-year study period that was not explained by a change in the primary ROP risk factors in either the ROP registry cohort or the Colorado statewide data.

Perceptions of Marijuana Use for Glaucoma from Patients, Cannabis Retailers, and Glaucoma Specialists.

PURPOSE: As marijuana's popularity continues to grow, patients with glaucoma will encounter conflicting opinions on marijuana's role in glaucoma therapy. This study seeks to define the differing perceptions among glaucoma specialists, medical marijuana dispensaries, and glaucoma patients in a state with legalized marijuana. DESIGN: Cross-sectional study. PARTICIPANTS: Medical marijuana dispensaries in Colorado, members of the American Glaucoma Society (AGS), and patients with glaucoma at the University of Colorado glaucoma clinic. METHODS: First, medical marijuana dispensary employees were surveyed using a mystery call approach and a brief phone script. Dispensary employees were questioned as to whether marijuana was recommended and whether marijuana was safe and effective. Second, a self-administered survey was distributed to AGS members to determine the history of recommending marijuana and influencing factors for or against this recommendation. Third, the self-administered glaucoma patient survey assessed demographics, history of glaucoma, knowledge and rate of marijuana use, and perceptions of marijuana use. All surveys were conducted from October 2018 to March 2019. MAIN OUTCOME MEASURES: The proportion of medical marijuana dispensaries and glaucoma specialists recommending marijuana for the treatment of glaucoma, and the proportion of patients with glaucoma using marijuana as a treatment for glaucoma. RESULTS: A total of 203 of the 300 medical marijuana dispensaries called were successfully contacted (68%). Of these, 103 respondents (51%) recommended marijuana products for the treatment of glaucoma. The remaining 100 (49%) deferred making a recommendation or were unsure. Of the 1308 AGS members, 290 (22%) responded to the survey. Twenty-two respondents (7.6%) reported that they had recommended marijuana for the treatment of glaucoma, with the majority of these (86.4%) having done so infrequently. Among the 231 respondents with glaucoma, most (58.9%) had heard about the possible use of marijuana for glaucoma, but only 2.6% had used marijuana as a treatment for glaucoma. CONCLUSIONS: Few glaucoma specialists have recommended marijuana as a treatment for glaucoma, and an even smaller percentage of patients report its use as a treatment for their glaucoma. In contrast, many marijuana dispensary employees endorse its use. As legal access and public acceptance of marijuana escalate, physicians should be aware of these perceptions when educating patients.

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.

Keratoconus and corneal morphology in patients with Down syndrome at a pediatric hospital.

PURPOSE: To evaluate patients with Down syndrome for keratoconus and corneal abnormalities using Scheimpflug imaging (Pentacam HR) in a pediatric setting. METHODS: The Pentacam scans of patients with Down syndrome seen at Children's Hospital Colorado Ophthalmology Department were reviewed retrospectively, and the following data were collected: keratometry values, pachymetry values, components of the Belin ABCD Grading System, the Belin/Ambrosio enhanced ectasia display D value, and topometric indices, including ISV, IVA, and KI. Subjective interpretation was used to classify scans as normal, abnormal, keratoconus suspect, and definite keratoconus. RESULTS: A total of 56 eyes of 31 patients aged 4-24 years (mean, 12.4) were included. The average value for K1 was 44.95 ± 1.73 D (range, 40.90-49.3 D); for K2, 46.87 ± 2.16 D (range, 42.50-51.80 D); for Kmax, 48.20 ± 3.11 D (range, 43-61.7 D); and for Kmean, 45.81 ± 1.85 D (range, 41.7-50.35 D). Mean pachymetry at the thinnest point was 509 ± 44.24 µm (range, 410-612 µm) and at the apex was 519 ± 44.24 µm (range, 412-646 µm). The mean D value was 2.08 ± 1.57 (range, 0.08-9.71). There were 10 patients (32%) with either keratoconus suspect or definite keratoconus in at least one eye. CONCLUSIONS: We found a high frequency of keratoconus and keratoconus suspect in pediatric and young adult patients with Down syndrome. The corneas in this population had steeper K values and thinner pachymetry values compared to previously reported controls.

Ocular Findings in Pontine Tegmental Cap Dysplasia.

PURPOSE: To describe the ocular complications experienced by patients with pontine tegmental cap dysplasia (PTCD) and the management strategies used to care for these children. METHODS: Subjects with PTCD were recruited through social media advertisement and completed a survey gathering information on potential ocular problems related to the patient's PTCD disease and any current or previous treatments. RESULTS: Twenty-two patients or guardians completed the survey. Neurotrophic cornea was the most common ocular diagnosis (82%), followed by facial palsy (59%), dry eye syndrome (59%), and blepharitis (55%). Other diagnoses included cortical visual impairment (27%), strabismus (27%), amblyopia (18%), and nystagmus (18%). Common treatment modalities included lubricating eye drops (59%) or ointment (50%), contact lenses (14%), punctal plugs (27%), glasses (45%), and patching (18%). The most common surgical interventions were temporary or permanent tarsorrhaphy (64%) and amniotic membrane grafts (23%). In total, 68% of families reported self-injury to eyes and 91% reported the child to be primarily a visual learner. CONCLUSIONS: PTCD is a newly described, very rare disorder with a variety of vision-threatening ocular manifestations. It is essential that the ophthalmologist be aware of the potential for neurotrophic cornea because timely treatment could prevent corneal scarring, perforation, and blindness.

Comparison between weight gain and Fenton preterm growth z scores in assessing the risk of retinopathy of prematurity.

Several studies have shown that postnatal weight gain is a significant predictor for retinopathy of prematurity (ROP) in preterm infants. Using a cohort of 1,301 infants from a single-center ROP registry, we investigated whether incorporation of changes in Fenton preterm growth curve z scores (ie, deviation from the population average) provides improved predictive ability for developing ROP compared to weight gain alone. Three logistic regressions were fit to severe ROP: (1) baseline model that included gestational age and birth weight, (2) the baseline model adding weight gain, and (3) the baseline model adding change in z score. The area under the receiver operating characteristic curve (C index) was used to compare models. Both weight gain and change in z scores were significant predictors after adjusting for birth weight (P = 0.01) and gestational age (P < 0.01). The C indices were not significantly improved by including weight gain or z score to the baseline model; however, for a subset of subjects, change in weight z score may be a more useful measure compared to simple weight gain with regards to assessing risk for severe ROP.

COL4A1 mutations in two infants with congenital cataracts and porencephaly: an ophthalmologic perspective.

COL4A1 mutations present with a spectrum of clinical phenotypes often involving the cerebrovascular and ophthalmic systems. We report 2 cases of COL4A1 mutations that presented with congenital cataracts and porencephaly. Both patients had posterior cortical cataracts and radiographically defined bilateral posterior lenticonus. Considering the long-term clinical implications of these mutations, posterior cortical cataracts, bilateral posterior lenticonus, and porencephaly should raise clinical suspicion for COL4A1 mutations.

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

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.

Frequency of pediatric traumatic cataract and simultaneous retinal detachment.

PURPOSE: Traumatic cataract in children is a treatable cause of vision loss. In cases of simultaneous retinal detachment, the prognosis for visual recovery is often poor. The purpose of this study was to investigate risk factors for concurrent retinal detachment in patients with traumatic cataract. METHODS: A retrospective review of patients diagnosed with traumatic cataract at Children's Hospital Colorado between 2005 and 2014 was conducted. Demographics, mechanism of injury, and incidence of retinal detachment were recorded. Logistic modeling with generalized estimating equations to account for correlation of eyes within patients was used to analyze associations between potential risk factors and retinal detachment. RESULTS: A total of 62 total eyes with traumatic cataract were included: 52 patients presented with unilateral cataract; 5 presented with bilateral cataracts. Mean patient age was 8.4 ± 4.1 years (range, 0-16 years), and 83% of patients were male. A total of 9 eyes (14.5%) had comorbid retinal detachment. Traumatic cataracts caused by self-injurious hitting were more likely to present with simultaneous retinal detachment than those caused by other mechanisms of injury (OR = 24.0; 95% CI, 3.8-153.3; P = 0.0010). CONCLUSIONS: Patients with traumatic cataract who display self-injurious behavior are at higher risk for concurrent retinal detachment. These patients can often only be examined under sedation. Ophthalmologists should counsel families of high-risk patients and consider involving retinal specialists in surgical planning.

The role of the maternal and fetal inflammatory response in retinopathy of prematurity.

PROBLEM: There is a paucity of research on the contribution of placental inflammation to severe retinopathy of prematurity (ROP). METHOD OF STUDY: A retrospective cohort study (n = 1217) was conducted of infants screened for ROP (2006-2016). The outcomes of the study were severe ROP (type 1 or type 2 ROP) and low grade ROP. We categorized the placental pathology as the presence of (i) maternal plus fetal inflammatory response, (ii) maternal inflammatory response only, (iii) fetal inflammatory response only and, (iv) no evidence of a maternal or fetal inflammatory response. The data were analyzed using univariate and multivariate logistic regression analyses (P < .05). RESULTS: In this cohort, the number of infants with the maternal plus fetal inflammatory response, the maternal inflammatory response only, the fetal inflammatory response only, and no maternal or fetal inflammatory response was 305 (25%), 82 (7%), 8 (1%), and 822 (67%), respectively. Adjusted for covariates, the maternal plus fetal inflammatory response was a significant risk factor for severe ROP (AOR = 2.6, 95% CI 1.1-5.9, P = .03). None of the categories of placental inflammation were significantly associated with low grade ROP. CONCLUSION: Placental pathology distinguished by the maternal plus fetal inflammatory response was a significant risk factor for severe ROP. Our study supports a link between intrauterine inflammatory events and the subsequent development of severe ROP.

Validation of the Colorado Retinopathy of Prematurity Screening Model.

Importance: The Colorado Retinopathy of Prematurity (CO-ROP) model uses birth weight, gestational age, and weight gain at the first month of life (WG-28) to predict risk of severe retinopathy of prematurity (ROP). In previous validation studies, the model performed very well, predicting virtually all cases of severe ROP and potentially reducing the number of infants who need ROP examinations, warranting validation in a larger, more diverse population. Objective: To validate the performance of the CO-ROP model in a large multicenter cohort. Design, Setting, Participants: This study is a secondary analysis of data from the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study, a retrospective multicenter cohort study conducted in 29 hospitals in the United States and Canada between January 2006 and June 2012 of 6351 premature infants who received ROP examinations. Main Outcomes and Measures: Sensitivity and specificity for severe (early treatment of ROP [ETROP] type 1 or 2) ROP, and reduction in infants receiving examinations. The CO-ROP model was applied to the infants in the G-ROP data set with all 3 data points (infants would have received examinations if they met all 3 criteria: birth weight, <1501 g; gestational age, <30 weeks; and WG-28, <650 g). Infants missing WG-28 information were included in a secondary analysis in which WG-28 was considered fewer than 650 g. Results: Of 7438 infants in the G-ROP study, 3575 (48.1%) were girls, and maternal race/ethnicity was 2310 (31.1%) African American, 3615 (48.6%) white, 233 (3.1%) Asian, 40 (0.52%) American Indian/Alaskan Native, and 93 (1.3%) Pacific Islander. In the study cohort, 747 infants (11.8%) had type 1 or 2 ROP, 2068 (32.6%) had lower-grade ROP, and 3536 (55.6%) had no ROP. The CO-ROP model had a sensitivity of 96.9% (95% CI, 95.4%-97.9%) and a specificity of 40.9% (95% CI, 39.3%-42.5%). It missed 23 (3.1%) infants who developed severe ROP. The CO-ROP model would have reduced the number of infants who received examinations by 26.1% (95% CI, 25.0%-27.2%). Conclusions and Relevance: The CO-ROP model demonstrated high but not 100% sensitivity for severe ROP and missed infants who might require treatment in this large validation cohort. The model requires all 3 criteria to be met to signal a need for examinations, but some infants with a birth weight or gestational age above the thresholds developed severe ROP. Most of these infants who were not detected by the CO-ROP model had obvious deviation in expected weight trajectories or nonphysiologic weight gain. These findings suggest that the CO-ROP model needs to be revised before considering implementation into clinical practice.

Maternal Serum Eye Drops in the Management of Pediatric Persistent Corneal Epithelial Defects: A Case Series.

PURPOSE: We report our experience with the use of maternally derived serum eye drops as adjunctive treatment in the management of pediatric persistent corneal epithelial defects. METHODS: Five eyes of 4 patients were identified in a retrospective review of pediatric patients with persistent corneal epithelial defects who received maternal serum drops. Diagnoses associated with the defects comprised pontine tegmental cap dysplasia with bilateral cranial nerve V1, V2, V3, and VII palsies; pontine tegmental cap dysplasia with left cranial nerve V1, VII, and VIII palsies; traumatic left cranial nerve II, V1, V2, and VI palsies due to a basilar skull fracture; and Stevens-Johnson syndrome with ocular involvement. We evaluated the feasibility of using maternally derived serum drops; thus, we looked at the ability to prepare and tolerate the drops as well as any complications that could have been associated with treatment. Other data collected included visual acuity, corneal examination, and current and previous treatments. RESULTS: Both the duration of therapy and time of follow-up ranged from 5 to 28 months. All patients experienced improvement or resolution of their corneal epithelial defects within 3 weeks of initiating serum eye drops. Furthermore, there were no adverse effects from the use of allogeneic serum drops. CONCLUSIONS: Maternal serum eye drops are a well-tolerated and potentially beneficial addition to the management of pediatric persistent corneal epithelial defects.