Coats' Disease in a Patient With Cornelia de Lange Syndrome: Management With Laser and Bevacizumab.

Cornelia de Lange syndrome is a congenital disorder with multisystem abnormalities including multiple ocular findings. The authors report a case of Coats' disease in a patient with Cornelia de Lange syndrome who was successfully treated with laser and intravitreal bevacizumab. This case demonstrates the importance of fluorescein angiography in making the diagnosis and directing treatment and the efficacy of combined laser with intravitreal anti-vascular endothelial growth factor therapy for persistent vascular leakage associated with Coats' disease in Cornelia de Lange syndrome. [J Pediatr Ophthalmol Strabismus. 2023;60(4):e45-e48.].

Use of sweep visual evoked potential in preverbal children with optic nerve hypoplasia.

PURPOSE: To evaluate sweep VEP (sVEP) in preverbal children with optic nerve hypoplasia (ONH) and to assess associations between sVEP results, patient clinical characteristics and future recognition visual acuity. METHODS: The medical records of children with ONH who had sVEP testing and documented recognition visual acuity at the University of Wisconsin from 2005 to 2013 were reviewed retrospectively. Optic nerve size, amblyopia treatment, and neurologic diagnoses were collected. RESULTS: A total of 57 patients were included: 41 (71%) with bilateral ONH and 27 (47%) with neurologic abnormality. Mean age at initial sVEP was 13.3 months (range, 1-32). Mean duration between initial sVEP and final recognition acuity was 5.5 years (range, 3.5-7). Sweep VEP was associated with ONH severity (P < 0.05). Sweep VEP, and the combination of ONH severity and neurologic status, were significant predictors (P < 0.05) of logMAR optotype acuity, together accounting for 54%-61% of the variance in final recognition acuity. CONCLUSIONS: Sweep VEP in preverbal children with ONH depends on ONH severity and correlates with final recognition visual acuity. Children with milder degrees of ONH without neurologic abnormalities had better final vision, and patients with severe ONH and neurologic diagnoses had worse vision outcomes.

Opioid prescribing to preteen children undergoing ambulatory surgery in the United States.

BACKGROUND: Overuse and misuse of opioids is a continuing crisis. The most common reason for children to receive opioids is postoperative pain, and they are often prescribed more than needed. The amount of opioids prescribed varies widely, even for minor ambulatory procedures. This study uses a large national sample to describe filled opioid prescriptions to preteen patients after all ambulatory surgical procedures and common standard procedures. METHODS: We analyzed Truven Health MarketScan data for July 2012 through December 2016 to perform descriptive analyses of opioid fills by age and geographic area, change over time, second opioid fills in opioid-naïve patients, and variation in the types and amount of medication prescribed for 18 common and standard procedures in otolaryngology, urology, general surgery, ophthalmology, and orthopedics. RESULTS: Over 10% of preteen children filled perioperative opioid prescriptions for ambulatory surgery in the period 2012 to 2016. The amount prescribed varied widely (median 5 days' supply, IQR 3-8, range 1-90), even for the most minor procedures, for example, frenotomy (median 4 days' supply, IQR 2-5, range 1-60). Codeine fills were common despite safety concerns. Second opioid prescriptions were filled by opioid-naïve patients after almost all procedures studied. The rate of prescribing declined significantly over time and varied substantially by age and across census regions. CONCLUSIONS: We identified opioid prescribing outside of the norms of standard practice in all of the specialties studied. Standardizing perioperative opioid prescribing and developing guidelines on appropriate prescribing for children may reduce the opioids available for misuse and diversion.

SVEP1 as a Genetic Modifier of TEK-Related Primary Congenital Glaucoma.

Purpose: Affecting children by age 3, primary congenital glaucoma (PCG) can cause debilitating vision loss by the developmental impairment of aqueous drainage resulting in high intraocular pressure (IOP), globe enlargement, and optic neuropathy. TEK haploinsufficiency accounts for 5% of PCG in diverse populations, with low penetrance explained by variable dysgenesis of Schlemm's canal (SC) in mice. We report eight families with TEK-related PCG, and provide evidence for SVEP1 as a disease modifier in family 8 with a higher penetrance and severity. Methods: Exome sequencing identified coding/splice site variants with an allele frequency less than 0.0001 (gnomAD). TEK variant effects were assayed in construct-transfected HEK293 cells via detection of autophosphorylated (active) TEK protein. An enucleated eye from an affected member of family 8 was examined via histology. SVEP1 expression in developing outflow tissues was detected by immunofluorescent staining of 7-day mouse anterior segments. SVEP1 stimulation of TEK expression in human umbilical vascular endothelial cells (HUVECs) was measured by TaqMan quantitative PCR. Results: Heterozygous TEK loss-of-function alleles were identified in eight PCG families, with parent-child disease transmission observed in two pedigrees. Family 8 exhibited greater disease penetrance and severity, histology revealed absence of SC in one eye, and SVEP1:p.R997C was identified in four of the five affected individuals. During SC development, SVEP1 is secreted by surrounding tissues. SVEP1:p.R997C abrogates stimulation of TEK expression by HUVECs. Conclusions: We provide further evidence for PCG caused by TEK haploinsufficiency, affirm autosomal dominant inheritance in two pedigrees, and propose SVEP1 as a modifier of TEK expression during SC development, affecting disease penetrance and severity.

Angiopoietin-1 is required for Schlemm's canal development in mice and humans.

Primary congenital glaucoma (PCG) is a leading cause of blindness in children worldwide and is caused by developmental defects in 2 aqueous humor outflow structures, Schlemm's canal (SC) and the trabecular meshwork. We previously identified loss-of-function mutations in the angiopoietin (ANGPT) receptor TEK in families with PCG and showed that ANGPT/TEK signaling is essential for SC development. Here, we describe roles for the major ANGPT ligands in the development of the aqueous outflow pathway. We determined that ANGPT1 is essential for SC development, and that Angpt1-knockout mice form a severely hypomorphic canal with elevated intraocular pressure. By contrast, ANGPT2 was dispensable, although mice deficient in both Angpt1 and Angpt2 completely lacked SC, indicating that ANGPT2 compensates for the loss of ANGPT1. In addition, we identified 3 human subjects with rare ANGPT1 variants within an international cohort of 284 PCG patients. Loss of function in 2 of the 3 patient alleles was observed by functional analysis of ANGPT1 variants in a combined in silico, in vitro, and in vivo approach, supporting a causative role for ANGPT1 in disease. By linking ANGPT1 with PCG, these results highlight the importance of ANGPT/TEK signaling in glaucoma pathogenesis and identify a candidate target for therapeutic development.

Cervical lymphadenopathy secondary to rhabdomyosarcoma presenting as Horner syndrome in an infant.

A 4-week-old boy with left ptosis, anisocoria, and a mass on his left hand was diagnosed with Horner syndrome. The diagnosis precipitated a work-up for a possible malignant etiology. Magnetic resonance imaging demonstrated enlarged left cervical and axillary lymph nodes. A biopsy of the hand lesion confirmed embryonal rhabdomyosarcoma, but a biopsy of the axillary lymph node was negative. Mechanical pressure by noncancerous enlarged lymph nodes is hypothesized to cause the Horner syndrome.

Intraobserver reliability of contact pachymetry in children.

BACKGROUND: Central corneal thickness (CCT) is an important measurement in the treatment and management of pediatric glaucoma and potentially of refractive error, but data regarding reliability of CCT measurement in children are limited. The purpose of this study was to evaluate the reliability of CCT measurement with the use of handheld contact pachymetry in children. METHODS: We conducted a multicenter intraobserver test-retest reliability study of more than 3,400 healthy eyes in children aged from newborn to 17 years by using a handheld contact pachymeter (Pachmate DGH55; DGH Technology Inc, Exton, PA) in 2 clinical settings--with the use of topical anesthesia in the office and with the patient under general anesthesia in a surgical facility. RESULTS: The overall standard error of measurement, including only measurements with standard deviation ≤5 µm, was 8 µm; the corresponding coefficient of repeatability, or limits within which 95% of test-retest differences fell, was ±22.3 µm. However, standard error of measurement increased as CCT increased, from 6.8 µm for CCT less than 525 µm, to 12.9 µm for CCT 625 µm and greater. The standard error of measurement including measurements with standard deviation >5 µm was 10.5 µm. Age, sex, race/ethnicity group, and examination setting did not influence the magnitude of test-retest differences. CONCLUSIONS: CCT measurement reliability in children via the Pachmate DGH55 handheld contact pachymeter is similar to that reported for adults. Because thicker CCT measurements are less reliable than thinner measurements, a second measure may be helpful when the first exceeds 575 µm. Reliability is also improved by disregarding measurements with instrument-reported standard deviations >5 µm.

Identification and treatment of amblyopia.

Amblyopia is the leading cause of vision loss in children. It is treatable if diagnosed early, making identification of affected children critical. The American Association for Pediatric Ophthalmology and Strabismus and the American Academy of Pediatrics recommend that clinicians routinely perform age-appropriate vision chart testing, red reflex testing, and examination for signs of strabismus. The U.S. Preventive Services Task Force recommends vision screening for all children at least once between three and five years of age to detect the presence of amblyopia or its risk factors. Photoscreening may be a useful adjunct to traditional vision screening, but there is limited evidence that it improves visual outcomes. Treatments for amblyopia include patching, atropine eye drops, and optical penalization of the nonamblyopic eye. In children with moderate amblyopia, patching for two hours daily is as effective as patching for six hours daily, and daily atropine is as effective as daily patching. Children older than seven years may still benefit from patching or atropine, particularly if they have not previously received amblyopia treatment. Amblyopia recurs in 25 percent of children after patching is discontinued. Tapering the amount of time a patch is worn each day at the end of treatment reduces the risk of recurrence.

Outcomes of Harada-Ito surgery for acquired torsional diplopia.

PURPOSE: To evaluate the outcomes of Harada-Ito surgery in correcting various types of torsional diplopia. METHODS: The medical records of patients who underwent Harada-Ito surgery at two academic institutions were retrospectively reviewed. Data collected included etiology of torsional diplopia, strabismus and torsion measurements, reoperation rate, patient symptoms, and use of prism. Postoperative success was defined as a lack of diplopia in the primary position at distance and downgaze at near with or without prism. Failure was defined as persistent torsional diplopia; partial success was defined as surgical success but with restrictive strabismus in the secondary gaze positions. RESULTS: A total of 26 patients (mean age, 46 years; range, 13-89 years) were included. Of these, 17 had superior oblique palsy. The mean follow-up duration was 2 years (range, 2-60 months). The surgical outcome was success in 73% of patients, partial success in 7%, and failure in 19%. All patients with ≤10° of torsion preoperatively obtained surgical success. Patients in the failure group had higher amounts of preoperative torsion compared to the success group (P = 0.009). The reoperation rate was 23%, including four patients with additional surgery for downgaze esotropia or torsion. One-third of the patients wore a prism immediately after surgery. CONCLUSIONS: Harada-Ito surgery successfully treated torsional diplopia. Patients with ≤10° of preoperative torsion had a better outcome. Downgaze diplopia was a common reason for additional surgery.

Comparison of Tono-Pen and Goldmann applanation tonometers for measurement of intraocular pressure in healthy children.

PURPOSE: To assess the agreement of intraocular pressure (IOP) measured with the Tono-Pen and the Goldmann applanation tonometer (GAT) in normal children and adolescents. METHODS: A total of 439 subjects from birth to <18 years of age without anterior segment anomalies or glaucoma had their IOP measured with the two instruments by separate, masked examiners in the office or under general anesthesia. RESULTS: On average, the Tono-Pen measured values slightly lower than the GAT for IOP <11 mm Hg and slightly higher than the GAT for IOP >11 mm Hg in the office setting. Using the average of GAT and Tono-Pen IOPs to estimate the true IOP, the average difference (GAT - Tono-Pen) was 0.4 mm Hg at IOP of 10 mm Hg and -3.0 mm Hg at IOP of 20 mm Hg. The 95% limits of agreement on the average difference between instruments were ± 6.4 mm Hg in the office setting and ± 6.8 mm Hg under general anesthesia. Larger differences between instruments were found with younger age. Standard error of measurement with the Tono-Pen was 1.44 mm Hg and 1.82 mm Hg for the office and anesthesia settings, respectively. Thicker corneas were associated with higher IOP with both the GAT and the Tono-Pen. CONCLUSIONS: In normal children, average differences between IOP measured by Tono-Pen and GAT were small, although there was substantial test-retest variability. Younger age was associated with larger average differences, as was higher IOP in the office setting.

Central corneal thickness in children.

OBJECTIVES: To determine the central corneal thickness (CCT) in healthy white, African American, and Hispanic children from birth to 17 years of age and to determine whether CCT varies by age, race, or ethnicity. DESIGN: Prospective observational multicenter study. Central corneal thickness was measured with a handheld contact pachymeter. RESULTS: A total of 2079 children were included in the study, with ages ranging from birth to 17 years. Included were 807 whites, 494 Hispanics, and 474 African Americans, in addition to Asian, unknown race, and mixed-race individuals. African American children had thinner corneas on average than that of both white and Hispanic children (P < .001 for both) by approximately 20 µm. Thicker median CCT was observed with each successive year of age from age 1 to 11 years, with year-to-year differences steadily decreasing and reaching a plateau after age 11 at 573 µm in white and Hispanic children and 551 µm in African American children. For every 100 µm of thicker CCT measured, the intraocular pressure was 1.5 mm Hg higher on average (P < .001). For every diopter of increased myopic refractive error, CCT was 1 µm thinner on average (P < .001). CONCLUSIONS: Median CCT increases with age from 1 to 11 years, with the greatest increase present in the youngest age groups. African American children on average have thinner central corneas than white and Hispanic children, whereas white and Hispanic children demonstrate similar CCT.

Chorioretinopathy and microcephaly with normal development.

PURPOSE: To report a pediatric patient with bilateral chorioretinopathy and microcephaly who from birth to 2 years of age is reaching appropriate developmental milestones. DESIGN: Retrospective case report with clinical findings and literature review. MAIN OUTCOME MEASURES: Clinical findings and visual acuity estimated by sweep visual evoked potentials (VEP), electroretinogram (ERG) and fundoscopic exam. RESULTS: A microcephalic child with normal motor and cognitive development had improving sweep VEP despite atypical fundoscopic findings of bilateral chorioretinopathy, attenuated retinal vessels, and anomalous optic nerves. The etiology for these collective findings despite extensive workup, including prenatal TORCH titers and neuro-imaging, has remained unidentified. CONCLUSIONS: Most published cases of microcephaly with chorioretinopathy have described patients with mild to severe mental retardation. Patients with chorioretinopathy and microcephaly may, however, reach all developmental milestones with improvement in visual development as was seen in this case. The long-term cognitive and visual prognosis may be better than previously reported.

Sweep visual evoked potential testing as a predictor of recognition acuity in albinism.

OBJECTIVE: To determine if sweep visual evoked potential (VEP) acuity is predictive of recognition acuity in children with albinism. METHODS: A retrospective review was performed in children with albinism who underwent sweep VEP testing from 1992 to 2003. All patients had a complete ophthalmologic examination with either binocular or monocular sweep VEP testing and at least 5 years of follow-up. Positive predictability of sweep VEP acuity was defined as final recognition acuity within 1 Snellen line of initial sweep VEP acuity. RESULTS: Of the 13 patients included in the study, 11 had nystagmus, iris transillumination defects, and foveal hypoplasia at initial examination. The mean age at initial sweep VEP testing was 3.1 years (range, 0.1-10.0 years). Five of 13 patients had initial sweep VEP acuity that was predictive of final recognition acuity. Five additional patients had final recognition acuity, which surpassed initial sweep VEP acuity by 2 to 3 lines. Of these 10 patients, the mean duration for recognition acuity to reach VEP acuity was 5.4 years. There was no correlation between predictive VEP acuity and foveal pigmentation, refractive error, strabismus, nystagmus, or longer follow-up. CONCLUSIONS: Sweep VEP testing can be used as a predictive tool for recognition acuity in children with albinism. Predictability was found in a clinical spectrum of albinism.

Pseudotumor cerebri in children with Down syndrome.

PURPOSE: To report 4 pediatric Down syndrome patients with optic nerve elevation and pseudotumor cerebri. DESIGN: Retrospective observational case series. PARTICIPANTS: Four pediatric Down syndrome patients found to have optic nerve elevation on ophthalmologic examination at a single institution. METHODS: Medical record review of 117 pediatric Down syndrome patients aged 0 to 18 years was performed. All patients were seen at the University of Wisconsin pediatric ophthalmology clinic between 1995 and 2005. MAIN OUTCOME MEASURES: Visual acuity, optic nerve appearance, and neurologic work-up. RESULTS: Four (3.4%) of 117 Down syndrome patients seen at the university's pediatric ophthalmology clinic were found to have optic nerve elevation. This included 2 boys and 2 girls, aged 2 to 10 years. None of the patients had a history of headache or transient visual obscuration. One of the patients had high hyperopia at the time of presentation, and all were referred for neurologic evaluation of suspected increased intracranial pressure. Three patients were diagnosed with pseudotumor cerebri (PTC) based on a normal brain magnetic resonance imaging (MRI) scan, an elevated opening cerebrospinal fluid (CSF) pressure on lumbar puncture, and normal CSF analysis results. The fourth patient's elevated optic nerve appearance was likely secondary to PTC after obtaining normal brain MRI results; however, this patient did not undergo a lumbar puncture. One child with PTC demonstrated improvement in visual acuity and optic nerve appearance after acetazolamide and weight loss therapy. The 2 additional patients with PTC were treated with either low-dose acetazolamide or weight loss therapy and experienced optic atrophy. The final patient, who did not undergo lumbar puncture, experienced spontaneous resolution of optic nerve elevation. Mean follow-up duration was 49 months. CONCLUSIONS: Only 3.4% (4/117) of Down syndrome children were found to have optic nerve elevation in a single institution. Pseudotumor cerebri should be considered in asymptomatic Down syndrome patients with elevated optic nerves. Medical therapy in PTC with acetazolamide can lead to improvement in visual acuity and optic nerve appearance, although optic atrophy also was seen.

Factors associated with recurrence of amblyopia on cessation of patching.

PURPOSE: In a prospective observational study, we previously reported that weaning (tapering or gradually reducing) treatment in children treated with 6 to 8 hours of daily patching for amblyopia resulted in a 4-fold reduction in odds of recurrence. We now report the association of additional factors with recurrence or regression of amblyopia in this same cohort. DESIGN: Prospective, nonrandomized, observational study. PARTICIPANTS: Sixty-nine children aged <8 years with successfully treated anisometropic or strabismic amblyopia (improved > or =3 logarithm of the minimum angle of resolution [logMAR] lines). METHODS: Patients were enrolled at the time they stopped patching for amblyopia. Patients were classified according to whether patching was stopped abruptly or weaned before cessation. They were followed off treatment for 52 weeks to assess recurrence of amblyopia. MAIN OUTCOME MEASURE: Recurrence of amblyopia defined as a > or =2-logMAR level reduction of visual acuity from enrollment (cessation of patching) confirmed by a second examination. Recurrence was also considered to have occurred if treatment was restarted with a > or =2-logMAR level reduction of visual acuity, even if it was not confirmed by a second examination. RESULTS: The risk of recurrence was higher with better visual acuity at the time of cessation of treatment (adjusted risk ratio [RR], 0.68 per line of worse visual acuity; 95% confidence interval [CI], 0.51-0.90), a greater number of lines improved during the previous treatment (adjusted RR, 1.5 per line increase; 95% CI, 1.1-2.0), and a history of recurrence (adjusted RR, 2.7; 95% CI, 1.5-4.9). Orthotropia or excellent stereoacuity at the time of patching cessation did not appear to have a protective effect on the risk of recurrence. CONCLUSIONS: The higher risk of recurrence in the most successfully treated children with amblyopia and absence of protection from orthotropia and excellent random dot stereoacuity suggests that careful and prolonged follow-up is needed for all children who have been previously treated for amblyopia.

Successful treatment of anisometropic amblyopia with spectacles alone.

BACKGROUND: The efficacy of treating anisometropic amblyopia with occlusion therapy is well known. However, this form of treatment can be associated with risks. Spectacle correction alone may be a successful and underutilized form of treatment. METHODS: The records of 28 patients treated successfully for anisometropic amblyopia with glasses alone were reviewed. Age, initial visual acuity and stereoacuity, and nature of anisometropia were analyzed to assess associations with time required for resolution, final visual acuity, and stereoacuity. Incidence of amblyopia recurrence and results of subsequent treatment, including patching, were also studied. RESULTS: Mean time to amblyopia resolution (interocular acuity difference

Ocular complications after organ and bone marrow transplantation in children.

BACKGROUND: Organ and bone marrow transplantation commonly are performed in children. Ocular complications usually are described as secondary to post-transplantation medications. The complication rate is unknown. METHODS: A retrospective chart review was performed of 93 children who were younger than 18 years of age and had transplantation surgery from 1989 to 2004. The rate and type of ocular complications, including those requiring ocular surgery, were analyzed. Medications and visual loss associated with adverse effects also were studied. RESULTS: Of the 93 patients, 74 patients met the entry criteria. Sixty-one patients had at least 1 year of follow-up, and the longest follow-up duration was 14 years. The 1-year post-transplantation complication rate was 16.0% (95% confidence interval 6.8-24.4%). Adverse effects included cytomegalovirus (CMV) retinitis, cataract, graft-versus-host disease, lymphoproliferative disorder, persistent strabismus, and transient visual loss. Four patients underwent eye surgery, including lensectomy for cataract, tarsorrhaphy for corneal ulcer, and iris biopsy. They had surgery 0.9 to 4.7 years after transplantation. Most patients were taking prednisone and cyclosporine when their complication was diagnosed. One patient's visual acuity deteriorated to no light perception in one eye and 20/250 in the other eye secondary to CMV retinitis. Most patients had a final visual acuity > or =20/40. CONCLUSION: Transplantation surgery in children produces a significant risk of ocular impairment. The 1-year complication rate was 16.0%. Eye surgery may be required within the first few years after transplantation. Although most patients maintained a final visual acuity of 20/40 or better, one patient became bilaterally legally blind.

Astigmatism after small-incision clear corneal cataract extraction and intraocular lens implantation in children.

PURPOSE: To investigate the magnitude of postoperative astigmatism in children having cataract extraction with intraocular lens (IOL) implantation through a 3.0 mm superior clear corneal incision. SETTING: Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA. METHODS: This retrospective chart review comprised all pediatric patients having cataract surgery with IOL implantation through a 3.0 mm clear corneal incision from 1997 to 2002. One hundred two eyes of 75 patients were included. All refractions were performed manually by an experienced pediatric ophthalmologist. RESULTS: The mean postoperative retinoscopic cylinder in all patients was 0.63 diopter (D) (range 0.0 to 4.50 D) at 1 month, 0.40 D (range 0.0 to 1.75 D) at 6 months, and 0.51 D (range 0.0 to 2.50 D) at 1 year. Patients aged 0 to 36 months at the time of surgery had a mean postoperative cylinder of 0.22 D at 1 month, 0.03 D at 6 months, and 0.21 D at 1 year. Patients between 36 months and 6 years of age at surgery had a mean refractive cylinder of 0.50 D, 0.38 D, and 0.75 D, respectively. Patients older than 6 years at surgery had a mean refractive cylinder of 0.94 D, 0.75 D, and 0.76 D, respectively. CONCLUSIONS: Small-incision clear corneal cataract extraction with IOL implantation in children led to minimal postoperative astigmatism that remained stable over time. Less astigmatism was observed in children having surgery before they were 36 months old.