Pediatric orbital lesions: neoplastic extraocular soft-tissue lesions.

Pediatric neoplastic extraocular soft-tissue lesions in the orbit are uncommon. Early multimodality imaging work-up and recognition of the key imaging features of these lesions allow narrowing of the differential diagnoses in order to direct timely management. In this paper, the authors present a multimodality approach to the imaging work-up of these lesions and highlight the use of ocular ultrasound as a first imaging modality where appropriate. We will discuss vascular neoplasms (congenital hemangioma, infantile hemangioma), optic nerve lesions (meningioma, optic nerve glioma), and other neoplastic lesions (plexiform neurofibroma, teratoma, chloroma, rhabdomyosarcoma, infantile fibrosarcoma, schwannoma).

Pediatric orbital lesions: ocular pathologies.

Orbital pathologies can be broadly classified as ocular, extra-ocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In part 1 of this orbital series, the authors will discuss the differential diagnosis and key imaging features of pediatric ocular pathologies. These include congenital and developmental lesions (microphthalmos, anophthalmos, persistent fetal vasculature, coloboma, morning glory disc anomaly, retinopathy of prematurity, Coats disease), optic disc drusen, infective and inflammatory lesions (uveitis, toxocariasis, toxoplasmosis), and ocular neoplasms (retinoblastoma, retinal hamartoma, choroidal melanoma, choroidal nevus). This pictorial review provides a practical approach to the imaging work-up of these anomalies with a focus on ocular US as the first imaging modality and additional use of CT and/or MRI for the evaluation of intracranial abnormalities. The characteristic imaging features of the non-neoplastic mimics of retinoblastoma, such as persistent fetal vasculature and Coats disease, are also highlighted.

Pediatric orbital lesions: bony and traumatic lesions.

Orbital pathologies can be broadly classified as ocular lesions, extraocular soft-tissue pathologies (non-neoplastic and neoplastic), and bony and traumatic lesions. In this paper, we discuss the key imaging features and differential diagnoses of bony and traumatic lesions of the pediatric orbit and globe, emphasizing the role of CT and MRI as the primary imaging modalities. In addition, we highlight the adjunctive role of ocular sonography in the diagnosis of intraocular foreign bodies and discuss the primary role of sonography in the diagnosis of traumatic retinal detachment.

Pediatric orbital lesions: non-neoplastic extraocular soft-tissue lesions.

Orbital pathologies can be broadly classified as ocular, extraocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In this paper, we discuss the key imaging features and differential diagnoses of congenital and developmental lesions (dermoid cyst, dermolipoma), infective and inflammatory pathologies (pre-septal cellulitis, orbital cellulitis, optic neuritis, chalazion, thyroid ophthalmopathy, orbital pseudotumor), and non-neoplastic vascular anomalies (venous malformation, lymphatic malformation, carotid-cavernous fistula), emphasizing the key role of CT and MRI in the imaging work-up. In addition, we highlight the adjunctive role of ocular ultrasound in the diagnosis of dermoid cyst and chalazion, and discuss the primary role of ultrasound in the diagnosis of vascular malformations.

Unilateral progressive anterior iris adhesions in Mowat-Wilson syndrome: a new ocular finding.

Ocular associations in Mowat-Wilson syndrome (MWS) are rare. Those involving the anterior segment are scarce in the literature. We describe a child with genetic confirmation of MWS that presented with acquired onset of unilateral anterior iris adhesions with no known trauma.

Acute-onset dacryoadenitis following immunisation with mRNA COVID-19 vaccine.

A 14-year-old boy was referred to the ophthalmology department with a 4-day history of rapid-onset right upper lid pain, swelling and erythema starting 9 hours after his first dose of COVID-19 mRNA vaccination (BNT162b2/Comirnaty, Pfizer-BioNTech). On examination, he had significant right upper lid ptosis, oedema and erythema, with associated limitation of right eye abduction and elevation. He was found to have acute dacryoadenitis with orbital inflammatory disease on clinical and laboratory investigations. He was given tapering oral prednisone and had full resolution of symptoms within 2 weeks. This is the first known case of orbital inflammation after COVID-19 mRNA vaccination. Given the temporal association between the patient's vaccination and symptom onset, we believe it is likely that immunisation prompted the onset of disease.

Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region.

Strabismus is a common condition, affecting 1%-4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the identification of multiple loci via linkage analyses, no specific genes have been identified from these studies. The current study is based on a seven-generation family with isolated strabismus inherited in an autosomal dominant manner. A total of 13 individuals from a common ancestor have been included for linkage analysis. Among these, nine are affected and four are unaffected. A single linkage signal has been identified at an 8.5 Mb region of chromosome 14q12 with a multipoint LOD (logarithm of the odds) score of 4.69. Disruption of this locus is known to cause FOXG1 syndrome (or congenital Rett syndrome; OMIM #613454 and *164874), in which 84% of affected individuals present with strabismus. With the incorporation of next-generation sequencing and in-depth bioinformatic analyses, a 4 bp non-coding deletion was prioritised as the top candidate for the observed strabismus phenotype. The deletion is predicted to disrupt regulation of FOXG1, which encodes a transcription factor of the Forkhead family. Suggestive of an autoregulation effect, the disrupted sequence matches the consensus FOXG1 and Forkhead family transcription factor binding site and has been observed in previous ChIP-seq studies to be bound by Foxg1 in early mouse brain development. Future study of this specific deletion may shed light on the regulation of FOXG1 expression and may enhance our understanding of the mechanisms contributing to strabismus and FOXG1 syndrome.

Management of Limbal Dermoids by Simple Excision in Young Children.

PURPOSE: To report the visual outcomes, refractive results, and complications of simple excision for limbal dermoid in the first 8 years of life. METHODS: This retrospective chart review included all children aged 8 years or younger who underwent excision of a grade I or II limbal dermoid without involvement of the visual axis between the years 2000 and 2019. RESULTS: Nineteen patients met the inclusion criteria. Their mean age was 4.2 ± 2.0 years (age range: 9 months to 8 years). The mean change in visual acuity was +1 ± 2.3 lines. The mean astigmatism was 3.20 ± 1.80 diopters (D) preoperatively and 3.50 ± 2.20 D at the last visit; the mean change in the astigmatism power was +0.20 ± 1.20 D (range: -1.50 to +2.75 D). Epithelial healing occurred in a mean of 8 days. No complications such as perforation were encountered. All patients had a good cosmetic outcome. CONCLUSIONS: Reepithelialization led to good cosmetic outcomes after this quick, simple, and uncomplicated procedure. There was no significant change in visual acuity or astigmatism, so amblyopia and astigmatism reduction are poor indications for limbal dermoid excision. Families should be counseled preoperatively that correction of the astigmatism and patching will remain essential in the postoperative management of amblyopia. [J Pediatr Ophthalmol Strabismus. 2021;58(3):196-201.].

Long-term Results of Ahmed Valve Implantation With Mitomycin-C in Pediatric Glaucoma.

PRECIS: Mitomycin was used with Ahmed valve implantation in 81 eyes of 63 children. After 5 years, probability of intraocular pressure (IOP) control without glaucoma medication was 35±6%; 57% achieved IOP control with topical medications after 10 years. PURPOSE: The purpose of this study was to determine the long-term outcomes of Ahmed glaucoma valve (AGV) implantation with intraoperative application of mitomycin-C (MMC) for the treatment of childhood glaucoma. METHODS: Retrospective review of children undergoing AGV implantation with subtenon application of MMC between 2000 and 2019. We defined surgical success as a final IOP of 5 to 21 mm Hg with no glaucoma medication, no subsequent glaucoma surgery, and no severe complication. Qualified success was defined if the above criteria were met with topical antiglaucoma medication. RESULTS: Eighty-one eyes of 63 patients were included. The probability of complete success was 72±5% (63% to 83%) at 1 year, 58±6% (48% to 70%) at 2 years, and 35±6% (25% to 48%) at 5 years. The probability of qualified success was 92±3% (87% to 98%) at 1 year, 79±5% (70% to 89%) at 5 years, 57±7% (44% to 73%) at 10 years, and 39±9% (24% to 62%) at 14 years. The IOP was reduced by an average of 10.7±9 mm Hg from preoperative visit to the last follow-up, and the number of medications decreased from 3.0±1.4 to 1.5±1.4 after implantation. CONCLUSIONS: A significant proportion of patients achieved long-term IOP control without glaucoma medication. The majority achieved IOP control with additional topical antiglaucoma medications. When compared with existing AGV implantation in childhood literature, the use of MMC appears to lengthen the drop-free (complete success) duration, as well as the long-term IOP control with topical medications.

Clinical evidence for an accessible modification to the Scott resection-recession procedure, using a matching duction technique.

PURPOSE: To evaluate the resection-recession procedure on a single muscle for the management of incomitant strabismus using an alternative calculation. METHODS: The medical records of adult patients undergoing combined adjustable resection-recession surgery on a single rectus muscle at one institution from 2008 to 2019 were reviewed retrospectively. Each patient had a full orthoptic evaluation before and at least 10 weeks after surgery. The main outcome measure was alignment at last follow-up examination in the primary position and eccentric gaze (field of action). RESULTS: A total of 20 procedures in 20 patients were included. The etiology was paretic in 14 cases and restrictive in 6. All rectus muscles were operated. An adjustable suture technique was used in every case, but only 5 required adjustment. The average length of follow-up was 1.7 years (range, 2.4 months to 11.1 years). Postoperative reduction of deviation in eccentric gaze was observed in all patients and averaged 70% (range, 5Δ-48Δ). The technique was particularly helpful for the inferior rectus muscle (85.8% reduction), followed by the medial rectus (66%), lateral rectus (55%), and superior rectus muscles (55%). Three-quarters of the patients became orthotropic in primary position. Good results were noted for both paretic and restrictive etiologies (64%, 83%, resp., reduction in eccentric gaze). Four of 20 patients (20%) were overcorrected in eccentric gaze. One patient required prism to control a small comitant deviation (6Δ). No complications or muscle slippage occurred. CONCLUSIONS: In our study cohort, the resection-recession operation was effective in reducing incomitance when used on any of the four rectus muscles.

Detectible mosaic truncating PPM1D mutations, age and breast cancer risk.

Mosaic protein truncating variants (PTVs) in the phosphatase, Mg2+/Mn2+dependent 1D (PPM1D) gene in blood-derived DNA have been associated with increased risk of breast cancer. We analyzed PPM1D PTVs in blood from 3817 breast cancer cases and 3058 controls by deep sequencing of a previously defined region in exon 6 of PPM1D. We identified 50 of 6875 (0.73%) participants having a mosaic PPM1D PTV. We observed a higher frequency of mosaic PPM1D PTVs with increasing age (Ptrend = 2.9 × 10-6). We did not observe an overall association between PPM1D PTVs and increased breast cancer risk (OR = 1.51, 95% CI = 0.84-2.71). Evidence for an association was observed in a subset of cases with DNA collected 1-year or more before breast cancer diagnosis (OR = 3.44, 95% CI = 1.62-7.30, P-value = 0.001); however, no significant association was observed for the larger series of cases with DNA collected post diagnosis (OR = 1.01, 95% CI = 0.51-2.01, P-value = 0.98). Our study indicates that the PPM1D PTVs are present at higher rates than previously reported and the frequency of PPM1D PTVs increases with age. We observed limited evidence for an association between mosaic PPM1D PTVs and breast cancer risk, suggesting mosaic PPM1D PTVs in the blood likely do not influence risk of breast cancer.

Correlating the Expression and Functional Activity of ABCA4 Disease Variants With the Phenotype of Patients With Stargardt Disease.

Purpose: Stargardt disease (STGD1), the most common early-onset recessive macular degeneration, is caused by mutations in the gene encoding the ATP-binding cassette transporter ABCA4. Although extensive genetic studies have identified more than 1000 mutations that cause STGD1 and related ABCA4-associated diseases, few studies have investigated the extent to which mutations affect the biochemical properties of ABCA4. The purpose of this study was to correlate the expression and functional activities of missense mutations in ABCA4 identified in a cohort of Canadian patients with their clinical phenotype. Methods: Eleven patients from British Columbia were diagnosed with STGD1. The exons and exon-intron boundaries were sequenced to identify potential pathologic mutations in ABCA4. Missense mutations were expressed in HEK293T cells and their level of expression, retinoid substrate binding properties, and ATPase activities were measured and correlated with the phenotype of the STGD1 patients. Results: Of the 11 STGD1 patients analyzed, 7 patients had two mutations in ABCA4, 3 patients had one detected mutation, and 1 patient had no mutations in the exons and flanking regions. Included in this cohort of patients was a severely affected 11-year-old child who was homozygous for the novel p.Ala1794Pro mutation. Expression and functional analysis of this variant and other disease-associated variants compared favorably with the phenotypes of this cohort of STGD1 patients. Conclusions: Although many factors contribute to the phenotype of STGD1 patients, the expression and residual activity of ABCA4 mutants play a major role in determining the disease severity of STGD1 patients.

Correlation of novel PAX6 gene abnormalities in aniridia and clinical presentation.

OBJECTIVE: To describe the clinical presentation and genotype of subjects with aniridia with a particular focus on foveal hypoplasia. DESIGN: Prospective cohort study. PARTICIPANTS: Thirty-three Canadian participants with aniridia and of various ethnic backgrounds residing in British Columbia. METHODS: Full ophthalmic examinations and posterior segment spectral domain-optical coherence tomography (SD-OCT) imaging were performed. Foveal hypoplasia was graded independently by 2 staff ophthalmologists. PAX6 sequencing was performed and chromosomal 11p anomalies investigated. Candidate gene and single-nucleotide polymorphism sequencing in genes functionally related to PAX6 were also studied. RESULTS: Best corrected visual acuities in the cohort ranged from 0.0 logMAR to no light perception. Total absence of iris tissue was seen in the majority (42 of 66 eyes). In those in whom SD-OCT was possible, foveal hypoplasia was seen in the majority (45 of 56 eyes, 80%). Molecular genetic defects involving PAX6 were identified in 30 participants (91%), including 4 novel PAX6 mutations (Gly18Val; Ser65ProfsX14; Met337ArgfsX18; Ser321CysfsX34) and 4 novel chromosome 11p deletions inclusive of PAX6 or a known PAX6 regulatory region. CONCLUSIONS: The number of PAX6 mutations associated with aniridia continues to increase. Variable foveal architecture despite nearly identical anterior segment disease in 4 participants with an Ex9 ELP4-Ex4 DCDC1 deletion suggested that molecular cues causing variation in disease in the posterior segment differ from those at play in the anterior segment. Results in 3 patients without identifiable PAX6 mutations and a review of the literature suggest that such cases be described as phenocopies rather than actual cases of the syndrome of aniridia.