Spontaneous collapse of an iris stromal cyst in a young child.

A 4-month-old girl was referred for evaluation of an anterior chamber cyst in the left eye. Examination under anesthesia (EUA) revealed a large iris stromal cyst in the anterior chamber involving the angle and the pupillary border, with touch of the corneal endothelium and anterior lens capsule. Intraocular pressure was normal. There was no anisometropic refractive error by retinoscopy. Close observation with amblyopia management was recommended as the pupil was only partially occluded by the cyst, and there was a clear red reflex around the cyst. Repeat EUA 6 months following diagnosis showed spontaneous collapse of the cyst. There was no recurrence noted at her most recent follow-up, 2 years after presentation, and most of the pupillary axis remains unobstructed by the cyst. The patient continues to be followed to monitor for possible cyst progression, anisometropia, and development of amblyopia. Though rare, spontaneous resolution of an iris stromal cyst may occur and thus, observation may be considered, particularly if the cyst is not causing anterior segment complications or obstruction of the visual axis.

LINC01638 sustains human mesenchymal stem cell self-renewal and competency for osteogenic cell fate.

The skeleton forms from multipotent human mesenchymal stem cells (hMSCs) competent to commit to specific lineages. Long noncoding RNAs (lncRNAs) have been identified as key epigenetic regulators of tissue development. However, regulation of osteogenesis by lncRNAs as mediators of commitment to the bone phenotype is largely unexplored. We focused on LINC01638, which is highly expressed in hMSCs and has been studied in cancers, but not in regulating osteogenesis. We demonstrated that LINC01638 promotes initiation of the osteoblast phenotype. Our findings reveal that LINC01638 is present at low levels during the induction of osteoblast differentiation. CRISPRi knockdown of LINC01638 in MSCs prevents osteogenesis and alkaline phosphatase expression, inhibiting osteoblast differentiation. This resulted in decreased MSC growth rate, accompanied by double-strand breaks, DNA damage, and cell senescence. Transcriptome profiling of control and LINC01638-depleted hMSCs identified > 2000 differentially expressed mRNAs related to cell cycle, cell division, spindle formation, DNA repair, and osteogenesis. Using ChIRP-qPCR, molecular mechanisms of chromatin interactions revealed the LINC01638 locus (Chr 22) includes many lncRNAs and bone-related genes. These novel findings identify the obligatory role for LINC01638 to sustain MSC pluripotency regulating osteoblast commitment and growth, as well as for physiological remodeling of bone tissue.

LINC01638 Sustains Human Mesenchymal Stem Cell Self-Renewal and Competency for Osteogenic Cell Fate.

The skeleton forms from multipotent human mesenchymal stem cells (hMSCs) competent to commit to specific lineages. Long noncoding RNAs (lncRNAs) have been identified as key epigenetic regulators of tissue development. However, regulation of osteogenesis by lncRNAs as mediators of commitment to the bone phenotype is largely unexplored. We focused on LINC01638, which is highly expressed in hMSCs and has been studied in cancers, but not in regulating osteogenesis. We demonstrated that LINC01638 promotes initiation of the osteoblast phenotype. Our findings reveal that LINC01638 is present at low levels during the induction of osteoblast differentiation. CRISPRi knockdown of LINC01638 in MSCs prevents osteogenesis and alkaline phosphatase expression, inhibiting osteoblast differentiation. This resulted in decreased MSC cell growth rate, accompanied by double-strand breaks, DNA damage, and cell senescence. Transcriptome profiling of control and LINC01638-depleted hMSCs identified > 2,000 differentially expressed mRNAs related to cell cycle, cell division, spindle formation, DNA repair, and osteogenesis. Using ChIRP-qPCR, molecular mechanisms of chromatin interactions revealed the LINC01638 locus (Chr 22) includes many lncRNAs and bone-related genes. These novel findings identify the obligatory role for LINC01638 to sustain MSC pluripotency regulating osteoblast commitment and growth, as well as for physiological remodeling of bone tissue.

Neuro-ophthalmic Complications in Pediatric Leukemia.

BACKGROUND: Optic neuropathy in childhood leukemia occurs through multiple direct and indirect mechanisms, including leukemic infiltration of the optic nerve, infection, blood dyscrasias, or adverse effects of treatment. We aimed to characterize visual outcomes in pediatric patients with leukemia-associated neuro-ophthalmic manifestations. METHODS: We retrospectively identified patients with leukemia and optic nerve pathology over 13 years by diagnostic billing codes. We collected information on demographics, presentation, treatment course, and visual outcomes directly from medical records. RESULTS: Of the 19 patients who met inclusion criteria, 17 (89.5%) had pseudotumor cerebri and 2 had direct optic nerve infiltration. Causes of increased intracranial pressure included central nervous system infiltration (6 of 17), hyperviscosity/leukemia (2 of 17), venous sinus thrombosis (3 of 17), medication induced (5 of 17), and bacterial meningitis (1 of 17). 47.1% (8 of 17) had papilledema at the time of leukemia diagnosis, and 94.1% (16 of 17) of patients with pseudotumor cerebri were treated with acetazolamide. At presentation, 3 patients had decreased vision secondary to macular ischemia, subhyaloid vitreous hemorrhage, or steroid induced glaucoma. Following treatment of pseudotumor cerebri, binocular visual acuity was ≥20/25 in all patients. One patient with optic nerve infiltration had a final visual acuity of count fingers in the affected eye. CONCLUSIONS: In our chart review, the most common mechanism of neuro-ophthalmic involvement in pediatric leukemia was elevated intracranial pressure from a myriad of causes. Visual outcomes from patients with elevated intracranial pressure were excellent. Understanding the mechanisms by which leukemia can cause optic nerve disease in pediatric patients can facilitate earlier diagnosis and treatment and potentially improve visual outcomes.

Two siblings with GAPO syndrome: Ophthalmic presentation and histopathologic findings.

BACKGROUND: GAPO syndrome (growth retardation, alopecia, pseudoanodontia, optic atrophy) is a rare, autosomal recessive connective tissue disorder with only 60 reported cases. Ophthalmic manifestations vary and include hypertelorism, optic atrophy, and glaucoma. There have been three reported cases of GAPO syndrome with craniosynostosis. MATERIALS/METHODS: We describe two new siblings with GAPO syndrome and craniosynostosis and the first histopathologic analysis of Tenon's capsule and extraocular muscle in this syndrome. RESULTS: Both siblings presented with papilledema and V-pattern strabismus in addition to the alopecia, brittle eyelashes, growth retardation, and pseudoanodontia that characterize GAPO syndrome. Cranial vault expansion, though successful, was complicated by lack of distinct periosteal layers, thin dural adherence to bone, and extensive venous bleeding. Tenons encountered during strabismus surgery was inelastic and highly vascular. Histopathological analysis revealed hyalinization of Tenon's and a thickened, homogenized, amorphous appearance, similar to the extracellular matrix abnormalities described in skin and other organs Histopathological analysis of extraocular muscle was, in contrast, unremarkable. CONCLUSIONS: GAPO impacts the extracellular matrix of Tenon's resulting in inelasticity and hypervascularity. Ophthalmologists should be mindful of these aberrant characteristics when planning surgery in this population.

Widefield SS-OCTA for Localization of Retinal Nematode in Diffuse Unilateral Subacute Neuroretinitis.

Diffuse unilateral subacute neuroretinitis (DUSN) is a rare form of chorioretinitis caused by retinal infestation by nematode larvae. Definitive diagnosis requires visualization of a motile nematode, but this can be challenging because the nematode is small, translucent, and usually motionless with overlying media opacity from cellular inflammation. The authors describe a case of DUSN in which widefield swept-source optical coherence tomography angiography was used to localize a midperipheral intraretinal nematode facilitating subsequent clinical observation of movement. Inflammation resolved after focal laser photocoagulation of the nematode with recovery of visual acuity to 20/20. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:345-349.].

Characteristics of diplopia in a pediatric population.

PURPOSE: To evaluate the characteristics of diplopia in children at a single tertiary eye care center. METHODS: The medical records of patients with diplopia onset at age 18 years or younger presenting during the period 2015-2018 were reviewed retrospectively. Demographic information, clinical characteristics, diagnoses, treatment, and outcome data were collected. The exact χ2 test was used to compare groups and select post hoc analyses were performed using the Fisher exact or exact χ2 tests. RESULTS: A total of 244 patients (average age, 12.2 years at presentation) were included. The most common clinical diagnoses were nonparalytic strabismus (49.2%), trauma (9.4%), and cranial nerve palsies (9%). There was no statistically significant difference in median age of diplopia onset in those with nonparalytic strabismus, cranial nerve palsies, and vision- or life-threatening conditions. There was a statistically significant difference in timing of onset of diplopia at presentation in vision- or life-threatening conditions compared to nonparalytic strabismus (P < 0.0001) and cranial nerve palsies (P = 0.01) and for neurologic symptoms in vision- or life- threatening conditions compared to nonparalytic strabismus (P = 0.032) and cranial nerve palsies (P = 0.0051). In patients with more than one neurologic symptom, the majority (58.3%) had a vision- or life-threatening condition. Initial interventions included observation (28.7%), prisms (18.4%), updating refractive correction (14.3%), and strabismus surgery (11.1%). In patients with follow-up data, 5.3% had resolution of diplopia prior to their clinic visit, and 46.6% had resolution after initial intervention. CONCLUSIONS: In our study cohort, most children who presented with diplopia had nonemergent conditions. In those with life-threatening conditions, diplopia tended to have an acute onset and associated neurologic signs and visual symptoms.

Clinical Diagnosis and Histopathologic Features of a Synthetic Fiber Granuloma.

The authors report a case of a synthetic fiber granuloma to demonstrate the challenges in diagnosing these lesions and to highlight their histopathologic features. This is the first report in the literature to use histopatho-logic and immunofluorescence studies to characterize the subtype and distribution of macrophages in synthetic fiber granuloma. [J Pediatr Ophthalmol Strabismus. 2020;57:e92-e95.].

Regulation of osteogenesis by long noncoding RNAs: An epigenetic mechanism contributing to bone formation.

Long noncoding RNAs (lncRNAs) have recently emerged as novel regulators of lineage commitment, differentiation, development, viability, and disease progression. Few studies have examined their role in osteogenesis; however, given their critical and wide-ranging roles in other tissues, lncRNAs are most likely vital regulators of osteogenesis. In this study, we extensively characterized lncRNA expression in mesenchymal cells during commitment and differentiation to the osteoblast lineage using a whole transcriptome sequencing approach (RNA-Seq). Using mouse primary mesenchymal stromal cells (mMSC), we identified 1438 annotated lncRNAs expressed during MSC differentiation, 462 of which are differentially expressed. We performed guilt-by-association analysis using lncRNA and mRNA expression profiles to identify lncRNAs influencing MSC commitment and differentiation. These findings open novel dimensions for exploring lncRNAs in regulating normal bone formation and in skeletal disorders.

Adenoid cystic carcinoma of the lacrimal gland in a 14-year-old male.

Adenoid cystic carcinoma (ACC) of the lacrimal gland is an aggressive, malignant epithelial neoplasm. This tumor is rarely seen in adults and even less commonly seen in children and adolescents; thus, there have been no large studies to date describing the optimal treatment of this malignancy in the pediatric population. Here, we report a case of lacrimal gland ACC in a 14-year-old male treated with neoadjuvant intra-arterial chemotherapy followed by globe-sparing tumor resection and chemoradiation. At 2-year follow-up, he remains disease free without evidence of tumor recurrence.