Peripheral Retinal Haemorrhages in a Patient with MOG-Associated Optic Neuritis.

A 15-year-old female presented with headaches and bilateral vision loss. Fundoscopic examination revealed bilateral optic nerve oedema as well as peripheral retinal haemorrhages. Magnetic resonance imaging of the brain showed findings consistent with bilateral optic neuritis. The patient was started on high dose intravenous corticosteroids but her vision failed to improve. The presence of retinal haemorrhages raised concern that a vasculitis was underlying her symptoms, prompting an extensive work-up, which was unrevealing. Plasmapheresis was initiated and the patient's vision eventually improved to 20/20 in both eyes. Ultimately, she was found to be positive for myelin oligodendrocyte glycoprotein (MOG) antibodies, consistent with a diagnosis of MOG-associated optic neuritis. The patient's course was typical for MOG-associated optic neuritis but her peripheral retinal haemorrhages were atypical, which created diagnostic uncertainty. It is important to be aware of the possibility of retinal findings in this disease. We also review potential causes for retinal haemorrhages in optic neuritis.

Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels.

The spatial presentation of mechanical information is a key parameter for cell behavior. We have developed a method of polymerization control in which the differential diffusion distance of unreacted cross-linker and monomer into a prepolymerized hydrogel sink results in a tunable stiffness gradient at the cell-matrix interface. This simple, low-cost, robust method was used to produce polyacrylamide hydrogels with stiffness gradients of 0.5, 1.7, 2.9, 4.5, 6.8, and 8.2 kPa/mm, spanning the in vivo physiological and pathological mechanical landscape. Importantly, three of these gradients were found to be nondurotactic for human adipose-derived stem cells (hASCs), allowing the presentation of a continuous range of stiffnesses in a single well without the confounding effect of differential cell migration. Using these nondurotactic gradient gels, stiffness-dependent hASC morphology, migration, and differentiation were studied. Finally, the mechanosensitive proteins YAP, Lamin A/C, Lamin B, MRTF-A, and MRTF-B were analyzed on these gradients, providing higher-resolution data on stiffness-dependent expression and localization.

ENDOGENOUS ENDOPHTHALMITIS CAUSED BY GROUP B STREPTOCOCCUS IN A HEALTHY, TERM NEONATE.

PURPOSE: The purpose of this study was to describe an unusual case of unilateral, endogenous endophthalmitis in an otherwise healthy, term neonate. METHODS: A 3-week-old otherwise healthy, term male infant was referred to St. Louis Children's Hospital for a second opinion of presumed panuveitis of the right eye. RESULTS: Diffusion-weighted magnetic resonance imaging demonstrating purulent intraocular contents facilitated the diagnosis of endophthalmitis. Examination of surgical vitreous samples by staining and cytology demonstrated gram-positive bacterial cocci in short chains, thereby confirming endophthalmitis. Polymerase chain reaction testing of vitreous fluid identified Streptococcus agalactiae , despite an unremarkable systemic workup and a negative prepartum maternal Group B streptococcal screen. CONCLUSION: Endogenous endophthalmitis is a rare but devastating cause of vision loss in otherwise healthy, term neonates. Prompt diagnosis may be facilitated by magnetic resonance imaging and diagnostic vitreous biopsy.

Identification of potential mediators of retinotopic mapping: a comparative proteomic analysis of optic nerve from WT and Phr1 retinal knockout mice.

Retinal ganglion cells (RGCs) transmit visual information topographically from the eye to the brain, creating a map of visual space in retino-recipient nuclei (retinotopy). This process is affected by retinal activity and by activity-independent molecular cues. Phr1, which encodes a presumed E3 ubiquitin ligase (PHR1), is required presynaptically for proper placement of RGC axons in the lateral geniculate nucleus and the superior colliculus, suggesting that increased levels of PHR1 target proteins may be instructive for retinotopic mapping of retinofugal projections. To identify potential target proteins, we conducted a proteomic analysis of optic nerve to identify differentially abundant proteins in the presence or absence of Phr1 in RGCs. 1D gel electrophoresis identified a specific band in controls that was absent in mutants. Targeted proteomic analysis of this band demonstrated the presence of PHR1. Additionally, we conducted an unbiased proteomic analysis that identified 30 proteins as being significantly different between the two genotypes. One of these, heterogeneous nuclear ribonucleoprotein M (hnRNP-M), regulates antero-posterior patterning in invertebrates and can function as a cell surface adhesion receptor in vertebrates. Thus, we have demonstrated that network analysis of quantitative proteomic data is a useful approach for hypothesis generation and for identifying biologically relevant targets in genetically altered biological models.

Visual Acuity Outcomes and Loss to Follow-up in the Treatment of Amblyopia in Children From Lower Socioeconomic Backgrounds.

PURPOSE: To compare visual acuity outcomes and loss to follow-up after initiation of treatment for unilateral amblyopia in children from different socioeconomic backgrounds. METHODS: Medical records of children diagnosed as having unilateral amblyopia at an initial encounter between 2015 and 2018 were reviewed. Medicaid and private insurance were used as proxies for socioeconomic status (SES). Data points were collected at the patients' initial, follow-up, and final visits. Visual acuity improvement was the primary outcome variable in patients with at least one follow-up appointment. In a separate analysis, failure to attend a single follow-up appointment was examined for associations with SES, race, sex, and distance traveled to appointments. RESULTS: Seventy-three patients met the inclusion criteria; of these, 28 had Medicaid and 45 had private insurance. Visual acuity improved by 2.86 lines in the Medicaid group and 2.98 lines in the private insurance group (P = .84). Number of missed appointments and distance traveled did not correlate with visual acuity improvement. In the loss to follow-up subanalysis, 40 of 141 (28.4%) patients with Medicaid and 11 of 107 (10.3%) patients with private insurance failed to attend a single follow-up visit (P = .001). No association was found between loss to follow-up and race, sex, or distance traveled. CONCLUSIONS: Visual acuity outcomes of treatment for amblyopia did not differ between patients with Medicaid and patients with private insurance who followed up. However, patients with Medicaid were much more likely to be immediately lost to follow-up. Measures should be taken by eye care providers and pediatricians to increase follow-up in patients from low SES populations. [J Pediatr Ophthalmol Strabismus. 2022;59(2):110-117.].

Income Disparities in Outcomes of Horizontal Strabismus Surgery in a Pediatric Population.

PURPOSE: To examine postoperative outcomes in pediatric patients undergoing strabismus surgery to determine the potential impact of socioeconomic disparities on ophthalmic outcomes. METHODS: This study included 284 children undergoing strabismus surgery at a tertiary institution with at least 11 months of follow-up and no prior strabismus surgery or other neurologic or ophthalmologic conditions. Demographics, insurance, operative parameters, and appointments scheduled/attended were collected via chart review. Ocular alignment was recorded preoperatively and postoperatively at 3, 12, and 24 months. Two-sided t tests and chi-squared analyses were used to compare demographic and operative parameters. Logistic regression was employed to determine predictive factors for ophthalmic outcomes. RESULTS: There was no difference in failure rates between patients with Medicaid and patients with private insurance 24 months postoperatively (45.9% vs 50.5%, respectively, P = .46). Patients with Medicaid were more likely to not follow up postoperatively (28.2% vs 9.6%, respectively, P < .01), whereas patients with private insurance were more likely to complete more than three follow-up appointments in 24 months (21.5% vs 39.0%, respectively, P < .01). Postoperative attendance was linked to Medicaid status (P < .01) but not travel time, neighborhood income levels, or social deprivation index factors. CONCLUSIONS: There was no difference in failure rates between patients with Medicaid and patients with private insurance. Medicaid status was significantly predictive of loss to follow-up. [J Pediatr Ophthalmol Strabismus. 2022;59(3):156-163.].

Iris Stromal Cyst in a 6-Month-Old With Rapid Progression to Angle Closure.

CASE REPORT: A 6-month-old female presented with an iris cyst in the left eye, first identified at age 4 months. The patient was seen by an ophthalmologist at age 6 months and referred for further management. Our examination 2 weeks later demonstrated a 6 mm diameter iris cyst originating from the anterior surface of the inferior iris, occupying the inferior two thirds of the anterior chamber and obscuring the pupil. Intraocular pressure was normal and the remainder of the anterior chamber was formed. Because of concern for the development of amblyopia, the patient was scheduled for an examination under anesthesia and iris cyst removal 2 days later. In the intervening 2 days, the patient's mother noted worsening photophobia and tearing. At the time of surgery, the intraocular pressure was 51 mm Hg in the left eye. Anterior examination demonstrated interval development of shallowing of the anterior chamber with irido-corneal and cyst-corneal touch. The iris cyst had increased to 8 mm in size and filled the entire pupillary aperture. The iris cyst was excised, and histopathology confirmed the diagnosis of an iris stromal cyst. CONCLUSIONS: Congenital stromal cysts of the iris can enlarge, threatening amblyopia and secondary glaucoma in children. Although angle closure is a known theoretical complication of iris stromal cysts, actual cases are rare in the literature. This case demonstrates the importance of serial examinations to monitor progression of iris stromal cysts, particularly in young children.

Atypical presentation of Cat Eye Syndrome in an infant with Peters anomaly and microphthalmia with cyst.

PURPOSE: To describe a unique ocular presentation of Cat Eye Syndrome and review the ocular and systemic findings associated with the syndrome. METHODS: Case report with multimodal imaging. RESULTS: A newborn female presented with a unilateral Peters anomaly with contralateral microphthalmia with cyst. The patient's other systemic findings included a hypoplastic right heart, persistent ductus arteriosus, intrauterine growth retardation, bilateral anotia, preauricular ear pits and skin tags, micrognathia, hypoplastic female genitalia, and unilateral cranial nerve VII palsy. Chromosomal microarray testing showed tetrasomy of chromosome 22 in the q11.1-q11.21 region consistent with Cat Eye Syndrome. The patient ultimately underwent a successful optical iridectomy on one side and orbitotomy with excision of the cystic mass on the other. CONCLUSIONS: The co-occurrence of unilateral Peters anomaly with contralateral microphthalmia with cyst in Cat Eye Syndrome is rare and demonstrative of the syndrome's phenotypic variability. The medical and surgical management of these patients may require a multidisciplinary approach and must be tailored to the individual findings and overall systemic health of the patient.

Risk factors for strabismus following glaucoma drainage device implantation for refractory childhood glaucoma.

BACKGROUND: Strabismus is common in children after glaucoma drainage device (GDD) implantation, but the risk factors for postoperative strabismus remain speculative. The purpose of this study was to investigate possible risk factors for strabismus following GDD implantation for refractory childhood glaucoma. METHODS: The medical records of consecutive patients who underwent GDD implantation for refractory childhood glaucoma at Duke Eye Center from 2005 to 2016 were reviewed retrospectively. Pre- and postoperative motility and alignment, best-corrected visual acuity, and demographic and surgical data were extracted from the record for analysis. RESULTS: A total of 81 patients (mean age, 7.9 ± 4.8 years) met inclusion criteria. The most common glaucoma type was glaucoma following cataract surgery (GFCS), and the most common GDD was a Baerveldt 250 mm2 device. Before GDD surgery, 38 patients (47%) had documented strabismus. After GDD implantation, 25 (31%) had new or worsened strabismus, with vertical (16% of new/worsened), horizontal strabismus (exotropia, 48% of new/worsened; esotropia, 12% of new/worsened) and vertical and horizontal (24% of new/worsened) noted. New motility limitation occurred in 32 of 81 (40%) patients. Risk factors including age, type/location/number of GDD, revision, motility limitation, glaucoma type, asymmetric visual acuity, and visual impairment were not significantly associated with new or worsened post-GDD strabismus. CONCLUSIONS: Children with refractory childhood glaucoma are at high risk for strabismus, which increases after GDD implantation; this study identified no clear risk factors for new or worsened post-GDD strabismus.

Strabismus surgery in the setting of glaucoma drainage devices in the pediatric population.

PURPOSE: To evaluate outcomes of strabismus surgery performed subequent to or concomitant with glaucoma drainage device (GDD) implantation for refractory childhood glaucoma. METHODS: The medical records of children who underwent strabismus surgery after or concomitantly with GDD implantation were reviewed retrospectively. Included were surgeries with motility and alignment data measured preoperatively and ≥3 months postoperatively. The following data were collected: demographics, visual acuity, glaucoma diagnosis, GDD type/location, pre- and postoperative sensorimotor/alignment measurements, and surgical details. Motor success was defined as ≤10Δ horizontal and ≤4Δ vertical residual heterotropia postoperatively. RESULTS: A total of 25 children were included: 11 in the post-GDD group and 14 in the concomitant-GDD group. In the former, peri-GDD capsule dissection was required in 9 of 11 patients (82%). All cases had preoperative motility restriction or intraoperative scarring. Mean preoperative deviation (26.7Δ ± 14.6Δ) decreased by 41% postoperatively, with improved alignment in 7 patients (64%). No patients met strict motor alignment criteria for success. In the concomitant-GDD group, mean preoperative deviation (28.5Δ ± 10.0Δ) decreased by 39% postoperatively, with improved alignment in 11 of 14 patients (79%). Four patients (29%) met strict criteria for success. There were no surgical complications in either group. CONCLUSIONS: Strabismus surgery in eyes with existing or planned GDDs for childhood glaucoma usually improves alignment but often does not result in success based on strict motor alignment criteria. Eyes with childhood glaucoma pose surgical technical challenges related to small orbits and exuberant GDD capsule-muscle scarring and postoperative challenges of poor vision and limited binocular function, that likely limit succcess.

TUBULOINTERSTITIAL NEPHRITIS AND UVEITIS SYNDROME WITH A PRIMARY PRESENTATION OF ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY.

PURPOSE: To report a case of tubulointerstitial nephritis and uveitis syndrome with a primary presentation of acute posterior multifocal placoid pigment epitheliopathy after use of lamotrigine. METHODS: Retrospective case report with ultra-widefield fundus imaging, optical coherence tomography, and fluorescein angiography. RESULTS: A 19-year-old woman presented with decreased visual acuity and acute renal failure after starting lamotrigine. Her examination demonstrated 1+ anterior chamber cell and numerous white deep retinal plaque-like lesions predominantly in the macula in both eyes. After extensive ophthalmic and systemic evaluation, the patient was diagnosed with tubulointerstitial nephritis and uveitis syndrome with a primary presentation of acute posterior multifocal placoid pigment epitheliopathy. She had excellent visual recovery with topical and systemic steroids. CONCLUSION: Acute posterior multifocal placoid pigment epitheliopathy is a rare but important clinical presentation of tubulointerstitial nephritis and uveitis syndrome. Oral corticosteroid treatment can be considered for tubulointerstitial nephritis but is generally not necessary for acute posterior multifocal placoid pigment epitheliopathy.

Multifocal iris melanoma in a 2-year-old managed with I-125 plaque brachytherapy.

We report a 23-month-old patient presenting with multifocal iris melanoma who underwent plaque brachytherapy with full corneal coverage. The lesion demonstrated several high-risk clinical and histopathologic features associated with iris melanoma in adults, including growth and angle seeding. The patient has been subsequently followed for 3.5 years with no evidence of recurrence. This report demonstrates the importance of serial examination of suspected melanocytic iris lesions in very young children and the effective treatment option of globe-sparing radiation therapy.

Mechanical derivation of functional myotubes from adipose-derived stem cells.

Though reduced serum or myoblast co-culture alone can differentiate adipose-derived stem cells (ASCs) into mesenchymal lineages, efficiency is usually not sufficient to restore function in vivo. Often when injected into fibrotic muscle, their differentiation may be misdirected by the now stiffened tissue. Here ASCs are shown to not just simply reflect the qualitative stiffness sensitivity of bone marrow-derived stem cells (BMSCs) but to exceed BMSC myogenic capacity, expressing the appropriate temporal sequence of muscle transcriptional regulators on muscle-mimicking extracellular matrix in a tension and focal adhesion-dependent manner. ASCs formed multi-nucleated myotubes with a continuous cytoskeleton that was not due to misdirected cell division; microtubule depolymerization severed myotubes, but after washout, ASCs refused at a rate similar to pre-treated values. BMSCs never underwent stiffness-mediated fusion. ASC-derived myotubes, when replated onto non-permissive stiff matrix, maintained their fused state. Together these data imply enhanced mechanosensitivity for ASCs, making them a better therapeutic cell source for fibrotic muscle.

The alignment and fusion assembly of adipose-derived stem cells on mechanically patterned matrices.

Cell patterning is typically accomplished by selectively depositing proteins for cell adhesion only on patterned regions; however in tissues, cells are also influenced by mechanical stimuli, which can also result in patterned arrangements of cells. We developed a mechanically-patterned hydrogel to observe and compare it to extracellular matrix (ECM) ligand patterns to determine how to best regulate and improve cell type-specific behaviors. Ligand-based patterning on hydrogels was not robust over prolonged culture, but cells on mechanically-patterned hydrogels differentially sorted based on stiffness preference: myocytes and adipose-derived stem cells (ASCs) underwent stiffness-mediated migration, i.e. durotaxis, and remained on myogenic hydrogel regions. Myocytes developed aligned striations and fused on myogenic stripes of the mechanically-patterned hydrogel. ASCs aligned and underwent myogenesis, but their fusion rate increased, as did the number of cells fusing into a myotube as a result of their alignment. Conversely, neuronal cells did not exhibit durotaxis and could be seen on soft regions of the hydrogel for prolonged culture time. These results suggest that mechanically-patterned hydrogels could provide a platform to create tissue engineered, innervated micro-muscles of neural and muscle phenotypes juxtaposed next to each other in order better recreate a muscle niche.

Natural sphingadienes inhibit Akt-dependent signaling and prevent intestinal tumorigenesis.

Sphingolipid metabolites regulate cell proliferation, migration, and stress responses. Alterations in sphingolipid metabolism have been proposed to contribute to carcinogenesis, cancer progression, and drug resistance. We identified a family of natural sphingolipids called sphingadienes and investigated their effects in colon cancer. We find that sphingadienes induce colon cancer cell death in vitro and prevent intestinal tumorigenesis in vivo. Sphingadienes exert their influence by blocking Akt translocation from the cytosol to the membrane, thereby inhibiting protein translation and promoting apoptosis and autophagy. Sphingadienes are orally available, are slowly metabolized through the sphingolipid degradative pathway, and show limited short-term toxicity. Thus, sphingadienes represent a new class of therapeutic and/or chemopreventive agents that blocks Akt signaling in neoplastic and preneoplastic cells.