Orbital Abscess Secondary to Nasolacrimal Duct Obstruction in an Extremely Preterm Infant.

Orbital abscesses are rarely encountered in children younger than 1 year. The literature is limited to isolated case reports and a few case series. Most such cases are reported in infants born at term, with the earliest reported gestational birth age at 34 weeks. Children are more prone to orbital cellulitis compared with adults due to their underdeveloped sinuses and immature immune systems, and the origin is most commonly an ethmoid sinus infection. Orbital cellulitis secondary to dacryocystitis is even less common, with only a few isolated cases reported in infants and children. Herein, the authors present a case of a large extraconal and intraconal orbital abscess secondary to nasolacrimal duct obstruction and dacryocystitis in an extremely preterm infant. We discuss the diagnosis and multidisciplinary management of this challenging case.

An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans.

To define the C. elegans aging process at the molecular level, we used DNA microarray experiments to identify a set of 1294 age-regulated genes and found that the GATA transcription factors ELT-3, ELT-5, and ELT-6 are responsible for age regulation of a large fraction of these genes. Expression of elt-5 and elt-6 increases during normal aging, and both of these GATA factors repress expression of elt-3, which shows a corresponding decrease in expression in old worms. elt-3 regulates a large number of downstream genes that change expression in old age, including ugt-9, col-144, and sod-3. elt-5(RNAi) and elt-6(RNAi) worms have extended longevity, indicating that elt-3, elt-5, and elt-6 play an important functional role in the aging process. These results identify a transcriptional circuit that guides the rapid aging process in C. elegans and indicate that this circuit is driven by drift of developmental pathways rather than accumulation of damage.

Idiopathic Intracranial Hypertension in Female-to-Male Transgender Patients on Exogenous Testosterone Therapy.

PURPOSE: To present four female-to-male (FTM) transgender patients on testosterone therapy diagnosed with idiopathic intracranial hypertension (IIH). METHODS: The authors report 4 consecutive FTM transgender patients on exogenous testosterone diagnosed with IIH at a single institution. RESULTS: Patient 1 presented with progressive blurred vision and a central scotoma 10 weeks after starting testosterone cypionate injections for hormonal gender transition. Bilateral grade 5 papilledema was present; the patient underwent bilateral optic nerve sheath fenestration with improved vision and resolution of edema. Patient 2 presented with transient vision loss, pulsatile tinnitus, and blurred vision 13 months after starting testosterone cypionate injections. The patient had grade 4 and 3 disc edema of the right and left eyes, respectively. Patient 3 presented with headaches and pulsatile tinnitus and was on testosterone injections at an unknown dose. The examination revealed grade 1 and 2 disc edema of the right and left eyes, respectively. Patient 4 presented with decreased vision, transient visual obscurations, and daily migraines while using topical testosterone gel every other day. Color vision was reduced, and lumbar puncture revealed elevated intracranial pressure. All patients had neuroimaging findings consistent with increased intracranial pressure. CONCLUSIONS: Testosterone therapy plays an essential role in FTM hormonal transitioning and may play a role in IIH. Patients undergoing testosterone therapy for gender transition should be informed of the possibility of developing IIH while on treatment, with obesity possibly increasing this risk. Comprehensive eye examinations should be considered in these patients before initiating hormone therapy.

Recurrent Periorbital Edema Associated With Retained Foreign Body After Filler Injection.

A 34-year-old man presented with recurrent bilateral periorbital swelling and pain for 16 years after receiving facial fillers of an unknown substance in a hotel room from a stranger claiming to work in a medical office. Exam demonstrated a firm, mildly tender nodule along the right upper cheek. Imaging revealed a tubular hyperdensity in the right premaxillary soft tissues. Lower eyelid and upper cheek dissection resulted in retrieval of a tubular metallic foreign body consistent with a needle. Histopathology of surrounding tissue demonstrated iron deposition with granulomatous inflammation. Periocular fillers are a common aesthetic procedure. Although generally well-tolerated, complications include inflammatory reactions, infection, necrosis, and vision loss. This case highlights retention of a metallic foreign body, a complication of filler injection that has not been previously reported, emphasizing the importance of careful injection technique by licensed professionals and imaging and surgical exploration if a foreign body is suspected.

Orbital Involvement in Multiple Myeloma.

PURPOSE: To characterize clinical and radiographic features, management, and outcomes of patients with orbital involvement of multiple myeloma (MM). METHODS: A retrospective chart review identified patients with MM and orbital involvement confirmed by histopathology at a single institution between 1995 and 2021. A comprehensive literature review was performed via PubMed to identify all previously reported cases of orbital MM. RESULTS: Retrospective review identified 7 patients (43% male, mean age 68.7 years). Presenting symptoms included proptosis and diplopia. Orbital lesions were primarily located laterally (42.8%) with associated extraocular muscle (57.1%) or lacrimal gland (42.9%) involvement. Five patients (71.4%) had a previous diagnosis of systemic MM. Six patients received chemoradiation (85.7%). All patients had improvement of orbital disease with 2 patients deceased due to disease at follow-up (mean 8.9 months). Literature review identified 111 cases (46.8% male, mean age 58.6 years). 48.6% presented with orbital disease as the first manifestation of systemic MM. Lesions were most commonly located superolaterally (20.2%) with extraocular muscle infiltration (25.2%), lacrimal gland involvement (7.2%), and orbital bony destruction (39.6%). Treatments included chemoradiation, chemotherapy, or radiation alone. Approximately half (51.4%) of patients experienced improvement in orbital disease following treatment, and 48.6% were deceased at follow-up (mean 20.1 months). CONCLUSIONS: This study provides a new retrospective study and updated comprehensive literature review regarding orbital MM. Given its poor prognosis, characterization of orbital MM is essential for early diagnosis. Orbital MM is often unilateral, located superolaterally, and may represent the first manifestation of systemic disease. Treatment includes chemotherapy and radiation, which may improve orbital disease; however, the overall prognosis remains poor.

A rare case of mucoepidermoid carcinoma ex pleomorphic adenoma of the lacrimal gland.

Carcinoma ex pleomorphic adenoma (CEPA) of the lacrimal gland is a rare malignant tumor that arises from a pre-existing pleomorphic adenoma. Lacrimal gland CEPA with mucoepidermoid histological subtype is exceedingly rare. Diagnosis can be aided by radiographic findings, though the gold standard is histopathological analysis following excisional biopsy. Management options include complete surgical excision with or without adjuvant radiation therapy based on tumor grade and invasiveness. We present a 76-year-old woman with 6 months of diplopia and unilateral proptosis. Her initial exam was remarkable for hypoglobus, proptosis, and limited elevation of the right eye. Computed tomography (CT) scan demonstrated a superior, well-circumscribed, extraconal orbital mass. An excisional biopsy was performed, and histopathological findings were consistent with mucoepidermoid carcinoma ex pleomorphic adenoma with positive margins in the tumor capsule. The patient received radiation therapy and remains markedly improved with no disease recurrence at 5 months post-operatively.

Antimicrobial-eluting cement orbital implant: a case report of staged enucleation for infectious panophthalmitis with extraocular extension.

There are various orbital implant options following enucleation. In cases of severe infection, such as panophthalmitis with extraocular extension, it is reasonable to consider a two-staged approach to decrease the risk of infectious complications. One option, illustrated by this case, is enucleation with insertion of an antimicrobial-eluting cement implant, followed by a secondary procedure to exchange the cement with a permanent orbital implant. We report on a patient with clinical, ultrasound, and radiographical findings consistent with infectious panophthalmitis with extra-scleral extension. Intolerable pain and progressive orbital involvement in a blind eye were the indications for enucleation. To reduce the risk of persistent infection, a gentamycin-eluting cement implant (Palacos® R + G as an intraorbital implant) was utilized in the initial procedure. Two months later, the cement implant was removed, and a scleral-wrapped porous implant was placed into a quiet socket without signs of inflammation or infection. In the setting of severe infection, a two-staged procedure utilizing an antimicrobial-eluting implant can be considered.

Spatial analysis of future climate risk to stormwater infrastructure.

Climate change is expected to result in more intense precipitation events that will affect the performance and design requirements of stormwater infrastructure. Such changes will vary spatially, and climate models provide a range of estimates of the effects on events of different intensities and recurrence. Infrastructure performance should be evaluated against the expected range of events, not just rare extremes. We present a national-scale, spatially detailed screening assessment of the potential effects of climatic change on precipitation, stormwater runoff, and associated design requirements. This is accomplished through adjustment relative to multiple future climate scenarios of precipitation intensity-duration-frequency analyses presented in NOAA Atlas 14, which are commonly used in infrastructure design. Future precipitation results are estimated for each Atlas 14 station (these currently omit the Pacific Northwest). Results are interpolated using a geographically conditioned regression kriging approach to provide information about potential climate change impacts in a format more directly useful to local stormwater managers. The intensity of 24-h events with 2-year or greater recurrence is likely to increase in most areas of the United States leading to increased runoff and potential need for increased storage volumes. Changes in more frequent events (e.g., the 90th percentile event) commonly used in design of green infrastructure are relatively less.

Acute Onset Endophthalmitis Following Bilateral Upper and Lower Eyelid Blepharoplasty.

A 59-year-old woman presented with iritis and uveitis in the OD approximately 3 weeks after she underwent a bilateral upper and lower blepharoplasty by an outside oculoplastic specialist. Examination revealed a visual acuity of hand motion in the OD, scleral ulceration suspicious for prior globe perforation, dense vitritis, and loculations and membranes on echography. The patient was diagnosed with acute onset exogenous endophthalmitis. Vitreous aspiration and intravitreal injection of vancomycin and ceftazidime were performed. The patient underwent a pars plana vitrectomy, and vitreous culture demonstrated Streptococcus pseudoporcinus . Postoperative vision improved to 4/200 but was limited by a full-thickness macular hole. Despite silicone oil removal and macular hole repair, the macular hole remained open at month 7 and limited vision to 5/200. During eyelid surgery, surgeons should take precautions against intraoperative needle perforation including possible use of protective shield. Postoperative vision loss after eyelid surgery requires further evaluation.

Response to Miles Kiernan Re: a rare case of mucoepidermoid carcinoma ex pleomorphic adenoma of the lacrimal gland.

Our goal is to contribute to the medical literature with our case of CEPA and hope to better help fellow clinicians diagnose and treat these rare tumors.

Chronic anophthalmic socket pain in the setting of deep orbital pseudocysts.

An 89-year-old woman presented with chronic pain and foreign body sensation in a healthy-appearing anophthalmic socket. Computed tomography of the orbits showed hyperdense, cystic lesions superior and posterior to the orbital implant. Orbital exploration was performed; the orbital implant and lesions were removed. Histopathology revealed cystic structures composed of fibrocellular tissue lined with histiocytes and multinucleated giant cells, consistent with pseudocysts. Postoperatively, the patient noted the resolution of her symptoms. While the etiology of the pseudocysts remains unclear, we hypothesize that the answer can be traced back to the original surgery. The cysts may have formed after extravasation of fluid or proteinaceous material from the eye, from glycerin on the donor sclera, or after introduction of foreign material during retrobulbar injection of local anesthesia. This is the first report of pseudocysts occurring in the orbit posterior to an implant.

Bilateral Leukemic Infiltration of the Lacrimal Sac in a Child.

An 8-year-old boy with a history of refractory acute lymphoblastic leukemia presented with left-sided periorbital erythema and painless enlargement of the lacrimal sac. MRI revealed a soft tissue mass on the floor of the left orbit, extending into the nasolacrimal sac and duct. Lacrimal sac biopsy was consistent with B-lymphoblastic leukemia. The patient was treated with chemotherapy and radiation with satisfactory remission of local disease. However, similar symptoms emerged shortly after on the contralateral side, and repeat MRI was concerning for new leukemic infiltration of the right lacrimal sac. Bone marrow biopsy revealed concurrent medullary relapse. Systemic chemotherapy was adjusted and radiation therapy of the right orbit was initiated. This is the first reported pediatric case of bilateral leukemic involvement of the lacrimal sac.

Eye-sparing Treatment of Localized Orbital Medulloepithelioma With Neoadjuvant Chemoradiation.

A 9-year-old girl presented with a 3-day history of progressive proptosis accompanied by transient discomfort and blurry vision in the OD. MRI revealed a heterogeneously enhancing intraconal lesion that partially encased and displaced the optic nerve. There was no intraocular or intracranial involvement, nor were there signs of distant metastasis. Histopathologic evaluation and immunohistochemistry were consistent with orbital medulloepithelioma. The patient received 4 cycles of chemoradiation per a retinoblastoma protocol. Repeat MRI scans showed significant tumor regression, and further surgical debulking was performed. There has been no evidence of recurrence for over 14 months. Herein, the authors describe an eye-sparing, multimodal treatment of a rare case of localized orbital medulloepithelioma.

Orbital Bony Reconstruction With Presized and Precontoured Porous Polyethylene-Titanium Implants.

PURPOSE: Complex bony orbital defects are reconstructively challenging due to loss of intraoperative anatomical landmarks and adjacent support. Presized and precontoured porous polyethylene-titanium implants (Medpor Titan 3D Orbital Floor Implant) are designed to reestablish normal orbital floor and medial wall anatomy and are modeled after anatomically averaged orbits. This is the first study to report clinical outcomes with this implant. METHODS: This retrospective case series reviewed clinical data and outcomes for patients undergoing orbital reconstruction with a presized and precontoured porous polyethylene-titanium orbital implant from January 2016 to June 2018. RESULTS: A total of 34 orbits of 33 patients were identified (mean age: 43 ± 16 years, 70% men). Most bony defects were a result of trauma and included large orbital floor deformities (100%), medial wall defects (74%), disrupted inferomedial struts (68%), and broken posterior ledges (82%). Symptomatic diplopia (73%) and enophthalmos (89%, mean: 3.7 ± 2.1 mm) were common preoperatively. Many cases were revisions (44%). Mean follow up was 7.8 ± 6.7 months. All patients had improved globe positioning, enophthalmos, and hypoglobus. Seven patients had persistent postoperative diplopia: 6 responded to prism therapy and 1 required strabismus surgery. One patient required retrobulbar hematoma drainage and 1 patient required implant explantation due to chronic infection. CONCLUSIONS: Commercially available presized and precon toured porous polyethylene-titanium implants are useful for complex orbital bony defects and can achieve functional improve ments in diplopia, enophthalmos, and extraocular motility with a low incidence of postoperative complications or revisional surgery.

BRCA1 and BARD1 mediate apoptotic resistance but not longevity upon mitochondrial stress in Caenorhabditis elegans.

Interventions that promote healthy aging are typically associated with increased stress resistance. Paradoxically, reducing the activity of core biological processes such as mitochondrial or insulin metabolism promotes the expression of adaptive responses, which in turn increase animal longevity and resistance to stress. In this study, we investigated the relation between the extended Caenorhabditis elegans lifespan elicited by reduction in mitochondrial functionality and resistance to genotoxic stress. We find that reducing mitochondrial activity during development confers germline resistance to DNA damage-induced cell cycle arrest and apoptosis in a cell-non-autonomous manner. We identified the C. elegans homologs of the BRCA1/BARD1 tumor suppressor genes, brc-1/brd-1, as mediators of the anti-apoptotic effect but dispensable for lifespan extension upon mitochondrial stress. Unexpectedly, while reduced mitochondrial activity only in the soma was not sufficient to promote longevity, its reduction only in the germline or in germline-less strains still prolonged lifespan. Thus, in animals with partial reduction in mitochondrial functionality, the mechanisms activated during development to safeguard the germline against genotoxic stress are uncoupled from those required for somatic robustness and animal longevity.

Solitary Fibrous Tumor of the Orbit: A Case Series With Clinicopathologic Correlation and Evaluation of STAT6 as a Diagnostic Marker.

PURPOSE: To retrospectively describe the clinical characteristics, management, and outcomes of a series of patients with solitary fibrous tumor (SFT) of the orbit and to evaluate signal transducer and activator of transcription 6 (STAT6) as a diagnostic marker. METHODS: Review of a retrospective, noncomparative, consecutive series of patients treated at a single institution with a histopathologic diagnosis of SFT. Demographic, clinical, and imaging data were collected, and paraffin-embedded tissue sections were stained to evaluate for the presence of STAT6 and other pertinent markers. RESULTS: Twenty-one patients were identified. Most presented with painless progressive proptosis or eyelid swelling for less than 6 months. Imaging revealed well-circumscribed, firm, variably vascular contrast-enhancing lesions with low to medium reflectivity on ultrasound. Four tumors were histopathologically malignant. All tumors were primarily excised, and 1 patient required exenteration. Two patients were treated with adjuvant radiation therapy. Six patients had recurrent disease of which 3 underwent repeat excision, and 2 were observed. No metastatic disease or attributable deaths were observed. All lesions with available tissue stained positively for both CD34 and STAT6. CONCLUSION: This is the largest single institution case series of orbital SFT with clinicopathologic correlation and the largest series to confirm the presence of STAT6 in orbital lesions. The management of SFT remains challenging due to unpredictable tumor behavior, and complete excision is the generally recommended treatment. It remains unclear whether a subset of asymptomatic patients with histopathologically benign disease can be durably observed without negative sequelae.

Cryoprotectant toxicity in Caenorhabditis elegans.

We have looked at the effects of the cryoprotectant M22 upon viability in the model organism C. elegans. M22 is a well-known vitrification solution which has been successfully used in the laboratory to preserve organs destined for transplantation. M22 reduces survival of C. elegans in a concentration-dependent manner. M22 at concentrations of 10% (v/v) or higher inhibits progeny production and development. A few mutants in the ILS (insulin-like signaling) pathway of C. elegans are more resistant to the toxic effect of M22 compared to wild-type worms. Afatinib, an anti-cancer drug, protects against M22 toxicity. Afatinib by itself does not increase longevity.

Genetic suppression of cryoprotectant toxicity.

We report here a new, unbiased forward genetic method that uses transposon-mediated mutagenesis to enable the identification of mutations that confer cryoprotectant toxicity resistance (CTR). Our method is to select for resistance to the toxic effects of M22, a much-studied whole-organ vitrification solution. We report finding and characterizing six mutants that are resistant to M22. These mutants fall into six independent biochemical pathways not previously linked to cryoprotectant toxicity (CT). The genes associated with the mutations were Gm14005, Myh9, Nrg2, Pura, Fgd2, Pim1, Opa1, Hes1, Hsbp1, and Ywhag. The mechanisms of action of the mutations remain unknown, but two of the mutants involve MYC signaling, which was previously implicated in CT. Several of the mutants may up-regulate cellular stress defense pathways. Several of the M22-resistant mutants were also resistant to dimethyl sulfoxide (Me2SO), and many of the mutants showed significantly improved survival after freezing and thawing in 10% (v/v) Me2SO. This new approach to overcoming CT has many advantages over alternative methods such as transcriptomic profiling. Our method directly identifies specific genetic loci that unequivocally affect CT. More generally, our results provide the first direct evidence that CT can be reduced in mammalian cells by specific molecular interventions. Thus, this approach introduces remarkable new opportunities for pharmacological blockade of CT.

Reflectance-Based Vegetation Index Assessment of Four Plant Species Exposed to Lithium Chloride.

This study considers whether a relationship exists between response to lithium (Li) exposure and select vegetation indices (VI) determined from reflectance spectra in each of four plant species: Arabidopsis thaliana, Helianthus annuus (sunflower), Brassica napus (rape), and Zea mays (corn). Reflectance spectra were collected every week for three weeks using an ASD FieldSpec Pro spectroradiometer with both a contact probe (CP) and a field of view probe (FOV) for plants treated twice weekly in a laboratory setting with 0 mM (control) or 15 mM of lithium chloride (LiCl) solution. Plants were harvested each week after spectra collection for determination of relevant physical endpoints such as relative water content and chlorophyll content. Mixed effects analyses were conducted on selected endpoints and vegetation indices (VI) to determine the significance of the effects of treatment level and length of treatment as well as to determine which VI would be appropriate predictors of treatment-dependent endpoints. Of the species considered, A. thaliana exhibited the most significant effects and corresponding shifts in reflectance spectra. Depending on the species and endpoint, the most relevant VIs in this study were NDVI, PSND, YI, R1676/R1933, R750/R550, and R950/R750.