Efficacy of adjuvant mitomycin-C and triamcinolone-impregnated nasal packing for endoscopic dacryocystorhinostomy.

AIM: To compare the success rate and complications of adjuvant use of mitomycin C and triamcinolone-impregnated biodegradable nasal packing (TABP) in endoscopic dacryocystorhinostomy (DCR). And to evaluate the efficacy of combining intraoperative mitomycin C and TABP for endoscopic DCR. METHODS: A total of 198 eyes of 148 patients who underwent endoscopic DCR for acquired nasolacrimal duct obstruction were retrospectively analysed. The patients were randomly divided into three groups: Group A included patients treated without intraoperative mitomycin C but with TABP, Group B included patients treated without triamcinolone but with intraoperative mitomycin C and normal saline-impregnated nasal packing, and Group C included patients treated with intraoperative mitomycin C and TABP. RESULTS: The results revealed no significant difference in the overall success rates between Groups A (86.8%) and B (89.2%; P=0.377). However, Group C (97.5%) showed a significantly higher overall success rate than Groups A and B. The incidence of granulomas was significantly lower in group C (5%) than in Groups A (20.8%) and B (15.2%; P=0.009). Other complications, such as crust, synechiae, and revision surgery, did not differ significantly among the three groups. CONCLUSION: The combination of intraoperative mitomycin C and TABP effectively prevents granulomas and enhances surgical success rate. Additionally, there is no statistically significant difference observed between the use of mitomycin C or TABP alone.

A mass spectrometry assay for detection of endogenous and lentiviral engineered hemoglobin in cultured cells and sickle cell disease mice.

Sickle cell disease (SCD) results from a sequence defect in the ß-globin chain of adult hemoglobin (HbA) leading to expression of sickle hemoglobin (HbS). It is traditionally diagnosed by cellulose-acetate hemoglobin electrophoresis or high-performance liquid chromatography. While clinically useful, these methods have both sensitivity and specificity limitations. We developed a novel mass spectrometry (MS) method for the rapid, sensitive and highly quantitative detection of endogenous human ß-globin and sickle hß-globin, as well as lentiviral-encoded therapeutic hßAS3-globin in cultured cells and small quantities of mouse peripheral blood. The MS methods were used to phenotype homozygous HbA (AA), heterozygous HbA-HbS (AS) and homozygous HbS (SS) Townes SCD mice and detect lentiviral vector-encoded hßAS3-globin in transduced mouse erythroid cell cultures and transduced human CD34+ cells after erythroid differentiation. hßAS3-globin was also detected in peripheral blood 6 weeks post-transplant of transduced Townes SS bone marrow cells into syngeneic Townes SS mice and persisted for over 20 weeks post-transplant. As several genome-editing and gene therapy approaches for severe hemoglobin disorders are currently in clinical trials, this MS method will be useful for patient assessment before treatment and during follow-up.

Threading the Needle: A Case of Periorbital Gold Threading.

While a rare periorbital finding, the aesthetic practice of gold threading is increasingly identified in Western care setting and may be misidentified as the practice of inserting charm needles (susuk). The authors present a unique case of gold threading discovered incidentally during workup of chronic sinusitis and report a rarely seen delayed local site reaction. The practice of gold threading and mimickers including the practice of inserting charm needles (susuk) are reviewed with emphasis on clinical and radiographic differentiation by oculoplastic surgeons.

Orbital resection by intranasal technique (ORBIT): A new classification system for reporting endoscopically resectable primary benign orbital tumors.

BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs. METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class. RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05). CONCLUSION: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs.

Orbital Fractures.

Orbital fractures are common in facial trauma and can be a challenge to treat. Understanding anatomy of the orbit, the clinical evaluation, indications for surgery, surgical approaches, complications, and postoperative are essential in providing appropriate treatment for patients who have sustained orbital fractures. In this article, the authors review the diagnostic evaluation, acute management, treatment options, and common complications of orbital fractures, as well as recent advancements in orbital fracture repairs.

Factors Associated with Ocular Injury in Orbital Fracture Patients: Who Requires Urgent Ophthalmic Evaluation?

Importance: Create validated criteria to identify orbital fracture patients at higher risk for significant ocular injuries. Objective: Determine history and physical examination findings in orbital fracture patients who are associated with ocular injury and warrant urgent assessment by an ophthalmologist. Design, Setting, and Participants: Retrospective chart review of 535 adult orbital fracture patients evaluated at a Level I emergency department between 2014 and 2017, without prior history of orbital fracture, ocular injury, or ocular/orbital surgery. Main Outcomes and Measure: Presence of ocular injury. Results: In total, 195 (36%) patients had an ocular injury. Those with and without ocular injury were compared in a multivariate logistic regression model including demographics, fracture characteristics, injury mechanism, and physical examination findings. Visual acuity change, radiographic retrobulbar hemorrhage, abnormal pupillary reaction, and inability to open the injured eye all had significant associations with ocular injury when other findings were controlled. Conclusion: This study shows a significant association between ocular injury and visual acuity change, retrobulbar hemorrhage, abnormal pupillary reaction, and inability to open the injured eye. These factors can help triage when to obtain an urgent ophthalmology consult.

Elevated levels of Merkel cell polyoma virus in the anophthalmic conjunctiva.

The human ocular surface hosts a paucibacterial resident microbiome and virome. The factors contributing to homeostasis of this mucosal community are presently unknown. To determine the impact of ocular enucleation and prosthesis placement on the ocular surface microbiome, we sampled conjunctival swabs from 20 anophthalmic and 20 fellow-eye intact conjunctiva. DNA was extracted and subjected to quantitative 16S rDNA PCR, biome representational karyotyping (BRiSK), and quantitative PCR (qPCR) confirmation of specific organisms. 16S ribosomal qPCR revealed equivalent bacterial loads between conditions. Biome representational in silico karyotyping (BRiSK) demonstrated comparable bacterial fauna between anophthalmic and intact conjunctiva. Both torque teno virus and Merkel cell polyoma virus (MCPyV) were detected frequently in healthy and anophthalmic conjunctiva. By qPCR, MCPyV was detected in 19/20 anophthalmic samples compared with 5/20 fellow eyes. MCPyV copy number averaged 891 copies/ng in anophthalmic conjunctiva compared with 193 copies/ng in fellow eyes (p < 0.001). These results suggest that enucleation and prosthesis placement affect the ocular surface flora, particularly for the resident virome. As MCPyV has been shown to be the etiologic cause of Merkel cell carcinoma, understanding the mechanisms by which the ocular surface regulates this virus may have clinical importance.

Diseases of the Eyelids and Orbit.

The eyelids and orbit encompass intricate bony and soft tissue structures that work harmoniously in concert to protect, support, and nourish the eye in order to facilitate and maintain its function. Insult to periorbital and orbital anatomy can compromise orbital and ocular homeostasis. This article provides a foundational overview of eyelid and orbital anatomy, as well as common and key disorders that may confront internists and medical subspecialists.

Ophthalmic changes in patients with hemifacial atrophy (Parry-Romberg syndrome).

PURPOSE: Parry-Romberg syndrome (PRS) is a rare condition characterized by progressive, unilateral facial atrophy. We hypothesize that patients with this condition may have involvement of the ocular structures. Here, we report our ophthalmic, clinical and anatomical findings in an observational study of six patients with long-standing PRS. METHODS: Patients diagnosed with PRS were invited to participate in a clinic visit during which the following tests were administered and data recorded: best-corrected vision, refractive error, Ishihara color plates, Hertel exophthalmometry, gonioscopy, complete slit-lamp and dilated fundus examination, Intra Ocular Lens Master measurements and keratometry. Two-sample T tests were used to compare data between affected and unaffected eyes, as well as affected eyes and a normative population. RESULTS: Six patients underwent complete eye examinations. The mean spherical equivalent of the affected eye was + 3.83 D, while that of the unaffected eye was + 0.13 D. The atrophic hemiface averaged 2.8 mm of enophthalmos on Hertel exophthalmometry. The axial length of the atrophic eye was 0.91 mm shorter than the unaffected eye. Compared to normative data, in patients with PRS, the difference between eyes was statistically different for each of the following variables: visual acuity, spherical equivalent, corneal diameter, axial length and flat and steep keratometry. CONCLUSIONS: This is one of the first quantitative, exploratory studies with ophthalmic measurements in patients with PRS. Our results suggest the globe may demonstrate atrophic changes similar to other soft tissues in the face known to be affected by this condition.

Renal cell tumors convert natural killer cells to a proangiogenic phenotype.

Natural killer (NK) cells are classically associated with immune surveillance and destruction of tumor cells. Inconsistent with this function, NK cells are found in advanced human tumors including renal cell carcinoma (RCC). NK cells with non-classical phenotypes (CD56+CD16dim/neg; termed decidua NK (dNK) cells) accumulate at the maternal-fetal interface during embryo implantation. These dNK cells are poorly cytotoxic, proangiogenic, and facilitate placenta development. As similarities between embryo implantation and tumor growth exist, we tested the hypothesis that an analogous shift in NK cell phenotype and function occurs in RCC tumors. Our results show that peripheral NK (pNK) cells of RCC patients were uniformly CD56+CD16bright, but lacked full cytotoxic ability. By comparison, RCC tumor-infiltrated NK (TiNK) cells were significantly enriched for CD56+CD16dim-neg cells, a phenotype of dNK cells. Gene expression analysis revealed that angiogenic and inflammatory genes were significantly increased for RCC TiNK versus RCC pNK populations, with enrichment of genes in the hypoxia inducible factor (HIF) 1α pathway. Consistent with this finding, NK cells cultured under hypoxia demonstrated limited cytotoxicity capacity, but augmented production of vascular endothelial growth factor (VEGF). Finally, comparison of gene expression data for RCC TiNK and dNK cells revealed a shared transcriptional signature of genes with known roles in angiogenesis and immunosuppression. These studies confirm conversion of pNK cells to a dNK-like phenotype in RCC tumors. These characteristics are conceivably beneficial for placentation, but likely exploited to support early tumor growth and promote metastasis.

Comparative analysis of lentiviral gene transfer approaches designed to promote fetal hemoglobin production for the treatment of ß-hemoglobinopathies.

ß-Hemoglobinopathies are among the most common single-gene disorders and are caused by different mutations in the ß-globin gene. Recent curative therapeutic approaches for these disorders utilize lentiviral vectors (LVs) to introduce a functional copy of the ß-globin gene into the patient's hematopoietic stem cells. Alternatively, fetal hemoglobin (HbF) can reduce or even prevent the symptoms of disease when expressed in adults. Thus, induction of HbF by means of LVs and other molecular approaches has become an alternative treatment of ß-hemoglobinopathies. Here, we performed a head-to-head comparative analysis of HbF-inducing LVs encoding for: 1) IGF2BP1, 2) miRNA-embedded shRNA (shmiR) sequences specific for the γ-globin repressor protein BCL11A, and 3) γ-globin gene. Furthermore, two novel baboon envelope proteins (BaEV)-LVs were compared to the commonly used vesicular-stomatitis-virus glycoprotein (VSV-G)-LVs. Therapeutic levels of HbF were achieved for all VSV-G-LV approaches, from a therapeutic level of 20% using γ-globin LVs to 50% for both IGF2BP1 and BCL11A-shmiR LVs. Contrarily, BaEV-LVs conferred lower HbF expression with a peak level of 13%, however, this could still ameliorate symptoms of disease. From this thorough comparative analysis of independent HbF-inducing LV strategies, we conclude that HbF-inducing VSV-G-LVs represent a promising alternative to ß-globin gene addition for patients with ß-hemoglobinopathies.

Quantifying Eye Alignment in Orbital Fracture Patients: The Digital Hess Screen.

Background: Quantifying diplopia to determine management and track outcomes for orbital fracture patients is vital for standardization between visits, physicians, and coordination among the multiple specialties that manage these patients. However, standardization is challenging, as diplopia is often reported subjectively. This study sought to describe the utility of the digital Hess screen in patients with orbital fractures compared with a control group. Materials and Methods: A prospective pilot study was designed in which adult patients who presented with orbital fractures between November 2017 and January 2019 without prior history of orbital pathology were recruited. Subjects underwent digital Hess screen testing, in which they wore anaglyph glasses and aligned targets on a computer screen to quantify static eye alignment. The degree of any eye misalignment was analyzed and compared with controls. Results: Ninety-one patients and 35 controls were enrolled. All participants were able to complete the digital Hess screen. Average cumulative deviation score of orbital fracture patients within 1 month of injury was 0.65°, compared with 0.28° in controls. This was a statistically significant difference (p < 0.01, 95% confidence interval -0.18 to 0.18). Conclusion: The Hess screen has been used to quantify phoria as a correlate of eye alignment and diplopia, but older versions were cumbersome and difficult to analyze. This study is the first to report on using the digital Hess screen to quantify phoria in orbital fracture patients and provides a more concise and standardized means to track clinical and surgical outcomes of eye alignment.

The mRNA-Binding Protein IGF2BP1 Restores Fetal Hemoglobin in Cultured Erythroid Cells from Patients with ß-Hemoglobin Disorders.

Sickle cell disease (SCD) and ß-thalassemia are caused by structural abnormality or inadequate production of adult hemoglobin (HbA, α2ß2), respectively. Individuals with either disorder are asymptomatic before birth because fetal hemoglobin (HbF, α2γ2) is unaffected. Thus, reversal of the switch from HbF to HbA could reduce or even prevent symptoms these disorders. In this study, we show that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is one factor that could accomplish this goal. IGF2BP1 is a fetal factor that undergoes a transcriptional switch consistent with the transition from HbF to HbA. Lentivirus delivery of IGF2BP1 to CD34+ cells of healthy adult donors reversed hemoglobin production toward the fetal type in culture-differentiated erythroid cells. Analogous studies using patient-derived CD34+ cells revealed that IGF2BP1-dependent HbF induction could ameliorate the chain imbalance in ß-thalassemia or potently suppress expression of sickle ß-globin in SCD. In all cases, fetal γ-globin mRNA increased and adult ß-globin decreased due, in part, to formation of contacts between the locus control region (LCR) and γ-globin genes. We conclude that expression of IGF2BP1 in adult erythroid cells has the potential to maximize HbF expression in patients with severe ß-hemoglobin disorders by reversing the developmental γ- to ß-globin switch.

Current treatment and management of infantile hemangiomas.

Infantile hemangiomas, otherwise known as infantile capillary hemangiomas, strawberry hemangiomas, or strawberry nevi, are nonmalignant vascular tumors that commonly affect children. The natural disease course typically involves growth for up to a year, followed by regression without treatment over a period of years with no cosmetic or functional sequelae. Less commonly, however, infantile hemangiomas can become a threat to vision or even life depending on location and size of the lesion. In addition, infantile hemangiomas, particularly those involving the face, may be disfiguring and result in lifelong sequelae. ß-blockers have become a mainstay of therapy given their relatively low-risk profile and efficacy. Other treatment modalities previously described in the literature include corticosteroids (both intralesional and systemic), imiquimod, vincristine, bleomycin A5, and interferon α. More recently, angiotensin-converting enzyme inhibitors such as captopril have been used. Laser therapy and, less commonly, surgical excision are also available treatment options. We review current recommended management and treatment of capillary hemangiomas and discuss the benefits and risks of all previously reported treatment modalities.

Orbital peripheral nerve sheath tumors.

Peripheral nerve sheath tumors of the orbit and ocular adnexa are a rare group of neoplasms hallmarked by nonspecific clinical presentations, variable tumor locations, challenging therapeutic efforts, and occasional diagnostic dilemmas. We review these tumor types and provide an updated summary on their clinical, histopathologic, radiological, and emerging molecular features.

Periorbital Scar Correction.

Periorbital scarring with eyelid retraction can have serious visual effects and can lead to loss of vision or even loss of the eye. Understanding of eyelid anatomy and the delicate balance of its structural supports is critical for the identification of the eyelid disorder responsible for the cicatrix and helps to guide treatment. The 2-finger test and lateral distraction of the lid can also be of significant help in proper diagnosis of the underlying disorder. Proper reconstruction with respect to the anterior and posterior lamellae helps to ensure a favorable outcome.

Data in support of transcriptional regulation and function of Fas-antisense long noncoding RNA during human erythropoiesis.

This paper describes data related to a research article titled, "Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death" [1]. Long noncoding RNAs (lncRNAs) are increasingly appreciated for their capacity to regulate many steps of gene expression. While recent studies suggest that many lncRNAs are functional, the scope of their actions throughout human biology is largely undefined including human red blood cell development (erythropoiesis). Here we include expression data for 82 lncRNAs during early, intermediate and late stages of human erythropoiesis using a commercial qPCR Array. From these data, we identified lncRNA Fas-antisense 1 (Fas-AS1 or Saf) described in the research article. Also included are 5' untranslated sequences (UTR) for lncRNA Saf with transcription factor target sequences identified. Quantitative RT-PCR data demonstrate relative levels of critical erythroid transcription factors, GATA-1 and KLF1, in K562 human erythroleukemia cells and maturing erythroblasts derived from human CD34(+) cells. End point and quantitative RT-PCR data for cDNA prepared using random hexamers versus oligo(dT)18 revealed that lncRNA Saf is not effectively polyadenylated. Finally, we include flow cytometry histograms demonstrating Fas levels on maturing erythroblasts derived from human CD34(+) cells transduced using mock conditions or with lentivirus particles encoding for Saf.

Fas-antisense long noncoding RNA is differentially expressed during maturation of human erythrocytes and confers resistance to Fas-mediated cell death.

Long noncoding RNAs (lncRNAs) interact with other RNAs, DNA and/or proteins to regulate gene expression during development. Erythropoiesis is one developmental process that is tightly controlled throughout life to ensure accurate red blood cell production and oxygen transport to tissues. Thus, homeostasis is critical and maintained by competitive outcomes of pro- and anti-apoptotic pathways. LncRNAs are expressed during blood development; however, specific functions are largely undefined. Here, a culture model of human erythropoiesis revealed that lncRNA Fas-antisense 1 (Fas-AS1 or Saf) was induced during differentiation through the activity of essential erythroid transcription factors GATA-1 and KLF1. Saf was also negatively regulated by NF-κB, where decreasing NF-κB activity levels tracked with increasing transcription of Saf. Furthermore, Saf over-expression in erythroblasts derived from CD34(+) hematopoietic stem/progenitor cells of healthy donors reduced surface levels of Fas and conferred protection against Fas-mediated cell death signals. These studies reveal a novel lncRNA-regulated mechanism that modulates a critical cell death program during human erythropoiesis.

Long noncoding RNA Saf and splicing factor 45 increase soluble Fas and resistance to apoptosis.

In multicellular organisms, cell growth and differentiation is controlled in part by programmed cell death or apoptosis. One major apoptotic pathway is triggered by Fas receptor (Fas)-Fas ligand (FasL) interaction. Neoplastic cells are frequently resistant to Fas-mediated apoptosis, evade Fas signals through down regulation of Fas and produce soluble Fas proteins that bind FasL thereby blocking apoptosis. Soluble Fas (sFas) is an alternative splice product of Fas pre-mRNA, commonly created by exclusion of transmembrane spanning sequences encoded within exon 6 (FasΔEx6). Long non-coding RNAs (lncRNAs) interact with other RNAs, DNA, and proteins to regulate gene expression. One lncRNA, Fas-antisense or Saf, was shown to participate in alternative splicing of Fas pre-mRNA through unknown mechanisms. We show that Saf is localized in the nucleus where it interacts with Fas receptor pre-mRNA and human splicing factor 45 (SPF45) to facilitate alternative splicing and exclusion of exon 6. The product is a soluble Fas protein that protects cells against FasL-induced apoptosis. Collectively, these studies reveal a novel mechanism to modulate this critical cell death program by an lncRNA and its protein partner.