Association of mucus eosinophil-derived neurotoxin levels with disease control status in patients with chronic rhinosinusitis.

OBJECTIVE: Identifying the biomarkers for uncontrolled chronic rhinosinusitis (CRS) is important for directing treatment decisions. Eosinophilia has been reported to be involved in the poor disease control of CRS and mucus eosinophil-derived neurotoxin (EDN) is potentially a biomarker of intense eosinophil activation. This study aimed to assess the relationship between mucus EDN levels, disease severity, and degree of CRS control. METHODS: A total of 150 adult patients with CRS and 25 healthy controls were prospectively enrolled. The nasal mucus and tissue specimens were collected to analyze EDN levels. Disease severity was assessed by Lund-Mackay score and 22-item Sino-Nasal Outcome Test (SNOT-22) score. Five CRS symptom severities during the prior month (nasal blockage, rhinorrhoea/postnasal drip, facial pain/pressure, smell, sleep disturbance or fatigue), use of rescue medications in the last six months, and the presence of diseased mucosa on nasal endoscopy were obtained. Consistent with the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 CRS control criteria, uncontrolled CRS was defined as meeting at least three items. RESULTS: 40% of patients with CRS presented with uncontrolled status. Patients with uncontrolled CRS had significantly higher nasal mucus EDN levels (P = 0.010), percentage of blood eosinophil (P = 0.015), SNOT-22 score (P < 0.001), Lund-Mackay score (P = 0.008), and a more eosinophilic dominant phenotype of CRS (P < 0.001) than patients with controlled CRS. Furthermore, mucus EDN levels were positively correlated with blood eosinophils (r = 0.541, P = 0.005), SNOT-22 score (r = 0.460, P = 0.021), and Lund-Mackay score (r = 0.387, P = 0.039). Mucus EDN levels were the significant parameter related to uncontrolled CRS in multivariable analysis after adjusting for patient demographics and comorbidities (odds ratio = 1.323; P = 0.004). CONCLUSIONS: Mucus EDN levels may be a potential biomarker for identifying the CRS control status.

Cold exposure impairs extracellular vesicle swarm-mediated nasal antiviral immunity.

BACKGROUND: The human upper respiratory tract is the first site of contact for inhaled respiratory viruses and elaborates an array of innate immune responses. Seasonal variation in respiratory viral infections and the importance of ambient temperature in modulating immune responses to infections have been well recognized; however, the underlying biological mechanisms remain understudied. OBJECTIVE: We investigated the role of nasal epithelium-derived extracellular vesicles (EVs) in innate Toll-like receptor 3 (TLR3)-dependent antiviral immunity. METHODS: We evaluated the secretion and composition of nasal epithelial EVs after TLR3 stimulation in human autologous cells and fresh human nasal mucosal surgical specimens. We also explored the antiviral activity and mechanisms of TLR3-stimulated EVs against respiratory viruses as well as the effect of cool ambient temperature on TLR3-dependent antiviral immunity. RESULTS: We found that polyinosinic:polycytidylic acid, aka poly(I:C), exposure induced a swarm-like increase in the secretion of nasal epithelial EVs via the TLR3 signaling. EVs participated in TLR3-dependent antiviral immunity, protecting the host from viral infections through both EV-mediated functional delivery of miR-17 and direct virion neutralization after binding to virus ligands via surface receptors, including LDLR and ICAM-1. These potent antiviral immune defense functions mediated by TLR3-stimulated EVs were impaired by cold exposure via a decrease in total EV secretion as well as diminished microRNA packaging and antiviral binding affinity of individual EV. CONCLUSION: TLR3-dependent nasal epithelial EVs exhibit multiple innate antiviral mechanisms to suppress respiratory viral infections. Furthermore, our study provides a direct quantitative mechanistic explanation for seasonal variation in upper respiratory tract infection prevalence.

Topical Administration of Verapamil in Poly(ethylene glycol)-Modified Liposomes for Enhanced Sinonasal Tissue Residence in Chronic Rhinosinusitis: Ex Vivo and In Vivo Evaluations.

Verapamil is a calcium channel blocker that holds promise for the therapy of chronic rhinosinusitis (CRS) with and without nasal polyps. The verapamil-induced side effects limit its tolerated dose via the oral route, underscoring the usefulness of localized intranasal administration. However, the challenge to intranasal administration is mucociliary clearance, which diminishes localized dose availability. To overcome this challenge, verapamil was loaded into a mucoadhesive cationic poly(ethylene glycol)-modified (PEGylated) liposomal carrier. Organotypic nasal explants were exposed to verapamil liposomes under flow conditions to mimic mucociliary clearance. The liposomes resulted in significantly higher tissue residence compared with the free verapamil control. These findings were further confirmed in vivo in C57BL/6 mice following intranasal administration. Liposomes significantly increased the accumulation of verapamil in nasal tissues compared with the control group. The developed tissue-retentive verapamil liposomal formulation is considered a promising intranasal delivery system for CRS therapy.

CNS Delivery of Nucleic Acid Therapeutics: Beyond the Blood-Brain Barrier and Towards Specific Cellular Targeting.

Nucleic acid-based therapeutic molecules including small interfering RNA (siRNA), microRNA(miRNA), antisense oligonucleotides (ASOs), messenger RNA (mRNA), and DNA-based gene therapy have tremendous potential for treating diseases in the central nervous system (CNS). However, achieving clinically meaningful delivery to the brain and particularly to target cells and sub-cellular compartments is typically very challenging. Mediating cell-specific delivery in the CNS would be a crucial advance that mitigates off-target effects and toxicities. In this review, we describe these challenges and provide contemporary evidence of advances in cellular and sub-cellular delivery using a variety of delivery mechanisms and alternative routes of administration, including the nose-to-brain approach. Strategies to achieve subcellular localization, endosomal escape, cytosolic bioavailability, and nuclear transfer are also discussed. Ultimately, there are still many challenges to translating these experimental strategies into effective and clinically viable approaches for treating patients.

Mechanisms and pathogenesis of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and is historically divided into 2 main phenotypes: CRS with nasal polyps and CRS without nasal polyps. Inflammation in CRS is mainly characterized by 3 endotypes based on elevation of canonical lymphocyte cytokines: type (T) 1 (T1) by TH1 cytokine IFN-γ, T2 by TH2 cutokines IL-4, IL-5, and IL-13, and T3 by TH17 cytokines including IL-17. Inflammation in both CRS without nasal polyps and CRS with nasal polyps is highly heterogeneous, and the frequency of various endotypes varies geographically around the world. This finding complicates establishment of a unified understanding of the mechanisms of pathogenesis in CRS. Sinonasal epithelium acts as a passive barrier, and epithelial barrier dysfunction is a common feature in CRS induced by endotype-specific cytokines directly and indirectly. The sinonasal epithelium also participates in both innate immunity via recognition by innate pattern-recognition receptors and promotes and regulates adaptive immunity via release of chemokines and innate cytokines including thymic stromal lymphopoietin. The purpose of this review was to discuss the contribution of the epithelium to CRS pathogenesis and to update the field regarding endotypic heterogeneity and various mechanisms for understanding pathogenesis in CRS.

Cystatin SN is a potent upstream initiator of epithelial-derived type 2 inflammation in chronic rhinosinusitis.

BACKGROUND: Cystatin SN (CST1) and cystatin SA (CST2) are cysteine protease inhibitors that protect against allergen, viral, and bacterial proteases. Cystatins are overexpressed in the setting of allergic rhinitis and chronic rhinosinusitis with nasal polyps (CRSwNP); however, their role in promoting type 2 inflammation remains poorly characterized. OBJECTIVE: The purpose of this study was to use integrated poly-omics and a murine exposure model to explore the link between cystatin overexpression in CRSwNP and type 2 inflammation. METHODS: In this institutional review board- and institutional animal care and use committee-approved study, we compared tissue, exosome, and mucus CST1 and CST2 between CRSwNP and controls (n = 10 per group) by using matched whole exome sequencing, transcriptomic, proteomic, posttranslational modification, histologic, functional, and bioinformatic analyses. C57/BL6 mice were dosed with 3.9 µg/mL of CST1 or PBS intranasally for 5 to 18 days in the presence or absence of epithelial ABCB1a knockdown. Inflammatory cytokines were quantified by using Quansys multiplex assays or ELISAs. RESULTS: Of the 1305 proteins quantified, CST1 and CST2 were among the most overexpressed protease inhibitors in tissue, exosome, and mucus samples; they were localized to the epithelial layer. Multiple posttranslational modifications were identified in the polyp tissue. Exosomal CST1 and CST2 were strongly and significantly correlated with eosinophils and Lund-Mackay scores. Murine type 2 cytokine secretion and TH2 cell infiltration increased in a time-dependent manner following CST1 exposure and was abrogated by epithelial knockdown of ABCB1a, a regulator of epithelial cytokine secretion. CONCLUSION: CST1 is a potent upstream initiator of epithelial-derived type 2 inflammation in CRSwNP. Therapeutic strategies targeting CST activity and its associated posttranslational modifications deserve further interrogation.

Role of 3D Printing in the Development of Biodegradable Implants for Central Nervous System Drug Delivery.

Increased life expectancy has led to a rise in age-related disorders including neurological diseases such as Alzheimer's disease and Parkinson's disease. Limited progress has been made in the development of clinically translatable therapies for these central nervous system (CNS) diseases. Challenges including the blood-brain barrier, brain complexity, and comorbidities in the elderly population are some of the contributing factors toward lower success rates. Various invasive and noninvasive ways are being employed to deliver small and large molecules across the brain. Biodegradable, implantable drug-delivery systems have gained lot of interest due to advantages such as sustained and targeted delivery, lower side effects, and higher patient compliance. 3D printing is a novel additive manufacturing technique where various materials and printing techniques can be used to fabricate implants with the desired complexity in terms of mechanical properties, shapes, or release profiles. This review discusses an overview of various types of 3D-printing techniques and illustrative examples of the existing literature on 3D-printed systems for CNS drug delivery. Currently, there are various technical and regulatory impediments that need to be addressed for successful translation from the bench to the clinical stage. Overall, 3D printing is a transformative technology with great potential in advancing customizable drug treatment in a high-throughput manner.

Endoscopic surgery for intraconal orbital tumors.

Traditionally, external craniofacial approaches have been used for orbital tumor resection. Over the last 30 years, endoscopic sinonasal and skull base techniques have become widely used throughout the world. These experiences paved the way for the extension of transnasal endoscopic techniques to the intraconal orbit. Transnasal endoscopic intraconal surgery has several advantages regarding morbidity and outcome as compared with purely external approaches. However, the anatomical knowledge and experience of the surgeon is crucial for the success of the surgery. Endoscopic approaches for intraconal tumor removal are feasible for medial and inferior lesions as well as for lesions lateral to the optic nerve provided they remain inferior to the "plane of resectability" and no optic nerve retraction is required. As intraorbital tumors are rare, new international staging systems including CHEER (Cavernous Hemangioma Exclusively Endonasal Resection) and ORBIT (Orbital Resection by Intranasal Technique) help to standardize safety, efficacy, and outcome.

In vivo analysis of endocanalicular light pipe transillumination in endoscopic dacryocystorhinostomy: Anatomic considerations and cautions for the transitioning.

PURPOSE: Localization of the lacrimal sac is a critical step during endoscopic dacryocystorhinostomy (endo-DCR). A "light pipe" can be used to transilluminate the lacrimal sac endonasally. We hypothesized that this may misguide the surgeon learning endo-DCR to create an osteotomy mostly posterior to the maxillary line if only the bone overlying the transillumination was to be removed, as the thinner lacrimal bone will transmit light more readily than the thicker maxillary bone of the frontal process of the maxilla that forms the anterior lacrimal sac fossa. METHODS: The charts of 32 patients with primary acquired nasolacrimal duct obstruction in whom a lighted system was used during endo-DCR at Massachusetts Eye and Ear from April 2015 through October 2016 were reviewed. Patients with prior history of lacrimal surgery or trauma directly to the lacrimal sac fossa were excluded. Location of the maximal point of transillumination in relation to the maxillary line was observed and noted intraoperatively. RESULTS: Of a total of 39 endo-DCR surgeries performed, the intraoperative transillumination point was entirely posterior to the maxillary line in 32 instances (82%). CONCLUSIONS: Use of an endocanalicular light pipe preferentially illuminates posterior to the maxillary line endonasally. The anterior lacrimal sac fossa (maxillary line and anterior as visualized endonasally) is rarely transilluminated, likely due to thicker bone in that region. Surgeons learning how to perform endo-DCR using a light pipe should be aware of this phenomenon.

Endoscopic endonasal resection of orbital schwannoma assisted with small-incision medial orbitotomy: case series and surgical technique.

PURPOSE: To describe a surgical approach for the resection of schwannomas occurring in the medial aspect of the orbit and to review a series of patients who underwent this novel technique. METHODS: This retrospective, non-comparative case series presents the surgical technique and outcomes of patients who underwent removal of a medial orbital schwannoma via an endoscopic endonasal approach combined with a small-incision medial orbitotomy by a team of two surgeons (BSB and SKF). Patient demographics, pre- and post-operative clinical examination findings, visual field testing, and radiographic studies were reviewed. Operative reports were reviewed for technical details and complications. RESULTS: The patients included a 12 year-old male, 73 year-old female and 8 year-old male. Indications for surgery included: decreased visual acuity, diplopia, proptosis and Humphrey visual field (HVF) deficit, in the presence of a medial orbital biopsy-proven schwannoma. The surgical approach in all three patients was primarily endoscopic endonasal. Additionally, two had transcaruncular orbitotomies and one had a small-incision medial lid crease orbitotomy to assist with lateral tumor dissection. Tumor resection was complete in one case and near-total in two cases. There were no intra-operative surgical complications. Average resected specimen volume was 3.41 cm3 ± 2.20. All patients had post-operative improvement in visual acuity (VA) and proptosis. Post-operative follow-up intervals were 27.5 months, 12.3 months and 3.5 months, respectively. CONCLUSION: Resection of orbital schwannomas using an endoscopic endonasal approach with small-incision medial transorbital assistance is a safe and effective option for a multidisciplinary surgical team.

Superior turbinate eosinophilia predicts olfactory decline in patients with chronic rhinosinusitis.

BACKGROUND: Predicting postoperative olfactory decline in patients with chronic rhinosinusitis (CRS) remains a considerable challenge. OBJECTIVE: To evaluate patterns of postoperative olfactory function in patients with CRS and explore potential predictors of postoperative olfactory decline. METHODS: A total of 76 patients with CRS electing endoscopic sinus surgery (ESS) were enrolled in this prospective study. Olfaction was assessed with Sniffin' Sticks preoperatively and 3 months postoperatively. Preoperative peripheral venous blood and superior turbinate at surgery were collected for eosinophil quantification. Olfactory cleft was evaluated by computed tomography and endoscopy. Postoperative olfactory decline was defined by a decrease in threshold-discrimination-identification (TDI) score more than 0 point. Multivariable logistic regression analysis was conducted to identify potential predictors associated with postoperative olfactory decline in TDI score. RESULTS: A total of 30.26% of patients with CRS (23/76) presented with olfactory decline 3 months post-ESS. Patients with CRS with olfactory decline showed significantly higher preoperative tissue eosinophils (P < .001), blood eosinophil count (P = .002), blood eosinophil percentage (P = .009), and preoperative TDI scores (P = .017) than patients with CRS without olfactory decline. After adjusting for patient demographics and comorbidities, the preoperative tissue eosinophilia was significantly associated with patients with CRS with postoperative olfactory decline (odds ratio = 1.103; P = .038). An absolute count of 23.5 eosinophils per high-power field in superior turbinate was the best predictor of olfactory decline with the highest area under the receiver operating characteristic curve of 0.901. CONCLUSION: Superior turbinate eosinophilia is highly associated with olfactory decline in patients with CRS 3 months after ESS.

Exosome swarms eliminate airway pathogens and provide passive epithelial immunoprotection through nitric oxide.

BACKGROUND: Nasal mucosa-derived exosomes (NMDEs) harbor immunodefensive proteins and are capable of rapid interepithelial protein transfer. OBJECTIVES: We sought to determine whether mucosal exposure to inhaled pathogens stimulates a defensive swarm of microbiocidal exosomes, which also donate their antimicrobial cargo to adjacent epithelial cells. METHODS: We performed an institutional review board-approved study of healthy NMDE secretion after Toll-like receptor (TLR) 4 stimulation by LPS (12.5 µg/mL) in the presence of TLR4 inhibitors. Interepithelial transfer of exosomal nitric oxide (NO) synthase and nitric oxide was measured by using ELISAs and NO activity assays. Exosomal antimicrobial assays were performed with Pseudomonas aeruginosa. Proteomic analyses were performed by using SOMAscan. RESULTS: In vivo and in vitro LPS exposure induced a 2-fold increase in NMDE secretion along with a 2-fold increase in exosomal inducible nitric oxide synthase expression and function through TLR4 and inhibitor of nuclear factor κB kinase activation. LPS stimulation increased exosomal microbiocidal activity against P aeruginosa by almost 2 orders of magnitude. LPS-stimulated exosomes induced a 4-fold increase in NO production within autologous epithelial cells with protein transfer within 5 minutes of contact. Pathway analysis of the NMDE proteome revealed 44 additional proteins associated with NO signaling and innate immune function. CONCLUSIONS: We provide direct in vivo evidence for a novel exosome-mediated innate immunosurveillance and defense mechanism of the human upper airway. These findings have implications for lower airway innate immunity, delivery of airway therapeutics, and host microbiome regulation.

Revision eDCR using a superior pedicled mucosal flap.

BACKGROUND: Endoscopic dacryocystorhinostomies (eDCRs) show patency rates between 81% and 94%. However, dacryocystorhinostomy (DCR) failure and the need for revision remain a significant challenge. One of the principal challenges in revision eDCR is the need to surgically identify the correct osteotomy site and maintain long-term patency in the setting of previously instrumented and potentially scarred tissue. At the same time, the surgeon must assume that the blood supply to the commonly described anterior and posteriorly pedicled flaps has been compromised. OBJECTIVE: The objective of the study is to describe a novel flap technique for revision eDCR. METHODS: The superior based mucosal flap is a novel technique that provides a vascularized mucosa preserving technique in revision eDCR despite previous instrumentation of the lacrimal system. This technique provides wide exposure of the revision osteotomy site while simultaneously allowing a viable mucosal flap to be replaced at the conclusion of the procedure, thereby minimizing bone exposure and cicatricial restenosis. RESULTS: The authors have utilized this technique in 13 procedures with 100% positive identification of the lacrimal sac, a 0% complication rate, and a 100% success rate after a mean follow-up of 26.93 ± 10.33 months (range 6-35 months). CONCLUSION: The eDCR using the superior pedicled mucosal flap provides excellent exposure of the maxillary bone and the lacrimal sac. This method preserves vascularity of the flap using a superiorly based pedicle which is typically inviolate during both open and endoscopic primary DCR. The mucosal flap can then be replaced, thereby minimizing bone exposure and optimizing patency.

Oxidative Post-translational Modifications Accelerate Proteolytic Degradation of Calprotectin.

Oxidative post-translational modifications affect the structure and function of many biomolecules. Herein we examine the biophysical and functional consequences of oxidative post-translational modifications to human calprotectin (CP, S100A8/S100A9 oligomer, MRP8/MRP14 oligomer, calgranulins A/B oligomer). This abundant metal-sequestering protein contributes to innate immunity by starving invading microbial pathogens of transition metal nutrients in the extracellular space. It also participates in the inflammatory response. Despite many decades of study, little is known about the fate of CP at sites of infection and inflammation. We present compelling evidence for methionine oxidation of CP in vivo, supported by using 15N-labeled CP-Ser (S100A8(C42S)/S100A9(C3S)) to monitor for adventitious oxidation following human sample collection. To elucidate the biochemical and functional consequences of oxidative post-translational modifications, we examine recombinant CP-Ser with methionine sulfoxide modifications generated by exposing the protein to hydrogen peroxide. These oxidized species coordinate transition metal ions and exert antibacterial activity. Nevertheless, oxidation of M81 in the S100A9 subunit disrupts Ca(II)-induced tetramerization and, in the absence of a transition metal ion bound at the His6 site, accelerates proteolytic degradation of CP. We demonstrate that native CP, which contains one Cys residue in each full-length subunit, forms disulfide bonds within and between S100A8/S100A9 heterodimers when exposed to hydrogen peroxide. Remarkably, disulfide bond formation accelerates proteolytic degradation of CP. We propose a new extension to the working model for extracellular CP where post-translational oxidation by reactive oxygen species generated during the neutrophil oxidative burst modulates its lifetime in the extracellular space.

Exosome function in aerodigestive mucosa.

Exosomes are 30-150 nm membrane-bound vesicles which are secreted by virtually all cell types. Exosomes have been studied in a wide range of both normal and pathologic human tissues, most notably cancer. The role of exosomes in immune surveillance and in non-invasive biomarker sampling, and their potential to act as therapeutic carriers lend particular importance to mucosal barrier derived exosomes. This review focuses specifically on current knowledge regarding exosomes derived from aerodigestive membranes. Specific topics covered include: isolation and characterization techniques, physiological function, protein expression, function as biomarkers of disease, and potential therapeutic uses.

Temporary olfactory improvement in chronic rhinosinusitis with nasal polyps after treatment.

PURPOSE: Olfactory dysfunction in chronic rhinosinusitis with nasal polyps (CRSwNP) is a severe type of inflammatory olfactory disorders which greatly impair quality of life. The aim of this review is to summarize the current literature and to provide a comprehensive guide to the key metrics of the olfactory dysfunction, evaluations, treatment responses, and pathophysiological mechanisms in CRSwNP patients with olfactory dysfunction. METHODS: A review of the literature for olfaction in CRSwNP was conducted. The key terms ("chronic rhinosinusitis", "nasal polyps", and "olfaction") were used to search relevant articles in Pubmed. RESULTS: Inflammation within the olfactory cleft is a well-recognized cause of the olfactory loss in patients with CRSwNP. Although the current treatment could significantly improve the olfactory function, olfaction in patients with CRSwNP tends to deteriorate after temporary improvement. Recent research has focused on the change of olfactory cleft and its association with the olfactory function which shed light on the mechanisms of both conductive and sensorineural olfactory dysfunctions in patients with CRSwNP. The state of the olfaction in patients with CRSwNP is directly associated with the degree of inflammation control and disturbed normal turnover of the olfactory sensory neurons induced by chronic inflammation, especially the eosinophilic inflammation contributes to the olfactory dysfunction. Refractory factors contributing to the olfactory deterioration are the promising therapeutic target to maintain the olfactory function in patients with CRSwNP. CONCLUSIONS: The current evidence supports temporary olfactory improvement in CRSwNP patients which accords with the refractory nature of CRSwNP. Future treatment should aim to the continuous elimination of inflammation and promote the normal turnover of the olfactory epithelium.

Morphometric Analysis of the Orbital Process of the Palatine Bone and its Relationship to Endoscopic Orbital Apex Surgery.

BACKGROUND: Endoscopic approaches to the orbit improve the ability to directly access apical lesions while minimizing manipulation of normal structures. Inferomedial orbital access is limited by the orbital process of the palatine bone (OPPB) which prevents dissection and retraction in the inferolateral vector. OBJECTIVE: The objective of this study was to examine the morphometric characteristics of the OPPB and quantify the benefit of complete resection to surgical access. METHODS: Morphometric osteologic measurements of the OPPB were performed in 59 human skulls. A radius subtended by the OPPB was calculated to generate a hemispheric dissection corridor achievable by complete resection of the OPPB. Cadaveric and live surgical dissections were then performed on 15 orbits to develop discreet endoscopic surgical landmarks which could be used to both identify the OPPB and verify complete resection. RESULTS: The mean(± SD) radius of the OPPB was 0.47 ± 0.28 cm. Complete OPPB resection provided an additional 0.36 ± 0.42 cm of surgical exposure within the inferomedial apex. Relative to the Caucasian (n = 27) skulls, the radii in the Asian (n = 27) and African (n = 5) skulls were significantly smaller (p < 0.001 and p = 0.02, respectively). CONCLUSION: The OPPB significantly limits surgical access to the inferomedial orbital apex during endoscopic approaches. Complete surgical resection of the OPPB improves surgical exposure facilitating retraction of the inferior rectus muscle and circumferential dissection of lesions within this space. Knowledge of the morphology and clinical relevance of this structure provides an opportunity to improve surgical exposure for relevant pathologic assessment and optimize endoscopic surgical outcomes.

Purely endoscopic trans-nasal management of orbital intraconal cavernous haemangiomas: a systematic review of the literature.

The surgical management of medial and inferior orbital lesions is demanding via traditional external approach, since the conic-shaped surgical field is narrow and damage to neural, muscular or vascular structures of the orbit can have serious consequences. In recent years, the evolution of endoscopic endonasal approaches for lesions that goes beyond the nose brought the orbit to the attention of rhinosurgeons. If procedures such as transnasal orbital decompression and lacrimal pathways surgery have been described some decades ago, the last frontier of transnasal orbital surgery, namely intraconal tumor surgery, is a new and rapidly expanding field. Papers describing endoscopic endonasal approaches to the orbit appeared in the international literature, but most of them contain a small number of cases, also because the relatively rarity of intraorbital lesions. We herein report the results of a systematic review of the literature regarding the endoscopic endonasal approach to intraconal cavernous haemangiomas, the most common benign orbital lesion. The endoscopic management of intraconal cavernous haemangiomas results feasible and safe. A critical step of this kind of surgery is the management of the medial rectus muscle, mandatory to expose the intraconal space.

Pseudomonas Aeruginosa: A Masquerader in Sino-Orbital Infections.

PURPOSE: To report 2 immunocompromised patients with sino-orbital necrotizing pseudomonas infections and review the literature. METHODS: This is a noncomparative, retrospective case series, and review. The clinical data of 2 patients with histopathologic and microbiologic diagnoses of pseudomonas sinus infections causing orbital cellulitis were obtained from medical records. A retrospective literature review was performed on all reported cases of periorbital pseudomonas infections. RESULTS: One patient with acquired immune deficiency syndrome was noted to have orbital cellulitis with clear visualization of eschar in the middle turbinate on nasal endoscopy. A second patient also had orbital cellulitis with ophthalmoplegia and presence of eschar in the sinus. Both patients had some degree of erosion through the lamina papyracea found on orbital imaging and both had intact vision without optic neuropathy. Pseudomonas infection was confirmed in both cases with permanent histopathology and cultures from conservative sinus debridement. CONCLUSIONS: Pseudomonas sino-orbital infections must be considered in the differential diagnosis in cases of eschar and orbital wall erosion especially when vision is preserved in immunocompromised individuals. This finding obviates the need for radical debridement including orbital exenteration, which can be indicated in cases of invasive fungal disease.