Orbital subperiosteal abscess in adolescents and adults: predictors and outcomes of nonsurgical management and surgical approaches.

PURPOSE: The aim of this study was to assess predictors and outcomes of subperiosteal abscess (SPA) management in adolescents and adults at two tertiary care centers. METHODS: This retrospective cohort study included cases of SPA from January 1 2000 to October 9 2022 at two institutions. Patients 9 years or older were categorized into surgical and nonsurgical cohorts. Surgical subgroups included those who underwent functional endoscopic sinus surgery (FESS) alone, external (transcutaneous or transconjunctival) orbitotomy alone, or combined FESS and external surgery. The presented features were assessed as potential treatment predictors. Outcomes included length of stay (LOS), final best-corrected visual acuity (BCVA), readmission rate, and reoperation rate. RESULTS: Of the 159 SPA cases included, 127 (79.9%) underwent surgery and 32 (20.1%) were managed nonsurgically. The nonsurgical cohort was younger (p = .003) with smaller abscesses (p < .001) that were more likely to be medial (p < .001). The nonsurgical cohort had shorter LOS (p < .001); final BCVA and readmission rates were similarly favorable. Abscess location was correlated with surgical approach. Superior SPA that underwent FESS or external surgery alone had higher reoperation rates (57.1.0% and 58.3%, respectively) than combined (17.9%). External approach and FESS alone resulted in lower reoperation rates (15.4% and 15.0%, respectively) than combined (27.3%) for medial SPA. Subgroup analysis in the sinusitis cohort yielded similar results. CONCLUSIONS: A trial of nonsurgical management may be safe and effective for select patients aged 9 years and older with sinusitis-derived, medial, and small SPA. When surgery is indicated, approach should be guided by abscess location to minimize reoperation risk.

Orbital Subperiosteal Abscess: The Role of Nonsurgical Management Among Adolescents and Adults.

PURPOSE: To investigate the role of nonsurgical management in the treatment of orbital cellulitis complicated by subperiosteal abscess (SPA) in adolescent and adult populations. METHODS: A retrospective cohort study to assess the demographic, clinical, and outcome profiles of adolescent and adult patients with orbital SPA treated nonsurgically versus those who received surgical intervention. Primary outcome measures included hospitalization length and best-corrected visual acuity (BCVA) in the final evaluation. RESULTS: The study comprised 76 patients diagnosed with SPA in the setting of orbital cellulitis. Twelve were stratified into the nonsurgical cohort, while 64 represented the surgical group. Sinusitis was the most prevalent risk factor among both populations, and the rate did not differ significantly. SPA was located medially at a significantly higher rate in the nonsurgical cohort compared with the surgical. No patients in the nonsurgical population had a relative afferent pupillary defect (RAPD) on presentation. The proportion of patients who received adjunctive systemic corticosteroid therapy was comparable in both groups. Hospitalization length was significantly higher in the surgery cohort. BCVA in the final evaluation was favourable in both groups. Sinusitis subgroup analysis including eight nonsurgical patients produced overall consistent results. CONCLUSIONS: Findings from the largest study of orbital cellulitis complicated by SPA to date demonstrate a role for nonsurgical management in adolescent and adult patients who present with a medial SPA and/or ophthalmic examination without an RAPD. Among these populations, visual prognosis is favourable whether management includes surgical debridement or not, and surgical intervention may not predict a shorter duration of hospitalization.

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.

IgG4-positive Cell Quantification Distinguishes Between Inflammatory and Noninflammatory Diseases of the Orbit.

IgG4-related ophthalmic disease (IgG4-ROD) is a rare inflammatory disorder often refractory to corticosteroids and prone to recurrence. IgG4-ROD may frequently lack the characteristic histopathological features seen in other organs. Thus, the criteria for diagnosis of IgG4-ROD relies on elevated IgG4 cells seen on biopsied tissue. Proposed threshold levels of IgG4 to diagnose IgG4-ROD are currently based on a limited understanding of this cell type's presence in the orbit. This study seeks to describe the population of IgG4 in inflammatory and noninflammatory orbital tissues. A tertiary care center's pathology database was searched with keywords "orbit" or "orbital" from 1995 to 2013. Specimens meeting the selection criteria were evaluated, and regions of highest inflammation were identified and immunostained with IgG4 and CD138 antibodies. Immunohistochemical quantification proceeded as previously established by the international consensus criteria. Eighteen cases without a history of orbital inflammation were included as controls and were evaluated as above. Specimens from 68 inflammatory and 18 noninflammatory orbits met the selection criteria. Pathologist interreader correlation coefficient on quantification was >0.70 (P<0.001). The mean IgG4+/high powered field (HPF) and IgG4+/CD138 was 10.3 and 0.1 in inflammatory tissues and 0.5 and 0.01 in noninflammatory tissues, respectively. The spearman rho correlation coefficient between IgG4/HPF and IgG4+/CD138+ was >0.95 (P<0.0001). The mean IgG4/HPF in our study reached previously proposed threshold values for diagnosis of IgG4-ROD, illustrating the need for further discussion regarding diagnostic criteria of IgG4-ROD.

Ophthalmic Changes Following Maxillectomy With or Without Postoperative Radiation Therapy.

PURPOSE: To evaluate ophthalmic complications and quantitatively assess anatomic changes following maxillectomy with or without adjuvant radiotherapy in patients with midface malignancy. METHODS: Twenty-four patients who underwent maxillectomy for sinus and/or paranasal cancer were included for retrospective review. Patients with complete ophthalmic examinations were evaluated for postoperative findings corresponding to sequelae of treatment. When available, anatomical changes including eyelid position were quantified from preoperative and postoperative full-face photos using computer software. RESULTS: The most common complications identified in patients after maxillectomy were retraction/ectropion (50%), epiphora (29%), and exposure keratopathy/dry eye syndrome (25%). Patients treated with maxillectomy with adjuvant radiation therapy were more frequently found to have ophthalmic complications following treatment. In patients with available postoperative photos (n = 10), the mean ipsilateral margin reflex distance (MRD)2 and inferior scleral show were 8.4 mm and 2.4 mm, respectively. In patients with available preoperative photos (n = 5), the mean change in MRD2 and inferior scleral show following maxillectomy was 3.4 mm and 2.8 mm, respectively. CONCLUSION: Patients undergoing maxillectomy for the treatment of head and neck malignancy may be at significant risk for development of specific periocular complications. Lower eyelid malposition was the most significant postoperative quantitative eyelid change following maxillectomy, which may be exacerbated by adjuvant radiotherapy and inferior orbital rim removal.

Incidence, Risk Factors, and Management of Blindness after Orbital Surgery.

PURPOSE: Severe vision loss is a risk of orbital surgery which physicians should counsel patients about, but the overall risk rate is unknown. This research was conducted to determine the risk of severe vision loss related to orbital surgery. DESIGN: Retrospective review. PARTICIPANTS: Patients who underwent orbital surgery at either of 2 academic medical centers between January 1994 and December 2014. METHODS: A billing database search was conducted to identify all patients who had orbital surgery during the study period, cross-checked against diagnostic codes related to vision loss. Charts were screened to determine baseline demographic and medical history, surgical procedure, intraoperative and perioperative management, and visual acuity. Patients with preoperative visual acuity ≥20/200 that worsened ≤20/400 after orbital surgery were included for detailed review. Statistical analysis was conducted to identify factors posing particular risk or benefit to visual outcome in these patients. MAIN OUTCOME MEASURES: Visual acuity after orbital surgery. RESULTS: A total of 1665 patients underwent orbital surgery during the inclusion period, with 14 patients sustaining severe vision loss ranging from counting fingers at 1 foot to no light perception (overall risk, 0.84%). The causes of vision loss included retrobulbar hemorrhage, malpositioned implant, optic nerve ischemia, or direct optic nerve insult. When stratified by surgical approach, the risk of a blinding surgical complication was significantly higher for patients undergoing orbital floor repair in the setting of multiple facial fractures (subgroup risk, 6.45%), bony decompression of the optic canal (subgroup risk, 15.6%), or intracranial approach to the orbital roof (subgroup risk, 18.2%). Seven of 8 patients with a potentially reversible cause of postoperative vision loss underwent urgent repeat surgery, and 2 regained substantial vision (20/20 and 20/25). Administration of intravenous corticosteroids had no significant effect on visual acuity outcome. CONCLUSIONS: The overall risk of severe vision loss after orbital surgery is 0.84%. The subgroup risk is higher in patients undergoing facial polytrauma repair, optic canal decompression, or orbital apex surgery from an intracranial approach. Close postoperative monitoring and urgent assessment and management of acute vision loss may improve visual outcome in some patients.

The role of external eyelid weights in acute facial palsy: functional and aesthetic considerations.

PURPOSE: Patients with acute paralytic lagophthalmos are at high risk for ocular surface breakdown due to exposure. External eyelid weights are a temporary solution for paralytic lagophthalmos that aim to reduce exposure and optimize blink excursion. Despite easy application and high efficacy, this product is under-utilized in clinical practice with few physicians employing this treatment adjunct. RESULTS: Ocular surface health was maintained in all patients, and overall aesthetic satisfaction was high. CONCLUSION: External eyelid weights are a valuable adjunct in the treatment of facial palsy but are under-utilized in clinical practice. This article highlights the benefits of external eyelid weights as an accessible adjunct to restore eyelid function and maintain cosmesis. The device can be implemented without specialist involvement and adds a dimension of independence for general practitioners to manage ocular complications of facial palsy.

Outcomes of Endoscopic Dacryocystorhinostomy in Secondary Acquired Nasolacrimal Duct Obstruction: A Case-Control Study.

INTRODUCTION: Secondary acquired nasolacrimal duct obstruction (SANDO), where the obstruction is caused by a known process, is becoming more commonly treated by endoscopic dacryocystorhinostomy (endoDCR). This study evaluates outcomes of endoDCR for cases of SANDO in comparison to endoDCR outcomes treating primary acquired nasolacrimal duct obstruction (PANDO). METHODS: All patients undergoing endoDCR from 2006 to 2015 at a tertiary referral center were reviewed for etiology of nasolacrimal duct obstruction (NLDO) and success of procedure. Inclusion criteria were preoperative determination of NLDO via probing and irrigation, greater than 60-day follow up with assessment of duct patency via probing and irrigation after silicone tube removal, and postoperative survey for recurrent epiphora. Exclusion criteria were cases treating partial NLDO, patients undergoing concurrent conjunctivodacryocystorhinostomy, and patients lost to follow up or with incomplete records. Preanalysis stratification was performed for the following preexisting conditions: PANDO, granulomatosis with polyangiitis, sarcoidosis, midfacial radiotherapy, radioactive iodine therapy, severe prolonged sinusitis, prior failed DCR, and midface trauma. The primary outcome was postoperative anatomical patency of the nasolacrimal system with resolution of epiphora. Fisher-Freeman-Halton exact tests were performed comparing each SANDO group to the PANDO group with statistical significance set at p < 0.05. RESULTS: Fifty-nine cases of NLDO underwent endoDCR in this series, 21 of which had a diagnosis consistent with SANDO. All patients treated with the aggressive perioperative management protocol the authors describe achieved anatomical patency. Patients with history of radioactive iodine therapy and radiotherapy had statistically worse outcomes compared with patients with PANDO, p = 0.011, p = 0.045, respectively. Stratified groups with increased intranasal sinus inflammation trended toward worse outcomes, but were not statistically different. CONCLUSIONS: EndoDCR is a viable approach for the treatment of SANDO. In patients with history of radiotherapy or radioactive iodine therapy, however, endoDCR demonstrated decreased success rates as compared with patients with PANDO. Modifications of operative and postoperative management based on underlying etiology of NLDO may improve outcomes of endoDCR in SANDO cases. The authors describe an aggressive protocol for perioperative management of patients with pathologic nasal inflammation undergoing endoDCR.

Endoscopic dacryocystorhinostomy following head and neck radiation therapy.

This article determines the efficacy of endoscopic dacryocystorhinostomy (endoDCR) in patients who have undergone adjuvant external beam radiation therapy (XRT) following head and neck cancer resection. A retrospective chart review was performed on all patients who underwent endoDCR between 2006 and 2014 at a tertiary referral center. Cases were reviewed and selected for the following inclusion criteria: history of adjuvant sinonasal XRT following head and neck cancer resection, preoperative probing and irrigation demonstrating nasolacrimal duct obstruction (NLDO), postoperative probing and irrigation following silicone tube extubation. Exclusion criteria included active dacryocystitis, postoperative follow-up of less than 4 months, presence of epiphora prior to XRT, lack of probing/irrigation at preoperative or postoperative visit, and lid malposition including ectropion, facial palsy, and/or poor tear pump. Six patients (7 eyes) met the selection criteria. EndoDCR was performed at a mean time of 30 months following last radiation treatment (range, 3-71 months). Mitomycin C was used in 4/7 cases. Silicone tube removal occurred between 3-8 months postoperatively. Five out of 6 patients had postoperative sinonasal debridement and nasal saline/corticosteroid irrigation. Five out of 6 patients (83%) had both resolution of epiphora and anatomic patency confirmed by probing and irrigation. Our experience suggests that endoDCR procedures can be effective in patients with NLDO following prior sinonasal XRT for head and neck neoplasms. Postoperative management with sinonasal debridement and combined saline/corticosteroid nasal irrigation may help to improve surgical success in patients with increased post-radiotherapy mucosal inflammation.

Malignant Peripheral Nerve Sheath Tumor of the Lower Eyelid: Case Presentation and Literature Review.

Solitary benign neurogenic tumors are common in the orbit, but only rarely arise from peripheral nerves in the eyelids. In contrast, malignant tumors of neural or nerve sheath elements are exceedingly rare in the orbit and, to date, have never been reported in the lower eyelid. The authors report a 55-year-old man with multiple recurrent lower eyelid masses initially treated as chalazia then misdiagnosed as neurotropic malignant melanoma on pathology. Diagnosis of malignant peripheral nerve sheath tumor was ultimately confirmed histopathologically after surgical resection. The patient has since undergone multiple resections and adjuvant radiotherapy. Twenty-two months since the last procedure, the patient remains disease-free.

Acute Orbital Syndrome in Herpes Zoster Ophthalmicus: Clinical Features of 7 Cases.

PURPOSE: To report a series of patients with herpes zoster ophthalmicus and associated acute orbital syndrome with corresponding radiographic findings. METHODS: Medical records of 7 patients with herpes zoster ophthalmicus with acute orbital findings were reviewed. Clinical presentation, radiography, and treatment outcomes were assessed. RESULTS: One man and 6 women with a median age of 70 years (range 47-84) presented with herpes zoster ophthalmicus with acute clinical orbital signs. Two of the 7 patients had compromised immune systems, with 1 patient having chronic lymphocytic leukemia and another infected with human immunodeficiency virus. Clinical orbital findings included proptosis, blepharoptosis, ophthalmoplegia, diplopia, and visual loss. Orbital imaging detailed such findings as myositis in all 7 patients, dacryoadenitis in 2 patients, and optic nerve sheath enhancement in 1 patient. Treatment with intravenous acyclovir was universal in all 7 patients and in 2 cases systemic corticosteroids were also administered. Orbital signs improved in all patients over several months. CONCLUSIONS: Herpes zoster ophthalmicus can rarely cause an acute orbital syndrome and the authors present what may be the largest series of such patients to date. Herpes zoster ophthalmicus can affect various orbital structures including the lacrimal gland, extraocular muscles, cranial nerves and optic nerve sheath. A careful clinical examination and detailed orbital radiography are critical in proper diagnosis and treatment of such patients. Improvement of symptoms and signs with antiviral therapy can be expected; however, complete resolution does not always occur. The role of systemic steroids in treatment of orbital disease is yet to be determined.

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.

Topical Plasminogen as Adjunctive Treatment in Recurrent Ligneous Conjunctivitis.

Ligneous conjunctivitis is a rare, autosomal recessive, membranous conjunctivitis characterized by a deficiency in type 1 plasminogen. The absence of normal plasmin activity results in the formation of fibrin-rich, membranous material that typically manifests on the palpebral conjunctiva. Surgical treatment often causes irritation of the conjunctiva and accelerated recurrence of pseudomembranes. In this interventional case report, the authors document the results of treatment with topical plasminogen following conjunctival pseudomembrane excision in a 32-year-old woman. The patient underwent pseudomembrane excision in the OS followed immediately by hourly topical application of plasminogen eye drops. The plasminogen was prepared from pooled human plasma purchased under Food and Drug Administration approval from DiaPharma. Follow-up evaluation at 1 week, 1 month, and 5 months showed no evidence of recurrent pseudomembranous change. Adjunctive topical plasminogen application appears to be an effective and safe method of controlling pseudomembrane recurrence in patients with ligneous conjunctivitis.

Hemostasis in Orbital Surgery.

This article highlights the major vascular supply of the orbit and structures supplied by these vessels. Key anatomic principles are then reviewed as they pertain to endoscopic orbital surgery in order to avoid serious orbital hemorrhages. Next, preoperative planning and patient education are outlined as well as description of orbital compartment syndrome. This is followed by discussion of various techniques for managing orbital hemorrhage in the intraoperative and postoperative setting.

Mutational status of IDH1 in uveal melanoma.

Uveal (intraocular) melanoma is an uncommon malignancy that comprises a small percentage of all melanoma cases. While many uveal melanomas harbor mutations in the BRCA-Associated Protein 1 (BAP1) gene, the genetics of non-BAP1 associated tumors are not completely understood. Recent studies have shown that a small subset of non-uveal melanomas hold mutations in isocitrate dehydrogenase (IDH), but the mutational status of IDH in uveal melanoma is unclear. Mutations in IDH are strongly prognostic and predictive of tumor behavior in other cancers, mainly diffuse gliomas, which commonly contain the IDH1-R132H mutation. For this study, we hypothesized that uveal melanoma may contain the IDH1-R132H mutation, similar to non-uveal melanoma and other cancers. A search of our institutional pathology files identified 50 consecutive cases of uveal melanoma with additional material utilized for retrospective IDH1-R132H immunohistochemical testing. The demographics of these patients included similar ages, gender distributions, and other clinical characteristics as described in previous studies. Similarly, histological subtype distributions and the presence of high risk pathologic features were consistent with other reports. All 50 of the uveal melanoma cases demonstrated negativity for IDH1-R132H by immunohistochemistry. This rate is unlike that of non-uveal melanoma and further supports their distinct molecular oncogenic profile.

Indications for Keratoplasty at 3 Academic Centers from 2002 to 2012.

OBJECTIVES: To determine whether indications for keratoplasty differ between academic centers and the Eye Bank Association of America (EBAA) annual statistics from 2002 to 2012. METHODS: A retrospective review was performed for the indications for keratoplasty from 2002 to 2012 based on surgical specimens originating from three different academic centers. Data were compared with statistical reports obtained from the EBAA for the corresponding years. RESULTS: From 2002 to 2007, at Washington University in St Louis (WU), the most common indication for keratoplasty was graft failure at 31.6%. At St Louis University, the most common indications for keratoplasty were pseudophakic and aphakic bullous keratopathy (PBK/ABK) at 34.6% followed closely by graft failure at 32.7%. Combining the 2002 to 2007 EBAA data, the most common indication for keratoplasty was PBK/ABK at 19.5%, whereas regrafts accounted for only 13.0% of keratoplasties. From 2008 to 2012, regrafts accounted for 41.9% of keratoplasties at WU and 33.1% of keratoplasties at University of California, Davis. In contrast, the EBAA data showed that only 11.4% of keratoplasties were regrafts. CONCLUSIONS: Graft failure accounted for approximately 30% to 40% of indications for keratoplasties at three academic centers from 2002 to 2012, which was more than double and in some cases triple that of the EBAA data during this period. These higher frequencies of regrafting may represent a referral bias of patients with complicated cases to academic centers who then require multiple keratoplasties.

Ocular Trauma From Dog Bites: Characterization, Associations, and Treatment Patterns at a Regional Level I Trauma Center Over 11 Years.

PURPOSE: Canine bites frequently result in periocular injury. The authors aimed to further characterize the dog breeds, types of injuries inflicted, and treatment outcomes. METHODS: A retrospective chart review was performed on all dog bites recorded in the University of Washington trauma registry from 2003 to 2013. Cases involving ocular injury were further investigated to identify ocular tissues affected, treatment patterns, and outcomes. RESULTS: A total of 342 dog bite victims were identified, of whom 91 sustained ocular trauma (27%). The mean age of patients with ocular injuries was significantly lower than those without (14.1 ± 1.9 vs. 30.0 ± 1.3 years, p < 0.001). Children bitten by dogs were 4.2 times more likely to sustain ocular injuries than adults (45.2% vs. 10.8%). The most common breed of dog inflicting ocular injury was the pit bull (25%). Forty percent of patients with ocular trauma sustained canalicular lacerations and epiphora was noted in only 3 patients (8%) after repair. Three percent had orbital fractures and 2% sustained ruptured globes. Infections were rare, affecting only 2% of patients. CONCLUSIONS: To our knowledge, this study is the largest to date to report the incidence and characteristics of ocular injuries sustained from dog bites. These injuries were disproportionately more common in children and have a high incidence of canalicular laceration. Though rare, globe injuries and orbital fractures were seen in this population. Importantly, this study establishes that pit bulls are the most frequent breed associated with ocular injuries from dog bites.

External Compression Versus Intravascular Injection: A Mechanistic Animal Model of Filler-Induced Tissue Ischemia.

PURPOSE: Soft tissue ischemia is a devastating and unpredictable complication following dermal filler injection. Multiple mechanisms to explain this complication have been proposed, including vascular compression, vessel damage, and intraarterial filler emboli. To elucidate the mechanism of injury, the authors introduce a mouse model, imaged with optical microangiography and laser speckle contrast imaging technologies, to demonstrate in vivo microvascular response to soft tissue and intravascular filler injection. METHODS: To determine the effect of external vascular compression on distal perfusion, the authors attempted to occlude vessels with subcutaneous hyaluronic acid gel (HAG) bolus injections into the pinna of hairless mice. The authors also performed suture ligation of a major vascular bundle. Following these interventions, laser speckle and optical microangiography were performed serially over 1 week follow up. To determine the effect of intravascular HAG injection, the authors devised and validated a novel method of cannulating the mouse external carotid artery for intraarterial access to the pinna vasculature. Using this model, the authors performed intraarterial HAG injections and completed optical microangiography and laser speckle contrast imaging. RESULTS: Despite large HAG bolus injections directly adjacent to vascular bundles, the authors were unable to induce compressive occlusion of the mouse pinna vessels. Vascular occlusion was successfully performed with suture ligation, but optical microangiography and laser speckle contrast imaging confirmed undisturbed distal capillary bed perfusion. With intravascular HAG injection, large segments of pinna showed distinct perfusion reduction along a vascular distribution when compared with preinjection images, most noticeably at the capillary level. CONCLUSIONS: The novel mouse pinna model combining intravascular access and in vivo microvascular perfusion imaging has furthered the understanding of the mechanism of filler-induced tissue ischemia. Distal capillary perfusion was maintained despite external vascular compression. Intraarterial HAG filler injection, however, resulted in large areas of capillary nonperfusion and is the most likely etiology for filler-induced tissue necrosis that is observed clinically.

Synthesis and fungicidal activity of novel 2-aryl-3-(1,3,4-thiadiazolyl)-6(8)-methyl-1,3-benzoxazines.

A class of novel 2-aryl-3-(1,3,4-thiadiazolyl)-6(8)-methyl-1,3-benzoxazines was prepared by reactions of 2-methyl-6-((1,3,4-thiadiazolylamino)methyl)phenols or 4-methyl-2-((1,3,4-thiadiazolylamino)methyl)phenols and 2- or 4-nitrobenzaldehyde in the presence of TMSCl in refluxing toluene. The electron-donating methyl group on the benzene ring played an essential role on the reactivity of the substituted phenols, which was proved by DFT calculation. The fungicidal activity of the resultant products were also preliminarily evaluated, most of which displayed moderate to good fungicidal activity. Especially, compound 6f showed 98.0% activity against Sclerotonia sclerotiorum and Botrytis cinerea at concentration of 25µg/mL.