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Purpose: To comprehensively review the literature about numerical aberrations of the orbital muscles of ocular motility (here referred to as extraocular muscles [EOMs]) and the levator palpebrae superioris (LPS)., Methods: The authors summarize the embryologic bases and the possible etiopathogenetic causes of numerical aberrations of the EOMs and the LPS and organize these lesions into several broad categories. The clinical and radiologic diagnostic challenges are discussed., Results: Numerical aberrations of the EOMs include: 1) the complete absence of EOMs, 2) duplication of an entire EOM, 3) the presence of muscle bands that connect 2 EOMs, and 4) minor morphological variations such as bifid muscles (partial splitting of the muscle). Some cases may defy categorization into any of the above or may resemble atavistic remnants of the retractor bulbi muscle. Broadly speaking, numerical aberrations of the LPS generally fall into the same categories although the LPS has several peculiar numerical anomalies of its own., Conclusions: Although numerical EOM and LPS variations are relatively rare and of little clinical significance, raising awareness about their presence is a fundamental clinical keystone not just for the strabismus surgeon but for the orbital surgeon as well. During orbital surgery, this may spare the surgeon from pursuing an orbital witch hunt for these benign innocuous accessory orbital structures that were accidentally discovered by the radiologist and misinterpreted as sinister etiologies. For the strabismus surgeon, the failure to identify them may result in an unfavorable surgical outcome if these structures are missed because of a lack of awareness despite being responsible for generating complex strabismus patterns or having a restrictive potential of their own., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Objectives: Automated immunoassays for 1,25-dihydroxyvitamin D (1,25(OH) 2 D) have increased the use of serum measurements in clinical and research settings, but disagreement with LC-MS/MS methods remains an issue., Methods: In this study, we examined this problem using samples obtained from healthy young adults, n=80, mean age 21.7 (18-32) years, and a large cohort of paediatric samples, n=422, mean age 7.3 (0-17) years. We compared serum concentrations of 1,25(OH) 2 D3/D2 produced by the DiaSorin LIAISON ® XL immunoassay against an LC-MS/MS method with immunoaffinity enrichment and DAPTAD derivation., Results: Both assays showed intra/inter-assay imprecision of ≤9.4 % across their respective assay range. DEQAS between April 2020 to Jan 2024 (n=80) showed mean bias (SD, 95 %CI) for DiaSorin -0.6 % (6.2, -12.8 to 11.6) and LC-MS/MS of +1.3 % (7.4, -13.3 to 15.8) against their respective method group means. Comparison of measurements in the adult samples showed a strong correlation (r 2 =0.9331) and concordance (CCC=0.959) between the two methods. LC-MS/MS values were lower than DiaSorin by an overall mean (±SD, 95 %CI) of -1.6 (±14.3, -29.6 to 26.5) pmol/L with an increased negative bias at higher concentrations. In the paediatric samples, weaker correlation (r 2 =0.6536) and concordance (CCC=0.782) were observed, with greater bias mean (±SD, 95 %CI) of -9.8 (±23.4, -55.7 to 35.9) pmol/L. The variability in the paediatric samples was not associated with concentration or participant age. There was an increase in the correlation and concordance when 1,25(OH) 2 D2 was included in the analysis., Conclusions: It is likely that the metabolites of vitamin D present in the paediatric population contributed to the measurement of 1,25(OH) 2 D. The inconsistent agreement highlights the need for better assay harmonisation and paediatric reference intervals using LC-MS/MS method., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Vitamin D 3 synthesis in human skin is initiated by solar ultraviolet radiation (UVR) exposure of precursor 7-dehydrocholesterol (7DHC), but influence of age on the early stage of vitamin D 3 metabolism is uncertain. We performed a prospective standardised study in healthy ambulant adults aged ≥65 and ≤40 years examining (1) if baseline skin 7DHC concentration differs between younger and older adults and (2) the impact of older age on serum vitamin D 3 response to solar simulated UVR. Eleven younger (18-40 years) and 10 older (65-89 years) adults, phototype I-III, received low-dose UVR (95% UVA, 5% UVB, 1.3 SED) to ~35% of the body surface area. Biopsies were taken for 7DHC assay from unexposed skin, skin immediately and 24 h post-UVR, and blood sampled at baseline, 24 h and 7 d post-UVR for vitamin D 3 assay. Samples were analysed by HPLC-MS/MS. Baseline skin 7DHC (mean ± SD) was 0.22 ± 0.07 and 0.25 ± 0.08 µg/mg in younger versus older adults (no significant difference). Baseline serum vitamin D 3 concentration was 1.5 ± 1.5 and 1.5 ± 1.7 nmol/L in younger versus older adults, respectively, and showed a significant increase in both groups post-UVR (no significant differences between age groups). Thus, skin 7DHC concentration was not a limiting factor for vitamin D 3 production in older relative to younger adults. This information assists public health guidance on sun exposure/vitamin D nutrition, with particular relevance to the growing populations of healthy ambulant adults ≥65 years.

Competing Interests: The authors declare that they have no conflicts of interest to disclose.

Purpose: Apraxia of eyelid opening (AEO) has been defined by the presence of an intermittent nonparalytic bilateral loss of the volitional ability to open the eyes or to maintain the eyelids in a sustained elevated position. It is not known whether the condition represents an apraxia, a dystonia, or a freezing phenomenon, and several different nomenclatorial terms have been suggested for this condition including the so-called AEO (scAEO), blepahrocolysis, focal eyelid dystonia, and so on. The primary goal of this review is to attempt to clarify the pathogenetic mechanisms underlying scAEO as a clinical phenomenon. This review also addresses the issue of whether scAEO is part of the spectrum of blepharospasm (BSP) which includes BSP, dystonic blinks and other dystonic eyelid conditions, or whether it is a separate phenomenologically heterogeneous disease with clinical features that merely overlap with BSP., Methods: A literature review was conducted in PubMed, MEDLINE, PubMed Central (PMC), NCBI Bookshelf, and Embase for several related keywords including the terms "apraxia of eyelid opening," "pretarsal blepharospasm," "blepharocolysis," "eyelid freezing," "eyelid akinesia," "levator inhibition," "blepharospasm-plus," as well as "blepharospasm." The clinical findings in patients with scAEO who fulfilled the classic diagnostic criteria of the disease that were originally set by Lepore and Duvoisin were included, while patients with isolated blepharospasm or dystonic blinks (DB) were excluded. In addition, electromyographic (EMG) studies in patients with scAEO were reviewed in detail with special emphasis on studies that performed synchronous EMG recordings both from the levator muscle (LPS) and the pretarsal orbicularis oculi muscle (OO)., Results: The apraxia designation is clearly a misnomer. Although scAEO behaves clinically as a hypotonic freezing phenomenon, it also shares several cardinal features with focal dystonias. The authors broadly categorized the EMG data into 3 different patterns. The first pattern (n = 26/94 [27.6%]) was predominantly associated with involuntary discharges in the OO muscle and has been termed pretarsal blepharospasm (ptBSP). The commonest pattern was pattern no. 2 (n = 53/94 [56.38%]), which was characterized by involuntary discharges in the OO muscle, together with a disturbed reciprocal innervation of the antagonist levator muscle and is dubbed disturbed reciprocal innervation (DRI). This EMG pattern is difficult to discern from the first pattern. Pattern no. 3 (n = 15/94 [15.9%]) is characterized by an isolated levator palpebrae inhibition (ILPI). This levator silence was observed alone without EMG evidence of contractions in the pretarsal orbicularis or a disturbed reciprocal relation of both muscles., Conclusion: EMG evidence shows that the great majority (84%) of patients show a dystonic pattern, whereas ILPI (16%) does not fit the dystonic spectrum. The authors propose that a spasmodic contraction of the muscle of Riolan may be the etiological basis for levator inhibition in patients with ILPI. If this is true, all the 3 EMG patterns observed in scAEO patients (ptBSP, DRI, and ILPI) would represent an atypical form of BSP. The authors suggest coining the terms Riolan muscle BSP ( rmBSP ) for ILPI, and the term atypical focal eyelid dystonia ( AFED ) instead of the term scAEO, as both terms holistically encompass both the clinical and EMG data and concur with the authors' theorem., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2022 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background: UVB absorption by 7-dehydrocholesterol (7DHC) in the skin triggers the production of vitamin D and its metabolites, which maintain calcium homeostasis. Detection and measurement of 7DHC in skin using modern liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques have been lacking, yet there is need for such a technique to provide more information on 7DHC concentration and its UVB responses in human skin., Objectives: To develop and validate a reliable method to measure 7DHC concentration in skin., Methods: Human skin punch biopsies of 5 mm diameter obtained through the Manchester Skin Health Biobank were utilised. 7DHC was extracted with ethyl acetate:methanol 1:1 (v/v) and derivatised using 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD), to allow for improved ionisation of 7DHC through Electrospray Ionisation Mass Spectrometry (ESI-MS). Solid supported liquid extraction (SLE) was also employed to allow the removal of larger lipids from 7DHC and minimise potential matrix effects., Results: The LC-MS/MS assay satisfied International Council for Harmonisation research standards for method validation. Calibration curve was linear with a typical r 2 of 0.997, coefficient of variation was 11.1% and 4.32% for inter-assay and intra-assay imprecision, respectively. Lower limit of quantification was 1.6 µg/g and upper limit of quantification was 100 µg/g, SLE recovery of 7DHC was on average 91.4%., Conclusions: We have developed a robust, precise and accurate assay for the detection and quantification of 7DHC in small samples of human skin (0.2 cm 2 surface area). This novel method of extraction and quantification will be valuable to future vitamin D photobiology research., (© 2022. The Author(s).)

Purpose: Vascular anomalies are a heterogeneous group of disorders that frequently present in the periorbital region. They encompass 2 broad entities: vascular tumors, which possess a proliferative endothelium, and vascular malformations, which are basically localized defects of vascular morphogenesis. The primary goal of this review was to address inaccurate or controversial terminology in the oculoplastic literature concerning orbital and periorbital vascular anomalies and to categorize these lesions in an abridged and simplified hierarchical list that adheres as much as possible to the most recent (2018) iteration for the classification of vascular lesions proposed by the International Society for the Study of Vascular Anomalies (ISSVA). The secondary goal of this review was to review and update information regarding the genetic underpinnings of vascular anomalies and the downstream signaling pathways that are subsequently affected as a result of these genetic errors., Methods: A literature review was conducted in PubMed, MEDLINE, PubMed Central, National Center for Biotechnology Information Bookshelf, and Embase for several related keywords including "vascular anomalies, vascular malformations, vascular tumors, and cavernous venous malformation," both with and without adding the keywords "eyelid," "orbital," and "periorbital." In addition, a detailed search was conducted for controversial or obsolete keywords like "cavernous hemangioma," "lymphangioma," and "varices," again in their systemic and orbital/periorbital context., Results: Crucial issues in the 2018 ISSVA classification regarding the proper categorization of orbital vascular anomalies, particularly venous lesions, were critically evaluated and revised, and a regional, simplified, and abridged modification of the ISSVA 2018 classification was proposed., Conclusions: Interdisciplinary and intradisciplinary dialogue concerning orbital vascular anomalies is seriously compromised due to the lack of a unanimous agreement on terminology and the absence of a unified classification concept system. The authors recommend that oculoplastic surgeons adopt ISSVA terminology whenever technically possible and scientifically sound. However, they also propose modifying the ISSVA 2018 classification specifically to adapt to the peculiarities of vascular anomalies in the periorbital region. At present, the simplified classification proposed here is a preliminary first step towards managing patients with orbital vascular anomalies with greater diagnostic and therapeutic precision, until such time in the future when the entire genetic makeup of orbital vascular anomalies is more completely elucidated. Optimistically, this could pave the way for a more robust classification and the ultimate therapeutic cure., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: Intravenous antibiotic prophylaxis is used for many clean-contaminated surgeries or clean surgeries with an implant, but its value for clean orbital surgery has not been determined. This study investigated infection risks and adverse effects related to antibiotics in patients undergoing orbital surgery., Methods: A prospective, nonrandomized comparative case series of all patients undergoing orbital surgery with participating surgeons between October 1, 2013, and March 1, 2015. Types of surgery, antibiotic regimens, corticosteroid use, antibiotic side effects, and surgical site infections (SSIs) were entered into an electronic database and subsequently analyzed. Cases in which patients received postoperative oral antibiotics were analyzed separately., Results: Of 1,250 consecutive orbital surgeries, 1,225 met inclusion criteria. A total of 1208 patients were included in the primary analysis: 603 received no antibiotic prophylaxis (group A), and 605 received a single dose of intravenous antibiotic (group B). Five patients (0.42%) developed an SSI, 3 in group A and 2 in group B. The difference in SSI rates was not statistically significant between the 2 groups (p = 0.66). Antibiotic prophylaxis, alloplastic implants, paranasal sinus entry, and corticosteroid use were not associated with differences in SSI rates. All SSIs resolved on a single course of oral antibiotics; an implant was removed in 1 case. There were no complications associated with a single dose of intravenous prophylaxis. However, 12% of 17 patients (group C) who received 1 week of oral postoperative prophylactic antibiotics developed antibiotic-related complications (diarrhea, renal injury), yielding a number needed to harm of 8.5., Conclusions: In this large series, antibiotic prophylaxis does not appear to have reduced the already low incidence of SSI following orbital surgery. Given the detriments of systemic antibiotics, the rarity of infections related to orbital surgery, and the efficacy of treating such infections should they occur, patients undergoing orbital surgery should be educated to the early symptoms of postoperative infection and followed closely, but do not routinely require perioperative antibiotics.

The demand for measurement of vitamin D metabolites for clinical diagnosis and to advance our understanding of the role of vitamin D in human health has significantly increased in the last decade. New developments in technologies employed have enabled the separation and quantification of additional metabolites and interferences. Also, developments of immunoassays have changed the landscape. Programmes and materials for assay standardisation, harmonisation and the expansion of the vitamin D external quality assurance scheme (DEQAS) with the provision of target values as measured by a reference measurement procedure have improved standardisation, quality assurance and comparability of measurements. In this article, we describe developments in the measurement of the commonly analysed vitamin D metabolites in clinical and research practice. We describe current analytical approaches, discuss differences between assays, their origin, and how these may be influenced by physiological and experimental conditions. The value of measuring metabolites beyond 25 hydroxyvitamin D (25(OH)D), the marker of vitamin D status, in routine clinical practice is not yet confirmed. Here we provide an overview of the value and application of the measurement of 1,25 dihydroxyvitamin D, 24,25 dihydroxyvitamin D and free 25OHD in the diagnosis of patients with abnormalities in vitamin D metabolism and for research purposes.

Idiopathic subepidermal calcinosis, also known as idiopathic calcinosis cutis, is a rare condition, which typically presents as a small, hard, subepithelial mass in the absence of systemic disease and trauma. We report on an atypical case of idiopathic calcinosis, which appeared in an otherwise healthy 61-year-old female along the tarsus of her right upper eyelid. The purpose of this case report is to demonstrate idiopathic calcinosis in an unusual location that is deep to the dermis and to discuss the vast differential diagnosis of this entity.

Purpose: To review the recent data about orbital development and sort out the controversies from the very early stages during embryonic life till final maturation of the orbit late in fetal life, and to appreciate the morphogenesis of all the definitive structures in the orbit in a methodical and timely fashion., Methods: The authors extensively review major studies detailing every aspect of human embryologic and fetal orbital morphogenesis including the development of extraocular muscles, orbital fat, vessels, nerves, and the supportive connective tissue framework as well as bone. These interdisciplinary studies span almost a century and a half, and include some significant controversial opposing points of view which the authors hopefully sort out. The authors also highlight a few of the most noteworthy molecular biologic studies regarding the multiple and interacting signaling pathways involved in regulating normal orbital morphogenesis., Results: Orbital morphogenesis involves a successive series of subtle yet tightly regulated morphogenetic events that could only be explained through the chronological narrative used by the authors. The processes that trigger and contribute to the formation of the orbits are complex and seem to be intricately regulated by multifaceted interactions and bidirectional cross-talk between a multitude of cellular building raw materials including the developing optic vesicles, neuroectoderm, cranial neural crest cells and mesoderm., Conclusions: Development of the orbit is a collective enterprise necessitating interactions between, as well as contributions from different cell populations both within and beyond the realm of the orbit. A basic understanding of the processes underlying orbital ontogenesis is a crucial first step toward establishing a genetic basis or an embryologic link with orbital disease.

Purpose: Seminomas are solid tumors in young men, but which rarely metastasize to the orbit. The authors review the known literature on seminoma metastatic to the orbit, and describe an additional case in a 33-year-old man., Methods: A literature search was performed on the MEDLINE database using keywords "seminoma," "testicular germ-cell tumors," "testicular cancer," "testicular neoplasm," "orbital metastasis," and "germ-cell neoplasms.", Results: Malignant neoplasms of the testis account for only 1% of cancers in men. None-the-less, testicular germ cell seminoma is the most common solid tumor found in young men between the ages of 15 and 39. Only seven previous cases have been mentioned in the literature. The pathogenesis remains unclear although genetic, environmental, and maternal factors may play a role. The number of cases is too few to determine the best treatment options, but surgical excision and adjunctive orbital radiotherapy appear to be most appropriate., Conclusions: Although metastases to the orbit are rare, seminoma should be considered in the differential diagnosis of all young men with proptosis.

Purpose: To review and summarize the clinical findings in thyroid eye disease (TED) related to the unique anatomical structures of the eyelids and orbit., Methods: A PubMed search was performed searching for anatomical relationships between eyelid and orbital anatomy and the clinical findings of TED., Results: The major clinical findings associated with TED are varied. They typically involve both the eyelid and the orbit. In the eyelid, usual findings include upper eyelid retraction, contour abnormalities, eyelid edema, prolapsed orbital fat, conjunctival injection and chemosis, caruncular edema, and meibomian gland dysfunction. The exact causes of these changes remain a matter of controversy, but numerous hypotheses have been proposed, most with limited experimental support. In the orbit, inflammation and congestion characterize the acute active phase, with tissue expansion and fibrosis persisting into the chronic inactive phase. All of these findings result, at least in part, from the unique anatomy of the eyelids and orbit and their interaction with the immunologic processes underlying TED. Here we review these major characteristics of TED, with special reference to their anatomic relationships., Conclusions: The major findings characterizing TED are related to unique anatomic features in the eyelid, including Müller muscle, the levator palpebrae superioris muscle, and suspensory ligaments of the conjunctiva. In the orbit, Graves-related remolding results from the special physiologic features of the extraocular muscles, the structure of the orbital walls and their relations to adjacent paranasal sinuses, and the reaction of orbital fat to immunologic challenges.

Purpose: To review the clinical and histopathologic findings associated with subepidermal calcinosis of the eyelids., Methods: A systematic review of the literature on subepidermal calcinosis of the eyelids was performed. Cases included were idiopathic in nature and met the histologic criteria for subepidermal calcinosis with calcium deposits in the dermis of the skin., Results: Twenty-one publications presenting 53 cases of subepidermal calcinosis involving the eyelids were published between 1970 and 2016. Males were affected more than females (67% vs. 33%), and 89% of patients were 21 years of age or younger. A total of 63% were non-Caucasian. Most cases involved a single lesion (82%), and lesions were most frequently located on the upper eyelid (63%). In 81% of cases, the lesion was less than 5 mm in diameter. When reported, the treatment of choice was complete surgical excision., Conclusions: Subepidermal calcinosis should be considered in the differential diagnosis of idiopathic lesions on the eyelid, particularly in young males with no history of systemic disease or laboratory abnormalities. These nodules usually present as painless, small, firm, mobile solitary cutaneous lesions with a predilection for the upper eyelid. Diagnosis is confirmed by histopathology, and treatment is with surgical excision.

Purpose: To evaluate low- vs high-dose plaque brachytherapy for juxtapapillary choroidal melanoma., Design: Retrospective interventional case series., Methods: Setting: Single institution., Study Population: Forty-seven patients with juxtapapillary choroidal melanoma., Intervention: Iodine-125 plaque brachytherapy. Eyes were divided into apex low-dose (LD) and high-dose (HD) groups (≤ or > median apex dose 84.35 Gy). Main outcome measures were time to distant failure, local failure, death, enucleation, radiation retinopathy, optic neuropathy, and best-corrected visual acuity (BCVA)., Results: Freedom from distant failure rates were 96% and 95% in apex LD and HD groups at 5 years and 77% and 95% at 10 years, respectively (P = .84). Freedom from local failure rates were 90% in the apex LD group vs 89% in the HD group at 5 and 10 years (P = .96). Apex LD and HD groups did not differ for time to death or enucleation. Five- and 10-year freedom from radiation retinopathy and optic neuropathy rates were higher in the apex LD than HD group. Loss of ≥3 BCVA lines, final BCVA 20/40 or better, and final BCVA 20/200 or worse were more favorable in the 5 mm LD compared to HD group. Visual acuity outcomes did not differ between apex LD and HD groups., Conclusions: Low-dose iodine-125 plaque brachytherapy (67.5-81 Gy at tumor apex) provides safe and effective tumor control for juxtapapillary choroidal melanoma and may be associated with reduced radiation toxicity. Larger trials are needed to determine the optimal therapeutic dose for juxtapapillary choroidal melanoma., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To report surgical site infection (SSI) rates of eviscerations and enucleations with implants performed without perioperative intravenous (IV) antibiotics or postoperative oral antibiotics, and to give SSI prevention recommendations., Methods: A single-center retrospective chart review was performed after obtaining institutional review board approval. Charts were found by Current Procedural Terminology codes. Demographics, surgical indication, procedure, implant, antibiotic use, and postoperative course were recorded. SSIs occurring within 30 days after surgery were reviewed and postoperative infection rates were determined., Results: Four hundred eighty-one cases from January 1999 to December 2015 were analyzed. There were 102 eviscerations with implants, 314 enucleations with implants, 23 enucleations without implants, 23 implant exchanges, 15 implants placed secondarily after enucleation, and 4 implant removals. Seventy cases (14.6%) were given perioperative IV antibiotics, and in this group one periorbital infection occurred unrelated to orbital surgery (1.4%). Of the 411 cases (85.4%) not given perioperative IV antibiotics, 1 of 87 eviscerations with implants developed an SSI (1.1%), 2 of 273 enucleations with implants developed SSIs (0.7%), and none of the 13 enucleations without implants developed SSIs., Conclusions: To our knowledge, this is the first published case series reporting SSI rates of enucleations and eviscerations with implants performed without perioperative IV antibiotics or postoperative oral antibiotics. With infection rates comparing favorably to other case series where antibiotics were given, the routine use of perioperative IV antibiotics and postoperative oral antibiotics for enucleations and eviscerations may not be indicated.

Purpose: To describe the results and potential benefit of direct muscle release from the globe during enucleation surgery without identifying sutures in the rectus muscle insertion sites, a technique referred to as the hook and release technique., Methods: Single center, retrospective chart review of patients who underwent enucleation with direct removal of the rectus muscles without identifying sutures in their insertion sites between January 2011 and September 2015 was carried out. The inclusion criteria were primary enucleation without previous strabismus surgery, retinal detachment surgery, or orbital surgery that entered the fibrous connective tissue framework. Forty charts of enucleated patients that had direct release of their extraocular muscles without identifying sutures before releasing them from the globe were identified and reviewed. The primary outcome measure was intraoperative or immediate postoperative complications. This retrospective chart review was performed with research ethics board approval and in compliance with the Declaration of Helsinki., Results: Data show that following the hook and release technique, the rectus muscles were easily located and reconnected to the orbital implant wrap. The oblique muscles were not reattached. In each of the 40 patients, the 4 rectus muscles were easily located by gently applying traction anteriorly at the conjunctiva/Tenons' edge using double-pronged skin hooks. There was no instance of a lost or slipped muscle following the hook and release technique., Conclusion: The hook and release technique is a simple and efficient method to remove the 4 rectus muscles from the globe and still easily locate them. They are not "lost" and do not "slip out of position" but held in place by the orbital connective tissue framework and the extraocular muscle pulley system. This technique has been very helpful teaching resident staff how to do enucleation surgery as it avoids the more time consuming placement of double-armed locking sutures through the rectus muscle insertions and the potential risk of globe penetration while the muscles remain attached to the eye. If the surgeon desires to attach the muscles to the orbital implant, then sutures are passed after the eye is removed, thus eliminating the worry of globe penetration and avoiding accidentally cutting preplaced extraocular muscle sutures during the remaining enucleation procedure.

Purpose: To describe a technique for localizing a lost rectus muscle during strabismus or retinal surgery or following trauma., Methods: In this single center, retrospective chart review, 5 patients were identified between January 2012 and June 2016 with a lost rectus muscle; 3 during strabismus surgery and 2 post trauma. The inclusion criteria included a lost rectus muscle during strabismus surgery, or a disinserted/lacerated rectus muscle following ocular/orbital trauma. The primary outcome measure was successful reattachment of the rectus muscle., Results: The lost rectus muscle was identified in each patient and reattached to the globe by gently applying traction anteriorly at the conjunctiva/Tenon edge using double-pronged skin hooks and following the path of the rectus muscle through its Tenon capsule tunnel where it remained attached by suspensory ligaments. There was no instance where orbital fat was obscuring or blocking the view of the lost rectus muscles. There were no other complications associated with the procedure., Conclusions: The authors describe a simple and effective method in 5 patients to localize a lost rectus muscle based on knowledge of the orbital connective tissue framework.

24,25(OH) 2 D is the product of 25(OH)D catabolism by CYP24A1. The measurement of serum 24,25(OH) 2 D concentration may serve as an indicator of vitamin D catabolic status and the relative ratio with 25(OH)D can be used to identify patients with inactivating mutations in CYP24A1. We describe a LC-MS/MS method to determine: (1) the relationships between serum 24,25(OH) 2 D and 25(OH)D; (2) serum reference intervals in healthy individuals; (3) the diagnostic accuracy of 24,25(OH) 2 D measurement as an indicator for vitamin D status; 4) 24,25(OH) 2 D cut-off value for clinically significant change between inadequate and sufficient 25(OH)D status. Serum samples of healthy participants (n=1996) from Army recruits and patients (n=294) were analysed. The LC-MS/MS assay satisfied industry standards for method validation. We found a positive, concentration-dependent relationship between serum 24,25(OH) 2 D and 25(OH) 2 D concentrations. The 25(OH)D:24,25(OH) 2 D ratio was significantly higher (P<.001) at 25(OH)D<50 nmol/L. The reference interval for 25(OH)D:24,25(OH) 2 D ratio in healthy subjects was 7-23. Measurement of serum 24,25(OH) 2 D can be used as predictor of vitamin D status, a concentration of>4.2 nmol/L was identified as a diagnostic cut-off for 25(OH)D replete status. One patient sample with an elevated 25(OH)D:24,25(OH) 2 D ratio of 32 and hypercalcaemia who on genetic testing confirmed to have a biallelic mutation of CYP24A1. Our study demonstrated the feasibility of a combined 24,25(OH) 2 D and 25(OH)D assessment profile. Our established cut-off value for 24,25(OH) 2 D and ratio reference ranges can be useful to clinicians in the investigation of patients with an impaired calcium/phosphate metabolism and may point towards the existence of CYP24A1 gene abnormalities., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Background: Dacryocystorhinostomy (DCR) can be performed via an external or endoscopic approach. The use of ultrasonic or piezosurgery has been well described for endoscopic DCRs but is lacking for external DCRs. This study presents a case series of external DCRs performed using piezosurgery evaluating results and complications., Methods: Prospective, consecutive case series of patients undergoing primary external DCR for lacrimal drainage insufficiency. A standard external DCR technique was used using 1 of 2 piezosurgery systems for all bone incision. All patients received silicone intubation to the lacrimal system. Surgical outcome was measured in terms of patient-reported epiphora as follows: 1) complete resolution, 2) improvement >50%, 3) improvement <50%, and 4) No improvement. Intra and postoperative complications were also recorded., Results: Fifty-two patients, 14 male and 38 female, were included in the study, with 2 patients having bilateral surgery. The average age of the patients was 55.8 years. The average length of follow up was 221 days. Surgical outcomes showed 72% of patients with complete resolution of epiphora and 21% with >50% improvement. There were 4 patients (7%) who had <50% improvement. There was 1 (2%) intraoperative complication and 2 (4%) postoperative complications recorded., Conclusions: Piezourgery is a viable modality for performing external DCRs. The lack of surgical complications shows a potential for decreased soft tissues damage. The surgical success rate based on patient-reported epiphora is similar to those published for mechanical external DCRs. This modality may benefit the novice surgeon in the reduction of soft and mucosal tissue damage.

Purpose: To review the recent data about eyelid morphogenesis, and outline a timeline for eyelid development from the very early stages during embryonic life till final maturation of the eyelid late in fetal life., Methods: The authors extensively review major studies detailing human embryologic and fetal eyelid morphogenesis. These studies span almost a century and include some more recent cadaver studies. Numerous studies in the murine model have helped to better understand the molecular signals that govern eyelid embryogenesis. The authors summarize the current findings in molecular biology, and highlight the most significant studies in mice regarding the multiple and interacting signaling pathways involved in regulating normal eyelid morphogenesis., Results: Eyelid morphogenesis involves a succession of subtle yet strictly regulated morphogenetic episodes of tissue folding, proliferation, contraction, and even migration, which may occur simultaneously or in succession., Conclusions: Understanding the extraordinary process of building eyelid tissue in embryonic life, and deciphering its underlying signaling machinery has far reaching clinical implications beyond understanding the developmental abnormalities involving the eyelids, and may pave the way for achieving scar-reducing therapies in adult mammalian wounds, or control the spread of malignancies., Competing Interests: The authors have no financial or conflicts of interest to disclose.

Background: Pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of collagen degradation. Measurement of PYD and DPD can be used to evaluate changes in bone turnover in patients with metabolic bone disease and to monitor response to anti-resorptive treatment., Objective: To develop a method to extract and measure urine free PYD (fPYD) and free DPD (fDPD) by liquid chromatography tandem mass spectrometry (LC-MS/MS). The method was used to quantify urine samples from 172 healthy individuals and 63 patients diagnosed with metabolic bone disease., Method: Acidified urine samples were extracted using solid phase extraction with cellulose slurry. PYD and DPD were separated by reversed-phase, ion-paired chromatography prior to MS/MS detection., Results: The fully validated method showed good agreement with other laboratories in the UK National External Proficiency Scheme (UK NEQAS). The method was compared against two commercial immunoassays for fDPD and pyridinium cross-links, r 2 were 0.906 and 0.816 respectively. Urine concentrations of fDPD/Cr and fPYD/Cr were significantly higher in the patients than healthy individuals ( p  < 0.001). An average (±SD) fDPD:fPYD ratio of 0.29 (±0.08) was consistently observed across all subgroups. A markedly increased fDPD:fPYD ratio of 8.9 was observed in a patient with type VI Ehlers-Danlos Syndrome (EDS)., Conclusion: Simultaneous measurement of two free pyridinium cross-links provides a valuable, cost effective assessment tool for use in the diagnostic work-up of patients with metabolic bone disease. Improvements in sample extraction efficiency have increased assay specificity and analysis throughput. The use of the fDPD:fPYD ratio can assist in the diagnosis of type VI EDS., (© 2016 The Association for Mass Spectrometry: Applications to the Clinical Lab (MSACL). Published by Elsevier B.V.)

Purpose: To evaluate the features of periocular cutaneous malignancies that may contribute to larger surgical defects or require more complex reconstructive procedures., Methods: A retrospective review of 181 patients with biopsy proven periocular cutaneous malignancies seen between April 2005 and September 2010, and undergoing Mohs micrographic surgery was performed. The longest horizontal and vertical diameters of the tumor and the post-Mohs surgical defect were measured in each patient. These measurements were used to calculate the relative margin of resection (MOR) required for tumor eradication as well as the size of the surgical defect. The date of surgery, histologic diagnosis and location of the tumor, type of reconstruction, and the presence of recurrence were also recorded., Results: The average MOR for all tumor subtypes taken together was 3.4 mm horizontally and 2.6 mm vertically for basal cell carcinomas (BCCA). The post-Mohs defect area was 3.2 times greater than the preoperative tumor area for all BCCA subtypes, and 3.9 times greater for morphea type (p = 0.8083). The average MOR for squamous cell carcinomas (SCCA) was 5.1 mm horizontally and 3.7 mm vertically. The post-Mohs defect area was 3.8 times greater than the preoperative tumor area for SCCAs. When comparing the preoperative horizontal tumor diameter to the horizontal MOR of BCCAs and SCCAs, the correlation was 0.23 (p < 0.0001) and 0.31 (p < 0.0001), respectively. While the average MOR was within standard limits, a significant number of tumors required a greater MOR. On review of the data, 30.6% of patients with BCCA required a MOR greater than 3 mm, 17.3% of patients with BCCA required a MOR greater than 4 mm, and 29.1% of patients with SCCA required a MOR of greater than 5 mm. Tumors located at the lateral canthus required the largest MOR (p < 0.01), while those on the lower eyelid were associated with the smallest MOR in BCCAs. As expected from anatomical considerations, tumors at the medial canthus required significantly more complex reconstruction procedures (p < 0.01). An ordered logistic regression model demonstrated that BCCA preoperative clinical tumor surface area was a significant indicator for the degree of reconstruction required (p < 0.01)., Conclusions: Standard 3 mm to 4 mm MOR for BCCAs, and 5 mm MOR for SCCAs could result in an unacceptable risk of tumor recurrence if the surgical margins are not examined histologically. With increasing preoperative tumor size, there is an increase in the MOR required for BCCA and SCCA, supporting that large tumors require a greater MOR.

Background: Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied., Methods: Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone., Findings: A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy., Conclusions: In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range., Trial Registration Number: EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Alkaptonuria is a rare debilitating autosomal recessive disorder of tyrosine metabolism, where deficiency of homogentisate 1,2-dioxygenase results in increased homogentisic acid. Homogentisic acid is deposited as an ochronotic pigment in connective tissues, especially cartilage, leading to a severe early onset form of osteoarthritis, increased renal and prostatic stone formation and hardening of heart vessels. Treatment with the orphan drug, nitisinone, an inhibitor of 4-hydroxyphenylpyruvate dioxygenase has been shown to reduce urinary excretion of homogentisic acid., Method: A reverse phase liquid chromatography tandem mass spectrometry method has been developed to simultaneously analyse serum homogentisic acid, tyrosine and nitisinone. Using matrix-matched calibration standards, two product ion transitions were identified for each compound (homogentisic acid, tyrosine, nitisinone) and their respective isotopically labelled internal standards ((13)C6-homogentisic acid, d2-tyrosine, (13)C6-nitisinone)., Results: Intrabatch accuracy was 94-108% for homogentisic acid, 95-109% for tyrosine and 89-106% for nitisinone; interbatch accuracy (n = 20) was 88-108% for homogentisic acid, 91-104% for tyrosine and 88-103% for nitisinone. Precision, both intra- and interbatch were <12% for homogentisic acid and tyrosine, and <10% for nitisinone. Matrix effects observed with acidified serum were normalized by the internal standard (<10% coefficient of variation). Homogentisic acid, tyrosine and nitisinone proved stable after 24 h at room temp, three freeze-thaw cycles and 24 h at 4℃. The assay was linear to 500μmol/L homogentisic acid, 2000μmol/L tyrosine and 10μmol/L nitisinone; increased range was not required for clinical samples and no carryover was observed., Conclusions: The method developed and validated shows good precision, accuracy and linearity appropriate for the monitoring of alkaptonuria patients, pre- and post-nitisinone therapy., (© The Author(s) 2015.)

Despite the large number of metal-organic frameworks that have been studied in the context of post-combustion carbon capture, adsorption equilibria of gas mixtures including CO2, N2, and H2O, which are the three biggest components of the flue gas emanating from a coal- or natural gas-fired power plant, have never been reported. Here, we disclose the design and validation of a high-throughput multicomponent adsorption instrument that can measure equilibrium adsorption isotherms for mixtures of gases at conditions that are representative of an actual flue gas from a power plant. This instrument is used to study 15 different metal-organic frameworks, zeolites, mesoporous silicas, and activated carbons representative of the broad range of solid adsorbents that have received attention for CO2 capture. While the multicomponent results presented in this work provide many interesting fundamental insights, only adsorbents functionalized with alkylamines are shown to have any significant CO2 capacity in the presence of N2 and H2O at equilibrium partial pressures similar to those expected in a carbon capture process. Most significantly, the amine-appended metal organic framework mmen-Mg2(dobpdc) (mmen = N,N'-dimethylethylenediamine, dobpdc (4-) = 4,4'-dioxido-3,3'-biphenyldicarboxylate) exhibits a record CO2 capacity of 4.2 ± 0.2 mmol/g (16 wt %) at 0.1 bar and 40 °C in the presence of a high partial pressure of H2O.

Advantages of transcanalicular laser-assisted dacryocystorhinostomy (TCDCR) over conventional, external, and endonasal dacryocystorhinostomy (DCR) have been purported to include decreased operating time, reduced morbidity, enhanced cosmesis, avoidance of general anesthesia, and a shorter recovery time. However, 1 case of skin necrosis has recently been reported to have occurred following diode laser-assisted TCDCR, and the authors now report 3 additional cases that were evaluated by the Ophthalmic Plastic Surgery services at the University of North Carolina, North Carolina, and the University of California, San Francisco. Three patients developed full-thickness tissue necrosis over the medial canthus following TCDCR, and 2 of these patients experienced persistent tissue breakdown at the site following reconstructive repair.

Alkaptonuria (AKU) is a rare debilitating autosomal recessive disorder of tyrosine metabolism. Deficiency of homogentisate 1,2-dioxygenase results in increased homogentisic acid (HGA) which although excreted in gram quantities in the urine, is deposited as an ochronotic pigment in connective tissues, especially cartilage. Ochronosis leads to a severe, early-onset form of osteoarthritis, increased renal and prostatic stone formation and hardening of heart vessels. Treatment with the orphan drug, Nitisinone, an inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase has been shown to reduce urinary excretion of HGA, resulting in accumulation of the upstream pre-cursor, tyrosine. Using reverse phase LC-MS/MS, a method has been developed to simultaneously quantify urinary HGA and tyrosine. Using matrix-matched calibration standards, two product ion transitions were identified for each compound and their appropriate isotopically labelled internal standards. Validation was performed across the AKU and post-treatment concentrations expected. Intrabatch accuracy for acidified urine was 96-109% for tyrosine and 94-107% for HGA; interbatch accuracy (n=20 across ten assays) was 95-110% for tyrosine and 91-109% for HGA. Precision, both intra- and interbatch was <10% for tyrosine and <5% for HGA. Matrix effects observed with acidified urine (12% decrease, CV 5.6%) were normalised by the internal standard. Tyrosine and HGA were proved stable under various storage conditions and no carryover, was observed. Overall the method developed and validated shows good precision, accuracy and linearity appropriate for the monitoring of patients with AKU, pre and post-nitisinone therapy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The management of active thyroid eye disease (TED) can be a challenging therapeutic dilemma. The pathogenic complexity, disease heterogeneity, clinical unpredictability, and ocular morbidity associated with TED necessitate a team approach., Evidence Acquisition: A literature search ending on December 31, 2013, was performed using PubMed (http://www.ncbi.nlm.nih.gov/pubmed) with the following search terms: Graves' disease, hyperthyroidism, hypothyroidism, Graves' orbitopathy, Graves' ophthalmopathy, thyroid eye disease, thyroidectomy, antithyroid medications, radioactive iodine, orbital decompression, orbital radiotherapy (ORT), proptosis, and optic neuropathy. The search included manuscripts in English only. Additional articles and textbooks were retrieved from the reference list of articles that were obtained from the original PubMed literature search., Results: Corticosteroids, ORT, and orbital decompression have been the mainstay treatment modalities for active TED for more than 50 years. Few randomized controlled studies have systematically evaluated these treatment strategies, and of those trials that have been executed, they are difficult to compare and contrast because of inconsistencies in study design and outcome measures. Newer immunosuppressive and immunomodulating agents are being investigated with anecdotal evidence of improved efficacy compared with traditional treatments., Conclusions: All patients with TED must be assessed for disease activity and severity to determine the best course of action. Risk factor modification begins with smoking cessation and attaining euthyroid status. The first-line treatment for moderate-to-severe TED or dysthyroid optic neuropathy is systemic corticosteroids; but often a multimodality approach with the addition of ORT or orbital decompression may be required. The development of novel therapeutic agents against specific immunological targets will improve upon the current treatment armamentarium available to clinicians and patients with TED. Uniformly accepted, scientifically reliable and clinically valid outcome measures integrated into well-designed clinical trials are needed to advance the management of TED to a more evidence-based approach.

Purpose: To investigate, in the treatment of uveal melanomas, how tumor control, radiation toxicity, and visual outcomes are affected by the radiation dose at the tumor apex., Methods and Materials: A retrospective review was performed to evaluate patients treated for uveal melanoma with (125)I plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary endpoints included time to local failure, distant failure, and death. Secondary endpoints included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine associations between radiation dose and the endpoint variables., Results: One hundred ninety patients with sufficient data to evaluate the endpoints were included. The 5-year local control rate was 91%. The 5-year distant metastases rate was 10%. The 5-year overall survival rate was 84%. There were no differences in outcome (local control, distant metastases, overall survival) when dose was stratified by apex dose quartile (<69 Gy, 69-81 Gy, 81-89 Gy, >89 Gy). However, increasing apex dose and dose to 5-mm depth were correlated with greater visual acuity loss (P=.02, P=.0006), worse final visual acuity (P=.02, P<.0001), and radiation complications (P<.0001, P=.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (P=.0001)., Conclusions: Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis-free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Metallic foreign bodies in the lacrimal outflow tract are a rarely reported cause of nasolacrimal duct obstruction. Among the few cases in the literature, 1 consisted of a BB in the nasolacrimal duct. This case report presents a second case of chronic, recurrent dacryocystitis in a child, which occurred secondary to a BB that had become lodged in the lacrimal sac. The metallic foreign body was identified on CT and successfully removed surgically. Exogenous sources of lacrimal sac foreign bodies should be considered in patients with a history of periorbital trauma and signs of chronic nasolacrimal duct obstruction. Evaluation with CT is recommended. Removal of the foreign body, with dacryocystorhinstomy as needed, is curative.

Solitary fibrous tumors (SFTs) are rare spindle cell neoplasms of mesenchymal origin that most commonly arise within pleura and have also been reported in many extrapleural sites including the orbit. Cavitary changes within SFT of both pleura and extrapleural sites have been documented, but remain very rare. To the authors' knowledge, the third known case of an orbital solitary fibrous tumor containing large pseudocystic cavities is described. MRI demonstrated a heterogeneous enhancing mass with multiple cavities. Excisional biopsy revealed solid tumor with large cavities filled with straw-colored fluid and tumor cells that stained positive for CD34 and CD99 antigens, consistent with SFT. The patient had an uncomplicated postoperative course with no sign of recurrence and resolution of the proptosis after 12 months of follow up. SFT are rare benign orbital neoplasms that rarely present with cavitary changes. Current treatment options include complete surgical excision, which was performed in this case. Close follow up is advised to monitor for recurrence.

Purpose: To describe the effect of radiation therapy on intraocular pressure in patients who have had orbital radiation for Graves' orbitopathy, and to provide a descriptive analysis of these patients., Design: Retrospective case series., Participants: 24 consecutive patients referred for orbital radiation therapy for Graves' orbitopathy from December 1st, 2001 through July 31st, 2009., Intervention: Patients received a total of 2000 cGy fractionated over 10 days., Main Outcome Measures: Medical records were reviewed for: demographics, tobacco history, ocular history, history related to Graves' disease, medications, visual field tests, retinopathy, and physical exam findings. The two-tailed Student's t-test was used to determine statistically significant differences in intraocular pressure before radiation therapy and 0-3 (T1), 4-6 (T2), 7-12 (T3), and 13-18 (T4) months following radiation therapy., Results: 34 eyes were available for analysis. There was no correlation between intraocular pressure and SPECS scores. Mean intraocular pressure prior to radiation therapy was 18.15 ± 3.83 mm Hg. Patients who had orbital decompression, eye muscle surgery, or glaucoma were excluded from the final analysis. There were 7, 11, 14, and 11 eyes with data at times T1, T2, T3, and T4 following radiation therapy, respectively. There was a significant decrease in mean intraocular pressure at T2, T3 and T4 of 26.00% ± 9.25%, 11.75% ± 27.58%, and 16.72% ± 13.94%, respectively., Conclusions: There was a significant drop in mean intraocular pressure between 4 and 18 months after radiation therapy in our patient population. The mechanism by which this decrease in intraocular pressure occurs is not understood.

Purpose: The purpose of this study was to characterize the relationships among orbital dimensions, globe diameter, and subject age., Methods: A cross-sectional, retrospective analysis of 124 CT scans of subjects with no appreciable orbital or globe disease was performed by 1 observer (G.K.E.). Seventeen length measurements and 5 angle measurements of various aspects of the orbit were obtained. Subjects of similar age were grouped and analysis was performed to define the changes in these parameters in association with age., Results: One hundred twenty-four CT scans of 124 subjects without identifiable globe or orbital disease were included in this study. Twenty-one subjects ≥ 17 years of age were considered mature adults and grouped together, while the remaining 106 subjects were grouped according to age. Intraobserver variability between orbital measurements was excellent, r > 0.95 (p ≤ 0.01) for most measurements. There was no difference between right and left orbital measurements, as each was highly correlated to its contralateral counterpart. Globe diameter and all length measurements except globe protrusion increased most rapidly over the first 12 to 24 months and reached 86% to 96% of their respective adult means by age 8 years. Globe diameter and linear orbital measurements were highly correlated. Globe protrusion and measurements of orbital angles exhibited a different pattern., Conclusions: The pattern of human orbital growth is strongly correlated with the pattern of ipsilateral globe growth. This change is most rapid during the first 12 to 24 months of life and maintains a significant pace until reaching 86% to 96% of adult values for most parameters at age 8 years. After this age, the rate slows considerably until maturity. With this attempt to define normal age-related orbital change, the authors report a pattern of growth which may be clinically applicable in the management of pediatric anophthalmos.

Background: Teicoplanin is an antibiotic used for the treatment of endocarditis, osteomyelitis, septic arthritis and methicillin-resistant Staphylococcus aureus. Teicoplanin is emerging as a suitable alternative antibiotic to vancomycin, where their trough serum levels are monitored by immunoassay routinely. This is the first report detailing the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring teicoplanin in patients' serum., Methods: An Acquity™ UPLC (ultra-pressure liquid chromatography) tandem mass spectrometer was used to measure teicoplanin concentrations in samples from patients, quality assurance schemes and quality control preparations. Ristocetin was successfully implemented as a suitable internal standard. Ion suppression, linearity, stability, matrix effects, recovery, imprecision, lower limits of quantification and detection, interference and method comparison against immunoassay were all assessed., Results: Teicoplanin and ristocetin had elution times of 1.39 and 1.24 min, respectively. Ion suppression was shown to be negligible, and linear calibration curves (0-200 μg/mL) were consistently reproduced to have r(2) values >0.99. Postextraction stability was achieved up to 20 h, while matrix effects were minimal coupled with sample recovery of >93%. The lower limit of quantification was 1 μg/mL, and 0.2 μg/mL was the lower limit of detection. Interference with other antibiotics was dependent on the combination of drugs present in patients' serum. A method comparison between immunoassay and LC-MS/MS suggested a negative bias for tandem mass spectrometry., Conclusions: This novel method of teicoplanin determination by LC-MS/MS is proven to be a robust protocol that is consistent and reproducible. Clinicians searching for alternatives in therapeutic drug monitoring may have an additional option that is potentially more accurate and specific.

An 11-year-old boy presented with progressive right-sided proptosis and an orbital mass on neuroimaging. Incisional biopsy revealed an epithelioid hemangioma. The patient underwent an orbitotomy with subtotal excision of the mass. However, the tumor recurred and progressed to the cavernous sinus, despite oral steroids, tacrolimus, and a second subtotal excision. Because of encouraging results reported with beta-blockers in the treatment of pediatric capillary hemangiomas, the patient was subsequently started on oral propranolol, 2 mg/kg/day, with discontinuation of steroids and tacrolimus. A rapid and impressive interval decrease in tumor size was observed, with improvement in proptosis and exposure keratopathy. The patient remains without recurrence approximately 9 months after initiation of propranolol. Our results suggest that oral propranolol may be a potential alternative therapy when complete excision of an epithelioid hemangioma is not practical.

Purpose: To describe an unusual presentation of lipoblastomatosis and review the existing literature on lipoblastomatosis and lipoblastoma., Methods: Case report and literature review., Results: A 9-year-old girl was originally diagnosed as having preseptal cellulitis. After failure of systemic therapy, a CT scan showed a mass in the orbit. Biopsy of the lesion confirmed the presence of lipoblastomatosis, consisting of immature lipoblasts admixed with more-mature adipocytes., Conclusions: Lipoblastomatosis is a rare benign diffuse lipomatous tumor of embryonal fat that is uncommonly found in the head and face of children.

Spontaneous subperiosteal orbital hemorrhage is rare. The authors describe a case of acute bilateral eyelid swelling, eyelid ptosis, and double vision in a patient immediately following endoscopic retrograde cholangiopancreatography. CT revealed bilateral subperiosteal orbital hemorrhages. The patient demonstrated no signs of optic nerve compromise, and the hemorrhages resolved spontaneously without sequela. Previous reports in the literature have documented subperiosteal hemorrhages following increased intracranial venous pressure, coagulopathies, and prone positioning during procedures. To the authors' knowledge, subperiosteal orbital hemorrhages have not been previously described following endoscopic retrograde cholangiopancreatography. Ophthalmologists and gastroenterologists should be aware of this potential complication associated with this procedure.