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PURPOSE To determine the efficacy of a frontalis muscle flap eyelid reanimation technique for correction of severe congenital ptosis and associated amblyopia in infants. METHODS The authors performed a retrospective chart review of patients 12 months of age or younger with unilateral or bilateral congenital ptosis and associated amblyopia or deemed at high risk for amblyopia due to visual deprivation. Following ptosis repair via a frontalis muscle flap technique, primary outcomes of postoperative eyelid position and amblyopia reversal were assessed. RESULTS Seventeen eyes of 12 participants were included for study. Seven of these patients had simple congenital ptosis, and the remainder had ptosis as part of a syndrome. Nine were diagnosed with amblyopia preoperatively, and the remaining 3 were too young for acuity testing but had occlusion of the visual axis by the ptotic eyelid in primary gaze. Postoperatively, the mean margin-to-reflex distance 1 was 2.4 mm (range: 0.0-4.0), and 9 patients (75%) demonstrated no evidence of amblyopia. Only 2 patients had eyelid asymmetry greater than 2 mm, which in both cases was due to lack of frontalis activation by the patient secondary to ongoing visual impairment. The most common complication was lagophthalmos in 6 eyes (35.3%), with no significant associated surface keratopathy. CONCLUSIONS The frontalis muscle flap technique may offer a new and effective approach to treating infants with severe congenital ptosis causing poor eyelid excursion and associated amblyopia while avoiding use of an implant.

Purpose Conjunctival cicatrizing conditions are vision threatening, with poor outcomes despite aggressive systemic therapy. This study tests the utility of serial injections of 5-fluorouracil (5-FU) into the fornices to treat conjunctival scarring in patients with ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis. Methods Retrospective cohort study. Fisher exact test and multivariable logistic regression analyses were used to compare clinical outcomes of patients who were administered 5-FU injections versus patients who were not injected. Model fit was examined for multivariable regression. Results One hundred twelve eyes (56 patients) met the inclusion criteria. Thirty-eight eyes (34%) had Stevens-Johnson syndrome/toxic epidermal necrolysis, and 74 eyes (66%) were diagnosed with ocular cicatricial pemphigoid. Twenty-five eyes received ≥1 injection of 5-FU. Sixteen eyes received 1-4 injections, while 9 received ≥5. Median follow-up until last encounter was 18 months. Analysis of each disease entity alone and in combination revealed that 5-FU injections were associated with improvement in final visual acuity, corneal scarring, trichiasis, need for/number of mucous membrane graft surgeries, and severity of symblephara. Conclusions Serial injection of 5-FU in the affected fornices is a promising treatment for severe vision-threatening conjunctival scarring from ocular cicatricial pemphigoid and Stevens-Johnson syndrome/toxic epidermal necrolysis. Given the excellent safety profile of 5-FU around the eye, the solid biologic foundation for using 5-FU in this setting, and the severe risk of vision loss from these disorders, the authors suggest that serial 5-FU injections be adopted as therapy for conjunctival scarring from ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis despite the limitations of this retrospective study.

Purpose To perform a comprehensive review of dermis fat graft (DFG) in socket reconstruction and illustrate the technical nuances and outcomes using a retrospective case review. Methods A literature search of 143 texts was reviewed. A retrospective case series of 34 patients following primary or secondary DFG after enucleation at a single institution (2009-2019) was performed. Clinical outcomes were statistically analyzed. Variables investigated included age, sex, race, surgical indication, muscle reattachment, complications, motility, eyelid position, prosthesis fit, and need for additional surgery. Results The history of DFG, use in socket reconstruction, primary and secondary indications, and surgical techniques are described. Thirty-two adults and 2 pediatric cases of DFG were reviewed; 18.75% indications were primary and 81.25% were secondary. Good eyelid position was observed in 83.3% of patients with primary DFG versus 37.5% with secondary DFG (p = 0.07). Postoperative complications occurred in 58.8% of patients, were typically mild, and resolved with minimal or no intervention. No statistically significant differences were found between occurrence of any particular complication in primary versus secondary DFG placement (p = 0.36) or between primary and secondary DFG placement and the need for additional surgery (p = 1.0). Among the 67.7% patients who had implant exposure or extrusion as an indication for DFG, 39.1% required additional surgery within 2 years. Advanced age was not associated with higher complication rates (p = 0.12). Conclusions DFG is an excellent option for socket reconstruction, particularly in cases involving pediatric patients, complicated orbits, history of multiple previous surgeries, and inflamed, contracted, or scarred sockets.

We describe a case of an 18-year-old male who developed a supraorbital neuroma following facial trauma that occurred 2 years earlier. He presented with complaints of persistent facial pain and migraines despite successful laceration repair and removal of foreign bodies at the time of injury. A non-contrast computed tomography (CT) scan of the orbits revealed an enlarged supraorbital nerve with remodeling and expansion of the supraorbital notch, suggesting a neuroma. The patient underwent orbitotomy with excision of neuroma (confirmed histologically) and experienced a complete resolution of periorbital pain.

To date, there are no studies on healthcare resource utilization (HRU) and costs for treating periocular basal cell carcinoma (pBCC). We investigated real-world HRU and costs of patients with limited versus extensive pBCC.This was a retrospective cost analysis.Administrative claims database was mined for basal cell carcinoma (BCC)-related claims from January 2011 to December 2018. Patients had ≥1 inpatient or ≥2 outpatient nondiagnostic claims for pBCC ≥30 days apart, ≥6 months of continuous enrollment in a health plan before the index date, and ≥18 months of continuous enrollment after the index date. Patients were categorized by disease severity (limited or extensive) using Current Procedural Terminology codes. A total of 1368 patients were propensity matched 1:1 for limited and extensive pBCC (n = 684 each). Outcomes were cost and HRU measures during the 18-month follow-up period.Patients with extensive disease had a higher number of outpatient visits (32.47 vs 28.81; P.0001), radiation therapies (0.53 vs 0.17; P = .001), surgeries (1.82 vs 1.24; P.001), days between first and last surgery (40.82 vs 16.51 days; P.001), outpatient pBCC claims (3.89 vs 3.38; P.001), and days between pBCC claims (170.43 vs 144.01 days; P.001). Patients with extensive disease incurred higher total all-cause costs ($36,986.10 vs $31,893.13; P = .02), outpatient costs ($20,450.26 vs $16,885.87; P = .005), radiation therapy costs ($314.28 vs $89.81; P = .01), and surgery costs ($3,697.08 vs $2,585.80; P.001) than patients with limited disease.Patients with extensive pBCC incurred higher costs, greater HRU, and longer time between first and last surgery versus patients with limited pBCC. Early diagnosis and early treatment of pBCC have economic benefits.

Background Basal cell carcinoma (BCC) is a common skin cancer often curable by excision; however, for patients with BCC around the eye, excision places visual organs and function at risk. In this article, we test the hypothesis that use of the hedgehog inhibitor vismodegib will improve vision‐related outcomes in patients with orbital and extensive periocular BCC (opBCC). Materials and Methods In this open‐label, nonrandomized phase IV trial, we enrolled patients with globe‐ and lacrimal drainage system–threatening opBCC. To assess visual function in the context of invasive periorbital and lacrimal disease, we used a novel Visual Assessment Weighted Score (VAWS) in addition to standard ophthalmic exams. Primary endpoint was VAWS with a score of 21/50 (or greater) considered successful, signifying globe preservation. Tumor response was evaluated using RECIST v1.1. Surgical specimens were examined histologically by dermatopathologists. Results In 34 patients with opBCC, mean VAWS was 44/50 at baseline, 46/50 at 3 months, and 47/50 at 12 months or postsurgery. In total, 100% of patients maintained successful VAWS outcome at study endpoint. Compared with baseline, 3% (95% confidence interval [CI], 0.1–15.3) experienced major score decline (5+ points), 14.7% (95% CI, 5 to 31.1) experienced a minor decline (2–4 points), and 79.4% experienced a stable or improved score (95% CI, 62.1–91.3). A total of 56% (19) of patients demonstrated complete tumor regression by physical examination, and 47% (16) had complete regression by MRI/CT. A total of 79.4% (27) of patients underwent surgery, of which 67% (18) had no histologic evidence of disease, 22% (6) had residual disease with clear margins, and 11% (3) had residual disease extending to margins. Conclusion Vismodegib treatment, primary or neoadjuvant, preserves globe and visual function in patients with opBCC. Clinical trail identification number.NCT02436408. Implications for Practice Use of the antihedgehog inhibitor vismodegib resulted in preservation of end‐organ function, specifically with regard to preservation of the eye and lacrimal apparatus when treating extensive periocular basal cell carcinoma. Vismodegib as a neoadjuvant also maximized clinical benefit while minimizing toxic side effects. This is the first prospective clinical trial to demonstrate efficacy of neoadjuvant antihedgehog therapy for locally advanced periocular basal cell carcinoma, and the first such trial to demonstrate end‐organ preservation., This article reports the results of a prospective clinical trial of vismodegib for patients with basal cell carcinoma occurring in the orbital and periocular regions to assess whether such treatment helps to preserve visual organs and function.

PURPOSE To test whether intraoperative stereotactic navigation during orbital decompression surgery resulted in quantifiable surgical benefit. METHODS This retrospective cohort study examined all consecutive patients who underwent primary orbital decompression surgery for thyroid associated orbitopathy performed by a single surgeon (A.K.) during the periods of 2012-2014 (non-navigated), and 2017-2018 (navigated). The study was HIPAA-compliant, was approved by the Institutional Review Board, and adhered to the tenets of the Helsinki declaration. Recorded parameters included patient age, sex, race, decompression technique (side of operation and walls decompressed), estimated blood loss (EBL), intraoperative complications, times that patient entered and exited the operating room (OR), times of surgical incision and dressing completion, pre- and postoperative best corrected visual acuity (BCVA), proptosis, diplopia, postoperative change in strabismus deviation, and need for subsequent strabismus surgery. Recorded times were used to calculate operating time (initial incision to dressing) and maintenance time (time between OR entry and initial incision and time between dressings and OR exit). The total maintenance time was averaged over total number of operations. Student t test was used to compare surgical times, maintenance times, EBL, and proptosis reduction. Fisher exact test was used to compare BCVA change, strabismus deviation change, resolution or onset of diplopia, and need for corrective strabismus surgery. RESULTS Twenty-two patients underwent primary orbital decompression surgery without navigation, and 23 patients underwent navigation-guided primary orbital decompression surgery. There were no intraoperative complications in either group. The average operative time was shorter in the navigated group for a unilateral balanced decompression (n = 10 vs. 19; 125.8 ± 13.6 vs. 141.3 ± 19.4 min; p-value = 0.019), and a unilateral lateral wall only decompression (n = 13 vs. 3; 80.5 ± 12.8 vs. 93.0 ± 6.1 min; p-value = 0.041). The average maintenance time per surgery was not significantly different between the non-navigated group (51.3 ± 12.7 min) and the navigated group (50.5 ± 6.4 min). There was no significant difference between the navigated and non-navigated groups in average EBL per surgery. There was no significant difference in BCVA change. Average proptosis reduction was larger in the navigated group, but this was not significant. There was a significantly lower proportion of patients who required corrective strabismus surgery following decompression in the navigated group than in the non-navigated group (39.1% vs. 77.3%, p-value = 0.012). CONCLUSIONS Intraoperative stereotactic navigation during orbital decompression surgery has the potential to provide the surgeon with superior spatial awareness to improve patient outcomes. This study found that use of intraoperative navigation reduced operative time (even without factoring in a resident teaching component) while also reducing the need for subsequent strabismus surgery. This study is limited by its size but illustrates that use of intraoperative navigation guidance has substantive benefits in orbital decompression surgery.

The transcranial approach to the orbit requires specialized knowledge, skill, and instrumentation. It can be performed by neurosurgeons but is commonly approached collaboratively, with an orbital, skull base, and/or craniofacial plastic surgeon joining the neurosurgical team to provide specialized skills. The role of the ophthalmic plastic surgeon, as an orbital specialist, includes preoperative evaluation and planning, intraoperative anatomic expertise, and postoperative care.

Surgical management of thyroid eye disease (TED) has two general aims: (1) relieve symptoms of orbital congestion and fibrosis, including possibly compressive optic neuropathy, and (2) reconstruct the periocular region to reduce deformity and renormalize appearance. Surgical management follows a sequence that is tailored to individual patient needs. The signs and symptoms of TED that can be addressed surgically include proptosis, orbital pressure/pain, orbital inflammatory signs, diplopia secondary to restrictive strabismus, ocular surface exposure secondary to lagophthalmos, and eyelid retraction. Because orbital decompression surgery can improve lagophthalmos and eyelid retraction, and can affect strabismus (positively or negatively), these issues are traditionally addressed sequentially by orbital decompression first, followed by strabismus surgery, and finally eyelid retraction repair, as needed. In this chapter, we focus primarily on orbital decompression surgery and eyelid surgery, although key aspects of strabismus surgery are also discussed.

Thyroid eye disease (TED) is caused by an inflammatory process involving the orbit and periorbital tissues in the setting of autoimmune thyroiditis. TED has been shown not only to impact visual and social functioning but also to reduce patients’ quality of life. Thyroid dysfunction in TED most frequently involves hyperthyroidism secondary to Graves’ disease (GD); hypothyroidism secondary to Hashimoto’s thyroiditis, or subclinical inflammation, are involved less commonly. Approximately 25–50% of patients with GD will develop clinically apparent TED some time during their lifetime. Sight-threatening disease is infrequent and occurs in approximately 3–5% of patients. In contrast, subclinical manifestations, including radiographic evidence of enlargement of extraocular muscles, may be present in a larger subset of patients.

Stereotaxy involves the use of computerized technology to identify a point in three dimensions using a Cartesian coordinate system, which can be used for preoperative surgical planning and intraoperative computer-assisted surgical navigation. Stereotactic technology allows for the visualization of surgical anatomy and instrument placement intraoperatively in real-time on preoperatively acquired images, typically computed tomography (CT), magnetic resonance imaging (MRI), or CT-MRI fusion studies. Image-guided surgery has modernized a variety of surgical interventions, including radiosurgery, biopsy, implantation, resection, stimulation, and reconstruction. Although neurosurgery is the field that most frequently utilizes stereotaxy, skull base surgery, otolaryngology, oral and maxillofacial surgery (OMFS), orthopedic surgery, and other medical specialties have also appropriated image-guided surgery into their armamentarium, with notable improvements in patient outcomes. Importantly, the use of stereotactic navigation has been extended to orbital surgery by neurosurgeons, skull base surgeons, and OMF surgeons – a natural extension of this useful surgical tool.

Periocular skin is highly prone to malignancies, especially basal cell and squamous cell carcinomas. Because of the complex anatomy and eye-protecting functions of the periocular tissues, treatment of these cancers requires special considerations. Mohs micrographic surgery is usually the treatment of choice, whenever possible, in order to enhance margin control while limiting collateral damage to nearby normal structures. Cancer excision, whether by Mohs or other techniques, will leave a complex defect that requires careful anatomical and functional reconstruction. This study presents some of the challenges of treating periocular skin cancer and associated reconstructive surgery and provides an intellectual framework for addressing these challenges. The key topics are adherence to anatomical landmarks and aesthetic units, proper distribution of tension, and matching the correct reconstructive approach, that is, type of flap or graft, to the defect at hand. This review is not meant to be exhaustive, but it will provide both basic and advanced considerations.

Gliomas are primary brain tumors characterized by their invasiveness and heterogeneity. Specific histological patterns such as pseudopalisades, microvascular proliferation, mesenchymal transformation and necrosis characterize the histological heterogeneity of high-grade gliomas. Our laboratory has demonstrated that the presence of high densities of mesenchymal cells, named oncostreams, correlate with tumor malignancy. We have developed a unique approach to understand the mechanisms that underlie glioma’s growth and invasion. Here, we describe a comprehensive protocol that utilizes laser capture microdissection (LMD) and RNA sequencing to analyze differential mRNA expression of intra-tumoral heterogeneous multicellular structures (i.e., mesenchymal areas or areas of tumor invasion). This method maintains good tissue histology and RNA integrity. Perfusion, freezing, embedding, sectioning, and staining were optimized to preserve morphology and obtain high-quality laser microdissection samples. The results indicate that perfusion of glioma bearing mice using 30% sucrose provides good morphology and RNA quality. In addition, staining tumor sections with 4% Cresyl violet and 0.5% eosin results in good nuclear and cellular staining, while preserving RNA integrity. The method described is sensitive and highly reproducible and it can be utilized to study tumor morphology in various tumor models. In summary, we describe a complete method to perform LMD that preserves morphology and RNA quality for sequencing to study the molecular features of heterogeneous multicellular structures within solid tumors.

The development of orbit-eroding mucocele associated with inverted papilloma has been rarely reported., Here, the authors present a case and surgical management of a patient with orbit-eroding mucocele associated with inverted papilloma who declined craniotomy. A combined approach utilizing frontal endoscopic sinus surgery and external sub-brow anterior orbitotomy was used to explore, drain, and excise the mucocele and inverted papilloma. Gelatin sponges soaked in gentamicin were used to cover the exposed dura and to protect the orbital content from the frontal sinus cavity.A fronto-ethmoidal sinus inverted papilloma associated with recurrent orbit-eroding mucocele was excised by combined transnasal endoscopic and external sub-brow anterior orbitotomy approach using stereotactic navigation.

Orbital arteriovenous malformations are rare congenital vascular anomalies that can cause eyelid distortion, proptosis, diplopia, and vision loss. The current treatment paradigm involves endovascular embolization followed by resection, with delayed reconstruction. The authors report 2 young adult patients with orbital arteriovenous malformations, who underwent embolization followed days to months later by resection with immediate soft tissue reconstruction. For both patients, the immediate outcome provided good functionality and cosmesis. The authors conclude that immediate reconstruction after embolization-resection of orbital arteriovenous malformations may facilitate early return of form and function for patients, improve quality of life, and potentially reduce the need for further reconstructive procedures.

Geriatric patients (age ≥ 65) are prone to complications after surgery and are at risk for severe thyroid eye disease (TED). In this study, we aim to identify preoperative demographic and TED patterns associated with geriatric patients who underwent decompression surgery, to examine the effect of age on postoperative strabismus rates, and to identify factors that may contribute to postoperative strabismus in the geriatric subgroup. We retrospectively reviewed patients who underwent thyroid-related orbital decompression surgery at the Kellogg Eye Center, University of Michigan, between 1999 and 2014. Primary outcome was postoperative strabismus requiring palliation with prisms and/or strabismus surgery. Descriptive, univariate, and multivariable logistic regression analyses were used to define association of geriatric age with postoperative strabismus and determine predictors of postoperative strabismus. Of 241 patients, 41 (17.0%) were geriatric. They were less likely to undergo bilateral decompression (P = 0.012), less likely to be current smokers at time of decompression (P = 0.002), and more likely to have preoperative primary gaze diplopia (P = 0.001). Postoperative strabismus rates for geriatric patients (≥ 65 years of age), versus ages 50–65, 30–50, and < 30, were 73.2%, 41.3%, 31.9%, and 15.8%, respectively (P = 0.002). On multivariable analysis, geriatric age remained an independent risk factor for postoperative strabismus when compared to each age group (P ≤ 0.001). Among geriatric patients in subgroup multivariable analysis, balanced as opposed to lateral wall decompression (P = 0.038) and shorter TED duration (P = 0.031) were independently predictive of postoperative strabismus.

Microphthalmia is defined by a globe axial length greater than or equal to 2 standard deviations below the age-adjusted mean and can occur as part of a broader syndrome. The presence of a colobomatous cyst with microphthalmia signifies failure of the embryonic neuroectodermal fissure to close appropriately during development of the globe, creating a protuberant globular appendage that inhibits normal growth and development of the eye itself. Cystic reaccumulation of fluid is common after aspiration or surgical removal. Here, the authors describe a case of a young boy with a colobomatous cyst who underwent eyelid-sparing orbital exenteration followed by reconstruction with absorbable gelatin sponge (Gelfoam, Pfizer, Inc.) and the chemotherapeutic agent bleomycin to promote scarring, achieving the equivalent of a biointegrated implant and facilitating satisfactory placement of an ocular prosthesis. A 2-year follow-up MRI revealed adequate volume in the posterior orbit.

Purpose Thyroid eye disease (TED) is an inflammatory orbitopathy with significant impact on visual function and quality of life. Although studies have shown that patients who are deficient in vitamin D are more likely to develop autoimmune conditions, there are no studies demonstrating a definitive correlation between serum 25-hydroxyvitamin D (25(OH)D) deficiency and an increased risk of TED. Methods This retrospective case-control study compared serum 25(OH)D levels among 4 groups: 1) Graves disease (GD) patients with TED (n = 89); 2) GD patients without TED (n = 89); and healthy control patients matched to 3) the TED group (n = 356); and 4) the GD group (n = 356). The authors compared 25(OH)D level in the TED group measured within 1 year of TED diagnosis to the most recently measured 25(OH)D level in the GD group using Student t test of the log transformation of serum levels. Linear regression was used to control for other risk factors. Thyroid eye disease patients and GD patients were compared separately to their matched healthy control patients with linear mixed models. Results Thyroid eye disease patients displayed significantly lower serum 25(OH)D levels than GD patients (24.8 ± 13.2 ng/ml vs. 29.4 ± 13.3 ng/ml; p = 0.006). Controlling for smoking status and previous radioactive iodine treatment did not affect this statistically significant difference. Conclusions Low serum vitamin D is associated with TED diagnosis. Assessing and supplementing vitamin D levels may be an important addition to the early management of GD patients. Future research should include longitudinal studies and prospective clinical trials to further explore the mechanism responsible for the observed association.Thyroid eye disease is an inflammatory orbitopathy associated with Graves disease. Vitamin D is a known immune system regulator. The authors show that vitamin D deficiency is associated with the development of thyroid eye disease.

PURPOSE Congenital ptosis can threaten visual function and is usually treated with surgical correction. This study tests the hypothesis that congenital ptosis involves not only the levator muscle but also the orbital septum, which may tether the eyelid in the primary position. METHODS A retrospective chart review was performed on 30 patients (41 eyelids) with congenital ptosis who underwent surgical correction that included partial septum excision. Histologic analysis was performed by a masked pediatric pathologist, with grading of septal tissue disorganization and fibrosis based on standard histologic criteria. An independent comparison of histologic grading with clinical ptosis measures was then performed. RESULTS Fifteen eyelids demonstrated significant septal fibrosis, 19 were mild, and 7 were not fibrotic. Thirty-six eyelids demonstrated histologic disorganization. Mildly fibrotic eyelids were found to have reduced preoperative levator function than those that were not fibrotic (2.84 ± 1.92 vs. 9.57 ± 4.76 mm; p < 0.0001). Samples that demonstrated significant fibrosis were also found to have reduced preoperative levator function (4.67 ± 2.12 vs. 9.57 ± 4.76 mm; p = 0.0007). Histologically disorganized samples were also found to have a lower preoperative levator function (9.50 ± 6.04 vs. 3.99 ± 2.49; p = 0.0052). CONCLUSIONS Orbital septae in patients with congenital ptosis demonstrate histologic disorganization and fibrosis. When decreased levator function is observed clinically, septal fibrosis and/or disorganization is likely present. These observations suggest that debulking the fibrotic septum during congenital ptosis surgery may improve outcomes by releasing the eyelid from its congenitally tethered position, improving eyelid elasticity.

Purpose To compare the visual and exophthalmometry outcomes of simultaneous versus staged balanced decompression in patients with thyroid-related compressive optic neuropathy (CON). Methods All consecutive patients who underwent simultaneous or staged balanced decompressions for clinically diagnosed thyroid-related CON performed by 4 surgeons at the Kellogg Eye Center of the University of Michigan between 1999 and 2014 were included in the study. Demographic, medical, and surgical covariates were collected. Orbits were stratified by decompression technique. Primary outcomes were improvement in CON score (which quantifies visual dysfunction using logarithm of the minimum angle of resolution, color vision, and Humphrey visual field mean deviation), and improvement in proptosis. The authors performed univariate and descriptive statistics to identify baseline differences and covariates associated with the outcomes of interest; multivariate mixed linear regression models (to adjust for interorbit correlation) were then constructed with inclusion of potential confounders with p value ≤0.1. Results In total, 80 orbits of 53 patients were included in the study. Of the 80 orbits, 61% underwent simultaneous balanced decompression, and 39% underwent staged balanced decompression. Mean CON score reduction was 6.12 ± 9.7 and mean proptosis reduction was 5.63 ± 2.6 mm. Staged balanced decompression was significantly associated with greater CON score reduction (p = 0.038). However, staged (vs. simultaneous) decompression technique did not remain an independent predictor (p = 0.950) after multivariate analysis adjusted for confounders. For proptosis reduction, there were no statistically significant differences between simultaneous and staged balanced decompression on univariate (p = 0.122) or multivariate mixed linear regression models (p = 0.812). Conclusion Simultaneous and staged balanced decompression are equally efficacious in treating visual dysfunction and exophthalmos due to thyroid eye disease in patients with clinically diagnosed CON. Patient choice should be the primary consideration and care should be individualized. Further studies validating the CON score used in the study and comparative studies individualizing surgical treatment of thyroid eye disease are warranted.

Thyroid eye disease (TED) usually has mild manifestations in pediatric patients, and orbital decompression is rarely necessarily. The authors present the clinical course of 3 pediatric patients age 16 or younger at the time of decompression surgery with severe orbitopathy. Case 1 is a 9-year-old prepubertal Asian-American female with Graves' disease and TED who underwent balanced decompression for compressive optic neuropathy. Case 2 is a 14-year-old white female with Graves' disease and TED who underwent balanced decompression for compressive optic neuropathy, stretch optic neuropathy, and globe subluxation. Case 3 is a 14-year-old African-American male with unilateral euthyroid TED who underwent staged right-sided lateral, medial, and floor decompressions for asymmetric proptosis. All cases also had disfiguring proptosis and exposure keratopathy, and in all cases, surgery successfully ameliorated the indications. Children, both pre- and post-pubertal, can rarely manifest visually threatening severe orbitopathy due to TED. This represents the first reports of thyroid-related optic neuropathy and globe subluxation in pediatric patients. Further studies examining the mechanism responsible for the disparities in pediatric and adult TED are warranted.

Thyroid-associated orbitopathy (TAO) is a disfiguring periocular connective tissue disease associated with autoimmune thyroid disorders. It is a potentially blinding condition, for which no effective pharmacological treatment has been established. Despite a suggested role played by autoimmune thyrotropin receptor activation in the pathogenesis of TAO, the cellular and molecular events contributing to the fibrotic and inflammatory disease process of TAO are not fully defined. By developing a three-dimensional organoid culture of human orbital fibroblasts (OFs), we sought to determine the molecular mechanism underlying the fibrotic disease process of TAO. In this ex vivo model, we have demonstrated that hypoxia-inducible factor (HIF) 2α (HIF2A), but not its paralog HIF1A, accelerates extracellular matrix (ECM) deposition by inducing a collagen-cross-linking enzyme, lysyl oxidase (LOX). Inhibiting HIF2A and LOX with short hairpin RNA or small molecular antagonists effectively ameliorated fibrotic disease process within TAO organoids. Conversely, the overexpression of a constitutively active HIF2A in mouse OFs was sufficient to initiate LOX-dependent fibrotic tissue remodeling in OF organoids. Consistent with these findings, HIF2A and LOX were highly expressed in human TAO tissues paralleling excess ECM deposition. We propose that the HIF2A-LOX pathway can be a potential therapeutic target for the prevention and treatment of TAO.

PURPOSE To review physician-based clinical surveys published in Ophthalmic Plastic and Reconstructive Surgery. METHODS Complementary Ovid and PubMed searches of Ophthalmic Plastic and Reconstructive Surgery journal content were performed for the term "survey." Results were narrowed to studies that specifically addressed physicians' clinical practices. This search resulted in 162 articles, and after dual-investigator independent screening, 13 surveys met inclusion criteria. RESULTS Of the 13 surveys published from 2007 to January 2017, 6 were published since 2015, showing an increased trend in survey-based publications. Topics included assessing practice patterns regarding eyelid disorders, thyroid eye disease, optic nerve sheath fenestration, anophthalmic socket, and diagnosing lacrimal disorders. Average response rate was 38.7% (range 17.5-60%), with 201 average number of replies (range 72-310). Nine out of 13 surveys included some form of statistical analysis with the remainder presenting data in percentages. CONCLUSIONS There has been an increased rate of survey-type publications in Ophthalmic Plastic and Reconstructive Surgery over the past 10 years. The low response rate and frequent lack of statistical analysis raise concerns regarding the validity and usefulness of such studies. The authors believe that survey studies can be improved through better standardization and the use of author guidelines. They have made specific recommendations to improve the impact of survey papers in the future.

Poly-DL-lactide polymer implants absorb over a period of 6 to 12 months and have been used with increasing frequency for repair of orbital fractures. The authors describe the case of a 7-year-old boy who presented with orbital inflammation 10 months following repair of a white-eyed blowout fracture with a poly-DL-lactide implant. Rapid improvement in symptoms followed initiation of oral steroids, with excellent long-term result. Clinical presentation and treatment response implicated a foreign body inflammatory reaction as the underlying etiology of symptoms. Ophthalmologists and orbital surgeons should be aware that absorbable implants can demonstrate this late idiosyncratic complication.

Purpose Evaluate the effectiveness of vismodegib in the management of basal cell carcinoma with orbital extension and/or extensive periocular involvement. Methods Retrospective chart review of 6 consecutive patients with biopsy-proven orbital basal cell carcinoma and 2 additional patients with extensive periocular basal cell carcinoma who were treated with oral vismodegib (150 mg/day) was performed. Results Basal cell carcinoma extended in the orbit in 6 of 8 patients (involving orbital bones in 1 patient), and 2 of 8 patients had extensive periocular involvement (1 with basal cell nevus syndrome). Vismodegib therapy was the only treatment in 6 patients, off-label neoadjuvant in 1 patient, and adjuvant treatment in 1 patient. Orbital tumors in all 4 patients who received vismodegib as sole treatment showed partial response with a mean 83% shrinkage in tumor size after a median of 7 months of therapy. In the 2 patients receiving vismodegib as neoadjuvant or adjuvant therapies, there was complete response after a median of 7 months of therapy and no evidence of clinical recurrence after discontinuing therapy for a median of 15 months. The 2 patients with extensive periocular involvement experienced complete clinical response after a median 14 months of treatment. During treatment, the most common side effects were muscle spasm (75%) followed by alopecia (50%), dysgeusia (25%), dysosmia, and episodes of diarrhea and constipation (13%). Conclusions Basal cell carcinoma with orbital extension and extensive periocular involvement responds to vismodegib therapy. The long-term prognosis remains unknown, and additional prospective studies are indicated.

Despite the number of publications on orbital decompression surgery for thyroid eye disease, there are few comparative studies and most studies are underpowered. The goal of the study is to use multivariable analysis to identify independent patient and disease-related predictors of response to decompression surgery and of need for secondary decompressions. The authors retrospectively reviewed all patients who underwent transorbital thyroid-related orbital decompression surgery at the Kellogg Eye Center of the University of Michigan between 1999 and 2014. Demographic, medical, and surgical covariates were collected. Decompression techniques included medial, lateral, and balanced decompressions, with or without orbital fat removal. Main outcomes included proptosis reduction and secondary decompressions, both analyzed at the orbital level. Univariate and multivariable analyses (with adjustment for interorbit correlation) were conducted to determine predictors of the outcomes of interest. Mean proptosis reduction was 3.8 ± 2.4 mm (mean ± standard deviation, N = 420 orbits). The secondary decompression rate was 13.8% (82/594). On multivariable mixed linear regression, larger preoperative proptosis (p < 0.0001), balanced decompression (p = 0.0002), thyroid eye disease duration < 4 years (p = 0.0093), and history of orbital radiation (p = 0.0111) were all predictive of greater proptosis reduction. On multivariable survival modeling, factors associated with increased hazard for secondary decompression include younger age (p = 0.0434), larger preoperative proptosis (p = 0.0001), unilateral decompression (p = 0.0272), preoperative steroid treatment (p = 0.0200), and normal thyroid function (p = 0.0148). Factors associated with decreased hazard include adjunctive fat decompression (p = 0.0004), balanced decompression (vs. lateral, p = 0.0039), and African-American ethnicity (p = 0.0076). Despite a diverse study cohort, the authors have identified factors associated with clinically relevant outcomes of decompression surgery for thyroid eye disease, including proptosis reduction and incidence of secondary decompression. Randomized controlled trials of different treatment algorithms for TED are needed to devise optimized guidelines for individualizing surgical care.

Purpose: To describe the clinical course of a patient with a retrobulbar orbital tumor causing myopic shift and macular pucker. Observation: Following complete surgical removal of a retrobulbar orbital cavernous hemangioma, the myopic shift improved but the macular pucker persisted even 3 years after orbital surgery, with no sign of tumor recurrence. Conclusion and importance: Chorioretinal folds secondary to chronic mechanical force from an orbital tumor may persist long after the tumor is removed. This case may assist ophthalmologists in their discussions with, and counseling of, patients regarding visual prognosis following excision of orbital tumors that are causing retinal changes. Keywords: Cavernous hemangioma, Macular pucker, Choroidal folds, Orbit tumor, Orbit mass

The purpose of this case report is to describe reversible systemic symptoms associated with ocular torticollis due to blepharoptosis. A retrospective chart review identified patients with symptomatic ocular torticollis due to bilateral congenital or acquired blepharoptosis who underwent surgical correction (levator resection or frontalis sling). Preoperative and postoperative assessment of systemic symptoms in adults and developmental milestones are reported. The authors present 4 cases, 1 adult and 3 young children, all with severe bilateral upper eyelid ptosis. In the adult patient, it caused debilitating back pain that required orthopedic evaluation but was completely relieved with ptosis repair surgery. In the toddlers, subjective developmental motor delay was rapidly reversed following ptosis repair surgery. The authors suggest that primary care physicians, and spine and neuromuscular specialists, consider the possibility of ocular torticollis due to eyelid ptosis in the evaluation of patients with unexplained back and/or neck pain or with gross motor developmental delay. The authors propose that symptomatic ocular torticollis is an indication for ptosis repair.

Objective: To present our indications, technique, and results for a modified subcutaneous forehead lift. Methods: Retrospective chart review of 16 patients who underwent a subcutaneous forehead lift. Results: Tumescent anesthesia was used in all 16 patients. Seven patients underwent the procedure without the use of a fibrin sealant, whereas a commercially available fibrin sealant was used in the other 9 surgeries. In 1 of 7 patients in whom a fibrin sealant was not used, a postoperative seroma was evacuated in the first 24 hours after surgery. In patients in whom a fibrin sealant was used, there were no cases of hematomas or seromas. Twelve patients had concomitant upper eyelid surgery (ptosis repair and/or blepharoplasty), and 4 patients had no upper eyelid surgery. Two patients had a small dehiscence with no long-term sequelae. There were no instances of keloid formation. Postoperative brow position was judged to be good in 9 patients, adequate in 4 patients, and undercorrected in 3 patients. Forehead rhytids were improved in all patients. There were 2 cases of asymmetry, 1 of them in a patient with a history of Bell's palsy. There were no cases of symptomatic postoperative scalp hypoesthesia or decreased forehead movement. Our analysis revealed a trend toward improved postoperative brow position with increasing experience, which was manifested in a more aggressive release of the subcutaneous attachments of the lateral brow and a larger skin excision. Conclusions: Subcutaneous forehead lift with tumescent anesthesia and a fibrin sealant is a safe and effective technique that provides the surgeon with good control of brow positioning while directly addressing forehead rhytids. It avoids significant postoperative scalp hypoesthesia. In our series, the use of a fibrin sealant was correlated with elimination of postoperative hematoma or seroma, even though these patients had no postoperative pressure dressings. This technique can be an important addition to the oculofacial surgical armamentarium.

PURPOSE To review the treatment modalities available to clinicians who treat orbital and periocular vascular anomalies, with a focus on newer approaches. METHODS The authors' experience, along with a literature review, was used to provide a concise summary of the available approaches to the treatment of periocular vascular anomalies. Emerging diagnostic tools and therapies are highlighted. RESULTS The treatment of orbital and periocular vascular anomalies, including vascular malformations and tumors, increasingly utilizes a multidisciplinary team and a combination of endovascular, percutaneous, and open surgical techniques. CONCLUSIONS A growing reliance on new instrumentation and tools in a team-oriented approach to treatment may lead to better results with improved visual function and cosmesis and with reduced risk of complications.

Carcinoid tumors are rare, slow-growing, low-grade neuroendocrine tumors with a propensity for orbital metastatic spread. The typical treatment paradigm for localized orbital disease involves excision, adjuvant radiotherapy, and/or receptor-targeted chemotherapy, followed by delayed evaluation for reconstructive strabismus surgery. We present a 58-year-old female patient with carcinoid tumor metastatic to the right inferior rectus muscle who presented with worsening binocular diplopia. The patient underwent coordinated "tag-team" orbital and strabismus surgeries that included excision of the right inferior rectus muscle to the annulus of Zinn followed immediately by reconstructive strabismus surgery. The patient required 1 additional strabismus surgery 1 year later. Follow up revealed no tumor recurrence at 4 years, and excellent binocular vision with good function. Deep orbital and strabismus surgeries, when performed simultaneously in a "tag-team" approach, may offer superior functional outcomes and improved patient quality of life, with expedited functional recovery. This approach may become a new treatment paradigm for surgical disease processes localized to the extraocular muscles.

PURPOSE To characterize the presenting characteristics, preoperative clinical activity score (CAS), surgical approach, and visual outcomes in patients with thyroid eye disease undergoing repeat orbital decompression for recurrent or recalcitrant compressive optic neuropathy (CON). METHODS The medical records of patients with recurrent or recalcitrant CON undergoing repeat orbital decompressions were retrospectively reviewed. The primary outcome measures included pre- and postoperative Humphrey visual field mean deviation, visual acuity (VA) measured in logarithm of the minimal angle of resolution, color vision measured by Ishihara plates, and presence of relative afferent pupillary defect. Details of the surgical procedure and each patient's CAS at presentation were also recorded. RESULTS Six patients, 9 orbits, with a mean preoperative CAS of 3.8 were included in this review. The mean time between initial decompression and presentation to our center for recurrent or persistent CON symptoms was 8.6 years (range, 1 to 15 years). At presentation, the average Humphrey visual field mean deviation was -16.5 (standard deviation: 8.8), improving to -3.8 (2.4) postoperatively with a mean of 9.3 months follow up (mean improvement of 75%). Preoperative VA was 0.34 (0.23) LogMAR, improving to 0.05 (0.10) LogMAR with a mean follow up of 10.4 months. Pre- to postoperative comparisons of clinical measures all showed statistically significant improvement (p < 0.05). Eight eyes presented with decreased VA (any VA < 20/20), 4 with decreased color vision (any color vision < 11), and 1 with a relative afferent pupillary defect, and all these patients demonstrated improvement following repeat orbital decompression. CONCLUSIONS In patients with thyroid eye disease, symptoms of recurrent CON occurred up to 15 years following initial orbital decompression underscoring the smoldering, progressive nature of the disease. Repeat decompression that focused on the orbital apex resulted in visual improvement in all 6 patients. Despite clinical evidence of CON, the mean CAS of these patients at presentation was only 3.8, highlighting the importance of close monitoring of patients with thyroid eye disease following decompression regardless of the external manifestations of disease activity.

Purpose To alert ophthalmologists to the recognition of cortical visual loss as the presenting feature in patients with reversible posterior leukoencephalopathy syndrome (RPLES). Unique radiologic findings are paramount to the diagnosis. Design Interventional case report. Methods A patient was seen with perioperative bilateral cerebral visual loss that was misinterpreted initially as an irreversible ischemic event. Further detailed analysis of the radiologic findings and clinical history led to the correct diagnosis. Main outcome measures Visual acuity and magnetic resonance imaging (MRI) of the brain. Results Recognition of the correct diagnosis of RPLES led to the institution of antihypertensive therapy and recovery of normal vision. Conclusions The diagnosis of RPLES should be considered in all patients with acute cerebral visual loss, especially in the setting of recent surgery, blood transfusion, chemotherapy, immunosuppressant use, hypertension, eclampsia, or seizures. Prompt diagnosis requires close collaboration with a radiologist and an emergent MRI study, which ideally should include diffusion-weighted imaging with calculation of an apparent diffusion coefficient map. Differentiation from acute cerebral ischemia is important in order to avoid permanent visual loss by prompt and vigorous treatment of exacerbating factors such as intermittent hypertension. Prompt diagnosis will also help to avoid potentially dangerous invasive procedures such as thrombolytic therapy.

PURPOSE To report 3 cases of epidermal inclusion cyst that arose within the tarsus, an unusual site of origin. METHODS A retrospective review of medical records of patients undergoing excision of eyelid epidermal inclusion cysts by one surgeon (MJL) over a decade revealed 3 cases of intratarsal epidermal inclusion cyst. Initially, these lesions resembled chalazia and were first addressed with incision and curettage. There was recurrence of the cyst in all the 3 cases from 1 to 4 months, and subsequent complete excision was necessary. RESULTS At surgery in each of these cases a cyst arising within the tarsus was encountered. Eventually, the tarsus containing the base of the cyst was excised to ensure complete removal. The cysts were approximately 8 mm to 10 mm in greatest dimension and had yellowish-white gelatinous contents. Histopathologic evaluation revealed keratin-filled cysts arising from tarsus and lined by stratified keratinized epithelium. In one of the cases the tarsal tissue around the cyst wall showed epidermal elements presumably derived from sebaceous gland. There have been no recurrences after complete excision (follow-up range, 9-60 months). CONCLUSIONS Intratarsal epidermal inclusion cysts share some clinical features with chalazia. Lack of inflammation, lack of fluctuation in size, gradual continued slow growth, and delayed onset of recurrence may help to differentiate tarsal cyst from recurrent chalazion. Incision and curettage, however, is not effective long-term treatment for this entity. Total excision of the cyst including full-thickness excision of tarsus at the cyst's base of origin is suggested for definitive treatment.

Cancer stem cells (CSCs) are those cells within a malignant tumor that can self-renew and initiate new tumors, with the ability to produce all the cell lineages that comprise the tumor. Recent studies have revealed that cancer treatments that target the tumor without addressing CSCs might reduce the tumor load but be unable to achieve a cure. Generation and maintenance of CSCs through genetic and epigenetic reprogramming is essential for tumor maintenance and resistance to therapy. Therefore, developing therapies targeted at CSCs is critical to achieving cures for cancer1. Yet the biology of CSCs, and particularly the process of cellular reprogramming, is still not well understood, in part because of the many mutations carried by these cells, only a few of which are deterministic. In order to develop a better understanding of the mechanistic underpinnings of adult cell dedifferentiation, we developed a zebrafish model that utilizes adult myocyte reprogramming in the context of muscle regeneration. Our model utilizes the lateral rectus muscle of the eye, which can recover from >50% myectomy by reprogramming the residual (i.e. “post-mitotic”) myocytes to reenter the cell cycle, remodel the extracellular matrix, proliferate, migrate and then redifferentiate into myocytes that reform a functional muscle (as determined by an optokinetic response). The proliferative burst of reprogrammed myocytes is particularly robust, with >70% of cells undergoing mitosis during the regeneration process. Such a robust in vivo model of cell dedifferentiation represents a unique opportunity to study the cellular, genetic and epigenetic processes involved. We find that the dedifferentiation process begins with activation of epigenetic regulators to remodel chromatin, followed by activation of autophagy to remodel the cytoplasm, followed by cell cycle reentry. Epigenetic changes include changes in DNA and histone methylation, along with activation of genes encoding transcription factors that are frequently found to be involved with oncogenesis, such as myc, jun, fos, and twist. A transcriptome analysis using deep sequencing reveals significant similarities between the genetic signatures of dedifferentiated zebrafish myocytes and human cancer cells. This analysis also identifies long non-coding RNAs that are induced early during the dedifferentiation process, and work is ongoing to annotate these lncRNAs with reference to human cancer. In summary, an in vivo zebrafish non-cancer model of cancer can provide unique mechanistic insights into the biology of CSCs. In addition, as an aquatic species this model is particularly well suited for drug screening, providing an innovative new approach to developing drugs that target reprogramming/dedifferentiating cells. Citation Format: Ke’ale Louie, Alfonso Saera-Vila, Phillip E. Kish, Alon Kahana. Zebrafish adult cell dedifferentiation as a noncancer model of cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2541.

Craniofacial and ocular morphogenesis require proper regulation of cranial neural crest migration, proliferation, survival and differentiation. Although alterations in maternal thyroid hormone (TH) are associated with congenital craniofacial anomalies, the role of TH on the neural crest has not been previously described. Using zebrafish, we demonstrate that pharmacologic and genetic alterations in TH signaling disrupt cranial neural crest migration, proliferation, and survival, leading to craniofacial, extraocular muscle, and ocular developmental abnormalities. In the rostral cranial neural crest that gives rise to the periocular mesenchyme and the frontonasal process, retinoic acid (RA) rescued migratory defects induced by decreased TH signaling. In the caudal cranial neural crest, TH and RA had reciprocal effects on anterior and posterior pharyngeal arch development. The interactions between TH and RA signaling were partially mediated by the retinoid X receptor. We conclude that TH regulates both rostral and caudal cranial neural crest. Further, coordinated interactions of TH and RA are required for proper craniofacial and ocular development.

Vascular anomalies are classified into vascular tumors and vascular malformations based on the classification system of the International Society for the Study of Vascular Anomalies (ISSVA) [1, 2]. Vascular tumors are characterized by proliferation and tumor enlargement, and the most common vascular tumor is infantile hemangioma, while a less common vascular tumor is hemangiopericytoma. Vascular malformations consist of non-proliferating vascular lesions in which blood flow is misdirected through anomalous channels. Malformations exist on a spectrum, ranging from high-flow arteriovenous malformation (AVM), low-flow venous (varix) and lymphovenous malformations, and capillary-venous malformations. Flow characteristics influence the natural history of vascular anomalies and are helpful in making the correct diagnosis.

Purpose: To describe the use of intraoperative fluoroscopy as an aid in the removal of radio-opaque orbital foreign bodies. Methods: A retrospective interventional case series of 12 patients with orbital foreign bodies that required removal for various indications. All patients underwent orbitotomy and removal of the foreign bodies with the aid of real-time intraoperative fluoroscopic localization. Results: The orbital foreign body was successfully removed without complication in all 12 patients. One patient with ethmoid sinusitis preoperatively had resolution of the infection after surgery. Two patients with extraocular motility deficits preoperatively experienced significant improvement in motility after surgery. Three patients who required MRI studies for unrelated conditions were able to undergo scanning postoperatively without complications. Two patients were combat casualties treated by US medical personnel during Operation Iraqi Freedom. There were no cases of visual or ocular morbidity directly attributable to foreign body removal. Conclusion: Intraoperative fluoroscopy is a valuable tool that can aid in the removal of radio-opaque orbital foreign bodies.

Purpose: Severe or recurrent lower eyelid ectropion can be challenging to correct. Studies on the role of upper midface ptosis in lower eyelid malposition have been published. The authors describe their technique of supporting the lateral cheek by lifting and reestablishing support for the orbitomalar ligament through a 10-mm canthotomy incision as an adjunct to a lateral tarsal strip procedure. In many cases, this technique allows the eyelid to be properly repositioned without skin grafting. Methods: A retrospective chart review of patients with severe multifactorial or recurrent lower eyelid ectropion. A preperiosteal dissection over the malar eminence and resuspension of the lateral aspect of the suborbicularis oculi fat was performed through a 10-mm lateral canthotomy at the time of lateral tarsal strip procedure. The longest follow-up was 20 months, with an average of 7.8 months postoperatively. Postoperative eyelid position and patient symptoms were used as outcome measures. Results: Twelve patients underwent repair of severe ectropion with a lateral tarsal strip procedure and adjunctive transcanthotomy lateral suborbicularis oculi fat lift with orbitomalar ligament resuspension. In 3 cases of severe paralytic ectropion and in 1 patient with poor healing, a small lateral tarsorrhaphy was also performed. The patients achieved excellent improvement in lower eyelid position, with resolution of symptoms and satisfactory aesthetic outcomes. Conclusions: Elevating the lateral suborbicularis oculi fat by resuspending the orbitomalar ligament was effective in supporting the lateral cheek. This resulted in recruitment of anterior lamella and allowed for good lower eyelid repositioning. The extent of dissection could be graded to achieve the desired surgical objectives. More invasive surgery such as full-thickness skin grafting was avoided. This technique can be a relatively noninvasive, yet powerful adjunct in the treatment of severe or recurrent lower eyelid ectropion.

Objective To evaluate the clinical utility of time-resolved contrast-enhanced magnetic resonance angiography (MRA) in the evaluation of vascular orbital tumors. Methods Retrospective medical record review of patients with vascular orbital lesions imaged with Time-Resolved Imaging of Contrast KineticS (TRICKS; GE Healthcare [Chalfont St Giles, England]) MRA, a noninvasive dynamic imaging modality. Results Five patients with orbital vascular tumors were evaluated using TRICKS MRA. These included 1 patient with a cavernous hemangioma, 2 patients with orbital varices, 1 patient with an orbitocutaneous arteriovenous malformation, and 1 patient who had a solitary fibrous tumor with features of a hemangiopericytoma. In 2 patients, diagnoses were altered as a result of TRICKS MRA. In addition, a young patient with a large orbitocutaneous arteriovenous malformation involving the ophthalmic artery was followed perioperatively and noninvasively using TRICKS MRA, which produced exquisite images and added substantial value in the care of these patients. Conclusion Dynamic MRA in the form of TRICKS is a newly available imaging modality with great potential for improving the evaluation and management of patients with complex orbital tumors.

Binocular vision requires intricate control of eye movement by 6 pairs of extraocular muscles (EOMs). Congenital and acquired strabismus secondary to EOM dysfunction cause misaligned binocular inputs, which can lead to amblyopia (neurologic vision loss) or diplopia, collectively affecting as much as 5% to 10% of the US population.1,2 More broadly, skeletal muscle injury and degenerative conditions are common and debilitating and represent important causes of morbidity and mortality worldwide.3,4 Mammalian myonuclei are defined as being postmitotic, and muscle growth and repair are achieved by myogenic progenitor cells termed satellite cells.5–11 These cells are identified by expression of the paired box transcription factor family members Pax7 and/or Pax3. Pax7 is expressed by most adult muscle satellite cells, whereas Pax3 is present only in satellite cells of particular muscles and is transiently expressed by activated satellite cells.12–15 Muscle injury can be a focal injury (e.g., stab wound) or a major injury with significant tissue loss and every degree of injury in between. Response to focal injury would require a local repair process, whereas significant tissue loss would require more extensive tissue generation (i.e., “whole-organ” regeneration). In mammals, muscle repair following focal injury involves the proliferation of satellite cells to form myoblasts that express the transcription factor MyoD. Some myoblasts maintain MyoD expression, downregulate Pax7, and commit to differentiation by activation of myogenin. These differentiated myoblasts fuse to form myocytes. Other myoblasts maintain Pax7 expression, downregulate MyoD, and eventually withdraw from the cell cycle to maintain the satellite cell population of the muscle.14,16,17 In contrast, whole-organ muscle regeneration is much more limited in mammals despite the presence of satellite cells. In salamanders, limb amputation is followed by limb regeneration in which Pax7-positive cells play an important role in some but not all salamander species.18 Pax7-positive satellite cells have also been described in mammalian EOMs.19 Additionally, progenitor cells that express PITX2 have been described.20 EOMs are a specialized form of skeletal muscle derived from branchial and cephalic mesoderm,21–23 and EOM satellite cells may have certain distinguishing features compared to their somitic counterparts. However, published results are somewhat inconsistent. Some results suggest that the EOM stem cell niche is protected from aging and disease24,25 and maintains proliferative potential longer than somitic muscles.26 Other results argue that aged EOM stem cells lose their ability to fuse to form multinucleated myotubes.26 This disagreement in published conclusions may be the result of using different species and/or different experimental approaches. To investigate the potential for adult whole-organ skeletal muscle regeneration, we exploited the well-documented regenerative capacity of adult zebrafish. With its genome nearly fully sequenced and with well-developed molecular tools, the zebrafish (Danio rerio) has become an important model for human disease research. In particular, adult zebrafish have robust regenerative capacity in organs as diverse as the brain, retina, fins, and heart.27–32 In regenerating complex tissues, zebrafish use both resident stem cells (e.g., melanocyte precursors in fins33) and lineage-restricted dedifferentiated cells (e.g., cardiac myocytes,34 retinal Muller glia,31,35 and osteoblasts32,36), suggesting that zebrafish might be an ideal model for studying de novo whole-organ muscle regeneration. Our model uses a large EOM myectomy in sexually mature adult zebrafish. We focused on the lateral rectus (LR) muscle because of its anatomic isolation from the other EOMs37 and its surgical accessibility and the ability to assess its function using horizontal gaze eye movement. Here we report that, following myectomy of approximately 50% of the LR muscle, adult zebrafish regenerated an anatomically correct and functional muscle. Unlike embryonic EOM development, the regeneration process appears to be independent of pax7-positive satellite cells, as classic satellite cells are not detectable in zebrafish adult EOMs by electron microscopy or immunofluorescence techniques. Instead, our data reveal that residual EOM myocytes undergo dedifferentiation to form myoblasts, followed by robust myoblast proliferation and redifferentiation into functional muscle fibers. We propose that the ability of residual EOM myocytes to dedifferentiate following severe injury underlies their whole-organ regenerative capacity in zebrafish, compared with other species in which dedifferentiation is actively blocked. Furthermore, adult zebrafish EOM regeneration via dedifferentiation offers a powerful model for studying the mechanistic underpinnings of cellular reprogramming and dedifferentiation.

An orbital venous varix is rare and can present with diplopia, proptosis, or hemorrhage. Treatment can be challenging, especially if the varix is in a posterior location within the orbit, since surgical exposure becomes difficult. A few case reports have been published describing transcatheter embolization of an orbital varix with coils, direct percutaneous injection of n-butyl cyanoacrylate glue, and the percutaneous injection of bleomycin. We present a case of a symptomatic orbital venous varix of the left inferior ophthalmic vein successfully treated with transvenous endovascular sclerotherapy using a microcatheter balloon and bleomycin.