Expert Consensus on the Use of Teprotumumab for the Management of Thyroid Eye Disease Using a Modified-Delphi Approach.

BACKGROUND: Teprotumumab is the first treatment for thyroid eye disease (TED), a debilitating autoinflammatory condition, approved by the Food and Drug Administration in the United States, which reduces proptosis and improves quality of life. In the absence of guidelines, clinical recommendations were developed for using teprotumumab in patients with TED in the United States. METHODS: A 3-round modified-Delphi panel was conducted between October 2020 and February 2021 with experts in the management of patients with TED. Key areas regarding the use of teprotumumab were investigated, including eligible patient populations, concomitant treatments, and assessment of response and adverse events. This used 2 survey rounds via an online questionnaire, where statements were scored using 9-point Likert scales. Statements with conflict were included in the third round, involving a consensus meeting via videoconference. RESULTS: Consensus was obtained for all statements (n = 75); of which, 56% were revised to enable agreement of the group. The consensus meeting provided agreement regarding which populations should receive teprotumumab therapy, including all adult patients with TED with a clinical activity score of ≥4. Treatment with teprotumumab can also be considered for TED patients displaying the following characteristics: a CAS of <3, lid retraction of ≥2, and mild or early optic neuropathy with close clinical observation. Further recommendations included suitability of treatment for those beyond 16 months following the initial diagnosis of TED, low CAS concomitant treatment with steroids in some cases, retreatment for those who have relapses, and finally a recommendation to continue therapy for all 8 infusions despite the lack of response by the fourth infusion. CONCLUSIONS: This work constitutes the first consensus on guidelines for the use of teprotumumab. The modified Delphi approach involved physicians with significant experience with the clinical use of teprotumumab, and recommendations were based on current evidence.

Vismodegib for Preservation of Visual Function in Patients with Advanced Periocular Basal Cell Carcinoma: The VISORB Trial.

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.

The Use of Umbilical Amnion for Conjunctival Socket, Fornix, and Eyelid Margin Reconstruction.

PURPOSE: To describe outcomes using umbilical amnion for conjunctival fornix, socket, and eyelid margin reconstruction. METHODS: A medical record review was performed to identify patients who had received umbilical amnion over a 2-year period in their department. Patient demographics, disease etiology, and data regarding surgical outcomes were collected. The primary outcome was the success rate of the surgical intervention. RESULTS: Twenty-one patients received umbilical amnion for anophthalmic socket contracture (n = 16), orbital implant exposure (n = 3), ocular surface burn (n = 1), and cicatricial entropion repair (n = 1). The primary outcome was met in 76% of patients overall. In anophthalmic socket contracture, the primary outcome was met in 86% and 0% of patients with acquired and congenital anophthalmia, respectively. The primary outcome was met in all cases of orbital implant exposure and cicatricial entropion. The primary outcome was not met in a Roper-Hall grade IV ocular surface burn. CONCLUSIONS: Umbilical amnion is an ideal substrate graft for reconstruction of the conjunctival fornix, socket, and eyelid margin. Umbilical amnion appears to be efficacious for the management of socket contracture in acquired anophthalmia, orbital implant exposure, and cicatricial entropion. Further experience is needed to determine the efficacy of umbilical amnion in ocular surface burns.

Warfarin-associated delayed orbital hemorrhage after orbital fracture repair with smooth nylon foil implant.

The authors describe the first report in the literature of delayed orbital hemorrhage that may be partly caused by supratherapeutic anticoagulation. A 52-year-old man with supratherapeutic international normalized ratio (INR) presented with acute proptosis, orbital pain and diplopia 9 months after the floor and medial orbital wall fracture repair using nylon foil implant. He was found to have hemorrhaged into the capsule surrounding the orbital implant. Three weeks later, the patient underwent implant removal after warfarin was discontinued for 5 days and INR was normalized. His symptoms resolved postoperatively. This case describes a unique risk factor of delayed orbital hemorrhage in patients with previous orbital fracture repair, and highlights that coagulopathy should be investigated in patients presenting with acute proptosis with a history of orbital fracture repair. The authors also provide a comprehensive and up-to-date literature review on previously reported cases with delayed hemorrhagic complications from alloplastic orbital implants.

An Aesthetic Orbicularis Oculi Myectomy Technique for Blepharospasm: Use of Topical 5-Fluorouracil and Fibrin Sealant.

PURPOSE: To describe a modified technique of orbicularis oculi myectomy for refractory blepharospasm. This technique includes removal of orbicularis muscle, reformation of the eyelid crease and pretarsal platform using fibrin sealant (Tisseel), and topical 5-fluorouracil to reduce scar formation and improve aesthetic outcome. METHODS: Retrospective chart review of 7 patients who underwent bilateral orbicularis oculi myectomy with our technique from 2013 to 2016. Outcome measures were postoperative botulinum toxin dose, frequency, duration between treatments, the amount of lagophthalmos, severity of dry eye, and patient satisfaction with aesthetic and functional outcome. RESULTS: Patients who underwent the aesthetic myectomy technique had significantly decreased botulinum toxin use with relief of symptoms postoperatively. Only 1 of 7 patients experienced mild dry eye symptoms postoperatively, managed with artificial tears. All patients were satisfied with the aesthetic and functional outcome. CONCLUSIONS: The aesthetic myectomy technique provides effective treatment for blepharospasm with good functional and aesthetic outcome.

Association of a Statewide Opioid Legislation with Opioid Prescribing Patterns in Facial Plastic and Reconstructive Procedures.

Background: The Michigan Opioid Laws are legislation enacted between 2017 and 2018 as a strategy to combat the growing opioid crisis. Objective: To compare opioid prescription rates and morphine milligram equivalents (MMEs) of opioid prescribed to patients undergoing various facial plastic and reconstructive surgery (FPRS) procedures before, during, and after legislation enactment. Materials and Methods: This is a cross-sectional retrospective review of subjects undergoing any of 10 FPRS procedures between July 2016 and November 2019 at a tertiary care hospital with analysis of demographic factors, opioid prescription rates, and MMEs over time. Results: Of 863 patients included, 107 and 575 patients were prescribed postoperative opioids before and after opiate legislation enactment, respectively, with no difference in baseline demographics between groups. Regression analysis showed no change in MME prescribing in the year before legislation (p = 0.70), followed by a decrease of 0.13 MME per day (p = 0.00), with a subsequent stabilization of MME at a reduced rate for the remainder of the study period (p = 0.74). Conclusion: Enactment of the Michigan Opioid Laws was temporally associated with a decrease in opioid prescriptions for common facial plastic surgery procedures.

Efficacy and Safety of Teprotumumab in Thyroid Eye Disease.

Thyroid eye disease (TED; also known as thyroid-associated ophthalmopathy) is an autoimmune condition with disabling and disfiguring consequences. Teprotumumab is the first and only medication approved by the United States Food and Drug Administration for the treatment of TED. We review the efficacy and safety of teprotumumab in TED, highlighting results from the 2 randomized, double-masked, placebo-controlled trials. Post-approval case reports of teprotumumab use in patients with compressive optic neuropathy (CON) and inactive TED were similarly favorable to those from the trials. The preliminarily results of teprotumumab for CON and inactive TED should be investigated in formal clinical trials. Teprotumumab should be avoided in pregnancy. Evidence also suggests that teprotumumab may exacerbate pre-existing inflammatory bowel disease, worsen hyperglycemia, and be associated with hearing impairment. Patients at risk for these adverse events need to be closely monitored with baseline and periodic assessments.

Change in Postoperative Opioid Prescribing Patterns for Oculoplastic and Orbital Procedures Associated With State Opioid Legislation.

Importance: Understanding whether statewide legislation, such as the Michigan Opioid Laws, is associated with reduction in postoperative opioid prescriptions is informative in guiding future legislation. Objective: To identify changes in opioid prescribing patterns for oculoplastic and orbital procedures associated with the enactment of the Michigan Opioid Laws in 2017 and 2018. Design, Setting, and Participants: This cross-sectional study included 3781 patients who underwent any of 10 common oculoplastic and orbital procedures between June 1, 2016, and November 30, 2019, at a tertiary care institution. Exposures: From 2017 to 2018, Michigan enacted a series of laws to address the state's worsening opioid epidemic. Two major components of this legislation enacted on June 1, 2018, required prescribers to review a report of patients' opioid use history and obtain signed consent after educating patients on the use and disposal of opioids prior to prescribing. Main Outcomes and Measures: Demographic information, type of surgery, type and amount of opioid prescriptions, and morphine milligram equivalent (MME) were analyzed. MME was calculated as the product of dose, quantity, and opioid-specific conversion factor for each prescription. Linear interpolation spline regression was used to evaluate the association of prescription MME with time. Results: Of 3781 patients, 1614 (42.7%) were male. The mean (SD) age at the time of surgery was 63.3 (16.6) years. Of 2026 patients undergoing surgery before June 1, 2018, 1782 (88.0%) were prescribed postoperative opioids; of 1755 patients undergoing surgery after June 1, 2018, 878 (50.0%) were prescribed postoperative opioids (P < .001). There was no difference in age, sex, race/ethnicity, surgery type, or opioids prescribed between these 2 cohorts. Linear interpolation spline regression showed a decrease of 26.025 MMEs (equivalent to a 36.2% reduction of mean MME) between June 1, 2017, and September 30, 2018 (ß, -1.735; 95% CI, -0.088 to -0.024; P < .001), stabilizing at a persistently reduced rate of MME prescribed through the end of the study period (October 1, 2018, to November 30, 2019; ß, -0.005; 95% CI, -0.039 to 0.016; P = .42). Changes in MME in the 12 months before or 12 months after the period of legislation enactment were not identified. Conclusions and Relevance: In this cross-sectional study, reduction in opioid prescriptions for oculoplastic and orbital procedures was observed during the enactment period of the Michigan Opioid Laws and appeared to be sustained through the end of the study period. Similar statewide or national legislations aimed at increasing prescriber awareness and patient education on opioid use may help curtail the prescription opioid epidemic.

Feasibility of a Risk-Based Approach to Cataract Surgery Preoperative Medical Evaluation.

IMPORTANCE: In 2019, the US Centers for Medicare & Medicaid Services implemented the Patients Over Paperwork initiative, allowing hospitals and ambulatory surgery centers to establish their own policies on preoperative history and physical requirements. A risk-based approach to preoperative medical evaluation may allow surgeons to provide high-value patient care. OBJECTIVE: To assess the feasibility of a risk-based approach to cataract surgery preoperative medical evaluation through a lens of safety and throughput. DESIGN, SETTING, AND PARTICIPANTS: A pilot study was performed to evaluate the implementation of a risk-based approach to preoperative medical evaluation for cataract surgery using a virtual medical history questionnaire. The intervention group, seen from June to September 2020, received the risk assessment and those who were low risk proceeded to surgery without further preoperative evaluation prior to the day of surgery. The preintervention control group included patients who received standard care from January to December 2019. MAIN OUTCOMES AND MEASURES: Primary outcomes included rates of intraoperative complications, noneye-related emergency department visits within 7 days, inpatient admissions within 7 days of surgery, case delays, and rates of case cancellation. The secondary outcome included patient perception regarding preoperative care. RESULTS: A total of 1095 patients undergoing cataract surgery were included in the intervention group (1813 [58.2%] female) and 3114 were in the control group (621/1095 [56.7%] female). The mean (SD) age was 68.6 (11.0) in the control group and 68.4 (10.5) in the intervention group. The intervention group included 126 low-risk individuals (11.5%) and 969 individuals who received standard care (88.5%). There were no differences between the control and intervention groups in terms of rates of intraoperative complications (control group vs intervention group: 21 [0.7%] vs 3 [0.3%]; difference, -0.4% [95% CI, -0.82 to 0.02]), 7-day noneye-related ED visits (5 [0.2%] vs 3 [0.3%]; difference, 0.1% [95% CI, -0.23 to 0.45]), 7-day inpatient admissions (6 [0.2%] vs 2 [0.2%]; difference, -0.01% [95% CI, -0.31 to 0.29]), or same-day cancellations (31 [0.8%] vs 10 [0.6%]; difference, -0.15% [95% CI, -0.63 to 0.34]). The control group had more case delays (59 [1.9%] vs 7 [0.6%]; difference, -1.3% [95% CI, -1.93 to -0.58]). CONCLUSIONS AND RELEVANCE: This study suggests that a virtual, risk-based approach to preoperative medical evaluations for cataract surgery is associated with safe and efficient outcomes. These findings may encourage health care systems and ambulatory surgery centers to tailor preoperative requirements for low-risk surgery patients.

Mohs Reconstruction and Scar Revision.

Facial reconstruction may be effectively performed in an office setting using a variety of techniques. Careful patient selection is paramount for achieving successful outcomes in this setting. The most common reconstructive techniques used in the office setting include local flaps and skin grafts. Scar management is complementary to all facial reconstructive procedures, and the reconstructive surgeon has a large variety of scar management techniques available. Scar management should be individualized based on clinical setting and available resources.

Objectively Measuring Observer Attention in Severe Thyroid-Associated Orbitopathy: A 3D Study.

OBJECTIVE: Measure the attentional distraction of facial deformity related to severe thyroid-associated orbitopathy using three-dimensional (3D) images and eye-tracking technology. METHODS: Observers recruited at an academic tertiary referral center viewed 3D facial images of patients with severe thyroid-associated orbitopathy (TAO) and controls without TAO. An infrared eye-tracking monitor recorded their eye movements and fixations in real time. Multivariate Hotelling's analysis, followed by planned posthypothesis testing, was used to compare fixation durations for predefined regions of interest, including the eyes, nose, mouth, central triangle, and remaining face without the central triangle between severe TAO patients and controls. RESULTS: One hundred sixteen observers (mean age 26.4 years, 51% female) successfully completed the eye-tracking experiment. The majority of their attention was directed toward the central triangle (eyes, nose, mouth). On multivariate analysis, there were significant differences in the distribution of attention between control and severe TAO faces (T2 = 49.37; F(5,922) = 9.8314, P < 0.0001). On planned posthypothesis testing, observers attended significantly more to the eyes (0.77 seconds, P < 0.0001, 95% confidence interval [CI], 0.51, 1.03 seconds) and less to the nose (-0.42 seconds, P < 0.0001, 95% CI, -0.23, -0.62 seconds) in severe TAO patients. There was no significant difference in time spent on the mouth, the total time spent on the central triangle, or time spent in the remaining face between the two groups. CONCLUSION: Severe TAO distracted observer attention toward the eyes compared to control patients. These data lend insight into how TAO may alter observers' perceptions of these patients. Future studies should investigate how these changes in observer gaze patterns may reflect the social perception of TAO patients. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1250-1254, 2019.

Orbital progressive transformation of germinal centers as part of the spectrum of IgG4-related ophthalmic disease: Clinicopathologic features of three cases.

Progressive transformation of germinal centers (PTGC) is a form of follicular hyperplasia recently associated with immunoglobulin G4-related disease (IgG4-RD), but the ophthalmic manifestations of this combination are poorly described. In this retrospective case series, we present three cases of IgG4-related orbital disease (IgG4-ROD) showing varying degrees of PTGC involving the orbit and lacrimal gland. Three adult women presented with ill-defined lacrimal gland enlargement. Histologic sections showed variable fibrosis and large, irregular lymphoid follicles with prominent mantle zones penetrating the germinal centers, highlighted by Bcl-2 and/or IgD immunostains. The interfollicular areas contained a mixture of plasma cells, scattered histiocytes and eosinophils. Mixed T and B-cells were present, and no signs of monoclonality were identified. All cases showed more than 100 IgG4 positive cells per high power field. Epstein-Barr virus in situ hybridization performed in one case was negative. The serum IgG4 level was tested in one case and showed elevation above the normal range. After 2-10 months of follow-up, the patients showed either near-complete resolution or no remaining signs of ophthalmic disease. Increasing awareness of these PTGC in extra-nodal locations, including the orbit, may provide a better understanding of the histologic spectrum of this disease.

Characteristics, Diagnosis, and Management of Ehlers-Danlos Syndromes: A Review.

IMPORTANCE: Ehlers-Danlos syndromes (EDSs) are a group of heritable connective tissue disorders. Patients with EDSs can develop excessive facial rhytids, nasal deformities, and facial scarring, for which they may seek consultation with a facial plastic surgeon. Ehlers-Danlos syndromes can be associated with serious surgical complications and should be identified preoperatively to facilitate optimal treatment. To our knowledge, no management guidelines for patients with EDSs exist in the facial plastic surgery literature. We present a review of the literature and management recommendations for the facial plastic surgeon. OBSERVATIONS: We performed a PubMed/MEDLINE search for all publications in the English language related to surgical experience in patients with EDSs. A total of 37 publications (including reviews and case series) were included. Ehlers-Danlos syndromes are more common than appreciated, with an overall point prevalence between 1 in 2500 and 1 in 5000 according to existing literature. There are 6 main subtypes of EDSs that have significant phenotypic heterogeneity. Patients with classic type and hypermobile EDS (the 2 most common subtypes) can typically undergo elective facial plastic surgery without major complications. However, specific preoperative, intraoperative, and postoperative issues, as outlined in this review, must be taken into consideration. Vascular EDS should serve as a contraindication to elective surgery given its potential for life-threatening complications. CONCLUSIONS AND RELEVANCE: Because of their skin laxity, patients with EDSs may present more frequently to facial plastic surgeons' offices. Simple screening questions can help the surgeon identify potential patients with EDSs. Treatment should be individualized and performed with extreme care to ensure optimal outcomes.

Evaluation of Patients with Facial Palsy and Ophthalmic Sequelae: A 23-Year Retrospective Review.

PURPOSE: Facial palsy (FP) can result in serious ophthalmic sequelae including loss of vision. We describe the clinical characteristics of FP patients presenting for ophthalmologic evaluation and the timing for initiating ophthalmologic care. METHODS: We performed a retrospective review of 96 consecutive FP patients presenting between 1992 and 2015 at a tertiary eye center. The main outcome measures were time interval from the diagnosis of FP and onset of ocular symptoms to the initial ophthalmologic evaluation (IOE), and the severity of exposure keratopathy and eyelid malposition on IOE. RESULTS: The median time interval from the diagnosis of FP to the IOE was 1.6 years (interquartile range; IQR = 0.5-9.2), and from the onset of ocular symptoms to IOE was 0.8 years (IQR = 0.3-2.3). The most common ocular symptoms were dryness (47.9%; n = 46), irritation (39.6%; n = 38), and tearing (30.2%; n = 29). A total of 26.0% (n = 25) of patients were bothered by the appearance of their eyes. Only 13.5% (n = 13) noted change in vision. On IOE, 81.6% (n = 75) of patients had punctate epithelial erosions (PEE), of which 52.3% (n = 35) had moderate to severe PEE, 3.3% (n = 3) had corneal ulcers and 2.2% (n = 2) had corneal abrasions. The average margin-reflex distance 2 was 6.4 mm (SD = 2.4) with average lagophthalmos of 3.5 mm (SD = 3.1). CONCLUSIONS: Among FP patients presenting for ophthalmologic evaluation, exposure keratopathy (as evidenced by PEE and corneal ulcers/abrasions) is highly prevalent and moderately severe on IOE, despite only 13.5% of patients noting decreased vision. These findings underscore the importance of timely and thorough ophthalmologic evaluation of FP patients.

Prevalence of Body Dysmorphic Disorder and Surgeon Diagnostic Accuracy in Facial Plastic and Oculoplastic Surgery Clinics.

IMPORTANCE: Body dysmorphic disorder (BDD) is a relative contraindication for facial plastic surgery, but formal screening is not common in practice. The prevalence of BDD in patients seeking facial plastic surgery is not well documented. OBJECTIVE: To establish the prevalence of BDD across facial plastic and oculoplastic surgery practice settings, and estimate the ability of surgeons to screen for BDD. DESIGN, SETTING, AND PARTICIPANTS: This multicenter prospective study recruited a cohort of 597 patients who presented to academic and private facial plastic and oculoplastic surgery practices from March 2015 to February 2016. METHODS: All patients were screened for BDD using the Body Dysmorphic Disorder Questionnaire (BDDQ). After each clinical encounter, surgeons independently evaluated the likelihood that a participating patient had BDD. Validated instruments were used to assess satisfaction with facial appearance including the FACE-Q, Blepharoplasty Outcomes Evaluation (BOE), Facelift Outcomes Evaluation (FOE), Rhinoplasty Outcomes Evaluation (ROE), and Skin Rejuvenation Outcomes Evaluation (SROE). RESULTS: Across participating practices (9 surgeons, 3 sites), a total of 597 patients were screened for BDD: 342 patients from site 1 (mean [SD] age, 44.2 [16.5] years); 158 patients, site 2 (mean [SD] age, 46.0 [16.2] years), site 3, 97 patients (mean [SD] age, 56.3 [15.5] years). Overall, 58 patients [9.7%] screened positive for BDD by the BDDQ instrument, while only 16 of 402 patients [4.0%] were clinically suspected of BDD by surgeons. A higher percentage of patients presenting for cosmetic surgery (37 of 283 patients [13.1%]) compared with those presenting for reconstructive surgery (21 of 314 patients [6.7%]) screened positive on the BDDQ (odds ratio, 2.10; 95% CI, 1.20-3.68; P = .01). Surgeons were only able to correctly identify 2 of 43 patients (4.7%) who screened positive for BDD on the BDDQ, and the positive likelihood ratio was only 1.19 (95% CI, 0.28-5.07). Patients screening positive for BDD by the BDDQ had lower satisfaction with their appearance as measured by the FACE-Q, ROE, BOE, SROE, and FOE. CONCLUSIONS AND RELEVANCE: Body dysmorphic disorder is a relatively common condition across facial plastic and oculoplastic surgery practice settings. Patients who screen positive on the BDDQ have lower satisfaction with their facial appearance at baseline. Surgeons have a poor ability to screen for patients with BDD when compared with validated screening instruments such as the BDDQ. Routine implementation of validated BDD screening instruments may improve patient care. LEVEL OF EVIDENCE: NA.

Periocular Reconstruction in Patients with Facial Paralysis.

Facial paralysis can result in serious ocular consequences. All patients with orbicularis oculi weakness in the setting of facial nerve injury should undergo a thorough ophthalmologic evaluation. The main goal of management in these patients is to protect the ocular surface and preserve visual function. Patients with expected recovery of facial nerve function may only require temporary and conservative measures to protect the ocular surface. Patients with prolonged or unlikely recovery of facial nerve function benefit from surgical rehabilitation of the periorbital complex. Current reconstructive procedures are most commonly intended to improve coverage of the eye but cannot restore blink.