Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multicenter Study.

PURPOSE: To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab. DESIGN: Multicenter, retrospective, observational cohort study. PARTICIPANTS: Patients with TED of all stages and activity levels treated with at least 4 infusions of teprotumumab. METHODS: Patients were treated with teprotumumab between February 2020 and October 2022 at 6 tertiary centers. Adverse event metrics were recorded at each visit. MAIN OUTCOME MEASURES: The primary outcomes measure was AE incidence and onset. Secondary outcome measures included AE severity, AE reversibility, AE duration, proptosis response, clinical activity score (CAS) reduction, and Gorman diplopia score improvement. RESULTS: The study evaluated 131 patients. Proptosis improved by 2 mm or more in 77% of patients (101/131), with average proptosis improvement of 3.0 ± 2.1 mm and average CAS reduction of 3.2 points. Gorman diplopia score improved by at least 1 point for 50% of patients (36/72) with baseline diplopia. Adverse events occurred in 81.7% of patients (107/131). Patients experienced a median of 4 AEs. Most AEs were mild (74.0% [97/131]), 28.2% (37/131) were moderate, and 8.4% (11/131) were severe. Mean interval AE onset was 7.9 weeks after the first infusion. Mean resolved AE duration was 17.6 weeks. Forty-six percent of patients (60/131) demonstrated at least 1 persistent AE at last follow-up. Mean follow-up was 70.2 ± 38.5 weeks after the first infusion. The most common type of AEs was musculoskeletal (58.0% [76/131]), followed by gastrointestinal (38.2% [50/131]), skin (38.2% [50/131]), ear and labyrinth (30.5% [40/131]), nervous system (20.6% [27/131]), metabolic (15.3% [20/131]), and reproductive system (12.2% [16/131]). Sixteen patients (12.2%) discontinued therapy because of AEs, including hearing loss (n = 4), inflammatory bowel disease flare (n = 2), hyperglycemia (n = 1), muscle spasms (n = 1), and multiple AEs (n = 8). CONCLUSIONS: Adverse events are commonly reported while receiving teprotumumab treatment. Most are mild and reversible; however, serious AEs can occur and may warrant treatment cessation. Treating physicians should inform patients about AE risk, properly screen patients before treatment, monitor patients closely throughout therapy, and understand how to manage AEs should they develop. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Transcutaneous retrobulbar amphotericin B for rhino-orbital-cerebral mucormycosis: a multi-center retrospective comparative study.

PURPOSE: To assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM). METHODS: In this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality. RESULTS: Among eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality. CONCLUSIONS: Patients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.

PURPOSE: Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. METHODS: This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. RESULTS: Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. CONCLUSIONS: Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab.

PURPOSE: In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen. METHODS: This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events. RESULTS: The study included 74 patients. Mean age was 57.8 years, and 77% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (-2.9 mm in active and -2.8 mm in minimal to no clinical activity patients, P < 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS ( P < 0.01) and reduction in ocular motility restriction ( P < 0.01) were maintained during interruption. CONCLUSIONS: Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.

Erdheim-Chester disease and vemurafenib: a review of ophthalmic presentations and clinical outcomes.

PURPOSE: To provide a comprehensive review of ocular and orbital manifestations of Erdheim-Chester Disease (ECD) and compare clinical outcomes with vemurafenib (INN) to historical treatments (HT). Primary outcomes are ophthalmic findings on presentation, changes in visual acuity, and mortality rate. Secondary outcomes include the progression of ocular findings, systemic involvements, and treatment modalities. METHODS: All published literature from January 1983 to March 2021 was searched for ophthalmic manifestations of ECD. Clinical outcomes following HT were collected and compared with INN. RESULTS: Forty-seven patients with ECD and ophthalmic presentations were identified. The mean age was 49.6 years (SD = 15.0). Proptosis (65.6%) and extraocular muscle restrictions (42.5%) were the most common presenting signs. Of 41 (87.2%) patients with orbital masses on radiologic examination, 90.2% were bilateral, and 53.7% were located in the intraconal space. Ophthalmic examination was significant for xanthelasma (27.2%), optic disc edema (34.0%), and subretinal changes (21.3%). Common treatments were systemic steroids (76.6%), interferon-α (17.0%), and cyclophosphamide (14.9%). INN was less commonly used (12.8%). The mean change in logMAR visual acuity declined with HT (29.9%) but improved with INN (79.1%) (p > 0.05). The proportion of eyes with complete vision loss increased after HT (p < 0.05). The overall mortality rate was 27.7% and notably higher in the HT group (29.3%) when compared to the INN group (16.7%) (p > 0.05). CONCLUSION: ECD presents with many ophthalmic manifestations. Although the intraocular treatments remain controversial, INN should be highly considered in treating orbital ECD patients with BRAF-V600E mutations to prevent and reverse vision loss.

Ophthalmic artery occlusion following n-butyl cyanoacrylate embolization of an orbital arteriovenous malformation.

A 33-year-old pregnant woman presented with six months of right-sided proptosis. Neuroimaging revealed a right orbital arteriovenous malformation arising from the second segment of the ophthalmic artery. As she was 9 weeks pregnant, the decision was made to monitor her closely. Over the following six months, her proptosis progressed, accompanied by decreased visual acuity, afferent pupillary defect, and red desaturation concerning for compressive optic neuropathy. After planned c-section, she underwent embolization with n-butyl cyanoacrylate. Upon awakening after embolization, she had no light perception vision from her right eye and was found to have ophthalmic artery obstruction. She ultimately developed a blind painful right eye and underwent enucleation with histopathology demonstrating glue in the central retinal artery, posterior ciliary arteries, and choroid. This case highlights ophthalmic artery occlusion as a rare complication of orbital arteriovenous malformation embolization and demonstrates correlating histopathological findings, which have not previously been reported.

Advances in the Treatment of Thyroid Eye Disease Associated Extraocular Muscle Myopathy and Optic Neuropathy.

PURPOSE OF REVIEW: To review emerging treatments for thyroid eye disease (TED) associated extraocular muscle myopathy and dysthyroid optic neuropathy (DON). RECENT FINDINGS: Emerging targeted biologic therapies may alter the disease course in TED. Teprotumumab, a type I insulin-like growth factor receptor inhibitor, is the most recent addition to the treatments available for TED-associated extraocular muscle myopathy causing diplopia. Small studies also suggest a potential therapeutic benefit for DON. Various recent studies have also expanded our knowledge on conventional TED therapies. The therapeutic landscape of TED and its sequelae has evolved in recent years. New targeted therapies have the potential to reduce the extraocular muscle and orbital volume expansion which can lead to diplopia and vision loss from optic nerve compression. Longer term efficacy and durability data is needed to determine the role biologics, such as teprotumumab, should play in the treatment of TED patients compared to the current standard of care.

A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface.

BACKGROUND: Teprotumumab, a monoclonal antibody that blocks the insulin-like growth factor-1 receptor, has recently been approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED). Since its approval, aside from data on the safety and clinical efficacy of teprotumumab from Phase-2 and Phase-3 trials, only a handful of reports have been published regarding its use in the wider population. In this review, we briefly describe the mechanism of action of teprotumumab and review the literature to provide an overview of published clinical experience. This information was used to provide recommendations for patient selection, management of patient expectations, infusion details and site options, tips to optimize the authorization process, and how to monitor and mitigate side effects. EVIDENCE ACQUISITION: A systemic review of the literature was performed regarding teprotumumab, focusing on its mechanisms of action and published reports on its use on patients with TED. A review of Embase, Medline (PubMed), Web of Science, and Google Scholar was conducted. RESULTS: Clinical experience following the approval of teprotumumab has confirmed its efficacy in reducing inflammation and proptosis in patients with acute TED (<2 years). The reduction in proptosis occurs due to a reduction in orbital fat and muscle volume. Furthermore, there is evidence for its use in patients with compressive optic neuropathy. There are also reports that show its efficacy in reducing proptosis, inflammation, and diplopia in patients with chronic TED (>2 years). Teprotumumab was associated with side effects, such as muscle spasm, hearing loss, and hyperglycemia. To date, 2 case reports have shown a possible association with flares of inflammatory bowel disease. CONCLUSIONS: Teprotumumab is a powerful therapeutic option for the treatment of TED. Clinical experience following FDA approval has demonstrated efficacy in treating patients with acute and chronic TED. It is the only therapeutic option that has been shown to reduce orbital soft tissue expansion in TED. However, it is expensive, and sometimes, obtaining insurance authorization can be time consuming and difficult. Further work will reveal its full side effect profile and help to establish its role in the armamentarium used to treat TED.

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.

Ocular, Orbital, and Adnexal Toxicity With High-dose Volumetric Modulated Arc Radiation Therapy for Orbital Malignancies.

PURPOSE: Conventional modalities of external-beam radiation therapy (EBRT) are associated with high incidences of severe vision-threatening ocular and orbital toxicities when used to treat orbital malignancies. We investigate toxicities associated with high-dose volumetric modulated arc therapy (VMAT), a commonly used contemporary treatment modality for these tumors. METHODS: Retrospective analysis of malignant orbital tumors managed with adjuvant high-dose VMAT preceded by globe-salvaging surgical therapy (GST) or exenteration. Dosimetric quantitation of target volumes and critical structures was performed. Incidence and severity of ocular, orbital, and adnexal toxicities were evaluated and assessed with regard to conventional EBRT toxicities for orbital malignancies described in the literature. RESULTS: Eighty-four subjects (mean age = 65.9 ± 9.7 years) were included (N = 48 and N = 36 in GST and exenteration subgroups, respectively). Mean dose was 64.8 ± 2.1 Gy to the planning target volume. Dosing to critical structures typically did not surpass known tissue tolerance limits. Median follow up was 18.3 months. Visual acuity in the GST subgroup was not significantly different after VMAT (0.25 ± 0.06) compared with baseline (0.23 ± 0.02; P = 0.302). Whereas severe toxicities reported by major systematic analyses in the literature with older EBRT modalities were relatively common-for example, retinopathy (16-40%), optic neuropathy (16%), and corneal perforation (13%)-toxicities with VMAT were typically mild and less common. The most common toxicities with VMAT were mild dry eye (81.3%; 39/48), cataract (21.1%; 8/38 phakic eyes), and periocular dermatitis (15.5%; 13/84). Vision-threatening toxicities, including severe corneal pathologies, retinopathy, or optic neuropathy, were rare. There were no contralateral ocular or adnexal toxicities. CONCLUSIONS: High-dose VMAT for orbital malignancies demonstrated low incidence and severity of eye-related toxicity, in contradistinction to adverse events reported from conventional forms of radiotherapy.

Genome Sequencing and Apoptotic Markers to Assess Treatment Response of Lacrimal Gland Adenoid Cystic Carcinoma to Intra-Arterial Cytoreductive Chemotherapy.

Adenoid cystic carcinoma of the lacrimal gland is an aggressive, malignant epithelial neoplasm. We report the case of a 30-year-old male with lacrimal gland adenoid cystic carcinoma treated with neoadjuvant intra-arterial chemotherapy through the internal carotid artery, followed by orbital exenteration and chemoradiation. Treatment response was evaluated using a novel combination of pre- and posttreatment genome sequencing coupled with immunohistochemical evaluation, which showed diffuse tumor apoptosis. A posttreatment decrease in variant allele frequency of the NOTCH1 mutation, and robust tumor cytoreduction on imaging, supports exploration of NOTCH1 analysis as a potential marker of cisplatin sensitivity. The use of genome sequencing and immunohistochemical evaluation could provide a more targeted therapeutic assessment of neoadjuvant intra-arterial chemotherapy in the management of lacrimal gland adenoid cystic carcinoma.

#PlasticsTwitter: The Use of Twitter Data as a Tool for Evaluating Public Interest in Cosmetic Surgery Procedures.

BACKGROUND: Plastic surgeons are increasingly turning to social media to market their services. The newly released Twitter Academic Research Product Track (TARPT) database provides free, customizable analysis of keywords that are included in tweets on the Twitter platform. The TARPT tool may provide valuable insight into public interest in cosmetic surgery procedures. OBJECTIVES: The aim of this study was to determine TARPT's utility in tracking and predicting public interest in cosmetic surgery procedures and to examine temporal trends in tweets related to cosmetic facial and body procedures. METHODS: The TARPT tool was used to calculate the total number of tweets containing keywords related to 10 facial cosmetic procedures and 7 cosmetic body procedures from 2010 to 2020. Annual volumes for respective procedures were obtained from annual statistics reports of The Aesthetic Society from 2010 to 2020. Tweet volumes and procedure volumes were compared by univariate linear regression, taking P < 0.05 as the cutoff for significance. RESULTS: Variations in tweet volume were observed. Univariate linear regression analysis demonstrated statistically significant positive correlations between tweet volumes and procedure volumes for 7 search terms: "eyelid lift," "facelift," "lip injections," "mastopexy," "butt lift," "butt implants," and "liposuction." Many procedure-related keywords were not significant, demonstrating the importance of careful selection of Twitter search terms. CONCLUSIONS: The TARPT database represents a promising novel source of information for plastic surgeons, with the potential to inform marketing and advertising decisions for emerging trends in plastic surgery interest before these patterns become apparent in surgical or clinical volumes.

#CosmeticsTwitter: Predicting Public Interest in Nonsurgical Cosmetic Procedures Using Twitter Data.

BACKGROUND: The utilization of social media in plastic surgery is expanding. The Twitter Academic Research Product Tract (TARPT) database provides plastic surgeons the opportunity to monitor public interest in plastic surgery procedures. Previously, TARPT was shown to be effective in tracking public interest in surgical cosmetic facial and body procedures. OBJECTIVES: The authors sought to determine the ability of the TARPT tool to track and predict public interest in nonsurgical cosmetic procedures and to examine temporal public interest trends in nonsurgical cosmetic procedures. METHODS: The authors employed the TARPT tool to calculate the total number of tweets containing keywords related to 15 nonsurgical cosmetic procedures from 2010 to 2020. Annual case volumes were obtained for each of the 15 procedures from annual reports provided by the American Society of Plastic Surgeons. Univariate linear regression was employed to compare tweet volumes and procedure volumes, with P < 0.05 as a threshold for significance. RESULTS: Univariate linear regression revealed significant positive correlations between tweet volumes and American Society of Plastic Surgeons procedure volumes for 10 search terms representing 6 nonsurgical cosmetic procedures: "xeomin," "microdermabrasion," "facial filler," "fat filler," "fat injections," "fat transfer," "hyaluronic acid filler," "hyaluronic acid injection," "HA filler," and "PRP filler." Thirty-two search terms did not demonstrate a significant relationship. CONCLUSIONS: The TARPT tool is an informative data source for plastic surgeons with the potential to guide marketing and advertising strategies, and monitor public interest in nonsurgical cosmetic procedures, helping surgeons respond to patients' evolving needs.

Radiation-Induced Hyalinizing Clear Cell Carcinoma of the Orbit.

Radiation-induced malignancy is rare, occurring in approximately 0.4%-1.0% of patients receiving external beam radiation therapy. Sarcomas and squamous cell carcinomas are among the most common types of cancers to occur. A 74-year-old woman presented with redness and swelling in the right periorbital region. She had history of multiple recurrent ameloblastoma of the right maxilla, invading the right orbital floor status post 4 surgical resections and 66 Gray external beam radiotherapy 5 years prior. MRI showed a poorly circumscribed mass involving the inferior and lateral orbit. Orbital biopsy revealed clear cell carcinoma with hyalinizing sclerosis and Ewing sarcoma breakpoint region 1 gene arrangement. Due to the extent of orbital disease and presence of perineural invasion, she underwent orbital exenteration. Hyalinizing clear cell carcinoma, a rare cancer, has not been reported to occur in the orbit following radiation. This case highlights the importance of lifetime monitoring in patients who have undergone radiation therapy.

Teprotumumab for Dysthyroid Optic Neuropathy: Early Response to Therapy.

A 45-year-old male presented with active progressive thyroid eye disease refractory to intravenous steroids and right orbital radiation. Visual acuity, left relative afferent pupillary defect, and Humphrey visual field defects were consistent with worsening left dysthyroid optic neuropathy. Orbital MRI demonstrated extraocular muscle enlargement and effacement of the left optic nerve sheath. After 2 infusions of teprotumumab, the patient's visual acuity, relative afferent pupillary defect, Humphrey visual fields, proptosis, and extraocular muscle size improved. This is the first report of dysthyroid optic neuropathy responsive to teprotumumab, and it supports the need for further studies to better understand the role of teprotumumab in treating sight-threatening thyroid eye disease.

Progress Towards Parity: Female Representation in the American Society of Ophthalmic Plastic and Reconstructive Surgery.

PURPOSE: To report female representation within the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) at all levels of career achievement over 50 years. METHODS: Data were extrapolated from published ASOPRS directories and the 50th anniversary booklet. Fellowship, membership, leadership, and awards data were evaluated over 5 decades. Comparisons were made between the first and second 25 years, proportions of early and late career achievements, and time to career progression between males and females. RESULTS: During the first decade, 5.6% of ASOPRS fellows were female (n = 2), which rose to 6.6% (n = 8), 17.6% (n = 32), 22.4% (n = 35), and 39.4% (n = 97) in the second, third, fourth, and fifth decades, respectively. These patterns were echoed in ASOPRS membership. When comparing the first half (1969-1994) to the second half (1995-2018), fellowship (10.5% vs. 30.0%, p < 0.001), membership (8.0% vs. 30.3%, p < 0.001), early career awards (5.6% vs. 28.9%, p = 0.047), program directorship (0.0% vs. 15.7%, p = 0.017), and executive committee female representation (4.5% vs. 16.8%, p < 0.001) increased significantly. However, females were proportionally underrepresented as program directors (p = 0.003), late career award winners (p = 0.001), executive committee members (p < 0.001), and presidents (p = 0.020). Among those reaching leadership positions, females took longer than males to become program directors by a median of 4 years (p = 0.025). CONCLUSIONS: There has been a steady increase in female representation in ASOPRS fellowship training and membership. While significant progress has been made, growth in female leadership and award recognition is still needed.

Pseudoprogression of Metastatic Melanoma to the Orbit With Pembrolizumab.

The management of metastatic melanoma to the orbit may involve a variety of therapeutic modalities including external-beam radiation, chemotherapy, and varying degrees of surgical resection or debulking. Pembrolizumab is an immunotherapeutic agent that has demonstrated efficacy in the treatment of metastatic melanoma. The authors present a case of metastatic melanoma to the orbit demonstrating profound pseudoprogression within hours of beginning pembrolizumab therapy, with associated mass effect and vision loss. Systemic corticosteroids, orbital external-beam radiation therapy, and a brief interruption in pembrolizumab halted expansion of the orbital lesion and vision loss. This case illustrates that rapid increase in orbital melanoma size, due to acute inflammatory response, may occur after initiation of systemic pembrolizumab therapy. Clinicians should be aware of this pseudoprogression mechanism as a potential cause of vision compromise in metastatic orbital melanoma. Prompt recognition and treatment may be needed to prevent permanent vision loss.

Corneal Neurotization: A Review of Pathophysiology and Outcomes.

PURPOSE: The objective of this study is to provide a systematic review of the clinical outcomes of corneal neurotization and present the pathophysiology of corneal wound healing, neurotrophic keratopathy, and corneal neurotization. METHODS: A literature review of published articles and meeting abstracts between December 2008 and February 2019 in the English language with the terms "corneal neurotization," "corneal neurotisation," "corneal reinnervation," and "neurotrophic keratopathy" was performed. Reported clinical data before and after corneal neurotization, and surgical techniques, were collected and analyzed. RESULTS: A total of 54 eyes that underwent corneal neurotization were identified. Final Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity improved to 0.85 (standard deviation [SD] = 0.65) from 1.25 (SD = 0.71) with a mean improvement of 0.41 (SD = 0.55; p < 0.0001). Central corneal sensation measured using Cochet-Bonnet esthesiometer improved from 2.18 mm (SD = 0.4) to 40.10 mm (SD = 18.66) with a mean filament length change of 38.00 mm (SD = 18.95; p < 0.0001). The median time to the reported maximal sensation return was 8 months (interquartile range 6-10). The most common reported limitation to visual recovery was corneal scarring (31.5%). Children (ages 0-17 years) as compared with adults (ages 18-82 years) had significantly greater final central corneal sensation esthesiometry readings, central corneal sensation return, and improvement in the logMAR best-corrected visual acuity (p < 0.011). CONCLUSIONS: Neurotrophic keratopathy disturbs the homeostatic balance of trophic factors and trigeminal nerve reflexes needed to support ocular surface health and corneal healing. Corneal neurotization can significantly improve corneal sensation and visual acuity and should be considered for the treatment of refractory neurotrophic keratopathy, especially in pediatric populations.

Current Trends in Upper and Lower Eyelid Blepharoplasty Among American Society of Ophthalmic Plastic and Reconstructive Surgery Members.

PURPOSE: To assess current practice patterns for management of upper and lower eyelid blepharoplasty by active American Society of Ophthalmic Plastic and Reconstructive Surgery members. METHODS: An invitation to participate in a web-based anonymous survey was sent to the active American Society of Ophthalmic Plastic and Reconstructive Surgery membership via email. The survey consists of 34 questions, both multiple choice and free response, regarding upper and lower eyelid blepharoplasty surgery. Practice patterns for both aesthetic and functional blepharoplasty are assessed. RESULTS: Thirty-four percent (161/472) of American Society of Ophthalmic Plastic and Reconstructive Surgery members polled responded to the survey. Members perform an average of 196 upper eyelid, 46 lower eyelid, and 53 four-eyelid blepharoplasty procedures per year, with 70% of cases being functional and 30% purely aesthetic. Most members prefer monitored care (71%) to local (21%) or general (8%) anesthesia. Eighty-nine percent of surgeons use topical antibiotics after surgery, erythromycin being the most common (51%). Fourteen percent of members use postoperative oral antibiotics, with cephalexin (81%) being most common. In upper eyelid blepharoplasty, orbicularis muscle is excised by 86% of respondents. Orbital fat is excised, when deemed appropriate, in 97% of cases, with nasal fat excised most commonly (88%). Less commonly, fat repositioning (36%) and adjunctive fat grafting (33%) are performed. In lower eyelid blepharoplasty, surgeons report using one or more of the following approaches: transconjunctival (96%), transcutaneous (82%), and both transconjunctival and transcutaneous (51%). Common adjunctive procedures include orbital fat excision (99%), fat repositioning (80%), and lateral canthal suspension (96%). Less common adjunctive procedures include laser skin resurfacing (36%) and chemical peels (29%). CONCLUSIONS: This report outlines contemporary practice patterns among active American Society of Ophthalmic Plastic and Reconstructive Surgery members in the management of upper and lower eyelid blepharoplasty. It is important to quantify such data periodically to update the membership as to how this common surgical procedure is approached. This also allows eyelid surgeons to compare their practice patterns with a national group specializing in such surgery.