Transcutaneous Retrobulbar Amphotericin B Injection for Invasive Fungal Sinusitis with Orbital Involvement: A Systematic Review.

BACKGROUND: Orbital involvement of invasive fungal sinusitis (IFS) is an ominous prognostic marker that should prompt rapid intervention. Transcutaneous retrobulbar administration of amphotericin B (TRAMB) is an off-label adjunctive treatment that can increase drug penetrance into diseased orbital tissue. To date, there is a lack of consensus regarding the use of TRAMB for treatment of IFS with orbital involvement. OBJECTIVE: This systematic review aims to synthesize the indications, efficacy, and potential complications of TRAMB. METHODS: PubMed, EMBASE, and Web of Science databases were probed for systematic review. Article search was conducted through June 2023 using the keywords "invasive fungal sinusitis," "invasive fungal rhinosinusitis," "rhino-orbital mucormycosis," "rhinosinusitis," "orbital," "retrobulbar," and "amphotericin." RESULTS: In suitable cases as determined by radiologic and clinical evaluation, TRAMB administration has the potential to improve orbital salvage rates and improve versus stabilize visual acuity. Treatment complications are more likely with deoxycholate than with liposomal amphotericin formulations. The existing literature describing use of TRAMB is limited due to its retrospective nature, but the increase in IFS cases since 2020 due to the COVID pandemic has broadened the literature. CONCLUSIONS: TRAMB is an effective adjunctive treatment in IFS with mild-to-moderate orbital involvement when used in combination with standard of care debridement, systemic antifungal therapy, and immunosuppression reversal. Prospective longitudinal studies and multi-institutional randomized trials are necessary to determine the definitive utility of TRAMB.

Probing versus primary nasal endoscopy for the treatment of congenital dacryocystoceles.

PURPOSE: To compare outcomes and complications of three surgical techniques for the treatment of congenital dacryocystoceles: nasolacrimal probing and irrigation (P+I), P+I plus nasal endoscopy (NE) with intranasal cyst marsupialization, and primary NE with intranasal cyst marsupialization. METHODS: The medical records of children ≤2 years of age at a single academic center with a diagnosis of dacryocystocele from 2012 to 2022 were retrospectively identified and reviewed. The primary outcome was resolution of the dacryocystocele (ie, elimination of the medial canthal mass and resolution of tearing or discharge) after a single procedure ("primary success"). Surgical techniques were compared using exact logistic regression. RESULTS: Of 54 patients, 21 (39%) underwent P+I, 23 (43%) underwent P+I plus nasal endoscopy, and 10 (18%) underwent primary NE. Primary success was 76% for P+I and 100% for the other two cohorts. Most patients (89%) who underwent P+I received general anesthesia compared with none who underwent primary nasal endoscopy. Most complications were related to the use of general anesthesia, with a complication rate of 10% for P+I, 48% for P+I plus NE, and 0% for primary NE. Most P+I procedures required hospital admission compared to half of primary NE procedures. CONCLUSIONS: In our study cohort, primary NE provided good outcomes and was associated with a lower complication rate than P+I with or without NE.

Evaluating for unrecognized deficits in perimetry associated with functional upper eyelid malposition.

Objective: To investigate whether functional upper eyelid malposition is associated with unrecognized deficits in automated perimetry among glaucoma patients by examining patients undergoing eyelid surgery who had not been identified as requiring eyelid taping during glaucoma field testing. Methods: In this retrospective pre-post study, an automated database search followed by manual chart review was used to identify eligible patients from January 2012 to March 2020. Included patients had reliable visual field testing within two years before and after functional upper blepharoplasty or ptosis repair and no comorbid ocular diagnoses. As part of routine practice, glaucoma visual field technicians taped patients with pupil-obstructing eyelid malposition; taped examinations were excluded from analysis. Clinical and demographic characteristics, mean deviation, and pattern standard deviation were evaluated within a two year period before and after eyelid surgery. Results: The final analysis included 60 eyes of 38 patients. Change in visual field parameters after eyelid surgery did not reach statistical significance in crude or adjusted analyses. Among patients with ptosis, the margin reflex distance-1 was not associated with change in mean deviation after surgery (Pearson R2 â€‹= â€‹0.0061; P â€‹= â€‹0.700). Five of 17 eyes excluded from analysis due to unreliable pre-operative visual fields demonstrated substantial improvement after surgery. Conclusions: Functional upper eyelid malposition does not appear to cause spurious visual field abnormalities among glaucoma patients with reliable visual fields who were determined not to require eyelid taping at the time of their visual fields. Unreliable visual fields could be a sign of eyelid interference in this population.

Outcomes for expanded polytetrafluoroethylene strip in frontalis suspension surgery.

PURPOSE: This study evaluates surgical outcomes and complication rates of frontalis suspension with expanded polytetrafluoroethylene (ePTFE). METHODS: This retrospective cohort study reviewed all patients undergoing frontalis suspension surgery using ePTFE as the sling material from January 1 2012 to March 3 2020 by a single surgeon at a single academic center. Two different surgical techniques were evaluated in the placement of the sling material. Demographic, clinical, and operative data were extracted. Outcome data including postoperative lid height, reoperation, and complication rate were extracted for the cohort and compared between the two surgical techniques. Descriptive statistics were utilized. RESULTS: Sixty-four eyes from 49 unique patients were included in this study. Forty-three (67.2%) patients had isolated congenital blepharoptosis; 14 (21.9%) had blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES); and 2 (3.1%) had cranial nerve III palsy. Fifty-one (79.7%) patients had no prior blepharoptosis surgery. Lid crease incision and stab incision techniques were utilized for 24 (37.5%) and 40 (62.5%) eyes, respectively. Overall, 21 (32.8%) eyes required reoperation with ePTFE to achieve appropriate eyelid height or contour. Only one patient experienced implant infection, requiring removal of ePTFE sling after a second reoperation. There were no cases of implant exposure or granuloma formation noted during the study period. CONCLUSION: An ePTFE strip soaked in cefazolin prior to utilization in surgery is a viable material for frontalis suspension surgery, with a lower infectious or inflammatory complication rate than previously reported. However, reoperation rate was still relatively high.

Cutaneous Mucormycosis of the Eyelid Treated With Subcutaneous Liposomal Amphotericin B Injections.

Cutaneous mucormycosis is a rare, opportunistic fungal infection that typically affects immunocompromised hosts. Current treatment consists of systemic antifungal therapy, surgical debridement, and when applicable, restoration of immune function. Despite intervention, the morbidity and mortality of invasive fungal disease remains high. There are few reports of primary or secondary cutaneous mucormycosis involving the ocular adnexa. The authors describe the course of 2 children with cutaneous mucormycosis of the eyelid treated with subcutaneous liposomal amphotericin B (LAmB) injections (3.5 mg/ml) in an off-label application as an adjunct to debridement and systemic antifungal therapy. To the authors' knowledge, these are the first 2 cases of invasive fungal disease involving the eyelid treated with subcutaneous LAmB injections, and the first reported case of disseminated fungal infection with secondary cutaneous involvement of the eyelid.

Dacryoscintigraphy as a guide for surgery in patients with functional epiphora.

OBJECTIVE: To investigate how dacryoscintigraphy (DSG) may benefit surgical planning for functional epiphora. METHODS: A retrospective multicenter case series was performed on patients with symptomatic tearing despite no identified external cause and normal lacrimal probing and irrigation (i.e., functional epiphora). All patients had preoperative DSG testing. Patients were excluded if DSG testing failed to detect a tear flow abnormality. Those with delayed tear flow prior to entering the lacrimal sac (presac) on DSG underwent surgery aimed at improving flow into the lacrimal sac. Those with delayed tear flow after the lacrimal sac (postsac) on DSG underwent dacryocystorhinostomy. Surgical success was defined as epiphora being completely resolved, significantly improved, or partially improved. Surgical failure was defined as epiphora being unchanged or worse than at the preoperative timepoint. RESULTS: A total of 77 cases (53 patients) of DSG-guided surgery were included. A presac delay was observed in 14 cases (18.2%) and post-sac delay in 63 (81.8%). Overall surgical success was 83.1% across the cohort. Success was 100% in the presac group and 79.4% in the postsac group (p = 0.06). Mean follow-up time was 22 months (SD = 21 months). CONCLUSION: A role was demonstrated for DSG in the planning of surgery for patients with functional epiphora. The DSG-guided approach, when compared with empirical lacrimal intubation or dacryocystorhinostomy, may be especially useful in cases of functional epiphora that are presac in nature.

A Case of Orbital Sarcoidosis with Caseating Granulomatous Inflammation.

The authors report a rare case of orbital sarcoidosis with caseating granulomatous inflammation. A 55-year-old man presented with a 2-month history of progressively worsening diplopia and proptosis of the OS. Orbital CT demonstrated a diffuse orbital mass. Diagnostic anterior orbitotomy demonstrated caseating granulomas. Infectious testing, including special stains, cultures, and polymerase chain reaction testing, were negative for infectious causes. Chest CT demonstrated the presence of hilar lymphadenopathy with bronchoscopic biopsy showing noncaseating granulomas, supporting a diagnosis of sarcoidosis. The patient achieved clinical and symptomatic improvement at 8-month follow-up on methotrexate. While sarcoidosis is typically characterized by non-necrotizing granulomatous inflammation, sarcoid granulomas with necrosis have been previously described in pulmonary histopathology. This case emphasizes the importance of a comprehensive systemic workup, keeping systemic sarcoidosis on the differential, for necrotizing granulomatous inflammation of the orbit.

Metagenomic Deep Sequencing for Orbital Inflammatory Disease.

PURPOSE: Orbital inflammatory disease (OID) is a heterogeneous group of immunologic disorders whose etiology is often non-specific despite routine investigation. In this proof-of-concept study, metagenomic deep sequencing (MDS) is applied to examine host gene expression in two subtypes of OID. METHODS: Prospectively collected lacrimal gland tissue from patients with OID was processed for MDS. Differential gene expression analysis was performed to evaluate for host transcriptome signatures. Proof-of-concept comparison was made between histologically confirmed samples of idiopathic dacryoadenitis and IgG4-related disease (IgG4-RD). RESULTS: Twelve genes were identified to be differentially expressed between idiopathic dacryoadenitis and IgG4-RD. Differences in innate humoral immunity gene expression were observed. Several additional genes of interests were also found to be upregulated in idiopathic dacryoadenitis. CONCLUSIONS: A unique transcriptome signature was found when comparing idiopathic dacryoadenitis to IgG4-RD. This suggests that MDS can identify differentially expressed genes in OID. Such insight could potentially provide a better understanding of host gene expression and the inflammatory pathways involved in OID.

Prevalence and Predictors of Hering's Response in Müller's Muscle-conjunctival Resection.

PURPOSE: Determine the prevalence and predictors of Hering's response following Muller's muscle-conjunctival resection (MMCR). METHODS: Seventy-five consecutive patients undergoing unilateral MMCR were recruited in this prospective, multicenter, cohort study. Margin-reflex distance-1 (MRD1) of both eyelids was recorded preoperatively and postoperatively. One hundred forty-three variables were investigated as potential predictors of a late postoperative (≥3 months) Hering's response using regression analyses. Main outcome measures were Hering's response (≥0.5 mm descent of the unoperated eyelid from baseline), and a clinically relevant Hering's response (descent of the unoperated from baseline to a MRD1 ≤ 2.0 mm, or descent from baseline such that the MRD1 of the unoperated eyelid became >1 mm lower than the operated eyelid). RESULTS: Twenty-four (32.0%) patients had a late postoperative Hering's response, but only 6 (8.0%) responses were clinically relevant. A Hering's response at the immediate (OR 16.24, p = 0.02) and 1-week postoperative (OR 8.94, p = 0.04) timepoints predicted a late postoperative response. However, the presence (OR 7.84, p = 0.07) and amplitude (OR 8.13, p = 0.06) of a preoperative phenylephrine Hering's response did not predict a late postoperative response. Of the 10 patients with a clinically relevant phenylephrine Hering's response, only 1 demonstrated a clinically relevant response late postoperatively. CONCLUSION: Unilateral MMCR induces a clinically relevant Hering's response in 8% of patients. A preoperative phenylephrine Hering's response does not predict a late postoperative Hering's response. Therefore, when unilateral phenylephrine testing unmasks contralateral blepharoptosis, only the side with blepharoptosis at baseline should be operated.

Müller Muscle Conjunctival Resection: A Multicentered Prospective Analysis of Surgical Success.

PURPOSE: This is a multicenter prospective cohort study investigating Müller muscle conjunctival resection success rates based on marginal reflex distance-1 (MRD1) and symmetry criteria. A secondary objective was to identify predictors of success. METHODS: One hundred fifty-two patients with unilateral or bilateral blepharoptosis (229 eyelids) undergoing Müller muscle conjunctival resection were consecutively recruited from 2015 to 2020 at the Université de Montréal and University of California San Francisco. Ptosis was defined as MRD1 ≤ 2.0 mm or MRD1 > 1 mm lower than the contralateral eyelid. Patients were selected for Müller muscle conjunctival resection surgery if they demonstrated significant eyelid elevation following phenylephrine 2.5% testing. MRD1 success (operated eyelid achieving MRD1 ≥ 2.5 mm) and symmetry success (patient achieving an intereyelid MRD1 difference ≤ 1 mm) were evaluated for the patient cohort. Predictors of MRD1 and symmetry success were analyzed using multivariate regression analysis. RESULTS: MRD1 success was achieved in 72.1% (n = 165) of 229 operated eyelids. Symmetry success was achieved in 75.7% (n = 115) of 152 patients. MRD1 before phenylephrine testing was the only statistically significant predictor of MRD1 success (odds ratio [OR] 2.69, p = 0.001). Symmetry following phenylephrine testing was the only variable associated with increased odds of symmetry success (OR 2.71, p = 0.024), and unilateral surgery (OR 0.21, p = 0.004), the only variable associated with reduced odds of symmetry success. CONCLUSIONS: Müller muscle conjunctival resection effectively achieves postoperative MRD1 and symmetry success. MRD1 before phenylephrine testing is the strongest determinant of MRD1 success. Neither a large rise in MRD1 with phenylephrine nor increasing tissue resection length adequately counterbalance the effect of a low MRD1 before phenylephrine. Unilateral surgery and the absence of symmetry following phenylephrine predict greater odds of symmetry failure.

Augmentation of telemedicine post-operative follow-up after oculofacial plastic surgery with a self-guided patient tool.

PURPOSE: This study evaluates a web-based tool designed to augment telemedicine post-operative visits after periocular surgery. METHODS: Adult, English-speaking patients undergoing periocular surgery with telemedicine follow-up were studied prospectively in this interventional case series. Participants submitted visual acuity measurements and photographs via a web-based tool prior to routine telemedicine post-operative visits. An after-visit survey assessed patient perceptions. Surgeons rated photographs and live video for quality and blurriness; external raters also evaluated photographs. Images were analyzed for facial centration, resolution, and algorithmically detected blur. Complications were recorded and graded for severity and relation to telemedicine. RESULTS: Seventy-nine patients were recruited. Surgeons requested an in-person assessment for six patients (7.6%) due to inadequate evaluation by telemedicine. Surgeons rated patient-provided photographs to be of higher quality than live video at the time of the post-operative visit (p < 0.001). Image blur and resolution had moderate and weak correlation with photograph quality, respectively. A photograph blur detection algorithm demonstrated sensitivity of 85.5% and specificity of 75.1%. One patient experienced a wound dehiscence with a possible relationship to inadequate evaluation during telemedicine follow-up. Patients rated the telemedicine experience and their comfort with the structure of the visit highly. CONCLUSIONS: Augmented telemedicine follow-up after oculofacial plastic surgery is associated with high patient satisfaction, rare conversion to clinic evaluation, and few related post-operative complications. Automated detection of image resolution and blur may play a role in screening photographs for subsequent iterations of the web-based tool.

Magnetic Resonance Imaging Prognostic Findings for Visual and Mortality Outcomes in Acute Invasive Fungal Rhinosinusitis.

PURPOSE: To identify initial, preintervention magnetic resonance imaging (MRI) findings that are predictive of visual and mortality outcomes in acute invasive fungal rhinosinusitis (AIFRS). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with histopathologically or microbiologically confirmed AIFRS cared for at a single, tertiary academic institution between January 2000 and February 2020. METHODS: A retrospective review of MRI scans and clinical records of patients with confirmed diagnosis of AIFRS was performed. For each radiologic characteristic, a modified Poisson regression with robust standard errors was used to estimate the risk ratio for blindness. A multivariate Cox proportional hazards model was used to study AIFRS-specific risk factors associated with mortality. MAIN OUTCOME MEASURE: Identification of initial, preintervention MRI findings associated with visual and mortality outcomes. RESULTS: The study comprised 78 patients (93 orbits, 63 with unilateral disease and 15 with bilateral disease) with AIFRS. The leading causes of immunosuppression were hematologic malignancy (38%) and diabetes mellitus (36%). Mucormycota constituted 56% of infections, and Ascomycota constituted 37%. The overall death rate resulting from infection was 38%. Risk factors for poor visual acuity outcomes on initial MRI included involvement of the orbital apex (relative risk [RR], 2.0; 95% confidence interval [CI], 1.1-3.8; P = 0.026) and cerebral arteries (RR, 1.8; 95% CI, 1.3-2.5; P < 0.001). Increased mortality was associated with involvement of the facial soft tissues (hazard ratio [HR], 4.9; 95% CI, 1.3-18.2; P = 0.017), nasolacrimal drainage apparatus (HR, 5.0; 95% CI, 1.5-16.1; P = 0.008), and intracranial space (HR, 3.5; 95% CI, 1.4-8.6; P = 0.006). Orbital soft tissue involvement was associated with decreased mortality (HR, 0.3; 95% CI, 0.1-0.6; P = 0.001). CONCLUSIONS: Extrasinonasal involvement in AIFRS typically signals advanced infection with the facial soft tissues most commonly affected. The initial, preintervention MRI is prognostic for a poor visual acuity outcome when orbital apex or cerebral arterial involvement, or both, are present. Facial soft tissues, nasolacrimal drainage apparatus, intracranial involvement, or a combination thereof is associated with increased mortality risk, whereas orbital soft tissue involvement is correlated with a reduced risk of mortality.

Efficacy of Care and Antibiotic Use for Chalazia and Hordeola.

OBJECTIVES: To evaluate whether use of an antibiotic improves the efficacy of care for a chalazion or hordeolum. METHODS: A cross-sectional retrospective review was performed. All patients treated for a newly diagnosed chalazion or hordeolum at the University of California, San Francisco from 2012 to 2018 were identified. Patients were excluded when clinical notes were inaccessible or there was inadequate documentation of treatment modality or outcome. Patient demographics, setting of initial presentation, treatment modalities, antibiotic use, and outcomes were analyzed. RESULTS: A total of 2,712 patients met inclusion criteria. Management with an antibiotic was observed in 36.5% of patients. An antibiotic was 1.53 times (95% confidence interval [CI], 1.06-2.22, P=0.025) more likely to be prescribed in emergency or acute care setting for a chalazion. Older age was associated with a higher risk of receiving an antibiotic for a hordeolum (adjusted RR 1.07 per decade, 95% CI, 1.05-1.11, P<0.001). The addition of an antibiotic to conservative measures for a chalazion (adjusted RR, 0.97, 95% CI, 0.89-1.04, P=0.393) or hordeolum (adjusted RR, 0.99, 95% CI, 0.96-1.02, P=0.489) was not associated with an increased likelihood of treatment success. CONCLUSION: Although frequently prescribed, an antibiotic is unlikely to improve the resolution of a chalazion or hordeolum.

Neonatal corneal ulcer secondary to congenital entropion.

PURPOSE: To describe a case of central corneal ulceration in a newborn secondary to congenital entropion. OBSERVATIONS: Corneal ulcers during infancy are rare and may occur secondary to congenital structural anomalies, including congenital entropion. Correct anatomic eyelid position in newborns is challenging to determine with closed eyelids, and eyelid squeezing during crying and discomfort adds to this challenge. CONCLUSIONS AND IMPORTANCE: This report reinforces the importance of careful examination of the adnexa in infants with corneal ulcers while they are most comfortable, usually after topical anesthesia and prior to placement of eyelid speculum. Ophthalmologists caring for infants must be able to detect this condition because prompt entropion repair is necessary for corneal ulcer resolution and prevention of permanent vision loss.

Perceived Barriers to Increasing Diversity within Oculofacial Plastic Surgery.

Purpose Physician diversity is limited in ophthalmology and oculofacial plastic surgery. Determination of barriers within the application process for oculofacial plastic surgery may help target efforts to improve the recruitment of underrepresented groups. This study aimed to illuminate perceived barriers to increasing diversity in oculofacial plastic surgery trainees, according to the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) fellows and fellowship program directors (FPDs). Methods During the month of February 2021, we sent surveys out to 54 current oculofacial plastic surgery fellows and 56 FPDs at 56 oculofacial plastic surgery programs recognized by the ASOPRS nationwide using a 15-question Qualtrics survey. Results Sixty-three individuals (57%) responded to the survey: 34 fellows (63%) and 29 FPDs (52%). Eighty-eight percent of fellows and 68% of FPDs identified as non-underrepresented in medicine (UiM). Forty-four percent of fellows and 25% of FPDs identified as men. FPDs most commonly noted, "Not enough minorities applying to our program" and "The objective data (Ophthalmic Knowledge Assessment Program score, United States Medical Licensing Examination Step scores, clinical honors, Alpha Omega Alpha status, letter of recommendation) for minority applicants often do not meet the threshold required to offer an interview or to be ranked to match" as barriers. Among fellows, the lowest-rated considerations when applying to oculofacial plastic surgery were "Racially/ethnically diverse faculty" and "Perceptions of minority candidates by fellowship programs," whereas "Likelihood of matching in program of choice" was ranked highest in considerations. Fellows identifying as men indicated greater concern for "Financial factors related to fellowship (e.g., loans, salary, cost of living, or cost of interviewing)" compared to fellows identifying as women who noted greater concern for "Program or preceptor acceptance of starting or having a family during fellowship." Conclusion Responses from FPDs suggest that efforts focused on recruiting and supporting diverse students to medicine and ophthalmology, mentoring applicants interested in oculofacial plastic surgery, and restructuring the application process to decrease bias, may improve diversity within the subspecialty. The lack of UiM representation in this study, 6% fellows and 7.4% FPDs identified as UiM, shows both the stark underrepresentation and the need for further research into this topic.

Outcomes of a Modified Treatment Ladder Algorithm Using Retrobulbar Amphotericin B for Invasive Fungal Rhino-Orbital Sinusitis.

PURPOSE: To assess whether a modified treatment ladder algorithm incorporating transcutaneous retrobulbar amphotericin B (TRAMB) for invasive fungal rhino-orbital sinusitis can reduce the risk of exenteration without compromising survival. DESIGN: Retrospective, comparative clinical study with historical control subjects. METHODS: Fifty consecutive patients with biopsy-proven invasive fungal sinusitis and radiographic evidence of orbital involvement were evaluated at a single tertiary institution from 1999-2020. TRAMB was incorporated as part of the treatment algorithm in 2015. Demographics, underlying immune derangement, infective organism, ophthalmic examination, surgical care, and survival were compared in a quasiexperimental pre-post format, dividing patients into a pre-2015 group and a post-2015 group. Risk of exenteration and mortality were the primary outcomes. RESULTS: Baseline characteristics did not differ significantly between the 2 groups. Nearly all patients underwent a surgical intervention, most commonly functional endoscopic sinus surgery with debridement. TRAMB was administered to 72.7% of the post-2015 group. Exenteration was more common in the pre-2015 group (36.4% vs 9.1% [95% confidence interval {CI} 5.2-48.8]; P = .014), while mortality was similar (40.0% vs 36.7% [95% CI -22.1 to 29.3]; P = .816). After adjusting for potential confounders, patients treated after 2015 were found to have lower risk of exenteration (relative risk 0.28 [95% CI 0.08-0.99]; P = .049) and similar risk of mortality (relative risk 1.04 [95% CI 0.50-2.16]; P = .919). CONCLUSION: Compared with historical control subjects, patients with invasive fungal rhino-orbital sinusitis who were treated with a modified treatment ladder algorithm incorporating TRAMB had a lower risk of disfiguring exenteration without an apparent increase in the risk of mortality.

Quality-of-Life Outcomes for Excision and Reconstruction of Periocular Nonmelanoma Skin Cancer.

Background: Understanding how periocular nonmelanoma skin cancer (NMSC) impacts quality of life (QoL) provides insight into the patient experience. Objective: To prospectively measure QoL of individuals with surgically treated periocular NMSC. Methods: Responses to the skin cancer index (SCI) and FACE-Q questionnaires were obtained at preoperative (PRE), postoperative week 1 (POW1), and postoperative month 3 (POM3) visits. Statistical analysis was performed using paired t-test and stepwise linear regression. Results: Forty-five patients participated in the study. Improved QoL as reflected in an increased mean difference of the total SCI score at PRE and POM3 visits (25.8, 95% confidence interval [CI 20.0 to 31.6]) and FACE-Q early life impact of treatment score at POW1 and POM3 visits (19.0, 95% CI [14.9 to 23.0), and a decreased mean difference of the FACE-Q adverse effects score at POW1 and POM3 visits (-1.3, 95% CI [-2.4 to -0.1]) was observed. Linear regression of the SCI and FACE-Q scores using demographic and clinical attributes revealed several predictors of postoperative QoL. Conclusions: Surgical management of periocular NMSC results in improved QoL, demonstrated at the final postoperative visit.

Teprotumumab: Interpreting the Clinical Trials in the Context of Thyroid Eye Disease Pathogenesis and Current Therapies.

Teprotumumab, a monoclonal antibody targeted against the insulin-like growth factor 1 (IGF-1) receptor, was recently approved by the United States Food and Drug Administration for the treatment of thyroid eye disease (TED). Phase 1 studies of teprotumumab for the treatment of malignancies demonstrated an acceptable safety profile but limited effectiveness. Basic research implicating the IGF-1 receptor on the CD-34+ orbital fibrocyte in the pathogenesis of TED renewed interest in the drug. Two multicenter, randomized, double-masked, clinical trials (phase 2 and 3) evaluated the efficacy of 8 infusions of teprotumumab every 3 weeks versus placebo in 170 patients with recent-onset active TED, as defined by a clinical activity score (CAS) of at least 4. Teprotumumab was superior to placebo for the primary efficacy end points in both studies: overall responder rate as defined by a reduction of 2 or more CAS points and a reduction of 2 mm or more in proptosis (69% vs. 20%; P < 0.001; phase 2 study) and proptosis responder rate as defined by a reduction of 2 mm or more in proptosis (83% vs. 10%; P < 0.001; phase 3 study). In both studies, treatment with teprotumumab compared with placebo achieved a significant mean reduction of proptosis (-3.0 mm vs. -0.3 mm, phase 2 study; -3.32 mm vs. -0.53 mm, phase 3 study) and CAS (-4.0 vs. -2.5, phase 2 study; -3.7 vs. -2.0, phase 3 study). Teprotumumab also resulted in a greater proportion of patients with a final CAS of 0 or 1, higher diplopia responder rate, and a larger improvement in the Graves' Ophthalmopathy Quality of Life overall score. More than half of patients (62%, phase 2 trial; 56%, phase 3 trial) who were primary end point responders maintained this response at 51 weeks after the last dose of therapy. The most common adverse events reported with teprotumumab included muscle spasms (25%), nausea (17%), alopecia (13%), diarrhea (13%), fatigue (10%), hearing impairment (10%), and hyperglycemia (8%). Teprotumumab is contraindicated for those with inflammatory bowel disease and who are pregnant. Although the current dosing regimen has proven effective for TED, dose-ranging studies including variable concentrations, infusion frequencies, and durations of teprotumumab therapy in the setting of TED have not been performed.

New-Onset of Inflammatory Bowel Disease in a Patient Treated With Teprotumumab for Thyroid Associated Ophthalmopathy.

A patient with thyroid-associated ophthalmopathy was treated with teprotumumab and developed symptoms concerning for inflammatory bowel disease after her sixth infusion. Colonoscopy was performed, and mucosal biopsies identified evidence of active colitis consistent with a diagnosis of ulcerative colitis. Despite treatment with budesonide and mesalamine, the patient continued to be symptomatic one and a half months after cessation of teprotumumab and required infliximab to achieve good control of her inflammatory bowel disease. This case represents the first report of new-onset inflammatory bowel disease arising during treatment with teprotumumab.