Mohs Micrographic Surgery With Immunohistochemistry for the Treatment of Periocular Melanoma In Situ.

PURPOSE: Mohs micrographic surgery with immunohistochemistry allows for same-day comprehensive margin assessment of melanoma in situ prior to subspecialty reconstruction. This study describes the oncologic and reconstructive outcomes of eyelid and periorbital melanoma in situ and identifies risk factors for complex reconstructive demands. METHODS: Retrospective case series of all patients treated with Mohs micrographic surgery with immunohistochemistry for melanoma in situ affecting the eyelids or periorbital region from 2008 to 2018 at a single institution. Tumors were assigned to the eyelid group if the clinically visible tumor involved the skin inside the orbital rim. Reconstructive variables were compared between the eyelid and periorbital cohorts. RESULTS: There were 24 eyelid and 141 periorbital tumors included. The initial surgical margin for all tumors was 5.34 ± 1.54 mm and multiple Mohs stages were required in 24.2% of cases. Eyelid tumors included more recurrences (p = 0.003), and the average defect size was larger (14.0 ± 13.3 cm2 vs. 7.7 ± 5.4 cm2, p = 0.03). Risk factors for complex reconstruction included: initial tumor diameter >2 cm (odds ratio [OR]: 3.84, 95% confidence interval [CI]: 1.95-7.57) and eyelid involved by initial tumor (OR: 4.88, 95% CI: 1.94-12.28). At an average follow-up of 4.8 years, there were no melanoma-related deaths and 1 local recurrence (0.6% recurrence rate). CONCLUSIONS: Mohs micrographic surgery with immunohistochemistry achieves excellent local control rates for periocular melanoma in situ. An initial surgical margin of 5 mm is frequently insufficient to achieve clear margins. The resulting defects are large, and the complexity of reconstruction can be predicted by tumor size and clinical involvement of eyelid skin.

Impact of Teprotumumab on Clinical Practice in Thyroid Eye Disease.

BACKGROUND: Following its FDA approval in January 2020, we examined the impact of teprotumumab on thyroid eye disease (TED) clinical practices. METHODS: Across three referral centers from January 1, 2018, to December 30, 2022, we retrospectively analyzed demographics, clinical features, treatment choices, and insurance status of patients with active, moderate to severe TED. RESULTS: Of 74 patients recommended for medical therapy, 53% received collaborative recommendations from endocrinologists and ophthalmologists in a TED clinic. Prior to teprotumumab availability, 19 patients were recommended medical therapy, and all received medical therapy (100%), which consists of corticosteroids (14, 73.7%) or tocilizumab (5, 26.3%). After teprotumumab became available, out of 55 patients that were recommended medical therapy, only 41 (74.6%) received medical therapy, mostly teprotumumab (33, 60%), followed by corticosteroids (5, 9.1%) or tocilizumab (3, 5.4%), while 14 (25.4%) did not receive medical therapy. Discordance between physicians' recommendations and therapy received or lack thereof was explained by patients' refusal (9, 64.3%), mostly due to side effect concerns (8, 88.9%), and insurance denial (5, 35.7%). Teprotumumab use was mostly associated with otic changes (10, 30.3%), weight loss (9, 27.3%), and hyperglycemia (6, 18.2%), but 2 (6.1%) patients developed serious infections. Corticosteroids were associated with insomnia (4, 21.1%), and one patient in the tocilizumab group had an infusion reaction requiring hospitalization. CONCLUSION: Teprotumumab introduction increased TED therapy evaluations, yet not all received recommended treatment due to safety concerns or accessibility issues. Enhancing collaborative care, medication accessibility, and adverse effect management is crucial.

Eyelid and Brow Rejuvenation: Technical Pearls and Outcomes of Upper Blepharoplasty with or without Ptosis Correction and Browlift.

BACKGROUND: Eyelid ptosis may present with upper lid dermatochalasis and brow ptosis. When indicated, ptosis correction (PC) is advocated during upper blepharoplasty (UB). Here, we aimed to report our outcomes following UB and PC. METHODS: A retrospective review of patients that underwent UB from November 2018 to March 2020 was performed. Patient demographics, clinical characteristics, and revisions were recorded. Cox regression was performed to assess predictors of revision. RESULTS: Overall, 278 patients with 533 UB were included. Mean age was 67.3 years. Mean follow-up was 8.3 months. In 169 (31.7%) cases, a browlift was performed. UB and PC were performed in 109 (20.5%) cases, of which 60 (55%) involved Müller's muscle conjunctival resection, and 49 (45%) were levator repairs. New dry eye symptoms lasting ≥3 months occurred in 4 (0.8%) cases, all of which resolved. Revision rate was 3.8% after UB (residual skin [n=11], hypertrophic scar [n=4], Herring's law-related ptosis [n=1]); versus 9.2% after UB and PC (overcorrection [n=4], residual skin [n=4], asymmetry [n=2]). Multivariable analysis demonstrated increased revision rates after UB and PC (p-value=0.008). There was no difference in revision rates between different techniques of PC. CONCLUSIONS: In our study of 278 patients presenting for dermatochalasis, up to 21% of cases required ptosis correction in addition to upper blepharoplasty. Ptosis correction is a safe procedure when combined with upper blepharoplasty, regardless of technique used. The revision rate in our series was 9.2% after the combined procedure, which is greater than the revision rate of upper blepharoplasty only, however, comparable to the literature.

Obstructive Sleep Apnea Associated With Increased Failure Rate of Ptosis Repair.

PURPOSE: This study investigates how Obstructive sleep apnea (OSA) affects the outcomes of ptosis repair. We hypothesized that patients with OSA have an increased rate of reoperation after ptosis repair. METHODS: This retrospective cohort study included patients age >18 from the Mayo Clinic who underwent ptosis repair by levator advancement or Müller muscle-conjunctiva resection between 2018 and 2021. Outcomes were measured at 1 to 3 months of follow-up with surgical failure defined as asymmetry or unsatisfactory eyelid height requiring revision surgery within 1 year. RESULTS: A total of 577 patients met the inclusion criteria. There was a statistically significant difference in surgical failure between patients with OSA and those without (20.5% vs. 13.1%, p = 0.02). Patients with OSA showed a statistically significant difference in risk of revision by a factor of 1.70 (95% CI: 1.06-2.07). Revisions were attributed to unsatisfactory eyelid height in 72.6% of patients and eyelid asymmetry in 21.1%. All patients who had revision surgery had satisfactory outcomes. On logistic regression analysis, when adjusting for age and sex, OSA was significantly associated with ptosis revision ( p = 0.007). CONCLUSIONS: OSA increases risk of surgical failure and need for revision surgery in patients undergoing blepharoptosis repair but is not a sole risk factor.

Surgical Anatomy of the Microscopic and Endoscopic Transorbital Approach to the Middle Fossa and Cavernous Sinus: Anatomo-Radiological Study with Clinical Applications.

BACKGROUND: The transorbital approaches (TOAs) have acquired growing notoriety, thanks to their ability to offer alternative corridors to the skull base. However, the limited access and the unfamiliarity with this surgical perspective make recognition of key landmarks difficult, especially for less experienced surgeons. The study wants to offer a detailed description of the anatomy to comprehend the potential and limitations of TOAs. METHODS: Measurements of the orbit region and the surrounding areas were performed on two hundred high-resolution CT scans and thirty-nine dry skulls. Five specimens were dissected to illustrate the TOA, and one was used to perform the extradural clinoidectomy. Three clinical cases highlighted the surgical applications. RESULTS: A step-by-step description of the key steps of the TOA was proposed and a comparison with the transcranial anterior clinoidectomy was discussed. The mean work distance was 6.1 ± 0.4 cm, and the lateral working angle increased 20 ± 5.4° after removing the lateral orbital rim. CONCLUSIONS: TOAs are indicated in selected cases when tumor involves the lateral portion of the cavernous sinus or the middle skull base, obtaining a direct decompression of the optic nerve and avoiding excessive manipulation of the neurovascular structures. Comprehension of surgical anatomy of the orbit and its surrounding structures is essential to safely perform these approaches.

Leptospirosis and the Environment: A Review and Future Directions.

Leptospirosis is a zoonotic disease of global importance with significant morbidity and mortality. However, the disease is frequently overlooked and underdiagnosed, leading to uncertainty of the true scale and severity of the disease. A neglected tropical disease, leptospirosis disproportionately impacts disadvantaged socioeconomic communities most vulnerable to outbreaks of zoonotic disease, due to contact with infectious animals and contaminated soils and waters. With growing evidence that Leptospira survives, persists, and reproduces in the environment, this paper reviews the current understanding of the pathogen in the environment and highlights the unknowns that are most important for future study. Through a systematic Boolean review of the literature, our study finds that detailed field-based study of Leptospira prevalence, survival, and transmission in natural waters and soils is lacking from the current literature. This review identified a strong need for assessment of physical characteristics and biogeochemical processes that support long-term viability of Leptospira in the environment followed by epidemiological assessment of the transmission and movement of the same strains of Leptospira in the present wildlife and livestock as the first steps in improving our understanding of the environmental stage of the leptospirosis transmission cycle.

Medical Therapy in Patients with Moderate to Severe, Steroid-Resistant, Thyroid Eye Disease.

Background: Corticosteroid therapy is often employed in thyroid eye disease (TED), but its efficacy is variable. Teprotumumab and tocilizumab have been considered as effective alternatives. This study aims to evaluate their clinical outcomes and safety in patients with steroid-resistant TED. Methods: A retrospective case-control study was conducted between 2018 and 2022 within a national multicenter health system. Thirty-seven patients with moderate to severe steroid-resistant TED treated with teprotumumab or tocilizumab (cases) were compared with steroid-naïve patients treated with similar therapy (controls). Due to lack of steroid-naïve patients treated with tocilizumab, a control subgroup for tocilizumab was not included in the analysis. Demographic and clinical characteristics were described. Proptosis, diplopia, clinical activity score (CAS), and disease severity (European Group on Graves' orbitopathy classification) were evaluated at weeks 0, 12, 24, and 52 after therapy initiation. Results: Thirty-one patients received teprotumumab (13 cases and 18 controls) and 6 received tocilizumab (cases). The mean age was 57 years (standard deviation ±14.3), median duration of TED was 11.5 months (interquartile range [IQR]: 7.2-17.7), and median excess proptosis was 4 mm (IQR: 2-8) above the upper limit of normal for sex and race. At week 24, in the teprotumumab cases, 81% had proptosis response (reduction of ≥2 mm), 45.5% resolution of diplopia, 85.7% disease inactivation (CAS <3), and 58.3% reverted to mild disease severity. There were comparable results in teprotumumab controls, with no significant differences between subgroups. In the tocilizumab cases, 50% had a proptosis response, 16.7% resolution of diplopia, 100% disease inactivation, and 75% returned to mild disease. In the teprotumumab cases, there was a trend toward worsening proptosis and diplopia between weeks 24 and 52. In the same time frame, the tocilizumab cases had a trend toward worsening diplopia, disease activity, and severity. In the teprotumumab subgroup, 46.2% experienced otic changes and 23.1% hyperglycemia. In the tocilizumab subgroup, there were no reported adverse events. Conclusions: Teprotumumab and tocilizumab improved inflammation in patients with moderate to severe TED who had failed previous steroid therapy. Additionally, the teprotumumab cases demonstrated similar improvement in proptosis and diplopia to the teprotumumab controls. Further evaluation, particularly regarding the long-term response and side effect profile, of these medications in steroid-resistant TED is needed.

Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease.

CONTEXT: Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED). OBJECTIVE: We report the first clinical studies of an FcRn inhibitor, batoclimab, in TED. DESIGN: Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials. SETTING: Multicenter. PARTICIPANTS: Patients with moderate-to-severe, active TED. INTERVENTION: In the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks. MAIN OUTCOME: Change from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial). RESULTS: The randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P < .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P < .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P < .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation. CONCLUSIONS: These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.

Incidence and Characteristics of Facial and Ophthalmic Injuries From Domestic Mammal Bites: Parts of the data in the manuscript were presented at the American Academy of Ophthalmology Annual Meeting, 2022.

PURPOSE: To determine population-based incidence and characteristics of facial and ophthalmic injuries from domestic mammal bites in Olmsted County, Minnesota. DESIGN: Retrospective, population-based cohort study. METHODS: The Rochester Epidemiology Project (REP) was used to identify all potential cases of facial injuries from domestic mammal bites in Olmsted County, Minnesota from January 1, 1999, to December 31, 2015. Subjects were categorized into 2 cohorts: the ophthalmic cohort, which included persons with ocular and periocular injuries with or without facial injuries, and the non-ophthalmic cohort, which included persons with facial injuries only. The incidence and characteristics of facial and ophthalmic injuries from domestic mammal bites were assessed. RESULTS: There were 245 patients with facial injuries, 47 ophthalmic and 198 non-ophthalmic. The overall age- and sex-adjusted incidence of facial injuries was 9.0 (CI = 7.9-10.1) per 100,000 persons per year, 1.7 (CI = 1.2-2.2) ophthalmic and 7.3 (CI = 6.3-8.3) non-ophthalmic. Rates of facial injuries were highest in patients younger than 5 years and lowest in patients 50 years or older, 49.1 (CI = 41.3-61.6) and 1.3 (CI = 0.7-2.5), respectively (P < .001). All facial injuries were caused by either dog (92%) or cat (8%) bites. Patients with ophthalmic injuries received more intravenous prophylactic antibiotics (18% vs 1%, P < .001), wound closure (83% vs 58%, P < .001), and hospital admission (6% vs 0%, P = .007) than patients with non-ophthalmic injuries. Facial injury complications were infrequent (14, 6%) and included soft tissue infection and prominent scar. CONCLUSIONS: Although domestic mammal bites to the face are quite common, ocular injury occurs in a minority of cases.

Alemtuzumab-Induced Thyroid Eye Disease: A Comprehensive Case Series and Review of the Literature.

PURPOSE: To present 5 cases of alemtuzumab-induced thyroid eye disease (AI-TED) and review the literature to highlight the natural history, severity, and outcomes as compared with conventional thyroid eye disease (TED). METHODS: A multi-institutional retrospective case series of patients with AI-TED was compiled. Chart review evaluated for clinical characteristics, imaging findings, and treatment for AI-TED. Additionally, a comprehensive review of the literature identified all previously published cases of AI-TED. RESULTS: Five new patients with AI-TED were included in this series. The average clinical activity score on presentation was 2.8 (range 1-4) and reached an average peak of 5.0 during the active phase of the disease (4-7). Patients were treated medically with selenium (40%) or monoclonal antibodies including teprotumumab or tocilizumab (40%). Surgical treatment with orbital decompression for compressive optic neuropathy was performed on 2 (40%) patients. Combined with 11 previously reported cases, these 16 patients with AI-TED had an average clinical activity score on presentation of 3.3. The average length of the AI-TED phase was 14.0 months, and all patients were treated with medical and/or surgical interventions for their disease. CONCLUSIONS: Clinical and imaging findings in AI-TED mirror that of conventional TED, however, AI-TED may present with greater severity. AI-TED may develop many months after Graves' disease; therefore, providers should be aware of this association and monitor patients for the development of severe TED.

Thyroid eye disease or Graves' orbitopathy: What name to use, and why it matters.

There is currently no universally accepted name for inflammatory disease of the eye and orbit associated with thyroid autoimmune disease. Variability in terminology impedes the evaluation of scientific literature and clinical collaboration and can affect patients' understanding of a disease process. The goals of this perspective article are 1. To compare the frequency of different terms used for eye disease associated with autoimmune thyroid disease in the scientific literature between 2000, 2010 and 2020 publications; 2. To investigate potential associations of terminology with author and journal specialty, and multidisciplinary vs. mono-disciplinary author teams; 3. To determine preferential terms used by professional societies; and 4. To propose standardized terminology based on our data analysis. The methods for this study included review of all English language articles listed in PubMed, with publication dates in the years 2000, 2010 and 2020, that included one of 6 terms currently used to describe eye disease associated with autoimmune thyroid disease. Characteristics pertaining to authors, journals, and article type were recorded. Results showed that the most used term in the 2000 literature was Graves' Ophthalmopathy (61%). In the 2010 literature, Graves' Orbitopathy (31%) became most common, followed by Graves' Ophthalmopathy (30%). Between 2010 and 2020, thyroid eye disease (37%) became the most common term, followed by Graves' Orbitopathy (35%). This perspective article proposes "thyroid eye disease" (TED) as the preferred name for this entity and discusses supporting terminology patterns and trends over time in scientific literature and in professional societies.

Virtual Surgical Planning and 3D-Printed Surgical Guides in Facial Allotransplantation.

The complex three-dimensional (3D) anatomy in facial allotransplantation creates a unique challenge for surgical reconstruction. Evolution of virtual surgical planning (VSP) through computer-aided design and computer-aided manufacturing has advanced reconstructive outcomes for many craniomaxillofacial indications. Surgeons use VSP, 3D models, and surgical guides to analyze and to trial surgical approaches even prior to entering the operating room. This workflow allows the surgeon to plan osteotomies and to anticipate challenges, which improves surgical precision and accuracy, optimizes outcomes, and should reduce operating room time. We present the development, evolution, and utilization of VSP and 3D-printed guides in facial allotransplantation at our institution, from guide conception to first clinical case.

Telemedicine for Preoperative Evaluation of Upper Eyelid Malposition: Reliability of Diagnosis and Surgical Plan.

PURPOSE: Outpatient visits and surgeries for nonurgent indications in ophthalmology have intermittently been restricted during the COVID-19 pandemic. Telemedicine services have rapidly gained acceptance during this period, and could improve patient access for routine oculoplastic evaluations in the future. The objective of this study is to investigate interobserver and intraobserver reliability of eyelid and brow position assessment and surgical plan when comparing photography-based and face-to-face evaluation. METHODS: This was an observational study conducted at a single academic center. Thirty randomly selected patients who had completed an in-office evaluation for chief complaint of "drooping eyelids" between June 2019 and March 2020 were included. Virtual assessment of brow position, dermatochalasis, blepharoptosis, and margin-reflex distance 1 was performed by 2 oculoplastic surgeons based on external photographs, and a surgical plan was formulated. Fraction of agreement and Cohen's κ were determined to evaluate reliability of the virtual assessment compared to face-to-face examination. RESULTS: For 60 eyes from 30 study subjects, diagnostic reliability for observer A was near perfect for brow ptosis, substantial for blepharoptosis and moderate for dermatochalasis (κ = 0.86, 0.67, and 0.57, respectively); for observer B, reliability was moderate for brow and blepharoptosis and substantial for dermatochalasis (0.47, 0.59, and 0.79). Fraction of agreement for blepharoptosis was 94% in eyes where the eyelid margin was visible, and 66% in eyes where the eyelid margin was obscured by overhanging skin. Virtual margin-reflex distance 1 measurements were highly correlated with those obtained face to face (r = 0.77, p < 0.01). Fraction of agreement for surgical plan after virtual examination by observer A/B, respectively, was 100%/94% for brow lift, 90%/87% for blepharoptosis repair and 83%/83% for functional upper blepharoplasty. CONCLUSIONS: Virtual evaluation of upper eyelid and brow malposition can be performed with acceptable reliability. Co-existing dermatochalasis or brow ptosis may require special photographic technique or video examination to ensure an appropriate diagnosis. A photography-based preliminary surgical plan offers a viable alternative to face-to-face encounters.

Delayed periorbital hemorrhage in oculoplastic surgery patients on oral anticoagulants.

Periorbital hemorrhage is a potentially sight threatening surgical complication. The effect of new oral anticoagulants (NOACs) on hemorrhagic events after periorbital surgery has not been investigated. We describe four cases of severe delayed postoperative hemorrhage associated with NOACs, in addition to three cases in patients on traditional antithrombotic agents. Time of delayed hemorrhage ranged from postoperative day 2 to 6. Six patients required surgical intervention to achieve control of bleeding, and two patients required transfusion of blood products. Risk factors and management of this rare complication are discussed.

An Assessment of Globe Position Dynamics following Transcranial Lateral and Superior Orbital Wall Resections without Rigid Reconstruction: A Case Series of 55 Patients.

Background There is no consensus exists regarding which reconstructive approach, if any, should be used after performing transcranial lateral orbital wall resections. Rigid reconstruction is often done to prevent enophthalmos; however, it is not clear if this is a risk with extensive orbital wall resections for transcranial surgery. Objective To assess globe position dynamics in patients that underwent transcranial lateral and superior orbital wall resections without rigid reconstruction to determine if enophthalmos is a significant risk. Methods Preoperative (PO) and postoperative data were retrospectively collected from the electronic medical records of 55 adult patients undergoing lateral and superior orbital wall resections as part of a skull base approach. The globe positions were assessed radiologically at all available time points and used to track relative globe displacements over time. Results An evaluation of PO variables identified a relationship between maximum lesion diameters and globe positions dynamics. The composition of globe position presentations in the population remained relatively stable over time, with only 1 out of 55 patients (1.81%) developing postoperative enophthalmos. An assessment of mean globe displacements revealed improvements in the patients presenting with PO exophthalmos, and stability in the patients presenting with normal PO globe positions. Conclusions Excellent results in long-term postoperative globe position dynamics can be achieved without the use of rigid reconstruction after transcranial lateral and superior orbital wall resections, regardless of the PO globe positioning.

Accelerated visual recovery from protracted hypoxic cortical blindness in a child.

PURPOSE: This report describes accelerated visual recovery in a child following protracted hypoxic cortical visual loss and reviews mechanisms responsible for visual recovery. OBSERVATIONS: A 12-year-old boy developed cortical blindness after a severe snowboarding crash. Magnetic resonance imaging showed severe multifocal hypoxic brain injury, with multifocal restricted diffusion and extensive T2/FLAIR hyperintensities throughout the visual cortex, basal ganglia and midbrain. The mismatch of affected areas on FLAIR and DWI sequences indicated a combination of cytotoxic and vasogenic edema, which suggested partial reversibility with potential for recovery. Two weeks after his injury, he began to experience an accelerated improvement in vision with recovery of 20/20 visual acuity and 40 sec/arc stereoacuity over the following week. Three months later, visual field examination showed a steep-margined horizontal band of spared visual field, which showed further expansion on repeat testing 1 year later. CONCLUSIONS AND IMPORTANCE: Protracted hypoxic cortical visual loss can be followed by dramatic visual recovery in children. Magnetic resonance imaging can provide useful prognostic information.

Pre-aponeurotic Fat Prolapse Following Levator Resection for Congenital Ptosis.

The authors describe three children who developed excess overhanging upper eyelid tissue following unilateral levator resection for congenital ptosis. This was thought to be pre-aponeurotic fat herniation. A second procedure, a variation of sulcoplasty, was performed at a mean 4.3 months later and all three children showed improved sulcus and crease symmetry. [J Pediatr Ophthalmol Strabismus. 2019;56:e1-e4.].