Quantitative Assessment of Subjective Symptoms and Corneal Sensitivity in Chronic Orbital Pain Patients.

PURPOSE: To objectively evaluate the subjective symptoms and characteristics of chronic orbital pain as well as to quantify sensitization of peripheral trigeminal nerves. METHODS: In this prospective cohort study, patients who previously showed a response to peripheral trigeminal nerve blocks for unilateral, idiopathic chronic orbital pain and healthy subjects completed validated questionnaires assessing headaches, neuropathic signs and symptoms, photophobia, and pain qualities. Corneal sensitivity was measured in both eyes for all subjects with a Cochet-Bonnet aesthesiometer. For pain patients, the full assessment protocol was repeated 2-4 weeks after the study injection, and corneal sensitivity was also measured 30 minutes postinjection. Outcomes assessed were headache, neuropathic pain, and photophobia scores; pain qualities; and corneal sensitivity. RESULTS: Six female chronic orbital pain patients (mean age 48.2 years) and 11 female controls (mean age 47.5) were included. The mean headache, neuropathic pain, and photophobia questionnaire scores were significantly higher for pain patients than for controls (p < 0.001). On sensory testing, 5 pain patients (83.3%) endorsed allodynia, and all 6 (100%) had hyperalgesia in the ipsilateral frontal nerve dermatome. No controls had allodynia or hyperalgesia. Corneal sensitivity was similar between eyes in pain patients and between groups. Questionnaire scores and corneal sensitivity did not change significantly after the injection. CONCLUSIONS: Chronic orbital pain patients have a measurable reduction in quality of life due to headaches and photophobia. The supraorbital and supratrochlear nerves are sensitized, resulting in cutaneous hypersensitivity in the corresponding dermatome, but corneal nerves have normal sensitivity.

Retrospective Optimization of the Hawkeye Orbital Fracture Prioritization and Evaluation Algorithms for Triaging Ophthalmic Care.

Objectives: Many orbital fracture patients are transferred to tertiary care centers for immediate ophthalmology consultation, though few require urgent ophthalmic evaluation or intervention. This overutilizes limited resources and overburdens patients and the health care system with travel and emergency department (ED) expenses. A simple, easy-to-use, clinical decision-making tool is needed to aid local EDs and triage services in effectively identifying orbital fracture patients who need urgent ophthalmic evaluation. Design: Single center, retrospective cohort study. Subjects: Orbital fracture patients aged ≥ 18 years who presented to the study institution's emergency department and received an ophthalmology consultation. Methods: Ocular injuries that required close monitoring or an intervention within the first few hours after presentation were termed urgent. Two Hawkeye Orbital Fracture Prioritization and Evaluation (HOPE) algorithms were developed to identify orbital fracture patients needing urgent evaluation; including 1 algorithm incorporating computerized tomography (CT) scans interpreted by ophthalmology (HOPE+CT). Algorithms were compared with 3 previously published protocols: the University of Texas Health Science Center at Houston (UTH), the South Texas Orbital Fracture Protocol (STOP), and Massachusetts Eye and Ear (MEE) algorithms. Main Outcome Measures: Correct triage of patients with orbital fractures who have urgent ocular or orbital conditions. Results: In the study institution's ED, 134 adult patients (145 orbits) were seen with orbital fractures in 2019. Eighteen (13.4%) had ocular or orbital conditions categorized as urgent. The HOPE tool resulted in 100% sensitivity and 78.4% specificity. The HOPE+CT tool resulted in 100.0% sensitivity and 94.0% specificity. The UTH algorithm was 91.7% sensitive and 76.5% specific. South Texas Orbital Fracture Protocol and MEE were both 100% sensitive but only 35.1% and 32.8% specific, respectively. Conclusions: The HOPE and HOPE+CT algorithms were superior or equal to the UTH, STOP, and MEE algorithms in terms of specificity while detecting all urgent cases. Implementation of a triage protocol that uses the HOPE or HOPE+CT algorithms could improve resource utilization and reduce health care costs through identification of orbital fracture patients needing urgent evaluation. An online tool that deploys the HOPE+CT algorithm in a user-friendly interface has been developed and is undergoing prospective validation before public dissemination. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Neural activation associated with outgroup helping in adolescent rats.

Prosocial behavior, helping others in need in particular, occurs preferentially in response to the perceived distress of one's own group members or ingroup. To investigate the development of ingroup bias, neural activity during a helping test was analyzed in adolescent and adult rats. Although adults selectively released trapped ingroup members, adolescent rats helped both ingroup and outgroup members, suggesting that ingroup bias emerges in adulthood. Analysis of brain-wide neural activity, indexed by expression of the early-immediate gene c-Fos, revealed increased activity for ingroup members across a broad set of regions previously associated with empathy. Adolescents showed reduced hippocampal and insular activity and increased orbitofrontal cortex activity compared to adults. Non-helper adolescents demonstrated increased amygdala connectivity. These findings demonstrate that biases for group-dependent prosocial behavior develop with age in rats and suggest that specific brain regions contribute to prosocial selectivity, pointing to possible targets for the functional modulation of ingroup bias.

The Effect of Teprotumumab on Eyelid Position in Patients with Thyroid Eye Disease.

Teprotumumab has been shown to improve proptosis and clinical activity scores (CAS) in patients with thyroid eye disease, but little has been published regarding its effects on eyelid retraction. The purpose of this work was to evaluate changes in eyelid position in thyroid eye disease patients after teprotumumab. Eight patients completed eight cycles of teprotumumab. Data collected included exophthalmometry; clinical activity scores; margin reflex distance (MRD) 1; MRD2; and pre-, during, and posttreatment photographs. ImageJ analysis was also used to evaluate eyelid position in photographs. Proptosis significantly improved in 15 of 16 orbits [mean 4.75 ± 2.07 mm reduction (P = 0.0001) in study orbits and mean 3.00 ± 2.14 mm reduction (P = 0.0048) in nonstudy orbits]. CAS was significantly reduced (pretreatment mean 4.88 mm and posttreatment mean 1.88 mm, P = 0.006). MRD1 decreased in 11 of 16 orbits and increased in five orbits (P = 0.18 in study orbits and P = 0.22 in nonstudy orbits). MRD2 decreased in six of 16 orbits and increased in eight orbits (P = 0.49 in study orbits and P = 0.43 in nonstudy orbits). Patients exhibited variable changes in eyelid position with teprotumumab. There was a statistically insignificant decrease in MRD1 after teprotumumab. Proptosis reduction led to unpredictable changes in MRD1 and MRD2. Severity of eyelid retraction did not correlate with clinical activity score response to teprotumumab. There are inherent difficulties in evaluating eyelid position in thyroid eye disease, which may necessitate a paradigm shift in how patients are examined, measured, and photographed.

Peripheral Trigeminal Nerve Blocks for Chronic Orbital Pain: Clinical Features and Outcomes.

PURPOSE: To characterize chronic orbital pain in patients who benefitted from peripheral trigeminal nerve blocks and to explore the relationship between pain etiologies and phenotypes, injection attributes, and positive response to treatment. METHODS: In this single-center retrospective descriptive study, patients who underwent peripheral trigeminal nerve blocks for chronic orbital pain from November 2016 to May 2021 were selected. Data reviewed included inciting factors, neuropathic symptoms of orbital pain, injection composition (anesthetic alone versus anesthetic + dexamethasone), and corneal epitheliopathy grades. Primary outcomes assessed were response to injection, duration of injection effectiveness, and overall treatment efficacy. Associations between subgroups of chronic orbital pain, injection attributes, and treatment outcomes were examined. RESULTS: Nineteen patients who underwent a total of 94 peripheral trigeminal nerve blocks for chronic orbital pain were included. During a mean follow-up period of 2.4 years after initial injection (range 7 days-4.6 years), 16 (84.2%) patients achieved either partial or complete improvement. Ocular versus nonocular origin of orbital pain or the presence of neuropathic sensory characteristics was not associated with a treatment outcome. Injections containing dexamethasone had a lower positive efficacy (relative risk, 0.88; 95% CI, 0.81-0.97) and no statistically significant association with prolonged effect. Twenty-nine (50.9%) of the 57 injections for which effect duration was recorded produced a response lasting greater than 6 weeks. CONCLUSIONS: Modulation of trigeminal afferent nerve activity with peripheral trigeminal nerve blocks containing anesthetic with or without dexamethasone may be a promising treatment strategy for chronic orbital pain of diverse etiologies and phenotypes.

Single-stage repair of large full thickness lower eyelid defects using free tarsoconjunctival graft and transposition flap: experience and outcomes.

BACKGROUND: Lid-sharing approaches are often advocated for repair of large full thickness lower eyelid defects, however result in temporary visual obstruction and the need for a second-stage procedure. The authors describe and report outcomes using a one-stage technique utilizing a free tarsoconjunctival graft (TCG) and musculocutaneous transposition flap (MCT) to repair defects up to 90% of the lower eyelid. METHODS: A retrospective chart review on patients that had undergone full thickness lower eyelid reconstruction using a TCG and MCT between the dates of 1/1/2015 to 3/1/2020 was performed. Demographic and clinical information including indication for repair, size of defect, post-operative complications, and outcomes were recorded and analyzed. RESULTS: Six cases of lower eyelid reconstruction using this technique were identified. Fifty percent were male, average age was 61.3 years (range 36-91, SD = 18.9), and follow up was 36.7 weeks (range 3-129, SD = 48.1). All defects were due to malignancy (4/6 for basal cell carcinoma, 1/6 each for sebaceous cell carcinoma and merkel cell carcinoma). Average horizontal defect size was 80% of lower eyelid width (range 57%-90%, SD = 12.3), while average vertical defect size was 8 mm (range 5-10 mm, SD = 1.7). There were no instances of post-operative infection, lid malposition, or dehiscence. A pyogenic granuloma was noted in one case and was managed with excision. CONCLUSION: A single-stage procedure using a TCG and MCT can be used to repair laterally based full-thickness lower eyelid defects up to 90% with satisfactory outcomes and few complications.

Echographic Assessment of Extraocular Muscle Response to Teprotumumab.

PURPOSE: To evaluate extraocular muscle response to teprotumumab using orbital echography in thyroid eye disease. METHODS: This retrospective study included adult thyroid eye disease patients with pre- and post-teprotumumab orbital echography. Data collected included: age, Hertel measurements, clinical activity score, Gorman diplopia scores, ocular motility, and recti muscle diameters measured by echography. The patient's more proptotic eye before treatment initiation was designated as the study orbit. Ocular motility was assessed by totaling the ductions in all 4 cardinal directions. Orbital echography was obtained pre- and post-treatment to assess response of extraocular muscle diameters. RESULTS: Six patients with a mean age of 67 years were included. There was a mean improvement in proptosis of 4.3 mm in the study eye with 11/12 orbits showing improvement in globe position ( p < 0.05). All patients had a decrease in clinical activity score with a mean reduction of 2.5. Four patients had an improvement in Gorman diplopia score. Ocular motility in the study orbits improved by a total mean of 26.9° ( p < 0.05). Mean total extraocular muscle diameter was reduced from 27.4 to 23.4 mm ( p < 0.001). On average, superior recti were largest pre- and post-treatment, followed by inferior, medial, then lateral recti. However, inferior recti showed the greatest reduction of 23% ( p < 0.02). CONCLUSIONS: Orbital echography demonstrated extraocular muscle reduction in all patients after teprotumumab, correlating with improved clinical activity score, ocular motility, and proptosis. Orbital echography is a safe and cost-effective imaging alternative to monitor therapeutic response to teprotumumab.

Extrascleral Tumor Extension Associated with Localized Scleral Melt following Plaque Brachytherapy for Uveal Melanoma: Clinical and Histologic Findings.

BACKGROUND/AIMS: Our study aims to better characterize the clinical and histopathologic features of eyes with extrascleral uveal melanoma associated with scleral melt following brachytherapy. METHODS: A retrospective review was performed on patients who had undergone 125I (iodine-125) brachytherapy for uveal melanoma at our institution between 1992 and 2015. Patients with postradiation scleral necrosis who required enucleation were identified, and an analysis including a review of histopathology results was performed on those cases. RESULTS: A total of 301 patients underwent plaque brachytherapy for uveal melanoma, of whom 31 required eventual enucleation. The histologic analysis showed extraocular extension through full-thickness scleral discontinuities in 6 cases. All but 1 (5 of 6) of these eyes exhibited either mitotic figures or Ki-67 positivity. Mitotic figures were noted in 4 specimens, including 3 eyes exhibiting mitoses within or adjacent to the extrascleral portion of the tumor. Two eyes exhibiting mitoses, as well as the case with Ki-67 positivity, also had clinical evidence of tumor regrowth. CONCLUSION: We found evidence of mitotic activity at the area of scleral discontinuity in some eyes with and in some without clinical evidence of tumor regrowth. Protruding pigmented material in areas of scleral necrosis after plaque brachytherapy may represent actively proliferating tumors even without internal evidence of tumor regrowth.

Oculocardiac reflex elicited by orbital floor fracture and inferior globe displacement.

PURPOSE: To review the physiology, presentation and management of the oculocardiac reflex (OCR) by describing a case of the OCR associated with an orbital foreign body and complete ocular prolapse through a large orbital floor fracture in a 40-year-old male following a motor vehicle accident. OBSERVATIONS: The patient demonstrated marked bradycardia and hypotension necessitating intubation and medical therapy for autonomic shock. A computed tomography (CT) showed a total blow out floor fracture and complete dislocation of a radiographically intact globe with uninterrupted rectus muscle attachments into the left maxillary sinus. He was taken to the operating room for urgent repair resulting in subsequent termination of severe OCR. CONCLUSIONS AND IMPORTANCE: The oculocardiac reflex can precipitate marked bradycardia and hypotension in the setting of trauma with significant orbital and maxillofacial injury. Prompt identification and management with vagolytic agents or definitive surgical intervention may prevent morbidity or mortality.

Comparison of primary and secondary enucleation for uveal melanoma.

We investigated operative course and post-operative findings of patients undergoing primary enucleation for uveal melanoma versus those requiring secondary enucleation after brachytherapy. A retrospective chart review was performed with IRB approval on patients receiving treatment for uveal melanoma. Patients with enucleation as initial treatment and patients enucleated after plaque brachytherapy were analyzed for demographic data, operative course, and post-enucleation outcome. Further cause analysis for secondary enucleations was investigated. No significant difference was seen in age, laterality, or gender between the primarily enucleated (n = 54) and secondarily enucleated (n = 34) groups. Greater difficulty with surgery was noted in 28/32 (87.5%) of secondary enucleations compared to 1/54 (1.8%) of primary enucleations (p < 0.0001). Operative time was >2 hours in 3/51 (6%) of primary enucleations (vs. 8 of 32, 25%, p = 0.02). Average implant size was similar in the 2 groups (20.6 mm), however 2/34 (6%) of secondary enucleations required dermis fat grafting. Post-enucleation anophthalmic ptosis occurred after 8/49 (16%) of primary cases (vs. 13/30, 43%, p = 0.02) and prosthetic enophthalmos after none (0%) of primary cases (vs. 5/30, 17%, p = 0.006). Class 2 gene expression profile was found in 6/8 (60%) of eyes enucleated for treatment failure. Secondary enucleation performed after plaque brachytherapy was technically more difficult, and had more anophthalmic socket and eyelid complications compared to primary enucleation for uveal melanoma. Primary enucleation may avoid additional surgery and morbidity in a subset of patients with contraindications to plaque brachytherapy.

Acute Angle Closure Precipitated by Hemorrhage and Necrosis of a Large Uveal Melanoma in the Setting of Systemic Immunomodulatory Therapy.

Management of nonmetastatic uveal melanoma has been well studied and a large body of work has been published by the Collaborative Ocular Melanoma Study (amongst many others). Management of uveal melanoma that is found to be metastatic upon initial diagnosis, however, is less well defined. We report an interesting case of acute angle closure caused by necrosis and hemorrhage into a large uveal melanoma occurring shortly after initiation of immunomodulatory therapy with ipilimumab and nivolumab for metastatic disease. The use of these immunomodulatory agents in the setting of metastatic uveal melanoma is not well studied, and our case illustrates the importance of interdisciplinary communication in order to best decide the timing of surgical and systemic medical management to optimize outcomes and minimize morbidity.