Disease Modulation Versus Modification: A Call for Revised Outcome Metrics in the Treatment of Thyroid Eye Disease.

PURPOSE: This perspective introduces the concepts of disease-modulating and -modifying therapy for thyroid eye disease and offers novel metrics for therapeutic outcomes. METHODS: A focused literature review was performed. RESULTS: Modulators are treatments that suppress disease symptoms whereas modifiers alter the natural history of a disease. Though many drugs are capable of exhibiting both effects, consideration of a drug's primary effect is useful when considering therapeutic options. For thyroid eye disease, corticosteroids and teprotumumab are effective at modulating many signs and symptoms of the disease, particularly those related to soft tissue inflammation. Orbital radiotherapy and rituximab have demonstrated effectiveness at durably modifying the natural history of thyroid eye disease. CONCLUSIONS: Outcome metrics should reflect the unique therapeutic objectives associated with disease modulation and modification. This conceptual framework should guide treatment of thyroid eye disease.

Menstrual Irregularities and Amenorrhea in Thyroid Eye Disease Patients Treated With Teprotumumab.

PURPOSE: To evaluate the rates of amenorrhea and menstrual irregularities in patients with active thyroid eye disease treated with teprotumumab. METHODS: A retrospective review was conducted of patients with active thyroid eye disease treated between 2020 and 2022 at a single institution. Female thyroid eye disease patients with regular menstruation at baseline who completed 8 infusions of teprotumumab were assessed. Patient-reported irregularities in menstruation or amenorrhea were recorded during routine clinic visits. Two sample t tests were used to assess differences between patients endorsing and denying menstrual irregularities. RESULTS: Twelve patients met the inclusion criteria. The mean age was 38.33 ± 9.6 years (range 25-53 years). The average follow-up after treatment completion was 11.43 months. Nine patients (75%) reported changes from their baseline menstruation. Four patients (33.3%) reported irregularities during treatment only. Three patients (25%) had persistence of irregularities after treatment; these patients regained normal cycles at an average of 3 months following teprotumumab completion. Two patients (16.7%) did not regain their normal cycles at the time of their last follow-up. One 53-year-old patient-reported persistent amenorrhea after treatment completion. One patient-reported menorrhagia at a 4-month follow-up. No significant age difference was found between patients with or without reported menstrual changes ( p = 0.43). CONCLUSION: Abnormalities of menstruation, including amenorrhea, were reported by 75% of patients treated with teprotumumab. These changes reverted to baseline after treatment in most affected patients.

Inferior Ophthalmic Vein-Dominant Dural Cavernous Fistula Embolization via Combined Orbitotomy and Direct Puncture of Inferior Ophthalmic Vein: A Case Report and Literature Review.

Dural carotid-cavernous fistulas (DCF) typically drain into the superior ophthalmic vein. Predominant involvement of the inferior ophthalmic vein (IOV) is rare, with only 4 documented cases in the literature. Here, the authors describe a case of a 51-year-old man who presented with acute left-sided proptosis, dysmotility, and vision loss and was found to have an IOV-dominant type D dural carotid-cavernous fistulas. The fistula could not be embolized by transfemoral endovascular access or orbitotomy alone and was ultimately managed with combined orbitotomy and direct IOV puncture. All previous reports of IOV-dominant dural carotid-cavernous fistulas in the literature were similarly inaccessible via the transfemoral approach. This case highlights the challenges of IOV cutdown and proposes an alternative management strategy. When IOV cutdown is precluded by the fragile, collapsed, or deep nature of the vessel, conversion to percutaneous IOV puncture may offer a safe and effective approach and mitigate the risks of direct puncture alone.

Qualitative use of ICG angiography and lymphography in periorbital surgery.

PURPOSE: Open imaging fluorescence devices have been utilized in surgical oncology, vascular and plastic surgery; however, the role of indocyanine green (ICG) in periorbital surgery and lymphatics has not been explored. METHODS: A prospective, single-center diagnostic study was conducted from 2021 to 2022 utilizing ICG to assess both the periorbital vasculature and lymphatics. Fluorescence was captured with open-imaging fluorescent devices. For ICG angiography, a total of 5-10 mg of ICG was given intravenously at various time points to visualize intraoperative blood flow to eyelid flaps, vascular tumors, or extraocular muscles. For ICG lymphography, 0.03-0.06 mg of ICG was injected subcutaneously to visualize the periorbital and facial lymphatic drainage. RESULTS: Twenty-two patients underwent ICG angiography. Periorbital vascular supply was seen in eyelid reconstructions (n = 8), anophthalmic reconstructions (n = 2), lacrimal gland tumors (n = 2), orbital venous malformations (n = 2), tumor metastasis (n = 1) and benign tumors (n = 1). The anterior ciliary arteries were visualized to the extraocular muscles in fracture repairs (n = 3) and muscle biopsies (n = 2). Ten patients underwent ICG lymphangiography highlighting the global periorbital lymphatic system. CONCLUSION: ICG allows for visualization of the vasculature of extraocular muscles and tumors, assessing perfusion of flaps during reconstruction and the global periorbital lymphatic drainage pathways.

Medical Accuracy of Patient Discussions in Oculoplastic Surgery on Social Media.

PURPOSE: The aim of this study was to characterize major topics of discussion in oculoplastic surgery on a social media forum and to evaluate the medical accuracy of the content discussed on these platforms. METHODS: A cross-sectional analysis of oculoplastics key search terms was performed on 2 active forums (r/PlasticSurgery and r/CosmeticSurgery) on Reddit. The content analysis involved the top posts in Reddit's history from 2008 to 2022. Medical accuracy was determined by actively practicing, board-certified, and fellowship-trained oculoplastic surgeons. RESULTS: The most common topics of patient discussions involved inquiring for advice regarding a procedure (44%) and sharing before-and-after photos (34%). The most common topics of patient discussions included providing support, encouragement, or sympathy for a patient (80%) and the cost of a procedure (62%). Misunderstanding of the medical pathophysiology of the patient's condition was seen in 68% of discussions on this social media platform. Medically inaccurate information was seen in 31% of all analyzed statements. When the type of physician performing a given procedure was disclosed, half reported an oculoplastic surgeon performed the surgery. CONCLUSIONS: The social media platform, Reddit, is a popular source of advice and information for current and prospective oculoplastic surgery patients. Such social media forums should be used as a sort of psychosocial and psychological support rather than as a primary source of medical information.

Globe Compression by Bone Fragments in Orbital Blow-in Fractures: A Case Series and Systematic Review.

PURPOSE: The purpose of this study was to describe the clinical characteristics, management, and outcomes of orbital blow-in fractures involving compression of the globe by bone fragments. METHODS: A retrospective case series and systematic literature review were performed. RESULTS: Three male patients (mean age 29 years) with orbital blow-in fractures causing globe indentation presented with extraocular movement restriction, choroidal folds, and B-scan ultrasonography demonstrating deformation of the globe contour by a hyperechoic bone fragment. All underwent surgical repair within 1 day of presentation resulting in improved visual outcomes. An additional 10 cases were identified in the literature review. The majority of patients were male (80%) with a mean age of 29 years. Fractures originated primarily from the lateral orbital wall (50%) or the orbital roof (40%). Globe compression was evident on CT of the orbit (100%) and ultrasonography (30%). Common presenting signs included decreased visual acuity (70%), restriction of supraduction (40%) or abduction (40%), choroidal folds (30%), brow laceration (40%), periorbital edema (40%), and hypoglobus (40%). Most patients underwent surgical intervention (80%) involving fracture reduction (50%) or fragment removal (38%). Reported postsurgical outcomes were excellent with resolution of diplopia, motility, and visual acuity. CONCLUSION: Globe indentation from blow-in fractures are rare. Clinicians should be suspicious in cases of high-velocity trauma to the superolateral orbit with hypoglobus, motility limitation, and indentation of the globe upon dilated exam. Prompt diagnosis and early surgical removal of the compressive orbital bone fragments in a multidisciplinary fashion can lead to good visual, functional, and cosmetic outcomes.

Spheno-Orbital Meningioma - Treatment Outcomes and Factors Influencing Recurrence.

PURPOSE: To determine treatment outcomes, recurrence rates, and predictors of recurrence, to inform future therapeutic approaches for spheno-orbital meningiomas (SOM). METHODS: A retrospective single-center study of SOM treated from 1990 to 2021 was conducted with comprehensive neuro-ophthalmologic follow-up at Columbia University Medical Center (CUMC). Recurrence requiring reintervention was defined clinically as worsening of visual acuity, visual field defect, or ocular motility after an initial period of stabilization or 6 months of improvement following treatment, or radiologically as either a regrowth with an increase in tumor size by 20% at the site of previous growth or a new region of tumor growth. RESULTS: In total 46 patients met the inclusion criteria. The mean follow-up was 106 months (range 1-303). Dictated by the phenotype of the disease, patients underwent either gross- (50%), near- (17%), or subtotal resection (26%). Removal of the anterior clinoid process (ACP) was performed in 52% of patients. Nine patients (20%) required an enucleation or exenteration. Radiotherapy was employed at some point of treatment in 50% of cases. Inherited cases (24%) were referred to CUMC for treatment following 1 or more recurrences. The total recurrence rate, including inherited cases, was 54%, occurring at a mean interval of 43 months. The recurrence rate of patients treated solely at CUMC was 40%, occurring at a mean interval of 41 months. A subset of patients (32%) had 2 or more recurrences. Histopathology at the first surgery was WHO grade I (87%) and II (13%) and at the final surgery was WHO grade I (74%), II (21%), and III (4%). A subset of grade I tumors that received radiotherapy (35%) evolved to a higher grade or developed multiple recurrences without a change in histologic grade I. Grade II tumors and treatment with radiotherapy increased the odds of recurrence. Removal of the ACP and gross total resection decreased the odds of recurrence. CONCLUSION: Due to the routinely long interval to tumor recurrence, lifelong surveillance of patients with SOM is prudent. ACP resection and gross total resection, where possible, reduce tumor recurrence and the need for further treatment. Radiotherapy should be reserved for higher-grade meningiomas and select grade I tumors.

Association of Patient Age and the Thyroid Eye Disease-Clinical Activity Score.

PURPOSE: To investigate the association between age and clinical activity score (CAS) in patients with active, untreated thyroid eye disease. METHODS: A retrospective review was conducted of patients with active, untreated thyroid eye disease at a single institution between 2010 and 2020 whose ophthalmologic symptoms began no more than 9 months prior to the initial visit. Exclusion criteria included surgical or systemic thyroid eye disease treatment before or during the study period. Demographic and clinical data were collected for all patients, including a 7-point CAS at visit 1 (CAS1) and a 10-point score at visit 2 (CAS2). Patients were stratified by age: Group 1 (18-45), Group 2 (46-70), and Group 3 (71-85). RESULTS: A total of 156 patients were included: mean age 51.7 ± 15.8 years, 79.5% female. CAS1 differed significantly across groups: 1.9 ± 1.0 (Group 1), 2.7 ± 1.4 (Group 2), and 2.2 ± 1.6 (Group 3), p = 0.005. Findings were similar for CAS2: 2.2 ± 1.4 (Group 1), 3.0 ± 1.8 (Group 2), and 2.8 ± 1.9 (Group 3), p = 0.030. Post hoc analysis showed a statistically significant difference between Groups 1 and 2 (p = 0.004, visit 1; p = 0.025, visit 2) but not between other pairs. Patients with CAS1 of 0-3 (n = 129) were younger on average than those with CAS1 4-7 (n = 27): 50.4 ± 16.2 versus 58.2 ± 12.8 years (p = 0.009). Conjunctival redness (p = 0.019) and chemosis (p ≤ 0.001) were more common in older patients at both visits. CONCLUSIONS: Patients aged 46-70 years with active, untreated thyroid eye disease had significantly higher CAS1 and CAS2 than younger patients in this study, largely driven by differences in conjunctival redness and chemosis.

Chronic canaliculitis with canaliculoliths due to Providencia stuartii infection.

Canaliculitis, inflammation of the lacrimal canaliculi, can be caused by numerous pathogens, most commonly bacteria from the genera Actinomyces, Streptococcus, and Staphylococcus. Primary canaliculitis often requires surgical canaliculolith removal and appropriate antibiotic coverage. The authors report a case of a 77-year-old woman with a history of punctal plugs who presented with chronic canaliculitis with canaliculoliths that grew Providencia stuartii. P. stuartii has not previously been described as a cause of primary canaliculitis. This case highlights a new organism that causes canaliculitis with canaliculoliths and stresses the importance of speciation and antibiotic sensitivity testing following canaliculotomy and curettage. P. stuartii should be considered in the differential for bacterial canaliculitis with canaliculoliths, especially in patients with persistent symptoms on topical antibiotic therapy without canaliculotomy.

Spontaneous regression of a presumed orbital apex cavernous venous malformation.

A 42-year-old non-menopausal, non-pregnant woman presented with an incidentally noted right orbital apex lesion producing mild compressive optic neuropathy. Imaging revealed an apical, intraconal, inhomogenously enhancing mass consistent with a cavernous venous malformation displacing the optic nerve. The patient was monitored over a 15-year period with serial orbital imaging and clinical examinations and ultimately demonstrated significant regression in the size of the lesion, accompanied by the complete resolution of optic neuropathy. She was non-menopausal when the regression was noted and remained non-pregnant throughout the follow-up period.

Evolution of asymmetric proptosis during the active phase of thyroid eye disease.

PURPOSE: To assess the evolution of proptosis asymmetry during the active phase of bilateral thyroid eye disease (TED). METHODS: A retrospective study was conducted on patients with bilateral, active TED. Patients were measured by a single observer, using Hertel exophthalmometry from the time of initial presentation, during the active phase of TED, to the stable phase, 24-months later. Asymmetric proptosis was defined as a >2 mm intra-orbital difference in Hertel measurements. RESULTS: Fifty-one patients were enrolled. Patients presented at a mean time of 1.1 ± 2.9 months following the onset of TED symptoms. Stability of TED was established at 15.7 ± 12.3 months. At initial presentation, 41% of patients demonstrated asymmetric proptosis. Upon reaching the stable phase, asymmetric proptosis persisted in only 22% of patients. A decline in the rate asymmetric proptosis was greatest within the first 3 months of the active phase. CONCLUSIONS: Asymmetric proptosis is common in the setting of early active TED and decreases by 50% when the stable phase is reached. Therefore, diagnostic imaging is not routinely required to exclude alternative pathology in the cases of asymmetric TED. Perhaps more importantly, this finding supports the surgical paradigm of stable phase, graded orbital decompression, performed when the ultimate globe positions are achieved to avoid late postoperative asymmetry, resulting from the unanticipated evolution of proptosis when surgery is performed during the active phase of TED.

Congenital Eyelid Imbrication and Floppy Eyelid Syndrome in a Patient With Cat Eye Syndrome.

A newborn male with cat eye syndrome presented with progressively worsening bilateral upper eyelid imbrication, floppy eyelids, and ptosis. Despite conservative management, he remained unable to open his eyelids. Surgical correction was planned to prevent bilateral sensory deprivation amblyopia and was delayed until 5 months of age due to systemic health concerns. Bilateral full-thickness wedge excision and frontalis suspension with silicone rods in a double rhomboid fashion was performed. Postoperatively, the patient demonstrated spontaneous eyelid opening, resolution of spastic eversion of the upper eyelids, and adequate eyelid closure. The authors present the first case of concurrent floppy eyelid syndrome and upper eyelid imbrication reported in a cat eye syndrome patient.

GNA11 Mutation in an Intracranial Melanocytoma with Orbital Involvement and Nevus of Ota.

The prognostic value of mutations in G-protein genes GNAQ and GNA11 in patients with intracranial and orbital melanocytomas is unknown. The authors present a case of GNA11 mutation (GNA11Q209L) in a 32-year-old male suffering from a meningeal melanocytoma with orbital involvement and ipsilateral Nevus of Ota. The patient underwent gamma knife stereotactic radiosurgery without biopsy and later partial transcranial resection of the melanocytic tumor that was subject to immunohistochemical and molecular analysis. A 50-gene next-generation sequencing panel revealed a 626A>T mutation in the GNA11 gene. One year later, intracranial extension of the melanocytoma necessitated a ventriculoperitoneal shunt and immunotherapy. Future work is needed to determine how GNA11 mutations in melanocytomas influence prognosis and monitoring strategies.

Natural killer T-cell lymphoma causing bilateral recurrent recalcitrant dacryocystitis.

A 35-year-old female with a history of chronic extensive rhinosinusitis, previously treated twice with functional endoscopic sinus surgery, presented with recurrent dacryocystitis despite prior dacryocystorhinostomy. Histopathological specimens taken at the most recent sinus surgery demonstrated a lymphocytic inflammatory reaction without evidence of angiodestruction or necrosis. Flow cytometry was normal. Over the following 9 months, the patient developed worsening hypertelorism and bilateral recurrent acute dacryocystitis with a fistula tract to the skin. Neuroimaging revealed a hyperintense enhancing soft tissue expansion into the periorbital regions, invading the nasolacrimal canals, and obstructing the paranasal sinuses. A skin biopsy at the fistula site revealed natural killer T-cell lymphoma. Metastatic work-up disclosed lung, spleen, and bone marrow involvement. The patient underwent chemotherapy with mixed clinical response, and ultimately passed away from metastatic disease. The authors present a rare case of natural killer T-cell lymphoma involving the nasolacrimal sac, presenting as recurrent dacryocystitis and diagnosed by skin biopsy of the fistula site.

Lower eyelid malposition following repair of complex orbitofacial trauma.

PURPOSE: To compare the incidence of lower eyelid malposition following repair of isolated orbital floor fractures with that of complex orbitofacial fractures (defined as multi-wall fractures or prior orbital fracture repairs requiring revision) by oculofacial plastic surgeons via a transconjunctival or swinging eyelid approach. METHODS: Retrospective review of 175 patients who underwent surgical repair of orbital fractures at our institution. The primary outcomes were the occurrence of lower eyelid malposition (ectropion, entropion, and eyelid retraction) and the need for subsequent surgical correction. RESULTS: Of 95 patients with isolated orbital floor fractures, 4 developed eyelid malposition (4.2%), 1 of which required surgical repair (1.1%). Of 80 patients with complex orbitofacial fractures (48 multi-wall fractures, 32 secondary revisions), 10 had pre-operative eyelid malposition and were excluded from further analysis. Fourteen of the remaining 70 patients developed postoperative eyelid malposition (20%), 3 of which required surgical repair (4.3%). The difference in the occurrence of eyelid malposition between groups was statistically significant (p = .001), but the difference in rates of those requiring subsequent repair was not (p = .182). There was no statistically significant difference in the occurrence of eyelid malposition when considering other surgical factors including lateral canthotomy, conjunctival closure, implant material, or anterior rim screws. CONCLUSIONS: The incidence of lower eyelid malposition following orbital fracture repair via a fornix-based approach was significantly higher for the repair of complex orbitofacial fractures than for isolated floor fractures. However, very few patients in either group required surgical repair for eyelid malposition. Surgical factors including implant material did not affect outcomes.

Subfoveal Choroidal Thickness and Associated Changes of Angiogenic Factors in Women with Severe Preeclampsia.

OBJECTIVE: Severe preeclampsia complicates roughly 1% of all pregnancies. One defining feature of severe preeclampsia is new onset visual disturbance. The accessibility of the choroid to high-resolution, noninvasive imaging makes it a reasonable target of investigation for disease prediction, stratification, or monitoring in preeclampsia. This study aimed to compare subfoveal choroidal thickness between women with severe preeclampsia and those with normotensive pregnancies, and to investigate associations between such findings and other indicators of disease severity, including gestational age and serum angiogenic factors. STUDY DESIGN: We designed a case-control study comprised of 36 women diagnosed with severe preeclampsia (cases) matched to 37 normotensive women (controls) by race/ethnicity and parity, all diagnosed in the postpartum period. All patients underwent enhanced depth imaging spectral-domain optical coherence tomography and serum analysis. RESULTS: Cases showed no difference in subfoveal choroidal thickness compared with controls (p = 0.65). Amongst cases, subfoveal choroidal thickness and gestational age at delivery were inversely related (r = 0.86, p < .001). There was a positive association of placental growth factor with subfoveal choroidal thickness amongst cases (r = 0.54, p = 0.002). CONCLUSION: This study suggests a relationship between the degree of disease severity and the magnitude of choroidal thickening. We also show an association between this index and placental growth factor level in the postpartum period.

Orbital Lipofibromatosis in a Pediatric Patient.

A 10-month-old boy presented with a 3-month history of progressive left lower eyelid swelling. Examination demonstrated left lower eyelid fullness and hyperglobus with a fatty appearing inferior fornix mass. Imaging showed a mass isointense to fat in the left lower eyelid extending posteriorly, surrounding the inferior oblique with complete fatty infiltration, obscuration of the inferior rectus, and adherence to the globe. The patient underwent orbitotomy with biopsy and debulking of the tumor. Surgical pathology showed multiple fragments of adipose tissue with foci of plump and spindle-shaped cells arranged in bundles and fascicles, consistent with lipofibromatosis. This case illustrates a rare presentation of orbital lipofibromatosis in a pediatric patient.

Globe Subluxation After Proning in a Coronavirus Disease 2019 Patient.

A 79-year-old male was hospitalized for respiratory failure secondary to coronavirus disease 2019 pneumonia. Approximately 6 hours after initiating proning, left globe subluxation with darkening of the superior sclera consistent with tache noir was noted. The left globe was thought to be hypotonus secondary to ciliary body shut down after a prolonged period of high intraocular pressure. The globe was reduced in the supine position with gentle traction of the eyelids. Over the next 24 hours, the left intraocular pressure improved to 10 mm Hg, and the tache-noir de la sclérotique resolved. The authors report the first known case of globe subluxation secondary to proning.

Double Frost Suture Technique for Simultaneous Skin Grafting of the Upper and Lower Eyelids.

The double Frost suture is a useful supplement to the reconstruction of ipsilateral upper and lower eyelid defects with full-thickness skin grafts. This technique involves silk traction sutures that overlap the upper and lower eyelids to place them on maximal stretch after placement of 2 full-thickness skin grafts. It has the added benefit of protecting the cornea and compressing both grafts under 1 bolster. The authors illustrate this technique in 2 pediatric cases-a congenital melanocytic kissing eyelid nevus and a periocular burn. Each case resulted in large upper and lower anterior lamellar defects, which were reconstructed with supraclavicular and retroauricular free skin grafts. The double Frost sutures counter vertical cicatricial forces during graft healing, obviating the need for staged procedures. Both described cases resulted in excellent graft survival with minimal contracture.