Ocular Neuromyotonia: Clinical Features, Diagnosis, and Outcomes.

PURPOSE: The purpose of this study was to describe the clinical features, management, outcomes, and diagnostic pitfalls in a large series of patients with ocular neuromyotonia. DESIGN: Retrospective cohort. METHODS: Patients diagnosed with ocular neuromyotonia from January 1, 2004, through January 1, 2023, seen at one of the 3 Mayo Clinic sites in Rochester, MN, Scottsdale, AZ, and Jacksonville, FL, comprised the study population. We ascertained patients with ocular neuromyotonia through a search using the medical records database. Only patients with an observed episode of ocular neuromyotonia were included and the medical records were reviewed. The main outcome measures were clinical features and outcomes of patients with ocular neuromyotonia. RESULTS: Forty-two patients who were diagnosed with ocular neuromyotonia were included. The median age was 58 years (range, 16-80 years). A history of cranial radiation therapy was present in 39 patients (93%). The sixth cranial nerve was involved in 31 patients (74%). Bilateral disease was found in 2 patients (5%). The median time from onset of diplopia to diagnosis was 8 months (range, 1 month-25 years), with a high rate of initial misdiagnosis in 52%. Twenty of 42 patients (48%) were treated with oral medication, of whom 95% had significant improvement or resolution of symptoms. CONCLUSION: Prior cranial irradiation is the most common cause for ocular neuromyotonia, affecting the sixth cranial nerve most often. Although delayed and initial misdiagnosis is common, most patients show improved symptoms on medical treatment.

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.

Ophthalmologic Involvement in Adults with Histiocytic Disorders: Clinical Presentation and Treatment Outcomes.

PURPOSE: To evaluate the clinical presentation, treatment, and outcomes in adult patients with histiocytic disorders with ocular, orbital, optic nerve, or cavernous sinus involvement. DESIGN: Observational, retrospective chart review. PARTICIPANTS: Adult patients (age ≥ 18 years) at Mayo Clinic from January 1, 1996, to July 1, 2021, with histiocytic disorders. Inclusion criteria were (1) histiocytic disorder by biopsy and appropriate clinical phenotype; (2) available medical records; and (3) ocular, orbital, optic nerve, or cavernous sinus involvement. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Response to therapy, measured in clinical and radiographic impact. RESULTS: Thirty-two patients were identified: 7 with Langerhans cell histiocytosis (LCH); 15 with Erdheim-Chester disease (ECD); 1 with mixed LCH/ECD phenotype; 8 with Rosai-Dorfman disease (RDD); and 1 with mixed RDD/ECD phenotype. Ophthalmologic involvement was part of the initial presentation in 69% of patients (22/32). Eyelid edema (13/32, 41%) and proptosis (12/32, 38%) were the most frequent presentations. Isolated orbital or cavernous sinus involvement was present in 3 of 7 patients with LCH and 1 of 8 patients with RDD. Optic nerve sheath involvement was present in 2 of 7 LCH patients, 14 of 15 ECD patients, and 1 RDD/ECD patient. Diffuse (> 75%) orbital involvement was seen in 12 of 15 ECD patients and 1 of 7 LCH patients. Ocular involvement was seen in 1 of 15 ECD patients, 6 of 8 RDD patients, and 1 of 1 mixed RDD/ECD patient. The cavernous sinuses were involved in 1 of 7 LCH patients, 5 of 15 ECD patients, and both mixed phenotype patients. Visual acuity was affected in 14 patients (14/24, 58%) with a median logarithm of the minimum angle of resolution visual acuity of 0.1 (range, -0.12 to 3). BRAF V600E mutations were found in 75% (3/4) of LCH patients and 91% (10/11) of ECD patients. Patients received a variety of treatment, and response was variable across disease types. CONCLUSIONS: Orbital involvement was more commonly seen in LCH and ECD, whereas ocular involvement was more common in RDD. Visual acuity may be impacted from ocular involvement or compression of the optic nerve with diffuse orbital involvement.

Differentiating intradiploic orbital dermoid and epidermoid cysts utilizing clinical features and machine learning.

Purpose: The purpose of this study was to characterize intradiploic dermoid and epidermoid orbital cysts to determine any differences in clinical, radiographic, or surgical features. Methods: A retrospective review was performed of patients presenting with intradiplopic dermoid or epidermoid cysts. Additionally, a complete review of the literature was performed to identify cases of intradiplopic orbital dermoid and epidermoid cysts. Data collected included age, sex, presenting symptoms, location of intradiplopic cyst, ophthalmic findings, treatment, and follow-up. Clinical features of dermoid versus epidermoid cyst were compared. Additionally, machine-learning algorithms were developed to predict histopathology based on clinical features. Results: There were 55 cases of orbital intradiploic cysts, 49 from literature review and six from our cohort. Approximately 31% had dermoid and 69% had epidermoid histopathology. Average age of patients with dermoid cysts was significantly lesser than that of patients with epidermoid cysts (23 vs. 35 years, respectively; P = 0.048). There was no difference between sex predilection, presenting symptoms, radiographic findings, or surgical treatment of dermoids and epidermoids. The majority of patients (64%) underwent craniotomy for surgical removal. Machine-learning algorithms KStar and Neural Network were able to distinguish dermoid from epidermoid with accuracies of 76.3% and 69%, respectively. Conclusion: Orbital intradiploic cysts are more commonly epidermoid in origin. Dermoid cysts presented in younger patients; however, there were no other significant differences in features including ophthalmic or radiographic findings. Despite similar features, machine learning was able to identify dermoid versus epidermoid with good accuracy. Future studies may examine the role of machine learning for clinical guidance as well as new surgical options for intervention.

Not a Tumor-Nonspecific Orbital Inflammation.

Objective This study was aimed to illustrate the features and complexities of nonspecific orbital inflammation via discussion of two representative cases. Design Present study is a retrospective case review. Setting The study was conducted at a tertiary care medical center. Participants Two patients with nonspecific orbital inflammation were participants of this retrospective study. Main Outcome Measures Outcome of the study was disease-free patients and off all medications. Results At follow-up, both patients are disease free and off all medications. Conclusion Surgery plays a diagnostic and therapeutic role. While the clinical subtype is important for differential diagnosis and symptomatic treatment, the histologic subtype is similarly important. For inflammatory dacryoadenitis, surgery can be therapeutic. For extensive granulomatosis with polyangiitis, debulking surgery may allow better penetration of medications, especially rituximab.

The "Quiet TED"-A Special Subgroup of Thyroid Eye Disease.

PURPOSE: Thyroid eye disease (TED) or Graves' orbitopathy starts with an active inflammatory stage (active disease) followed by resolution of inflammation and progression to a fibrotic, inactive stage. In our practice, we have encountered cases that have not had active disease despite presence of fibrotic sequelae and disease progression. We aim to delineate the clinical characteristic of this unique group of patients. METHODS: We conducted a single-center (Mayo Clinic Rochester) retrospective chart review of TED patients who throughout the course of their disease had only evidence for inactive TED, defined as clinical activity score <3. RESULTS: Median age in the cohort (n = 19) was 54 years (IQR 47-61). 58% had a prior diagnosis of Graves' disease (GD) before referral. 80% (n = 15) were euthyroid at the time of TED onset (median thyroid-stimulating hormone 1.7 mIU/L). The most common finding was diplopia (100%, n = 19) followed by proptosis (63%, n = 12). Interestingly the disease was asymmetric in 42% of cases. Overall median clinical activity score on presentation was 1 (IQR 0-1). Severity wise, 85% (n = 16) of patients were classified as moderate-to-severe during follow up. Orbital decompression was performed in only 1 case, while extraocular muscle surgery was performed in 13 cases. CONCLUSIONS: Quiet TED is a subgroup of TED patients that defies the classic disease paradigm. It presents primarily with diplopia and proptosis. Further evaluation of this group might identify useful insights in TED pathophysiology and help optimize therapeutic choices.

Trochleaectomy: An Effective Treatment of Trochlear Pain in Monocular Patients.

BACKGROUND: Conventional treatment options for trochlear pain arising from trochleitis or primary trochlear headache include oral anti-inflammatory medications and/or local injection of corticosteroids and local anesthetic. Trochleaectomy is an additional option to consider for monocular patients with intractable trochlear pain. METHODS: We report 3 patients undergoing trochleaectomy for refractory trochlear pain syndromes. RESULTS: Trochleaectomy resulted in resolution of their periocular discomfort. CONCLUSIONS: Trochleaectomy is an effective procedure to treat trochlear pain syndrome in functionally monocular patients.

Incidence of Ischemic Optic Neuropathy After Cardiopulmonary Bypass: 20-Year Experience.

OBJECTIVE: This study evaluated the incidence and risk factors for ischemic optic neuropathy (ION) as a complication of cardiac surgery requiring cardiopulmonary bypass (CPB). DESIGN: Retrospective chart review of prospectively collected data at a tertiary care center. SETTING: Single tertiary academic referral center. PARTICIPANTS: This study comprised 44,568 cardiac surgery patients who underwent CPB between January 1, 1995, and January 5, 2017, using the Society of Thoracic Surgeons database and cross-matching it with International Classification of Diseases codes for visual changes. INTERVENTIONS: None; this was a retrospective chart review. MEASUREMENTS AND MAIN RESULTS: Six patients initially were identified as experiencing visual changes. Only 1 patient from 44,568 cardiac surgeries with CPB between January 1, 1995, and January 5, 2017, experienced ION, for an incidence 0.22 per 10,000. Because only 1 patient experienced ION, the authors were unable to determine risk factors for this complication; however, the nadir perioperative hemoglobin in the affected patient was 7.3 g/dL (postoperative). CONCLUSION: The incidence of ION decreased from 6 per 10,000 in the authors' previous study from 1976-1994 to 0.22 per 10,000 in the present study. Because of the low incidence of this dreaded complication, the authors were not able to identify risk factors for ION. Practice improvements (eg, transition to membrane oxygenators, blood transfusion guidelines, less- invasive surgical options for high-risk patients) during the time between the authors' studies likely affected the incidence reduction.

A multi-center case series of sarcoid optic neuropathy.

OBJECTIVE: The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes. METHODS: We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers. Inclusion criteria were: 1) clinical optic neuropathy; 2) optic nerve/sheath enhancement on neuroimaging; 3) pathological confirmation of systemic or nervous system sarcoidosis. RESULTS: Fifty-one patients were included. The median onset age of sarcoid optic neuropathy was 50 years (range, 17-70 years) and 71% were female. The median visual acuity at nadir in the most affected eye was 20/80 (range, 20/20 to no-light-perception). Thirty-four of 50 (68%) patients had radiologic evidence of other nervous system involvement and 20 (39%) patients had symptoms/signs of other cranial nerve dysfunction. Cerebrospinal fluid analysis revealed an elevated white blood cell count in 22 of 31 (71%) patients (median: 14/µL; range: 1-643/µL). Pathologic confirmation of sarcoidosis was by biopsy of systemic/pulmonary site, 34 (67%); optic nerve/sheath, 9 (18%); or other nervous system region, 8 (16%). Forty patients improved with treatment (78%), 98% receiving corticosteroids and 65% receiving steroid-sparing immunosuppressants, yet 11/46 patients (24%) had a visual acuity of 20/200 or worse at last follow-up. CONCLUSIONS: Sarcoid optic neuropathy frequently occurs with other clinical and radiologic abnormalities caused by neurosarcoidosis and diagnostic confirmation occasionally requires optic nerve/sheath biopsy. Improvement with treatment is common but most patients have some residual visual disability. Improved recognition and a more expeditious diagnosis and treatment may spare patients from permanent vision loss.

A Prospective, Randomized, Double-blind, Placebo-controlled Study of Orbital Radiotherapy for Graves' Ophthalmopathy.

CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.

Intracranial Pure Germinoma With Optic Nerve Infiltration.

A 19-year-old man presented with a 3-year history of episodic headaches, right hemiparesis, and progressive vision loss in both eyes. Initially, extensive laboratory testing was unrevealing. MRI later demonstrated progressive enlargement and enhancement of the left optic nerve poorly correlated with the timing of his clinical manifestations. There was no clinical or radiological response to treatment with corticosteroids, mycophenolate mofetil, or rituximab administered empirically for possible inflammatory processes. Later in the disease course, he developed diabetes insipidus (DI), worsening vision to light perception bilaterally, severe cognitive decline, and spastic quadriparesis. Cerebrospinal fluid (CSF) beta human chorionic gonadotropin (ß-hCG) was elevated. Eventually, a left optic nerve biopsy was performed, which was consistent with an intracranial pure germinoma with infiltration of the optic nerve and disseminated leptomeningeal disease. Although rare, intracranial germ cell tumors can primarily involve the anterior visual pathways and should be considered in the setting of DI and elevated CSF ß-hCG.

Ultrasonic Aspiration for Debulking Infiltrative Masses of the Orbit.

PURPOSE: To demonstrate the utility of an ultrasonic aspirator (Sonopet, Stryker Corporation; Kalamazoo, MI) for debulking firm, soft tissue masses of the orbit. METHODS: Case series. The ultrasonic aspirator was used to debulk firm, soft tissue masses in 3 cases. The initial patient had a large orbitofacial mass extending to the inferior and lateral orbital apex secondary to IgG4 disease. The second patient had a lacrimal sac adenocarcinoma extending to the medial orbital apex. The third patient had a large orbital mass extending to the apex secondary to granulomatosis with polyangiitis. RESULTS: The ultrasonic aspirator facilitated debulking of infiltrative firm soft tissue masses of the orbit. The device's ability to emulsify, irrigate, and aspirate, along with its small footprint, facilitated precise sculpting and debulking to an extent which would have been difficult otherwise due to location. CONCLUSIONS: The ultrasonic aspirator allows precise sculpting of infiltrative firm soft tissue masses in the orbit and is particularly useful in cases with challenging anatomical access.

Thyroid eye disease presenting with superior rectus/levator complex enlargement.

Purpose: To describe the demographic and clinical characteristics of patients with thyroid eye disease (TED) who present with predominate superior rectus/levator complex involvement.Methods: A multi-institutional retrospective review was performed to identify patients with TED who presented with superior isolated or predominate rectus/levator involvement. Baseline and subsequent visits were reviewed to characterize the clinical course.Results: Nineteen patients were identified. All patients had imaging demonstrating an enlarged levator/superior rectus complex. At presentation, the mean clinical activity score (CAS) was 2.1 (range: 0-5). Nineteen (100%) patients had proptosis on the affected side. Lid abnormalities, including upper/lower eyelid retraction and ptosis were higher on affected side compared to the unaffected side. Eleven (58%) patients had vertical misalignment. Mean thyroid stimulating immunoglobulin (TSI) was 3.7 (range: 1-7.1). Mean follow-up time was 18 months (range: 0-60 months). At last follow-up, the mean CAS was 1.3 (range 0-5). Ten (53%) patients had proptosis. Eleven (58%) patients had vertical misalignment. Repeat imaging in eight patients showed interval enlargement of other extraocular muscles.Conclusions: The presentation of TED with superior rectus/levator complex enlargement may be under-appreciated. Orbital imaging, as well as laboratory evaluation, may help support a diagnosis of TED. In the setting of abnormal TSI and/or thyrotropin receptor antibody, presence of upper eyelid retraction, and an otherwise unremarkable laboratory and systemic evaluation, a presumptive diagnosis of TED may be made, and the patient can be followed closely, as he/she is likely to develop involvement of other extraocular muscles, consistent with a more typical presentation of TED.

Sclerotherapy for low-flow vascular malformations of the orbital and periocular regions: Systematic review and meta-analysis.

Percutaneous sclerotherapy is an alternative strategy for the treatment of vascular malformations of the orbital and periorbital regions. The safety and efficacy of sclerotherapy in this setting have not been fully established. We present the results of a systematic review and meta-analysis examining the safety and efficacy of percutaneous sclerotherapy for the treatment of vascular malformations of the orbit. We searched PubMed, MEDLINE, and EMBASE from 2000 to 2018 for studies evaluating the safety and efficacy of percutaneous sclerotherapy for orbital and periorbital vascular malformations. Two independent reviewers selected studies and abstracted data. The primary outcome of this study is the efficacy of sclerotherapy which includes complete response, partial response, or no response to sclerotherapy. Data were analyzed using random-effects meta-analysis. Thirteen studies reporting on 154 patients were included. The rate of complete cure after percutaneous sclerotherapy was 54.9% (95% confidence interval [CI] = 34.2%-75.7%). The rate of emergent decompressive surgery was 3.4% (95% CI = 0.5%-6.2%), and the rate of vision loss was 2.7% (95% CI = 0.1%-5.3%). I2 values were above 50% for most outcomes indicating substantial heterogeneity. Our systematic review and meta-analysis of 13 studies and over 150 patients found that percutaneous sclerotherapy is a safe and effective treatment modality for the treatment of low-flow vascular malformations of the orbit.

Clinical and histopathological findings of patients with orbital granulomatosis with polyangiitis cases refractory to rituximab.

OBJECTIVE: Rituximab, a monoclonal antibody that targets CD20 receptors on mature B lymphocytes, is used in various diseases, including granulomatosis with polyangiitis (GPA) and difficult-to-treat orbital inflammatory diseases. We aimed to describe clinical and histopathologic findings in patients treated with rituximab refractory GPA who had post-rituximab orbital biopsies. DESIGN: Retrospective review. PARTICIPANTS: Patients with orbital GPA refractory to rituximab. METHODS: We examined the clinical outcomes, imaging results, and histopathological findings of all patients from September 1, 1994, through July 1, 2017, with a diagnosis of orbital GPA who, after treatment with rituximab, required an orbital excisional biopsy for refractory orbital disease. RESULTS: Among the 7 patients included the clinical indication for biopsy was pain (n = 3), new mass lesion despite treatment (n = 2), and persistent lesion despite treatment (n = 2). Post-rituximab biopsies showed marked collagenized fibrous tissue, with areas of concentric fibrosis resembling the framework of pre-existing lymphoid follicles, and minimal residual lymphocytic infiltrates (n = 7). Three patients had entrapped nerves. Four biopsies showed active inflammation; clinically, all patients were not responding to treatment. CONCLUSIONS: This study highlights the clinical and histopathological changes seen in patients with orbital GPA refractory to rituximab therapy. The post-rituximab biopsies show marked fibrosis in all patients. Four patients had active inflammation without evidence of entrapped nerves, whereas 3 patients had entrapped nerves and no active inflammation on their biopsies. Knowledge of the histopathology may guide future management decisions in patients with orbital GPA refractory to rituximab treatment.

Sphenoorbital meningioma: a unique skull base tumor. Surgical technique and results.

OBJECTIVE: Sphenoorbital meningioma (SOM) is a unique skull base tumor, characterized by infiltrative involvement and hyperostosis primarily of the lesser wing of sphenoid bone, with frequent involvement of the orbital compartment. SOM often manifests with proptosis and visual impairment. Surgical technique and outcome are highly variable among studies reported in the literature. The authors present a single-surgeon experience with SOM. METHODS: A retrospective review of a prospectively maintained institutional database was performed. A blinded imaging review by 2 study team members was completed to confirm SOM, after which chart review was carried out to capture demographics and outcomes. All statistical testing was completed using JMP Pro version 14.1.0, with significance defined as p < 0.05. RESULTS: Forty-seven patients who underwent surgery between 2000 and 2017 were included. The median age at surgery was 47 years (range 36-70 years), 81% of patients were female, and the median follow-up was 43 months (range 0-175 months). All operations were performed via a frontotemporal craniotomy, orbitooptic osteotomy, and anterior clinoidectomy, with extensive resection of all involved bone and soft tissue. Preoperatively, proptosis was noted in 44 patients, 98% of whom improved. Twenty-eight patients (60%) had visual deficits before surgery, 21 (75%) of whom improved during follow-up. Visual field defect other than a central scotoma was the only prognostic factor for improvement in vision on multivariate analysis (p = 0.0062). Nine patients (19%) had recurrence or progression during follow-up. CONCLUSIONS: SOM is a unique skull base tumor that needs careful planning to optimize outcome. Aggressive removal of involved bone and periorbita is crucial, and proptosis and visual field defect other than a central scotoma can improve after surgery.

The management of large-angle esotropia in Graves ophthalmopathy with combined medial rectus recession and lateral rectus resection.

PURPOSE: To describe surgical management and outcomes for large-angle esotropia of ≥50Δ secondary to Graves ophthalmopathy using combined initial nonadjustable medial rectus recessions and lateral rectus resections. METHODS: The medical records of consecutive patients undergoing strabismus surgery for large-angle esotropia secondary to Graves ophthalmopathy from 1995 to 2012 by a single surgeon at each of two institutions was performed. Patient characteristics, surgical technique, and pre- and postoperative measurements of ocular alignment were analyzed. A modified Gorman diplopia scale was used to assess outcome. RESULTS: Of 38 patients, 36 had bilateral nonadjustable medial rectus recessions and lateral rectus resections as initial treatment for esotropia, and 6 patients underwent simultaneous vertical muscle surgery. Mean preoperative horizontal deviation was 60Δ and mean preoperative vertical deviation was 10Δ. Of the 38 patients, 19 (50%) reached the primary outcome, including 5 of 6 (85%) who had no preoperative vertical strabismus. The indications for reoperation were vertical strabismus in 13 of 21 patients (62%), residual esotropia in 7 of 21 (33%), and consecutive exotropia in 1 of 21 (5%). With a median follow-up of 13.2 months after first surgery, 32 of 38 patients (84%) reached the secondary outcome. CONCLUSIONS: Combining nonadjustable medial rectus recessions with lateral rectus resections can be a beneficial primary treatment for large-angle esotropia in patients with Graves ophthalmopathy, especially in those patients with small or no associated vertical strabismus.