Ophthalmologic Findings in Pediatric Erdheim-Chester Disease: A Literature Review With a Novel Case Report.

PURPOSE: The authors aim to describe the ophthalmologic manifestations of pediatric Erdheim-Chester disease (ECD). METHODS: The authors describe a novel case of ECD presenting as isolated bilateral proptosis in a child and provide a comprehensive review of the documented pediatric cases to observe overall trends and ophthalmic manifestations of disease. Twenty pediatric cases were identified in the literature. RESULTS: The mean age at presentation was 9.6 years (1.8-17 years) with a mean time of symptom presentation to diagnosis of 1.6 years (0-6 years). Nine patients (45%) had ophthalmic involvement at diagnosis, 4 who presented with ophthalmic complaints: 3 with observable proptosis and 1 with diplopia. Other ophthalmic abnormalities included eyelid findings of a maculopapular rash with central atrophy on the eyelids and bilateral xanthelasmas, neuro-ophthalmologic findings of a right hemifacial palsy accompanied by bilateral optic atrophy and diplopia, and imaging findings of orbital bone and enhancing chiasmal lesions. No intraocular involvement was described, and visual acuity was not reported in most cases. CONCLUSIONS: Ophthalmic involvement occurs in almost half of documented pediatric cases. Typically presenting with other symptoms, the case highlights that isolated exophthalmos may be the only clinical sign, and ECD should be included in the differential diagnosis of bilateral exophthalmos in children. Ophthalmologists may be the first to evaluate these patients, and a high index of suspicion and an understanding of the varied clinical, radiographic, pathologic, and molecular findings are critical for prompt diagnosis and treatment of this unusual disease.

Ultrasound Verification of Plaque Brachytherapy Placement in Patients Treated for Primary Uveal Melanoma: A Single-Center Experience.

Introduction: Proper plaque positioning is essential for effective episcleral plaque brachytherapy and can be verified using ultrasound. In this study, we show our center's protocol for intraoperative ultrasound verification of plaque placement and present our single-center local recurrence data in patients with primary UM involving the choroid and/or ciliary body. We also indicate our center's distance metastasis rate for patients presenting with primary UM. Methods: All patients who presented to our institution with UM of the choroid and/or ciliary body between May 2017 and March 2022 and treated with plaque brachytherapy were enrolled. Endpoints include the 24-month local recurrence-free rate (primary) and 24-month metastasis rate (secondary), both estimated using the Kaplan-Meier method (KM). Results: Local Recurrence: 176 patients met the study criteria with median follow-up of 23.2 months. The 24-month recurrence-free probability for this cohort was estimated at 99.1% (95% confidence interval: 0.974-1.00). Metastatic Recurrence: 136 of these patients underwent at least one follow-up surveillance scan. The 24-month metastasis-free survival probability in our cohort was estimated at 87% (95% confidence interval: 81-94%). Conclusions: We show improved local control utilizing ultrasound verification compared to historical controls who received TTT and brachytherapy without intraoperative ultrasound confirmation.

Characterizing metastatic uveal melanoma patients who develop symptomatic brain metastases.

Metastatic uveal melanoma (mUM) is an advanced ocular malignancy characterized by a hepatotropic pattern of spread. As the incidence of brain metastases (BM) in mUM patients has been thought to be low, routine CNS surveillance has not been recommended. Notably, no formal assessment of BM incidence in mUM has to date been published to support this clinical practice. We aimed to determine the true rate of BM in mUM and to clarify the clinical and genomic risk factors associated with BM patients through a collaborative multicenter, retrospective research effort. Data collected from 1,845 mUM patients in databases across four NCI-designated comprehensive cancer centers from 2006-2021 were retrospectively analyzed to identify patients with BM. Brain imaging in most cases were performed due to onset of neurological symptoms and not for routine surveillance. An analysis of demographics, therapies, gene expression profile, tumor next generation sequencing (NGS) data, time to metastasis (brain or other), and survival in the BM cohort was completed. 116/1,845 (6.3%) mUM patients were identified with BM. The median age at time of UM diagnosis was 54 years old (range: 18-77). The median time to any metastasis was 4.2 years (range: 0-30.8). The most common initial metastatic site was the liver (75.9%). 15/116 (12.9%) BM patients presented with BM at the time of initial metastatic diagnosis. Median survival after a diagnosis of BM was 7.6 months (range: 0.4-73.9). The median number of organs involved at time of BM diagnosis was 3 (range: 1-9). DecisionDX-UM profiling was completed on 13 patients: 10-Class 2, 2-Class 1B, and 1-Class 1A. NGS and cytogenetic data were available for 34 and 21 patients, respectively. BM was identified in 6.3% of mUM cases and was associated with high disease burden and a median survival of under 8 months once diagnosed. Since most patients in this cohort were symptomatic, the incidence of asymptomatic BM remains unknown. These data suggest the use of routine brain imaging in all mUM patients at risk for developing BM for early detection.

Two cases of von Hippel-Lindau syndrome-associated retinal hemangioblastoma treated with belzutifan.

PURPOSE: To describe two cases of retinal hemangioblastoma (RH) regression following treatment with belzutifan in patients with von Hippel-Lindau (VHL) syndrome. METHODS: Clinical information was extracted from the charts and tumor imaging of two patients with VHL-associated RH. RESULTS: In case 1, a 40-year-old man was treated with belzutifan for spine hemangioblastomas after diagnosis of a 2.0x2.0x1.3 mm left eye RH temporal to the macula associated with intraretinal edema, subretinal fluid, and mild retinal traction. In case 2, a 66-year-old woman presented with a right eye 2.0x1.5x1.3 mm juxtapapillary lesion with subretinal fluid, intraretinal fluid, and nasal traction, and a 4.0x3.5x1.1 mm inferior mid-periphery lesion with subretinal fluid, intraretinal fluid, and active exudation. She was treated for 2.5 years with belzutifan for renal cell carcinoma on the National Institutes of Health trial. The patient in case 1 demonstrated a 10% reduction in largest tumor diameter and 8% reduction in thickness, along with improving subretinal fluid, intraretinal edema, and retinal traction, after 4 weeks of treatment. After 2.5 years of treatment, the patient in case 2 demonstrated similar margins of her now fibrotic-appearing juxtapapillary lesion with a 45% reduction in thickness, along with resolved subretinal fluid and greatly improved intraretinal fluid and traction. The inferior lesion demonstrated 12.5% reduction in largest diameter, 36% reduction in thickness, and was without active subretinal fluid or exudation. Neither patient demonstrated new lesions while on-treatment. CONCLUSION: Belzutifan is a promising treatment for RH with the potential for both rapid and sustained tumor regression.

Relief of symptomatic pseudo-polycoria due to iris biopsy using a daily contact lens.

PURPOSE: To report a case of pseudo-polycoria from iris biopsy managed by a daily disposable prosthetic colored hydrogel lens. OBSERVATIONS: A 55-year-old- Caucasian female presented with complaints of photophobia in her right eye, that was exacerbated when going from a dark to light environment. Her past ocular history included a diagnosis by another outside physician of presumed multifocal iris melanoma in the right eye, followed by an iris biopsy performed one month later. Upon presentation to our clinic two months later, best corrected visual acuity was 20/20- in the right eye and 20/25 in the left eye. Slit lamp exam of the right eye revealed iris abnormalities, full-thickness biopsy defects at 2, 3 and 6 o'clock and a 0.8 × 0.7mm area of iris hyperpigmentation at 8 o'clock (Fig A,B,C, and D). The patient was provided with three non-surgical options to manage her symptoms: a commercially available soft daily replacement printed prosthetic hydrogel lens, a commercially available soft monthly replacement silicone printed prosthetic hydrogel lens, or a custom soft yearly replacement prosthetic hydrogel lens with dark inlay. The soft daily printed prosthetic hydrogel lens was chosen because of its ease in hygiene regimen and did not limit peripheral vision as the yearly dark inlay lens would. RESULTS: The patient now wears Alcon Dailies® Color, Base curvature 8.6, Diameter 13.8, color mystic green in the right eye and her symptoms of photophobia have been resolved (Figure F). CONCLUSION: There are limited options to manage photophobia in patients with polycoria or pseudo-polycoria. Surgical intervention is dictated by how many quadrants of iris are involved and therefore how symptomatic a patient may be. A less invasive alternative to surgical intervention is the use of a contact lens. In this case, traditional hand painted or printed yearly or monthly replacement hydrogel contact lenses were not used. Instead, a daily disposable hydrogel was successfully fit, highlighting that there is often a simple solution to a seemingly complicated issue.

Correlation between functional MRI and voice improvement following Type I thyroplasty in unilateral vocal fold paralysis--a case study.

The objectives of this study are to describe central nervous system modulation associated with voice improvement following Type I thyroplasty in a patient with glottic insufficiency secondary to unilateral vocal fold paralysis. Serial functional magnetic resonance imaging scans were performed before as well as one and six months after thyroplasty. Paradigms consisting of four voice production tasks and a motor control task were completed. Volumes of activation within regions activated during each task were measured. Acoustic and aerodynamic measures were also obtained. A widespread network of neural activations was shown for all tasks. Differences in volumes of activation 1-month postsurgery positively correlated with acoustic and aerodynamic improvements. Sixth months following medialization, lesser volumes of activation were observed in all regions. Prior to this session, however, the patient's mediastinal disease progressed, leading to a significant deterioration in voice. Functional differences between patient brain maps yield new information about the central nervous system's ability to reorganize sensorimotor representations associated with voice improvement following Type I thyroplasty in a patient with glottic insufficiency secondary to unilateral vocal fold paralysis (UVFP).

Event-related functional MRI investigation of vocal pitch variation.

Voice production involves precise, coordinated movements of the intrinsic and extrinsic laryngeal musculature. A component of normal voice production is the modification of pitch. The underlying neural networks associated with these complex processes remains poorly characterized. However, several investigators are currently utilizing neuroimaging techniques to more clearly delineate these networks associated with phonation. The current study sought to identify the central cortical mechanism(s) associated with pitch variation during voice production using event-related functional MRI (fMRI). A single-trial design was employed consisting of three voice production tasks (low, comfortable, and high pitch) to contrast brain activity during the generation of varying frequencies. For whole brain analysis, volumes of activation within regions activated during each task were measured. Bilateral activations were shown in the cerebellum, superior temporal gyrus, insula, precentral gyrus, postcentral gyrus, inferior parietal lobe, and post-cingulate gyrus. In the left hemisphere, activations in the medial and middle frontal gyri were also observed. Regions active during high pitch production when compared to comfortable pitch were evident in the bilateral cerebellum, left inferior frontal gyrus, left cingulate gyrus, and left posterior cingulate. During low pitch generation, activations were present in the inferior frontal gyrus, insula, putamen, and cingulate gyrus in the left hemisphere. The inferior frontal gyrus in the right hemisphere produced greater activity than the area of the left hemisphere during high and low pitch generation. These results suggest that a single-trial design is sensitive enough to begin to delineate a widespread network of activations in both hemispheres associated with vocal pitch variation.

The effect of prior surgery on blood oxygen level-dependent functional MR imaging in the preoperative assessment of brain tumors.

BACKGROUND AND PURPOSE: Blood oxygen level-dependent functional MR imaging (BOLD fMRI) is a clinically useful technique for preoperative mapping of eloquent cortices in patients with brain tumors. The purpose of this study was to determine the effect on BOLD fMRI accuracy of susceptibility artifacts caused by prior surgery by comparing volumes of activation in the primary motor cortex (PMC) of patients with and without prior brain surgery. METHODS: The volumes of fMRI activation of the PMC were measured for the tumor and nontumor sides in patients with (n = 13) and without (n = 30) prior neurosurgery. Statistical comparisons of the volumes were performed by using paired t tests and linear regression analysis. The location and degree of susceptibility artifact were subjectively assessed. RESULTS: No significant difference was found between the mean tumor and nontumor volumes of fMRI activations in patients without prior surgery (P = .51). In patients who had prior surgery, the volume of activation was significantly smaller on the side of the prior operation when compared with the contralateral side (P = .001). The volume of activation on the side of the tumor was also significantly smaller in the patients with prior surgery compared with those without prior surgery (P < .001). Nevertheless, the PMC was identified in all cases, and its location was confirmed intraoperatively. CONCLUSION: Prior surgery is associated with a decrease in the volume of fMRI activation in patients with prior surgery; however, by examining the T2 images, an astute radiologist can recognize this phenomenon, draw the appropriate conclusions, and correctly identify the PMC.

Functional MRI in the brain tumor patient.

Functional magnetic resonance imaging (fMRI) has been adopted almost universally by disciplines that endeavor to understand how the brain works. As basic scientists tune the technique, clinicians are increasingly able to apply brain mapping with fMRI to their clinical practice. We present here a guide to using fMRI in a clinical setting. We discuss the basic considerations of functional brain mapping in patients with brain tumors including: patient screening and training, paradigm design, data analysis and interpretation of the fMRI scans.