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.

Familial Chiari malformation: a systematic review and illustrative cases.

OBJECTIVE: Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is considered largely sporadic-however, there exists growing evidence of transmissible genetic underpinnings. The purpose of this systematic review of all familial studies of CM was to investigate the existence of an inherited component and provide recommendations to manage and monitor at-risk family members. METHODS: This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included. RESULTS: Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%). CONCLUSIONS: Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.

Carotid-Cavernous Sinus Fistula Masquerading as Thyroid Eye Disease.

A 29-year-old man with a medical and social history notable for smoking presented with progressive orbital congestion, conjunctival injection, and extraocular muscle enlargement consistent with thyroid eye disease (TED). On ophthalmologic examination, tortuous episcleral vessels and blood in Schlemm's canal on gonioscopy clued an alternative diagnosis. Cavernous sinus enhancement on computed tomography also suggested a retro-orbital process. Digital subtraction angiography confirmed a low-flow indirect carotid-cavernous fistula (CCF). He subsequently underwent endovascular embolization treatment. Ocular symptoms resolved by seven weeks, and he remained ocular symptom free at six months. Eye redness and proptosis frequently cause patients to seek medical attention. In the absence of a mass or signs of infection, TED is high on the differential, especially with a smoking history and even with normal thyroid parameters. However, CCF may lurk; the authors describe key diagnostic features and management.

Age-Related Macular Degeneration (AMD) Transmitochondrial Cybrids Protected from Cellular Damage and Death by Human Retinal Progenitor Cells (hRPCs).

PURPOSE: One of the leading causes of irreversible blindness worldwide, age-related macular degeneration (AMD) is a progressive disorder leading to retinal degeneration. While several treatment options exist for the exudative form of AMD, there are currently no FDA-approved treatments for the more common nonexudative (atrophic) form. Mounting evidence suggests that mitochondrial damage and retinal pigment epithelium (RPE) cell death are linked to the pathogenesis of AMD. Human retinal progenitor cells (hRPCs) have been studied as a potential restorative therapy for degenerative conditions of the retina; however, the effects of hRPC treatment on retinal cell survival in AMD have not been elucidated. METHODS: In this study, we used a cell coculture system consisting of hRPCs and AMD or age-matched normal cybrid cells to characterize the effects of hRPCs in protecting AMD cybrids from cellular and mitochondrial damage and death. RESULTS: AMD cybrids cocultured with hRPCs showed (1) increased cell viability; (2) decreased gene expression related to apoptosis, autophagy, endoplasmic reticulum (ER) stress, and antioxidant pathways; and (3) downregulation of mitochondrial replication genes compared to AMD cybrids without hRPC treatment. Furthermore, hRPCs cocultured with AMD cybrids showed upregulation of (1) neuronal and glial markers, as well as (2) putative neuroprotective factors, responses not found when hRPCs were cocultured with age-matched normal cybrids. CONCLUSION: The current study provides the first evidence that therapeutic benefits may be obtainable using a progenitor cell-based approach for atrophic AMD. Our results suggest that bidirectional interactions exist between hRPCs and AMD cybrids such that hRPCs release trophic factors that protect the cybrids against the cellular and mitochondrial changes involved in AMD pathogenesis while, conversely, AMD cybrids upregulate the release of these neuroprotective factors by hRPCs while promoting hRPC differentiation. These in vitro data provide evidence that hRPCs may have therapeutic potential in atrophic AMD.

A Novel Epidemiological Approach to Geographically Mapping Population Dry Eye Disease in the United States Through Google Trends.

PURPOSE: Our study fills the spatiotemporal gaps in dry eye disease (DED) epidemiology by using Google Trends as a novel epidemiological tool for geographically mapping DED in relation to environmental risk factors. METHODS: We used Google Trends to extract DED-related queries estimating users' intent from 2004 to 2019 in the United States. We incorporated national climate data to generate heat maps comparing geographic, temporal, and environmental relationships of DED. Multivariable regression models were constructed to generate quadratic forecasts predicting DED and control searches. RESULTS: Our results illustrated the upward trend, seasonal pattern, environmental influence, and spatial relationship of DED search volume across the US geography. Localized patches of DED interest were visualized in urban areas. There was no significant difference in DED queries across the US census regions (P = 0.3543). Regression model 1 predicted DED queries per state (R2 = 0.61), with the significant predictor being urban population [r = 0.56, adjusted (adj.) P < 0.001, n = 50]; model 2 predicted DED searches over time (R2 = 0.97), with significant predictors being control queries (r = 0.85, adj. P = 0.0169, n = 190), time (r = 0.96, adj. P < 0.001, n = 190), time2 (r = 0.97, adj. P < 0.001, n = 190), and seasonality (winter r = -0.04, adj. P = 0.0196, n = 190; spring r = 0.10, adj. P < 0.001, n = 190). CONCLUSIONS: Our study used Google Trends as a novel epidemiologic approach to geographically mapping the US DED. Importantly, urban population and seasonality were stronger risk factors of DED searches than temperature, humidity, sunshine, pollution, or region. Our work paves the way for future exploration of geographic information systems for locating DED and other diseases through online population metrics.

Oculofacial plastic surgery-related online search trends including the impact of the COVID-19 pandemic.

Purpose: The authors aim to characterize oculofacial plastic surgery-related online interest that may be useful in forecasting demand and in designing patient-directed online resources. Methods: The authors queried Google Trends for over 100 oculofacial plastic surgery terms. The main outcome measure was the top 50 oculofacial plastic surgery-related search terms from 2004 to 2020. Secondary outcomes were trends, including seasonality, and search volume changes during the COVID-19 lockdown (March-May 2020) compared to 2018-2019. Terms were analyzed individually and in thematic categories; controlled against generic search terms to account for general internet traffic. Results: Between 2004 and 2020, searches for oculofacial plastic surgery altogether increased, surpassing the rate of internet traffic growth. One thematic category - eyelid malpositions - decreased month-over-month. The top five terms were "face lift," "Bell's palsy," "puffy eyes," "dark circles under eyes," and "chalazion." Eyelid neoplasms searches peaked in summer (R2  = 0.880) whereas cosmetic (R2  = 0.862), symptoms (R 2 = 0.907), and surgeries (R 2 = 0.140) peaked in winter. Overall, oculofacial-related searches decreased during the COVID-19 lockdown, although thyroid eye disease interest increased compared to 2018 or 2019 (+68.6%; adj. p = .005). Oculofacial plastic surgery interest in 2020 was inversely correlated to "COVID-19" searches (r = -0.76, p < .001). Conclusions: Oculofacial plastic surgery searches increased since 2004 at a pace greater than that ascribed to internet traffic growth. The most searched terms were "face lift," "Bell's palsy," "puffy eyes," "dark circles under eyes," and "chalazion." Almost all oculofacial-related searches decreased during the COVID-19 lockdown.

A Case Report of Moyamoya Disease Presenting as Headache in a 35-year-old Hispanic Man.

Moyamoya disease (MMD) is a rare, chronic vaso-occlusive disease affecting the arteries of the Circle of Willis, leading to the development of characteristic collateral vessels. In this paper, we present a case of a 35-year-old Hispanic male who presented to the emergency department with new onset headaches. On examination, Glasgow Coma Scale score was 3T. The patient was investigated with head CT scan and cerebral angiogram, diagnosed as MMD, and treated with emergent ventriculostomy. Ultimately, the patient underwent extracranial-intracranial (EC-IC) bypass surgery for treatment of Moyamoya.

A molecular cascade modulates MAP1B and confers resistance to mTOR inhibition in human glioblastoma.

Background: Clinical trials of therapies directed against nodes of the signaling axis of phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin (mTOR) in glioblastoma (GBM) have had disappointing results. Resistance to mTOR inhibitors limits their efficacy. Methods: To determine mechanisms of resistance to chronic mTOR inhibition, we performed tandem screens on patient-derived GBM cultures. Results: An unbiased phosphoproteomic screen quantified phosphorylation changes associated with chronic exposure to the mTOR inhibitor rapamycin, and our analysis implicated a role for glycogen synthase kinase (GSK)3B attenuation in mediating resistance that was confirmed by functional studies. A targeted short hairpin RNA screen and further functional studies both in vitro and in vivo demonstrated that microtubule-associated protein (MAP)1B, previously associated predominantly with neurons, is a downstream effector of GSK3B-mediated resistance. Furthermore, we provide evidence that chronic rapamycin induces microtubule stability in a MAP1B-dependent manner in GBM cells. Additional experiments explicate a signaling pathway wherein combinatorial extracellular signal-regulated kinase (ERK)/mTOR targeting abrogates inhibitory phosphorylation of GSK3B, leads to phosphorylation of MAP1B, and confers sensitization. Conclusions: These data portray a compensatory molecular signaling network that imparts resistance to chronic mTOR inhibition in primary, human GBM cell cultures and points toward new therapeutic strategies.