Disorders with Ophthalmic and Thoracic Involvement.

A variety of systemic conditions involve the thorax and the eyes. While subtle or nonspecific eye symptoms can be the initial clinical manifestation of some disorders, there can be additional manifestations in the thorax that lead to a specific diagnosis and affect patient outcomes. For instance, the initial clinical manifestation of Sjögren syndrome is dry eye or xerophthalmia; however, the presence of Sjögren lung disease represents a fourfold increase in mortality. Likewise, patients with acute sarcoidosis can initially present with pain and redness of the eye from uveitis in addition to fever and parotitis. Nearly 90% of patients with sarcoidosis have thoracic involvement, and the ophthalmologic symptoms can precede the thoracic symptoms by several years in some cases. Furthermore, a diagnosis made in one system can result in the screening of other organs as well as prompt genetic evaluation and examination of family members, such as in the setting of Marfan syndrome or Ehlers-Danlos syndrome. Multimodality imaging, particularly CT and MRI, plays a vital role in identification and characterization of these conditions. While it is helpful for ophthalmologists to be knowledgeable about these conditions and their associations so that they can order the pertinent radiologic studies, it is also important for radiologists to use the clues from ophthalmologic examination in addition to imaging findings to suggest a specific diagnosis. Systemic conditions with thoracic and ophthalmologic manifestations can be categorized as infectious, inflammatory, autoimmune, neoplastic, or hereditary in origin. The authors describe a spectrum of these conditions based on their underlying cause. ©RSNA, 2024.

Detecting Eye Disease Using Vision Transformers Informed by Ophthalmology Resident Gaze Data.

We showcase two proof-of-concept approaches for enhancing the Vision Transformer (ViT) model by integrating ophthalmology resident gaze data into its training. The resulting Fixation-Order-Informed ViT and Ophthalmologist-Gaze-Augmented ViT show greater accuracy and computational efficiency than ViT for detection of the eye disease, glaucoma.Clinical relevance- By enhancing glaucoma detection via our gaze-informed ViTs, we introduce a new paradigm for medical experts to directly interface with medical AI, leading the way for more accurate and interpretable AI 'teammates' in the ophthalmic clinic.

Needle aspiration for management of acute intraoperative fluid misdirection during phacoemulsification.

Purpose: Acute intraoperative fluid misdirection is a serious complication that may occur during phacoemulsification. We provide a detailed description and a video of our preferred technique for prompt management of acute intraoperative fluid misdirection. Observations: A 79-year-old male developed sudden shallowing of the anterior chamber and marked elevation of intraocular pressure at hydrodissection during phacoemulsification surgery. Treatment consisted of a needle aspiration of trapped fluid from the retrolental space, employing a 5/8th inch, 25-gauge needle on a medium-size syringe leading to immediate softening of the globe and deepening of the anterior chamber. The rest of the case proceeded uneventfully. The patient had uncomplicated recovery and final best-corrected visual acuity of 20/20. Conclusions and importance: Acute subcapsular infusion fluid entrapment may occur during uneventful phacoemulsification. Needle aspiration of retrolental fluid is a simple and inexpensive method for immediate resolution of high IOP and deepening of the anterior chamber, allowing the case to proceed.

Glaucoma Treatment Outcomes in Open Angle Glaucoma Patients of African Descent.

Open angle glaucoma (OAG), characterized by structural changes to the optic nerve head and retinal nerve fiber layer, is a progressive multifactorial optic neuropathy and a leading cause of irreversible blindness globally. Currently, intraocular pressure is the only modifiable risk factor; however, others have been identified, including genetics and race. Importantly, OAG is much more prevalent in persons of African descent (AD) compared with those of European descent (ED). OAG patients of AD are also known to have a more severe course of the disease, a finding potentially explained by structural and/or vascular differences within eye tissues. In addition, disparities in treatment outcomes have been identified in OAG patients of AD. Specifically, prostaglandin analogues have been suggested to be more effective in patients of AD than in those ED, while beta-adrenergic receptors have been suggested to be less effective, although the evidence is inconsistent. AD has also been identified as a risk factor for trabeculectomy failure while laser trabeculoplasty has been conversely found to be very effective in lowering intraocular pressure in patients of AD. Alternative surgical options, including Ex-Press shunt implantation, viscocanalostomy, and canaloplasty are promising in equivalence but require further research to evaluate disparity in outcome properly. In addition to treatment outcomes, social disparities affecting clinical care also exist for AD persons in the form of reduced adherence, access, and choice. Overall, data suggest the need for properly designed prospective trials with AD populations as a primary focus to identify the potential mechanisms driving disparities in treatment and address overall potential bias in glaucoma management.

Sustained release glaucoma therapies: Novel modalities for overcoming key treatment barriers associated with topical medications.

Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness. The disease has conventionally been characterized by an elevated intraocular pressure (IOP); however, recent research has built the consensus that glaucoma is not only dependent on IOP but rather represents a multifactorial optic neuropathy. Although many risk factors have been identified ranging from demographics to co-morbidities to ocular structural predispositions, IOP is currently the only modifiable risk factor, most often treated by topical IOP-lowering medications. However, topical hypotensive regimens are prone to non-adherence and are largely inefficient, leading to disease progression in spite of treatment. As a result, several companies are developing sustained release (SR) drug delivery systems as alternatives to topical delivery to potentially overcome these barriers. Currently, Bimatoprost SR (DurystaTM) from Allergan plc is the only FDA-approved SR therapy for POAG. Other SR therapies under investigation include: bimatoprost ocular ring (Allergan) (ClinicalTrials.gov identifier: NCT01915940), iDose® (Glaukos Corporation) (NCT03519386), ENV515 (Envisia Therapeutics) (NCT02371746), OTX-TP (Ocular Therapeutix) (NCT02914509), OTX-TIC (Ocular Therapeutix) (NCT04060144), and latanoprost free acid SR (PolyActiva) (NCT04060758). Additionally, a wide variety of technologies for SR therapeutics are under investigation including ocular surface drug delivery systems such as contact lenses and nanotechnology. While challenges remain for SR drug delivery technology in POAG management, this technology may shift treatment paradigms and dramatically improve outcomes.

Artificial Intelligence to Aid Glaucoma Diagnosis and Monitoring: State of the Art and New Directions.

Recent developments in the use of artificial intelligence in the diagnosis and monitoring of glaucoma are discussed. To set the context and fix terminology, a brief historic overview of artificial intelligence is provided, along with some fundamentals of statistical modeling. Next, recent applications of artificial intelligence techniques in glaucoma diagnosis and the monitoring of glaucoma progression are reviewed, including the classification of visual field images and the detection of glaucomatous change in retinal nerve fiber layer thickness. Current challenges in the direct application of artificial intelligence to further our understating of this disease are also outlined. The article also discusses how the combined use of mathematical modeling and artificial intelligence may help to address these challenges, along with stronger communication between data scientists and clinicians.

Physiology-Enhanced Data Analytics to Evaluate the Effect of Altitude on Intraocular Pressure and Ocular Hemodynamics.

Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.

Prevalence Rates and Risk Factors for Primary Open Angle Glaucoma in the Middle East.

Glaucoma is a multifactorial disease and a leading cause of irreversible blindness worldwide. Current data has demonstrated the approximate distribution of primary open-angle glaucoma (POAG) in patients of European, African, Hispanic, and Eastern Asian descent. However, a significant gap in the literature exists regarding the prevalence of POAG in Middle Eastern (ME) populations. Current studies estimate ME POAG prevalence based on a European model. Herein we screened 65 total publications on ME prevalence of POAG and specific risk factors using keywords: "glaucoma", "prevalence", "incidence", "risk factor", "Middle East", "Mideast", "Persian", "Far East", as well as searching by individual ME countries through PubMed, Embase, Ovid, Scopus, and Trip searches with additional reference list searches from relevant articles published up to and including March 1, 2021. Fifty qualifying records were included after 15 studies identified with low statistical power, confounding co-morbid ophthalmic diseases, and funding bias were excluded. Studies of ME glaucoma risk factors that identify chromosomes, familial trend, age/gender, socioeconomic status, lifestyle, intraocular pressure, vascular influences, optic disc hemorrhage, cup-to-disc ratio, blood pressure, obstructive sleep apnea, and diabetes mellitus were included in this systematic review. We conclude that the prevalence of POAG in the ME is likely higher than the prevalence rate that European models suggest, with ME specific risk factors likely playing a role. However, these findings are severely limited by the paucity of population-level data in the ME. Well-designed, longitudinal population-based studies with rigorous inclusion and exclusion criteria are ultimately needed to accurately assess the epidemiology and specific mechanistic risk factors of glaucoma in ME populations.

Agreement of rebound and applanation tonometry intraocular pressure measurements during atmospheric pressure change.

This study investigated the agreement of intraocular pressure measurements using rebound tonometry and applanation tonometry in response to atmospheric changes in a hyperbaric chamber. Twelve eyes of 12 healthy subjects were included in this prospective, comparative, single-masked study. Intraocular pressure measurements were performed by rebound tonometry followed by applanation tonometry in a multiplace hyperbaric chamber at 1 Bar, followed by 2, 3 and 4 Bar during compression and again at 3 and 2 Bar during decompression. Mean differences between rebound and applanation intraocular pressure measurements were 1.6, 1.7, and 2.1 mmHg at 2, 3, and 4 Bar respectively during compression and 2.6 and 2.2 mmHg at 3 and 2 Bar during decompression. Lower limits of agreement ranged from -3.7 to -5.9 mmHg and upper limits ranged from -0.3 to 1.9 mmHg. Multivariate analysis showed that the differences between rebound and applanation intraocular pressure measurements were independent of atmospheric pressure changes (p = 0.79). Intraocular pressure measured by rebound tonometry shows a systematic difference compared to intraocular measured by applanation tonometry, but this difference is not influenced by changes of atmospheric pressure up to 4 Bar in a hyperbaric chamber. Agreement in magnitude of change between devices suggests rebound tonometry is viable for assessing intraocular pressure during atmospheric changes. Future studies should be designed in consideration of expected differences in IOP values provided by the two devices.

Glaucoma Heritability: Molecular Mechanisms of Disease.

Glaucoma is one of the world's leading causes of irreversible blindness. A complex, multifactorial disease, the underlying pathogenesis and reasons for disease progression are not fully understood. The most common form of glaucoma, primary open-angle glaucoma (POAG), was traditionally understood to be the result of elevated intraocular pressure (IOP), leading to optic nerve damage and functional vision loss. Recently, researchers have suggested that POAG may have an underlying genetic component. In fact, studies of genetic association and heritability have yielded encouraging results showing that glaucoma may be influenced by genetic factors, and estimates for the heritability of POAG and disease-related endophenotypes show encouraging results. However, the vast majority of the underlying genetic variants and their molecular mechanisms have not been elucidated. Several genes have been suggested to have molecular mechanisms contributing to alterations in key endophenotypes such as IOP (LMX1B, MADD, NR1H3, and SEPT9), and VCDR (ABCA1, ELN, ASAP1, and ATOH7). Still, genetic studies about glaucoma and its molecular mechanisms are limited by the multifactorial nature of the disease and the large number of genes that have been identified to have an association with glaucoma. Therefore, further study into the molecular mechanisms of the disease itself are required for the future development of therapies targeted at genes leading to POAG endophenotypes and, therefore, increased risk of disease.

Antimicrobial resistance and recurrent bacterial urinary tract infections in hospitalized patients following kidney transplantation: A single-center experience.

PURPOSE: The burden of urinary tract infections (UTIs) and risk factors for developing infections with multidrug resistant organisms (MDROs) post-kidney transplantation (KT) are poorly understood. METHODS: Single-center retrospective cohort study (January 2015-December 2017) evaluating first and recurrent episodes of bacteriuria and subsequent analysis of episodes caused by MDROs up to 6 months post-KT. Donor and recipient variables were reviewed. RESULTS: A total of 743 adults underwent single KT during the study period, and 106 patients were hospitalized with bacteriuria. 45% were asymptomatic in their first episode. 73.6% had a single episode, and 26.4% had 2 or more episodes. A total of 28 patients had recurrent episodes; 64.3% had an MDRO on the first episode and 78.6% on the second episode. Escherichia coli was the most common organism isolated, 88.5% were resistant to trimethoprim-sulfamethoxazole (TMP-SMX), 9.3% were extended-spectrum beta-lactamase (ESBL) producers, and 38.1% were MDROs. Body mass index ≥30 was significantly associated with the presence of MDROs in both univariate and multivariate analyses (RR 1.37, 95% CI 1.01-1.88; OR 3.26, CI 1.29-8.25). A total of 12 donors had bacteremia or bacteriuria and 6 (50%) with E coli. A total of 10 KT recipients received antibiotic prophylaxis to prevent donor-derived infections. CONCLUSIONS: Our results suggest that a significant proportion of patients develop recurrent bacteriuria post-transplantation; of those, more than half caused by MDROs. There is a possible association between obesity and MDROs in KT recipients that merits further investigation. With the global crisis in antimicrobial resistance, innovative strategies are needed to prevent and treat UTIs in KT patients.

Molecular Genetics of Glaucoma: Subtype and Ethnicity Considerations.

Glaucoma, the world's leading cause of irreversible blindness, is a complex disease, with differential presentation as well as ethnic and geographic disparities. The multifactorial nature of glaucoma complicates the study of genetics and genetic involvement in the disease process. This review synthesizes the current literature on glaucoma and genetics, as stratified by glaucoma subtype and ethnicity. Primary open-angle glaucoma (POAG) is the most common cause of glaucoma worldwide, with the only treatable risk factor (RF) being the reduction of intraocular pressure (IOP). Genes associated with elevated IOP or POAG risk include: ABCA1, AFAP1, ARHGEF12, ATXN2, CAV1, CDKN2B-AS1, FOXC1, GAS7, GMDS, SIX1/SIX6, TMCO1, and TXNRD2. However, there are variations in RF and genetic factors based on ethnic and geographic differences; it is clear that unified molecular pathways accounting for POAG pathogenesis remain uncertain, although inflammation and senescence likely play an important role. There are similar ethnic and geographic complexities in primary angle closure glaucoma (PACG), but several genes have been associated with this disorder, including MMP9, HGF, HSP70, MFRP, and eNOS. In exfoliation glaucoma (XFG), genes implicated include LOXL1, CACNA1A, POMP, TMEM136, AGPAT1, RBMS3, and SEMA6A. Despite tremendous progress, major gaps remain in resolving the genetic architecture for the various glaucoma subtypes across ancestries. Large scale carefully designed studies are required to advance understanding of genetic loci as RF in glaucoma pathophysiology and to improve diagnosis and treatment options.

Nutritional interventions for autism spectrum disorder.

Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental disorder with considerable clinical heterogeneity. With no cure for the disorder, treatments commonly center around speech and behavioral therapies to improve the characteristic social, behavioral, and communicative symptoms of ASD. Gastrointestinal disturbances are commonly encountered comorbidities that are thought to be not only another symptom of ASD but to also play an active role in modulating the expression of social and behavioral symptoms. Therefore, nutritional interventions are used by a majority of those with ASD both with and without clinical supervision to alleviate gastrointestinal and behavioral symptoms. Despite a considerable interest in dietary interventions, no consensus exists regarding optimal nutritional therapy. Thus, patients and physicians are left to choose from a myriad of dietary protocols. This review, summarizes the state of the current clinical and experimental literature on nutritional interventions for ASD, including gluten-free and casein-free, ketogenic, and specific carbohydrate diets, as well as probiotics, polyunsaturated fatty acids, and dietary supplements (vitamins A, C, B6, and B12; magnesium and folate).

Cell communication by tunneling nanotubes: Implications in disease and therapeutic applications.

Intercellular communication is essential for the development and maintenance of multicellular organisms. Tunneling nanotubes (TNTs) are a recently recognized means of long and short distance communication between a wide variety of cell types. TNTs are transient filamentous membrane protrusions that connect cytoplasm of neighboring or distant cells. Cytoskeleton fiber-mediated transport of various cargoes occurs through these tubules. These cargoes range from small ions to whole organelles. TNTs have been shown to contribute not only to embryonic development and maintenance of homeostasis, but also to the spread of infectious particles and resistance to therapies. These functions in the development and progression of cancer and infectious disease have sparked increasing scrutiny of TNTs, as their contribution to disease progression lends them a promising therapeutic target. Herein, we summarize the current knowledge of TNT structure and formation as well as the role of TNTs in pathology, focusing on viral, prion, and malignant disease. We then discuss the therapeutic possibilities of TNTs in light of their varied functions. Despite recent progress in the growing field of TNT research, more studies are needed to precisely understand the role of TNTs in pathological conditions and to develop novel therapeutic strategies.