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Purpose: Dry-eye disease (DED) is a chronic progressive ocular surface disorder with limited studies in the pediatric population. The Academy of Ophthalmology's IRIS® Registry was leveraged to investigate the prevalence of DED in the pediatric population (PDED, patients <18 years old) and the demographic differences of DED between pediatric and adult patients (ADED)., Methods: Retrospective cohort study. Patients with DED between January 1st, 2013 and December 31st, 2019 (N = 4,795,979) were included. Descriptive statistics, Pearson's chi-squared tests and two-sample proportions tests were conducted to compare key demographic distributions between the ADED and PDED cohorts., Results: The average age at onset for ADED patients was 61.06 (±14.75) years and for PDED patients was 12.51 (±3.86). The overall tests for independence and the individual tests of proportions of each category were statistically significant for all demographic characteristics (p < 0.001). Characteristics with the largest discrepancies between patients of PDED and the IRIS Registry pediatric patient pool (PIRIS) included female sex (58.08 % vs. 50.60 %), male sex (41.58 % vs. 48.78 %) and Asian race (6.02 % vs. 3.11 %) respectively. Within the PDED cohort, females were at higher risk of PDED (58 % vs. 42 %). PDED was more prevalent in children with refractive errors (76 %) and eyelid/conjunctival disorders (41 %). Characteristics with the largest discrepancies between PDED and ADED patients included female sex (58.08 % vs. 68.12 %), male sex (41.58 % vs. 31.55 %) and Caucasian race (50.24 % vs. 67.06 %) respectively., Conclusions: Significant differences in the PDED cohort are demonstrated in this study. PDED was more prevalent in the female sex and Caucasian race compared to PIRIS and was more commonly associated with refractive errors and eyelid/conjunctival disorders., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A number of congenital and inherited diseases present with both ocular and psychiatric features. The genetic inheritance and phenotypic variants play a key role in disease severity. Early recognition of the signs and symptoms of those disorders is critical to earlier intervention and improved prognosis. Typically, the associations between these two medical subspecialties of ophthalmology and psychiatry are poorly understood by most practitioners so we hope to provide a narrative review to improve the identification and management of these disorders. We conducted a comprehensive review of the literature detailing the diseases with ophthalmic and psychiatric overlap that were more widely represented in the literature. Herein, we describe the clinical features, pathophysiology, molecular biology, diagnostic tests, and the most recent approaches for the treatment of these diseases. Recent studies have combined technologies for ocular and brain imaging such as optical coherence tomography (OCT) and functional imaging with genetic testing to identify the genetic basis for eye-brain connections. Additional work is needed to further explore these potential biomarkers. Overall, accurate, efficient, widely distributed and non-invasive tests that can help with early recognition of these diseases will improve the management of these patients using a multidisciplinary approach., Competing Interests: Declaration of Competing Interest CK, K.A.A.D. and V.P.D have no disclosures to report. J.B.M. is a consultant for Alcon, Allergan, Carl Zeiss, Sunovion, Topcon and Genentech. P.L. has received financial support by Harvard Medical School and National Institute of Health with grant numbers 1K23MH122701 and UL1TR002541., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Inherited retinal degenerations (IRDs) represent a genetically and clinically heterogeneous group of progressive and visually debilitating disorders that can lead to irreversible visual loss. Our understanding of IRD pathogenesis at both the genetic and cellular levels has increased tremendously over the past two decades, but the exact pathogenic mechanisms remain incompletely understood. Enhanced understanding of the pathophysiology of these diseases can result in new treatment targets. Alterations in the human gut microbiome play a key role in the pathogenesis of many ocular and nonocular diseases, such as age-related macular degeneration, neurologic and metabolic disorders, and autoimmune conditions. The gut microbiome regulates the susceptibility of mice to develop experimental autoimmune uveitis, a model for autoimmune disease of the posterior portion of the eye elicited by the systemic response to retinal antigens. Because of the mounting evidence in favor of a role for local and systemic inflammatory and autoimmune-mediated components to IRD pathogenesis, this review presents the current knowledge of gut microbiome in IRDs and discusses the association between possible changes in gut microbiome and pathogenesis of these diseases, with special attention to their possible contribution to the inflammatory underpinnings of IRDs., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Optical coherence tomography angiography (OCTA) is a novel, noninvasive imaging technique, which provides depth resolved visualization of microvasculature of the retina and choroid. Although OCTA has been widely used for the evaluation of a number of retinal diseases, its use in the field of neuro-ophthalmology has been less studied. In this review, we provide an update on the utility of OCTA in neuro-ophthalmic conditions., Recent Findings: Peripapillary and macular microvasculature analyses have indicated that OCTA can be a promising tool for early detection of a number of neuro-ophthalmic diseases, differential diagnosis, and monitoring of disease progression. Recent studies have demonstrated that structural and functional impairment can develop at early stages in some conditions such as in multiple sclerosis and Alzheimer's disease even in the absence of overt clinical symptoms. Furthermore, this dye-less technique can be a valuable adjunct tool in the detection of complications commonly seen in some congenital entities such optic disc drusen., Summary: Since its introduction, OCTA has emerged as an important imaging approach shedding light on unrevealed pathophysiological mechanisms of several ocular diseases. The use of OCTA as a biomarker in the field of neuro-ophthalmology has recently gained considerable attention with studies supporting its role in clinical setting while larger studies are warranted for correlating these findings with traditional diagnostic procedures and clinical features and outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: While structural changes within the retina of psychosis patients have been established, no detailed studies of choroidal microvasculature in these patients have been performed. Given evidence of microvascular disruption in psychosis patients, this study sought to determine whether there exists evidence of microvascular disruption in the choroids in these patients., Methods: Fifty-six subjects (20 controls and 36 psychosis patients) were recruited from April 2018 to February 2020. Five were excluded due to imaging artifact or missing demographic information. Swept-source optical coherence tomography angiography (SS-OCTA) images were obtained. Choroid vascular enface images (12 mm × 9mm) were exported every 2.6 μm from Bruch's membrane to the choroid-scleral interface from Topcon to ImageJ. The images were binarized using Otsu's method, signal from the optic disk and retinal vasculature was removed, and average choroid vascular density (CVD) was calculated as the average of percent area occupied by choroidal vasculature across images in the stack. Choroid vascular volume (CVV) was calculated as the CVD multiplied by maximum CT and image area. During image analysis, study staff were blinded to the phenotype of the study subjects., Results: Compared with same-sex controls, male psychiatric patients had significantly lower CVD. Compared with same-sex controls, female psychiatric patients had significantly lower maximum CT with correspondingly decreased CVV, after adjusting for age. When all psychiatric patients were compared with all healthy controls, no significant differences in CT, CVD, or CVV were noted., Conclusion: These results suggest that the pathogenesis of psychotic illness affects choroidal microvasculature in a sex-specific manner., Competing Interests: P.L., D.B., and M. Keshavan. were supported in part by the Harvard Medical School Dupont Warren Fellowship and Livingston Grant; Sydney R. Baer Jr Foundation; National Institute of Health Harvard Catalyst [grant number 1KL2TR002542]; National Institute of Mental Health [grant number R01 MH078113]; and National Institute of Mental Health [grant number R01 MH077945]. We would like to thank the following B-SNIP2 principal investigators (Carol Tamminga, Brett Clementz, Elliot Gershon, and Godfrey Pearlson) for their input and support of this study.L.A.K. has received financial support from the National Eye Institute and CureVac AG and has financial arrangement with Pykus Therapeutics.J.B.M. is a consultant for Alcon, Allergan, Carl Zeiss, Sunovion, Topcon and Genentech.C.Y.L., I.G., M. Kasetty, R.K., I.A., K.D., and J.C.W. have no conflicts of interest to report., (© 2022 Li et al.)

Objective: To investigate the clinical and magnetic resonance imaging (MRI) characteristics of patients with varicella zoster virus (VZV) reactivation involving the cranial nerves and central nervous system (CNS)., Methods: This is a retrospective, multi-center case-series of 37 patients with VZV infection affecting the cranial nerves and CNS., Results: The median age was 71 years [IQR 51.5-76]; 21 (57%) were men. Cerebrospinal fluid (CSF) was available in 24/37 (65%); median CSF white blood cell count was 11 [IQR 2-23] cells/μL and protein was 45.5 [IQR 34.5-75.5] mg/dL. VZV polymerase chain reaction (PCR) assays were positive in 6/21 (29%) CSF and 8/9 (89%) ocular samples. Clinical involvement included the optic nerve in 12 (32%), other cranial nerves in 20 (54%), brain parenchyma in 12 (32%) and spinal cord or nerve roots in 4 (11%). Twenty-seven/28 immunocompetent patients' MRIs were available for review (96%). Of the 27, 18 had T1 postcontrast fat saturated sequences without motion artifact to evaluate for cranial nerve enhancement and optic perineuritis (OPN). Eight/18 (44%) demonstrated OPN. All 8 experienced vision loss: 3 optic neuritis, 1 acute retinal necrosis, and 3 CNS vasculitis with 1 central and 1 branch retinal artery occlusion and 1 uveitis. Diplopic patients had cranial nerve and cavernous sinus enhancement. All immunosuppressed patients were imaged. Seven/9 (88%) had extensive neuraxis involvement, including encephalitis, vasculitis and transverse myelitis; one case had OPN., Conclusion: OPN is a frequent manifestation in VZV-associated vision loss among immunocompetent patients. Immunosuppressed patients had greater neuraxis involvement. Optimizing MRI protocols may improve early diagnosis in VZV reactivation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To investigate the short- and long-term impact of COVID-19—related lockdown on the vision of patients requiring intravitreal injections (IVI) for neovascular Age-related Macular degeneration (nvAMD), diabetic retinopathy (DR), central retinal vein occlusion (CRVO), or branch retinal vein occlusion (BRVO). Methods: This is a retrospective study from the Retina department of three Mass Eye and Ear centers. Charts of patients age of ≥ 18 years with any of the abovementioned diagnoses who had a scheduled appointment anytime between 17 March 2020 until 18 May 2020 (lockdown period in Boston, Massachusetts) were reviewed at baseline (up to 12 weeks before the lockdown), at first available follow-up (=actual f/u) during or after the lockdown period, at 3 months, 6 months, and at last available completed appointment of 2020. Results: A total of 1001 patients met the inclusion criteria. Of those patients, 479 (47.9%) completed their intended f/u appointment, while 522 missed it (canceled and “no show”). The delay in care of those who missed it was 59.15 days [standard deviation (SD) ± 49.6]. In these patients, significant loss of vision was noted at actual f/u [Best corrected visual acuity (BCVA) in LogMAR (Logarithm of the Minimum Angle of Resolution)—mean (±SD)—completed: 0.45 (±0.46), missed: 0.53 (±0.55); p = 0.01], which was more prominent in the DR group [Visual acuity (VA) change in LogMAR—mean (±SD); completed: 0.04 (±0.28), missed: 0.18 (±0.44); p = 0.02] and CRVO [completed: −0.06 (±0.27), missed: 0.11 (±0.35); p = <0.001] groups followed by nvAMD [completed: 0.006 (±0.16), missed: 0.06 (±0.27); p = 0.004] and BRVO [completed: −0.02 (±0.1), missed: 0.03 (±0.14); p = 0.02] ones. Overall, a higher percent of people who missed their intended f/u experienced vision loss of more than 15 letters at last f/u compared to those who completed it [missed vs. completed; 13.4% vs. 7.4% in nvAMD (p = 0.72), 7.8% vs. 6.3% in DR (0.84), 15.5% vs. 9.9% in CRVO (p < 0.001) and 9.6% vs. 2% in BRVO (p = 0.48)]. Conclusions: Delay in care of about 8.45 weeks can lead to loss of vision in patients who receive IVI with DR and CRVO patients being more vulnerable in the short-term, whereas in the long-term, CRVO patients followed by the nvAMD patients demonstrating the least vision recovery. BRVO patients were less likely to be affected by the delay in care. Adherence to treatment is key for maintaining and improving visual outcomes in patients who require IVI.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in people over the age of 50 worldwide. Exudative or neovascular AMD is a more severe subset of AMD which is characterized by the presence of choroidal neovascularization (CNV). Recent advancements in multimodal ophthalmic imaging, including optical coherence tomography (OCT) and OCT-angiography (OCT-A), have facilitated the detection and characterization of previously undetectable neovascular lesions and have enabled a more refined classification of CNV in exudative as well as nonexudative AMD patients. Subthreshold exudative CNV is a novel subtype of exudative AMD that typically presents asymptomatically with good visual acuity and is characterized by stable persistent or intermittent subretinal fluid (SRF). This review aims to provide an overview of the clinical as well as multimodal imaging characteristics of CNV in AMD, including this new clinical phenotype, and propose effective approaches for management.

Abstract: A 55-year-old Caucasian man presented to the neuro-ophthalmology department for follow-up evaluation due to long-standing bilateral optic nerve head drusen (ONHD). On examination, the BCVA was 20/20-2 in both eyes. Dilated fundus examination revealed extensive ONHD in both eyes, retinal hemorrhages, exudates inferonasal to the macula, and macular edema inferotemporal to the disc margin. Automated visual field testing revealed generalized depression in both eyes. Late phase leakage was observed on fluorescein angiography (FA). Optical coherence tomography angiography identified a small juxtapapillary choroidal neovascular membrane inferonasal to the macula in the right eye correlating with the area of retinal hemorrhage and exudates., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Globe injury is a serious worldwide public health issue frequently leading to permanent vision impairment. The plethora of different types of globe injuries is classified into categories, including open and closed globe injuries. Globe injury occurs mainly in the workplace and at home, affecting predominantly middle-aged working men. Socioeconomic status (SES) is defined by income level, educational attainment, and employment status. Low socioeconomic status has been associated with a higher incidence of globe injury and can be utilized to identify at-risk populations. For managing open and closed globe injuries, different strategies are applied and the implementation of adequate globe injury prevention measures is needed for reducing the occurrence of globe injury. The following article aims to provide an overview of globe injury characteristics and their correlation with socioeconomic status and to highlight the significance of considering SES as a variable in globe injury prevention., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Kousiouris et al.)

Purpose of Review: Dementia is a term for loss of memory, language, problem-solving, and other thinking abilities, which significantly interferes with daily life. Certain dementing conditions may also affect visual function. The eye is an accessible window to the brain that can provide valuable information for the early diagnosis of people who suffer from Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies as well as from more rare causes of dementias, such as Creutzfeldt-Jacob and Huntington's diseases. Herein, we present the ocular manifestations of neurocognitive disorders focusing on the neuro-ophthalmic ones and further discuss potential ocular biomarkers that could help in early detection of these disorders., Recent Findings: Ophthalmic examination along with the recent developments in in-vivo testing have provided a strong foundation of useful knowledge about brain disorder in neurodegenerative diseases without the need for invasive studies. Currently, a number of visual measures, such as visual acuity, contrast sensitivity, pupil response, and saccades in addition to various ophthalmic tests, such as electroretinogram, visual evoked potential, optical coherence tomography (OCT), and OCT-angiography have been widely used and evaluated as potential biomarkers for different stages of dementia., Summary: Ophthalmologic and neuro-ophthalmic evaluation is evolving as an important part of the early diagnosis and management of people with dementia. A particular focus on ocular biomarkers in dementing illnesses has arisen over the past few years and there are several promising measures and imaging tools that have been proposed as potential biomarkers for these diseases., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (Her2) - targeted antibody-drug conjugate that is approved for patients previously treated with trastuzumab and a taxane for Her2-positive advanced breast cancer and those who have progressed within 6 months of completion of adjuvant chemotherapy, as well as for patients with residual invasive Her2-positive disease after the completion of adjuvant chemotherapy. Peripheral neuropathy is a common adverse event; however, ocular events have also been described. With the current report we present the case of a 67-year old woman who developed transient grade 2-3 blurred vision after the first T-DM1 infusion, which was complicated with grade 2 diplopia causing vertigo after the second infusion. After extended investigation, this symptomatology was attributed to central neurotoxicity, and gradually resolved after T-DM1 discontinuation., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Ultrasound elastography has become available in everyday practice, allowing direct measurement of tissue elasticity with important and expanding clinical applications. Several studies that have evaluated pathological and non-pathological tissues have demonstrated that ultrasound elastography can actually improve the diagnostic accuracy of the underlying disease process by detecting differences in their elasticity. Ocular and periocular tissues can also be characterized by their elastic properties. In this context, a comprehensive review of literature on ultrasound elastography as well as its current applications in Ophthalmology is presented., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Competing Interests: The authors report no conflicts of interest.

History A 24-year-old right-handed woman presented to a neuro-ophthalmology clinic in Massachusetts in the summer with acute binocular diplopia when looking down and to the left, which started about 1 month earlier. Her medical history was notable for Raynaud syndrome, recurrent streptococcal pharyngitis, and an allergy to amoxicillin. Three days prior to developing diplopia, she presented to an outside emergency department due to fever, chills, and back pain. She received ciprofloxacin for presumed urinary tract infection based on urinalysis, which demonstrated few bacteria and was negative for leukocyte esterase, nitrites, and white blood cells. She then presented again to an outside emergency department for diplopia evaluation. Initial MRI and MR angiography of the brain at that time did not demonstrate any relevant findings, and the patient was referred to our department for neuro-ophthalmic evaluation, where she was seen 4 weeks later. Neuro-ophthalmic examination revealed 20/20 visual acuity in both eyes, and a right hypertropia in left gaze, downgaze and right head tilt, with right eye excyclotorsion. There were no ocular signs of myasthenia gravis or thyroid eye disease, nor did the patient report ocular or systemic symptoms. She denied recent travel. High-spatial-resolution MRI of the brain and orbit were performed.

Competing Interests: The authors report no conflicts of interest.

History A 24-year-old right-handed woman presented to a neuro-ophthalmology clinic in Massachusetts in the summer with acute binocular diplopia when looking down and to the left, which started about 1 month earlier. Her medical history was notable for Raynaud syndrome, recurrent streptococcal pharyngitis, and an allergy to amoxicillin. Three days prior to developing diplopia, she presented to an outside emergency department due to fever, chills, and back pain. She received ciprofloxacin for presumed urinary tract infection based on urinalysis, which demonstrated few bacteria and was negative for leukocyte esterase, nitrites, and white blood cells. She then presented again to an outside emergency department for diplopia evaluation. Initial MRI and MR angiography of the brain at that time did not demonstrate any relevant findings, and the patient was referred to our department for neuro-ophthalmic evaluation, where she was seen 4 weeks later. Neuro-ophthalmic examination revealed 20/20 visual acuity in both eyes, and a right hypertropia in left gaze, downgaze and right head tilt, with right eye excyclotorsion. There were no ocular signs of myasthenia gravis or thyroid eye disease, nor did the patient report ocular or systemic symptoms. She denied recent travel. High-spatial-resolution MRI of the brain and orbit were performed (Figs 1, 2).

Abstract: A 44-year-old woman presented with 2 painful and self-limited episodes of binocular horizontal diplopia within 1 year that at the beginning were thought to be secondary to microvascular insult. Her medical history was significant for Cushing syndrome status post transsphenoidal resection with bilateral adrenalectomy 4 years prior, hypertension, and diabetes mellitus. Neuro-ophthalmic evaluation was significant for left abduction deficit and incomitant esotropia consistent with left abducens nerve palsy. Of note, the patient had experienced a similar episode but on the contralateral side a few months prior. Although initially MRI of the brain demonstrated stable residual postoperative finding in the sella, upon review, an heterogenous T-1 hypointense marrow in the clivus was noted. Hypermetabolism of the clivus was also noted on computed tomography positron emission tomography of the skull base. A clival biopsy demonstrated a corticotroph adenoma with elevated proliferation index and scattered mitoses. A corticotroph pituitary adenoma after adrenalectomy, also known as Nelson syndrome, was diagnosed. Radiation therapy was offered to the patient, and resolution of symptoms was gradually observed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

Purpose of Review: Optic nerve sheath meningiomas (ONSMs) are rare benign tumors of the anterior visual pathway which present with slowly progressive and painless vision loss and account for approximately 2% of all orbital tumors. This article provides an overview as well as an update on the ONSMs with regards to cause, epidemiology, clinical presentation, diagnosis, and management in adults and pediatric population., Recent Findings: The clinical presentation and prognosis of ONSMs can vary and largely depend on the location of tumor as well as the histologic type. Overall, the diagnosis is based on clinical presentation, examination, and neuroimaging findings. Nevertheless, delays in diagnosis or misdiagnosis are not uncommon and can result in higher morbidity rates. Recent advances in diagnostic as well as more effective and less-invasive treatment options are discussed in this review., Summary: ONSMs are a rare cause of slowly progressive and inexorable visual loss. Although ONSM diagnosis depends on the characteristic clinical and radiologic findings, prompt diagnosis, and appropriate management is critical for favorable visual outcomes. Thus, current focus is optimizing diagnostic as well-treatment methods for patients with ONSMs.

Background: Visualization during scleral buckling is traditionally achieved via indirect ophthalmoscopy. Recent advances have utilized the surgical microscope and a 25 gauge cannula-based endoillumination system, also known as a Chandelier lighting system. This report details an improved approach using a guarded 25 or 27 gauge light pipe and the Ngenuity digital three dimensional platform., Methods: A standard Alcon light pipe is modified with a silicone guard to expose only 5 mm of the tip of the light pipe. The guard is created from the silicone that is already opened to secure the ends of the encircling band most often employed sleeve (e.g. 70, 270). This guarded light pipe is then inserted into the cannula as an alternative to a Chandelier lighting system., Results: This is a technical report of a surgical visualization technique using a three dimensional digital visualization platform with a modified handheld vitrectomy light pipe., Conclusion: The utilization of a guarded light pipe for visualization during primary scleral buckling is a promising, effective, and efficient technique. The three dimensional digital display allows for better educational impact and surgical communication with trainees and ancillary members of the surgical team., Competing Interests: Competing interestsDr. Miller is a consultant for Alcon., (© The Author(s) 2020.)

A healthy 56-year-old man presented with vision changes and left upper extremity motor and sensory changes. MRI of the brain without contrast was significant for multifocal areas of restricted diffusion in multiple vascular territories. Neuro-Ophthalmic evaluation revealed an inferonasal visual field defect in the left eye, thickened choroid on optical coherence tomography, and bilateral delayed arteriovenous and choroidal filling on fluorescein angiogram. Repeat MRI demonstrated interval enlargement of many of the same foci of abnormal diffusion-weighted imaging signal. Computed tomography of the abdomen and pelvis revealed 3 distinct lobulated retroperitoneal masses that were biopsied and found to be consistent with diffuse large B-cell lymphoma. Brain biopsy specimens showed intravascular lymphocytes, confirming a diagnosis of intravascular lymphoma (IVL). In this diagnostically challenging case, a link was established between the presence of multiple strokes (some of which showed slow evolution over time) and retinochoroidal hypoperfusion, which provided a critical clue to the ultimate diagnosis of IVL.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in the city of Wuhan in December of 2019 and since then more than 5,000,000 people have been infected, with approximately 338,000 deaths worldwide. The virus causes the coronavirus disease 2019 (COVID-19), which is characterized by fever, myalgia and cough, with severe acute respiratory syndrome being the most fearsome complication. Nevertheless, the vast majority of cases present mild symptoms or none. Central nervous system and cardiovascular manifestations have been reported. The range of ocular manifestations, either as a result of the infection or as a result of the treatment, has not yet been discussed. In this study, a systematic review of current literature relevant to COVID-19 was performed with focus on modes of transmission, ocular manifestations related to infection and medications, as well as the control of infection in ophthalmic practice., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose of Review: Immune checkpoint inhibitors are currently an exceedingly powerful tool in the management of hitherto incurable malignancies and their use in clinical practice is expected to increase in the near future. The purpose of this review is to discuss the current medical uses of checkpoint inhibitors with a focus on their neuro-ophthalmic side-effects., Recent Findings: Immune checkpoint inhibitors have emerged as a promising breakthrough in the treatment of several tumor types. However, these targeted therapies can induce a wide range of immune-related ophthalmic and neuro-ophthalmic toxicities. It is important for neuro-ophthamologists to promptly recognize and manage these adverse events that can potentially threaten vision., Summary: There are currently seven FDA-approved immune checkpoint inhibitors and several ones are under investigation. In general, immunotherapy is considered a well tolerated, safe and efficacious treatment option for many cancer patients. Nevertheless, because of their unique mechanism of action, these molecules can alter the immune response and result in immune-related adverse effects in almost every organ with an estimated incidence of ophthalmic side effects in this patient population of less than 1%.

Aims: GLP-1 analogs have recently risen to the forefront as effective medications for lowering weight through actions in the central nervous system (CNS). However, their actions in the CNS have not yet been studied in the human brain after longer-term administration at the highest dose approved for obesity (liraglutide 3.0 mg)., Materials and Methods: A total of 20 participants with obesity were treated with placebo and liraglutide (3.0 mg) in the context of a randomized, placebo-controlled, double-blind, cross-over trial after 5 weeks of dose escalation. Neurocognitive and neuroimaging (fMRI) responses to food cues were examined at the clinical research center of Beth Israel Deaconess Medical Center., Results: While using liraglutide, patients lost more weight (placebo-subtracted -2.7%; P < .001), had decreased fasting glucose (P < .001) and showed improved cholesterol levels. In an uncontrolled analysis, brain activation in response to food images was not altered by liraglutide vs placebo. When controlled for BMI/weight, liraglutide increased activation of the right orbitofrontal cortex (OFC) in response to food cues (P < .016, corrected for multiple comparisons)., Conclusions: In contrast to prior studies, we demonstrate for the first time that liraglutide treatment, administered over a longer period at the highest doses approved for obesity, does not alter brain activation in response to food cues. A counter-regulatory increase in reward-related OFC activation in response to food cues can be observed when neuroimaging data are controlled for BMI changes, indicating changes in CNS that could lead to later plateaus of weight loss. These data point to a promising focus for additional interventions which, by contributing to the CNS reward system, could provide tangible benefits in reversing the plateauing phenomenon and promoting further weight loss., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Purpose of Review: The phakomatoses are a group of inherited disorders with variable clinical manifestations that are characterized by brain, cutaneous, ocular and other distinct lesions in multiple organs. Correctly recognizing the neuro-ophthalmic signs and symptoms can lead to early diagnosis and treatment. The group is composed of neurofibromatosis (type 1 and 2), tuberous sclerosis complex, von Hippel-Lindau, ataxia-telangiectasia and Sturge-Weber syndromes. However, more than 60 syndromes have been described in the medical literature. This review provides an update on the diagnosis and management of phakomatoses with a focus on their clinical neuro-ophthalmic manifestations., Recent Findings: Phakomatoses are a group of inherited syndromes with variable clinical manifestations that are characterized by brain, cutaneous, ocular and other distinct lesions in multiple organs. Recent advances in diagnostic and treatment options that have contributed to prompt recognition and management of these disorders are discussed with an emphasis on the beneficial effects on vision., Summary: Phakomatoses, also known as neuro-oculo-cutaneous syndromes, are inherited disorders with characteristic lesions in multiple organs. Because of their frequent ocular involvement thorough ophthalmologic and neuro-ophthalmic evaluation is critical in this patient population in order to prevent vision loss and life-threatening complications that are often associated with these disorders.

Introduction: Significant advances in three-dimensional (3D) imaging technology have allowed for the incorporation of 3D digital displays into medical and surgical devices. Despite initial adoption of the NGENUITY ® 3D Visualization System in vitreoretinal surgery, there are limited publications regarding its use. The generally accepted main benefits include improved ergonomics, enhanced surgical team communication and education, reduced retinal phototoxicity, increased depth of field, and display image manipulation. Despite these potential benefits, many retina specialists have questioned its universal applicability to a wide variety of vitreoretinal surgeries., Objective: To report on the variety of indications and surgical efficacy of the NGENUITY ® 3D Visualization System in vitreoretinal surgery via a review of surgical experience at two vitreoretinal practices in both the academic and community settings., Methods: A retrospective review was conducted of consecutive surgical cases performed on the NGENUITY ® 3D Visualization System at Massachusetts Eye and Ear Infirmary and Florida Retina Institute from June 1st, 2017 to November 1st, 2018. Age, presenting diagnosis, surgical procedure, and intraoperative details were recorded., Results: 272 vitreoretinal surgeries on the Alcon NGENUITY ® 3D Visualization System were identified between June 1st, 2017 and November 1st, 2018 at the participating institutions. A detailed breakdown of the indications for surgery and related procedures is reported. During all 272 cases on the 3D digital system, there were no complications attributed to the visualization system., Conclusion: This series illustrates the diversity of vitreoretinal surgeries that can be performed on this system without compromising surgical viewing or increasing surgical complications. The Alcon NGENUITY ® 3D Visualization System possesses favorable ergonomics, illumination levels, depth of field, display filters, and trainee experience., Competing Interests: John B Miller and Samuel K Houston III report personal fees from Alcon, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2019 Agranat et al.)

Patients with type 2 diabetes mellitus (T2DM) develop thrombotic abnormalities strongly associated with cardiovascular diseases. In addition to the changes of numerous coagulation factors such as elevated levels of thrombin and fibrinogen, the abnormal rheological effects of red blood cells (RBCs) and platelets flowing in blood are crucial in platelet adhesion and thrombus formation in T2DM. An important process contributing to the latter is the platelet margination. We employ the dissipative particle dynamics method to seamlessly model cells, plasma, and vessel walls. We perform a systematic study on RBC and platelet transport in cylindrical vessels by considering different cell shapes, sizes, and RBC deformabilities in healthy and T2DM blood, as well as variable flowrates and hematocrit. In particular, we use cellular-level RBC and platelet models with parameters derived from patient-specific data and present a sensitivity study. We find T2DM RBCs, which are less deformable compared to normal RBCs, lower the transport of platelets toward the vessel walls, whereas platelets with higher mean volume (often observed in T2DM) lead to enhanced margination. Furthermore, increasing the flowrate or hematocrit enhances platelet margination. We also investigated the effect of platelet shape and observed a nonmonotonic variation with the highest near-wall concentration corresponding to platelets with a moderate aspect ratio of 0.38. We examine the role of white blood cells (WBCs), whose count is increased notably in T2DM patients. We find that WBC rolling or WBC adhesion tends to decrease platelet margination due to hydrodynamic effects. To the best of our knowledge, such simulations of blood including all blood cells have not been performed before, and our quantitative findings can help separate the effects of hydrodynamic interactions from adhesive interactions and potentially shed light on the associated pathological processes in T2DM such as increased inflammatory response, platelet activation and adhesion, and ultimately thrombus formation., (Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.)