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Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A. Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow 2023 Florida Atlantic University

Autophagy Requirements For Eye Lens Differentiation And Transparency, Lisa Brennan, M Joseph Costello, J Fielding Hejtmancik, A. Menko, S Amer Riazuddin, Alan Shiels, Marc Kantorow

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Recent evidence points to autophagy as an essential cellular requirement for achieving the mature structure, homeostasis, and transparency of the lens. Collective evidence from multiple laboratories using chick, mouse, primate, and human model systems provides evidence that classic autophagy structures, ranging from double-membrane autophagosomes to single-membrane autolysosomes, are found throughout the lens in both undifferentiated lens epithelial cells and maturing lens fiber cells. Recently, key autophagy signaling pathways have been identified to initiate critical steps in the lens differentiation program, including the elimination of organelles to form the core lens organelle-free zone. Other recent studies using ex vivo lens culture …


Refractory Age-Related Macular Degeneration Due To Concurrent Central Serous Chorioretinopathy In Previously Well-Controlled Eyes, Chikako Hara, Taku Wakabayashi, Kaori Sayangi, Kohji Nishida 2023 Osaka University

Refractory Age-Related Macular Degeneration Due To Concurrent Central Serous Chorioretinopathy In Previously Well-Controlled Eyes, Chikako Hara, Taku Wakabayashi, Kaori Sayangi, Kohji Nishida

Wills Eye Hospital Papers

Background: During the treatment of age-related macular degeneration with anti-vascular endothelial growth factor (VEGF) drugs, we often see cases with anti-VEGF-resistant refractory subretinal fluid. In this report, we present two cases of anti-VEGF-resistant refractory age-related macular degeneration (AMD) due to the concurrent development of central serous chorioretinopathy (CSCR) in eyes previously well controlled with intravitreal anti-VEGF injections. Case presentation: Two patients underwent intravitreal aflibercept for the treatment of neovascular AMD. Initially, both patients responded well to intravitreal aflibercept, resulting in the complete resolution of the subretinal fluid. However, both patients subsequently developed sudden-onset refractory subretinal fluid that did not respond …


Direct Selective Laser Trabeculoplasty In Open Angle Glaucoma Study Design: A Multicentre, Randomised, Controlled, Investigator-Masked Trial (Glaurious), Nathan Congdon, Augusto Azuara-Blanco, Yoram Solberg, Carlo E Traverso, Michele Iester, Carlo Alberto Cutolo, Alessandro Bagnis, Tin Aung, Scott J Fudemberg, Richard Lindstrom, Thomas Samuelson, Kuldev Singh, Eytan Z Blumenthal, Gus Gazzard, GLAUrious study group 2023 Queen's University Belfast

Direct Selective Laser Trabeculoplasty In Open Angle Glaucoma Study Design: A Multicentre, Randomised, Controlled, Investigator-Masked Trial (Glaurious), Nathan Congdon, Augusto Azuara-Blanco, Yoram Solberg, Carlo E Traverso, Michele Iester, Carlo Alberto Cutolo, Alessandro Bagnis, Tin Aung, Scott J Fudemberg, Richard Lindstrom, Thomas Samuelson, Kuldev Singh, Eytan Z Blumenthal, Gus Gazzard, Glaurious Study Group

Wills Eye Hospital Papers

Introduction: Laser trabeculoplasty is an effective and widely used treatment for glaucoma. A new laser technology, the Eagle direct selective laser trabeculoplasty (DSLT) device, may provide automated, fast, simple, safe and effective laser treatment for glaucoma in a broader range of clinical settings. This trial aims to test the hypothesis that translimbal DSLT is effective and not inferior to selective laser trabeculoplasty (SLT) in reducing intraocular pressure (IOP) in open angle glaucoma (OAG).

Methods and analysis: This is a multicentre, randomised, controlled, investigator-masked study. The primary efficacy outcome is intergroup difference in mean change from baseline IOP measured at 6 …


Late Descemet Membrane Detachment After Uneventful Cataract Surgery, Lovaglio Cançado Trindade, Renata Attanasio de Rezende, Tiago Bisol, Christopher J Rapuano 2022 Medical Sciences Medical School-FELUMA

Late Descemet Membrane Detachment After Uneventful Cataract Surgery, Lovaglio Cançado Trindade, Renata Attanasio De Rezende, Tiago Bisol, Christopher J Rapuano

Wills Eye Hospital Papers

Purpose: To report 5 patients with late Descemet membrane (DM) detachment after uneventful cataract surgery.

Observations: After a retrospective chart analysis of consecutive patients that developed DM detachment after uneventful cataract surgery, six eyes of five patients were enrolled. In all cases, patients reported good vision initially after cataract surgery. Within days to months, these patients developed late DM detachment with decreased vision. In one patient, the detachment affected both eyes. Filtered air or diluted sulfur hexafluoride were injected in the anterior chamber to tamponade the DM detachment. In five eyes, the cornea cleared after DM reattachment. In two eyes …


The Associations Between Central Serous Chorioretinopathy And Muscle Relaxants: A Case-Control Study, Manish Jain, Sunir J. Garg, Mohammad Khan, Varun Chaudhary, Dena Zeraatkar, Dhanya Kurian, Sarath Lal 2022 Government Institute of Medical Sciences and Research, Uttarakhand

The Associations Between Central Serous Chorioretinopathy And Muscle Relaxants: A Case-Control Study, Manish Jain, Sunir J. Garg, Mohammad Khan, Varun Chaudhary, Dena Zeraatkar, Dhanya Kurian, Sarath Lal

Wills Eye Hospital Papers

PURPOSE: To evaluate the role of muscle-relaxants as risk factors for the development of central serous chorioretinopathy (CSC) - the second most common retinopathy in our settings; despite multiple risk factors seen in our patients, 21% were initially labelled as idiopathic.

MATERIALS AND METHODS: Retrospective case-control study at a tertiary hospital in the United Arab Emirates, where we reviewed the medical records of 273 patients with CSC examined between 2010 and 2019 for use of muscle-relaxants including tolperisone/eperisone, carisoprodol and gabapentin/pregabalin within a year of onset/recurrence of the disease. Intake of drugs with known association with CSC (including corticosteroids/sympathomimetics) was …


Study Design And Baseline Characteristics For The Reflect Gene Therapy Trial Ofm.11778g>A/Nd4-Lhon, Prem S. Subramanian, Nancy J. Newman, Mark Moster, An-Guor Wang, Patrick Yu-Wai-Man, Sean Donahue, Bart P. Leroy, Valerio Carelli, Valerie Biousse, Catherine Vignal-Clermont, Robert C. Sergott, Alfredo A. Sadun, Gema Rebolleda, Bart K. Chwalisz, Rudrani Banik, Fabienne Bazin, Eric Cox, Michel Roux, Magali Taiel, Jose-Alain Sahel 2022 University of Colorado

Study Design And Baseline Characteristics For The Reflect Gene Therapy Trial Ofm.11778g>A/Nd4-Lhon, Prem S. Subramanian, Nancy J. Newman, Mark Moster, An-Guor Wang, Patrick Yu-Wai-Man, Sean Donahue, Bart P. Leroy, Valerio Carelli, Valerie Biousse, Catherine Vignal-Clermont, Robert C. Sergott, Alfredo A. Sadun, Gema Rebolleda, Bart K. Chwalisz, Rudrani Banik, Fabienne Bazin, Eric Cox, Michel Roux, Magali Taiel, Jose-Alain Sahel

Wills Eye Hospital Papers

Objective REFLECT is the first randomised, double-masked, placebo-controlled multicentre phase 3 clinical trial that evaluated the efficacy and safety of bilateral intravitreal (IVT) injection of lenadogene nolparvovec in subjects with Leber hereditary optic neuropathy carrying the m.11778G>A mutation.

Methods and analysis A total of 98 subjects were enrolled with vision loss of ≤12 months. The subjects were randomised to one of two treatment arms with all subjects receiving an intravitreal (IVT) injection of lenadogene nolparvovec in their first affected eye and the second-affected eye randomised to receive IVT of either lenadogene nolparvovec or placebo.

Results The majority of subjects …


Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman 2022 Thomas Jefferson University

Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman

Wills Eye Hospital Papers

Purpose: To report three patients with an uncommon delayed complication of cataract extraction: corneal edema following dispersion of calcific lens particles from a degenerating Soemmering ring cataract.

Observations: We report three patients, 75-92 years old, presenting with corneal edema and dispersed, degenerated calcific lens material in the anterior chamber and vitreous 20-30 years after cataract surgery. In all patients, calcific particles studded the posterior surface of the cornea in a gravity-dependent distribution without apparent inflammation and were associated with localized corneal edema. In one patient, calcific particles were also associated with secondary open angle glaucoma. Deposits originated from the calcified …


Frosted Branch Angiitis Presenting After A Sars-Cov-2 Infection., Akhila Alapati, Nathaniel Cameron, Sean Gratton, Erin Stahl, Mary Champion 2022 Children's Mercy Kansas City

Frosted Branch Angiitis Presenting After A Sars-Cov-2 Infection., Akhila Alapati, Nathaniel Cameron, Sean Gratton, Erin Stahl, Mary Champion

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: To report a case of frosted branch angiitis presenting in a pediatric patient with unremarkable laboratory work-up apart from SARS-CoV-2 IgG antibodies.

OBSERVATIONS: Less than four weeks after a SARS-CoV-2 infection, a 10 year-old female presented to the emergency department with severe headache and intermittent fevers. During her hospital admission, the ophthalmology service was consulted for blurry vision. Subsequent eye examination revealed frosted branch angiitis. The patient initially received intravenous corticosteroids but was escalated to plasmapheresis to achieve resolution of her symptoms. Outpatient maintenance therapy consisted of an oral Prednisone taper and Infliximab infusion.

CONCLUSION AND IMPORTANCE: This case …


Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker 2022 Thomas Jefferson University

Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and …


Safety Of Simultaneous Bilateral Intravitreal Versus Unilateral Anti-Vasculo-Endothelial Growth Factors Injection In An Operating Room Setting, Irfan Kabiruddin Jeeva, Sidra Masud, Rehman Siddiqui, Hadees Murad Fahad 2022 Aga Khan University Hospital

Safety Of Simultaneous Bilateral Intravitreal Versus Unilateral Anti-Vasculo-Endothelial Growth Factors Injection In An Operating Room Setting, Irfan Kabiruddin Jeeva, Sidra Masud, Rehman Siddiqui, Hadees Murad Fahad

Department of Ophthalmology

Objectives: Chorioretinal diseases requiring the use of anti-vascular endothelial growth (anti-VEGF) injections often occur in both eyes simultaneously. This can necessitate injecting both eyes together rather than one eye at a time. The purpose of the study was to determine whether simultaneous bilateral intravitreal injections of anti-VEGF agents are safe when administered in an operation theatre setting.
Methods: Retrospective review of data was conducted. Single center study conducted in a tertiary care hospital in Karachi Pakistan. Approximately 30,000 eyes that received anti-VEGF injection during a 10-year study period were included (March 2008-February 2018). Patients who were lost to follow up …


A Reactivation Of Ocular Toxoplasmosis During Pregnancy, Brett Garee OD, MS, Sarah Dieter OD, Pete Liette OD 2022 Department of Veterans Affairs

A Reactivation Of Ocular Toxoplasmosis During Pregnancy, Brett Garee Od, Ms, Sarah Dieter Od, Pete Liette Od

Optometric Clinical Practice

Background: Toxoplasma gondii is a parasite estimated to affect over 500 million people worldwide. The feline is the definitive host for the parasite and infection may be acquired or congenital via maternal transmission. Humans may acquire the infection by ingestion of raw or undercooked meats and vegetables, contaminated water, or exposure to infected cat feces. The infection is often benign, self-limiting, and asymptomatic for humans, but potentially life threatening to infants or the immunocompromised patient.

Case Report: A 22 year-old Caucasian female, pregnant at 12 weeks gestation, presented to the optometry service with acute symptoms of hazy vision …


Advances In Retinopathy Of Prematurity Imaging, Taku Wakabayashi, Samir N. Patel, J. P. Campbell, Emmanuel Y. Chang, Eric D. Nudleman, Yoshihiro Yonekawa 2022 Thomas Jefferson University

Advances In Retinopathy Of Prematurity Imaging, Taku Wakabayashi, Samir N. Patel, J. P. Campbell, Emmanuel Y. Chang, Eric D. Nudleman, Yoshihiro Yonekawa

Wills Eye Hospital Papers

Retinopathy of prematurity (ROP) remains the leading cause of childhood blindness worldwide. Recent advances in ROP imaging have significantly improved our understanding of the pathogenesis and pathophysiological course of ROP including the acute phase, regression, reactivation, and late complications, known as adult ROP. Recent progress includes various contact and noncontact wide-field imaging devices for fundus imaging, smartphone-based fundus photography, wide-field fluorescein angiography, handheld optical coherence tomography (OCT) devices for wide-field en face OCT images, and OCT angiography. Images taken by those devices were incorporated in the recently updated guidelines of ROP, the International Classification of Retinopathy of Prematurity, Third Edition …


Ophthalmology Consult Order: “Rule Out Open Globe Injury, Ellen Ingram, Matthew Williams, Kevin Kirchner 2022 LSU Health Sciences Center- New Orleans

Ophthalmology Consult Order: “Rule Out Open Globe Injury, Ellen Ingram, Matthew Williams, Kevin Kirchner

Medical Research Day

Out of traumatic eye injuries, open globe injuries are associated with the highest patient morbidity. Computed tomography (CT) imaging of the orbits is routinely used by the emergency department physician during workup of traumatic eye injuries. Positive CT findings reliably indicate penetration of the globe with a specificity up to 98% [1]. However, studies have consistently shown that CT imaging fails to diagnose approximately 30% of open globe injuries [1,2]. Therefore, a negative CT scan does not definitively rule out an open globe. There are no defined exam parameters that have been established as reliable indicators for open globe injuries …


Night Vision Restored In Days After Decades Of Congenital Blindness, Samuel G Jacobson, Artur V Cideciyan, Allen Ho, Alejandro J Roman, Vivian Wu, Alexandra V Garafalo, Alexander Sumaroka, Arun K Krishnan, Malgorzata Swider, Abraham A Mascio, Christine N Kay, Dan Yoon, Kenji P Fujita, Sanford L Boye, Igor V Peshenko, Alexander M Dizhoor, Shannon E Boye 2022 University of Pennsylvania

Night Vision Restored In Days After Decades Of Congenital Blindness, Samuel G Jacobson, Artur V Cideciyan, Allen Ho, Alejandro J Roman, Vivian Wu, Alexandra V Garafalo, Alexander Sumaroka, Arun K Krishnan, Malgorzata Swider, Abraham A Mascio, Christine N Kay, Dan Yoon, Kenji P Fujita, Sanford L Boye, Igor V Peshenko, Alexander M Dizhoor, Shannon E Boye

Wills Eye Hospital Papers

Signaling of vision to the brain starts with the retinal phototransduction cascade which converts visible light from the environment into chemical changes. Vision impairment results when mutations inactivate proteins of the phototransduction cascade. A severe monogenically inherited blindness, Leber congenital amaurosis (LCA), is caused by mutations in the GUCY2D gene, leading to a molecular defect in the production of cyclic GMP, the second messenger of phototransduction. We studied two patients with GUCY2D-LCA who were undergoing gene augmentation therapy. Both patients had large deficits in rod photoreceptor-based night vision before intervention. Within days of therapy, rod vision in both …


Suspicious Retinal Lesion With A Distinctive Appearance, G Brandon Caudill, Mrittika Sen, Carol L. Shields 2022 Thomas Jefferson University

Suspicious Retinal Lesion With A Distinctive Appearance, G Brandon Caudill, Mrittika Sen, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.


Global Current Practice Patterns For The Management Of Hyphema, Sarah C Miller, Prajna Meeralakshmi, Michael J Fliotsos, Grant A Justin, Yoshihiro Yonekawa, Ariel Chen, Annette K Hoskin, Richard J Blanch, Kara M Cavuoto, Rebecca Low, Ximin Li, Matthew Gardiner, T Y Alvin Liu, Ankoor S Shah, James D Auran, Rupesh Agrawal, Fasika A Woreta, International Globe and Adnexal Trauma Epidemiology Study (IGATES) 2022 Johns Hopkins University School of Medicine

Global Current Practice Patterns For The Management Of Hyphema, Sarah C Miller, Prajna Meeralakshmi, Michael J Fliotsos, Grant A Justin, Yoshihiro Yonekawa, Ariel Chen, Annette K Hoskin, Richard J Blanch, Kara M Cavuoto, Rebecca Low, Ximin Li, Matthew Gardiner, T Y Alvin Liu, Ankoor S Shah, James D Auran, Rupesh Agrawal, Fasika A Woreta, International Globe And Adnexal Trauma Epidemiology Study (Igates)

Wills Eye Hospital Papers

Purpose: Hyphema is a sequela of ocular trauma and can be associated with significant morbidity. Management of this condition is variable and can depend on individual institutional guidelines. We aimed to summarize current practices in hyphema management across ophthalmological institutions worldwide.

Methods: A cross-sectional online survey was conducted across North America, Asia, South America, Africa, Europe, and Australia from August 2020 to January 2021. The survey assessed the existing practices in the management of hyphema at each institution.

Results: For layered hyphema, topical steroids were routinely administered by 34 (of 36 respondents, 94.4%) institutions, of which prednisolone was the preferred …


Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma., Mak B Djulbegovic, David J Taylor, Vladimir N Uversky, Anat Galor, Carol L Shields, Carol L Karp 2022 University of Miami

Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma., Mak B Djulbegovic, David J Taylor, Vladimir N Uversky, Anat Galor, Carol L Shields, Carol L Karp

Wills Eye Hospital Papers

BACKGROUND: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM.

METHODS: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms.

RESULTS: We show that BAP1's structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1's intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p …


Coats Plus Syndrome With New Observation Of Drusenoid Retinal Pigment Epithelial Detachments In A Teenager, Kushal U. Agrawal, Nicholas E. Kalafatis, Carol L. Shields 2022 Thomas Jefferson University

Coats Plus Syndrome With New Observation Of Drusenoid Retinal Pigment Epithelial Detachments In A Teenager, Kushal U. Agrawal, Nicholas E. Kalafatis, Carol L. Shields

Wills Eye Hospital Papers

Purpose: To describe a case of Coats Plus Syndrome (CPS), a vision and life threatening disease belonging to a family of diseases known as the Telomere Biology Disorders.

Observations: A 15-year-old girl with a history of small for gestational age, short stature, microcephaly, thinning/ greying of scalp hair, skin hyperpigmentation, nail ridging, and multiple pathological fractures presented with bilateral Coats-like retinopathy. We discovered a new observation of multiple peripheral pinpoint retinal pigment epithelial detachments (PEDs). Further genetic testing revealed CTC1 gene mutation and she was diagnosed with Coats plus syndrome with features of dyskeratosis congenita, a telomere biology disorder.

Conclusion …


Tnf-Α And Nf-Κb Signaling Play A Critical Role In Cigarette Smoke-Induced Epithelial-Mesenchymal Transition Of Retinal Pigment Epithelial Cells In Proliferative Vitreoretinopathy, Victor Wang, Alison Heffer, Elisa Roztocil, Steven E Feldon, Richard T Libby, Collynn F Woeller, Ajay E Kuriyan 2022 University of Rochester Medical Center

Tnf-Α And Nf-Κb Signaling Play A Critical Role In Cigarette Smoke-Induced Epithelial-Mesenchymal Transition Of Retinal Pigment Epithelial Cells In Proliferative Vitreoretinopathy, Victor Wang, Alison Heffer, Elisa Roztocil, Steven E Feldon, Richard T Libby, Collynn F Woeller, Ajay E Kuriyan

Wills Eye Hospital Papers

Proliferative vitreoretinopathy (PVR) is characterized by the growth and contraction of cellular membranes within the vitreous cavity and on both surfaces of the retina, resulting in recurrent retinal detachments and poor visual outcomes. Proinflammatory cytokines like tumor necrosis factor alpha (TNFα) have been associated with PVR and the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. Cigarette smoke is the only known modifiable risk factor for PVR, but the mechanisms are unclear. The purpose of this study was to examine the impact of cigarette smoke on the proinflammatory TNFα/NF-κB/Snail pathway in RPE cells to better understand the mechanisms through …


Wellness Study: Functional Visual Outcomes In Eye Disease Patients Following The Covid-19 Pandemic, Andrew Maher 2022 Western University

Wellness Study: Functional Visual Outcomes In Eye Disease Patients Following The Covid-19 Pandemic, Andrew Maher

Undergraduate Student Research Internships Conference

The COVID-19 pandemic has caused delays in health services and medical appointments, affecting approximately one in three Canadian adults. Elderly eye disease patients experienced delays in treatment for eye conditions including cataracts, glaucoma, and retinal diseases. The impact of these delays on functional visual outcomes and general health rating of elderly patients is not well understood. As part of the Wellness Study, we aimed to investigate the pandemic-related impacts on functional vision and general health rating in an elderly eye patient population in London, Ontario.


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