Ophthalmology Commons^™

Sakurabonsai: Protocol Design Of A Novel, Prospective Study To Explore Clinical, Imaging, And Biomarker Outcomes In Patients With Aqp4-Igg-Seropositive Neuromyelitis Optica Spectrum Disorder Receiving Open-Label Satralizumab, Jeffrey L Bennett, Kazuo Fujihara, Ho Jin Kim, Romain Marignier, Kevin C O'Connor, Robert C Sergott, Anthony Traboulsee, Heinz Wiendl, Jens Wuerfel, Scott S Zamvil, Veronica G Anania, Regine Buffels, Thomas Künzel, Annemarie N Lekkerkerker, Siân Lennon-Chrimes, Sean J Pittock

Wills Eye Hospital Papers

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD.

Objectives: …

Severe Ocular Alkali Injury Managed With An Externally Sutured Amniotic Membrane And Customized Symblepharon Ring, Sophia S. Lam, Bonnie Sklar, Marisa Schoen, Christopher J. Rapuano

Student Papers, Posters & Projects

Alkali injuries are ocular emergencies that require immediate evaluation and therapy to preserve vision. Severe alkali injuries can result in long‑term vision‑threatening sequelae including symblepharon, corneal ulceration, corneal scarring, limbal stem cell deficiency, xerophthalmia, cicatricial changes of the eyelid and adnexa, glaucoma, uveitis, and permanent vision loss. Treatment is aimed at neutralizing the pH, controlling inflammation, and restoring the ocular surface. Here, we present the case of a 35‑year‑old male who sustained direct ocular exposure to sodium hydroxide, resulting in significant corneal and conjunctival epithelial defects despite aggressive initial medical therapy. The patient subsequently received a large, externally sutured amniotic …

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 …

Risk Factors For Strabismus Surgery After Pediatric Cataract Surgery In The United States, Bryce Hwang, Isdin Oke, Scott R. Lambert

Wills Eye Hospital Papers

Purpose: To determine the cumulative incidence of strabismus surgery after pediatric cataract surgery and identify the associated risk factors.

Design: US population-based insurance claims retrospective cohort study.

Participants: Patients ≤ 18 years old who underwent cataract surgery in 2 large databases: Optum Clinformatics Data Mart (2003e2021) and IBM MarketScan (2007e2016). Methods: Individuals with at least 6 months of prior enrollment were included, and those with a history of strabismus surgery were excluded. The primary outcome was strabismus surgery within 5 years of cataract surgery. The risk factors investigated included age, sex, persistent fetal vasculature (PFV), intraocular lens (IOL) placement, nystagmus …

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

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

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 …

Safety Of Lenadogene Nolparvovec Gene Therapy Over 5 Years In 189 Patients With Leber Hereditary Optic Neuropathy, Catherine Vignal-Clermont, Patrick Yu-Wai-Man, Nancy J. Newman, Valerio Carelli, Mark L. Moster, Valerie Biousse, Prem S. Subramanian, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Alfredo A. Sadun, Thomas Klopstock, Robert C. Sergott, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Magali Taiel, Michel Roux, José-Alain Sahel

Wills Eye Hospital Papers

Purpose

To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy.

Design

Pooled analysis of safety data from 5 clinical studies.

Methods

A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2.

Results

Almost all patients (95.2%) received 9 × …

Indirect Comparison Of Lenadogene Nolparvovec Gene Therapy Versus Natural History In Patients With Leber Hereditary Optic Neuropathy Carrying The M.11778g>A Mt-Nd4 Mutation, Valerio Carelli, Nancy J. Newman, Patrick Yu-Wai-Man, Valerie Biousse, Mark L. Moster, Prem S. Subramanian, Catherine Vignal-Clermont, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Gema Rebolleda Fernández, Bart K. Chwalisz, Rudrani Banik, Jean François Girmens, Chiara La Morgia, Adam A. Debusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, François Montestruc, Michel Roux, Magali Taiel, José-Alain Sahel

Wills Eye Hospital Papers

INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174.

METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 …

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

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

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 …

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 …

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 …

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

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)

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

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 …