Ophthalmology Commons^™

Off Label Innovation: Discovering New Uses For Glaucoma Drops, Glenn Oh

inSIGHT

Dr. Jason Hsu and his team (Ophthalmic Consultants of Boston, Boston, Massachusetts; Retinal Consultants of Houston, Houston, Texas; Retina Service of Wills Eye Hospital and Mid Atlantic Retina, Philadelphia, Pennsylvania; Associated Retinal Consultants, Royal Oak, Michigan) performed a multicenter randomized placebo-controlled clinical trial in which patients with nAMD who were suboptimal responders despite frequent anti-VEGF injections were randomized to use either dorzolamide-timolol drops or artificial tears.16 Eligible patients were 45 years or older with nAMD who were receiving ranibizumab or aflibercept injections at 4 - 6 week intervals (i.e., at least four injections within six months prior to enrollment) and …

A Career Of Honor And Humility: Interview With A Pioneer In Ophthalmology, Eli Cehelyk

inSIGHT

Imagine being a first-time parent in your early 30s, and you have just learned that your three-month old infant has retinoblastoma. Thanksgiving is right around the corner and you have no idea what the future holds. How would you feel? What thoughts would be racing through your head? With both hope and anxiety, you make an appointment at Wills Eye to see Dr. Carol Shields, a world-renowned expert on ocular oncology. With confidence and compassion, she walks into the room with her entire team and says, “Don’t worry, we will get everything under control for you. We will take your …

An Experience In The Wills Academic Global Ophthalmology Fellowship And Beyond, Crystal Lee, Mph

inSIGHT

Even before medical school, Dr. John Anhalt knew he wanted to serve communities all over the globe—after college, he joined the Peace Corps for two years, teaching math and science in the Kingdom of Lesotho. After seeing the vast differences between the health care in Lesotho and in the United States, Dr. Anhalt was inspired to apply to medical school with the intention of pursing a specialty in infectious disease before launching a career in global medicine. It was not until his ophthalmology rotation in University of Texas San Antonio, that he realized that ophthalmology, with its mix of medical …

Insight, Volume 1, Issue 1, 2021

inSIGHT

Contents

10 - An Experience in the Wills Academic Global Ophthalmology Fellowship and Beyond
By Crystal Lee

14 - A Career of Honor and Humility: Interview with a Pioneer in Ophthalmology
By Eli Cehelyk

19 - Off Label Innovation: Discovering New Uses for Glaucoma Drops
By Glenn Oh

22 - The Present and Future of Artificial Intelligence in Ophthalmology
By Robert Abishek & Elliot Cherkas

26 - An Inside Look: Oculoplastics and “Droopy Eyelids”
By Payton Boere

31 - Narrative Medicine in Ophthalmology
By Martina Rama

Single-Cell Transcriptomics Identifies Limbal Stem Cell Population And Cell Types Mapping Its Differentiation Trajectory In Limbal Basal Epithelium Of Human Cornea, De-Quan Li, Sangbae Kim, Jin-Miao Li, Qianmiao Gao, Jongsu Choi, Fang Bian, Jiaoyue Hu, Yun Zhang, Jin Li, Rong Lu, Yumei Li, Stephen C Pflugfelder, Hongyu Miao, Rui Chen

Faculty, Staff and Students Publications

PURPOSE: This study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution.

METHODS: Single cells of human limbal basal epithelium were isolated from young donor corneas. Single-cell RNA-Sequencing was performed using 10x Genomics platform, followed by clustering cell types through the graph-based visualization method UMAP and unbiased computational informatic analysis. Tissue RNA in situ hybridization with RNAscope, immunofluorescent staining and multiple functional assays were performed using human corneas and limbal epithelial culture models.

RESULTS: Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters belonging to three lineages. …

Resident Immune Cells Of The Avascular Lens: Mediators Of The Injury And Fibrotic Response Of The Lens., A. Menko, Jodirae Dedreu, Caitlin M. Logan, Heather Paulson, Alex V Levin, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Tissues typically harbor subpopulations of resident immune cells that function as rapid responders to injury and whose activation leads to induction of an adaptive immune response, playing important roles in repair and protection. Since the lens is an avascular tissue, it was presumed that it was absent of resident immune cells. Our studies now show that resident immune cells are a shared feature of the human, mouse, and chicken lens epithelium. These resident immune cells function as immediate responders to injury and rapidly populate the wound edge following mock cataract surgery to function as leader cells. Many of these resident …

Properties Of Multivesicular Release From Mouse Rod Photoreceptors Support Transmission Of Single-Photon Responses, Cassandra L. Hays, Asia L. Sladek, Greg D. Field, Wallace B. Thoreson

Journal Articles: Ophthalmology

Vision under starlight requires rod photoreceptors to transduce and transmit single-photon responses to the visual system. Small single-photon voltage changes must therefore cause detectable reductions in glutamate release. We found that rods achieve this by employing mechanisms that enhance release regularity and its sensitivity to small voltage changes. At the resting membrane potential in darkness, mouse rods exhibit coordinated and regularly timed multivesicular release events, each consisting of ~17 vesicles and occurring two to three times more regularly than predicted by Poisson statistics. Hyperpolarizing rods to mimic the voltage change produced by a single photon abruptly reduced the probability of …

Serial Block-Face Scanning Electron Microscopy (Sbf-Sem) Of Biological Tissue Samples, Justin A Courson, Paul T Landry, Thao Do, Eric Spehlmann, Pascal J Lafontant, Nimesh Patel, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

Serial block-face scanning electron microscopy (SBF-SEM) allows for the collection of hundreds to thousands of serially-registered ultrastructural images, offering an unprecedented three-dimensional view of tissue microanatomy. While SBF-SEM has seen an exponential increase in use in recent years, technical aspects such as proper tissue preparation and imaging parameters are paramount for the success of this imaging modality. This imaging system benefits from the automated nature of the device, allowing one to leave the microscope unattended during the imaging process, with the automated collection of hundreds of images possible in a single day. However, without appropriate tissue preparation cellular ultrastructure can …

Umbilical Amnion And Amniotic Membrane Transplantation For Infectious Scleritis And Scleral Melt: A Case Series., Zeba Syed, Christopher J Rapuano

Wills Eye Hospital Papers

Purpose: To report the outcomes of two cases of infectious scleritis with severe scleral thinning managed using combined mechanical debridement, cryopreserved umbilical amnion (UA) and amniotic membrane (AM) grafts, and antimicrobial therapy.

Observations: Two patients presented with severe infectious scleritis with progressive scleral melts secondary to Pseudomonas aeruginosa subsequent to pterygium surgery and intravitreal injection, respectively. Surgical debridement was followed by UA grafting, AM transplantation, and antimicrobial therapy. Epithelialization and vascularization were seen within 1–4 weeks post-operatively. At last follow up of 5–6 months, the structural integrity of the sclera remained preserved with no infection recurrence, graft necrosis, or wound …

Differential Leukocyte And Platelet Profiles In Distinct Models Of Traumatic Brain Injury, William Brad Hubbard, Meenakshi Banerjee, Hemendra J. Vekaria, Kanakanagavalli Shravani Prakhya, Smita Joshi, Qingjun Wang, Kathryn E. Saatman, Sidney W. Whiteheart, Patrick G. Sullivan

Spinal Cord and Brain Injury Research Center Faculty Publications

Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood–brain barrier (BBB) dysfunction and blood–brain cell interactions. As such, platelets and leukocytes contribute to mechanisms of thromboinflammation after TBI. While these mechanisms have been investigated in experimental models of contusion brain injury, less is known regarding acute alterations following mild closed head injury. To investigate the role of platelet dynamics and bioenergetics after TBI, we employed two distinct, well-established models of TBI in mice: the controlled cortical impact (CCI) …

Addressing Artificial Intelligence Bias In Retinal Diagnostics, Philippe Burlina, Neil Joshi, William Paul, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

PURPOSE: This study evaluated generative methods to potentially mitigate artificial intelligence (AI) bias when diagnosing diabetic retinopathy (DR) resulting from training data imbalance or domain generalization, which occurs when deep learning systems (DLSs) face concepts at test/inference time they were not initially trained on.

METHODS: The public domain Kaggle EyePACS dataset (88,692 fundi and 44,346 individuals, originally diverse for ethnicity) was modified by adding clinician-annotated labels and constructing an artificial scenario of data imbalance and domain generalization by disallowing training (but not testing) exemplars for images of retinas with DR warranting referral (DR-referable) from darker-skin individuals, who presumably have greater …

Efficacy Of An Appointment Specialist In Reducing Loss To Follow Up In A Retina Practice, Turner D. Wibbelsman, Michael Ammar, Md, Anthony Obeid, Md, Mph, Jason Hsu, Md

Phase 1

Introduction:

Although a new armamentarium has greatly benefitted patients with retinal disease, novel therapeutic approaches require more frequent clinic visits, which may lead to missed treatments and vision loss. This study characterizes patient-reported reasons for missed visits and assesses the efficacy of calling patients for rescheduling missed visits.

Methods:

This retrospective cohort study included patients who missed an appointment for an intravitreal injection between January 2018 and February 2020 at the Retina Service of Wills Eye Hospital. Two calls were made to each patient by an appointment specialist to reschedule the visit and record a reason for the …

Likelihood Of Germline Mutation With Solitary Unilateral Retinoblastoma Based On Patient Age At Presentation. A Real-World Analysis Of 482 Consecutive Patients., Martin Calotti, Carol L. Shields, Md, Philip Dockery, Md, Mph, Megan Ruben, Antonio Yaghy, Md, Madalyne A. Sunday, Emily R. Duffner, Hannah J. Levin, Olivia S. Taylor, Sara E. Lally, Md, Jerry A. Shields, Md

Phase 1

Introduction: Retinoblastoma due to germline mutation has a greater risk of bilateral presentation, and multifocal or extraocular involvement. In solitary unilateral retinoblastoma, the inheritance pattern is less understood and assumed to be somatic. We assessed the likelihood of germline inheritance in children with unilateral retinoblastoma and whether it varies based on age at presentation.

Methods: This was a retrospective case study assessing 482 consecutive patients with solitary unilateral retinoblastoma at Wills Eye Hospital between 1972 and 2020 for the likelihood of germline inheritance based on age at presentation (≤1 year vs. >1 year). Germline inheritance was deemed likely if …

White Paper On Ophthalmic Imaging For Choroidal Nevus Identification And Transformation Into Melanoma, Carol Shields, Sara E. Lally, Lauren Dalvin, Mandeep Sagoo, Marco Pellegrini, Swathi Kaliki, Ahmet Kaan Gündüz, Minoru Furuta, Prithvi Mruthyunjaya, Adrian T. Fung, Jay S. Duker, Sara M. Selig, Antonio Yaghy, Sandor R. Ferenczy, Malvina B. Eydelman, Mark S. Blumenkranz

Wills Eye Hospital Papers

Purpose: To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process. Methods: White paper. Results: Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination. These risk factors have been derived from multiple large cohort research studies over the past several decades and have garnered widespread use …

Corneal Disease And Air Pollution Levels In Detroit: Preliminary Results And Future Directions​, Sachin Ketkar, Matthew Silbergleit, Vaama Patel

Medical Student Research Symposium

Purpose: To determine if Detroit zip codes with elevated air pollution levels demonstrate increased incidence of corneal disease.

Background: 82 million people in the United States live in counties with air quality concentrations above the National Ambient Air Quality Standards. Air pollution’s detrimental effects on an individual’s health has been well documented. Much of this research has focused on the pulmonary system. The eye, another mucous membrane exposed to the external environment, has been largely ignored

Methods: After an initial literature review of similar studies, 14 corneal diseases and 5 pollutants were selected to be evaluated. Kresge Eye Institute’s patient …

Professional Coaching In Residency: A Novel Approach To Decrease Resident Burnout, Matthew Silbergleit, Shibandri Das, Mark S. Juzych, Pradeepa Yoganathan

Medical Student Research Symposium

Purpose: To implement and analyze an organizational level coaching program for ophthalmology residents at the Kresge Eye Institute (KEI) as the front-line method for prevention and management of physician burnout.

Background: Burnout is a well-documented stressor in medicine and has been shown to significantly increase unprofessional conduct and medical errors. A recent, promising model to tackle burnout in the medical field is coaching. The Harvard Business Review and American Medical Association have demonstrated the positive effects of coaching on professional performance and well-being.

Methods: We plan on utilizing the Kern Method to develop a resident wellness curriculum addressing resident burnout. …

Complication Rates In Resident Cataract Surgery After Elective Operating Room Shutdown During The Covid-19 Pandemic, Michael Schneider, Christian Mehregan Md, Collin Richards, Shibandri Das Md, Xihui Lin Md

Medical Student Research Symposium

Purpose: To assess the types of cataract surgeries being performed at one large eye institute from before and after the COVID-19 induced shutdown of elective surgeries in Spring 2020.

Methods: This is a retrospective chart review study of operative reports from resident performed cataract surgeries from January 1st, 2020 through July 31st, 2020. Cataract surgeries were categorized into Pre-COVID (Jan – Mar 2020) if they occurred prior to operating room (OR) shutdown on March 18th, 2020 and Post COVID for all cases which occurred after the shutdown orders were lifted (May – July 2020). A resident survey was also used …

Post-Operative Day 1 Versus Day 0 Follow-Up For Uncomplicated Cataract Surgeries: A Comparison Of Post-Operative Outcomes And Managements, Harsh Parekh Bs, Shibandri Das Md, Vaama Patel Md, Ryan Freedman Md, Sabba Mansoor Bs, Amanda Ismail Md, Faisal Ridha Al-Timimi Md

Medical Student Research Symposium

Purpose: To compare the postoperative outcomes and management of uncomplicated cataract surgery (CEIOL) patients seen on post-operative day zero (POD 0) versus post-operative day one (POD 1).

Methods: A retrospective chart review of 533 patients who had CEIOL at the Kresge Eye Institute from December 2017 to September 2019 was performed. Visual acuity (VA) and intraocular pressure (IOP) were collected from the pre-operative visit, and the first and second post-operative day visits. In addition, changes in management were recorded from the first post-operative day visit. Patients were excluded if they had a complex cataract procedure, had combined glaucoma filtering surgery, …

Resident Heart Rate Variability During Cataract Surgery, Ahmad Baiyasi, Shibandri Das, Ferris Bayasi, Faisal Ridha Al-Timimi

Medical Student Research Symposium

Purpose: To evaluate ophthalmology resident anxiousness and cardiovascular response by tracking resident heart rate (HR) when performing cataract surgery during their last year of residency.

Methods: A prospective analysis of 31 cataract cases, completed by three residents (two females and one male), at the Kresge Eye Institute in August and September 2020 was performed. Inclusion criteria for cases included all cataract cases performed by PGY-4 residents at the Kresge Eye Institute who downloaded the Heart Graph app supported by iOS. Residents with android mobile devices were excluded from the study. Informed consent was obtained from all residents who utilized the …

A Systematic Review On Three Major Types Of Scleral-Fixated Intraocular Lens Implantation, Ho Ming Wong, Ka Wai Kam, Christopher J Rapuano, Alvin L Young

Wills Eye Hospital Papers

PURPOSE: We performed a systematic review on 3 major types of scleral-fixated intraocular lens (SFIOL) implantations and conducted subgroup analyses on pediatric population and subjects with Marfan syndrome.

DESIGN: Systematic review.

METHODS: We performed a search in PubMed, Ovid MEDLINE, and Embase for English language articles with keywords "(sutured intraocular lens) OR (SFIOL) OR (sutureless intraocular lens) OR (glued intraocular lens) OR (intrascleral intraocular lens) OR (SFIOL)" through October 16, 2019. Articles reporting individual outcomes after SFIOL were included in this systematic review. Recorded outcome measures included intraoperative and postoperative complications, endothelial cell changes, and intraocular lens-related outcomes.

RESULTS: Our …