Ophthalmology Commons^™

Diabetic Retinopathy: Variations In Patient Therapeutic Outcomes And Pharmacogenomics., Aniruddha Agarwal, Mohamed K. Soliman, Yasir J. Sepah, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

Diabetes and its microvascular complications in patients poses a significant challenge and constitutes a major health problem. When it comes to manifestations in the eye, each case of diabetic retinopathy (DR) is unique, in terms of the phenotype, genotype, and, more importantly, the therapeutic response. It is therefore important to identify factors that distinguish one patient from another. Personalized therapy in DR is a new trend aimed at achieving maximum therapeutic response in patients by identifying genotypic and phenotypic factors that may result in less than optimal response to conventional therapy, and consequently, lead to poorer outcome. With advances in …

A Comparison Of Clinical Trial And Model-Based Cost Estimates In Glaucoma – The Case Of Repeat Laser Trabeculoplasty In Ontario, Omar Akhtar

Electronic Thesis and Dissertation Repository

Background and objective: For cost-effectiveness analyses (CEA) of glaucoma interventions to be of use they require valid and accurate cost and effectiveness data. Costs remain understudied relative to effectiveness. The impact of cost estimation methods on resultant estimates is unknown in glaucoma. Direct measurement of costs is labour-intensive and expensive. Decision-analytic modelling of costs using literature sources, expert opinion, institutional experience and assumptions provides a quicker, less laborious alternative to empirical costing. A lack of long-term effectiveness data in chronic diseases like glaucoma means that modelling is widespread and inevitable, both for CEAs and budget impact projections. The same problem …

Neuroprotective Effects Of Retinal Ganglion Cells By Specific Alpha 7 Nicotine Acetylcholine Receptor Agonists And An Acetylcholineesterase Inhibitor, Sara Kaliszak

Honors Theses

In previous studies from this lab, an alpha7 nACh receptor was found to successfully modulate retinal ganglion cell neuroprotection against glutamate assault when bound to nicotinic acetylcholine receptors, or if an alpha7 nicotinic acetylcholine agonist, such as PNU-282987 was used in in vitro models (Wehrwein et al., 2004; Iwamoto et al., 2013). These in vitro studies support the hypothesis that activation of alpha7 nicotinic ACh receptors triggers neuroprotection against loss of retinal ganglion cells normally induced by excessive glutamate insult. The results from these in vitro studies instigated an in vivo study in our lab using a rat glaucoma model. …

Retinal Synaptic Function In The Absence Of The On Pathway., Kathryn Marie Heath Fransen

Electronic Theses and Dissertations

Complete Congenital Stationary Night Blindness (cCSNB) is a rare hereditary retinal disorder characterized by abnormal night vision. cCSNB is caused by postsynaptic defects in On bipolar cells (BCs) and is identified by the presence of an electroretinogram (ERG) with a normal a-wave, corresponding to photoreceptor function, and the absence of a b-wave, corresponding to a failure of On BC function. Through the study of genetic mutations in mouse that result in no b-wave ERG phenotypes, several proteins have been identified that play crucial roles in On BC signal transmission. I focused on four mouse models of cCSNB; Nyxnob (Nyctalopin mutant), …

Boundary Contour Based Surface Representation., Yong Su

Electronic Theses and Dissertations

We receive most information about our surrounding space and objects through the eyes. To reconstruct the 3D space and objects in the visual system from the 2D retinal images, surface representation must be a critical intermediate stage in the visual processing stream. It is hypothesized in the dissertation that the visual system represents textured surface by a border-to-interior strategy: boundary contours would be encoded first and then border-ownership assignments would be resolved. This process would solve the related problems such as figure-ground segregation, surface depth relationship, occlusion, transparency, etc. As a result, the boundary contours of the surfaces would be …

Utility Of Heidelberg Retinal Tomography As A Screening Tool For Analyzing Retinal Nerve Fiber Layer Defects, David A. Belyea, Rashed Alhabshan, Sankaranarayana P. Mahesh, Gregory S. Gertner, Mirsad M. Ibisevic, Abdullah S. Habib, Jacob A. Dan

Ophthalmology Faculty Publications

Context

Although Heidelberg retinal tomography (HRT)-generated topographic images have been studied extensively for the detection of retinal nerve fiber layer (RNFL) defects, little is known about the role of HRT-generated surface reflectivity images in the detection of RNFL defects in either patients with glaucoma or glaucoma suspects.

Aims

To evaluate the effectiveness of HRT version II (HRT II) optic nerve reflectivity images in uncovering RNFL defects in an outpatient population evaluated for glaucoma.

Study design/materials and methods

In 102 consecutive eyes from 60 patients evaluated for glaucoma in an academic-based practice, HRT II optic nerve images were prospectively imaged and …

Swelling And Eicosanoid Metabolites Differentially Gate Trpv4 Channels In Retinal Neurons And Glia., Daniel A. Ryskamp, Andrew O. Jo, Amber M M. Frye, Felix Vazquez-Chona, Nanna Macaulay, Wallace B. Thoreson, David Križaj

Journal Articles: Ophthalmology

Activity-dependent shifts in ionic concentrations and water that accompany neuronal and glial activity can generate osmotic forces with biological consequences for brain physiology. Active regulation of osmotic gradients and cellular volume requires volume-sensitive ion channels. In the vertebrate retina, critical support to volume regulation is provided by Müller astroglia, but the identity of their osmosensor is unknown. Here, we identify TRPV4 channels as transducers of mouse Müller cell volume increases into physiological responses. Hypotonic stimuli induced sustained [Ca(2+)]i elevations that were inhibited by TRPV4 antagonists and absent in TRPV4(-/-) Müller cells. Glial TRPV4 signals were phospholipase A2- and cytochrome P450-dependent, …

Low Vision Depression Prevention Trial In Age-Related Macular Degeneration: A Randomized Clinical Trial., Barry W. Rovner, Robin J Casten, Mark T Hegel, Robert W Massof, Benjamin E Leiby, Allen C Ho, William S Tasman

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD).

DESIGN: Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months.

PARTICIPANTS: Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188).

INTERVENTIONS: Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment …

Svegfr-2 And Its Role In Lymphangiogenesis Modulation, Jayakrishna Ambati, Romulo J. Albuquerque

Ophthalmology and Visual Science Faculty Patents

Disclosed herein are nucleic acid molecules comprising a nucleotide sequence of sVEGF-2, proteins encoded by those sequences and antibodies that bind to the protein. Also disclosed are methods for inhibiting or enhancing expression or activity of sVEGFR-2 and methods for inhibiting graft rejection, particularly cornea graph rejection. Also described are methods for inhibiting lymphangiogenesis and lymphatic endothelial cell proliferation by administering an effective amount of sVEGFR-2 and methods for treating lymphedema by inhibiting the activity of sVEGFR-2.

Pharmacotherapy For Uveitis: Current Management And Emerging Therapy., Robert J. Barry, Quan Dong Nguyen, Richard W. Lee, Philip I. Murray, Alastair K. Denniston

Journal Articles: Ophthalmology

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual …

Patients’ Visual Experience During Phacoemulsification Cataract Surgery And Associated Fear, Tanveer Anjum Chaudhry, Amash Aqil, Kanza Aziz, Ammar Asrar Javed, Mohammad Zain Tauqir, Khabir Ahmad

Department of Surgery

Abstract Background: Data from several published studies indicate that patients undergoing phacoemulsification cataract surgery can experience a variety of visual sensations which can result in fear. This phenomenon has not been studied in Pakistan to-date. We examined the visual experience and its associated fear among patients undergoing phacoemulsification cataract surgery under topical anaesthesia. Methods: This cross-sectional study was carried out in Aga Khan University Hospital, a tertiary care hospital, in Karachi, Pakistan from August 2010 to July 2011. Adults >18 years of age scheduled to undergo cataract surgery (phacoemulsification with intraocular lens implantation) under topical anaesthesia by a single surgeon …

Vogt-Koyanagi-Harada Syndrome, Sharmeen Akram, Khabir Ahmad

Department of Surgery

ABSTRACT Vogt-Koyanagi-Harada (VKH) syndrome is a rare multisystem disease of melanocyte containing organs. It is characterized by diffuse granulomatous inflammation involving various organs including eye. VKH syndrome is usually sporadic, but some familial cases have also been reported indicating a hereditary basis. VKH is not associated with mortality but it may result in long-term complications such as decreased vision associated with cataract, glaucoma and choroidal neovascularization. For successful outcomes, early aggressive treatment using systemic steroids with gradual tapering is essential. This report describes a case of VKH syndrome in a 26-year-old male of Pakistan origin who was successfully treated with …

Variation Of Choroidal Thickness And Vessel Diameter In Patients With Posterior Non-Infectious Uveitis, Millena G. Bittencourt, Saleema Kherani, Daniel A. Ferraz, Mehreen Ansari, Humzah Nasir, Yasir J. Sepah, Mostafa S. Hanout, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

Abstract

Background

Choroidal thickness (CTh) and choroidal vessel diameter (VD) in the Haler’s layer were evaluated as markers of inflammatory insult in non-infectious uveitis (NIU). Spectral-domain optical coherence tomography (Spectralis®, Heidelberg Engineering Inc.) scans were acquired from 23 normal subjects (39 eyes – group 1), 7 subjects with high myopia (14 eyes – group 2), and 19 patients with NIU (23 eyes – group 3). In groups 1 and 2, CTh and VD were measured at 3 different points of the same horizontal OCT scan passing through the fovea and a mean calculated. Mean CTh and VD were calculated in …

Intravitreal Triamcinolone Acetonide Injection For Macular Edema Due To Central Retinal Vein Occlusion Persisting Despite Multiple Intravitreal Bevacizumab Injections., Rayan A Alshareef, Sunir Garg, Jason Hsu, James Vander, Carl Park, Marc J Spirn

Wills Eye Hospital Papers

PURPOSE: To evaluate the response to intravitreal triamcinolone acetonide for macular edema persisting or recurring despite multiple intravitreal bevacizumab (IVB) treatments for central retinal vein occlusion (CRVO).

METHODS: Retrospective interventional case series of 21 eyes with CRVO from 21 patients who were diagnosed with persistent or recurrent macular edema secondary to CRVO and treated with 0.1mL (4mg) intravitreal triamcinolone acetonide (IVTA) after initial treatment with 3 or more IVB injections. Anatomic and visual responses were the study primary outcomes.

RESULTS: Mean logarithm of the minimum angle of resolution visual acuity was 1.19 (20/316) immediately before IVTA injection, and improved to …

Bilateral Maxillary Canine-First Premolar Transposition In Permanent Dentition, Sarwat Memon, Mubassar Fida

Department of Surgery

ABSTRACT Transposition is a dental anomaly characterized by the exchange of position between two adjacent teeth, especially in relation to their roots, or development and eruption of a tooth in a position normally occupied by a nonadjacent tooth. Transposition of the maxillary canine and first premolar has a low prevalence in the population and it primarily affects maxillary canines and premolars. The aetiology of the transposition remains unclear, although it has been associated with genetic factors. It may also be related to a combination of localised factors such as malformation of adjacent teeth, tooth agenesis, retention of the deciduous canine …

Review: Zinc’S Functional Significance In The Vertebrate Retina, Harris Ripps, Richard L. Chappell

Publications and Research

This review covers a broad range of topics related to the actions of zinc on the cells of the vertebrate retina. Much of this review relies on studies in which zinc was applied exogenously, and therefore the results, albeit highly suggestive, lack physiologic significance. This view stems from the fact that the concentrations of zinc used in these studies may not be encountered under the normal circumstances of life. This caveat is due to the lack of a zinc-specific probe with which to measure the concentrations of Zn2+ that may be released from neurons or act upon them. However, a …

Method Of Using Ccr3 Binding Agents To Detect Choroidal Neovascularization, Jayakrishna Ambati, Mark E. Kleinman

Ophthalmology and Visual Science Faculty Patents

The results presented herein demonstrate the specific expression of CCR3 in CNV endothelial cells in humans with AMD, and despite the expression of its ligands, eotaxin-1, -2, and -3, neither eosinophils nor mast cells are present in human CNV. The genetic or pharmacological targeting of CCR3 or eotaxins as disclosed herein inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation as it occurred in mice lacking eosinophils or mast cells and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing …

Sox11 Is Required To Maintain Proper Levels Of Hedgehog Signaling During Vertebrate Ocular Morphogenesis, Lakshmi Pillai-Kastoori, Wen Wen, Stephen G. Wilson, Erin Strachan, Adriana Lo-Castro, Marco Fichera, Sebastiano A. Musumeci, Ordan J. Lehmann, Ann C. Morris

Biology Faculty Publications

Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the …

Frequency Of Retinopathy Of Prematurity In Premature Neonates With A Birth Weight Below 1500 Grams And A Gestational Age Less Than 32 Weeks: A Study From A Tertiary Care Hospital In A Lower-Middle Income Country, Arjumand Sohaila, Shiyam Sunder Tikmani, Iqtidar Ahmed Khan, Huba Atiq, Ali Syed Muhammad Akhtar, Prem Kumar, Kishwer Kumar

Department of Emergency Medicine

Introduction: Retinopathy of prematurity (ROP) is a treatable cause of blindness in neonates. In Pakistan, ROP is often not recognized early because screening and treatment programs are not yet in place in most neonatal units, even in tertiary care hospitals. It is hoped that this report will help inform medical professionals of the magnitude of the problem and help to design appropriate management strategies.

Objectives: The aim was to determine the frequency of ROP in premature and very low birth weight (BW) neonates (BW(GA)weeks).

Study Design: Cross-sectional study.

Study Setting : Neonatal intensive care unit (NICU) of a tertiary care …

Phosphoinositides: Minor Lipids Make A Major Impact On Photoreceptor Cell Functions, Raju V. S. Rajala, Ammaji Rajala, Andrew J. Morris, Robert E. Anderson

Internal Medicine Faculty Publications

Activation of the phosphoinositide (PI) cycle generates the second messengers that control various aspects of cellular signaling. We have previously shown that two PI cycle enzymes, type II phosphatidylinositol 5-phosphate 4-kinase (PIPK IIα) and phosphoinositide 3-kinase (PI3K), are activated through light stimulation. In our earlier studies, we measured enzyme activities, instead of directly measuring the products, due to lack of sensitive analytical techniques. Cells have very low levels of PIs, compared to other lipids, so special techniques and sensitive analytical instruments are necessary for their identification and quantification. There are also other considerations, such as different responses in different cell …

Personality And Functional Vision In Older Adults With Age-Related Macular Degeneration, Barry W. Rovner, R. J. Casten, Mark T. Hegel, Robert W. Massof, Benjamin E. Leiby, Allen C. Ho, William S. Tasman

Department of Psychiatry and Human Behavior Faculty Papers

Introduction: The purpose of the study was to determine whether personality traits influence self-reported functional vision in patients with age-related macular degeneration (AMD). Methods: This is a prospective cross-sectional analysis of baseline data from the Low Vision Depression Prevention Trial. Participants (N = 182) over age 65 with bilateral AMD, visual acuity worse than 20/70 in the better-seeing eye, and subthreshold depression were recruited from the Wills Eye Hospital retina practice. Assessments included visual acuity, contrast sensitivity, National Eye Institute Visual Function Questionnaire-25 plus Supplement (NEI VFQ-25) near and distance subscales, depression, and personality testing. Structural equation models were used …

Withanolides, Probes And Binding Targets And Methods Of Use Thereof, Royce Mohan, Paola Bargagna-Mohan, Kyung Bo Kim

Ophthalmology and Visual Science Faculty Patents

Novel withanolide chemical genetic probes identify the in vivo binding target of withaferin A, which is the intermediate filament type III protein vimentin. In addition, a withanolide-based small molecule screening method screens drug candidates that target intermediate filament type III proteins. The method includes introducing a tagged linker covalently bonded to the withanolide molecule to form a withanolide probe. Better or alternative small molecule compounds as potential drug candidates can be generated based on their likely affinity for the determined binding site in vimentin. The affinity labeled withanolide can also be used to find intermediate filament-associated proteins using chemical proteomics …

Omics Technologies And Neovascular Ocular Disorders., Daniel Petrovič, Quan Dong Nguyen, Borut Peterlin, Goran Petrovski

Journal Articles: Ophthalmology

No abstract provided.

The Anatomical And Functional Benefit Of Bevacizumab In The Treatment Of Macular Edema Associated With Purtscher-Like Retinopathy, B. Lw. Nesmith, Maya Bitar, S. Schaal

Ophthalmology

We read the article by Miguel et al1 regarding Purtscher’s and Purtscher-like retinopathies with great interest. As the authors well describe, ‘Purtscher-like retinopathy’ is diagnosed in patients with fundus findings similar to Purtscher’s retinopathy, without a history of trauma but with known systemic associations.¹ Current proposed mechanisms for the underlying pathogenesis include leukocyte aggregation by activated complement factor 5 (C5a).² As noted by the authors’ systematic review, there is currently no established treatment for Purtscher-like retinopathy, although the literature consists of several case reports of treatment with corticosteroids, without certainty as to effect on the clinical course.1 Herein, …

Fundus Autofluorescence Imaging: Fundamentals And Clinical Relevance., Yasir J. Sepah, Abeer Akhtar, Mohammad Ali Sadiq, Yamama Hafeez, Humzah Nasir, Brian Perez, Narissa Mawji, Diana J. Dean, Daniel Ferraz, Quan Dong Nguyen

Journal Articles: Ophthalmology

Fundus autofluorescence (FAF), a relatively new imaging modality, focuses on the fluorescent properties of pigments in the retina to generate images that help us view various disease processes from a different perspective. It aids us in the understanding of the pathophysiology of different retinal disorders. Recently, FAF imaging is being used commonly to help us in the diagnosis, prognosis as well as in determining the treatment response of various retinal disorders. It generates an image based on the distribution pattern of a fluorescent pigment called lipofuscin. Knowing the distribution pattern of lipofuscin in the normal retina is key to understanding …

Ultrasound-Enhanced Ocular Delivery Of Dexamethasone Sodium Phosphate: An In Vivo Study, Marjan Nabili, Aditi Shenoy, Shawn Chawla, Sankaranarayana P. Mahesh, Craig Geist, Vesna Zderic

Ophthalmology Faculty Publications

Background

The eye's unique anatomy and its physiological and anatomical barriers can limit effective drug delivery into the eye.

Methods

An in vivo study was designed to determine the effectiveness and safety of ultrasound application in enhancing drug delivery in a rabbit model. Permeability of a steroid ophthalmic drug, dexamethasone sodium phosphate, was investigated in ultrasound- and sham-treated cases. For this study, an eye cup filled with dexamethasone sodium phosphate was placed on the cornea. Ultrasound was applied at intensity of 0.8 W/cm² and frequency of 400 or 600 kHz for 5 min. The drug concentration in aqueous humor …

Indirect Cyclopexy For Treatment Of A Chronic Traumatic Cyclodialysis Cleft With Hypotony, Nisha Chadha, Tania Lamba, David A. Belyea, Kunal Y. Merchant

Ophthalmology Faculty Publications

Cyclodialysis cleft is a rare clinical finding and therefore, reports on surgical repair techniques in the literature are limited. Additionally, hypotony can make repair technically challenging. We share a novel, simple surgical approach to management of a case of chronic traumatic cyclodialysis cleft with a successful outcome.

High-Speed Optical Coherence Tomography As A Reliable Adjuvant Tool To Grade Ocular Anterior Chamber Inflammation., Ann O. Igbre, Mario C. Rico, Sunir Garg

Wills Eye Hospital Papers

PURPOSE: To evaluate the high-speed anterior segment optical coherence tomography (AS-OCT) grading of the AS inflammation in patients with ocular inflammation.

METHODS: A retrospective consecutive case series study. Patients with clinically visible AS inflammation in at least one eye underwent AS-OCT (Visante; Zeiss Meditec) with three to eight line scans per eye, performed by a trained masked examiner. The images were reviewed for hyperreflective spots, noise, and artifact, and these were correlated to clinical examination.

RESULTS: Seventy-eight eyes of 41 patients were imaged. Forty-seven eyes had anterior chamber cells on clinical examination, and 68 had hyperreflective spots visible on AS-OCT. …

Retinopathy Of Prematurity: An Evaluation Of Existing Screening Criteria In Pakistan, Tanveer Anjum Chaudhry, Farzeen Khalid Hashmi, Muhammad Sohail Salat, Qazi Assad Khan, Abdul Ahad, Ather M Taqui, Reema Syed, Khabir Ahmad

Department of Surgery

Abstract

AIM:

To evaluate if broadening the criteria for retinopathy of prematurity (ROP) screening to include babies with gestational age ≥32 weeks and/or birth weight ≥1500 g, would have an impact on the number of babies diagnosed as having ROP.

METHODS:

A prospective cohort study was carried out at the Aga Khan University Hospital, Karachi, Pakistan. Infants with gestational age ≤35 weeks or birth weight ≤2000 g born in this hospital from May 2010 to December 2012 were screened for the presence of ROP 4-6 weeks after birth. Subsequent examinations were performed at intervals based on the findings of initial …

The Influence Of Soft Contact Lens Wear And Two Weeks Cessation Of Lens Wear On Corneal Curvature, Aoife Lloyd Mckernan, Veronica O'Dwyer, Luisa Simo Mannion

Articles

Abstract

Introduction

Accurate corneal measurements are crucial in corneal refractive surgery (CRS) to ensure successful outcomes. Soft contact lens (SCL) wear may result in changes to corneal curvature and structure. United States Food and Drug Administration (FDA) pre-operative guidelines recommend that prior to CRS, SCL wearers cease SCL wear for “at least two weeks before examination and treatment”[1]. Corneal curvature changes induced by SCL wear may take longer than two weeks to resolve.

Purpose

To examine the effect of SCL wear on corneal curvature before and following two weeks SCL wear cessation. To explore the possible impact of different SCL …