Ophthalmology Commons^™

Pediatric Ophthalmology And Strabismus: Something For Everyone., Alex V. Levin

Wills Eye Hospital Papers

This issue of Current Opinion in Ophthalmology highlights the uniquely broad range of pediatric ophthalmology and strabismus. Perhaps, unlike any other area of ophthalmology, our specialty covers virtually every part of the eye and a multitude of systemic disorders. Pediatric ophthalmology offers the practitioner the opportunity to impact a patient’s visual life for many decades giving them a lifetime of good vision. This issue of the journal highlights the many ways that this is so.

Convergence Insufficiency And Its Current Treatment., Judith B Lavrich

Wills Eye Hospital Papers

PURPOSE OF REVIEW: Considerable uncertainty and controversy has existed concerning the management of convergence insufficiency. Only recently there have been significant scientific studies published that compare the effectiveness of the commonly prescribed treatments. This paper reviews the most recent research and literature on convergence insufficiency and its treatment.

RECENT FINDINGS: The first large-scale placebo-controlled, randomized clinical trials to study the various treatments of convergence insufficiency have recently been published. Current research compares the effectiveness of base-in prism glasses, pencil push-ups, and vision therapy in reducing the signs and symptoms of convergence insufficiency and suggests that orthoptic therapy is the most …

Interferon Γ–Inducible Protein-10 (Ip-10) And Eotaxin As Biomarkers In Age-Related Macular Degeneration, F. M. Mo, A. D. Proia, W. H. Johnson, D. Cyr, K. Lashkari

Osteopathic Medicine, Jerry M. Wallace School of

No abstract provided.

Spontaneous Disconnection Of Glaucoma Tube Shunt Extenders., Oseluese Dawodu, Alex V. Levin

Wills Eye Hospital Papers

Glaucoma drainage implants are frequently used in children with severe forms of glaucoma, and tube extenders are sometimes required to compensate for ocular growth or when the intraocular portion of the tube is thought to be too short. We report 2 cases of spontaneous disconnection of a tube extender, occurring 8 months after insertion in one case and 3 years later in the other. In both cases the tube was removed and the patient treated with endoscopic diode laser photocoagulation.

Histamine Reduces Flash Sensitivity Of On Ganglion Cells In The Primate Retina, Nikolay P Akimov, David W Marshak, Laura J Frishman, Randolph D Glickman, Rafail G Yusupov

Faculty, Staff and Student Publications

PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded …

Management Of Devastating Ocular Trauma--Experience Of Maxillofacial Surgeons Deployed To A Forward Field Hospital, M. J. Ansell, J. Breeze, Vivian C. Mcalister, M. D. Williams

Surgery Publications

Combat-related eye injuries continue to increase in frequency and are generally secondary to Improvised Explosive Devices. Many ocular injuries are potentially preventable by the wearing of ballistic eye protection. The management of penetrating eye trauma is normally outside the routine practice of maxillofacial surgeons in the UK. The aim of this paper is to describe the surgical techniques used in the modern management of devastating ocular trauma including selected case examples managed by British military maxillofacial surgeons deployed to Afghanistan.

Cd4 T-Cell Suppression By Cells From Toxoplasma Gondii-Infected Retinas Is Mediated By Surface Protein Pd-L1, Elizabeth Charles, Sunil Joshi, John D. Ash, Barbara A. Fox

Dartmouth Scholarship

In the inflamed retina, CD4(+) T cells can cause retinal damage when they are not properly regulated. Since tissue expression of major histocompatibility complex (MHC) class II and costimulatory molecules is a key mechanism for regulating effector T cells, we tested the hypothesis that upregulation of these proteins in the retina contributes to the regulation of CD4 T cells. Here we report that in retinas infected with the protozoan parasite Toxoplasma gondii, MHC class II is upregulated on infiltrating leukocytes as well as on resident retinal cells, including photoreceptors. Flow cytometric analysis indicated that B7 costimulatory family members (CD80, CD86, …

The Assessment Of Disability Related To Vision Performance-Based Measure In Diabetic Retinopathy., Kevin J. Warrian, Luciano L. Lorenzana, Dara Lankaranian, Jyoti Dugar, Sheryl S. Wizov, George L. Spaeth

Wills Eye Hospital Papers

PURPOSE: To validate a third-generation performance-based measure of visual function titled "Assessment of Disability Related to Vision" (ADREV) in a study population of patients with diabetic retinopathy.

DESIGN: Prospective, cross-sectional study.

METHODS: Patients with nonproliferative or proliferative diabetic retinopathy, free from ocular comorbidity, were recruited from a single institute and completed the ADREV, the 25-Item National Eye Institute Visual Functioning Questionnaire (VFQ-25), and a clinical ophthalmic examination. Correlation, regression, and bootstrap analysis were conducted to determine the relationship between ADREV scoring and each of the study's clinical and self-report measures of visual ability, while controlling for potential confounders.

RESULTS: Ninety-one …

Clinical Outcome Of Iridotomy With Argon-Yag Laser At A Tertiary Care Center In Karachi, Pakistan, Rashid Baig, Aziz Khan

Section of Ophthalmology

Objective: To assess the the efficacy and early and late complications of Argon-YAG combined laser iridotomy in the outpatient department of a tertiary care hospital.
Methods: This was a prospective observational study conducted at Aga Khan University Hospital Karachi, Pakistan. After detailed history taking and clinical examination, patients who had goniscopically evident closed angles and a positive provocative test were selected for laser iridotomy. They underwent iridotomy using Argon laser followed by YAG laser. The main outcome measures were patency of iridotomy at 6 months, angle grading at 6 months and early and late complications.
Results: Overall 40 eyes of …

Elevated Albumin In Retinas Of Monkeys With Experimental Glaucoma, Louvenia Carter-Dawson, Yujin Zhang, Ronald S Harwerth, Ricky Rojas, Pramod Dash, Xinping C Zhao, Elizabeth Woldemussie, Guadalupe Ruiz, Alice Chuang, William P Dubinsky, John B Redell

Faculty, Staff and Student Publications

PURPOSE: To establish the identity of a prominent protein, approximately 70 kDa, that is markedly increased in the retina of monkeys with experimental glaucoma compared with the fellow control retina, the relationship to glaucoma severity, and its localization in the retina.

METHODS: Retinal extracts were subjected to 2-D gel electrophoresis to identify differentially expressed proteins. Purified peptides from the abundant 70 kDa protein were analyzed and identified by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) separation, and collision-induced dissociation sequencing. Protein identity was performed on MASCOT (Matrix Science, Boston, MA) and confirmed by Western blot. The relationship between the increase in this …

Anion-Sensitive Regions Of L-Type Cav1.2 Calcium Channels Expressed In Hek293 Cells., Norbert Babai, Nataly Kanevsky, Nathan Dascal, George J. Rozanski, Dhirendra P. Singh, Nigar Fatma, Wallace B. Thoreson

Journal Articles: Ophthalmology

L-type calcium currents (I(Ca)) are influenced by changes in extracellular chloride, but sites of anion effects have not been identified. Our experiments showed that CaV1.2 currents expressed in HEK293 cells are strongly inhibited by replacing extracellular chloride with gluconate or perchlorate. Variance-mean analysis of I(Ca) and cell-attached patch single channel recordings indicate that gluconate-induced inhibition is due to intracellular anion effects on Ca(2+) channel open probability, not conductance. Inhibition of CaV1.2 currents produced by replacing chloride with gluconate was reduced from approximately 75%-80% to approximately 50% by omitting beta subunits but unaffected by omitting alpha(2)delta subunits. Similarly, gluconate inhibition was …

Identifying Factors Associated With Falls In Postmenopausal Breast Cancer Survivors: A Multi-Disciplinary Approach, Kerri M. Winters-Stone, Britta Torgrimson, Fay Horak, Alvin Eisner, Lillian Nail, Micahel C. Leo, Steve Chui, Shiuh-Wen Luoh

Community Health Faculty Publications and Presentations

Objective—To identify neuromuscular, balance and vision factors that contribute to falls in recently treated breast cancer survivors (BCS) and explore links between fall risk factors and cancer treatment

Design—Case-control plus prospective observation

Setting—Comprehensive cancer center

Participants—BCS within two years chemotherapy completion and/or on adjuvant endocrine therapy (N=59; mean age: 58 yrs)

Intervention—not applicable

Main outcome measures—Objective measures of postural control, vision and neuromuscular function included 1) a sensory organization test (SOT), 2) a visual assessment battery, 3) muscle mass by DXA, and 4) neuromuscular function with strength by repetition maximum, power by timed stair …

Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome In A Pakistani Pedigree, Tanveer Anjum Chaudhry, Mirza Umair Khalid, Taimur Saleem, Khabir Ahmad

Section of Ophthalmology

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare developmental ocular disorder. We report this condition affecting 4 members of a Pakistani family across three generations. A 2-year-old girl was brought to the clinic by her father for the correction of her shortened palpebral fissures. Examination findings were consistent with BPES. The girl's father, paternal grandfather and paternal aunt also had identical features. The distance between the medial canthi of the index case was 30 mm, and the lengths of vertical and horizontal palpebral fissure were 6 mm and 20 mm, respectively. BPES must be considered an important differential diagnosis in patients …

Role Of Transforming Growth Factor Beta In Corneal Function, Biology And Pathology, Ashish Tandon, Jonathan C. K. Tovey, Ajay Sharma, Rangan Gupta, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Transforming growth factor-beta (TGFβ) is a pleiotropic multifunctional cytokine that regulates several essential cellular processes in many parts of the body including the cornea. Three isoforms of TGFβ are known in mammals and the human cornea expresses all of them. TGFβ1 has been shown to play a central role in scar formation in adult corneas whereas TGFβ2 and TGFβ3 have been implicated to play a critical role in corneal development and scarless wound healing during embryogenesis. The biological effects of TGFβ in the cornea have been shown to follow SMAD dependent as well as SMAD-independent signaling pathways depending upon cellular …

Gene Delivery In The Equine Cornea: A Novel Therapeutic Strategy, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To determine if hybrid adeno-associated virus serotype 2/5 (AAV5) vector can effectively deliver foreign genes into the equine cornea without causing adverse side effects. The aims of this study were to: (i) evaluate efficacy of AAV5 to deliver therapeutic genes into equine corneal fibroblasts (ECFs) using enhanced green fluorescent protein (EGFP) marker gene and (ii) establish the safety of AAV5 vector for equine corneal gene therapy.

Animal Material—Primary ECF cultures were harvested from healthy donor equine corneas. Cultures were maintained at 370C in humidified atmosphere with 5% CO2.

Procedure—AAV5 vector expressing EGFP under control of hybrid cytomegalovirus (CMV) + chicken …

Efficacy And Safety Of Mitomycin C As An Agent To Treat Corneal Scarring In Horses Using An In Vitro Model, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in-vitro model.

Procedure—An in-vitro model of equine corneal fibroblast (ECF) developed was used. The equine corneal fibroblast or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFβ1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion and MTT [(3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays …

Isolation And Cultivation Of Equine Corneal Keratocytes, Fibroblasts And Myofibroblasts, Dylan G. Buss, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To establish an in vitro model for the investigation of equine corneal wound healing. To accomplish this goal, a protocol to isolate and culture equine corneal keratocytes, fibroblasts and myofibroblasts was developed.

Animal material—Equine corneal buttons were aseptically harvested from healthy research horses undergoing humane euthanasia for reasons unrelated to this study. Slit-lamp biomicroscopy was performed prior to euthanasia by a board-certified veterinary ophthalmologist to ensure that all samples were harvested from horses free of anterior segment disease.

Procedure—Equine corneal stroma was isolated using mechanical techniques and stromal subsections were then cultured. Customized media at different culture conditions was used …

"Transduction Efficiency Of Aav 2/6, 2/8 And 2/9 Vectors For Delivering Genes In Human Corneal Fibroblasts ", Ajay Sharma, Arkasubhra Ghosh, Eric T. Hansen, Jason M. Newman, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

In the present study, cellular tropism and relative transduction efficiency of AAV2/6, AAV2/8 and AAV2/9 vectors have been tested for the cornea using primary cultures of human corneal fibroblasts. The AAV6, AAV8 and AAV9 serotypes having AAV2 ITR plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Primary cultures of human corneal fibroblasts were exposed to AAV infectious particles at two different doses (1×105 and 2×105 MOI). Cytochemistry and enzyme assays were used to measure delivered transgene expression in samples collected at 4 and 30 hours after AAV infection …

Vector Delivery Technique Affects Gene Transfer In The Cornea In Vivo, Rajiv R. Mohan, Ajay Sharma, Tyler C. Cebulko, Ashish Tandon

Pharmacy Faculty Articles and Research

Purpose: This study tested whether controlled drying of the cornea increases vector absorption in mouse and rabbit corneas in vivo and human cornea ex vivo, and studied the effects of corneal drying on gene transfer, structure and inflammatory reaction in the mouse cornea in vivo.

Methods: Female C57 black mice and New Zealand White rabbits were used for in vivo studies. Donor human corneas were used for ex vivo experiments. A hair dryer was used for drying the corneas after removing corneal epithelium by gentle scraping. The corneas received no, once, twice, thrice, or five times warm air for …

The Mozambique Eyecare Project: Implementing A Model That Addresses Uncorrected Refractive Error In Lusophone Africa., Stephen Thompson, Diane Wallace

Conference Papers

BACKGROUND

Optometric education and resources are drastically deficient in most of Africa, more so in Lusophone Africa where the problem is compounded by language barriers which isolate these countries from related developments in Africa and/or the developed world.

The Mozambique Eyecare Programme is a multi-partner collaboration between The International Centre for Eyecare Education (ICEE), Universidade Lúrio in Mozambique, Technological University Dublin, and the University of Ulster in Ireland, designed to address the need for optometric education in Lusophone Africa.

AIM

This paper aims to document the current situation with regards to human resource development in eyecare in Mozambique and offer …

Localization Of Angiotensin Converting Enzyme In Rabbit Cornea And Its Role In Controlling Corneal Angiogenesis In Vivo, Ajay Sharma, Daniel I. Bettis, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: The renin angiotensin system (RAS) has been shown to modulate vascular endothelial growth factor and angiogenesis. In this study we investigated (i) the existence of the RAS components angiotensin converting enzyme (ACE) and angiotensin II receptors (AT1 and AT2) in the rabbit cornea using in vitro and ex vivo models and (ii) the effect of enalapril, an ACE inhibitor, to inhibit angiogenesis in rabbit cornea in vivo.

Methods: New Zealand White rabbits were used. Cultured corneal fibroblasts and corneal epithelial cells were used for RNA isolation and cDNA preparation using standard molecular biology techniques. PCR was performed to …

Aav Serotype Influences Gene Transfer In Corneal Stroma In Vivo, Ajay Sharma, Jonathan C. K. Tovey, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study evaluated the cellular tropism and relative transduction efficiency of three AAV serotypes, AAV6, AAV8 and AAV9, for corneal gene delivery using mouse cornea in vivo and donor human cornea ex vivo. The AAV6, AAV8 and AAV9 serotypes having AAV2 plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Viral vectors (109 vg/μl) were topically applied onto mouse cornea in vivo and human cornea ex vivo after removing the epithelium. Human corneas were processed for transgene delivery at day 5 after viral vector application. Mouse corneas were harvested …

Defensins In Ocular Immunity, Minhao Wu

Wayne State University Dissertations

Corneal infection with P. aeruginosa results in corneal perforation in susceptible

B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal

infection, and their potential synergy. Immunostaining and real-time RT-PCR data

demonstrated that their expression was either constitutive (mBD1 and mBD2) or

inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately

regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA

treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in

ocular defense. Moreover, in vivo studies demonstrated individual and combined effects

of mBD2 and …

Differential Gene Expression Profile Of Retinoblastoma Compared To Normal Retina., Arupa Ganguly, Carol L Shields

Wills Eye Hospital Papers

PURPOSE: The retinoblastoma gene (RB1) is a tumor suppressor gene that was first discovered in a rare ocular pediatric tumor called retinoblastoma (RB). The RB1 gene is essential for normal progression through the cell cycle and exerts part of its function through the family of transcription factors (E2F) and many other intermediaries. In the absence of normal RB1, genomic instability and chromosomal aberrations accumulate, leading to tumor initiation, progression, and ultimately metastasis. The purpose of this report was to identify the molecular pathways that are deregulated in retinoblastoma.

METHODS: We compared gene expression signatures of matched normal retinal tissue and …

Molecular Confirmation Of The Causes Of Inherited Visual Impairment In Northern Pakistan, Mehreen Adhi, Yasmin Rashid, Syed Hussain Jafri, Chris F. Inglehearn, Martin Mc Kibbin

Department of Medicine

Families with inherited visual impairment were identified and examined from January 2000 to December 2005 and given a clinical diagnosis. Known genes and loci were screened for mutations or linkage at Institute of Ophthalmology and Neurosciences, University of Leeds, in order to provide molecular confirmation. Inherited retinal disease was the most common cause of inherited visual impairment in 38 of 57 families (66.6%) with Leber’s congenital amaurosis, rod-cone dystrophy and cone-rod dystrophy being the most common diagnoses in 22, 8 and 3 families respectively. Anterior segment dysgenesis was diagnosed in 8 families (14%). Mutations in known genes or linkage to …

Oculocardiac Reflex Elicited During Debridement Of An Empty Orbit, James C. Tsai, Md, James W. Heitz, Md, Edward H. Bedrossian Jr, Md Facs

Wills Eye Hospital Papers

87 yo male with history of hypertension and right periorbital basal cell carcinoma s/p previous right total ethmoidectomy, right maxillary antrostomy, and complete right orbital exenteration for basal cell carcinoma invading the right ethmoid sinus. Functional endoscopic sinus surgery and orbital exploration was scheduled for excision of recurrent basal cell carcinoma. Rapid sequence induction and intubation was uneventful. During right orbital base curettage, the patient experienced several precipitious episodes of profound bradycardia or brief asystole. After surgery, the patient denied cardiac symptoms, and cardiac enzymes were all normal. Oculocardiac-mediated bradyarrhythmias are rarely elicited from empty orbits.

Methods And Animal Model For Analyzing Age-Related Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Methods for testing candidate drugs for treatment of age-related macular degeneration are provided. Ccl2-deficient, and Ccr2-deficient mice are used to determine the effect of candidate drugs and treatments on development of age-related macular degeneration. Also provided is a Ccl2-deficient, Ccr2-deficient dual knockout mouse, which is a useful animal model for age-related macular degeneration.

Orbital Aspergillus Infection Mimicking A Tumour: A Case Report, Muhammad Ahsan Zafar, Syeda Sidra Waheed, Ather Enam

Section of Neurosurgery

A 14-year-old male presented to the neurosurgical clinic with swelling just above the right eye which had been growing slowly for the last eight years. The swelling first appeared following a non-penetrating trauma eight years ago. On examination it was a non-tender, non-erythematous, firm, round swelling causing marked proptosis and diplopia on downward gaze only. The visual acuity was intact. MRI showed an intraorbital, extraconal mass isointense on T1 and hypointense on T2 imaging. A diagnosis of orbital tumor was made. A white, friable mass consistent with meningioma was resected. However histopathology report later showed it to be an Aspergilloma. …

Calcium Homeostasis And Cone Signaling Are Regulated By Interactions Between Calcium Stores And Plasma Membrane Ion Channels., Tamas Szikra, Peter Barabas, Theodore M. Bartoletti, Wei Huang, Abram Akopian, Wallace B. Thoreson, David Krizaj

Journal Articles: Ophthalmology

Calcium is a messenger ion that controls all aspects of cone photoreceptor function, including synaptic release. The dynamic range of the cone output extends beyond the activation threshold for voltage-operated calcium entry, suggesting another calcium influx mechanism operates in cones hyperpolarized by light. We have used optical imaging and whole-cell voltage clamp to measure the contribution of store-operated Ca(2+) entry (SOCE) to Ca(2+) homeostasis and its role in regulation of neurotransmission at cone synapses. Mn(2+) quenching of Fura-2 revealed sustained divalent cation entry in hyperpolarized cones. Ca(2+) influx into cone inner segments was potentiated by hyperpolarization, facilitated by depletion of …

The Effect Of Endothelin-1 On The Expression Of Cdk Inhibitors P21 & P27 In Bovine Corneal Endothelial Cells, Lakshmi Reddy Bollu

Masters Theses & Specialist Projects

Mammalian corneal endothelial cells are considered to be non-proliferative due to the arrest of cells at the G1 phase of the cell cycle. The purpose of this study was to determine whether the down regulation of cyclin dependant kinase inhibitors (p21cip1 and p27kip1) levels by Endothelin-1 (ET-1), would overcome the G1 phase arrest and promote cell cycle progression and proliferation in cultured BCECs (Bovine corneal endothelial cells). BCECs were isolated from bovine corneas and cultured in DMEM supplemented with 10% serum. 5-Bromo 2-deoxy Uridine (BrdU) incorporation was determined in serum starved cultures in 24-well plates as a measure of cell …