Ophthalmology Commons^™

Retinal Angiogenesis Suppression Through Small Molecule Activation Of P53, Sai H. Chavala, Younghee Kim, Laura Tudisco, Valeria Cicatiello, Till Milde, Nagaraj Kerur, Nidia Claros, Susan Yanni, Victor H. Guaiquil, William W. Hauswirth, John S. Penn, Shahin Rafii, Sandro De Falco, Thomas C. Lee, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Neovascular age-related macular degeneration is a leading cause of irreversible vision loss in the Western world. Cytokine-targeted therapies (such as anti-vascular endothelial growth factor) are effective in treating pathologic ocular angiogenesis, but have not led to a durable effect and often require indefinite treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3 ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems. We found that a functional p53 pathway was essential for Nutlin-3-mediated retinal antiangiogenesis and disruption of the p53 transcriptional network abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit established, mature blood vessels …

Long-Term Outcomes Of Ranibizumab Therapy For Diabetic Macular Edema: The 36-Month Results From Two Phase Iii Trials: Rise And Ride., David M. Brown, Quan Dong Nguyen, Dennis M. Marcus, David S. Boyer, Sunil Patel, Leonard Feiner, Patricio G. Schlottmann, Amy Chen Rundle, Jiameng Zhang, Roman G. Rubio, Anthony P. Adamis, Jason S. Ehrlich, J. Jill Hopkins

Journal Articles: Ophthalmology

PURPOSE: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME).

DESIGN: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years.

PARTICIPANTS: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥ 275 μm on optical coherence tomography.

METHODS: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser …

Longitudinal Spectral Domain Optical Coherence Tomography Changes In Eyes With Intraocular Lymphoma, Hyun Soo Jang, Yasir J. Sepah, Raafay Sophie, Millena G. Bittencourt, Daniel Ferraz, Mostafa Hanout, Hongting Liu, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND:

Cases of patients with primary intraocular lymphoma (PIOL) were retrospectively analyzed to describe the longitudinal intra-retinal morphological changes in PIOL as visualized on images obtained by spectral domain optical coherence tomography (SD-OCT).

RESULTS:

In a retrospective case series, Heidelberg Spectralis SD-OCT images obtained in the longitudinal evaluation of patients with biopsy-proven PIOL were analyzed and assessed. The images were graded for the presence of macular edema (ME), pigment epithelial detachment (PED), subretinal fluid (SRF), and hyperreflective signals. SD-OCT scans of five eyes from five patients were assessed. Patients showed signs of inflammation, such as ME and SRF, which were …

Peripheral Laser Iridoplasty Opens Angle In Plateau Iris By Thinning The Cross-Sectional Tissues, Ji Liu, Tania Lamba, David A. Belyea

Ophthalmology Faculty Publications

Plateau iris syndrome has been described as persistent angle narrowing or occlusion with intraocular pressure elevation after peripheral iridotomy due to the abnormal plateau iris configuration. Argon laser peripheral iridoplasty (ALPI) is an effective adjunct procedure to treat plateau iris syndrome. Classic theory suggests that the laser causes the contraction of the far peripheral iris stroma, "pulls" the iris away from the angle, and relieves the iris-angle apposition. We report a case of plateau iris syndrome that was successfully treated with ALPI. Spectral domain optical coherence tomography confirmed the angle was open at areas with laser treatment but remained appositionally …

Long-Term Outcome Of Primary External Dacryocystorhinostomy, Rashid Baig, Qazi Assad Khan, Khabir Ahmad

Department of Surgery

bstract

OBJECTIVE:

To assess the long-term functional outcome of external dacryocystorhinostomy (DCR) in terms of epiphora.

STUDY DESIGN:

Single-group cohort study.

PLACE AND DURATION OF STUDY:

Section of Ophthalmology, The Aga Khan University Hospital, Karachi, from January 2000 to June 2010.

METHODOLOGY:

This study included adults who underwent external DCR surgery at the AKUH during January 2000 to June 2010. The main outcome measure was the proportion of patients reporting to have developed epiphora after surgery. During the telephonic interviews participants were asked if they had a recurrence (symptoms such as watering or discharge) after surgery. Individuals answering in affirmative …

Periocular Infantile Haemangioma And The Role Of Propranolol., Tanveer Anjum Chaudhry, Mustafa Kamal, Khabir Ahmad

Department of Surgery

ABSTRACT This case of a four and a half-month-old girl describes periocular infantile haemangioma which was treated successfully with propranolol. She developed a red coloured lesion around the left upper eye lid at one week of age. A gradual increase was noticed in the size of the lesion and by the age of four and a half months, the swelling had increased enough to cover her visual axis, completely occluding her left eye. Oral propranolol therapy was initiated with a daily dosage of 1 mg/kg body weight. The dose was increased gradually, and there was an excellent response to propranolol …

Improving Function 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 problem-solving therapy (PST) with supportive therapy (ST) to improve targeted vision function (TVF) in age-related macular degeneration (AMD).

DESIGN: Single-masked, attention-controlled, randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects).

PARTICIPANTS: Patients with AMD (n = 241) attending retina practices.

INTERVENTIONS: Whereas PST uses a structured problem-solving approach to reduce vision-related task difficulty, ST is a standardized attention-control treatment.

MAIN OUTCOME MEASURES: We assessed TVF, the 25-item National Eye Institute Vision Function Questionnaire plus Supplement (NEI VFQ), the Activities Inventory (AI), and vision-related quality of life …

Ultra-Small Rnas As Toll-Like Receptor-3 Antagonists, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Provided are methods and compositions for the treatment or prevention of macular degeneration or other diseases or disorders associated with activation of TLR3. Administration of double stranded RNAs having a length of 22 nucleotides or less treats or prevents macular degeneration or other diseases or disorders associated with activation of TLR3 due to the ability of the RNAs to bind to but not activate TLR3. Furthermore, all double stranded RNAs (both targeted and non-targeted) of 22 nucleotides or less in length can bind to but not activate TLR3 and thereby treat or prevent such conditions. Also provided of a method …

Horner's Syndrome Secondary To Neuroblastoma, Roberto A. Cruz, T. K. Tran, Nicky R. Holdeman, Christian Cajavilca, Rosa A. Tang

School of Medicine Publications and Presentations

Horner’s syndrome is classically characterized by a triad of miosis, partial ptosis and anhidrosis. The etiology is due to an interruption in the sympathetic innervation to the eye. A prompt diagnosis is crucial, given that Horner’s syndrome could be a manifestation of a life-threatening condition. A thorough case history and clinical evaluation must be employed to arrive at the diagnosis. An important means for confirming Horner’s syndrome is pharmacological testing, which is also used to localize the level where the sympathetic chain is compromised. Following the diagnosis and localization of the lesion, an algorithm should be followed to determine the …

Visual Outcome Of Cataract Surgery., Farzeen Khalid Hashmi, Qazi Assad Khan, Tanveer Anjum Chaudhry, Khabir Ahmad

Department of Surgery

bstract

The aim of this study was to assess whether the visual outcome of cataract surgery in the institution was in accordance with the World Health Organization recommendations. In this retrospective case series, all patients who underwent cataract surgery by a single surgeon from January 2009 till June 2011 were included. Date were collected from medical records on age, gender, visual acuity and causes of sub-optimal outcome. The main outcome was best-corrected visual acuity in the operated eye, measured 4 - 6 weeks after surgery. Data on visual outcome was grouped using WHO's classification. Of the 495 eyes that underwent …

Visual Outcome Of Cataract Surgery, Farzeen Khalid Hashmi, Qazi Assad Khan, Tanveer Anjum Chaudhry, Khabir Ahmad

Department of Surgery

Abstract

The aim of this study was to assess whether the visual outcome of cataract surgery in the institution was in accordance with the World Health Organization recommendations. In this retrospective case series, all patients who underwent cataract surgery by a single surgeon from January 2009 till June 2011 were included. Date were collected from medical records on age, gender, visual acuity and causes of sub-optimal outcome. The main outcome was best-corrected visual acuity in the operated eye, measured 4 - 6 weeks after surgery. Data on visual outcome was grouped using WHO's classification. Of the 495 eyes that underwent …

Withaferin A Effectively Targets Soluble Vimentin In The Glaucoma Filtration Surgical Model Of Fibrosis, Paola Bargagna-Mohan, Sunil P. Deokule, Kyle G. Thompson, John Wizeman, Cidambi Srinivasan, Sunil Vooturi, Uday B. Kompella, Royce Mohan

Ophthalmology and Visual Science Faculty Publications

Withaferin A (WFA) is a natural product that binds to soluble forms of the type III intermediate filament (IF) vimentin. Currently, it is unknown under what pathophysiological contexts vimentin is druggable, as cytoskeltal vimentin-IFs are abundantly expressed. To investigate druggability of vimentin, we exploited rabbit Tenon's capsule fibroblast (RbTCF) cell cultures and the rabbit glaucoma filtration surgical (GFS) model of fibrosis. WFA potently caused G₀/G₁ cell cycle inhibition (IC₅₀ 25 nM) in RbTCFs, downregulating ubiquitin E3 ligase skp2 and inducing p27(Kip1) expression. Transforming growth factor (TGF)-ß-induced myofibroblast transformation caused development of cell spheroids with numerous elongated invadopodia, which WFA blocked …

Reliability And Reproducibility Of Spectral And Time Domain Optical Coherence Tomography Images Before And After Correction For Patients With Age-Related Macular Degeneration., Mohammad A. Sadiq, Aymen Rashid, Roomasa Channa, Elham Hatef, Diana V. Do, Quan Dong Nguyen, Yasir J. Sepah

Journal Articles: Ophthalmology

PURPOSE: To evaluate the reproducibility and reliability of optical coherence tomography scans obtained using the time domain (TD-OCT) Stratus (TM) OCT, and the Spectral Domain (SD-OCT) Spectralis (TM) and Cirrus (TM) OCT devices before and after manual correction in eyes with either Neovascular (NV-AMD) or Non-Neovascular (NNV-AMD) age-related macular degeneration.

DESIGN: Prospective observational study.

SETTING: University-based retina practice.

PATIENTS: Thirty-six patients (50 eyes) with NV-AMD or NNV-AMD.

PROCEDURE: OCT scans were taken simultaneously using one TD-OCT and two SD-OCT devices.

MAIN OUTCOME MEASURES: Macular thickness measurements were assessed before and after correction of the algorithm by constructing Bland-Altman plots for …

Corticosteroids As Adjuvant Therapy For Ocular Toxoplasmosis., Smitha Jasper, Satyanarayana S. Vedula, Sheeja S. John, Saban Horo, Yasir J. Sepah, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND: Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae.

OBJECTIVES: The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean …

The Muranga Teleophthalmology Study: Comparison Of Virtual (Teleglaucoma) With In-Person Clinical Assessment To Diagnose Glaucoma, Dan Kiage, Irfan N. Kherani, Stephen Gichuhi, Karim F. Damji, Muindi Nyenze

Internal Medicine, East Africa

Purpose: While the effectiveness of teleophthalmology is generally accepted, its ability to diagnose glaucomatous eye disease remains relatively unknown. This study aimed to compare a web-based teleophthalmology assessment with clinical slit lamp examination to screen for glaucoma among diabetics in a rural African district.

Materials and Methods: Three hundred and nine diabetic patients underwent both the clinical slit lamp examination by a comprehensive ophthalmologist and teleglaucoma (TG) assessment by a glaucoma subspecialist. Both assessments were compared for any focal glaucoma damage; for TG, the quality of photographs was assessed, and vertical cup-to-disk ratio (VCDR) was calculated in a semi-automated manner. …

Lasik In Hyperopic Eyes With Congenital Nystagmus: A Case Report, Sharmeen Akram, Zarksis H, Khabir Ahmad

Department of Surgery

Patients with nystagmus are considered to be poor candidates for laser in situ keratomileusis (LASIK), because they are unable to fixate. This case report presents the first reported use of LASIK surgery with a solid-state laser in hypermetropia and congenital nystagmus. A 23 year old woman with congenital nystagmus had LASIK surgery to correct a refractive error of +2.25/+1.75 90º in the right eye and + 2.00 / +1.75 90º in the left one. Baseline uncorrected visual acuity (UCVA) was 20/200 in both eyes, and best spectacle corrected visual acuity was 20/40 in both the eyes. The procedure was performed …

Ultra-Wide-Field Retinal Imaging In The Management Of Non-Infectious Retinal Vasculitis., Henry A. Leder, John P. Campbell, Yasir J. Sepah, Theresa Gan, James P. Dunn, Elham Hatef, Brian Cho, Mohamed Ibrahim, Millena Bittencourt, Roomasa Channa, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND: The purpose of this study is to describe and quantify the benefit of ultra-wide-field imaging and fluorescein angiography (FA) in the management of non-infectious retinal vasculitis. In this prospective observational cohort series, patients with non-infectious retinal vasculitis were evaluated and enrolled by four investigators from the Divisions of Retina and Ocular Immunology at the Wilmer Eye Institute. In each patient, disease activity and the need for management changes were assessed, based on clinical examination with or without standard (60°) imaging and then with the addition of ultra-wide-field pseudo-color scanning laser ophthalmoscope (SLO) images and FA using the Optos ultra-wide-field …

Ocular Tolerability And Efficacy Of Intravitreal And Subconjunctival Injections Of Sirolimus In Patients With Non-Infectious Uveitis: Primary 6-Month Results Of The Save Study., Quan Dong Nguyen, Mohamed A. Ibrahim, Anthony Watters, Millena Bittencourt, Jithin Yohannan, Yasir J. Sepah, James P. Dunn, Joel Naor, Naveed Shams, Ovais Shaikh, Henry Alexander Leder, Diana V. Do

Journal Articles: Ophthalmology

BACKGROUND: The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0, 60, and 120, with primary endpoint at month 6.

RESULTS: At month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty …

Lateral Mobility Of L-Type Calcium Channels In Synaptic Terminals Of Retinal Bipolar Cells., Wallace B. Thoreson, Aaron J. Mercer, Karlene M. Cork, Robert J. Szalewski

Journal Articles: Ophthalmology

PURPOSE: Efficient and precise release of glutamate from retinal bipolar cells is ensured by the positioning of L-type Ca(2+) channels close to release sites at the base of the synaptic ribbon. We investigated whether Ca(2+) channels at bipolar cell ribbon synapses are fixed in position or capable of moving in the membrane.

METHODS: We tracked the movements of individual L-type Ca(2+) channels in bipolar cell terminals after labeling channels with quantum dots (QDs) attached to α(2)δ(4) accessory Ca(2+) channel subunits via intermediary antibodies.

RESULTS: We found that individual Ca(2+) channels moved within a confined domain of 0.13-0.15 μm(2) in bipolar …

Characterization Of High-Voltage-Activated Calcium Channels In Retinal Bipolar Cells, Qi Lu

Wayne State University Dissertations

Retinal bipolar cells, conveying visual information from photoreceptors to ganglion cells, segregate visual information into multiple parallel pathways through their diversified cell types and physiological properties. Voltage-gated Ca²⁺ channels could be particularly important underlying the diversified physiological properties of different BCs. In this dissertation, I investigated the high-voltage-activated (HVA) calcium current in retinal bipolar cells in mice. In the first part of my dissertation, I characterized multiple bipolar cell-expressing GFP and/or Cre transgenic mouse lines. In the second part of my dissertation, by performing whole-cell patch-clamp recordings, I examined the electrophysiological properties of HVA calcium currents among CBCs and …