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A Comparison Between Optical Coherence Tomography Angiography And Fluorescein Angiography For The Imaging Of Type 1 Neovascularization., Maiko Inoue, Jesse J. Jung, Chandrakumar Balaratnasingam, Kunal K. Dansingani, Elona Dhrami-Gavazi, Mihoko Suzuki, Talisa E. de Carlo, Abtin Shahlaee, Michael A. Klufas, Adil El Maftouhi, Jay S. Duker, Allen C. Ho, Maddalena Quaranta-El Maftouhi, David Sarraf, K. Bailey Freund 2016 Vitreous Retina Macula Consultants of New York

A Comparison Between Optical Coherence Tomography Angiography And Fluorescein Angiography For The Imaging Of Type 1 Neovascularization., Maiko Inoue, Jesse J. Jung, Chandrakumar Balaratnasingam, Kunal K. Dansingani, Elona Dhrami-Gavazi, Mihoko Suzuki, Talisa E. De Carlo, Abtin Shahlaee, Michael A. Klufas, Adil El Maftouhi, Jay S. Duker, Allen C. Ho, Maddalena Quaranta-El Maftouhi, David Sarraf, K. Bailey Freund

Wills Eye Institute Papers

Purpose: To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA.

Methods: Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA ...


Illness Cognitions And Coping Self-Efficacy In Depression Among Persons With Low Vision., Bonnie A Sturrock, Jing Xie, Edith E Holloway, Mark Hegel, Robin J. Casten, David Mellor, Eva Fenwick, Gwyneth Rees 2016 University of Melbourne

Illness Cognitions And Coping Self-Efficacy In Depression Among Persons With Low Vision., Bonnie A Sturrock, Jing Xie, Edith E Holloway, Mark Hegel, Robin J. Casten, David Mellor, Eva Fenwick, Gwyneth Rees

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: To investigate the mediating role of coping self-efficacy (CSE) between two types of illness cognitions (i.e., acceptance and helplessness) and depressive symptoms in persons with low vision.

METHODS: This was a single-group, cross-sectional study. Patients with visual acuity < 6/12 in the better eye and at least minimal depressive symptoms (≥5 on the Patient Health Questionnaire-9 [PHQ-9]) were recruited from vision rehabilitation services and participated in telephone-administered structured interviews at one time point. Measures were the PHQ-9, CSE Scale, and Illness Cognition Questionnaire. Structural equation modeling (SEM) devised the causal flow of illness cognitions and their observed indirect effects on depressive symptoms via the CSE mediators: problem focused, emotion focused, and social support.

RESULTS: The study comprised 163 patients (mean age 62 years; 61% female), most with age-related macular degeneration (26%) and moderate vision impairment (44%, <6/18-6/60). Structural equation modeling indices indicated a perfect fit (χ2 < 0.001, P = 1.00), accounting for 55% of the variance in depressive symptoms. Lower levels of acceptance and higher levels of helplessness illness cognitions were associated with lower self-efficacy in problem-focused coping (β = 0.38, P < 0.001, β = -0.28, P < 0.01, respectively), which in turn was associated with greater depressive symptom severity (β = -0.54, P < 0.001).

CONCLUSIONS: Lack of acceptance and greater helplessness relating to low vision led to a lack of perceived capability to engage in problem-focused coping, which in turn promoted depressive symptoms. Third-wave cognitive-behavioral treatments that focus on acceptance may ...


Radiotherapy For Iris Metastasis From Esophageal Carcinoma: A Series Of Three Cases., Chandana Das, Carol L Shields 2016 Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University

Radiotherapy For Iris Metastasis From Esophageal Carcinoma: A Series Of Three Cases., Chandana Das, Carol L Shields

Wills Eye Institute Papers

BACKGROUND: Description of three cases of metastatic esophageal carcinoma to the iris and focus on management strategies.

METHODS: A 48-year-old man (Case 1) with previously treated stage IV esophageal carcinoma presented with blurred vision in the left eye (OS) for 3 weeks. Initial fine needle aspiration biopsy (FNAB) was negative for malignant cells, so incisional biopsy was performed and confirmed metastatic carcinoma. A 53-year-old man (Case 2) with previously treated stage III esophageal cancer experienced 2 months of pain and 1 month of blurred vision OS. Documented tumor growth suggested esophageal carcinoma metastasis. A 65-year-old man (Case 3) with previously ...


Prenylated Retinal Ciliopathy Protein Rpgr Regulates Ciliary Localization Of Joubert Syndrome-Associated Protein Inpp5e In Cooperation With Pde6, Wei Zhang, Kollu N. Rao, Linjing Li, Manisha Anand, Hemant Khanna 2016 University of Massachusetts Medical School

Prenylated Retinal Ciliopathy Protein Rpgr Regulates Ciliary Localization Of Joubert Syndrome-Associated Protein Inpp5e In Cooperation With Pde6, Wei Zhang, Kollu N. Rao, Linjing Li, Manisha Anand, Hemant Khanna

UMass Center for Clinical and Translational Science Research Retreat

Ciliary dysfunction is an underlying cause of severe human disorders (collectively called ciliopathies), such as retinitis pigmentosa (RP), Joubert Syndrome (JBTS), and Bardet-Biedl Syndrome. Ciliary proteins form distinct functional networks for localization to cilia as well as regulation of ciliary function. However, not much is known about the mechanism of ciliary localization and function of RPGR (retinitis pigmentosa GTPase regulator), a ciliary protein frequently associated with RP worldwide. Using tandem mass spectrometry analysis, we show that RPGR interacts with two JBTS-associated proteins: PDE6Π (delta subunit of Phosphodiesterase; a prenyl-binding protein) and INPP5E (inositol polyphosphate-5-phosphatase 5E; a ciliary cargo). Whereas PDE6Π ...


Compositions And Methods For Treating Retinal Degradation, Jayakrishna Ambati, Benjamin J. Fowler 2016 University of Kentucky

Compositions And Methods For Treating Retinal Degradation, Jayakrishna Ambati, Benjamin J. Fowler

Ophthalmology and Visual Science Faculty Patents

The present disclosure relates to compositions and methods for treating retinal damage and/or retinal degradation. More specifically, this disclosure relates to methods for treating degradation of the retinal pigment epithelium by administering compositions comprising a nucleoside and/or a nucleoside or nucleotide reverse transcriptase inhibitor.


Validation Of Humanized Mouse Antibodies, MeiLing G. Norfolk, Rocco J. Rotello 2016 Cedarville University

Validation Of Humanized Mouse Antibodies, Meiling G. Norfolk, Rocco J. Rotello

The Research and Scholarship Symposium

Antibody therapy is being developed and tested as one of the most promising agents for treatment of various human diseases. As of March 2016, 350 antibody candidates are in clinical trials. Many of these antibodies have been taken from animals and “humanized” by genetic modification. Our experiment tests monoclonal antibodies that have been harvested from mouse hybridoma (spleen-derived) cells and cloned until the heavy and light chains of the antibody can be recognized by human cells. Because of this “humanization” procedure, basic antibody assays are needed to demonstrate that the binding, specificity and functional parameters of the antibodies are not ...


The Carboxyl Terminal Mutational Hotspot Of The Ciliary Disease Protein Rpgrorf15 (Retinitis Pigmentosa Gtpase Regulator) Is Glutamylated In Vivo, Kollu N. Rao, Manisha Anand, Hemant Khanna 2016 University of Massachusetts Medical School

The Carboxyl Terminal Mutational Hotspot Of The Ciliary Disease Protein Rpgrorf15 (Retinitis Pigmentosa Gtpase Regulator) Is Glutamylated In Vivo, Kollu N. Rao, Manisha Anand, Hemant Khanna

Open Access Articles

Mutations inRPGR(ORF15)(retinitis pigmentosa GTPase regulator) are a major cause of inherited retinal degenerative diseases. RPGR(ORF15)(1152 residues) is a ciliary protein involved in regulating the composition and function of photoreceptor cilia. The mutational hotspot in RPGR(ORF15)is an unusual C-terminal domain encoded by exon ORF15, which is rich in polyglutamates and glycine residues (Glu-Gly domain) followed by a short stretch of basic amino acid residues (RPGR(C2)domain; residues 1072-1152). However, the properties of the ORF15-encoded domain and its involvement in the pathogenesis of the disease are unclear. Here we show that RPGR(ORF15)is glutamylated ...


Ocular Surface Reconstruction In Laryngo-Onycho-Cutaneous Syndrome, Ashik Mohamed, Virender Sangwan 2016 Selected Works

Ocular Surface Reconstruction In Laryngo-Onycho-Cutaneous Syndrome, Ashik Mohamed, Virender Sangwan

Ashik Mohamed


Improved Cell Metabolism Prolongs Photoreceptor Survival Upon Retinal-Pigmented Epithelium Loss In The Sodium Iodate Induced Model Of Geographic Atrophy, Marina Zieger, Claudio Punzo 2016 University of Massachusetts Medical School

Improved Cell Metabolism Prolongs Photoreceptor Survival Upon Retinal-Pigmented Epithelium Loss In The Sodium Iodate Induced Model Of Geographic Atrophy, Marina Zieger, Claudio Punzo

Open Access Articles

Age-related macular degeneration (AMD) is characterized by malfunction and loss of retinal-pigmented epithelium (RPE) cells. Because the RPE transfers nutrients from the choriocapillaris to photoreceptor (PR), PRs are affected as well. Geographic atrophy (GA) is an advanced form of AMD characterized by severe vision impairment due to RPE loss over large areas. Currently there is no treatment to delay the degeneration of nutrient deprived PRs once RPE cells die. Here we show that cell-autonomous activation of the key regulator of cell metabolism, the kinase mammalian target of rapamycin complex 1 (mTORC1), delays PR death in the sodium iodate induced model ...


Cataract Surgery In Chronic Stevens–Johnson Syndrome: Aspects And Outcomes, Purvasha Narang, Ashik Mohamed, Vikas Mittal, Virender Sangwan 2016 Selected Works

Cataract Surgery In Chronic Stevens–Johnson Syndrome: Aspects And Outcomes, Purvasha Narang, Ashik Mohamed, Vikas Mittal, Virender Sangwan

Ashik Mohamed

Aims: To assess the outcomes of cataract surgery in patients with chronic sequelae of Stevens-Johnson Syndrome (SJS).

Methods: Setting: Tertiary eye care center in South India. Design: Retrospective, non-comparative, consecutive, interventional case series. Study period: Mar-2003 to May-2014. Of the 1662 consecutive SJS patients, 32 patients (40 eyes) with chronic sequelae of SJS who underwent cataract surgery were included. The main outcome measures were best-corrected visual acuity (BCVA) and ocular surface stabilization. The visual acuity was expressed with reference to the logMAR.

Results:The study included 12 males (37.5%) and 20 females (62.5%). Eight patients (25%) had bilateral ...


Ophthalmic Drugs 2016, Lorne Yudcovitch 2016 Pacific University

Ophthalmic Drugs 2016, Lorne Yudcovitch

Faculty Scholarship (COO)

This chart serves as a basic reference guide showcasing the most common ophthalmic drugs, updated as of the beginning of 2016. Both topical ophthalmic and oral medications indicated for the eye are included, with Food and Drug Administration/American Academy of Ophthalmology cap color representation when indicated. Medications with generic versions are noted with an asterisk(*).


Consecutive Bilateral Decompression Retinopathy After Mitomycin C Trabeculectomy: A Case Report., Ana Raquel Marcos Figueiredo, Isabel Coutinho Sampaio, Maria João Fernandes Dos Santos Menéres, George L. Spaeth 2016 Ophthalmology Department, Centro Hospital Do Porto, EPE - Hospital de Santo António, Largo Professor Abel Salazar, Porto, Portugal

Consecutive Bilateral Decompression Retinopathy After Mitomycin C Trabeculectomy: A Case Report., Ana Raquel Marcos Figueiredo, Isabel Coutinho Sampaio, Maria João Fernandes Dos Santos Menéres, George L. Spaeth

Wills Eye Institute Papers

BACKGROUND: After a successful trabeculectomy, a sudden intraocular pressure decrease may alter the intracranial to intraocular pressure ratio and cause decompression retinopathy. Frequent Valsalva maneuvers may also play a role in its pathogenesis. This condition may manifest as multiple retinal hemorrhages, edema of the optic disc, macular edema, or a sudden decrease in visual acuity postoperatively. Outcomes for patients are usually good, with spontaneous resolution occurring within a matter of weeks. It has been rarely reported in the literature as a bilateral condition.

CASE PRESENTATION: We present a case of consecutive bilateral decompression retinopathy in a 54-year-old severely obese Caucasian ...


Raav2/5 Gene-Targeting To Rods: Dose-Dependent Efficiency And Complications Associated With Different Promoters, William Beltran, Sanford Boye, Shannon Boye, Vince Chiodo, Alfred Lewin, William Hauswirth, Gustavo Aguirre 2016 University of Pennsylvania

Raav2/5 Gene-Targeting To Rods: Dose-Dependent Efficiency And Complications Associated With Different Promoters, William Beltran, Sanford Boye, Shannon Boye, Vince Chiodo, Alfred Lewin, William Hauswirth, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

A prerequisite for using corrective gene therapy to treat humans with inherited retinal degenerative diseases that primarily affect rods is to develop viral vectors that target specifically this population of photoreceptors. The delivery of a viral vector with photoreceptor tropism coupled with a rod-specific promoter is likely to be the safest and most efficient approach to target expression of the therapeutic gene to rods. Three promoters that included a fragment of the proximal mouse opsin promoter (mOP), the human G-protein-coupled receptor protein kinase 1 promoter (hGRK1), or the cytomegalovirus immediate early enhancer combined with the chicken β actin proximal promoter ...


Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna Kukekova, Gustavo Aguirre, Gregory Acland 2016 University of Pennsylvania

Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna Kukekova, Gustavo Aguirre, Gregory Acland

Gustavo D. Aguirre, VMD, PhD

Fine mapping followed by candidate gene analysis of erd — a canine hereditary retinal degeneration characterized by aberrant photoreceptor development — established that the disease cosegregates with a SINE insertion in exon 4 of the canine STK38L/NDR2 gene. The mutation removes exon 4 from STK38L transcripts and is predicted to remove much of the N terminus from the translated protein, including binding sites for S100B and Mob proteins, part of the protein kinase domain, and a Thr-75 residue critical for autophosphorylation. Although known to have roles in neuronal cell function, the STK38L pathway has not previously been implicated in normal or ...


Sudden Acquired Retinal Degeneration In The Dog: Clinical And Morphologic Characterization Of The "Silent Retina" Syndrome, Gregory Acland, Nita Irby, Gustavo Aguirre, Stephen Gross, Susan Nitroy, Kathleen Notarfrancesco 2016 University of Pennsylvania

Sudden Acquired Retinal Degeneration In The Dog: Clinical And Morphologic Characterization Of The "Silent Retina" Syndrome, Gregory Acland, Nita Irby, Gustavo Aguirre, Stephen Gross, Susan Nitroy, Kathleen Notarfrancesco

Gustavo D. Aguirre, VMD, PhD

Adult dogs occasionally become suddenly, totally and permanently blind. If examined soon after the onset of blindness, the dogs show no ophthalmologic evidence of disease sufficient to account for their problem and are usually in otherwise good health. The hallmark of this sudden, acquired retinal degeneration (SARD), that establishes it as a retinopathy, and distinguishes it from neurological disease, is the extinguished electroretinogram. The syndrome has been termed "Silent Retina Syndrome" and "Metabolic Toxic Retinopathy". Although uncommon, SARD has been diagnosed with increased frequency in recent years. Little retinal tissue has, however, become available for histopathologic characterization of the disease ...


Photoreceptor Dysplasia: An Inherited Progressive Retinal Atrophy Of Miniature Schnauzer Dogs, Charles Parshall, Milton Wyman, Susan Nitroy, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Photoreceptor Dysplasia: An Inherited Progressive Retinal Atrophy Of Miniature Schnauzer Dogs, Charles Parshall, Milton Wyman, Susan Nitroy, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

A progressive retinal atrophy (PRA) affecting Miniature Schnauzer dogs is reported. Of the 287 individuals (148 female, 139 male) comprising the study population, 66 (23 percent) were affected (33 female, 33 male) and 221 animals (115 female, 106 male) were phenotypically normal. There was no sex predilection for the disease. Results of histologic and electroretinographic studies indicate that the disease is a new and different type of PRA, characterized by unique morphologic and functional deficits during rod and cone development. Accordingly, the disease has been termed photoreceptor dysplasia. Clinically, and particularly ophthalmoscopically, diagnosis is only practicable in very late stages ...


Drug Delivery To Posterior Intraocular Tissues: Third Annual Arvo/Pfizer Ophthalmics Research Institute Conference, Henry Edelhauser, Jeffrey Boatright, John Nickerson, Gustavo Aguirre 2016 University of Pennsylvania

Drug Delivery To Posterior Intraocular Tissues: Third Annual Arvo/Pfizer Ophthalmics Research Institute Conference, Henry Edelhauser, Jeffrey Boatright, John Nickerson, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

The third Annual ARVO/Pfizer Ophthalmic Research Institute Conference was held Friday and Saturday, May 4 and 5, 2007 at the Fort Lauderdale Grande Hotel and Yacht Club, Fort Lauderdale, Florida. The conference, funded by the ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to develop strategies to address drug delivery to posterior intraocular tissues—a topic of great interest, as the major route of drug delivery is via intravitreous injection.


Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair Philip, Sarah Lindauer, Susan Pearce-Kelling, Roberts Mullins, Alexander Graphodatsky, Daniel Ripoll, Jeanette Felix, Edwin Stone, Gregory Acland, Gustavo Aguirre 2016 University of Pennsylvania

Identical Mutation In A Novel Retinal Gene Causes Progressive Rod-Cone Degeneration In Dogs And Retinitis Pigmentosa In Humans, Barbara Zangerl, Orly Goldstein, Alisdair Philip, Sarah Lindauer, Susan Pearce-Kelling, Roberts Mullins, Alexander Graphodatsky, Daniel Ripoll, Jeanette Felix, Edwin Stone, Gregory Acland, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Progressive rod–cone degeneration (prcd) is a late-onset, autosomal recessive photoreceptor degeneration of dogs and a homolog for some forms of human retinitis pigmentosa (RP). Previously, the disease-relevant interval was reduced to a 106-kb region on CFA9, and a common phenotype-specific haplotype was identified in all affected dogs from several different breeds and breed varieties. Screening of a canine retinal EST library identified partial cDNAs for novel candidate genes in the disease-relevant interval. The complete cDNA of one of these, PRCD, was cloned in dog, human, and mouse. The gene codes for a 54-amino-acid (aa) protein in dog and human ...


Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András Komáromy, John Alexander, Anne Cooper, Vince Chodo, Gregory Acland, William Hauswirth, Gustavo Aguirre 2016 University of Pennsylvania

Targeting Gene Expression To Cones With Human Cone Opsin Promoters In Recombinant Aav, András Komáromy, John Alexander, Anne Cooper, Vince Chodo, Gregory Acland, William Hauswirth, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Specific cone-directed therapy is of high priority in the treatment of human hereditary retinal diseases. However, not much information exists about the specific targeting of photoreceptor subclasses. Three versions of the human red cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin promoter HB569, were evaluated for their specificity and robustness in targeting green fluorescent protein (GFP) gene expression to subclasses of cones in the canine retina when used in recombinant adeno-associated viral vectors of serotype 5. The vectors were administered by subretinal injection. The promoter PR2.1 led to most effective and ...


The Briard Problem, Ronald Riis, Gustavo Aguirre 2016 University of Pennsylvania

The Briard Problem, Ronald Riis, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

The Briard breed has stimulated some ophthalmic interest in Canada, Europe, and the United States. Ophthalmoscopic changes similar to central progressive retinal atrophy have been diagnosed. This report adds further insight into the type of retinal degeneration and questions the associated physical findings as they may relate to the retinal disease.


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