Ophthalmology Commons^™

The Myopia Epidemic: Exploring The Pathology And Management Of The World’S Most Common Eye Disorder, Gabriella Baldassarre, Bs

inSIGHT

Myopia is the most common eye disorder in the world and an increasing cause of vision impairment in children.¹ Myopia is an imbalance in the refractive components of the eye and its length, leading to inaccurate focusing of light rays in front of the retina tissue instead of on it. There is a spectrum of severity of myopia, from mild nearsightedness to a more severe form known as high or degenerative myopia, which has the potential to cause vision loss and blindness. There is evidence of a developing myopia epidemic, with an estimated one-third of the world population affected …

Association Of Chronic Central Serous Chorioretinopathy With Subclinical Cushing's Syndrome., Rebecca Russ Soares, Annika Samuelson, Allen Chiang

Wills Eye Hospital Papers

Purpose: To report the clinical course of a patient with central serous chorioretinopathy (CSCR) secondary to subclinical hypercortisolism before and after adrenalectomy.

Observations: A 50-year-old female patient with multifocal, chronic CSCR was found to have an adrenal incidentaloma and was diagnosed with subclinical hypercortisolism. Patient elected to undergo minimally-invasive adrenalectomy and presented at 3 months after surgery without subretinal fluid.

Conclusions and importance: Subclinical Cushing's Syndrome (SCS) may present an underrecognized risk factor for developing chronic CSCR. Further investigation is needed to determine the threshold of visual comorbidity that may influence surgical management.

Understanding Blue Light Retinal Damages And The Methods Of Prevention, Amelia Lee

Senior Honors Theses

Light emitting diode (LED) lights that comprise television screens, phone displays, laptops, and tablets have been studied by scientists in order to understand the implications of blue light radiation and the effects that it has on the human body—especially the retina of the eye. The retina is comprised of highly metabolic cells, and when those cells are placed under oxidative stress, death occurs causing ocular disease. Additionally, excess blue light exposure causes shifts in biological rhythms that govern patterns of alertness and sleep. Recently scientists began studying the methods of blue light prevention. Some studies show that blue light radiation …

Conditional Analysis On New Tumor Formation With Solitary Unilateral Retinoblastoma In 482 Consecutive Patients, Carol L Shields, Philip W Dockery, Megan Ruben, Madalyne A Sunday, Martin Calotti, Antonio Yaghy

Wills Eye Hospital Papers

PURPOSE: The objective of the study was to understand dynamic risk (conditional analysis based on patient age) for new tumor development in patients with solitary unilateral retinoblastoma.

METHODS: This was a retrospective analysis.

RESULTS: Of 482 patients with solitary unilateral retinoblastoma, 55 new tumors developed in 20 patients (4%). Comparison (new tumor vs. no new tumor development) revealed those with new tumor demonstrated younger mean age at presentation (10 vs. 36 months,

CONCLUSION: Children (≤24 months) with solitary unilateral retinoblastoma showed decreasing risk for new tumors up to 24 months of life. Later onset of new tumor was more likely …

Glut1 Deficiency: Retinal Detrimental Effects Of Gliovascular Modulation, Matt Henry, John Kitchens, Juan M. Pascual, Ramiro S. Maldonado

Ophthalmology and Visual Science Faculty Publications

No abstract provided.

Melanopsin-Expressing Retinal Ganglion Cells In Control Vs. Glaucomatous Retinas, Edward Hamad

Williams Honors College, Honors Research Projects

Glaucoma is a common cause of vision loss worldwide and has a large scope of symptoms, ranging from pupillary reflex defects to sleep disorders. These issues can be explained partially by a recently found subtype of retinal ganglion cells that express melanopsin, denoted melanopsin-expressing retinal ganglion cells or mRGCs for short. These cells function primarily as photoreceptors in the non-image forming pathway, but can receive input from rods and cones. Since mRGCs play a role in the pupillary reflex and regulation of the sleep-wake cycle, I investigated if glaucoma leads to the degeneration of these cells in a mouse model …

Melanocytoma Of The Optic Disk: A Review., Jerry A. Shields, Hakan Demirci, Arman Mashayekhi, Ralph C. Eagle Jr., Carol L. Shields

Wills Eye Hospital Papers

Melanocytoma is a deeply pigmented variant of melanocytic nevus that classically occurs in the optic disk, sometimes with contiguous involvement of the adjacent retina or choroid. Historically, this tumor was often confused with malignant melanoma both clinically and histopathologically. Today, however, it is generally recognized by its typical clinical features that differ from most melanomas and erroneous enucleation is rarely done. Histopathologically, melanocytoma is composed of intensely pigmented round to oval nevus cells with benign features. Although traditionally believed to be a relatively stationary lesion, it is now known to exhibit minor enlargement in 10--15% of cases and can cause …

Neurofibromatosis Type-1 With Retinal Microvascular Corkscrew Tortuosity., Adrian J Battiston, Lauren A Dalvin, Carol L Shields

Wills Eye Hospital Papers

No abstract available.

Coats Disease In 351 Eyes: Analysis Of Features And Outcomes Over 45 Years (By Decade) At A Single Center., Carol L. Shields, Sanika Udyaver, Lauren A. Dalvin, Li-Anne S. Lim, Hatice T Atalay, Chloe T.L. Khoo, Mehdi Mazloumi, Jerry A. Shields

Wills Eye Hospital Papers

Purpose: To assess features and outcomes of Coats disease over 5-decades.

Methods: Retrospective review of Coats disease patients at a single center. Features and outcomes were compared based on decade of presentation.

Results: There were 351 patients with Coats disease. The presenting median age (6 years), male sex (84%), and unilaterality (100%) did not change per decade. Coats disease classification did not change per decade with Stage 1 (1%), Stage 2 (21%), Stage 3 (68%), Stage 4 (6%), and Stage 5 (1%). Clinical features that changed per decade (1970s vs. 1980s vs. 1990s vs. 2000s vs. 2010s) included 1980s features …

Commentary: Ganglion Cell Complex Of Retinal Layer Thickness By Optical Coherence Tomography In Cases Of Multiple Sclerosis Without Optic Neuritis Compared To Healthy Eyes, Padmaja Sudhakar

Neurology Faculty Publications

No abstract provided.

Submillimeter Retinoblastoma Monitoring Following Transpupillary Thermotherapy Using Hand-Held Optical Coherence Tomography, Mark Mcgarrey, Thamolwan Surakiatchanukul, Carol L. Shields

Wills Eye Hospital Papers

Background: Precise, submillimeter visualization of retinal microstructures is useful for treatment monitoring of retinoblastoma. Herein, we report the use of hand-held optical coherence tomography (HH-OCT) to document a nearly-invisible retinoblastoma and monitor tumor response to transpupillary thermotherapy (TTT). Case presentation: A 3-week-old boy was diagnosed with unilateral familial retinoblastoma in the left eye, classified as group B, and treated with intravenous chemoreduction. At 13-month follow-up, the tumor in the left eye was regressed, and evaluation of the right eye revealed a microscopic, nearly invisible tumor measuring 372 μm in thickness and 1.51 mm in basal dimension. The tumor was confirmed …

A Model For Investigating Developmental Eye Repair In Xenopus Laevis, Cindy X. Kha, Philip H. Son, Julia Lauper, Kelly Ai-Sun Tseng

Life Sciences Faculty Research

Vertebrate eye development is complex and requires early interactions between neuroectoderm and surface ectoderm during embryogenesis. In the African clawed frog, Xenopus laevis, individual eye tissues such as the retina and lens can undergo regeneration. However, it has been reported that removal of either the specified eye field at the neurula stage or the eye during tadpole stage does not induce replacement. Here we describe a model for investigating Xenopus developmental eye repair. We found that tailbud embryos can readily regrow eyes after surgical removal of over 83% of the specified eye and lens tissues. The regrown eye reached a …

Elevated Pressure Increases Ca2+ Influx Through Ampa Receptors In Select Populations Of Retinal Ganglion Cells, Xiangyi Wen, Asia L. Cahill, Cody Barta, Wallace B. Thoreson, Scott Nawy

Journal Articles: Ophthalmology

The predominate type of AMPA receptor expressed in the CNS is impermeable to Ca²⁺ (CI-AMPAR). However, some AMPA receptors are permeable to Ca²⁺ (CP-AMPAR) and play important roles in development, plasticity and disease. In the retina, ganglion cells (RGCs) are targets of disease including glaucoma and diabetic retinopathy, but there are many types of RGCs and not all types are targeted equally. In the present study, we sought to determine if there are differences in expression of AMPARs amongst RGC subtypes, and if these differences might contribute to differential vulnerability in a model of stress. Using cultured RGCs …

Farnesylation Of The Transducin G Protein Gamma Subunit Is A Prerequisite For Its Ciliary Targeting In Rod Photoreceptors, Celine Brooks, Joseph Murphy, Marycharmain Belcastro, Daniel Heller, Saravanan Kolandaivelu, Oleg Kisselev, Maxim Sokolov

Faculty & Staff Scholarship

Primary cilia are microtubule-based organelles, which protrude from the plasma membrane and receive a wide range of extracellular signals. Various cilia use G protein-coupled receptors (GPCRs) for the detection of these signals. For instance, vertebrate rod photoreceptors use their cilia (also called outer segments) as antennae detecting photons by GPCR rhodopsin. Rhodopsin recognizes incoming light and activates its G protein, transducin, which is composed of three subunits α, β, and γ. Similar to all G protein γ subunits, the transducin Gγ1 subunit undergoes C-terminal prenylation resulting in the addition of an isoprenoid farnesyl; however, the significance of this posttranslational modification …

Cgas Drives Noncanonical-Inflammasome Activation In Age-Related Macular Degeneration, Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J. Fowler, Elmira Baghdasaryan, Kenneth M. Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L. Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R. Hinton, Norbert Leitinger, John C. Cambier, Joseph D. Buxbaum, M. Cristina Kenney, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin …

Parafoveolar Retinoblastoma Regression With Foveal Preservation Following Intra-Arterial Chemotherapy Documented On Hand-Held Optical Coherence Tomography In A Newborn., Vera Yarovaya, Kareem Sioufi, Carol L Shields

Wills Eye Hospital Papers

Background: Optical coherence tomography (OCT) has become an invaluable tool in retinoblastoma management, providing submillimeter visualization of tumor control following treatment. Herein, we document OCT-detection of a subtle tumor recurrence, allowing early intervention and achieving foveal microanatomy preservation.

Case presentation: A 3-week-old girl was diagnosed with bilateral familial retinoblastoma, classified as group D in the right eye (OD) and group B in the left eye (OS), and treated with intravenous chemoreduction. At 6-months follow-up, the right eye was under control, but the left eye revealed a subtle juxtafoveal tumor recurrence, documented on handheld OCT (HH-OCT) and measuring 2750 µm in …

A Clinico-Pathological Study Of The Structural And Functional Changes In The Retina And Optic Nerve Following Diabetic Retinopathy Treatments, Richard Filek

Electronic Thesis and Dissertation Repository

Diabetic retinopathy (DR) is the result of microvascular changes in the retina due to hyperglycemia which alter the blood-retinal barrier (BRB). The increased permeability of BRB results in the accumulation of extracellular fluid, the development of diabetic macular edema (DME) and capillary occlusion. Capillary occlusion results in retinal ischemia which increases vascular endothelial growth factor (VEGF) levels, increases vascular permeability and results in neovascularization in proliferative diabetic retinopathy (PDR) patients. The treatments clinically used for DR are panretinal photocoagulation (PRP) for PDR and injectable vascular endothelial growth factor inhibitors (anti-VEGFs) for DME.

The safety of PRP and anti-VEGF therapy on …

Synaptic Ribbon Active Zones In Cone Photoreceptors Operate Independently From One Another., Justin J. Grassmeyer, Wallace B. Thoreson

Journal Articles: Ophthalmology

Cone photoreceptors depolarize in darkness to release glutamate-laden synaptic vesicles. Essential to release is the synaptic ribbon, a structure that helps organize active zones by clustering vesicles near proteins that mediate exocytosis, including voltage-gated Ca(2+) channels. Cone terminals have many ribbon-style active zones at which second-order neurons receive input. We asked whether there are functionally significant differences in local Ca(2+) influx among ribbons in individual cones. We combined confocal Ca(2+) imaging to measure Ca(2+) influx at individual ribbons and patch clamp recordings to record whole-cell ICa in salamander cones. We found that the voltage for half-maximal activation (V50) of whole …

Prevention Of Glaucoma-Induced Retinal Ganglion Cell Loss Using Alpha7 Nachr Agonists, P J. Birkholz, C A. Gossman, M K. Webster, David M. Linn, Cindy L. Linn

Peer Reviewed Articles

In this study, the neuroprotective effect of various nicotinic alpha7 acetylcholine receptor agonists in an in-vivo model of glaucoma using adult Long Evans rats was analyzed. Glaucoma-like conditions were induced in the eyes of Long Evans rats after injection of hypertonic saline into episcleral veins to create scar tissue and increase the animal’s intraocular pressure. This procedure produced significant loss of retinal ganglion cells within one month and was associated with an increase of intraocular pressure. Using this model system, various alpha7 nicotinic acetylcholine receptor (a7 nAChR) agonists were applied at different doses as eye drops to the right eye …

Raav2/5 Gene-Targeting To Rods: Dose-Dependent Efficiency And Complications Associated With Different Promoters, William Beltran, Sanford L. Boye, Shannon E. Boye, Vince A. Chiodo, Alfred S. Lewin, William W. Hauswirth, Gustavo D. 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 …

Photoreceptor Cell Death, Proliferation And Formation Of Hybrid Rod/S-Cone Photoreceptors In The Degenerating Stk38l Mutant Retina, Ágnes I. Berta, Kathleen Boesze-Battaglia, Sem Genini, Orly Goldstein, Paul J. O'Brien, Ágoston Szél, Gregory M. Acland, William Beltran, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

A homozygous mutation in STK38L in dogs impairs the late phase of photoreceptor development, and is followed by photoreceptor cell death (TUNEL) and proliferation (PCNA, PHH3) events that occur independently in different cells between 7–14 weeks of age. During this period, the outer nuclear layer (ONL) cell number is unchanged. The dividing cells are of photoreceptor origin, have rod opsin labeling, and do not label with markers specific for macrophages/microglia (CD18) or Müller cells (glutamine synthetase, PAX6). Nestin labeling is absent from the ONL although it labels the peripheral retina and ciliary marginal zone equally in normals and mutants. Cell …

Canine Retina Has A Primate Fovea-Like Bouquet Of Cone Photoreceptors Which Is Affected By Inherited Macular Degenerations, William Beltran, Artur V. Cideciyan, Karina E. Guziewicz, Simone Iwabe, Erin M. Scott, Svetlana V. Savina, Gordon Ruthel, Frank Stefano, Lingli Zhang, Richard Zorger, Alexander Sumaroka, Samuel G. Jacobson, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Retinal areas of specialization confer vertebrates with the ability to scrutinize corresponding regions of their visual field with greater resolution. A highly specialized area found in haplorhine primates (including humans) is the fovea centralis which is defined by a high density of cone photoreceptors connected individually to interneurons, and retinal ganglion cells (RGCs) that are offset to form a pit lacking retinal capillaries and inner retinal neurons at its center. In dogs, a local increase in RGC density is found in a topographically comparable retinal area defined as the area centralis. While the canine retina is devoid of a foveal …

Cloning And Characterization Of The Cdna Encoding The Α-Subunit Of Cgmp-Phosphodiesterase In Canine Retinal Rod Photoreceptor Cells, Weiquan Wang, Gregory M. Acland, Gustavo D. Aguirre, Kunal Ray

Gustavo D. Aguirre, VMD, PhD

No abstract provided.

Up-Regulation Of Tumor Necrosis Factor Superfamily Genes In Early Phases Of Photoreceptor Degeneration, Sem Genini, William Beltran, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

We used quantitative real-time PCR to examine the expression of 112 genes related to retinal function and/or belonging to known pro-apoptotic, cell survival, and autophagy pathways during photoreceptor degeneration in three early-onset canine models of human photoreceptor degeneration, rod cone dysplasia 1 (rcd1), X-linked progressive retinal atrophy 2 (xlpra2), and early retinal degeneration (erd), caused respectively, by mutations in PDE6B, RPGRORF15, and STK38L. Notably, we found that expression and timing of differentially expressed (DE) genes correlated with the cell death kinetics. Gene expression profiles of rcd1 and xlpra2 were similar; however rcd1 was more severe as demonstrated by the results …

Intravitreal Injection Of Ciliary Neurotrophic Factor (Cntf) Causes Peripheral Remodeling And Does Not Prevent Photoreceptor Loss In Canine Rpgr Mutant Retina, William Beltran, Rong Wen, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15. Four different treatment regimens of CNTF were tested in XLPRA2 dogs. Under anesthesia, the animals received at different ages an intravitreal injection of 12 μg of CNTF in the left eye. The right eye served as a control and was injected …

Iron Toxicity In The Retina Requires Alu Rna And The Nlrp3 Inflammasome, Bradley D. Gelfand, Charles B. Wright, Younghee Kim, Tetsuhiro Yasuma, Reo Yasuma, Shengjian Li, Benjamin J. Fowler, Ana Bastos-Carvalho, Nagaraj Kerur, Annette Uittenbogaard, Youn Seon Han, Dingyuan Lou, Mark E. Kleinman, W. Hayes Mcdonald, Gabriel Núñez, Philippe Georgel, Joshua L. Dunaief, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Excess iron induces tissue damage and is implicated in age-related macular degeneration (AMD). Iron toxicity is widely attributed to hydroxyl radical formation through Fenton's reaction. We report that excess iron, but not other Fenton catalytic metals, induces activation of the NLRP3 inflammasome, a pathway also implicated in AMD. Additionally, iron-induced degeneration of the retinal pigmented epithelium (RPE) is suppressed in mice lacking inflammasome components caspase-1/11 or Nlrp3 or by inhibition of caspase-1. Iron overload increases abundance of RNAs transcribed from short interspersed nuclear elements (SINEs): Alu RNAs and the rodent equivalent B1 and B2 RNAs, which are inflammasome agonists. Targeting …

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, …

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 …

Retina-Simulating Phantom For Optical Coherence Tomography., Jigesh Baxi, William Calhoun, Yasir Jamal Sepah, Daniel X. Hammer, Ilko Ilev, T. Joshua Pfefer, Quan Dong Nguyen, Anant Agrawal

Journal Articles: Ophthalmology

Optical coherence tomography (OCT) is a rapidly growing imaging modality, particularly in the field of ophthalmology. Accurate early diagnosis of diseases requires consistent and validated imaging performance. In contrast to more well-established medical imaging modalities, no standardized test methods currently exist for OCT quality assurance. We developed a retinal phantom which mimics the thickness and near-infrared optical properties of each anatomical retinal layer as well as the surface topography of the foveal pit. The fabrication process involves layer-by-layer spin coating of nanoparticle-embedded silicone films followed by laser micro-etching to modify the surface topography. The thickness of each layer and dimensions …

Complement Expression In The Retina Is Not Influenced By Short-Term Pressure Elevation, Konstantin Astafurov, Cecilia Q. Dong, Lampros Panagis, Gautam Kamtham, Lizhen Ren, Anna Rozenboym, Tarique D. Perera, Jeremy D. Coplan, John Danias

Publications and Research

Purpose: To determine whether short-term pressure elevation affects complement gene expression in the retina in vitro and in vivo.

Methods: Muller cell (TR-MUL5) cultures and organotypic retinal cultures from adult mice and monkeys were sub- jected to either 24-h or 72-h of pressure at 0, 15, 30, and 45 mmHg above ambient. C57BL/6 mice were subjected to microbead-induced intraocular pressure (IOP) elevation for 7 days. RNA and protein were extracted and used for analysis of expression levels of complement component genes and complement component 1, q subcomponent (C1q) and comple- ment factor H (CFH) immunoblotting. …