Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 4th International Conference on Clinical & Experimental Ophthalmology Baltimore, USA.

Day 2 :

  • Keynote Forum
Location: Harbor Room

Session Introduction

Sayon Roy

Boston University School of Medicine, USA

Title: Vascular homeostasis in diabetic retinopathy

Time : 09:00-09:25

Speaker
Biography:

Sayon Roy received his Ph.D. from Boston University and completed his postdoctoral training at Schepens Eye Research Institute, Harvard Medical School, Harvard University; Roy is currently a Professor of Medicine, Section of Diabetes, Endocrinology and Nutrition, and a Professor of Ophthalmology at Boston University School of Medicine. Recognized as an expert in retinal vascular biology, Dr. Roy’s seminal work has identified several genes in the retina that are abnormally expressed in diabetic retinopathy. His pioneering work has led to novel gene modulatory techniques in retinal vascular cells using antisense oligonucleotides via intravitreal injection. Dr. Roy has received numerous awards including the American Diabetes Association Research Award for the commitment and dedication towards the fight against diabetes, the 2006 Mentor of the Year Award from Boston University, and the 2008 Innovative Award from the Juvenile Diabetes Research Foundation. Research in Roy’s laboratory has been funded by several organizations including the National Eye Institute, NIH, National Medical Technology Testbed, American Diabetes Association, Juvenile Diabetes Research Foundation International, Fight for Sight, Research to Prevent Blindness, and the Lions Organization. Dr. Roy currently serves as a chartered member of the NEI Study Section of the National Institutes of Health.

Abstract:

Global increase in the diabetic population forecasts a significant rise in the number of people with diabetes-related retinal diseases. An overwhelming cause of vision loss in diabetic individuals is the breakdown of retinal vascular homeostasis, contributing to excess permeability and the development of macular edema, a prominent clinical manifestation of diabetic retinopathy. Despite the use of laser photocoagulation, and available therapeutics, majority of the patients do not fully recover functional vision. Research into areas involving cell-cell communication and blood retinal barrier characteristics has uncovered a significant underlying factor that contributes to both these functional changes. Our studies indicate that abnormal thickening of the vascular basement membrane (BM) can contribute to excess vascular permeability, breakdown in cell-cell communication, and retinal vascular cell loss. It has long been established that vascular BM thickening is a characteristic hallmark of diabetic microangiopathy, however, it is unclear how vascular BM thickening promotes the characteristic lesions seen in diabetic retinopathy. Recent studies have begun to shed light on this subject suggesting vascular BM thickening as a key player that not only compromises the BRB characteristics but also affects vascular homeostasis and promotes cell loss associated with the development and progression of diabetic retinopathy. Importantly, our research has identified several BM genes, fibronectin, collagen IV, and laminin that are abnormally expressed under hyperglycemic condition and contribute to abnormal cell-cell communication and retinal vascular leakage. A strategy for decreasing BM thickening and how this could prevent vascular leakage and contribute to the maintenance of vascular homeostasis in the diabetic retina will be the topic of this presentation.

Jayne S. Weiss

Louisiana State University Health Sciences Center, USA

Title: Schnyder corneal dystrophy- A case study in translational research

Time : 09:25-09:50

Speaker
Biography:

Jayne S. Weiss is Chair of the LSU Department of Ophthalmology, Herbert E Kaufman MD endowed Chair, Professor of Ophthalmology, Pharmacology and Pathology and Director of LSU Eye Center in New Orleans, Louisiana. She began her research on Schnyder corneal dystrophy 25 years ago recruiting patients internationally leading to the gene discovery. The misleading disease nomenclature led her to establish the International Committee for Classification of Corneal Dystrophies whose new nomenclature system including genetic information is now used for the dystrophies. She is a member of the National Advisory Eye Council, a consultant to the FDA Ophthalmic Devices Panel and Assistant Editor of the journal, Cornea.

Abstract:

Schnyder Corneal Dystrophy (SCD) has been an exceptional model for questions and answers that result from the bedside to bench approach of translational research. A medline search indicates the term translational research appeared as early as 1993, a few years after I examined the originalitial four large pedigrees of affected patients with Schnyder dystrophy. Initial investigation led to my simple clinical observation that only 50% of affected patients with Schnyder crystalline corneal dystrophy had corneal crystals. Patients without crystals were typically misdiagnosed. The nomenclature challenges later led to creation of the International Committee for Classification of Corneal Dystrophies and revision of the dystrophy nomenclature in 2008 to be based on genetic, histopathologic and clinical findings rather than just phenotype. Histopathologic changes of affected SCD corneas demonstrated abnormal collection of intra and extracellular cholesterol reminiscent of atherosclerosis. The assumption that that understanding pathogenesis of SCD might increase our understanding of lipid metabolism, led to the search for the affected chromosome, chromosome 1 and then the isolation of the abnormal gene, UBIAD1. Although arcus, a peripheral corneal ring composed of LDL is the most common type of cholesterol deposition in humans, the central corneal deposit of SCD was found to be HDL. Specific dog species often have deposition of cholesterol in the central cornea, while peripheral arcus occurs less commonly. Interestingly, the predominant blood cholesterol component in humans is LDL while in dogs is HDL. Can comparisons between human and dog cholesterol HDL and LDL distribution provide further understanding about SCD and lipid metabolism in the cornea and systemically?

  • Special session on
Location: Harbor Room
Speaker

Chair

Michael L. Nickerson

National Institutes of Health, USA

Speaker

Co-Chair

Michael Dean

National Cancer Institute at Frederick, USA

Session Introduction

Michael Dean

National Cancer Institute at Frederick, USA

Title: Insights into eye diseases and biology using genetics

Time : 09:50-10:10

Speaker
Biography:

Michael Dean obtained his Ph.D. from the Biochemistry Department at the Boston University School of Medicine. He performed his postdoctoral studies at the National Cancer Institute on the MET oncogene and cystic fibrosis gene. His laboratory's objective is to develop methods for analyzing complex diseases and to apply them to cancer and human genetic and infectious diseases. He has applied exome sequencing to detect novel and known cancer gene mutations in bladder, kidney, prostate, and adrenal tumors. Current projects include collaborations in Guatemala, Mexico, and Venezuela to study cervical cancer, HPV infection rates, retinoblastoma, and leukemia. He is a member of the American Society of Human Genetics, American Association of Cancer Research, Centre Etude du Polymorphisme Humaine (CEPH), the Human Genome Organization (HUGO), a Special Advisor to BGI-Shenzhen in China and an adjunct faculty member at Hood College.

Abstract:

The eye has represented the organ most accessible to clinical observation and one of the organs for which patients regularly seek treatment for dysfunction. As such, the genetics and biology of eye diseases have a rich history. In addition, because of the complexity of the visual cycle and architecture of vision, there are numerous inherited and complex disorders affecting vision. Examples will be provided of dominant, recessive, and X-linked ophthalmic diseases that have been analyzed and understood using molecular genetics and medicine. Furthermore, an update on the complex disease, age-related macular degeneration (AMD), the most common cause of vision loss will be presented. AMD is one of the more complex diseases that is best understood by genetic analysis, with examples of common variants with moderate effect (i.e. in genes CFH, CFH, ARMS2) as well as rare variants with strong effect (i.e. in genes ABCA4, CFH). These examples provide an informative context to understand recent progress on Schnyder Corneal Dystrophy.

Jayne S. Weiss

Louisiana State University Health Sciences Center, USA

Title: Schnyder corneal dystrophy- A window to insights on cholesterol, Vitamin K and Parkinson’s disease?

Time : 10:10-10:30

Speaker
Biography:

Jayne S. Weiss is Chair of the LSU Department of Ophthalmology, Herbert E Kaufman MD endowed Chair,Professor of Ophthalmology, Pharmacology and Pathology and Director of LSU Eye Center in New Orleans, Louisiana. She began her research on Schnyder corneal dystrophy 25 years ago recruiting patients internationally leading to the gene discovery. The misleading disease nomenclature led her to establish the International Committee for Classification of Corneal Dystrophies whose new nomenclature system including genetic information is now used for the dystrophies. She is a member of the National Advisory Eye Council, a consultant to the FDA Ophthalmic Devices Panel and Assistant Editor of the journal, Cornea.

Abstract:

Schnyder crystalline corneal dystrophy (SCD), first described in 1924, is an autosomal dominant inherited disease with corneal clouding resulting from abnormal cholesterol deposition in the front of the eye, the cornea. In the late 1980’s, I discovered four large pedigrees of Swede Finn individuals with SCD. At that time, there were less than 100 articles on the disease in the peer reviewed literature. In 1992, I published the clinical findings in 18 affected members of these families I had examined which was the largest number of affected patients ever described in one publication at that time. One new finding was that although the disease name was Schnyder crystalline corneal dystrophy, only 50% of affected individuals actually had corneal crystals. Both affected and unaffected members of SCD pedigrees may have elevated blood cholesterol making it difficult to determine if high circulating cholesterol is associated with SCD. The eye disease progresses with age, independent of blood cholesterol value. From the beginning, even though a clinician, I continued recruitment of affected individuals in my hope that understanding this rare eye disease, could lead to better understanding of systemic cholesterol and lipid metabolism. One early collaborator, Howard Kruth MD, shared my vision. Later on, Mike Nickerson Ph.D. also agreed with the importance of finding the gene for this rare disease. I performed corneal transplantation surgery on patients visually disabled from the corneal clouding of SCD and sent the tissue to Dr. Kruth’s laboratory for analysis which revealed that the abnormal lipid deposition was entirely HDL, not LDL suggesting a local abnormality of HDL metabolism. At the same time we found that the disease mapped to chromosome 1, but it took another decade before we and another group independently identified mutations in SCD patients in the UBIAD1 gene on chromosome 1p36. Recruitment efforts continued internationally. By 2007, I had followed 115 individuals who had SCD for up to 18 years. Although the disease had been thought to be visually benign, 54% of patients 50 and younger and 77% of patients 70 and younger had reported corneal transplant surgery. Many patients without corneal crystals eluded correct diagnosis because of the confusing nomenclature. For this reason, I founded the International Committee for Classification of Corneal Dystrophies (IC3D) which revised the entire corneal dystrophy nomenclature and also renamed this disease Schnyder corneal dystrophy. Most recently UBIAD1 has been found by others to be a human vitamin K2 (MK-4) biosynthetic enzyme and has been found to have links to bladder cancer and Parkinson’s disease.

Break: Coffee Break 10:30-10:45 @ Prefunction Area

Xueting Jin

National Health of Institutes, USA

Title: Schnyder corneal dystrophy - Abnormal cholesterol homeostasis in a connective tissue

Time : 10:45-11:05

Speaker
Biography:

Xueting Jin obtained her M.D. from the Medical Center of Fudan University, Shanghai, and qualified as a physician in 2012. During medical school, she participated in several research projects, mainly focused on the mechanism of atherosclerosis. She is currently a postdoctoral fellow at the National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland. Her research interests include disorders of cholesterol metabolism, focused on Schnyder corneal dystrophy and atherosclerosis.

Abstract:

Schnyder corneal dystrophy (SCD) is characterized by accumulation of lipids and lipid particles in the cornea similar to those lipid particles that accumulate in human atherosclerotic plaques. Cholesterol and phospholipid accumulate in the extracellular connective tissue space of both diseases in the form of crystals, liposomes, and droplets.Thus, there may be some pathogenic similarities between these disease-causing lipid accumulations. Cholesterol accumulation can result from an imbalance in deposition and removal. Some genetic disorders affecting HDL function (LCAT, ABCA1, and apoAI deficiencies) also result in corneal lipid deposition with similarities to SCD. In this regard, HDL-associated apolipoproteins (apo), apoAI and apoE, show increased accumulation in Schnyder corneas, and UBIAD1,the defective gene in SCD, interacts with the C-terminal portion of apoE. Because HDL functions to remove cholesterol from tissues, it is possible that cholesterol removal from the SCD corneas is impaired. On the other hand, UBIAD1, a prenyltransferase domain-containing protein,shows similarities to genes involved in regulation of the cholesterol synthesis pathway, and interacts with HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. Thus, it is also possible that increased cholesterol synthesis is the cause of cholesterol accumulation in SCD corneas. The predominantly mitochondrial location of UBIAD1 in corneal keratocytes suggests a possible link between mitochondrial and cholesterol metabolism. Identification of the gene defect in SCD makes it possible to test these different potential mechanisms of cholesterol accumulation, and to learn more about the regulation of cholesterol homeostasis in the cornea and other similar connective tissues such as the blood vessel wall.

Speaker
Biography:

Nickerson obtained a Ph.D. in Molecular Medicine from the George Washington University and has made significant contributions to the identification of disease genes, including the Birt-Hogg-Dubé gene in chromophobe kidney cancer, the dead-end gene in testicular cancer, the fumarate hydratase gene in leiomyomatosis and papillary kidney cancer, and the UBIAD1 gene in Schnyder Corneal Dystrophy (SCD). He has applied exome sequencing of tumor genomes to identify TET2 alterations in prostate cancer and BAP1 and CHD1 mutations in bladder cancer. UBIAD1 mutations in over 50 SCD families, and enzyme structure, function, and binding partners have been published.

Abstract:

Schnyder corneal dystrophy (SCD) is an autosomal dominant disease characterized by deposition of cholesterol in the cornea, progressive opacification, and loss of visual acuity. Germline variants in UBIAD1 introducing missense alterations have been characterized in over 50 SCD families, including four large families from Finland who share a likely founder mutation. UBIAD1 was recently shown to catalyze synthesis of two mitochondrial electron carriers, menaquinone-4 (MK-4) and coenzyme Q10/ubiquinone (CoQ10). MK-4 is the predominant active form of vitamin K and an important cofactor in bone metabolism and blood clotting. We show SCD-altered UBIAD1 resulted in reduced MK-4 synthesis and molecular models indicated mutations disrupted active site residues and transmembrane helices. Yeast two-hybrid screening, co-immunoprecipitation, and confocal microscopy indicated interactions between UBIAD1 and HMGCR and SOAT1, enzymes catalyzing cholesterol synthesis and storage. Molecular modeling indicated cholesterol and geranylgeranyl diphosphate, a substrate for MK-4 synthesis, bind the same substrate binding cleft and likely compete for occupancy of UBIAD1. Vitamin K was originally identified by depletion of dietary cholesterol in chickens, which co-depleted dietary vitamin K, and resulted in hemorrhages and uncontrolled bleeding. In addition to a role for vitamin K in blood clotting, our data suggests a first physiologic role for endogenously produced vitamin K in maintaining cornea health and visual acuity. The data indicates synthesis of vitamin K, CoQ10, and cholesterol are tightly linked and may have significant impact on oxidative stress, vision, cardiovascular health, and cancer.

Toshio Okano

Kobe Pharmaceutical University, Japan

Title: Emerging role of UBIAD1 in embryonic development of mammals

Time : 13:30-13:50

Speaker
Biography:

Toshio Okano received a Ph.D. in Pharmaceutical Sciences from Osaka University in 1979, and he is serving as a Professor and Chairman of the Department of Hygienic Sciences at Kobe Pharmaceutical University since 1996. He has made significant contributions to the basic and clinical sciences of vitamin D and vitamin K. In the past decade, his interests have been concentrating especially to explore additional functions and molecular mechanism of vitamin K beyond its canonical role as a co-factor for carboxylation in mammals. He and his co-workers succeeded in finding a first human vitamin K biosynthetic enzyme, UBIAD1 in 2010.

Abstract:

We recently demonstrated that dietary phylloquinone/vitamin K1 releases menadione/vitamin K3 by the cleavage of the side chain in the intestine, followed by delivery of menadione through the mesenteric lymphatic system and blood circulation to tissues, where menadione is converted into MK-4/vitamin K2, and accumulates in the form of MK-4. UBIAD1 is a novel MK-4 biosynthetic enzyme screened and identified from the human genome database. Surprisingly, UBIAD1 was recently shown to catalyze the CoQ10 biosynthesis in zebrafish and human cells. Enzymatic analysis using site-directed mutagenesis revealed that UBIAD1 is capable of generating various menaquinones including MK-4, and UBIAD1 missense mutations in Schnyder Corneal Dystrophy (SCD) lower MK-4 biosynthetic activity significantly. To clarify the function of UBIAD1 in vivo, we attempted to generate mice completely lacking ubiad1, a homolog of human UBIAD1 by gene targeting. Ubiad1-deficient (ubiad1-/-) mouse embryos failed to survive beyond embryonic day 7.5, exhibiting small-sized body and gastrulation arrest. Ubiad1+/- mice developed normally, exhibited normal growth and fertility. Their tissue concentrations and synthetic activity of MK-4 were approximately half of the wild-type levels, whereas their tissue concentrations and synthetic activity of CoQ9 were similar to the wild-type levels, respectively. Ubiad1-/- mouse embryos failed to be rescued, but their embryonic lifespans were extended to term by oral administration of MK-4 or CoQ10 to pregnant ubiad1+/- mice. These results suggest that ubiad1 plays a critical role in embryonic development through synthesizing MK-4, but may have additional functions beyond the MK-4 biosynthesis.

Speaker
Biography:

Massimo M. Santoro obtained is Master Diploma from University of Turin, Italy and his Ph.D. in Molecular and Cellular Biology from the Open University, London, UK. In 2001 he received his first post-doctoral training at University of Piemonte Orientale, and then he moved to University of California, San Francisco, USA, where he became interested in vascular development and in health and diseased angiogenesis. In 2008, he moved back to Italy at University of Turin where he established his laboratory of Cardiovascular Biology as Assistant Professor. In 2013 he was appointed VIB Group Leader and Professor at Vesalius Research Center, University of Leuven, Belgium. He is holding an HFSP Career Developmental Award and Marie Curie Reintegration Grant. His aim is to expand the current knowledge of how metabolism regulates endothelial redox homeostasis and vice-versa in healthy and diseased conditions. To accomplish this goal his lab has taken advantage of the innovative genetic and imaging technology as well as new molecular and biochemical approaches in vertebrate models, including zebrafish and mouse. Using a set of new cellular, molecular, and genetic approaches as well as advanced microscopy techniques he is willing to identify new redox mechanisms involved in vascular metabolism and homeostasis.

Abstract:

Protection against oxidative damage caused by excessive reactive oxygen species (ROS) by an anti- oxidant network is essential for the health of tissues, especially in the cardiovascular system. Here, we identified a gene with important antioxidant features by analyzing a null allele of zebrafish ubiad1, called barolo (bar). Bar mutants show specific cardiovascular failure due to oxidative stress and ROS-mediated cellular damage. Human UBIAD1 is a non-mitochondrial prenyltransferase that synthesizes CoQ10 in the Golgi membrane compartment. Loss of UBIAD1 reduces the cytosolic pool of the antioxidant CoQ10 and leads to ROS-mediated lipid peroxidation in vascular cells. Surprisingly, inhibition of eNOS prevents Ubiad1-dependent cardiovascular oxidative damage, suggesting a crucial role for this enzyme and non-mitochondrial CoQ10 in NO signaling. These findings identify UBIAD1 as a non-mitochondrial CoQ10-forming enzyme with specific cardiovascular protective function via the modulation of eNOS activity.

  • Track 5: Ocular Microbiology & Immunology
Location: Harbor Room
Speaker

Chair

Elizabeth A Berger

Wayne State University School of Medicine, USA

Speaker

Co-Chair

Eleftherios I. Paschalis

Harvard Medical School, USA

Session Introduction

Carlota Saldanha

University of Lisbon, Portugal

Title: Fibrinogen effects on erythrocyte nitric oxide mobilization in presence of timolol

Time : 14:10-14:30

Speaker
Biography:

Carlota Saldanha has completed her Ph.D. at the age of 39 years from Universidade Nova de Lisboa; postdoctoral studies from Faculdade de Medicina da Universidade de Lisboa (FMUL). She has a Master in Medical Education. She is Associate Professor with Habilitation in FMUL and Head of Unit of Microvascular Biology and Inflammation in Instituto de Medicina Molecular (IMM) of FMUL. She has published more than 80 papers in reputed journals and serving as an editorial board member of repute journal.

Abstract:

The objectives of this study were to evaluate the effects of high fibrinogen concentration on erythrocyte mobilization of nitric oxide (NO) and of its metabolites in presence of timolol in healthy human blood samples.
Main Methods – Levels of NO was evaluated by amperometric method. Nitrite, nitrate and S-nitrosoglutathione (GSNO) were measured using the spectrophotometric Griess reaction.
Key findings – In the presence of high concentrations of fibrinogen and timolol (10µM) in the blood samples from healthy humans the erythrocyte nitrites, nitrates and GSNO concentration increased without significant changes in NO efflux. Erythrocyte scavenging NO property was preserved in the presence of timolol and high fibrinogen levels.
Significance – These results suggest that during in inflammation when high levels of fibrinogen are present, NO delivery by erythrocytes might be compromised that acts as a compensatory mechanism against the overproduced NO by endothelial inducible nitric oxide synthase.

Elizabeth A Berger

Wayne State University School of Medicine, USA

Title: Immunoregulation of bacterial-inuced keratitis

Time : 14:30-14:50

Speaker
Biography:

Elizabeth Berger earned her Ph.D. in Anatomy & Cell Biology from Wayne State University School of Medicine (2007), where she focused on immunoregulatory mechanisms of ocular infectious disease, including the role of vasoactive intestinal peptide (VIP), a potent anti-inflammatory neuropeptide. Beth continued to characterize the immune response following P. aeruinosa-induced keratitis as a postdoctoral fellow (2007-2009). At this time, she also sought to expand her studies into the field of traumatic brain injury and subsequent effects on the visual system. In 2010, Beth joined the faculty at the WSU School of Medicine and currently holds a joint appointment with the Departments of Anatomy & Cell Biology and Ophthalmology. Presently, her laboratory uses models of both bacterial keratitis traumatic brain injury to study the events of the innate immune response, inflammation and disease pathogenesis. Her work is currently supported by a RO1 from the National Eye Institute and a Midwest Eye Bank grant.

Abstract:

Pseudomonas aeruginosa-induced keratitis is one of the most common and destructive of bacterial diseases, ultimately culminating in blindness. This opportunistic, Gram-negative organism is best known to cause bacterial keratitis in extended contact lens wearers. In the United States alone the incidence of microbial keratitis is 25,000-30,000 cases annually with cost of treatment estimated at $15-30 million. This sight-threatening disease is in large part a consequence of the inflammatory response invoked by the host, which depends on the regulation of immune cells, balance between pro- and anti-inflammatory factors released by these cells and the microenvironment, and effective restoration of tissue homeostasis. In this regard and in light of increasing incidence of antibiotic resistance, vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide, has been implicated as a potent endogenous immunomodulator that affects the immune response in an anti-inflammatory manner. Our studies examine the VIP-induced pro-resolving mechanisms of inflammation and innate immunity using a murine model of corneal infectious disease. Data from our laboratory indicate an essential role for VIP in the resolution of ocular infection and subsequent preservation of the visual nervous system and visual acuity.

Nicholas J. Butler

Johns Hopkins University School of Medicine, USA

Title: Interferon alpha-2b in the treatment of refractory uveitic cystoid macular edema

Time : 14:50-15:10

Speaker
Biography:

Nicholas J. Butler, MD completed his medical studies at McGill University in Montreal, Quebec in 2005, followed by residency in ophthalmology at Brown University in Providence, Rhode Island. He spent six months volunteering in Tamil Nadu, India from 2009 to 2010, providing medical and surgical care to indigent patients with eye disease. Upon returning to the U.S., he completed fellowship in uveitis at the Casey Eye Institute in Portland, Oregon in 2011. Currently he is an Assistant Professor of ophthalmology at the Wilmer Eye Institute and is the principal investigator for this site on the MUST-FS.

Abstract:

For patients suffering from uveitis, cystoid macular edema (CME) is a leading cause of vision loss. Depending upon the severity and duration of the CME, the loss of vision may or may not be reversible.
Interferon alphas are a family of cytokines produced by white blood cells which have antiviral, antiproliferative, and immunomodulatory properties. Systemic interferon alpha-2a has demonstrated efficacy in ocular inflammatory disease of non-infectious cause, most notably Behcet’s disease associated uveitis. Increasingly, the efficacy of systemically administered interferon alphas for uveitic CME, both in the setting of active and inactive uveitis, is being elucidated.
The author presents his experience, both published and non-published, with systemic interferon alpha-2b for refractory uveitic CME. The discussion will include a careful analysis of the manifold risks and adverse events associated with interferon alpha-2b and the clinical scenarios in which such a treatment may be considered.

Iris Kassem

University of Illinois at Chicago Eye and Ear Infirmary Chicago, USA

Title: Juvenile rabbit animal model of lensectomy to evaluate therapeutic interventions for postoperative inflammation and fibrosis

Time : 15:10-15:30

Biography:

Iris Kassem earned her MD and PhD degrees from Stony Brook University in 2006. She completed her residency in ophthalmology at North Shore-Long Island Jewish Health System followed by a fellowship in pediatric ophthalmology and strabismus at the University of Illinois at Chicago Eye and Ear Infirmary in 2011. She stayed at the Illinois Eye and Ear Infirmary as an Assistant Professor under the NIH/NEI K12 Independent Clinical Vision Scientist Development Program. These studies are supported from a grant by the Knights Templar Eye Foundation and NIH/NEI grant EY021475.

Abstract:

One of the most common pediatric intraocular surgeries is for congenital cataract. Left untreated, visual axis opacification resulting from a cataract can lead to deprivational amblyopia and potentially a lifetime of visual impairment. In general, the early treatment of a visually significant cataract leads to a better visual outcome. Complications of pediatric cataract surgery include obscuration of the visual axis from membrane formation, synechiae, correctopia, retinal detachment, high intraocular pressure, resulting in the potential need for additional surgery. The Infant Aphakia Treatment Study found in children up to age 6 months old treated with an intraocular lens implant compared to the children left aphakic, there was a higher rate of additional surgeries due to these complications, resulting in a higher cost. Because of the high risk of complications if a cataract is removed in an infant, an intraocular lens is typically not inserted. Rabbits are used as a model of juvenile lensectomy because the anterior chamber is anatomically similar to that of the human eye and they have a robust response to lens extraction surgery that may be similar to children. We performed a systematic evaluation of the postoperative course of a juvenile rabbit animal model after lensectomy. Objective and quantifiable postoperative measures are used, allowing us to compare the effect of pharmacologic interventions. We describe studies performed in the juvenile rabbit model with and without implantation of an intraocular lens implant. We correlate findings seen in rabbits with potential future applications to humans.

Break: Coffee Break 15:30-15:45 @ Prefunction Area

Eleftherios I. Paschalis

Harvard Medical School, USA

Title: Alkali burn to the eye: Protection using TNF-an inhibition

Time : 15:45-16:05

Speaker
Biography:

Paschalis completed his doctorate in Medicine, Ophthalmology, with excellence from Democritus University of Thrace, Greece in 2010. He began to work full-time as a senior research fellow at the Massachusetts Eye and Ear Infirmary (MEEI) under the guidance of professor Dohlman in 2011, and since then has become an integral and prolific member of the lab and the Boston keratoprosthesis group. Since his arrival, Paschalis’ Work has led to the filing of two patent applications, several published manuscripts in prominent peer-reviewed journals, and multiple presentations in national as well as international conferences. Paschalis’ research at MEEI extends to various areas of ophthalmology. His work involves improvements in Boston Keratoprosthesis, Development of novel implantable glaucoma valves and materials for vitreoretinal surgery. His recent research focus involves the mitigation of the ocular injuries following chemical burns. In 2013 Paschalis was promoted to Instructor at Harvard Medical School and Investigator at MEEI. In this role he continues to conduct research.

Abstract:

Purpose: The aim of this study was to evaluate early retinal damage after induction of ocular surface alkali burns and the protective effects of tumor necrosis factor alpha (TNF-a) blockade.
Methods: Alkali injury was induced in mouse corneas by using 1 N NaOH. Retinal damage was assessed using a terminal deoxynucleotidyl transferase 29-deoxyuridine 5-triphosphate nick end labeling (TUNEL) assay, 15 minutes to 14 days postburn. Immune cell infiltration was assessed by CD45 immunolocalization. Retinal cytokines were quantified using the enzyme-linked immunosorbent assay for interleukin (IL) 1b, IL2, IL6, TNF-a, CCL5, and macrophage inflammatory protein- 1a. Protection against retinal damage was attempted with a single dose of either anti–TNF-a antibody (infliximab, 6.25 mg/kg) or control immunoglobulin G (IgG), administered intraperitoneally 15 minutes after the burn was inflicted. Corneal injury was evaluated by using TUNEL and CD45 immunolocalization and by quantifying corneal neovascularization.
Results: There was significant damage to the retina within 24 hours of the corneal burn being inflicted. TUNEL+ labeling was present in 80% of the retinal ganglion cells, including a few CD45+ cells. There was a 10-fold increase in the retinal inflammatory cytokines in the study groups compared with that in controls. A single intra- peritoneal dose of anti–TNF-a antibody, administered 15 minutes after the burn was inflicted, markedly reduced retinal TUNEL+, CD45+ labeling, and inflammatory cytokine expression, compared with that in the controls. Additionally, TNF-a blockade caused a marked reduction in corneal neovascularization, and in cornea TUNEL and CD45 labeling, 5 days after the burn was inflicted.
Conclusions: This study shows that alkali corneal burns can induce significant retinal damage within 24 hours. A single dose of anti–TNF-a antibody, administered 15 minutes after inflicting the burn, provides significant retinal and corneal protection. This could lead to the discovery of novel therapies for patients with alkali injuries.

Speaker
Biography:

Shamim Ahmad obtained his Ph.D. at the Department of Microbiology, Central Drug Research Institute, Lucknow in 1982. Currently, he is serving as Professor of Ocular Microbiology and Officer in-charge & Teacher in-charge (Administrative Affairs) at Ocular Microbiology Section, Institute of Ophthalmology, JN Medical College, Faculty of Medicine, Aligarh Muslim University, India since January 10, 1983. Prof. Ahmad had has also served as Faculty for more than 5 years on deputation at Faculties of Medicine in the Department of Clinical Microbiology, Al-Arab Medical University, Libya and Department of Medical Microbiology, College of Medicine, King Khalid University, Saudi Arabia. Prof. Ahmad is the recipient of at least 6 International Fellowships including "DAAD”(W.Germany), "JSPS"(Japan), "ROYAL-SOC.-London" (UK), "DAAD"(Germany), "TUBA"(Turkey) and "SAIA" (Slovak Republic) as a visiting Professor. He is honored to be Chief Editor/Member/Reviewer in the Editorial team of 30 International journals of world repute, his current research interests being antibiotic resistance, MRSA and honey as antibacterial in ocular infections.

Abstract:

Medical uses of Honey for curing various ailments have been endorsed Holy Koran, Vedas and Bible. The Russians used it in World War I to prevent wound infection and to accelerate wound healing. Beside, it has occupied a prominent place in traditional medicines throughout history due to its conventional use as antibacterial/antifungal agent, reducing edema in wounds and ulcers. In view of the prevalence of alarming antibiotic-resistance in clinical bacteria all over the world, there is a rapidly increasing move towards using honey as an alternate- therapy on multi-resistant organisms including superbugs– Methicillin Resistant Staphylococcus aureus (MRSA) and others to clear infection in wounds, with no adverse effects on wound tissues. Branded Manuka honey and many commercial products which have now flooded world market appear to be highly effective for the treatment of many wound infections, burns, psoriasis, gastrointestinal disorders, arthritis, eczema, sore throat, dental carries, stomach aches, flu like symptoms and corneal ulcers. Large number of workers including our laboratory in India and abroad have observed Honey’s miracles in Ophthalmology, Dentistry, Surgery, Plastic Surgery, Paediatrics, Gynaecology, Dermatology and Gastroenterology. A large number of eye infections may pose a potential eye blinding threat particularly when not respond to common antibiotics due to emergence of resistance. In view of spread of multiple antibiotic-resistance in Ophthalmic conditions, our laboratory have explored honey as a possible antibacterial agent and found it to be potent during the treatment of corneal ulcers in rabbit models. Beside, topical application of branded Manuka Honey eye drops recently on 100 subjects (48 male and 52 female) in cases of dry eye syndrome led to reduction of bacterial colony counts obtained from eyes of such patients and tear film stability revealing honey’s role in contributing to the symptomatic relief. Beside, our concept of using honey against multi-resistant dreaded super bugs MRSA involving eye was further supported by our antibacterial studies conducted in India and abroad especially in UK where Honey was tested on various bacteria including MRSA, MSSA from eye patients. Based on available information, we can see potential prospects and scope of Honey as an alternate antibacterial option in future particularly for the treatment of non-responding life threatening multi-resistant pathogens especially superbug MRSA strains and probably easily the external bacterial eye infections including conjunctivitis, keratitis, blephritis, orbital cellulitis, and dacryosystitis.

  • Track 6: Research trends in Surgical & Medical Ophthalmology
Location: Harbor Room
Speaker

Chair

Miguel Rechichi

Magna Graecia University, Italy

Speaker

Co-Chair

Nir Shoham-Hazon

Shoham-Hazon EyeCare, Canada

Session Introduction

Kerry Goetz

National Eye Institute, USA

Title: The national ophthalmic genotyping and phenotyping network (eyegene®): Preserving vision through genetics

Time : 16:45-17:05

Speaker
Biography:

Kerry Goetz attended West Virginia University, where she earned a Bachelor of Science in Animal and Veterinary Science in 2002, a Multidisciplinary Studies Degree in Professional Writing, Business, and Communication in 2008, and a Master of Science in Genetics and Developmental Biology in 2006. In 2006, she began working under Dr. Visvanathan Ramamurthy at the West Virginia Eye Institute, where she studied Leber congenital amaurosis and congenital stationary night blindness. Kerry Goetz joined the NIH in the Office of Director Elias Zerhouni in the summer of 2008 and transitioned to the NEI in October 2008 working as a coordinator for the National Ophthalmic Disease Genotyping Network (eyeGENE®). Her knowledge and expertise in the field of genetics has expanded the number of patients and doctors participating in eyeGENE® throughout the United States and Canada and opened the eyeGENE® Biorepository to scientists to facilitate vision research. The eyeGENE® Network is working to bring advances in identifying ophthalmic disease genes to the clinical practice. It is a component of the NEI Intramural Research Program and is conducted in partnership with extramural academic clinic and research laboratories. Goetz interacts with patients and their families, eye healthcare providers, and vision researchers on a daily basis. She maintains the two eyeGENE® clinical protocols and shepherds them through various review processes both domestic and abroad. She also serves as the liaison between individuals and offices involved in the oversight of human subject research at NIH and expanding the science of biobanking. Kerry also is involved in several efforts on the NIH campus to standardize data sets to facilitate data sharing across studies. Outside of work, is active in the National Organization of Albinism and Hypopigmentation and The Way Eye See It, a Northern Virginia-based group of parents with visually impaired children. She is a Girl Scout leader and enjoys being outdoors with her family and dog. She also has a passion for cooking.

Abstract:

Molecular genetics is revolutionizing the diagnosis and treatment of inherited eye diseases. In 2003, the National Eye Institute of the National Institutes of Health- in an effort to facilitate future basic and clinical research in inherited eye disease-created The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE®). eyeGENE® is a DNA repository and patient registry for inherited eye diseases coupled to phenotypic descriptors and molecular genetic information for which health care professionals throughout the United States and Canada can enroll their patients. A portion of the DNA extracted from a blood sample from the donor may be used for CLIA-certified molecular diagnostics that can be returned to the referring clinician to be used in patient care. Most recently the program added the option for vision researchers to be able to request access to a de-identified database of phenotype and genotype information for participants enrolled in eyeGENE® and request DNA aliquots for their research studies. eyeGENE® also offers participants the option to be included in a patient registry so that they may be contacted if an approved clinical study for which they might qualify is offered. Several studies have now successfully recruited participants to studies and developed high throughput diagnostics using patient DNA samples. eyeGENE® anticipates increased study proposals on a variety of issues in the near future as more researchers discover the resource.

Speaker
Biography:

Miguel Rechichi has completed his training in ophthalmology at 28 and his Ph.D. at 32 from Magna Graecia University and Diploma of Specialist Superior in Ophthalmology from University of Lugano (Switzerland). He’s actually a researcher for Magna Graecia University and Director of corneal and refractive Surgery service of S.Lucia Eye Clinic, Cosenza, Italy. He was a pioneer of crosslinking clinical application and actually is involved in developing new accelerated cxl protocols for which he’s invited as opinion leader to several meetings.

Abstract:

Purpose: To evaluate central and peripheric corneal pachymetric variations by in-vivo HD-OCT mapping during corneal pulsed accelerated collagen cross-linking (PACXL) treatment with the use of dextran-free riboflavin and ultraviolet A irradiation (UVA).
Design: Prospective, noncomparative, interventional clinical study. Participants: Twentyfive keratoconic patients (25 eyes) were enrolled.
Methods: All patients underwent PACXL (30mw/cm2, pulsed ratio 1:1) using a dextran- free riboflavin solution with hydroxypropyl methylcellulose. Corneal thickness maps were performed during the procedure. Central (CCT) and inferior paracentral (IPCT) thickness measurements, centered on cornea, were obtained preoperative (PREOP), after epithelium removal (Epi-R), after 10 min riboflavin soaking with VibexRapid (RS), after 8 min irradiation (IR). Paracentral thickness was calculated as average of three inferior paracentral octants. Main Outcome Measures: Intraoperative central and paracentral corneal thickness measurements.
Results: Mean patient age was 26.9 years (range 17-40), 15 were male and 10 were female. Preop CCT and IPCT was 458.5 and 448 μ respectively. Epi-R CCT and IPCT was 415.7 and 403 μ. RS CCT and IPCT was 406.4 and 39289μ. IR CCT and IPCT was 395 and 38176 μ. There was a reduction CCT and IPCT reduction was mild but significative after IR phase but not significative after RS phase. No intra, operative, early postoperative, or late postoperative complications were observed in this patient series.
Conclusion: Intraoperative OCT showed that epi-off accellerated pulsed corneal CXL with the use of dextran-free riboflavin limits central and paracentral corneal thinning during the procedure. After epithelium removal a mild but statistically significant decrease of CCT was demonstrated only after irradiation phase.

Leonard Pinchuk

University of Miami Miller School of Medicine, USA

Title: The use of polyisobutylene polymers for glaucoma drainage tubes and intraocular lenses

Time : 17:25-17:45

Speaker
Biography:

Pinchuk is the inventor of the modern-day angioplasty balloon, various stents and stent-grafts, the polycarbonate urethanes and SIBS for implant applications, the TAXUS drug-eluting coronary stent, the InnFocus MicroShunt™ for glaucoma, the Surefire Catheter for liver tumors and xPIB for IOLs.He began his career at Cordis Corporation in 1983, left in 1987 to co-found Corvita Corporation, which went public in 1994, was purchased by Pfizer (1996) and then Boston Scientific (1998). Pinchuk founded Innovia LLC in 2002, which spun off InnFocus in 2004. Pinchuk received a B.Sc. in chemistry from McGill University in 1976, a Ph.D. interdisciplinary in Engineering and Chemistry from the University of Miami in 1984 and an honorary Doctor of Science degree from McGill University in 2005. He was inducted into the National Academy of Engineering in 2012.

Abstract:

This presentation discusses a new family of ocular biomaterials based upon polyisobutylene. Poly(styrene-block-isobutylene-block-styrene) (“SIBS”) has been used for over six years as a glaucoma drainage implant (the “InnFocus MicroShunt™”). A crosslinked form of polyisobutylene (xPIB) is a novel material for an intraocular lens (IOL). The InnFocus MicroShunt transports fluid from the anterior chamber to a shallow diffuse bleb formed under the conjunctiva and Tenons. The outer diameter is 350 µm, the lumen diameter is 70 µm and the length of the device is 8.5 mm. The lumen length and diameter serve as a flow resistor to prevent detrimental hypotony. Attached approximately half-way down the length of the tube are planar atraumatic fins that prevent migration of the device as well as seal around the needle tract into which the device is threaded. The subconjunctival flap is treated with 0.2 or 0.4 mg/mL of Mitomycin C for 2–3 minutes at the time of surgery. Thirty-five POAG patients were enrolled in the study. The mean pre-operative non-washed out IOP was 23.8 ± 5.3 (range 18–38) mmHg and the mean number of glaucoma medications per patient was 2.8 ± 0.9 (range 1-5). The qualified success rate was 100% in the first year (n=24) and 91% in the second year (n=22). The drop in IOP from baseline was 55% in the first year and 50% in the second year, with a mean IOP at one year of 10.7 ± 2.8 mmHg and 12.0 ± 3.6 mmHg at two years. The mean number of medications per patient at one and two years was 0.3 ± 0.8 with 90% of patients totally off of glaucoma medications. No serious long term sight-threatening adverse events were encountered. An FDA-approved clinical study for the MicroShunt is in progress in the U.S. Intraocular lenses formed from xPIB do not contain any cleavable groups that can dissociate with time to cause adverse inflammatory reactions in the surrounding tissue or detrimentally affect the clarity of the optic by crazing, hazing or glistening. A UV absorber is crosslinked into the matrix to create a UV cut-off at 400 nm. XPIB is unaffected by silicone oil, has a high index of refraction (>1.50); a low modulus of elasticity (<100 gf/mm2) and high elongation (>200%) which render them softer than PDMS while providing approximately twice the magnification of a PDMS lens having the same radius of curvature. These elastomeric properties enable single piece IOLs to elongate while being pushed through the bore of a small inserter (<1.5 mm diameter) and then recover to their original shape without damage; thereby making them ideal for microincision. This family of materials can be molded without the need for post-fabrication solvent extraction or other secondary processing. Superb biocompatibility, low manufacturing costs, minimally invasive placement and advanced performance make these next generation polyisobutylene-based materials used in glaucoma shunts and IOLs well-positioned in today’s challenging health care economic climate.

Speaker
Biography:

Shoham-Hazon has completed an Ophthalmology residency in Israel, in January 2010. During his residency he was appointed chief resident and was awarded two resident awards of excellence. Thereafter, Shoham-Hazon pursued the lucrative fellowship at the University of Toronto, with the world renowned, Ike Ahmed. This three year fellowship included clinical, surgical and research aspects of Glaucoma, Advanced Anterior Segment & IOL surgery (GAASS). During this fellowship, Shoham-Hazon received numerous awards for presentations in international conferences and research grants for research studies. Shoham-Hazon is a reviewer and guest reviewer for various international peer-review journals.

Abstract:

Purpose: The aim of this study is to evaluate the effectiveness of the novel ab-interno MIGS fistula – XEN45 in reducing intraocular pressure (IOP) and glaucoma medication in patients with Open-Angle Glaucoma (OAG).
Patients and Methods: This is a multicenter, open-labeled prospective study, in which 76 patients with OAG were enrolled. Effectiveness was assessed by comparing baseline intraocular pressure values to postoperative values. Success criteria were classified according to the Tube vs Trab study. All patients underwent the ab-interno XEN45 procedure. The surgery was performed as a primary procedure, or in combination with cataract surgery.
Results: Mean IOP ranged from 22.4 +/- 4.7 preoperatively, to 13.8 +/- 4.0 postoperatively. Mean IOP lowering was 10.0 mmHg at 9 months of follow-up, a drop of 38%. Preoperative medication classes were 3.2, which shown a statistically significant decline to 0.4 postoperatively. Eighty eight percent (88%) of patients reached an IOP of +/- 18mmHg or 20% drop, and 63% of patients reached an IOP of +/- 16 or 30% drop.
Conclusions: The novel XEN45 MIGS implant, has proven to be effective for Glaucoma in a MIGS approach. Intraocular pressure dropped by more than 30%, and was +/- 18, in almost 90% of the patients who were evaluated at last follow-up. The XEN45 showed a statistically significant decline in the amount of glaucoma medication classes used, from 3.2 to 0.4. The goal of this study is to investigate a larger number of patients over a longer follow-up period (up to 3 years).

Faiz Tanweer

Leeds General Infirmary, UK

Title: Naso lacrimal duct tumors in the era of endoscopic sinus surgery

Time : 18:05:18:25

Biography:

Faiz Tanweer has completed his M.S (ENT) at the age of 31 years from Patna Medical College, India and Membership studies from Royal College of surgeons of Edinburgh, United Kingdom. He has extensive experience of working in the specialty in different countries including India, Maldives and United Kingdom. Currently, he is the ENT Specialist registrar at Leeds General Infirmary, Leeds, UK. He has presented in many national and international scientific meetings and published more than 10 outstanding papers in peer reviewed reputed medical journals and has been serving as an editorial board member of BMJ case report, United Kingdom.

Abstract:

Nasolacrimal duct tumors are rare and are often found inadvertently during dacryocystorhinostomy. Anecdotal case reports have been published, mostly in ophthalmology journals. Since the era of endoscopic dacryocystorhinostomy, such cases are more frequently encountered by ENT surgeons. They comprise a large and variable spectrum of entities. Malignant tumours are more common. A retrospective chart review of patients who underwent endoscopic dacryocystorhinostomy over the last 10 years in our dedicated epiphora clinic was conducted to search for the incidence of nasolacrimal tumors in our cohort. An extensive web-based search (using Pubmed, Medline, Embase and Google Scholar) was also conducted. This focused on case reports and series or review articles on primary nasolacrimal duct and lacrimal sac tumours, and their endoscopic management, which had been published in the last 16 years (June 1995 to May 2011). The exclusion criteria were: metastatic nasolacrimal duct tumours or tumour extension from the surrounding area and non-English literature. In total, 77 papers were identified, comprising a total of 118 cases. Four of 525 endoscopic dacryocystorhinostomy procedures exposed a tumor (inverted papilloma, oncocytoma, lymphoma and solitary fibrous tumor). The literature review revealed that papilloma was the most frequently reported benign tumor and lymphoma was the most common malignant tumor. Since the advent of endoscopic dacryocystorhinostomy, tumors are being diagnosed relatively early when smaller in size and so have a better chance of cure. Because of the rarity of this condition, it is advisable that such cases are managed through a dedicated epiphora service framework.