International Conference on Eye Disorders and Treatment July 13-15, 2015 Baltimore, USA

Biography:

Arpitha Parthasarathy completed her PhD in Biomedical Sciences from Aravind Eye Hospitals, India and Postdoctoral Fellowship at National Institutes of health, Maryland. She was a Postdoctoral Scientist at George Washington University and Univ. of Kentucky. She has published in many peer reviewed ophthalmic journals and is now the “Director of Translational and Molecular Biology Research” at Plasma Medicine Life Sciences and heads the Translational and Molecular Biology Division of Jerome Canady Research Institute for advanced Biological and Technical Sciences, USA.

Abstract:

Cold atmospheric plasma (CAP) activates pro-apoptotic signaling pathways triggered through redox potential in cancer cells leading to and decreased cell survival (Drs. Keidar and Canady’s group). We hypothesize that CAP may have a dramatic effect on these apoptotic pathways in cancer and cancer stem cells (CSC) and thereby reducing the application of chemotherapeutics. The present study aims at identifying newer targets and pathways that are involved in the down regulation of retinoblastoma and other CSC’s, cancer cell lines Canady Hybrid Plasma scalpels to address some of these important questions in plasma medicine and cancer therapeutics. Quantitative Confocal Microscopy, Q-PCR, Immunoblots for Nf-Kb mediated and apoptotic pathways, analysis of stem cell signaling via Beta-catenin using TIRF microscopy are some of the methods used in the current study. On the basis of the background literature and our preliminary results we hypothesize that CAP has a selective mechanism to ablate the CSCs. The outcome of the current study will enable cancer researchers to develop newer strategies along with CAP in the treatment of cancer.

Biography:

Mary Beth Aronow is an Assistant Professor of Ophthalmology at the Wilmer Eye Institute at Johns Hopkins. She specializes in the medical and surgical management of adult and pediatric eye tumors. She received her Medical Degree from Yale University School of Medicine following an Internship in Internal Medicine at Brigham and Women’s Hospital in Boston. She has completed her Ophthalmology Residency at the Cole Eye Institute at the Cleveland Clinic. She then completed Subspecialty Fellowship Training in Ophthalmic Oncology at the Cole Eye Institute and as well as an additional Fellowship in Medical Retina at the National Eye Institute, National Institutes of Health.

Abstract:

Uveal melanoma is the most common primary intraocular malignancy in adults. Despite improvements in diagnosis and local tumor control using eye-sparing techniques, a commensurate improvement in mortality has not been observed. This current situation underlines the need for effective methods to predict and address metastatic disease. Prognostication for metastatic risk has evolved over the past two decades. Initial studies focused on clinical and histopathologic risk factors. More recently, prognostication has been based upon tumor cytogenetics and gene expression profiling. Our laboratory has extensive experience with FISH-based prognostication of uveal melanoma. Data regarding the use of this technique will be presented. As techniques have evolved, there are now commercially available assays for assessment of metastatic risk. As these technologies continue to improve the ultimate goals are to understand the underlying molecular mechanisms that impart metastatic potential and to develop targeted therapies.

Biography:

Lu Chen, MD and PhD, received her Postdoctoral training at the Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School and is now an Associate Professor and Morton D. Sarver Endowed Chair at University of California, Berkeley. She also holds Joint Faculty positions at the Proctor Foundation for Research in Ophthalmology at University of California, San Francisco, and the Schepens Eye Research Institute, Mass Eye and Ear, Harvard Medical School.

Abstract:

Lymphatic research has progressed rapidly in recent years. The cornea provides an ideal tissue for lymphatic research due to its accessible location, transparent nature, and lymphatic-free but –inducible features. Once induced, corneal lymphatics enhance high volume delivery of antigens and immune cells, and accelerate transplant rejection. Our research goal is to elucidate the molecular and cellular mechanisms of lymphangiogenesis and to identify new targets for therapeutic intervention. This presentation is to introduce our recent advances in corneal lymphatic research, which have broad implications for ocular and nonocular diseases.

Biography:

Qingguo Xu is Research Associate in the Center for Nanomedicine, Wilmer Eye Institute at Johns Hopkins University School of Medicine, Baltimore, USA. His research is focused on nanoparticle-based ocular drug delivery. He is an expert in translational nanomedicine for ocular therapy. He is the co-inventor for up to 12 patent applications including 3 eye treatment related applications.Previously, he was Post-doc Fellow in the Center for Nanomedicine, Wilmer Eye Institute from 2010 to 2013, and Process Scientist in the Unilever, United Kingdom from 2008-2010. He received his D.Phil. in Materials Sciences (biomaterials) from University of Oxford, United Kingdom. He was a recipient of 2013 Genentech-American Association for Pharmaceutical Scientists (AAPS) Innovation in Biotechnology Award.

Abstract:

Purpose: To evaluate the effect of biodegradable nanoparticles that provided sustained release of corticosteroid to prevent corneal allograft rejection following subconjunctival injection to rats. Methods: Biodegradable nanoparticles encapsulated with water-soluble dexamethasone sodium phosphate (DSP) were prepared by solvent diffusion method. Nanoparticles were characterized in terms of particle size, surface charge, and morphology. The drug loading efficiency and the in-vitro drug release were measured using HPLC method [1]. Histological examination was used to study the safety of nanoparticles after subconjunctival injection. DSP levels in various ocular tissues after subconjunctival administration to rats were quantified through the scintillation counting using [3H]-labelled DSP. The corneal transplantation was carried out by implanting the central corneal button of a Fisher rat to the corneal bed of a Lewis rat. After corneal transplantation, animals were treated with [2]: 1) saline, 2) placebo nanoparticles, 3) free DSP (2 mg DSP/mL) and 4) DSP-loaded nanoparticles (2 mg DSP/mL). Results: The biodegradable nanoparticles exhibited size of 200 nm, surface charge of -8 mV, and drug loading of 8% by weight. Nanoparticles provided a sustained in vitro drug release over 15 days. Histology showed that nanoparticles had no ocular toxicity after SC injection to rats. A constantly high ocular drug levels for at least 7 days after subconjunctival administration were observed, as comparison, the ocular drug levels rapidly dropped to undetectable levels after subconjunctival administration of free DSP. DSPloaded nanoparticles through weekly subconjunctival injection prevented corneal allograft rejection in rats over the entire 9-week study showing transparent cornea without neovascularization and edema. In comparison, corneal rejection in control treatment groups of either placebo nanoparticles, saline or free DSP occurred within less than 4 weeks accompanied by severe corneal edema, neovascularization and opacity. The corneas with the treatment of DSP-loaded nanoparticles had intact epithelial, stromal and endothelial layers, and no thickening or anterior chamber inflammation. In comparison, in the control treatment groups, corneas were all thickened, and the corneal grafts lost their structural integrity with extensive inflammatory cell and blood vessel infiltration throughout the cornea. We also did not observe increased intraocular pressure throughout the entire 9-week study for the weekly subconjunctival administration of DSP-loaded nanoparticles in rats. Conclusion: Corticosteroid-loaded nanoparticles effectively prevented the corneal allograft rejection in a rat model. The sustained drug release provided by nanoparticles may enhance patient compliance and improve efficacy for prevention of corneal graft rejection.

Biography:

Sandra Franco has a degree in Applied Physics – Optics (with specialization in optometry) and completed her PhD at University of Minho in 2005. She is currently an Assistant Professor in the Department of Physics, University of Minho. Her research focuses on the field of Ophthalmic Instrumentation and Visual Optics, particularly in imaging and evaluation of the anterior segment of the eye. She developed further research to assess the impact of ocular accommodation in both ocular and internal aberrations. She has published several scientific articles and book chapters and presented communications in various national and international conferences. She is referee of some scientific journals and was/is part of the research team of national and European research projects.

Abstract:

The optical properties of the eye are not static and change continuously over time with factors such as pupil size, the tear film stability and accommodation. Real-time measurement of the monochromatic ocular wavefront aberrations provides insights into the dynamics of the mechanisms that control accommodation. In addition, real-time wavefront analysis can be applied to evaluate the tear film dynamics providing data to understand how the tear film quality and dynamics affects the optical quality of the eye and retinal image quality. This work will review existing techniques to measure time ocular monochromatic wavefront aberrations in real time and will explore some of its clinical applications. Special attention will be given to techniques and studies undertaken at the Centre of Physics of University of Minho.

Biography:

Abstract:

Background: The corneal epithelium serves as a barrier and contributes to the maintenance of corneal transparency and rigidity. Ulcers and erosions of the corneal epithelium as well as delays in resurfacing of the cornea after wounding are major causes of ocular morbidity and visual loss. Corneal ulceration is very frequent and represents one of the most important eye diseases. Chemical burns of eye presents a major therapeutic challenge to the ophthalmologist. Corneal alkali burns represent between 7% and 10% of eye injuries. Aim: To investigate the structure and organization of corneal epithelium during the healing process of rabbit corneal wounds with monitoring of the corneal electrolyte contents with energy dispersive X-ray analyzer (EDAX) and to screen through immunohistochemistry corneal cellular changes for apoptosis and proliferation during healing process using Proliferating cell nuclear antigen (PCNA) and Tunnel Apoptosis Assay. Material and methods: 30 New Zealand rabbits weighing 2.5 kg were used. An alkali wound of the cornea was performed in the right eye of with round filter paper, 5.5 mm in diameter which were soaked in 0.5 mol/L NaOH for 5 seconds and then were placed centrally on the cornea for 60 seconds. The left eyes will serve as controls. The corneas (normal ulcerated and healed (epithelialized) were harvested at various time points (0, day one, 3 days, 7 days, 14 days of corneal injury and processed for examination with light and scanning electron microscopy with monitoring of the corneal electrolyte contents C, N, O, Na, P, Mo, Ag, Ca, K, Silica with an EDAX. Results: Inflammatory response with massive inflammatory cell infiltrates mainly leukocytes (PML) are the first cells that migrate into the tissues in response to injury insult in the first 24 hours cells were mainly neutrophils. Steadily other mononuclear cells begin to appear along with signs of new capillaries formation. Moreover, progressive increase in basal corneal epithelial cell proliferative activity both in limbal region and leading corneal ulcer edge, stromal keratocytes and endothelial capillaries cells. Labeling for apoptosis was found only on the epithelial surface of normal cornea and not in deeper layers. After alkali injury few positive deeper epithelial cell were seen. In addition, stromal cells apoptosis was present in all the alkali-burned corneas; Observable alterations of mineral concentrations in the rabbit cornea after alkali injury burns. Conclusion: Basal corneal epithelial cell proliferative activity starts earlier after 24 hour of alkali injury and was headed by massive leukocytes infiltrate in the stroma and within epithelial cells. PCNA was expressed in the vascular endothelium. The PCNA expression starts later in the keratocytes but lasts somewhat longer. In present investigations, we found alterations of mineral concentrations in the rabbit cornea both in epithelial and collagen contents after alkali injury burns Mo is an essential trace element was found to decline during the healing process of corneal wound injury. Medical intervention with appropriate solutions containing element such as Mo may require with other mineral deficient in restoring and maintaining the normal mineral composition of the denuded corneal stroma.

Biography:

Abstract:

Purpose: The aim of this study is to compare preoperative and postoperative quality of vision and life perception after Automated Lamellar Keratoplasty (ALK) in patients with moderate to severe keratoconus. Method: This is a retrospective review of 52 consecutive eyes (42 patients) with moderate to severe keratoconus managed with Automated Lamellar Keratoplasty as first choice of treatment between the year 2005 and 2015 by a single surgeon. Data collected was preoperative and postoperative uncorrected visual acuity (VA), best corrected visual acuity (BCVA), subjective quality of vision and life perception evaluation was performed with the Vision-Perception Clinical Questionnaire (VPCQ). Further refractive surgery for residual refraction also was evaluated and done as part of their visual recovery. Results: All operated eyes (100%) improved UCVA postoperative and 95 percent improved BCVA. All patients referred an increase in their quality of vision and decreased their dependence of glasses or contact lenses. All patients were more independent for daily life activities from which 50% started with sports and activities preoperatively impossible to do. Twenty six percent of the patients underwent LASEK refractive surgery for correction of residual myopia and astigmatism. Conclusion: Automated Lamellar Keratoplasty is a reproducible procedure that not only improves UCVA and BCVA in moderate and severe cases of Keratoconus but also has a beneficial and positive outcome in patient’s quality of vision and perception of life activities.

Biography:

Datiles M currently sees eye patients as part of clinical trials and research studies at NIH, including an ongoing study of ocular graft-versus-host disease in recipients of adult stem cell transplants. His long-term research focuses on cataract development and clinical trials involving anti-cataract drugs. He also collaborates with NEI lens researchers to study the genetic causes of cataracts, and with Johns Hopkins University researchers to study the aggregation of lens proteins, which may lead to cataract development. He is the author of more than one hundred scientific manuscripts and textbook chapters. He has also served as an ad hoc editorial board member and reviewer for major ophthalmology journals, including Archives of Ophthalmology, Ophthalmology and Investigative Ophthalmology & Visual Science.

Abstract:

Recently, hematopoetic stem cell transplant (formerly called Bone Marrow Transplant) has become an increasingly successful treatment not only for blood cancers but also for auto immune disorders and solid organ cancers. However, the main long term side effect is chronic graft versus host disease, wherein the donor t-cells are dysregulated and cause varying degrees of inflammation and scar formation in various tissues in the body, including eye and skin. In most cases,the inflammation is successfully controlled by steroids and anti T cell treatments. However, some patients experience severe GVHD which respond poorly to steroids and other treatments. We are currently conducting an FDA approved randomized double masked placebo controlled clinical trial of Autologous serum eye drops for severe ocular graft versus host disease in hematopoetic stem cell transplant. We would like to share experiences in developing the clinical protocol including various clinical tests of the ocular surface of the eye and dry eye questionnaires, and dealing with problems associated with drawing blood in these very ill patients as well as a preliminary analysis of data.

Biography:

Zheng-Rong Lu is M Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve University and a Fellow of the American Institute for Medical and Biological Engineering. He received his PhD from Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, China. His research efforts involve molecular imaging, MRI contrast agents, drug delivery and ocular therapeutics. He has over 140 peer-reviewed publications. He has served on numerous NIH study sections. He serves on Scientific Advisory Board of Pharmaceutical Research, Molecular Pharmaceutics and American Journal of Nuclear Medicine and Molecular Imaging.

Abstract:

Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal is considered responsible for photoreceptor cytotoxicity. Primary amines including retinylamine and its analogues are effective in lowering the concentration of all-trans-retinal within the retina and thus prevent retina degeneration in mouse models of human retinopathies. We designed and developed drug delivery systems including polymer-retinylamine conjugates and polymeric nanoparticles to improve its therapeutic efficacy. The polymer drug conjugate was effective to provide prolonged protection of light-induced retinal degeneration in Abca4−/−Rdh8−/− (DKO), an animal model of Stargardt disease/age-related macular degeneration after oral administration. Subcutaneous administration of the nanoparticles containing retinylamine reduced liver accumulation of the drug and resulted in effective prolonged prevention of light-induced retinal degeneration in the Abca4−/−Rdh8−/− (DKO) mice. We also designed and developed new therapeutics that could effectively sequester toxic all-trans-retinal without inhibiting the enzymes involved in retinoid cycle chemistry. The new therapeutics was also effective to prevent light-induced retinal degeneration in the Abca4−/−Rdh8−/− mice with minimal side effects ont reina functions. The drug delivery systems and new therapeutics have the potential to effectively treat retinal degenerative diseases with minimal side effects.

Biography:

Hudson Nakamura is a Medical Specialist in Ophthalmology and specialized in Retina and Vitreous. Completed School of Medicine at the Federal University of Goiás – UFG and residency from the Base Hospital of the Federal District - Brasília - DF. Presently member of American Academy of Ophthalmology, Brazilian Council of Ophthalmology, Canadian Society of Ophthalmology and also the member of most prestigious society ARVO - The Association for Research in Vision and Ophthalmology United States. Currently working as a professor in department of Retina and Vitreous Course of Medical Residency in Ophthalmology at the Bank of Goias Eye Foundation. Is also working as Specialist in vitreoretinal disease Fellowship - University of Toronto Canada, Specialist in Ophthalmology - University of Toronto Canada, Specialist in vitreoretinal disease Fellowship - Brazilian Center for Eye Surgery.

Abstract:

Background & Objective: Pseudophakic and aphakic retinal detachments are associated with a lower percentage of successful primary repairs with standard scleral buckling surgery than phakic retinal detachments. The objective of this study was to determine whether a combined scleral buckle and vitrectomy as a primary procedure offers any advantage over conventional scleral buckling in primary pseudophakic and aphakic retinal detachments without proliferative vitreoretinopathy. Materials & Methods: This was a prospective, non-randomized clinical study. Ninety-four consecutive pseudophakic and aphakic retinal detachments were included in the study. All patients were operated upon by the same surgeon. Each patient underwent a combined scleral buckle and pars plana vitrectomy with perfluorocarbon injection and air-fluid exchange. Each patient was followed by the operating surgeon for a minimum of 6 months. Patients were followed with respect to anatomic reattachment, visual acuity improvement and surgical complications. Results: All eyes were anatomically reattached after a single operation. All demonstrated an increase in their visual acuity and there were no complications attributable to the vitrectomy procedure. Conclusions: We conclude that such a combined approach to primary pseudophakic and aphakic retinal detachments offers significant benefits to scleral buckling alone. We believe that the improved success rate is a function of vitrectomy contributing to both an improved peripheral visibility, resulting in fewer missed peripheral breaks and a lower likelihood of proliferative vitreoretinopathy. We recommend this combined surgical approach for all primary pseudophakic and aphakic retinal detachments.

Biography:

Major Research Interests to understand the molecular basis for disease development and progression of diabetic retinopathy (DR); Targeted genomics, epigenomics and proteomics-based identification of early biomarkers of diabetes and its neuronal and vascular complications of the eyes – O-GlcNAc and S-nitrosylated proteins; RNAi technology and therapeutics to prevent/slow down the progression of DR.

Abstract:

Mitochondrial (MT) dysregulation, oxidative stress, and resultant energy imbalance is associated with various chronic diseases including neurodegeneration, ischemia/reperfusion, and retinal complications of diabetic retinopathy (DR). Recently, we published that pro-oxidant thioredoxin interacting protein (TXNIP) is significantly up-regulated early in DR and under hyperglycemia in retinal cells in culture including endothelial and Muller cells (MC) and mediates cellular oxidative/nitrosative stress and inflammation. TXNIP expression is also responsible for pericyte apoptosis under high glucose in culture. TXNIP binds to and inhibits the anti-oxidant function of thioredoxin (Trx), therefore, results in cellular oxidative/nitrosative (ROS/RNS) stress and apoptosis. Furthermore, MC are important for retinal neuronal health and reactive MC gliosis induces aberrant gene expression for cytokines and growth factors to maintain retinal homeostasis. However, prolonged MC activation is injurious in DR. We and others observed in the retina of diabetic animal models that dopaminergic (DAergic) amacrine neurons are vulnerable to early DR and the rate-limiting enzyme for dopamine biosynthesis, tyrosine hydroxylase (TH), is down regulated. However, the molecular mechanism(s) for DAergic neuron death in DR or under hyperglycemia is not understood yet. DAergic neuron death or dopamine deficiency and resultant gliosis could cause early visual defects in patients with diabetes. We hypothesize that TXNIP up-regulation cause oxidative stress, neuroinflammation and neurovascular dysfunction in early DR and disease progression of late blinding ocular complications. Therefore, TXNIP represents a potential therapeutic target to prevent disease onset and/or slow down the progression of DR.

Biography:

Clinician scientist in Ophthalmology with a special interest in stem cell therapies for retinal degeneration. Gregory-Evans Clinic specializes in patients with genetic eye disease. Full investigative assessments including DNA testing and medical treatment are undertaken for patients with macular degeneration, retinitis pigmentosa and other diseases of the retina. Genetic counseling work is also undertaken for patients with other genetic eye diseases such as glaucoma and aniridia. Currently Kevin Gregory-Evans is a Professor in Ophthalmology and Julia Levy BC Leadership Chair in Macular Research from University of British Columbia

Abstract:

Nonsense mutations, modifications of sense codons that instead of encoding for specific amino acids alternatively result in a chain-termination signal and truncated RNA are thought to cause as much as 12% of all human genetic disease. In the eye, nonsense mutations are particularly associated with diseases such as retinitis pigmentosa, Leber’s congenital amaurosis, choroideremia, macular degeneration (Stargardt’s disease) and developmental anomalies such as aniridia. Recently a number of small molecule therapeutics has been studied for their ability to over-write nonsense mutations resulting in full length RNA and disease inhibition. Approximately 50% of PAX6 mutations causing aniridia are in-frame nonsense mutations. Using the small eye (Pax6Sey/+; G194X) mouse model of aniridia we have looked at the effects of the nonsense suppression drug Ataluren. We have documented a remarkable reversal of phenotype using this drug in a topical formulation (START therapy) and have found that histologic and functional benefits (electroretinography, optokinetic tracking responses) are dose sensitive. Most recently we have seen that topical and systemic Ataluren is also effective in inhibiting progression of retinal disease phenotypes suggesting that ocular disease could be a particular target for nonsense suppression strategies.

Biography:

Tina Guanting Qiu is an accomplished ophthalmology physician, trained retinal surgeon, stem cell biologist, and ocular transplant specialist with over 20 years of international experience. She had led scientific research in drug discovery, drug delivery and cell/gene therapy, established and led scientific and medical advisory boards, and served as a strategic advisor to executives in large and small companies (Inotek, LambdaVision, Sucampo, Ocata, GLG). She was Chief Medical Officer at BetaStem Inc., Senior Director at Inotekand Program Leader at GlaxoSmithKline. She has a Medical Doctor degree (with honors) from Nanchang University, a PhD in Ophthalmology from National Sun Yat-sen University in collaboration with Sheie Eye Institute, UPenn followed by post-doctoral trainings at Boston University and Doheny Eye Institute, USC. She has developed, published and lectured across US, UK, Japan and China, and been featured at Scientific American and National Eye Research Center, UK.

Abstract:

Modern medicine development is alike unlocking the mystery of a black box. The 10-year drug development journey is about establishing a drug molecular biological trait along with its pharmacological behaviors in animal disease models and various human conditions. This talk will center on the paradigm shift in therapeutic intervention for retinal diseases. Topics include: 1) Emerging ocular drug delivery innovation from polymer-based sustained release drug delivery to genetic engineered protein bio factory and RNAi/mRNA based therapeutic target (superchoroid and subretinal routes begin to merge); 2) knowledge gaps in regenerative medicine and bio-nanotechnology at cutting edge front; 3) Parainflammation in retina and glaucoma disease management; 4) New highs in disease alteration by emerging therapies - the switch from “wet to dry” of vascular AMD (age-related macular degeneration) is a great example in the rising wave of anti-VEGF therapy; 5) Finally, understand disease staging and phenotype stratification is “A Must” in developing personalized treatment algorithm. New evidences suggest that AMD represents a group of heterogeneous clinical pathological entity that includes RPE aging, photoreceptor loss, Bruch’s membrane thickening, and choroid ischemia, among which one or more can be the primary trigger and predominant clinical phenotype. New appreciation of glaucoma as a neural degenerative disease involving pressure-dependent and pressure-independent risk factors may lead to a breakthrough of neural protection drug development in the 21st century. In summary, reduce photoreceptor and retinal ganglion cell loss is the ultimate goal of therapeutic intervention for a large spectrum of significant neurovascular abnormalities in the retina.