Day 2 :
- Retina | Glucoma | Cataract | Vision Therapy
Chair
Vadrevu K. Raju
West Virginia University, USA
Session Introduction
Clérin E
Institut de la Vision, France
Title: The development of a therapy for retinitis pigmentosa based on the nucleoredoxin-like 1 gene
Biography:
Clérin E is a Research Engineer and her main expertise is in the fields of Animal Experimentation, Gene Therapy, Tissue Culture, Immunohistochemistry and Biochemistry. He manages the research activities of the team. He developed an automated counting platform at the institute of vision, e-conome to measure cone density over the whole mouse retinal surface4. This system, developed as a part of the translational research projects on RdCVF was used in the majority of the team projects in a total of six publications. Also his main mission is focused currently on this preclinical research project and to assume daily the organization, the follow-up and the feasibility of the totality of the experiment.
Abstract:
Retinitis pigmentosa is an inherited retinal degeneration that processes from the death of rods followed by dysfunction and degeneration of cones. The nucleoredoxin-like 1 (NXNL1) gene encodes for two different proteins: the trophic factor rod-derived cone viability factor (RdCVF) and the long form, the thioredoxin (RdCVFL). RdCVF acts by stimulating aerobic glycolysis to sustain the outer cone segment renewal and RdCVFL protects the cones against hyperoxia. To translate this promising therapy towards the clinic, independently of the causative gene, we have evaluated the therapeutic benefit of delivering both products of the NXNL1 gene by subretinal injection with an AAV vector targeting retinal pigmented epithelial cells and cones in a mouse model of the disease. Unilateral subretinal delivery of AAV-RdCVF/RdCVFL as compared to AAV-GFP and sham were performed in rd10 mice at 15 days post-natal. The visual acuity test was carried out from 30 days to 55 days post-natal. Eye of animals were collected and used for automated counting after the labelling of cones. The quality control of AAV particles was made by transmission electron microscopy. The kinetics of the loss of visual acuity was significantly retarded statistically after injection of AAV-RdCVF-RdCVFL in three independent experiments. The results were validated by the increase of cone density. We have validated the quality of the viral productions by measuring the percentage of full to empty particles using electron microscopy. Poly-unsaturated fatty acids lipids of the external segment of photoreceptors are essential for phototransduction, prone to oxidation. We show a reduced amount of malondialdehyde (MDA), a marker of lipid peroxidation, for animals injected with AAV-RdCVF-RdCVFL demonstrating the additional protective effect of RdCVFL on cones, strengthening the interest to combine RdCVF and RdCVFL. Our results demonstrate that this treatment will likely be successful in preserving central vision in patients suffering from retinitis pigmentosa in the near future.
Maneli Mozaffarieh
Limmat Eye Center & University of Basel, Switzerland
Title: New insights in the pathogenesis of normal tension glaucoma
Biography:
Maneli Mozaffarieh is an Associate Professor and Glaucoma Specialist with particular focus on Microcirculation who completed her specialization with Professor Josef Flammer, former Head of the Department of Ophthalmology at the University of Basel. She currently teaches at the University of Basel and works clinically in Zürich.
Abstract:
Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage and reducing IOP improves prognosis. Nevertheless, there is little doubt that other risk factors besides IOP such as unstable ocular perfusion are involved. Blood flow is unstable if either the IOP fluctuates at a high level (or blood pressure fluctuates at a low level) or if the autoregulation of blood flow is disturbed. A common cause for a disturbed OBF autoregulation is a primary vascular dysregulation (PVD) also known as the Flammer-syndrome (FS), frequently observed in normal tension glaucoma patients. Patients with FS commonly have increased retinal venous pressures as measured by means of ophthalmodynamometry. An unstable blood flow leads to recurrent mild reperfusion injury (chronic oxidative stress) affecting particularly the mitochondria of the optic nerve head.
Carlota Saldanha
University of Lisbon, Portugal
Title: Erythrocyte nitric oxide in glaucoma patients
Biography:
Carlota Saldanha is the Professor of Biochemistry and Head of Unit of Institute of Molecular Medicine João Lobo Antunes, Faculty of Medicine, University of Lisbon. She is a Member of the European Society for Clinical Hemorheology and Microcirculation (ESCHM); Coordinating Committee and Editorial Board of the Clinical Hemorheology and Microcirculation; Strategic Group of the European Society for Microcirculation; President of Sociedade Portuguesa de Hemorreologia e Microcirculação and Collaborator of CEMAT–Center for Computational and Stochastic Mathematics of FCT. She has done basic and clinical research on Biochemistry: membrane properties, cell function, enzymology, metabolism, signal transduction. Her research interests include applied hemorheology and microcirculation, inflammation, erythrocyte signal transduction mechanism, fibrinogen binding, nitric oxide metabolism and signal transduction.
Abstract:
Erythrocyte or red blood cells (RBCs) are influents in the blood flow velocity and hemorheology. RBCs also participate in hemostasis systems and in body tissues oxygenation through the vessel endothelium. Endothelial cells and lymphocytes are able to synthesize acetylcholine (ACh) which is to release plasma. Depending on the endothelium integrity degree, the circulating ACh induce vasodilation or vasoconstriction according to the amount of nitric oxide (NO) synthesized and is released into smooth muscle cells (SMC) or to plasma. The NO released is scavenged by erythrocytes and blood cell free hemoglobin. NO enter into RBCs through its membrane protein band 3 and binds to oxyhemoglobin generating S-nitrosohemoglobin (SNO-Hb) and to glutathione originating nitrosoglutathione (GSNO). The NO efflux from erythrocyte is under dependence of mechanical or chemical stimuli bound to membrane receptors. Those affect the NO reservoir molecules inside erythrocyte in dependence of protein phosphorylation degree and redox thiol status. Timolol maleate is a compound used in treatment of patients with open angle glaucoma (OAG).Timolol is a weak inhibitor or erythrocyte membrane acetylcholinesterase (AChE) which behaves as an enzyme and a receptor of ACh. The erythrocytes obtained from blood samples of OAG patients’ present higher AChE enzyme activity and high NO efflux than those obtained from healthy persons. When blood samples taken from OAG patients were incubated in the presence of Ach, no changes in NO efflux in GSNO were verified. At variance, in presence of timolol, instead of ACh, both NO efflux levels and GSNO concentration increase. These data evidences show that the erythrocyte membrane of OAG patients have different molecular properties than healthy subjects which corroborate the increasing tendency of RBCs to aggregate as observed in previous studies. The NO efflux signal transduction pathway associated to AChE-ACh (Figure) and AChE-timolol will be described at the conference.
Fawzia Bardag-Gorce
Los Angeles Biomedical Research Institute at Harbor—UCLA Medical Center, Torrance, CA, USA
Title: Expression of ALDH in cultured autologous oral mucosal epithelial cell sheet (CAOMECS) grafts for ocular surface reconstruction
Biography:
Fawzia Bardag-Gorce has been studying Ocular Surface Disease for the last six years, and has since published and co‑authored six peer-reviewed publications in the field. She began her research on the treatment of limbal stem cell deficiency using cultured autologous oral mucosa epithelial cell sheet (CAOMECS). During these six years, and under her supervision and guidance, her lab has successfully completed pre-clinical studies related to the efficacy and safety of CAOMECS cell-based therapy. She is currently directing a new study approved by the Institutional Research Board in which subjects are being recruited for the human oral mucosal epithelial cell sheet characterization. The long-term goal of this study is to regenerate corneal epithelium in patient with severe ocular surface diseases using autologous oral mucosa epithelial cell sheet grafts.
Abstract:
Statement of the Problem: The transplantation of allogenic limbal epithelium in the form of a keratolimbal allograft from cadaveric tissue is one of the current treatments for patients suffering from injury to the ocular surface. However, transplantation of donor corneal tissue is dependent on the available supply, and the shortage of donor eyes is a well-known continuing problem worldwide. The use of allogeneic limbal grafts is not regarded as standard treatment; it requires systemic immunosuppression and has a poor rate of success. Recently, we have used a cultured non-limbal autologous cell type (Cultured autologous oral mucosa epithelial cell sheet or CAOMECS) to treat ocular surface disease (limbal stem cell deficiency or LSCD).
Aim: The purpose of this study is to focus on the expression of aldehyde dehydrogenases (ALDH1A1 and ALDH3A1) in CAOMECS. These enzymes reduce the levels of acetaldehyde, a highly reactive chemical that causes alterations in proteins and DNA. ALDH also protects against UV induced-oxidative damage and plays an important role in reducing ocular diseases associated with photophobia.
Methodology & Theoretical Orientation: To create LSCD, rabbits underwent surgical limbectomy. Rabbit oral mucosal epithelial cells were isolated and cultured to produce CAOMECS grafts. Microarray analysis profiling gene expression was used to detect gene expression of ALDH in cultured oral mucosal epithelial cells. Immunofluorescent staining and western blot analysis were used to examine ALDH protein levels in healthy and LSCD-diseased rabbit corneal epithelial cells.
Findings: Immunofluorescent staining showed that ALDH1A1 was highly expressed in healthy corneal epithelial cells. Staining of corneal epithelial cells in rabbits with LSCD showed greatly reduced expression. Western blot analysis confirmed the decrease of ALDH1A1 in LSCD-diseased corneal epithelial cells. Microarray analysis showed significant gene expression of exclusively ALDH1A1 in rabbit CAOMECS. Other investigators have shown that rabbit do not express ALDH3A1 in corneal tissue. Our data showed similar pattern in CAOMECS. The up regulated gene expression of ALDH1A1 suggests CAOMECS may have cytoprotective characteristics against ultraviolet radiation as well as oxidative damage.
Conclusion & Significance: These findings support the hypothesis that CAOMECS may protect against photophobia by grafting cells that contain ALDH, which may improve corneal epithelium cell function and corneal transparency.
André Pellizzer Marcondes
Leedsay Medical Products, Monte AprazÃvel, Brazil
Title: Evaluation of a new combined ophthalmic viscosurgical device in patients undergoing cataract surgery
Biography:
André Pellizzer Marcondes is a Pharmacist with specialization in Biochemistry. He works as Director of pharmaceutical companies with more than 30 years of experience in the sector. All your efforts and actions are directed towards the evolution, research and development of pharmaceutical products and processes, more focused on ophthalmology. He is passionate about technology and innovation and with a futuristic vision, in mid-2009 he decided to abandon the traditional work platforms definitively and began to work exclusively with his own system of organization, with the purpose of developing innovative processes and products, aiming for global reach.
Abstract:
Statement of the Problem: Ophthalmic viscosurgical devices (OVDs) are viscoelastic solutions used in cataract surgery to create and maintain space in the anterior chamber of the eye during phacoemulsification and implantation of the intraocular lens (IOL). They can be classified into two general categories: cohesive and dispersive. Cohesive OVDs maintain the anterior chamber during the capsulorhexis and IOL implantation and dispersive OVDs protect corneal endothelium during the phacoemulsification. In general, it is necessary to use a dye prior to filling the anterior chamber with OVDs. The most used dye in cataract surgery is the Trypan Blue. Because they are separate substances, it is mandatory to perform two different surgical steps during the phacoemulsification. Combined OVDs are a recent innovation and they allow the execution of two surgical steps simultaneously. The purpose of this study is to evaluate the use of a new combined viscoelastic agent in patients undergoing phacoemulsification.
Methodology & Theoretical Orientation: A longitudinal and prospective study of 20 eyes of consecutive patients with cataract was conducted at the Hilton Rocha Foundation, Brazil. All patients underwent a complete ophthalmologic examination before the phacoemulsification. During the perioperative period, a combined solution containing the viscosurgical HPMC 2% with 0.0012% trypan blue was used to fill the anterior chamber and stain the anterior lens capsule simultaneously. The efficacy of capsule staining was analyzed.
Findings: Capsulorhexis was performed in all eyes without any difficulty. Filling of the anterior chamber and visualization of the anterior lens capsule were possible because of the HPMC and trypan blue, respectively. In the postoperative period there were no cases of toxicity or persistent corneal edema.
Conclusion & Significance: The combined solution containing the viscosurgical HPMC 2% with 0.0012% trypan blue has the ability to fill spaces and blush the capsule simultaneously, resulting in greater safety, greater speed, simplicity and convenience in cataract surgery.
Osama Mohiey El Deen Al-Nahrawy
Suez Canal University, Egypt
Title: Measuring and quantifying the complications and lean of laser vision correction techniques
Biography:
Osama Mohiey El Deen Mohamed Al-Nahrawy, Presently working as a Professor of Ophthalmology, Faculty of Medicine, Suez Canal University and its hospital, Ismailia, Egypt. He is the CEO of Al-Nahrawy Eye and lasik Centers, Sharer founder of Private eye centers in Cairo:Al Hayat Eye center, 17 Mekka Street, Dokki, Giza, Cairo & Egyptian Eye Academy, 17 Beirut Street, Heliopolis, Cairo.
Abstract:
Introduction: Laser vision correction techniques include: Laser assisted in situ keratomelieusis (LASIK), Femtosecond laser-assisted LASIK and photo refractive Keratectomy (PRK). Such techniques have different complications, many of them are reported in literature. Those complications are not measured, not quantified and not analysed to know the most and the less serious, to know the root causes and use this in the management plans. Also, it is noticed that no lean analyses and assessment of waste steps inherent in such techniques.
Methods: Review articles and randomised controlled trials are being searched. Reported complications are summarised and analysed. For each technique, number of complications and their severity scores will be calculated. For each complication, further search about its root causes is done and reported. Safety and risk definitions are redefined or reconsidered. Technical steps, equipments, consumables and materials used and time consumed in these techniques are being analysed.
Findings: 22 types of complications related to the LASIK technique , 17 types of complications related to femto-LASIK and 3 types of complications related to PRK were found. Most complications related to the first two techniques were related to flap-lifting. Free caps, button holes, striae, epithelial downgrowths and post lasik ectasia were the most sever types of complications (scores 3-5). Steps of techniques were as follow: LASIK: 8 steps. PRK: 3 steps. Femtolasik: 7 steps.
Conclusion: Photorefractive keratectomy (PRK) is proved to be the least complications, the safest and the best lean technique. In the second order comes the femtolasik, being the second safe but the lowest lean. Conventional microkeratome LASIK is the most risky techniques but has an intermediate lean level.
Mikhail A Ostrovsky
Institute of Biochemical Physics—Russian Academy of Sciences, Russia
Title: Study of lipofuscin granules and melanosomes from human retinal pigment epithelium Mikhail A Ostrovsky
Biography:
Mikhail Ostrovsky is a Physiologist known for his work in Vision and Biology. He is a full member (Academician) of Russian Academy of Sciences, a Professor of Lomonosov Moscow State University and President of the Pavlov Physiological Society of Russia. He has published books on the Molecular Mechanisms of Visual Reception (2002), Spectral Correction of Vision (2005), Actual Tendency of Brain Investigation (2010), Molecular Physiology and Pathology of the Eye Lens (2013) and 200 scientific papers. Over the past two decades, he has been actively studying the lipofuscin granules. Together with co-authors, he found that lipofuscin granules are generators of free radicals under the action of visible light (1993). Recently, together with co-authors he described “changes in spectral properties and composition of lipofuscin fluorophores from human retinal pigment epithelium with pathology” (2015).
Abstract:
Lipofuscin granules (LGs) accumulate in the retinal pigment epithelium (RPE) cells with age, particularly in patients with hereditary diseases. Photosensitization of LGs with blue light can generate reactive oxygen species. Defined differences in fluorescence properties between chloroform extracts obtained from cadaver eyes with and without signs of pathology hold promise for the future improvement of fundus autofluorescence imaging. There is a significant age-related decrease for melanosomes in the RPE cell due to its biodegradation. Oxidants, such as hydrogen peroxide or superoxide radicals, easily lead to melanin destruction. For example, superoxide radicals lead simultaneously both to decrease the amount of melanosomes and concentration of paramagnetic centers of the melanin. We suggest that the age-related loss of melanosomes in the RPE cell is due to melanin destruction in the complex melanolipofuscin granules; superoxide radicals light-induced by LGs cause the destruction. The accumulation of LGs as source of free radicals along with autofluorescence and loss of melanosomes as screening and antioxidant pigment in the RPE cells with age can lead to photo-oxidative stress which is related to the progression of serious eye pathologies. The lecture reviews the recent advances in knowledge of the RPE lipofuscin granules and melanosomes.
- Myopia | Vision Disorders & Diseases | Ocular Injury
Chair
Ming Ronnier Luo
Zhejiang University, Hangzhou, China
Session Introduction
Ming Ronnier Luo
Zhejiang University, Hangzhou, China
Title: LED light for health and well-being
Biography:
Ming Ronnier Luo is a Global Expertise Professor at the College of Optical Science and Technology, Zhejiang University (China), a Visiting Professor of Colour Science and Imaging, University of Leeds (UK) and a Chair Professor at the National Taiwan University of Science and Technology, Chinese Taipei. He is also the CIE Vice-President of Publication. He received his PhD in 1986 at the University of Bradford in the field of Colour Science. He has published 600 publications in the areas of colour science, imaging science and LED illumination. He is a Fellow of the Society for Imaging Science and Technology (IS&T), and the Society of Dyers and Colourists (SDC). He has received numerous awards for his research in Colour Science and Technology including the recent AIC 2017 Judd Award.
Abstract:
With the advanced of LED lighting, it is envisaged that lighting can be used to improve not only our work efficiency but also well-being, including higher sleeping quality, less eye fatigue, better mood. This has become a hot topic called health integrated lighting (HIL). They are related to the human circadian system, which is affected by a newly found photoreceptor, ipRGC, intrinsic photosensitivity Retina Ganglion Cell (ipRGC). More recently, CIE recommended 5 terms in SI unit to measure ipRGC influenced light responses, e.g. Emel, Erd, Esc, Emc, Elc in irradiance. Rea et. al. also proposed CS Circadian Stimulus (CS) to estimate light response directly proportional to nocturnal melatonin suppression. This paper will be focused on the technology required to achieve high quality of HL.
Ali Demircan
Beyoglu Eye Research and Education Hospital, Istanbul, Turkey
Title: Five-year follow-up of small incision lenticule extraction in high myopia
Biography:
Ali Demircan completed his Residency at Beyoglu Eye Research and Education Hospital. He has worked as an Ophthalmologist for two years in Rize State Hospital. Then, he worked as an Assistant Professor for one year at Okmeydani Education and Research Hospital. He has been working as a Retina Fellow for two years at Beyoglu Eye Research and Education Hospital. He has published more than 16 papers in reputed journals
Abstract:
The aim of this study is to report long term visual and refractive results of small incision lenticule extraction (SMILE) in treatment of high myopia. For this purpose, medical records of patients who underwent SMILE for surgical correction of myopia or myopic astigmatism were retrospectively reviewed. Only patients with a preoperative spherical equivalent of subjective manifest refraction (SE) ≥6 D and a post-operative follow-up of five years were included in the study. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and manifest refraction SE were analyzed pre-operatively and at one, three and five year’s post-operative periods. Pre-operative and post-operative complications were also recorded. Thirty-seven eyes of 24 patients were included in the study. Eight (33%) patients were male and 16 (67%) were female. Mean patient age was 31±10 years. The mean pre-operative SE was −7.82±1.35 diopters (D) (range −6.00 to −11.00 D) and mean attempted correction was −7.47±1.10 D (range −6.00 to −10.00 D). Mean pre-operative UDVA and CDVA were 1.41±0.18 and 0.12±0.12 logMAR, respectively. At the five year follow-up, the mean spherical equivalent was −0.79±0.68 D (range −2.5 to 0 D) and the mean difference between achieved and attempted correction was −0.43±0.47 (0.50 to -1.25 D). Mean post-operative UDVA and CDVA were 0.20± 0.18 and 0.06 ± 0.08 logMAR, respectively. SE was within ±0.50 D of intended correction in 76% of patients and ±1.00 D of intended correction in 92% of patients. No patient lost one or more lines of CDVA. No vision threatening complications occurred during surgery or the post-operative period. We conclude that SMILE, with an intended correction of up to a spherical equivalent of 10 D is safe and effective in long term.
Rola N Hamam
American University of Beirut, Lebanon
Title: ¬¬¬¬Novel treatment for vision threatening uveitis
Biography:
Introduction: Uveitis is a leading cause of preventable blindness. It is responsible for 25% of blindness in the developing world and 30,000 new cases of blindness per year in the United States. 35% of all uveitis patients have visual impairment. As such, uveitis is a worldwide problem of significant proportions with peak onset during the wage-earning years (mean age at presentation of 40 years) which magnifies the socioeconomic impact of the disease. Furthermore, treatment of this disease in many cases involves the use of medications that are expensive and have significant systemic side effects. In this paper, we discuss the use of intraocular adalimumab for the treatment of vision threatening uveitis.
Methods: In a pilot study we investigated the safety and efficacy of intravitreal adalimumab (IVA) (1.5 mg/0.03 ml intravitreal injection every month) for the treatment of active uveitis as a de novo treatment and as a rescue therapy in patients on treatment with systemic adalimumab.
Results: 6/7 patients (12/13 eyes) completed 26 weeks of treatment. One patient (1 eye) failed treatment; 7/12 eyes had improvement of two ETDRS lines; 3/3 eyes had resolution of anterior chamber cells; 9/10 eyes with vitreous haze had zero haze at 26 weeks and 5/8 eyes with macular edema had complete resolution. Median fluorescein angiography score improved from 14 to 4 on last follow-up. Seven eyes of four patients with Behcet's panuveitis on systemic adalimumab therapy were treated for breakthrough attacks with IVA. 13 breakthrough attacks were documented over three years. The mean number of injections necessary for resolution of an attack was 2.4 over an average of 2.6 months. 3/13 attacks resolved after one injection.
Conclusion & Significance: Intravitreal adalimumab may be an effective, practical, safe and affordable adjunctive therapy for the control of de novo or breakthrough inflammation in select patients.
Abstract:
Rola N Hamam is an Associate Professor of Ophthalmology at the American University of Beirut. She is the Director of the Residency Training Program and the Medical Retina Fellowship Training Program. She completed her Residency in Ophthalmology at the American University of Beirut and Fellowship Training at Harvard University in Boston at the Beetham Eye Institute, the Massachusetts Eye and Ear Infirmary, and the Massachusetts Eye Research and Surgery Institution until 2008. She returned to her home country and joined the Faculty at the American University of Beirut in 2009 to start the first uveitis specialty referral clinic in Lebanon. She is a Member of several national and international societies. She has organized and lectured on Ocular Immunology and Uveitis in many national and international conferences and scientific meetings. She is involved in multiple research projects on ocular inflammatory and infectious disease.
Md Shafiqul Islam
Sher-e-Bangla Medical College Hospital, Barisal, Bangladesh
Title: Overview of ocular injury in southern part of Bangladesh: a hospital based study of 406 cases
Biography:
Abstract:
Background: Eye injury is a common ophthalmic problem. It is an important and preventable public health problem worldwide.
Purpose: To assess the magnitude, pattern, extent, severity, causes and visual outcome of ocular injury in a tertiary hospital.
Materials & Methods: This cross-sectional study was done at the Eye Department of Sher-e-Bangla Medical College Hospital, Barisal over a period of two years. All patients admitted with eye injury through the outpatient or emergency routes were included in the study. They were examined to note the areas injured, type and extent of injury and impact on vision.
Results: Ocular injuries were 18.5% of total admitted patients and 16.3% of all operative cases. Out of the total 406 cases, 74.3% were male and 25.6% were female. The average age was 26.3 years. Paediatric eye trauma constituted 29.8% of total cases which mostly occurred during playing. 71.4% cases arrived to our centre within 24 hours and 28.5% presented after 24 hours. Majority of the cases comprised of monocular trauma 93.8%. Blunt injuries constituted about 59.1%, while 19.7% had sharp injuries. Open globe injuries were 23.8%. More than 1/3 of the patients had visual acuity worse than 3/60 at presentation and 5.4% cases were NPL.
Conclusion: Ocular injuries are significant cause of morbidity in terms of visual loss or impairment and diminished quality of life. A preventive and educational strategy among the population is necessary to reduce eye injury burden.