Author Interviews, JAMA, Ophthalmology, Pediatrics / 16.08.2017

MedicalResearch.com Interview with: Mary Elizabeth Hartnett, MD, FACS, FARVO Professor of Ophthalmology, Vitreoretinal Service and Surgery Principal Investigator Retinal Angiogenesis Laboratory Director of Pediatric Retina, Adjunct Professor of Pediatrics John A. Moran Eye Center Salt Lake City UT 84132 On behalf of the co-authors: Julia Shulman, Cindy Weng, Jacob Wilkes, Tom Greene, M. Elizabeth Hartnett MedicalResearch.com: What is the background for this study? Response: Maternal preeclampsia causes morbidity to mothers and infants worldwide. Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. This study was done to gain insight into the effects of preeclampsia on ROP in a clinical population. The literature is mixed with some reports that preeclampsia increases risk of Retinopathy of prematurity, whereas others suggest preeclampsia is protective or has no effect. The presence of circulating anti-angiogenic factors in preeclamptic mothers that can enter the fetal circulation lends biologic plausibility to the notion that maternal preeclampsia might interfere with developing vascular beds in the fetus, such as the retina, and potentially lead to severe ROP. However, a report using an experimental model provided evidence that uteroplacental insufficiency, a characteristic of preeclampsia, led to protective mechanisms in the offspring that reduced oxygen-induced retinopathy and promoted overall growth. (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology, UC Davis / 30.07.2017

MedicalResearch.com Interview with: Jeffrey R. Willis MD, PhD UC Davis Eye Center University of California, Davis Sacramento California MedicalResearch.com: What is the background for this study? What are the main findings? Response: Diabetic retinopathy is one of the leading causes of blindness in the United States.  Yet there is limited national level data on the impact of worsening DR on quality of life and visual function. Our study aimed to address this knowledge gap by evaluating the functional burden of DR across severity levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES). We found that one-half of US adults with severe non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) had difficulty with ≥ 1 visual function task, possibly impacting their daily work/activities.  These patients reported a significantly greater vision-related functional burden relative to those with less severe forms of DR. (more…)
Author Interviews, Cancer Research, Dermatology, Ophthalmology / 24.07.2017

MedicalResearch.com Interview with: Dr.med.univ. Christoph Schwab Departement of Ophthalmology Medical University of Graz Graz, Austria  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Knowledge about risk factors and/or pathways involved in pathogenesis is from special importance in order of preventing diseases. The role of sunlight in several eye diseases is unclear. In our study we found a close relation between sun light exposure - evaluated by a full body skin examination and a personal questionnaire - and iris freckles. Therefore we suggest the presence of iris freckles as a novel biomarker indicating high ocular sun exposure. (more…)
Author Interviews, Genetic Research, Lancet, Ophthalmology / 17.07.2017

MedicalResearch.com Interview with: Stephen R. Russell, MD Dina J Schrage Professor of Macular Degeneration Research Service Director, Vitreoretinal Diseases and Surgery Professor of Ophthalmology and Visual Sciences The University of Iowa MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study examines the efficacy (and safety) of treating children and adults with a form of retinitis pigmentosa known as RPE65-associated Lebers congenital amaurosis, with an adeno-associated viral vector(AAV) delivered RPE65 construct.  Building on successful phase 1/2b trials from multiple centers, the AAV-hRPE65v2 agent now designated as voretigene neparvovec, contains a highly optimized enhancing sequence and promoter. The main findings were an improvement on a multiple light level mobility test (MLMT) and multiple additional supportive secondary endpoints which included improvements in full-field light sensitivity, Goldmann visual field, and others. (more…)
Author Interviews, Diabetes, Ophthalmology / 07.07.2017

MedicalResearch.com Interview with: Dr. David Kita, PhD Founder and Head of R&D Verseon CorporationDr. David Kita, PhD Founder and Head of R&D Verseon Corporation

MedicalResearch.com: What is the background for this study?

Dr. Kita: The preclinical data presented at the 2017 BIO International Conference provided details about Verseon’s plasma kallikrein inhibitors for the treatment of diabetic macular edema (DME). DME affects millions of people worldwide and is a major cause of vision loss in patients with diabetes mellitus. Upregulation of the kallikrein-kinin system in response to diabetes can result in retinal vascular permeability, which can damage the retina and eventually lead to the central vision loss associated with DME. The current treatment options for DME include intravitreal injections of anti-VEGF agents or corticosteroids into the eye and surgical laser treatments. Long-term use of intravitreal injections is associated with side effects such as inflammation, infections, and cataracts. For anti-VEGF drugs in particular, there is also a growing concern about geographic atrophy. In addition, about 50% of patients reported at most moderate vision improvements following anti-VEGF therapy in clinical trials. This highlights the need for a new treatment that can serve as a monotherapy or as an adjuvant to current therapies. At Verseon, we are working on inhibitors of the serine protease plasma kallikrein (KLKB1) that can be administered either topically or orally. Verseon’s unique computer-driven drug discovery platform allows us to design potent, selective drug candidates that are unlikely to be found using traditional approaches. We have generated a number of chemically distinct series of KLKB1 inhibitors and optimized multiple lead candidates, which show good activity, permeability, and solubility. (more…)
Author Interviews, Genetic Research, Ophthalmology, University Texas / 07.07.2017

MedicalResearch.com Interview with: Stephen P. Daiger, PhD Professor, Human Genetics Center Thomas Stull Matney, Ph.D. Professor in Environmental and Genetic Sciences Mary Farish Johnston Distinguished Chair in Ophthalmology The University of Texas Health Science Center at Houston   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thanks for your questions about our research.  My research group and I have a long-term interest in finding genes and mutations causing inherited retinal diseases.  Our main focus is on retinitis pigmentosa (RP) and, more specifically, the autosomal dominant form of RP. Inherited retinal diseases are progressive, degenerative diseases of the retina.  Onset can be very early in life, even at birth, or much later in life.  As the degeneration develops an affected person may first experienced limited loss of vision, progressing to severe loss of vision, ending, in many cases, in legal or complete blindness.  About 300,000 Americans are affected by inherited retinal disease and 50% of these have RP.  RP, like most hereditary conditions, can be inherited in an autosomal dominant, autosomal recessive or X-linked fashion. One of the surprising, and in some sense, disturbing findings in studying  retinitis pigmentosa is that mutations in many different genes can cause this disease.  We now know that mutations in more than 80 genes can cause RP and thousands of different mutations have been found in these genes.  With next-generations sequencing it is possible to find the cause of RP in from 50% to 80% of cases, depending on the underlying mode of inheritance.For example, in our research we can find the disease-causing mutation in about 75% of families with autosomal dominant RP.  Needless to say, a primary aim of our research is to find the cause in the remaining 25%. In looking for the cause of retinitis pigmentosa in the remaining 25%, that is, those in whom mutations were not detected by earlier methods, we found a potential dominant-acting mutation in the arrestin-1 gene (gene symbol “SAG”) using whole-genome sequencing.  Molecular modeling suggests this mutation is damaging.  This was unexpected because previously-reported mutations in this gene were associated with Oguchi disease, a recessive retinal disease with symptoms distinct from RP.  On further testing our cohort of patients with autosomal dominant RP, we found this mutation in nearly 4% of families.  Even more surprisingly, when we looked closely at the affected families, and worked with our collaborators to test other patients, we discovered that all of the families with the dominant-acting SAG mutation -- 12 total -- were of Hispanic origin.  By interviewing informative family members we learned that these families have their roots in the Southwestern United States.  Historically, the mutation may have arisen hundreds of years ago, consistent with genetic variation tracking with the mutation. (more…)
Author Interviews, Brigham & Women's - Harvard, NEJM, Ophthalmology / 08.06.2017

MedicalResearch.com Interview with: Elisabetta Patorno, MD, DrPH Assistant Professor of Medicine, Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital MedicalResearch.com: What is the background for this study? Response: Lithium, a widely used medicine to treat bipolar disorder, has been associated with a 400 fold increased risk of Ebstein’s anomaly, a congenital malformation of the heart, and a 5 fold increased risk of cardiac defects overall in infants when taken early in pregnancy, based on the results from the International Register of Lithium Babies in the 1970’s. Beyond this data, most of the information on the safety of lithium during pregnancy accumulated in the last 40 years is based on case reports and small studies with conflicting results. Despite these concerns and the limited information, lithium remains a first-line treatment for the 1% of women of reproductive age with bipolar disorder in the U.S. population, due to its recognized efficacy during pregnancy and the postpartum period, and due to the presence of a larger body of evidence showing increased risk of congenital malformations for other mood stabilizers, such as valproate. (more…)
Author Interviews, Lancet, Macular Degeneration, Ophthalmology / 18.05.2017

MedicalResearch.com Interview with: Prof Peter A Campochiaro MD Director, Retinal Cell and Molecular Laboratory Professor of Ophthalmology Johns Hopkins University School of Medicine Baltimore, MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with wet age-related macular degeneration (AMD) have increased levels of vascular endothelial growth factor (VEGF) in their eyes resulting in growth of abnormal blood vessels that leak fluid into the retina and reduce vision. The current treatment is to inject proteins that block VEGF which initially provides a very good effect, but repeated injections are needed. Patients sometimes are unable to keep up the frequency of visits and injections needed to keep the disease quiet and over time there is often gradual loss of vision. The aim of this study was to test a new approach through which a viral vector is injected into the eye resulting in production of a protein that block VEGF in the eye reducing the need for repeated injections. These are the major findings: 1) Intravitreous injection of an AAV2 vector expressing a protein that blocks vascular endothelial growth factor (VEGF) was safe and well-tolerated. (2) 5 of 10 patients injected with the highest dose (2 × 10¹⁰ vector genomes) had measurable levels of the therapeutic protein in samples removed from the front of the eye- all of these patients had no or very low levels of anti-AAV2 serum antibodies and 4 of the 5 patients who did not show expression had high anti-AAV2 serum antibodies (3) Eleven patients had fluid in or under the retina before vector injection and 6 of them showed substantial reduction of the fluid which is the desired outcome. (more…)
Author Interviews, Macular Degeneration, Ophthalmology, Technology / 17.05.2017

MedicalResearch.com Interview with: Dr Felicity de Cogan PhD Institute of Inflammation and Ageing University of Birmingham MedicalResearch.com: What is the background for this study? Response: The University of Birmingham has a unique approach to developing technologies. By locating chemists, engineers, biologists and clinicians in the same department it revolutionised the way research problems are solved. Initially, Felicity de Cogan was researching cell penetrating peptides (CPP) and their uses in microbiology. However, after joining forces with Neuroscientists, Dr Lisa Hill and Professor Ann Logan at the National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre (NIHR SRMRC) together with the clinicians and Vision Scientists, Dr Mei Chen and Professor Heping Xu at the Queen’s University Belfast it became evident that there was huge potential to deliver drugs in the eye. This was the start of the project and it developed rapidly from there. (more…)
Author Interviews, Genetic Research, Ophthalmology / 15.05.2017

MedicalResearch.com Interview with: Zheng-Rong Lu, Ph.D. M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering Department of Biomedical Engineering Case Western Reserve University Cleveland, OH 44106 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Genetic vision disorders are a major cause of severe vision loss and blindness, especially in children and young adults. Currently, there are no approved therapies to treat these types of disorders. This study focused on one such disease known as Leber’s congenital amaurosis type 2 (LCA2). Patients with LCA2 are born with some degree of vision loss, and are often legally blind by early adulthood. LCA2 is a recessive disease caused by a mutation in one of the genes responsible for visual processing. LCA2 is a good candidate for gene therapy, and clinical trials underway to test viral vectors that deliver a healthy copy of the mutated gene into the eye have demonstrated considerable therapeutic efficacy. These trials have validated the feasibility of gene therapy to treat this disease, however viral vectors are limited by potential safety issues, complex preparation methods, and limitations on the size of genes that can be delivered. In this study, we successfully treated LCA2 in mice for 120 days by delivering the gene responsible for LCA2 in a synthetic lipid nanoparticle instead of a viral vector. Our delivery system, called ECO, specifically targets the cells in the retinal pigmented epithelium, where the mutation behind LCA2 occurs. Our nanoparticle delivery system is easy to produce, safe, and has unlimited cargo capacity. Most important, our nanoparticle gene delivery system is a platform that can be used to deliver any gene into the retina, opening the door for safe and effective gene therapy for any genetic vision disorder. (more…)
Author Interviews, JAMA, Ophthalmology / 08.05.2017

MedicalResearch.com Interview with: John H Kempen, MD, PhD Protocol Chair, MUST Trial Follow-up Study; Vice Chair, MUST Research Group Director of Epidemiology for Ophthalmology, Massachusetts Eye and Ear Harvard Medical School Editor-in-Chief, Ophthalmic Epidemiology President, Sight for Souls MedicalResearch.com: What is the background for this study? Response: Uveitis is about the fifth leading cause of blindness in the united states.  Among types of uveitis, intermediate, posterior and panuveitis are the leading causes of blindness.  Before 2005, systemic therapy with corticosteroids—supplemented when indicated with immunosuppressive drugs (most of the time)—was the primary treatment recommended for these conditions.  With approval of the fluocinolone acetonide implant in 2005 for intermediate, posterior and panuveitis, it became unclear which of the alternative treatment approaches should be the treatment of choice. The multicenter uveitis steroid treatment (must) trial was initiated in 2005 to directly compare the alternative treatments.  Systemic therapy was administered using high dose prednisone followed by tapering of corticosteroids to maintenance doses of 10 mg/day or less (generally 7.5 mg/day or less) or to zero; this was supplemented by immunosuppressive corticosteroid-sparing drugs in 88% of participants.  Implant therapy was done by initial quieting of the anterior chamber of the eye with topical, injected or systemic corticosteroids followed by surgical implant placement within 28 days (first eye) and 56 days (second eye if it was indicated).  After this, systemic corticosteroids and immunosuppressive drugs were tapered off. (more…)
Author Interviews, JAMA, Ophthalmology, Pediatrics / 05.05.2017

MedicalResearch.com Interview with: Rohit Varma, MD, MPH Executive Director - USC Roski Eye Institute and Dean of the Keck School of Medicine of USC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Visual impairment in early childhood has profound impact on a child’s development. It can significantly impair development of visual, motor, and cognitive function1-3 and lead to adverse psychosocial consequences. There has been a lack of accurate data characterizing the current and expected numbers of visual impairment cases among preschool children in the United States from 2015 to 2060. The number of preschool children with visual impairment is projected to increase by 26% in 2060. And 69% of these visual impairment will result from simple uncorrected refractive error such hyperopia and myopia, which can be prevented or treated by low-cost refractive correction. (more…)
Author Interviews, JAMA, Macular Degeneration, Ophthalmology, Primary Care / 01.05.2017

MedicalResearch.com Interview with: David C Neely, MD The University of Alabama at Birmingham MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study examined the prevalence of eyes with age-related macular degeneration (AMD) in patients seen in primary eye care clinics who purportedly have normal macular health. Approximately 25.0% of eyes deemed to be normal based on dilated eye examination by primary eye care providers had macular characteristics that indicated age-related macular degeneration. (more…)
Author Interviews, Ophthalmology / 23.04.2017

MedicalResearch.com Interview with: Kang Zhang, M.D., Ph.D. Professor of Ophthalmology Chief, Ophthalmic Genetics Founding Director, Institute for Genomic Medicine Co-Director, Biomaterials and Tissue Engineering, Institute for Engineering in Medicine Board Certification in Ophthalmology Fellowship in Vitreoretinal Disease and Surgery Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Retinitis pigmentosa is a common blinding condition characterized by mutations in rod photoreceptor specific genes, night blindness and tunnel visual with eventual loss of day vision. Since it can be caused by numerous different mutations in many genes therefore it has been difficult to provide treatment benefits to a majority of patients. Traditional gene therapy has been in a piece-meal fashion, meaning to create a therapy for a particular gene or mutation. In this paper, we describe a universal gene therapy approach using the latest gene editing technology CRISPR/CAS9 to reprogram rod photoreceptors to cone photoreceptors with reversal of RP and restoration of vision. (more…)
Addiction, Author Interviews, Infections, JAMA, Ophthalmology / 22.04.2017

MedicalResearch.com Interview with: Aubrey Tirpack, PGY3 New England Eye Center Tufts Medical Center  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Intravenous drug abuse is a known risk factor for the development of endogenous fungal endophthalmitis (EFE), a severe intraocular infection cause by the seeding of mycotic organisms to the eye. Our institution noted a marked increase in cases of EFE beginning in May 2014, which correlates to increasing rates of opioid abuse throughout the New England region. Ten patients were found to have intravenous drug abuse related EFE over the two year time period studied. The most common presenting symptoms were floaters, decreased vision, and pain. All patients were treated with systemic antifungals and nine patients underwent intravitreal antifungal injection. All patients were ambulatory at presentation and the majority were without systemic signs of infection. (more…)
Author Interviews, Diabetes, NEJM, Ophthalmology, Personalized Medicine / 20.04.2017

MedicalResearch.com Interview with: John M. Lachin, Sc.D. Research Professor of Biostatistics and of Epidemiology, and of Statistics The George Washington University Biostatistics Center and David Matthew Nathan, M.D. Professor of Medicine, Diabetes Unit Massachusetts General Hospital  MedicalResearch.com: What is the background for this study? Response: Traditional guidelines for screening for retinopathy, based on indirect evidence, call for annual examinations. The automatic annual screening for retinopathy, without considering potential risk factors for progression,  appears excessive based on the slow rate of progression through sub-clinical states of retinopathy. (more…)
Addiction, Author Interviews, BMJ, Ophthalmology / 17.04.2017

MedicalResearch.com Interview with: Dr. Rebecca Rewbury Sussex Eye Hospital Brighton and Sussex University Hospitals Trust Brighton, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: ‘Poppers’ are recreational drugs which are illegal to sell for human ingestion, but are sold under the guise of household cleaning products. Inhalation leads to a brief sense of euphoria, enhanced sexual arousal and smooth muscle relaxation. The Psychoactive Substances Act 2016 was due to outlaw poppers, but they were excluded on the basis that they do not act directly on the central nervous system. The main constituent of poppers, isopropyl nitrite, replaced isobutyl nitrite when the latter was classified as a carcinogen in 2006. Since then, there have been several case reports of ‘poppers maculopathy.’ We noted an increase in patients presenting with central visual disturbances after using poppers and describe 12 such cases. They all demonstrated similar disruption of the photoreceptor layer on retinal imaging. Onset of symptoms was frequently linked to specific brands of poppers, with 3 people having used poppers for many years and only developing side effects on changing brand. Chemical analysis showed that these products contained isopropyl nitrite. One brand of poppers, used without side effects by one patient, contained amyl nitrite, 2-methyl butyl nitrite and isobutyl alcohol, but no isopropyl nitrite. The outcome of poppers maculopathy varied, but following abstention, visual disturbances and retinal damage tended to improve over months, if not fully resolve. Although in some cases, symptoms and/or imaging findings were prolonged. Ongoing use of implicated brands led to persistent, but not worsening maculopathy, whereas one patient that switched back to another brand showed full recovery. (more…)
Author Interviews, Boehringer Ingelheim, Diabetes, JAMA, Ophthalmology / 13.04.2017

MedicalResearch.com Interview with: Marco A Zarbin, MD, PhD, FACS Alfonse Cinotti, MD/Lions Eye Research Professor and Chair Institute of Ophthalmology & Visual Science Rutgers-New Jersey Medical School Rutgers University Newark, NJ 0710  MedicalResearch.com: What is the background for this study? What are the main findings?
  1. Most large, randomized clinical trials are powered to assess the efficacy of drugs or interventions, but they usually do not enroll enough patients to accurately assess the frequency of uncommon, undesirable side effects.
  2. In order to compensate for this deficiency in trial design, investigators aggregate the results of numerous studies all of which address the same clinical question with the same (or similar) drugs/interventions to increase the power to detect uncommon side effects. These aggregate studies can be meta-analyses.
  3. Unfortunately, most meta-analyses do not have the ability to answer some critical questions such as the timing of an adverse event relative to the last exposure to the drug, nor can they compensate fully for differences among the aggregated studies in trial design, length of patient follow-up, or presence pre-existing risk factors for the side effects in question.
  4. A pooled analysis of combined clinical trials using patient level data, however, allows a more in depth analysis of side effects than study level data, which are usually used for most published meta-analyses, because patient level data allow one to incorporate the per-patient duration of exposure to treatment, adjust for imbalances in predefined baseline risk factors, and adjust for the effect of results of single studies on the overall result.
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Author Interviews, Cost of Health Care, JAMA, Macular Degeneration, Ophthalmology, Telemedicine / 02.04.2017

MedicalResearch.com Interview with: John Wittenborn Senior research scientist NORC's Public Health Analytics University of Chicago MedicalResearch.com: What is the background for this study? What are the main findings? Response:The emergence of anti-VEGF treatment for wet-form AMD (choroidal neovascularization) has had a dramatic impact on preserving vision for many Americans. However, community-based studies show that most patients are not diagnosed with wet-form AMD until they have already lost a significant, and largely unrecoverable amount of their vision.  Early detection of wet-form AMD is key to effective treatment and the preservation of vision. The ForeseeHome telemonitoring technology provides patients with a means to check their own eyes on a daily basis to detect the earliest signs of vision loss from wet-form AMD. This is a novel technology that has the potential to improve visual health outcomes for AMD patients.  A prior clinical trial (the AREDS-2 HOME study) demonstrated that this technology can detect wet-form AMD earlier, and with less vision loss than standard care alone. However, that is exactly where that study ended as it reported no cost information nor follow-up. Since the end of this study, the device has been cleared by the FDA and approved for reimbursement by Medicare for certain higher risk patients, but no study has yet considered the long-term implications of adoption of this technology. In our analysis, we use a computer simulation model to essentially estimate what will come next, after patients realize earlier detection of wet-form AMD by utilizing home monitoring. Basically, we follow simulated patients from the time they begin monitoring for the rest of their lives, recording the likely impacts of home monitoring on patients’ long term outcomes including visual status, costs and quality of life. We find that home telemonitoring among the population indicated for reimbursement by Medicare would cost $35,663 per quality adjusted life year (QALY) gained.  Medicare would expect to incur $1,312 in net budgetary costs over 10 years for each patient who initiates monitoring.  However, Medicare patients may expect to achieve lifetime net savings when accounting for the chance of avoided vision loss and its associated costs later in life. (more…)
Abuse and Neglect, Author Interviews, Diabetes, JAMA, Ophthalmology, Technology / 21.03.2017

MedicalResearch.com Interview with: José Cunha-Vaz, M.D., Ph.D. Emeritus Professor of Ophthalmology University of Coimbra, Portugal President of AIBILI Association for Innovation and Biomedical Research on Light and Image Editor-in-Chief of Ophthalmic Research Coordinator, Diabetic Retinopathy and Retinal Vascular Diseases, European Vision Institute Clinical Research Network (EVICR.net)  MedicalResearch.com: What is the background for this study? What are the main findings? Response: In this study, we evaluated the clinical utility of quantitative measures of microvasculature in optical coherence tomographic angiography (OCTA). Although several studies have demonstrated the potential value of measures of microvasculature in the management of diabetic retinopathy (DR), our study uses the ROC curve to compare the overall value of different approaches. In this age matched population with a range of disease, the mean vessel density measured in the SRL had the highest AUC, indicating that it is best among the methods tested at differentiating normal eyes from eyes with diabetic retinopathy. (more…)
Author Interviews, NIH, Ophthalmology, Stem Cells / 06.02.2017

MedicalResearch.com Interview with: Ben Mead, BSc, MRes, PhD Section of Retinal Ganglion Cell Biology Laboratory of Retinal Cell and Molecular Biology National Eye Institute, National Institutes of Health Bethesda, Maryland 20892 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Retinal ganglion cells (RGC) in the back of the eye transmit visual information to the brain, via long thread-like extensions called axons, which make up the optic nerve. Loss of these cells is the leading cause of irreversible blindness and can occur through trauma or degenerative diseases, such as glaucoma or optic neuritis. While no treatment yet exists to directly protect RGC from death, mesenchymal stem cells, a type of stem cell isolated from adult bone marrow, have shown therapeutic efficacy in various animal models and are currently undergoing clinical trials. In this study, we aimed to isolate exosomes, which are small, membrane-enclosed vesicles secreted by bone marrow stem cells (BMSC) and that we believe are associated with the therapeutic effect of BMSCs. Injecting these exosomes into the eyes of animals following an optic nerve injury, was associated with significant neuroprotection of RGC, as well as preservation of RGC function. The protective effects of exosomes appeared to be through their delivery of microRNA, molecules that interfere with or silence gene expression. (more…)
Aging, Author Interviews, Genetic Research, JAMA, Macular Degeneration, Ophthalmology / 08.12.2016

MedicalResearch.com Interview with: dr-anneke-i-den-hollanderAnneke I. den Hollander, PhD Department of Ophthalmology and Department of Human Genetics Donders Institute for Brain, Cognition, and Behaviour Radboud University Medical Center Nijmegen, the Netherland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Age-related macular degeneration is caused by a combination of genetic and environmental factors. Rare genetic variants in the complement system have been described in AMD, but their effect remains largely unexplored. In this study we aimed to determine the effect of rare genetic variants in the complement system on complement levels and activity in serum. MedicalResearch.com: What are the main findings? Response: Carriers of CFI variants showed decreased FI levels, carriers of C9 Pro167Ser had increased C9 levels, while C3 and FH levels were not altered. Carriers of CFH and CFI variants had a reduced ability to degrade C3b, which for CFI was linked to reduced serum FI levels. (more…)
Author Interviews, FDA, JAMA, Ophthalmology / 02.12.2016

MedicalResearch.com Interview with: Malvina Eydelman, M.D. Division Director; Division of Ophthalmic and Ear, Nose and Throat Devices Office of Device Evaluation Center for Devices and Radiological Health FDA. MedicalResearch.com: What is the background for this study? Response: In October 2009, the FDA, the National Eye Institute (NEI), and the Department of Defense (DoD) launched the LASIK Quality of Life Collaboration Project (LQOLCP) to help better understand the potential risk of severe problems that can result from LASIK. The project aimed to develop a tool to determine the percent of patients who develop difficulties performing their usual activities following LASIK, and to identify predictors for those patients. At the time we developed our project, there was a limited amount of valid scientific data on certain patient-reported outcomes (PROs) related to LASIK. A PRO is a report of a condition experienced and reported by the patient, not the health care provider. Most LASIK studies used tools, such as questionnaires, to assess visual symptoms, but only after the surgery. The Patient-Reported Outcomes with LASIK (PROWL) studies in the LQOLCP assessed visual symptoms both before and after their LASIK surgery to identify changes over time. The studies also measured the impact symptoms directly had on performing usual activities, which had not previously been done. (more…)
Author Interviews, Gender Differences, Ophthalmology, Social Issues / 02.12.2016

MedicalResearch.com Interview with: Antoine Coutrot PhD CoMPLEX University College London London, UK MedicalResearch.com: What is the background for this study? What are the main findings? Response: The human face is central to our everyday social interactions. Recent studies have shown that while gazing at faces, each one of us has a particular eye-scanning pattern, highly stable across time. Although variables such as culture or personality have been shown to modulate gaze behavior, we still don't know what shapes these idiosyncrasies. Moreover, most previous observations rely on analyses of small-sized eye-position datasets, often from the WEIRD (western, educated, industrialized, rich, and democratic) population. Here we use a very large and diverse dataset (400+ participants from 58 nationalities) and show that among many observer characteristics, gender is the one that best explains the differences in gaze behaviour. When looking at faces, women are more exploratory than men and more biased toward the left side. We even trained a classifier able to infer the gender of observers only based on their gaze. (more…)
Author Interviews, Neurological Disorders, Ophthalmology, Pediatrics / 23.11.2016

MedicalResearch.com Interview with: Marius George Linguraru, DPhil, MA, MB Principal Investigator Associate Professor of Pediatrics and Radiology George Washington University School of Medicine and Health Sciences Children’s National Health System Washington, DC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome affecting the central nervous with an incidence of one in 3,000 births. Nearly one in five children with NF1 develops an optic pathway glioma (OPG), a low-grade tumor of the anterior visual pathway (i.e., optic nerves, chiasm and tracts). These tumors are not amenable to surgical resection and can cause permanent vision loss ranging from a mild decline in visual acuity to complete blindness. Only half of children with NF1-OPGs will experience vision loss, typically between 1 to 6 years of age. The other half will never lose vision or require treatment. All previous studies have consistently demonstrated that the change in NF1-OPG size is not related to the clinical outcome. For example, the optic pathway glioma size may be stable or even decrease, yet the vision will decline. Alternatively, the OPG size may increase, yet the clinical outcome remains stable or even improves. As no imaging or clinical features can identify which children with NF1-OPGs will ultimately lose vision, clinicians struggle to follow these children and decide when to intervene. We used quantitative imaging technology to accurately assess in magnetic resonance imaging (MRI) the total volume of OPGs in NF1. We also determined the retinal nerve fiber layer thickness in these children, a measure of axonal degeneration and an established biomarker of visual impairment. The results were outstanding, as we showed for the first time that the volume of an optic pathway glioma is indeed correlated with the likelihood of vision loss in children with Neurofibromatosis type 1. (more…)
Author Interviews, Ophthalmology, Technology / 20.11.2016

MedicalResearch.com Interview with: Dr. Andrew Bastawrous, Ophthalmologist Rolex Awards for Enterprise United Kingdom Dr. Bastawrous’ smartphone-based portable eye examination system, Peek Vision, allows patients in low resource setting, to be screened for vision problems and eye diseases, enabling accurate diagnosis and treatment. MedicalResearch.com: What is the background for Peek Vision? What are the main findings of your work with this system? Response: Mama Paul has been blind for almost 20 years, most of her time is spent within the safety of her tiny home. It is basic, but in her mind’s eye she can still picture where the door is, her son - Paul, lives next door and is always willing to help. Losing sight is the sense most people fear losing most. I am severely visually impaired, I am also fortunate to have perfect vision when wearing corrective glasses or contact lenses and privileged to be in the profession of ophthalmology where centuries of research and practice have brought us to a time when so much of blindness is now curable or preventable. There is no feeling like it: when the eye patch comes off someone who hasn’t seen for years, the sheer wonder as they take in their surroundings and their anticipation to see faces that have become voices and places that have become memories. Back in 2011, as I pondered and planned for the challenges that lay ahead of us in Kenya, I had the continual thought that there must be an easier way to reach people, a way that is less expensive, less resource hungry and therefore could be used on a much wider scale. In Kenya, and much of Africa, more people have access to a mobile phone than they do clean running water. It had to be possible to harness this connectivity. (more…)
Author Interviews, JAMA, Ophthalmology, Zika / 15.11.2016

MedicalResearch.com Interview with: Camila Ventura MD Pediatric Retina Research Fellow at Bascom Palmer Eye Institute (BPEI), USA PhD student at Federal University of São Paulo (Unifesp) Medical Retina, Ocular Oncology, and Uveitis Department at Altino Ventura Foundation Brazil MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Brazilian outbreak of Zika virus (ZIKV) began in April 2015 and since then, we have not been able to stop its rapid spread throughout the Americas. Not only has ZIKV been disseminating very rapidly, patients affected by the ZIKV have also been presenting with some findings never before reported in the literature. Until recently, ZIKV infection was only associated with mild symptoms such as headache, rash, arthralgia, and conjunctivitis. However, in October 2015, a twenty-fold increase in the prevalence of newborns with microcephaly was reported that was later confirmed to be associated to ZIKV infection during pregnancy. Although microcephaly and other central nervous system findings were the first abnormalities reported, recent publications have described other malformations associated with ZIKV congenital infection including hearing loss, limb anomalies and ocular findings. Due to all of these systemic findings, this new clinical condition has been named Congenital Zika Syndrome (CZS). In January 2016, our group published the first report on the ocular findings of infants with microcephaly and presumed congenital ZIKV infection, followed by another manuscript describing 10 additional cases. We have also contributed with an article published in JAMA Ophthalmology reporting the risk factors associated to the ocular findings in babies with CZS. Other authors such as De Paula Freitas et al and Miranda 2nd et al, have also contributed to the literature by describing similar ocular findings in these infants with CZS. In the present case series, we describe the Ocular Coherence Tomography (OCT) findings in ten eyes of eight infants with CZS. (more…)
Author Interviews, JAMA, Ophthalmology, Pediatrics, Technology / 11.11.2016

MedicalResearch.com Interview with: Krista Kelly, PhD Postdoctoral Fellow Crystal Charity Ball Pediatric Vision Evaluation Center Retina Foundation of the Southwest Dallas, TX 75231 MedicalResearch.com: What is the background for this study? Response: Amblyopia is one of the most common causes of monocular impairment in children, affecting 1 or 2 children in every US classroom. Patching of the fellow eye has been used for decades to improve visual acuity in the amblyopic eye. But patching does not always restore normal vision and does not teach the two eyes to work together. A novel technique originally designed by Drs Robert Hess and Ben Thompson at McGill University that works to reduce interocular suppression by rebalancing the contrast between the eyes has shown promising results in amblyopic adults. Dr Eileen Birch at the Retina Foundation of the Southwest worked with Dr Hess to adapt this contrast re-balancing approach to an iPad game platform suitable for children. Her research showed that the games were successful in improving visual acuity in amblyopic children as well. However, these initial games were rudimentary and resulted in low compliance. (more…)