Dr. Albert Siu[/caption]
Dr. Albert Siu M.D., M.S.P.H.
Chair of the U.S. Preventive Services Task Force
Chairman and professor of the Brookdale Department of Geriatrics and Palliative Medicine
Icahn School of Medicine at Mount Sinai
Director of the Geriatric Research, Education, and Clinical Center
James J. Peters Veterans Affairs Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Siu: Impaired vision is a serious and common problem facing older adults and can affect their independence, ability to function, and quality of life. When the Task Force reviewed the research around screening older adults for vision impairment in a primary care setting, we concluded that the current evidence is insufficient to assess the balance of benefits and harms. As a result, we issued an I statement, which is consistent with the 2009 final and 2015 draft recommendations.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Siu: Older adults who are having problems seeing should talk to their primary care doctor or an eye specialist. Primary care doctors can explore the various causes of vision problems and do an eye exam to check for refractive error. An eye specialist can do a full eye exam to look for and treat refractive errors and other eye conditions that affect vision, such as cataracts and age-related macular degeneration (AMD). With regards to clinicians, in the absence of clear evidence, they should use their clinical judgment when deciding whether to screen patients who have not reported any concerns about their vision.
Adam Glassman[/caption]
Adam Glassman, M.S.
Director, DRCRnet Coordinating Center
Jaeb Center for Health Research
Tampa, FL 33647
Medical Research: What is the background for this study? What are the main findings?
Response: Diabetic macular edema (DME) involves a build-up of blood and fluid in the macula, the part of the eye needed for sharp, straight-ahead vision. Diabetic macular edema can occur in people with diabetic retinopathy and is the most common cause of diabetes-related vision loss. Anti-VEGF agents are the first line treatment for most U.S. retinal specialists to treat vision loss from DME. There are three commonly used agents to treat DME, EYLEA, Avastin, and Lucentis. Eylea and Lucentis are FDA approved for Diabetic macular edema treatment. However, Avastin is used off-label in repacked aliquots containing approximately 1/500th of the systemic dose used in cancer therapy. The costs of these agents vary substantially, with Eylea priced at $1,850 per injection, Lucentis at $1,170, and repackaged Avastin at $60. Results of this study, conducted by the Diabetic Retinopathy Clinical Research Network (DRCR.net) and funded by the NIH, found that all three agents are effective at improving vision and reducing DME over 2 years. When vision loss is relatively mild at baseline (20/32-20/40), all three agents are similarly effective at improving visual acuity. However, when vision loss at baseline is worse, Eylea outperforms Avastin at 2-years and also outperforms Lucentis at one year, but the difference between Eylea and Lucentis diminishes and is no longer statistically different at 2 years. The percentage of participants that experienced a systemic adverse events such as heart attack, stroke, or death from an unknown cause was greater with Lucentis (12%) versus Eylea (5%) and Avastin (8%). However, similar findings have not been seen in most previous studies.
Dr. J. William Harbour[/caption]
J. William Harbour, MD
Professor & Vice Chairman
Dr. Mark J. Daily Endowed Chair
Director, Ocular Oncology Service
Bascom Palmer Eye Institute
Interim Associated Director for Basic Research
Leader, Eye Cancer Site Disease Group
Sylvester Comprehensive Cancer Center
Member Interdisciplinary Stem Cell Institute
University of Miami Miller School of Medicine
Biomedical Research Building, Room 824
Miami FL 33136
Medical Research: What is the background for this study? What are the main findings?
Dr. Harbour: Gene expression profiling has become the predominant means of molecular prognostic testing in uveal melanoma, with primary tumors being divided into Class 1 (low metastatic risk, about two thirds of cases) and Class 2 (high metastatic risk, about one third of cases). In this study, we identified a new biomarker for uveal melanoma that subdivides Class 1 tumors based on the mRNA expression of the oncogene PRAME. Class 1 tumors not expressing PRAME have an extremely low metastatic risk, whereas those expressing PRAME have an intermediate metastatic risk.
Dr. Jason Hsu[/caption]
Jason Hsu, MD
Retina Service, Wills Eye Hospital
Assistant Professor of Ophthalmology
Thomas Jefferson University
Mid Atlantic Retina
Medical Research: What is the background for this study? What are the main findings?
Dr. Hsu: There are some patients with the wet type of age-related macular degeneration (AMD) who have persistent swelling in the retina despite regular, repeated eye injections with the anti-vascular endothelial growth factor (anti-VEGF) medications (e.g., Avastin, Lucentis, and Eylea). I had postulated that if we could decrease the turnover of fluid inside the eye, it might allow the injected medicine to stay in the eye for a longer period of time. I chose dorzolamide-timolol (brand name: Cosopt), a commonly available prescription eye drop used for glaucoma, since it is a very potent aqueous suppressant. By slowing down the production of eye fluid, I theorized it might decrease the outflow of fluid and medicine from the eye.
Our study was a small, nonrandomized, exploratory pilot study. We enrolled 10 patients with wet AMD who had persistent retinal swelling despite chronic, fixed interval anti-VEGF injections. We kept patients on the exact same anti-VEGF medication and continued to see them at the exact same interval that they had been on before study enrollment. Once enrolled, the only difference is that we had them start using dorzolamide-timolol eye drops twice a day for the course of the study. The results were fairly striking with the retinal thickness decreasing from around 420 microns to 334 microns at the final visit. This decrease in swelling was significant at the first study visit after starting the drops and remained significant throughout the course of the study.
Dr. Yu-Chih Hou[/caption]
Yu-Chih Hou, MD
Department of Ophthalmology
National Taiwan University Hospital
Taipei, Taiwan
MedicalResearch: What is the background for this study?
Dr. Yu-Chih Hou: We have encountered 3 patients with right eye pain and corneal edema after left orofacial surgery under general anesthesia since December 6. 2010. The first patient underwent a left tongue tumor excision by an ENT doctor. Postoperative day one, corneal epithelial defect and edema with mild anterior chamber reaction were noted in the right eye. Because his presentation was different from corneal abrasion which was the most common eye injury after general anesthesia, we suspected this ocular complication could be due to toxic reaction to antiseptic. Although corneal edema decreased, corneal endothelial cell density decreased and cataract developed later in the first patient. Two months later, the second patient had a similar toxic keratopathy but with severe corneal edema in his right eye after wide tumor excision of left lower gingival cancer by dentist surgeons. We found the antiseptic they used contained alcohol. We recommended not to use alcohol-containing antiseptics in oral surgery. Unfortunately, more severe toxic keratopathy occurred in the third patient after a left nasal tumor excision by other ENT doctor one year later. Because these severe ocular complications may occur again, it raised us to do detail study and we found all antiseptics they used contained alcohol. We hope to prevent occurrence of this toxic keratopathy in nonocular surgery by reporting our findings to other clinicians.
Dr. Demetrios Vavvas[/caption]
Demetrios Vavvas, M.D., Ph.D.
Co-Director Ocular Regenerative Medical Institute
Clinician scientist at Mass. Eye and Ear and Co-Director of the Ocular Regenerative Medicine Institute at Harvard Medical School
Medical Research: What is the background for this study?
Dr. Vavvas: There is a lack of effective therapies for dry age-related macular degeneration (AMD), one of the leading causes of blindness affecting millions. Although AMD shares similarities with atherosclerosis, prior studies on statins and AMD have failed to show improvement. A limitation of these studies has been the heterogeneity of age-related macular degeneration disease and the lack of standardization in statin dosage. We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in age-related macular degeneration.
Medical Research: What are the main findings?
Dr. Vavvas: Here, we present for the first time evidence that treatment with high-dose atorvastatin (80mg) is associated with regression of lipid deposits and improvement in visual acuity, without atrophy or neovascularization, in high-risk age-related macular degeneration patients.
Medical Research: What should clinicians and patients take away from your report?
Dr. Vavvas:
Dr. Rick Fraunfelder[/caption]
MedicalResearch.com Interview with:
Frederick W. Fraunfelder, MD MBA
Chairman and Roy E. Mason and Elizabeth Patee Mason Distinguished ProfessorDepartment of Ophthalmology
Missouri University School of Medicine
Director of the Missouri University Health Care’s Mason Eye Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Fraunfelder: The background starts with a paper by Hwang et al (Cornea. 2013 Apr;32(4):508-9.Reactivation of herpes zoster keratitis in an adult after varicella zoster vaccination. Hwang CW Jr1, Steigleman WA, Saucedo-Sanchez E, Tuli SS.) After reading this paper, I started keeping track of keratitis cases that were reported to my registry (www.eyedrugregistry.com) and also to the FDA and WHO spontaneous reporting databases. We found case reports in adults and children of keratitis occurring soon after vaccination, and we presented this at the American Academy of Ophthalmology’s annual meeting that we just held in Las Vegas in November 2015.
The main findings are that in rare instances, relatively speaking, herpes infection can occur in the cornea of the eye within days to weeks after vaccination. This may especially be true in adults who have had shingles in the past which caused a keratitis in the past. This keratitis may reoccur after the vaccination, and primary care providers should inquire about this past medical/ocular history and advise of the risk of recurrent keratitis after the vaccination for shingles.
Dr. Benjamin Bakondi[/caption]
MedicalResearch.com Interview with:
Benjamin Bakondi, Ph.D. Postdoctoral Scientist
Laboratory of: Shaomei Wang, M.D., Ph.D.
Institute Director: Clive N. Svendsen, Ph.D.
Board of Governors Regenerative Medicine Institute
Cedars-Sinai Medical Center;
Dept. of Biomedical Sciences
Los Angeles, CA 90048
Medical Research: What is the background for this study? What are the main findings?
Dr. Bakondi: Retinitis Pigmentosa (RP) is an inherited disease that causes progressive retinal degeneration and continual vision loss. Over 130 mutations have been identified in over 60 genes that cause RP. Gene replacement therapy is being evaluated for the recessive form of RP, in which both inherited alleles are dysfunctional. Retinitis Pigmentosa arising from dominant mutations however, would not benefit from such a strategy, and alternative options have not demonstrated clear efficacy.
The idea for a therapeutic based on our approach is to use CRISPR/Cas9 to ablate the mutant copy of an allele and leave the wild-type copy unaffected. Barring haploinsufficiency, the wild-type allele should restore function and prevent retinal degeneration at levels commensurate with Cas9 cleavage efficiency. Our experimental findings provide proof-of-principle that a single DNA nucleotide difference in the genomic sequence between mutant and wild-type genes is enough to distinguish the mutant transcript for Cas9 cleavage with high fidelity. Eliminating production of the mutant rhodopsin protein prevented retinal degeneration and preserved vision. While Cas9/gRNA delivery improvement is underway, it should be noted that translational applicability of this approach is restricted to dominant mutations, not all of which may be targetable for ablation therapy.
Dr. Woodward[/caption]
MedicalResearch.com Interview with:
Maria A. Woodward, MD
Department of Ophthalmology and Visual Sciences
University of Michigan
Ann Arbor, MI 48105
Medical Research: What is the background for this study? What are the main findings?
Dr. Woodward: The research was sparked by questions whether changes to the eye with keratoconus affect other parts of the body. There is conflicting information from past research about connections between systemic diseases and keratoconus. This creates confusion for patients and for doctors treating these patients.
Dr. Christina Weng[/caption]
MedicalResearch.com Interview with:
Christina Y. Weng, MD, MBA
Assistant Professor-Vitreoretinal Diseases & Surgery
Baylor College of Medicine-Cullen Eye Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Weng: Telemedicine has been around for a long time, but only recently have technological advances solidified its utility as a reliable, effective, and cost-efficient method of healthcare provision. The application of telemedicine in the field of ophthalmology has been propelled by the development of high-quality non-mydriatic cameras, HIPAA-compliant servers for the storage and transfer of patient data, and the growing demand for ophthalmological care despite the relatively stagnant supply of eye care specialists. The global epidemic of diabetes mellitus has contributed significantly to this growing demand, as the majority of patients with diabetes will develop diabetic retinopathy in their lifetime.
Today, there are over 29 million Americans with diabetes, and diabetic retinopathy is the leading cause of blindness in working age adults in the United States. The American Academy of Ophthalmology’s and American Diabetes Association’s formal screening guidelines recommend that all diabetic patients receive an annual dilated funduscopic examination. Unfortunately, the compliance rate with this recommendation is quite dismal at an estimated 50-65%. It is even lower amongst minority populations which comprise the demographic majority of those served by the Harris Health System in Harris County, Texas, the third most populous county in the United States.
In 2013, the Harris Health System initiated a teleretinal screening program housed by eight of the district’s primary care clinics. In this system, patients with diabetes are identified by their primary care provider (PCP) during their appointments, immediately directed to receive funduscopic photographs by trained on-site personnel operating non-mydriatic cameras, and provided a follow-up recommendation (e.g., referral for in-clinic examination versus repeat imaging in 1 year) depending on the interpretation of their images. The images included in our study were interpreted via two different ways—once by the IRISTM (Intelligent Retinal Imaging Systems) proprietary auto-reader and then again by a trained ophthalmic specialist from the IRISTM reading center. The primary aim of this study was to evaluate the utility of the auto-reader by comparing its results to those of the reading center.
Data for 15,015 screened diabetic patients (30,030 eyes) were included. The sensitivity of the auto-reader in detecting severe non-proliferative diabetic retinopathy or worse, deemed sight threatening diabetic eye disease (STDED), compared to the reading center interpretation of the same images was 66.4% (95% confidence interval [CI] 62.8% - 69.9%) with a false negative rate of 2%. In a population where 15.8% of diabetics have STDED, the negative predictive value of the auto-reader was 97.8% (CI 96.8% - 98.6%).
MedicalResearch.com Interview with: Te-Chao Fang, MD, PhD. Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan Medical Research: What is the background for this study? What are the main findings? Dr. Fang: Patients undergoing hemodialysis (HD) often develop retinal ischemia due to underlying diseases (mostly such as diabetes and malignant...
Dr. Thompson[/caption]
MedicalResearch.com Interview with:
Professor Benjamin Thompson PhD
School of Optometry and Vision Science
Faculty of Science, University of Waterloo
Waterloo, Ontario
Canada
Medical Research: What is the background for this study?
Dr. Thompson: Our investigation was part of the longitudinal Infant Development and Environment and Lifestyle (IDEAL) study that was designed to investigate the effect of prenatal methamphetamine exposure on neurodevelopment. Although the negative impact of prenatal drug exposure on a wide range of neurodevelopmental outcomes such cognitive and motor function is established, the effect on vision is not well understood. To address this issue, vision testing was conducted when children in the New Zealand arm of the IDEAL study turned four and half years of age.
Although the primary focus of the IDEAL study was the impact of methamphetamine on neurodevelopment, the majority of children enrolled in the study were exposed to a range of different drugs prenatally including marijuana, nicotine and alcohol. Many children were exposed to multiple drugs. This allowed us to investigate the impact of individual drugs and their combination on the children’s visual development.
Alongside standard clinical vision tests such as visual acuity (the ‘sharpness’ of vision) and stereopsis (3D vision), we also tested the children’s ability to process complex moving patterns. This test, known as global motion perception, targets a specific network of higher-level visual areas in the brain that are thought to be particularly vulnerable to neurodevelopmental risk factors.
Dr. Berg[/caption]
MedicalResearch.com Interview with:
Karina Birgitta Berg MD
Department of Ophthalmology
Oslo University Hospital
Oslo, Norway
Medical Research: What is the background for this study? What are the main findings?
Dr. Berg: Neovascular age-related macular degeneration (nAMD) has been the leading cause of vision loss in the elderly population of Western countries. Inhibition of vascular endothelial growth factor (VEGF) with medications such as bevacizumab and ranibizumab injected into the eye, has dramatically reduced the incidence of social blindness from this disease. Bevacizumab was marketed for intravenous cancer treatment, while ranibizumab was later developed and approved for intraocular treatment of nAMD. Due to similar clinical effects and a strikingly low cost compared to ranibizumab, bevacizumab has remained widely used as an off-label treatment for the treatment of nAMD. In order to preserve vision results over time, most patients need injections repeatedly. Treatment on a monthly basis has shown good vision improvement, while monitoring monthly and treating only when signs of recurrences appear, is less successful. The aim of a treat-and-extend protocol is to gradually increase the treatment intervals, while avoiding potentially harmful recurrences. This treatment modality has become commonly used, entailing fewer patient visits and less burden upon health care systems.
The multicenter prospective randomized Lucentis Compared to Avastin Study (LUCAS) was aimed at comparing the efficacy and safety of bevacizumab versus ranibizumab when following a treat-and-extend protocol. The patients received monthly injection treatment until inactive disease was achieved. The treatment interval was then increased by two weeks at a time up to a maximum of 12 weeks. In the event of a recurrence, the treatment interval was reduced by two weeks at a time. The study demonstrated equivalent results in vision improvement with bevacizumab and ranibizumab after two years of treatment. Treatment according to a treat-and-extend protocol was safe with good visual results when extending up to 10 weeks, while recurrences at 12-week intervals had a negative impact on the final results on vision.
Dr. McKay[/caption]
MedicalResearch.com Interview with:
Brian S. McKay, Ph.D
Associate Professor
Department of Ophthalmology and Vision Science
University of Arizona
Medical Research Building, Room 212
Tucson, AZ 85724
Medical Research: What is the background for this study?
Dr. McKay: AMD (age-related macular degeneration) is a disease that is race-related. White people get the disease and lose vision to AMD at much higher rate than Blacks or Hispanics.
Thus, while race is complex, pigmentation may protect from the disease. With this starting point, my laboratory went after the pigmentation pathway to determine how pigment may affect photoreceptor (the retinal cells that actually catch the light) survival. The pigmented cells in the back of the eye are the retinal pigment epithelial cells (RPE), the rest of the retina does not pigment, it is clear not brown. We discovered that when the RPE make pigment they turn on molecular pathways to foster photoreceptor survival. Next we discovered the ligand for a receptor on the RPE that was tied to governing photoreceptor survival and pigmentation. That ligand was L-DOPA.
Knowing that L-DOPA is given to many aging individuals (those at risk of AMD), we developed a team to ask whether those taking L-DOPA for movement disorders are protected from AMD.
MedicalResearch.com Interview with:
Professor P. Elizabeth Rakoczy
Centre for Ophthalmology and Visual Sciences
The University of Western Australia
Head of Department - Molecular Ophthalmology
Lions Eye Institute Australia
Medical Research: What is the background for this study?
Prof. Rakoczy: Wet age related macular (wet-AMD) is the major cause of blindness in the developed world. It is treated with frequent anti-VEGF injections into the eye. Our preclinical studies demonstrated that following the subretinal injection of a recombinant adeno-associated vector (rAAV) carrying a natural inhibitor of neovascularization (sFlt-1), leaky new, abnormal vessels can be controlled and retinal anatomy improved. The rAAV.sFlt-1 based Ocular Biofactory™ platform has potentially significant advantages over existing technologies as it is designed to provide sustained production of a naturally occurring antiangiogenic agent, sFlt-1, in situ in the eye. In this trial we investigated the safety of rAAV.sFlt-1 in patients diagnosed with wet-AMD.
MedicalResearch.com Interview with:
Professor Jeremy A. Guggenheim
School of Optometry & Vision Sciences
Cardiff University
Cardiff, UK
Medical Research: What is the background for this study?
Dr. Guggenheim: An increased risk of myopia (nearsightedness) in first-born vs. non-first-born individuals was noticed in a 2013 study, which focused on 4 cohorts of children and young adults. We wanted to know whether the link between birth order and myopia was present in an earlier generation – before the invention of mobile phones and other gadgets. Also, first-born children tend to get slightly higher exam grades than do non-first-born children, an effect that has been attributed to slightly greater investment of time and energy by parents in the education of their first-born child. A high level of education is a well-known risk factor for myopia, therefore we were interested to find out whether the association between birth order and myopia was attributable to the slightly greater educational exposure of first-born individuals
MedicalResearch.com Interview with:
Ann-Cathrine Larsen MD, PhD-student
University of Copenhagen
Faculty of Health Sciences
Department of Neuroscience and Pharmacology, Eye Pathology Section
Copenhagen
Medical Research: What is the background for this study?
Dr. Larsen: Conjunctival melanoma is an uncommon malignancy with a high mortality. Population-based studies evaluating prognostic features and treatment are rare. The clinicopathological and prognostic features associated with BRAF-mutations in conjunctival melanoma are unclear.
Medical Research: What are the main findings?
Dr. Larsen: Extrabulbar tumor location and invasion of adjacent tissue structures were poor prognostic features. Incisional biopsy and excision without adjuvant therapy were associated with metastatic disease. Younger age at diagnosis, bulbar or caruncular tumor location, T1 stage tumor, lack of clinical melanosis and mixed or non-pigmented tumor color were features associated with BRAF-mutated conjunctival melanoma. Furthermore, Patients with BRAF mutated tumors seem to have an increased risk of distant metastatic disease.
MedicalResearch.com Interview with:
Paul Miller PhD student
The University of Queensland
Australia
Medical Research: What is the background for this study? What are the main findings?
Response: All humans have a blind spot in each eye where the optic nerve, which sends signals to the brain, passes through the retina, the light sensitive layer in each eye. Where this happens you cannot detect light, so people are blind to images that project to this location.
Behaviorally, people tend to report blindness for an area that is larger than physiology dictates. We found this curious, and thought it might be driven by people reporting blindness for regions that border the blind spot, where sensitivity is degraded, but not absent. If so, we thought that this could be improved by training. When we tested this theory, we found it was true - we were able to reduce the extent of functional blindness by about 10%.
MedicalResearch.com Interview with:
Professor Robert E MacLaren MB ChB DPhil FRCOphth FRCS
Nuffield Laboratory of Ophthalmology
Nuffield Department of Clinical Neurosciences
Oxford Biomedical Research Centre, University of Oxford,
Moorfields Eye Hospital & UCL NIHR Biomedical Research Centre for Ophthalmology
London, UK.
MedicalResearch.com Interview with:
Dr Ruth Hogg, Lecturer
Centre for Experimental Medicine (formerly Centre for Vision and Vascular Science)
Institute of Clinical Science Block
Belfast Northern Ireland
Medical Research: What is the background for this study? What are the main findings?
Dr. Hogg: The development of Diabetic macular edema (DME) in patients with diabetes can result in severe visual loss. Understanding the factors driving the development of these conditions is important for developing effective treatments. The role of lipids has been suggested by previous studies however as the evidence overall appeared to have significant uncertainty we decided to undertake a systematic review and where possible perform a meta-analysis or results.
The study revealed that the evidence of a relationship between blood lipid levels and Diabetic macular edema from cohort and case control studies was strong but evidence from the randomised control trials (RCTs) was weak. The RCTS evaluated however were often not designed to look at Diabetic macular edema as an primary outcome, and this was often part of a secondary analysis leaving uncertainty over the power to detect the association.
MedicalResearch.com Interview with: Pradeep Ramulu MD MHS PhD Associate Professor of Ophthalmology Wilmer Eye Institute Johns Hopkins University MedicalResearch: What is the background for this study? What are the main findings? Dr. Ramulu: Looking at what procedures are used allows us to understand what doctors are doing, and how the landscape of our field is changing....