Author Interviews, JAMA, Ophthalmology, Surgical Research, Toxin Research / 27.02.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Brigham & Women's - Harvard, Macular Degeneration / 15.02.2016

MedicalResearch.com Interview with: 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:
  • High dose lipophilic statin administration was associated with regression of large soft drusen and vision gain in 10/23 age-related macular degeneration patients.
  • Duration of treatment before a positive response was observed was usually 1-1.5 years.
  • Patients on high-dose statin appeared to be protected from progression to “wet” neovascular-AMD.
Cholesterol reduction was similarly drastic in responders and non-responders, which suggests that genetic variation may be important in determine who will benefit and who may not. Age-related macular degeneration is a heterogeneous disease and that targeting the lipid pathway in the appropriate manner and to the appropriate populations we may have the potential not only to slow down or arrest the disease but all to reverse it. (more…)
Author Interviews, Biomarkers, Genetic Research, Ophthalmology / 11.02.2016

MedicalResearch.com Interview with: Dr Shi Song Rong PhD and Guy Li-Jia CHEN MBBS, MMed, MRCSEd (Ophth), PhD Assistant Professor Department of Ophthalmology & Visual SciencesPrince of Wales Hospital Faculty of Medicine The Chinese University of Hong Kong Medical Research: What is the background for this study? What are the main findings? Response: Glaucoma is a leading cause of irreversible blindness worldwide. Primary angle-closure glaucoma (PACG) as a major form of glaucoma accounts for about half of the cases blinded from the disease. So far, more than 50 genes/loci have been assessed for their associations with PACG and a wider spectrum of relevant conditions, primary angle-closure disease (PACD).  In the article, we summarize the statistical associations of individual genes varying across different study cohorts and conducted meta-analysis to evaluate the associations of 28 polymorphisms in 11 genes/loci with PACD and its subtypes, including PACG, primary angle-closure (PAC) and/or primary angle-closure suspect (PACS). Thus, we affirmed the association of PACG and combined PACS/PAC/PACG with 10 polymorphisms in 8 genes/loci as potential biomarkers. Among them 3 were identified in the genome-wide association study (COL11A1,PLEKHA7 and PCMTD1-ST18), and 5 (HGF, HSP70, MFRP, MMP9 and NOS3) in candidate gene studies. (more…)
Author Interviews, Herpes Viruses, Ophthalmology, Vaccine Studies / 30.01.2016

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. (more…)
Author Interviews, Genetic Research, Ophthalmology / 18.01.2016

More on Gene Therapy on MedicalResearch.com 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. (more…)
Author Interviews, Exercise - Fitness, Ophthalmology, PLoS / 18.01.2016

More on Ophthalmology on MedicalResearch.com MedicalResearch.com Interview with: Robert Ritch, MD, FACS Shelley and Steven Einhorn Distinguished Chair Professor of Ophthalmology Surgeon Director Emeritus and Chief, Glaucoma Services Founder, Medical Director and Chairman, Scientific Advisory Board The Glaucoma Foundation Jessica V. Jasien MEn Einhorn Clinical Research Center The New York Eye and Ear Infirmary of Mount Sinai New York, NY 10003 Medical Research: What is the background for this study? What are the main findings? Response: Glaucoma is the leading cause of irreversible blindness in the United States and elevated intraocular pressure (IOP) is the most common known risk factor for glaucomatous damage. At the current time, IOP is the only modifiable risk factor for which treatment has a proven effect on preventing or slowing the progress of the disease. The story behind this study goes back to 1980, when we saw a 45-year-old woman with severe damage from normal-tension glaucoma, which then was thought to be a disease of the elderly and also thought to be rare, which we now realize was erroneous. The causes of normal-tension glaucoma were also poorly understood. It turned out on questioning that this particular patient had been performing yoga and standing on her head for 20 minutes a day for 20 years. We measured her IOP in this position and it rose from 15 mmHg in the sitting position to 60 mmHg. When measured lying flat, it was 30 mmHg. We measured everyone working in the department standing on their heads and the IOP roughly doubled in each of them. This was our first inkling that marked changes in IOP could result from changes in body position. The background for this study came from the lack of knowledge of IOP rises during yoga inversions, other than the headstand position. We looked at four common inverted yoga positions in glaucoma patients and healthy patients who were all experienced in practicing yoga. The four positions tested were downward facing dog, plow, legs up the wall, and forward bend. Each position showed a direct increase in IOP immediately assuming the yoga position, however the IOP dropped once assuming the seated position after two minutes in the yoga position. The most significant increase in IOP was seen during the downward facing dog position. IOP of each study participant was taken seated (baseline), immediately assuming the yoga position, which was held for two minutes, again at the two minutes of the yoga position, immediately in the seated position following the yoga position, and again after 10 minutes in the seated position. Each position was tested once in this order of IOP measurements. (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, Nutrition, Ophthalmology / 16.01.2016

More on Ophthalmology on MedicalResearch.com MedicalResearch.com Interview with: Jae Hee Kang, MSc, SC Associate Epidemiologist, Brigham and Women's Hospital Assistant Professor of Medicine, Harvard Medical School Brigham and Women's Hospital Department of Medicine Channing Division of Network Medicine Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Kang: Glaucoma is a leading cause of irreversible blindness worldwide, and primary open-angle glaucoma (POAG) is the most common form of the disease. Little is known on the causes of glaucoma but dysfunction in the regulation of blood flow to the optic nerve, which transmits visual information to the brain, may be involved. Nitric oxide is important for maintenance of blood flow and its signaling may be impaired in glaucoma. We were interested in whether dietary nitrates, an exogenous source of nitric oxide mostly found in green-leafy vegetables, may be related to lower risk of POAG. Medical Research: What is the background for this study? What are the main findings? Dr. Kang: We (Brigham and Women’s Hospital / Harvard Medical School and Massachusetts Eye and Ear researchers) used 25+ years of data from over 100,000 participants in the Nurses' Health Study (63,893 women) and the Health Professionals Follow-up Study (41,094 men). Participants were nurses or other health professionals and were aged 40 years or older and reported eye exams. We collected information on their diet and other health information every two years with questionnaires. During follow-up, 1,483 new cases of primary open-angle glaucoma with visual field loss were identified and confirmed with medical record review. Participants were divided into quintiles (one of five groups) of dietary nitrate intake (quintile 5, approximately 240 mg/day; quintile 1, approximately 80 mg/day) and of green leafy vegetables (quintile 5, approximately 1.5 servings/day; quintile 1, approximately one-third of a serving/day). We observed that greater intake of dietary nitrate and green leafy vegetables (e.g., romaine and iceberg lettuce and kale/chard/mustard greens) was associated with a 20 percent to 30 percent lower POAG risk; the association was particularly strong (40 percent-50 percent lower risk) for POAG with early paracentral visual field loss (a subtype of POAG most linked to dysfunction in blood flow autoregulation). (more…)
Author Interviews, Columbia, Cost of Health Care, JAMA, Ophthalmology / 15.01.2016

More on Health Care Costs on MedicalResearch.com MedicalResearch.com Interview with: Alisa Prager BS Bernard and Shirlee Brown Glaucoma Research Laboratory Department of Ophthalmology Edward S. Harkness Eye Institute Columbia University Medical Center, New York, New York MedicalResearch: What is the background for this study?  Response: The goal of this research was to better understand the impact of glaucoma on non-ophthalmic healthcare use and costs. While there have been other studies assessing costs associated with glaucoma, these studies were primarily derived from either claims data or chart review. Our study used the Medicare Current Beneficiary Survey, which is a dataset that links claims data with survey results. The advantage of this is that the survey data allowed us to assess patient reported outcomes that did not necessarily prompt an encounter with the health care system, such as recent falls or feelings of sadness. The MCBS also provides complete expenditure and source of payment data on health services, including those not covered by Medicare, which allowed us to look at a more full spectrum of both private and public healthcare use and costs among Medicare beneficiaries. MedicalResearch: What are the main findings? Response: We found that Medicare beneficiaries with glaucoma have 27% higher likelihood of inpatient hospitalizations and home health aide visits compared to those without glaucoma, even after adjusting for covariates and excluding individuals who were admitted to the hospital with a diagnosis of glaucoma. When we stratified glaucoma patients based on self-reported visual disability, we found that those with self-reported visual disability were more likely to complain of depression, falls and difficulty walking compared to those without. We also found that glaucoma patients incurred a predicted $2,903 higher mean annual total healthcare costs from all sources compared to those without glaucoma after adjusting for socioeconomic factors and comorbidities. Costs were higher among those who reported visual disability, and remained higher after excluding outpatient payments. (more…)
Author Interviews, Ophthalmology / 14.01.2016

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. (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology, Telemedicine / 23.12.2015

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%). (more…)
Addiction, Alcohol, Author Interviews, Cannabis, OBGYNE, Ophthalmology, Pediatrics / 28.11.2015

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. (more…)
Author Interviews, Diabetes, Macular Degeneration, Ophthalmology / 26.11.2015

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. (more…)
Accidents & Violence, Duke, Ophthalmology / 17.11.2015

MedicalResearch.com Interview with: Christina R. Prescott, M.D., Ph.D Assistant Professor of Ophthalmology Johns Hopkins Wilmer Eye Institute Medical Research: What is the background for this study? What are the main findings? Dr. Prescott: I wanted to look at the most common causes of severe ocular injuries, with the hope of helping to focus injury prevention strategies. From 2002 to 2011, the mean hospital charge for inpatient hospitalizations due to eye injuries increased from $12,430 to $20,116, when controlling for inflation.  This increase paralleled the increase of mean hospital charges for all inpatient stays during the same time period, even when controlling for length of stay, which actually decreased slightly.  Costs were highest at large hospitals and for older patients.  Race, insurance, and gender were less strongly correlated to cost. (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology / 16.11.2015

MedicalResearch.com Interview with: Adam R. Glassman, MS Jaeb Center for Health Research Tampa, FL 33647 Medical Research: What is the background for this study? What are the main findings? Response: Diabetic retinopathy is a complication of diabetes that affects blood vessels in the retina. When diabetic retinopathy worsens to proliferative diabetic retinopathy, blood vessels in the retina can leak fluid or bleed, distorting vision. Diabetic retinopathy is the most common cause of vision loss among people with diabetes and the leading cause of blindness among working-age adults. Scatter laser treatment, also called panretinal photocoagulation, has been standard therapy for the treatment of proliferative diabetic retinopathy since the 1970s. While effective in preserving central vision, laser therapy can reduce side vision and cause swelling in an area of the retina that is important for central vision. This study aimed to find an alternative therapy that avoided these undesirable side effects. Eyes in this study were assigned randomly to treatment with intraocular anti-VEGF injections of Lucentis® or scatter laser treatment. The results of this study demonstrate that eye injections of Lucentis® are as effective for vision outcomes at 2 years as laser therapy. On average, vision among eyes treated with Lucentis® improved by about half a line on an eye chart, with virtually no improvement among eyes treated with laser therapy. Compared with laser-treated eyes, eyes treated with Lucentis injection on average had less side vision loss, less frequent development of swelling in the central retina, and fewer complex retina surgeries for retinal bleeding or retinal detachment. (more…)
Author Interviews, Macular Degeneration, Parkinson's / 10.11.2015

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. (more…)
Author Interviews, Genetic Research, Lancet, Macular Degeneration, Ophthalmology / 12.10.2015

Professor P. Elizabeth Rakoczy Centre for Ophthalmology and Visual Sciences The University of Western Australia Head of Department - Molecular Ophthalmology Lions Eye Institute AustraliaMedicalResearch.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. (more…)
Author Interviews, JAMA, Ophthalmology / 08.10.2015

Prof-Jeremy-A-GuggenheimMedicalResearch.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  (more…)
Author Interviews, Genetic Research, Ophthalmology / 05.10.2015

MedicalResearch.com Interview with: Dr. Annabel Christ PhD Max-Delbrueck-Center for Molecular Medicine Berlin, Germany Medical Research: What is the background for this study? Dr. Christ: The development and function of the retina in all vertebrate species follow the same principles. Still, there is one important feature that distinguishes the mammalian eye from that of others inasmuch as it does not grow much after birth. In contrast, in fish or reptiles, the retina continuously grows, even in adults. The mechanism that restricts the growth of the mammalian eye remains enigmatic. Yet, understanding this mechanism may offer therapeutic strategies to block eye growth in cases of severe nearsightedness or to induce growth of the retina in patients with retina degeneration. To explore the mechanisms that control human eye growth we studied a genetic form of extreme eye overgrowth (buphthalmia). It is caused by an inherited defect in the gene encoding LRP2, a receptor in the retina. We reasoned that this exceptional form of eye disease might tell us something about the concepts governing eye growth in all humans. (more…)
Author Interviews, JAMA, Melanoma, Ophthalmology / 01.10.2015

Ann-Cathrine Larsen MD, PhD-student University of Copenhagen Faculty of Health Sciences Department of Neuroscience and Pharmacology, Eye Pathology Section CopenhagenMedicalResearch.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. (more…)
Author Interviews, Ophthalmology / 05.09.2015

Paul Miller PhD student The University of Queensland Australia 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%. (more…)
Author Interviews, JAMA, Neurological Disorders, Ophthalmology, Vanderbilt / 11.08.2015

MedicalResearch.com Interview with: Matthew Schrag MD Department of Neurology Yale University New Haven, Connecticut   Medical Research: What is the background for this study? What are the main findings? Dr. Schrag: Central retinal artery occlusion  (CRAO) is a relatively rare disorder that is caused by interruption of blood flow to the retina, usually by a clot or some other embolus.  Despite around 150 years of research, no compelling treatment has been found for this disease.  Treatment with fibrinolytics has been used experimentally for a long time and some of the results have been encouraging.  The point of the current study was to aggregate all of this observational data and compare how patients withCentral retinal artery occlusion do when treated with fibrinolytics versus when they are treated with other approaches or not treated at all. The biggest surprise in the data was the poor performance of conventional treatments at less than half the recovery rate of patients who were simply left alone.  The literature on treating central retinal artery occlusion with ocular massage, hemodilution or anterior chamber paracentesis has never been particularly compelling, but these treatments were thought to be harmless and are often practiced in the acute management of central retinal artery occlusion.  This new analysis strongly suggests that these interventions may be harmful.  While this data is not perfect (it is retrospective, non-randomized, acquired over long periods of time, etc), for me it raises enough doubt that I think ocular massage, anterior chamber paracentesis and hemodilution should be abandoned as treatments for acute CRAO. (more…)
Author Interviews, Genetic Research, Ophthalmology / 17.07.2015

Professor Robert E MacLaren MB ChB DPhil FRCOphth FRCS Nuffield Laboratory of Ophthalmology Nuffield Department of Clinical Neurosciences, University of Oxford Oxford Biomedical Research Centre, University of Oxford, Oxford, UK Moorfields Eye Hospital & UCL NIHR Biomedical Research Centre for Ophthalmology London, UK.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.
Medical Research: What is the background for this study? What are the main findings? Prof. MacLaren: The study shows that gene therapy can be used to release a protein in the eye that arrests the development of retinitis pigmentosa, a blinding disease caused by degeneration of the retina. The study was performed in mice which had a similar genetic defect to that found in humans with the disease. The mice also had fluorescent green “glow in the dark” light sensing cells known as cones, which we could see and count by looking into the eye – like counting stars in the night sky. By counting the green fluorescent cones we were able to work out the exact dose of gene therapy needed to keep these cells alive indefinitely. The study was funded by Fight for Sight, a UK charity that supports finding cures for eye diseases. (more…)
Author Interviews, Diabetes, Lipids, Ophthalmology / 06.07.2015

Dr Ruth Hogg, Lecturer Centre for Experimental Medicine (formerly Centre for Vision and Vascular Science) Institute of Clinical Science Block Belfast Northern IrelandMedicalResearch.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.  (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology, University of Michigan / 06.06.2015

Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of MichiganMedicalResearch.com Interview with: Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of Michigan Medical Research: What is the background for this study? Response: We have a special interest in how the developmental processes of aging increase the risk of late onset diseases. We wondered whether drugs that target known aging pathways might be able to reduce risk of late onset disease. In the aging field, an emerging area of interest has been the category of drugs called caloric restriction mimetic (CRM) drugs, which have been found to extend life span and to reduce risk or delay onset of some late-onset diseases. These caloric restriction mimetic drugs target a set of pathways that have come to be seen as playing roles in longevity. One of these caloric restriction mimetic drugs, metformin, happens to also be one of the most common drugs used in the treatment of type 2 diabetes. Glaucoma is a leading cause of blindness worldwide and classical open-angle glaucoma shows onset in late middle age or late age, so we hypothesized that a caloric restriction mimetic drug might be able to reduce the risk of open-angle glaucoma. We used data from a large health services database to compare the rate at which open-angle glaucoma developed in individuals with diabetes mellitus who used metformin versus those who did not use metformin. We predicted that metformin would be associated with reduced risk of open-angle glaucoma. Medical Research: What are the main findings? Response: We found that use of metformin was associated with reduced risk of open-angle glaucoma. A 2 gram per day dose of the CRM drug metformin for two years was associated with a 20.8% reduction in risk of developing open-angle glaucoma. When we looked at the highest quartile of drug prescribed (>1,100 grams over a two year period) we found a 25% reduction in risk relative to those taking no metformin. This risk reduction is seen even when we account for glycemic control in the form of glycated hemoglobin, and use of other diabetes drugs was not associated with reduced risk of open-angle glaucoma. A possible explanation for our findings might be that the mechanism of risk reduction is taking place by CRM drug mechanisms that target aging pathways rather than through glycemic control of diabetes. In the long run, the approaches to late onset diseases in general will become much more powerful if we can use parallel approaches that simultaneously target both the aging processes going on and the disease-specific pathways going on. In the literature we see caloric restriction mimetic drugs metformin, rapamycin and resveratrol all being explored for their ability to target points in aging pathways in ways that can impact the risk of a variety of late-onset diseases, so it will be important for those interested in the risk factors affecting late onset diseases to pay attention to how caloric restriction mimetic drugs might be altering risk for those late onset diseases. (more…)
Author Interviews, JAMA, Ophthalmology, Technology / 02.06.2015

Andrew Bastawrous, MRCOphth International Centre for Eye Health, Clinical Research Department London School of Hygiene and Tropical Medicine (LSHTM), London, EnglandMedicalResearch.com Interview with: Andrew Bastawrous, MRCOphth International Centre for Eye Health, Clinical Research Department London School of Hygiene and Tropical Medicine (LSHTM), London, England Medical Research: What is the background for this study? What are the main findings? Dr. Bastawrous: As part of my PhD with the International Centre for Eye Health at the London School of Hygiene & Tropical Medicine, I led the follow-up of a major cohort study of eye disease [http://www.biomedcentral.com/1471-2415/14/60] following up 5,000 people in 100 different locations across the Great Rift Valley in Kenya. It was really challenging, two-thirds of the locations had no road access or electricity and we were carrying over £100,000 worth of fragile eye equipment and a team of 15 people in two vans to be able to carry out high quality measures of eye disease and answer some important questions for planning eye services. What we found was that in the most difficult to reach locations we would find lots of people waiting to see us who had been unnecessarily blind from preventable/treatable diseases. Despite the locations having no roads, electricity and often no water, nearly all the locations had good phone signal. Together with a brilliant team of developers, engineers and ophthalmologists we developed a suite of smartphone based tests to see if we could replace some of the standard equipment being used, in the hope that we could make it more portable and easier for non-specialists to perform so that ultimately the most high-risk individuals could be reached and treated. This paper describes one of those tests, the visual acuity test - Peek Acuity. Our field workers tested patients in their own homes using a standard card based Snellen chart (the type of vision test most non-ophthalmic healthcare workers are familiar with and has been the most commonly used acuity test for several decades now) and Peek Acuity. The same tests were repeated by the same healthcare worker in the clinic the following day as well as a reference standard vision test (LogMAR ETDRS) performed by an eye trained clinical officer. This allowed us to perform "test re-test", a measure of a tests repeatability. i.e. if you have the same test at two separate time points we would expect the the measures to be very close. We found that for both Peek Acuity and Snellen they were highly repeatable. An advantage of Snellen is the speed of the test, Peek Acuity came out slightly quicker overall. We also found when compared to the reference standard test, Peek Acuity was highly comparable and within a clinically acceptable limit of difference. (more…)
Author Interviews, Diabetes, Johns Hopkins, Macular Degeneration, Ophthalmology, PNAS / 29.05.2015

MedicalResearch.com Interview with: Akrit Sodhi, M.D., Ph.D. Assistant Professor of Ophthalmology Retina Division Wilmer Eye Institute Johns Hopkins Medical Institutions Medical Research: What is the background for this study? What are the main findings? Dr. Sodhi: Diabetic eye disease is the most common cause of severe vision loss in the working age population in the developed world, and proliferative diabetic retinopathy (PDR) is its most vision-threatening sequela. In proliferative diabetic retinopathy, retinal ischemia leads to the upregulation of angiogenic factors that promote neovascularization. Therapies targeting vascular endothelial growth factor (VEGF) delay the development of neovascularization, in some, but not all diabetic patients, implicating additional factor(s) in proliferative diabetic retinopathy pathogenesis. In our study, we demonstrate that the angiogenic potential of aqueous fluid from PDR patients is independent of VEGF concentration, providing an opportunity to evaluate the contribution of other angiogenic factor(s) to PDR development. We identified angiopoietin-like 4 (ANGPTL4) as a potent angiogenic factor whose expression is upregulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. Expression of ANGPTL4 was increased in the aqueous and vitreous of PDR patients, independent of VEGF levels, correlated with the presence of diabetic eye disease, and localized to areas of retinal neovascularization. Inhibition of ANGPTL4 expression reduced the angiogenic potential of hypoxic Müller cells; this effect was additive with inhibition of VEGF expression. An ANGPTL4 neutralizing antibody inhibited the angiogenic effect of aqueous fluid from proliferative diabetic retinopathy patients, including samples from patients with low VEGF levels or receiving anti-VEGF therapy. Collectively, our results suggest that targeting both ANGPTL4 and VEGF may be necessary for effective treatment or prevention of proliferative diabetic retinopathy and provide the foundation for studies evaluating aqueous ANGPTL4 as a biomarker to help guide individualized therapy for diabetic eye disease. (more…)
Author Interviews, Genetic Research, NEJM, Ophthalmology / 05.05.2015

Professor James Bainbridge, MA, PhD, FRCOphthProfessor of Retinal Studies, UCL Institute of Ophthalmology NIHR Research Professor, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyMedicalResearch.com Interview with: Professor James Bainbridge, MA, PhD, FRCOphth Professor of Retinal Studies, UCL Institute of Ophthalmology NIHR Research Professor, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of OphthalmologyConsultant Ophthalmologist, Moorfields Eye Hospital NHS Foundation Trust Medical Research: What is the background for this study? What are the main findings? Prof. Bainbridge : Leber Congenital Amaurosis (LCA) is one of the most common causes of inherited, untreatable blindness in children. There are at least 14 different types of Leber Congenital Amaurosis of which LCA Type 2 (LCA2), caused by defects in the gene RPE65, affects around one in 100,000 people worldwide. Evidence from animal studies support that LCA2 may be amenable to treatment with RPE65 gene replacement therapy. The main findings of this phase I/II clinical trial confirm our preliminary findings (published in NEJM, 2008) that gene therapy can improve night vision. Improvements peak within the first 12 months after treatment but then decline during the three-year follow-up period which is consistent with the published results and interim findings from other studies of RPE65 gene therapy. (more…)