CRISPR Gene Editing May Lead To Cure For Retinitis Pigmentosa

MedicalResearch.com Interview with:

Kang Zhang, M.D., Ph.D.</strong> 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

Dr. Kang Zhang

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.

Continue reading

Outbreak of Severe Fungal Eye Infections Linked To IV Opioid Epidemic

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.

Continue reading

Frequency of Retinal Screening in Diabetes May Be Tailored to Individual

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.

Continue reading

Inhaling Poppers Associated With Visual Toxicity

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.

Continue reading

Vascular Safety of Ranibizumab in Patients With Diabetic Macular Edema

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

Dr. Zarbin

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.

Continue reading

Economic Evaluation of a Home-Based Age-Related Macular Degeneration Monitoring System

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.

Continue reading

Diabetic Retinopathy: OCTA May Improve Staging, Diagnosis and Monitoring

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)

Dr. Cunha-Vaz

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.

Continue reading

Transplanted Human Embryonic Stem Retinal Pigment Cells Survive 22 months in a Human Recipient

MedicalResearch.com Interview with:

Won Kyung Song MD.PhD Assistant Professor, Vitreoretinal service, Department of Ophthalmology CHA Bundang Medical Center CHA University Republic of Korea

Dr. Won Kyung Song

Won Kyung Song MD.PhD
Assistant Professor, Vitreoretinal service, Department of Ophthalmology
CHA Bundang Medical Center CHA University
Republic of Korea 

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

Response: The retina is a light-sensitive neural tissue lining the inner surface of the human eye. The center of this retina is called the “macula”, which is responsible for high quality vision and central visual field. Retinal pigment epithelium is a layer of cells in the outer layer of the retina which has a critical role in maintaining and supporting the retina, especially the macula.

Age-related macular degeneration(AMD) is the leading cause of vision loss in the elderly in Western countries. There are two types of AMD, wet (neovascular or exudative) and dry (atrophic). The retinal pigment epithelium and choroid, are closely related with the pathophysiology of AMD. In dry AMD, age-related degeneration of RPE cells leads to the loss of photoreceptor cells and visual deficit. Currently, some therapies are available for ameliorating the wet AMD. However, there are no effective therapy available for dry AMD.

Previous studies have shown that healthy RPE cells can be implanted to replace unhealthy RPE cells in lesion areas where RPE cells have been lost. Allogenic RPEs resulted in graft rejection and autologous RPEs are difficult to harvest leading to surgery related complications. Now, abundant RPEs with stable genotype and phenotye may be generated from embryonic stem cells. Therefore, we have undergone subretinal transplantation of human embryonic stem cell derived RPE cells. (Clinicaltrials.gov NCT 01674829) Among the patients enrolled for

this clinical trial, we noted epiretinal membrane(ERM) with pigmentations over the retina in a proportion of patients as an adverse event. One patient with dry AMD and an epiretinal membrane after the hES-RPE transplantation undergone removal of this ERM. The histologic examination of this ERM with pigmentations showed that the pigmented cells originated from the transplanted hES-RPE cells which survived in the recipient for 22 months without anaplasia.

MedicalResearch.com: What should readers take away from your report?

Response: The main concerns of clinical application of hES derived cells are tumorigenesis and immune rejection.

There are limitations of these trials lacking confirmative measurements of engraftment of the transplanted cells. Because biopsy of the retina results in focal loss of nurosensory retina and labelling the cells may cause additional clinical harm.

This is the first report showing that hES derived cells has survived upto 22 months in human organ without anaplasia and may form an ERM.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Objective measurement of engraftment is necessary, together with advancement of an objective visual function measurements.

MedicalResearch.com: Is there anything else you would like to add?

Response: The case reported in this journal is a finding from a patient enrolled in the clinical trial sponsored by CHAbiotech.Co,Ltd.

HI12C1794(A121941)

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Shim SH, Kim G, Lee DR, Lee JE, Kwon HJ, Song WK. Survival of Transplanted Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells in a Human Recipient for 22 Months. JAMA Ophthalmol. Published online February 09, 2017. doi:10.1001/jamaophthalmol.2016.5824

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Smaller and More Stable Than Stem Cells, Exosomes Can Preserve Retinal Cell Function

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

Dr. Ben Mead

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.

Continue reading

Regular Cannabis Use May Slow Down Visual Processing By Retina

MedicalResearch.com Interview with:
Dr Vincent Laprévote
Praticien Hospitalier (MD, PhD, HDR)
Pôle Hospitalo-Universitaire de Psychiatrie du Grand Nancy
Centre Psychothérapique de Nancy

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

Response: There was evidence in animal studies showing that cannabis use could impact visual processing, but lesser was known in humans.

We showed here an association between regular cannabis use and a delay in the later stage of visual processing in the retina.

MedicalResearch.com: What should readers take away from your report?

Response: Regular cannabis use may slightly slow down the early visual processing.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: We have to cautiously verify our result in a larger sample. We also have to explore if this delay is present in further stages of visual processing (i. e. in the brain) and has behavioral consequences. Dr Schwitzer also just begun new researches to verify if this delay is permanent or recedes with cannabis cessation.

MedicalResearch.com: Is there anything else you would like to add?

Response: Importantly, all the participants of this research were regular cannabis users before their participation to the study. We systematically proposed cannabis cessation solutions to the participants.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Schwitzer T, Schwan R, Albuisson E, Giersch A, Lalanne L, Angioi-Duprez K, Laprevote V. Association Between Regular Cannabis Use and Ganglion Cell Dysfunction . JAMA Ophthalmol. Published online December 08, 2016. doi:10.1001/jamaophthalmol.2016.4761

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Complement Genes Play Role in Age-Related Macular Degeneration

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.

Continue reading

FDA Reports on Patient Satisfaction With LASIX Procedure

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.

Dr. Malvina Eydelman

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.

Continue reading