Glaucoma: CBD (cannabidiol) May Raise Pressure in Eye

MedicalResearch.com Interview with:

Alex Straiker PhD Senior Scientist Psychological & Brain Sciences Indiana University 

Dr. Straiker

Alex Straiker PhD
Senior Scientist
Psychological & Brain Sciences
Indiana University 

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

Response: We’ve known for almost 50 years that cannabis can lower ocular pressure but the mechanism of action was still unknown.  Most of the work on this stopped well before the cannabinoid receptors were discovered in the early 1990s.

Over the last several years we have determined that three different cannabinoid receptors (CB1, GPR18, and GPR119) each can lower pressure in mice when activated.  Once this was established, it made sense to go back to THC (and CBD) to see how they act.

MedicalResearch.com: What are the main findings? 

Response: There are four main findings.

  • Probably the most interesting is that CBD raises ocular pressure in mice.  Ours isn’t the first study to show this but we do show how it works.
  • Our second major finding is that THC lowers pressure through a combination of CB1 and GPR18 receptors.
  • The third major finding is that the effect of THC is sex-dependent, with longer effects in male mice.
  • Lastly, CBD cancels out the pressure-lowering effects of THC, probably by blocking CB1 receptors.  

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

Response: There are two main take-homes.

  • There is a real possibility that CBD elevates ocular pressure and therefore the risk of glaucoma as a side-effect. This is significant given the widespread (and growing) availability of CBD and its recent FDA approval as a treatment for Dravet’s Syndrome.  Second, the sex-dependence is significant in and of itself but also because the current AAO position that topical THC is ineffective as a glaucoma therapy is based on four studies, three of which were small mixed-sex subject pools.  If the sex-dependence holds for humans, then it is possible that those studies yielded a false-negative result. 

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

Response: The question of whether CBD raises ocular pressure in humans should be revisited and should be monitored in patients being treated for Dravet’s Syndrome.

No disclosures.   

Citation:

Sally Miller, Laura Daily, Emma Leishman, Heather Bradshaw, Alex Straiker. Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Investigative Opthalmology & Visual Science, 2018; 59 (15): 5904 DOI: 10.1167/iovs.18-24838

 

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Results of the 2-Year Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) Randomized Trial

MedicalResearch.com Interview with:

Pravin U. Dugel, MD Retina Consultants of Arizona Phoenix, Arizona; USC Roski Eye Institute Keck School of Medicine University of Southern California Los Angeles, California

Dr. Pravin Dugel

Pravin U. Dugel, MD
Retina Consultants of Arizona
Phoenix, Arizona; USC Roski Eye Institute
Keck School of Medicine
University of Southern California
Los Angeles, California 

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

Response: OASIS is an acronym for “OcriplASmIn for Treatment for Symptomatic Vitreomacular Adhesion including Macular Hole”.  It was a Phase IIIB, randomized, prospective, sham-controlled, double-masked, multicenter clinical study. The goal of the study was to further evaluate the long-term (24 months) efficacy and safety of a single injection of 0.125mg of ocriplasmin in patients with symptomatic vitreomacular adhesion (VMA) and vitreomacular traction (VMT), including macular hole (MH).

OASIS evaluated 220 patients with symptomatic VMA/VMT.  One hundred forty-six patients received ocriplasmin while 74 served as a sham control group. In the latter group, no intravitreal injection was administered.  Continue reading

90% of Americans Live Within Short Driving Distance To Eye Care

MedicalResearch.com Interview with:

Dr. Cecelia Lee

Dr. Cecelia Lee

Cecilia S. Lee, MD
Department of Ophthalmology
University of Washington School of Medicine
Seattle, WA

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

Response: Access to eye care is a critical issue currently in the United States. With the expected increase in the aging US population, many eye diseases are age-related and there is an expected associated increase in demand for eye care. Prior studies have estimated access to care in many different ways including looking at providers per zipcode, utilization of billing codes, and distance to provider. We sought to estimate the access to eye care providers using a much more accurate way to estimate the driving distance to provider. Specifically, we recreated a driving route system similar to Google Maps or Apple Maps for navigation to plot direct driving routes.

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Teleretinal Screening Can Reduce Blindness and Costs in Diabetic Eye Disease

Christina Y. Weng, MD, MBA Assistant Professor-Vitreoretinal Diseases & Surgery Baylor College of Medicine-Cullen Eye Institute

Dr. Christina Weng

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%).

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VA Effectively Uses Telemedicine To Screen for Diabetic Eye Disease

Mary G. Lynch, MD Professor of Ophthalmology Atlanta Veterans Affairs Medical Center Decatur, Georgia. Department of Ophthalmology, Emory University School of Medicine, Atlanta, GeorgiaMedicalResearch.com Interview with:
Mary G. Lynch, MD
Professor of Ophthalmology
Atlanta Veterans Affairs Medical Center Decatur, Georgia.
Department of Ophthalmology, Emory University School of Medicine,  Atlanta, Georgia

Medical Research: What are the main findings of the study?

Dr. Lynch:

  • Since 2006, the VA has been systematically using teleretinal screening of patients with diabetes to screen for retinopathy in the Primary Care Clinics. Under this program, 90% of veterans with diabetes are evaluated on a regular basis. A number of patients who are screened have findings that warrant a face-to-face ophthalmic exam. No information exists on the effect of such a program on medical center resources.
  • 1,935 patients  underwent teleretinal screening through the Atlanta VA over a 6 month period.  We reviewed the charts of the 465 (24%) of the patients who were referred for a face to face exam in the Eye Clinic.
  • Data was collected for these patients to determine the reasons for referral, the accuracy of the teleretinal interpretation, the resources needed in the Eye Clinic of the Medical Center to evaluate and care for the referred patients over a two year period and possible barriers to patient care.
  • Of the 465 patients referred for an exam, 260 (55.9%) actually came in for an exam. Community notes were available for an additional 66 patients. Information was available for 326 (70.1%) of the referred patients.
  • The most common referring diagnoses were nonmacular diabetic retinopathy (43.2% of referrals), nerve related issues (30.8%), lens or media opacity (19.1%), age-related macular degeneration (12.9%) and diabetic macular edema (5.6%).
  • 16.9% of the referred patients had 2 or more concurrent problems that put them at high risk for visual loss.
  • The percentage agreement between teleretinal screening and the ophthalmic exam was high: 90.4%. Overall sensitivity was 73.6%. The detection of diabetic macular edema had the lowest sensitivity.
  • A visually significant condition was detected for the first time through teleretinal screening for 142 of the patients examined (43.6%).
  • The resource burden to care for referred patients was substantial.
  • 36% of patients required 3 or more visits over the ensuing 2 year period.
  • The treatment of diabetic macular edema had the highest resource use involving on average 5 clinic visits, 6 diagnostic procedures and 2 surgical procedures
  • The most common non-refractive diagnostic procedures were visual fields and optical coherence tomography.
  • The average cost to care for the referred patients (in Medicare dollars) in work RVUs alone was approximately $1,000 per patient. The cost to care for a patient with diabetic macular edema was $2673.36.

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Retinopathy of Prematurity: Bevacizumab vs Laser Treatment

Helen A. Mintz-Hittner, M.D., F.A.C.S. Alfred W. Lasher, III, Professor of Ophthalmology Department of Ophthalmology and Visual Science The University of Texas Health Science Center at Houston-Medical School Cizik Eye ClinicMedicalResearch.com Interview with:
Helen A. Mintz-Hittner, M.D., F.A.C.S.
Alfred W. Lasher, III, Professor of Ophthalmology
Department of Ophthalmology and Visual Science
The University of Texas Health Science Center
at Houston-Medical School
Cizik Eye Clinic

Medical Research: What are the main findings of the study?

Dr. Mintz-Hittner:

  • For retinopathy of prematurity (ROP), at age 2 ½ years, intravitreal bevacizumab (IVB) injections cause less myopia (nearsightedness) in diopters (D) compared to conventional laser therapy (CLT):f
  • or Zone I: -1.51 D versus -8.44 D (7 diopters difference: p = 0.001.
    for Posterior Zone II: -0.58 D versus -5.83 D (5 diopters difference: p = 0.001.

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Study Uses Dental Stem Cells To Promote Retinal Regeneration After Eye Injury

Ben Mead Molecular Neuroscience Group Neurotrauma and Neurodegeneration Section School of Clinical and Experimental Medicine University of Birmingham, BirminghamMedicalResearch.com Interview with:
Ben Mead
Molecular Neuroscience Group
Neurotrauma and Neurodegeneration Section
School of Clinical and Experimental Medicine
University of Birmingham, Birmingham

Medical Research: What are the main findings of the study?

Answer: Traumatic and neurodegenerative disease of the retina lead to an irreversible loss of retinal ganglion cells (RGC) which are the neuronal cells located in the inner retina that transmit visual signals to the brain. Thus RGC injury results in visual defects which can ultimately progress into permanent blindness. One promising therapeutic approach is the use of stem cells as a source of replacement for lost retinal cells. However a theory has emerged suggesting that stem cells can act through the secretion of signalling molecules (growth factors). One stem cell that has recently shown great promise for neuronal repair are dental pulp stem cells (DPSC), which are multipotent stem cells easily isolated from adult teeth, including third molars (Mead et al 2013, 2014).

In our research, we transplanted either dental pulp stem cells or the more widely studied bone marrow-derived mesenchymal stem cell (BMSC) into the vitreous chamber of the eye after optic nerve crush (Mead et al 2013). The main finding of this study was that DPSC, to a significantly greater degree than BMSC, promoted the survival of injured RGC and the regeneration of their axons. We also showed that the mechanism of action was not through differentiation and replacement of cells but was actually paracrine mediated, i.e. through DPSC-derived growth factors (Mead et al, 2013, 2014).
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