Research in Retinal Disease The Foundation Fighting Blindness Invests 2 1 Million in Seven New Research Efforts

As I continually search the web for interesting news about new technologies for treating retinal diseases, I came across this news from the Foundation Fighting Blindness’ website  yesterday afternoon. It relates to some of the annual grants to researchers that the FFB will be funding this year. It includes better ways of looking at retinal cells (via use of the adaptive optics laser scanning ophthalmoscope) and several projects involving gene therapy, along with a couple looking at ways of, hopefully, stopping the progression of dry AMD.

The following write up is reprinted with permission of the FFB.

The Foundation Invests $2.1 Million in Seven New Research Efforts

The Foundation Fighting Blindness

August 15, 2013

The Foundation's Scientific Advisory Board (SAB) recently completed its annual grants review process, leading to the allocation of $2.1 million in funding for seven new research projects, including those for identifying new disease-causing gene mutations, developing cross-cutting gene therapies and advancing potential treatments for dry age-related macular degeneration. The three-year grants were awarded after the SAB reviewed 117 proposals submitted to the Foundation last October.

"Grants review is a rigorous, multi-step process that takes most of the year to complete," says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness. "Due to revenue limitations, we can only fund a fraction of the high-quality projects we'd like to fund. That makes the selection process even more challenging. We had to leave several excellent proposals on the table."

Here are brief descriptions of the new research projects:

AOSLO: Detecting Retinal Degeneration Before Vision is Lost

The adaptive optics laser scanning ophthalmoscope (AOSLO) is like a powerful microscope that enables retinal researchers to see structural changes in the retina well before vision is lost from a retinal disease. That power can enable researchers to more quickly determine if a treatment is working in a clinical trial. Austin Roorda, Ph.D., of the University of California, Berkeley, is performing studies of AOSLO to correlate changes in the retina (e.g., loss of photoreceptors) with changes in vision.

Enhancing AOSLO for Expanded Clinical Use

Like Dr. Roorda, Stephen Burns, Ph.D., of the University of Indiana, is working with AOSLO to study the correlation between retinal and vision changes. He is also making AOSLO more affordable by using newer camera technology. In addition, he's employing state-of-the-art computing technologies derived from video games to decrease image-processing times and costs. The new technology will make the imaging process more comfortable for the patient by tolerating more head and eye movement.

Figuring Out Why Severity of Vision Loss Varies for People with XLRP

Researchers have reported for many years that the severity of vision loss for people with X-linked retinitis pigmentosa (XLRP) can vary greatly, even for people within the same family. Stephen Daiger, Ph.D., of the University of Texas Health Science Center at Houston, will be looking at the role of a various biological, genetic and environmental factors in vision-loss variability for those with XLRP. The identification of a significant factor that modulates vision-loss severity - perhaps a protective protein - could lead to a potential treatment.

Finding New Genes Linked to ADRP

Researchers have identified almost two dozen genes linked to autosomal dominant retinitis pigmentosa (adRP), but many are yet to be found. Rui Chen, Ph.D., of Baylor College of Medicine, is on the hunt for those remaining adRP genes. With DNA from 118 adRP families, including 18 families with at least nine affected members, Dr. Chen is well positioned to identify additional genes linked to adRP. Finding the new genes will provide researchers with targets for treatments and cures.

Developing Neuroprotective Gene Therapies to Preserve Vision

John Ash, Ph.D., is developing gene therapies that have the potential to preserve vision in people affected by a broad range of retinal diseases. Unlike corrective gene therapies, which work only for conditions caused by a specific gene, Dr. Ash's proposed treatments are designed to keep the retina healthy independent of the underlying disease-causing gene. He also believes the proteins delivered by his treatments - PIM-1 and STAT3 - will be less likely to cause damaging inflammatory side effects than some previously investigated neuroprotective proteins.

Targeting Inflammation to Halt AMD

Thanks to previous Foundation-funded genetic studies, researchers have strong evidence that the progression of age-related macular degeneration is associated with an over-active immune system. This ultimately leads to inflammation and cell death in the retinal pigment epithelium (RPE), a layer of cells that provides critical waste and nutritional support to photoreceptors. Loss of the RPE subsequently leads to loss of photoreceptors and vision. Jayakrishna Ambati, M.D., of the University of Kentucky, is developing a gene therapy that preserves the RPE by preventing the harmful sequence of immune-system events.

Boosting Cells' Energy Supplies to Save Vision in AMD

Based on prior research, Deborah Ferrington, M.D., of the University of Minnesota, believes that mitochondrial dysfunction in the RPE plays a significant role in the development of AMD. Mitochondria are like miniature organs (organelles) within all cells that provide energy. When not working properly in retinal cells, they can lead to cell death and vision loss. Dr. Ferrington is evaluating compounds that help protect mitochondrial function in the RPE.

Customized Ablation 1 Ive Seen the Future and its CustomCornea!

This Technology Update column is the first of a series of eight articles chronicling the development of Customized Ablation or Wavefront Driven LASIK. This column was published in the June 15th issue of Ocular Surgery News following both the 1999 ASLMS (American Society for Lasers in Medicine and Surgery) and ASCRS (American Society of Cataract and Refractive Surgery) meetings.

I've Seen the Future.....and it's Custom Cornea!

Technology Update

Irving J. Arons
Spectrum Consulting

What if you could more accurately predict and successfully restore a patients vision to 20/20 with refractive surgery. What if, in some cases, you could actually achieve "Ted Williams" type vision (20/16) or better for your patients who would want that. Would you be interested in finding out more?

Since I first heard Marguerite McDonald's presentation on custom cornea at last fall's AAO meeting (1998), I've been intrigued with the idea, and have wanted to know more about how it was going to be accomplished. The idea of not only correcting vision to emmetropia (20/20), but enhancing it to 20/16 or better was exciting and this was only reinforced by the presentations given at a Bausch & Lomb press conference at the AAO, where George Waring declared 20/12 by 2012, now changed to 20/10 by 2010 in current B&L Surgical advertisements! (For more on both of these presentations, see my columns from the AAO in the January 1st issue of OSN.)

Now, after hearing a presentation given by Tim Turner, director of research at Orbtek, on the "Orbscan Corneal Topography Laser-Link System" (at the recent American Society of Lasers in Medicine and Surgery [ASLMS] meeting in Orlando), and especially after viewing a tape of a course given at the recent ASCRS meeting by Marguerite McDonald, Ronald Krueger, Ray Applegate and George Pettit on "Wavefront-Guided Customized Ablations -- Beyond Topography-Assisted Refractive Surgery", sponsored by Autonomous Technology -- now a subsidiary of Summit Technology, I am convinced that topographically-linked ablation, and especially wavefront-guided ablations, are the future of refractive surgery.

As reported last January, several companies have announced that they are in the process of combining corneal topography with their excimer laser systems to be able to perform "custom" ablations. Among those are LaserSight, working with Humphrey-Zeiss and Orbtek; VISX, working with EyeSys Premier and Orbtek, among others; B&L Surgical/Chiron with Technomed and Orbtek; Schwind with Technomed; and Aesculap-Meditec, also with the Orbtek system and possibly Technomed.

In Dr. Turner's presentation, he explained how the first-generation of topographically linked laser ablations, which depend on the capture of topographic information (corneal curvature and elevation) supplied by such placido reflection systems as Computed Anatomy and EyeSys Premier, will probably be the first out of the block, along with the Orbscan slit scanning system. The Orbscan is capable of providing additional information such as the thickness of the cornea and the condition of its rear surface, through what Orbtek calls CIPTA, or Corneal Interactive Programmed Topographic Ablation. However, by combining the Orbscan with ultrasound to determine the ocular axial length and lens thickness, a simulation of the retinal point spread function (PSF) can be determined. Point spread functions can be calculated for any surface or any sequence of surfaces. Thus a PSF can be calculated from anterior corneal data alone, but it may or may not approximate the true retina PSF, depending on the optical importance of the other internal ocular surfaces. However, this does not include local aberration-inducing variations. So, Orbtek has created a simulated next-generation measurement technique called WAVE, or Wavefront Ablation Vision Enhancement. WAVE treats patient vision rather than corneal geometry (elevation and surface curvature), by targeting idealistic post-operative surface topography with the optical PSF optimized. It calculates wavefront aberration by reverse ray tracing of all of the rays emanating from a theoretical point source of light at the fovea and back through a modeled crystalline lens and the measured cornea. Orbscan measurements are used by WAVE to fully characterize the cornea (both anterior and posterior surfaces), and other data (refraction, ultrasonic axial length and lens thickness) are used to model the crystalline lens. These additions aid in the simulation of the true retinal PSF and the ocular wave aberration. When wave aberrations are directly measurable, they can also be included in the WAVE strategy. The WAVE system is still experimental and has not yet been used on any human patients.

The major difference between what Orbtek and Autonomous Technology are attempting to do is in the measurement of aberrations. As noted above, Orbtek uses theoretical measurements and modeling to simulate an aberration pattern, while Autonomous actually measures the total aberration of the eye by shooting a laser pulse onto the retina, through the lens, and obtains an actual aberration pattern of the return waves, thus getting a more accurate pattern of what aberrations are present in the complete optical system.

Autonomous uses a proprietary wavefront sensor to capture the wavefront pattern returning from the laser-induced spot on the retina. It then converts this information into a 3D map of the aberrations to determine what changes are needed in the corneal surface to compensate for the aberrations present in the eye, and to overcome them. Autonomous has built a prototype device, called the CustomCornea Measurement Device, and, under an IRB, has placed it in an ophthalmologist's office in Florida in order to take measurements on patients under a real-life situation, beginning in April. In an in-house study of 103 eyes, including some people with 20/20 or better vision and some with known pathologies, the custom cornea maps provided by a prototype device, appeared to bear out the theory -- emmetropes, as well as those with sharper vision have less aberrations and can be distinguished from those with aberrated vision. In the near future, this information will be programmed into the LadarVision small spot scanning laser system to provide the potentially enhanced vision, possibly reaching the theoretical diffraction limits of the retina of 20/8!

Of course, all of this would not be possible without the extremely accurate tracking system available on the Autonomous laser. Since the accurate placement of the "compensating" ablation pattern is necessary, by linking the wavefront analysis device to the LadarVision tracking laser, the precise pattern of ablation correction can be obtained, centered on the visual axis, and "customcornea" achieved. The company hopes to begin CustomCornea treatments this summer, depending on regulatory approvals and, hopefully, within the next two years, this technology could become a commercial reality.

Editors note: This column was not put online by OSN. The Janury 1st column mentioned, is also not online, but was picked up by a sister publication, OCULAR SURGERY NEWS EUROPE/ASIA-PACIFIC EDITION, and published in February 1999. (Which is linked.)

Unhelpful Strategies 1 Setting a Timer

I'm going to start a catalog of strategies that were not helpful for me in dealing with OCD. Last night's post about getting stuck at the computer reminded me of the advice a previous therapist gave me, "Set a timer." Essentially this results in adding the extra motion of resetting the timer repeatedly every time it goes off, but does nothing in helping me actually move away from the computer. It also results in a cascade of "What is wrong with me? Why can't I get up when the timer goes off?" The answer of course is that I have OCD.

On occasion I have used a timer as an exposure, and that is a whole different approach. That involves intentionally choosing to do something imperfectly, "wrong" or "badly" by limiting the amount of time spent on it. This can be effective, but I have to be in Exposure Mode so I don't slip back into "What's that beeping sound? Maybe it will go away so I can keep ritualizing."

Summary of Part 1 of The Mindfulness Workbook for OCD by Jon Hershfield and Tom Corboy

New Harbinger Publications offered to send a review copy of The Mindfulness Workbook for OCD by Jon Hershfield and Tom Corboy(2013).  Since I was in the middle of taking a mindfulness class, it was interesting to read this book with specific connections to OCD.

I am familiar with the writing of Jon Hershfield, as he was the moderator of the online support group PureO for many years, and he had a way of describing obsessive thoughts and ways to face them that was very helpful.

Part 1 covers definition of mindfulness and cognitive behavioral therapy(CBT) terms.

The authors define mindfulness as, "the state of acknowledging and accepting whatever is happening in the present moment exactly as it is(p. 8)."  In my experience, when I have an anxious thought or sensation, I race way ahead of the present moment in trying to figure out what it is or what it means.

The authors argue that, "The problem of OCD isn't that you think too much.  It's that you confuse the intensity, volume or visibility of your thoughts with their importance(p. 12)."  Practicing hanging in there with the intensity or stickiness of the thoughts can allow your mindful self to choose what you want to do with your life, rather than listening to the loudest voice.

The book provides a cognitive behavioral therapy background on distortions of thinking that you can identify in your own thoughts, not as a way to "solve" or "figure out" the thoughts, but to practice seeing them as thoughts.  One of the things that really helped me when I was in therapy for OCD was writing down my thoughts as they happened, as if it were a transcript, but then labeling the distortions in the margin, so I got better at identifying what my mind was up to.

One such distortion is Catastrophizing/Predicting/Jumping to Conclusions.  Accepting I can't predict the future is a bedrock of mindfulness.   As scary as the uncertainty can be, the racing ahead brings forth even more fear.

The book does an overview of Exposure and Response Prevention therapy, and the use of Imaginal Exposure Scripts, another component that helped me in therapy.

Part 2 of the book addresses mindfulness and CBT for specific obsessions with a 3 step process.

1. Acceptance of the presence of OCD thoughts and feelings.  You are accepting that the thoughts are there, not any meaning that you attribute to those thoughts.
2. Assessment using CBT to assess the value of the OCD thoughts, as a nonpartial observer, labeling possible distortions, and returning to the present.
3. Action using behavioral skills to expose yourself to OCD thoughts in order to habituate to them and overcome your fears.

I suspect many readers will turn immediately to Part 2 in hopes of clues to particular obsessions, as the authors say, "The reason we separate obsessions into categories is that for every obsessive-compulsive cycle, there's a way to break it.  There's a way in, and knowing the way in is important  When you understand the mechanics of an obsession can identify the compulsions that hold it in place, you can begin the process of letting both of them go(p. 84)."

I will discuss some of these chapters in future posts, as well as some thoughts on the book as a whole.  

Holding It All Together Part 1 Ligaments

by Baxter

Knee Joint (with ligaments)

As I was prepping for my upcoming workshop this Saturday on Yoga and the Musculoskeletal System out in Brentwood, CA (see Brentwood Yoga Center Workshops for registration information), I decided to look back at my old blog posts to see what I had written regarding tendons and ligaments, two of the main structures we’ll be talking about this weekend. And much to my surprise, I found that I had not yet addressed these basic and vital topics. So today I thought I’d begin a discussion on ligaments, anticipating that I’ll come back to tendons again in the future.

Let’s begin by looking at some basic definitions for these two structures. Both ligaments and tendons are composed of something anatomists call “connective tissue,” which is a collection of tissue types that often serve the function of keeping our different body structures together, and include such diverse tissues as the above tendons and ligaments, as well as fascia, intervertebral discs, cartilage in the ears and nose, cartilage coating the ends of bones and others. Connective tissues, depending on what their function in the body is, will either be more or less elastic by virtue of the proportions of the components that make up connective tissue: collagen and/or elastin fibers, which float in a semi-fluid gel called ground substance. According to Mel Robin, in his book A Physiological Handbook for Teachers of Yogasana, connective tissue works as a mechanical support or binder for other tissues, allows for food and waste from cells to move in and out, acts as a lubricant and is the body’s glue. 

So what then are the structures that ligaments glue together and what are the unique features of ligaments? Ligaments are specialized connective tissue that binds bones to bones. They keep the bones of your joints in close proximity so they don’t dislocate (which sometimes still can happen, in the shoulder joints, for example), and they allow for a certain amount of passive movement in some directions and restrict movement in others.  In fact, restraining movement is one of the main functions of ligaments. They happen to be high in collagen fibers and low in elastin fibers, which makes ligaments strong, but not very flexible. According to David Coulter in his book Anatomy of Hatha Yoga ligaments are:

“...made up of tough, ropey, densely packed inelastic connective tissue fibers, with only a few cells interspersed between large packets of fibers.”

Usually, the amount of stretch that can take place in a ligament is very minor, only around 4%, but there are exceptions, such as ligaments in the cervical spine region, which have been found to stretch up to 200%! In contrast, those around the knee joint have very little elastin, so are much more rigid to provide more stability to the joint. This can have relevance for our yoga practice. As an example, deep flexion (forward bending) of the neck as in Shoulderstand will not permanently overstretch the neck ligaments. But deep flexion (bending) of the knee as in Supta Virasana has to be approached cautiously and mindfully so as to not overstretch the supporting ligaments of the knee. If the ligaments are overstretched, they will not return to their original length and will be permanently loose and ineffective in stabilizing the knee. In general, you want to focus on stretching the muscle and not the ligaments in your yoga practice.

Another reason to avoid overstretching or, even worse, tearing a ligament, is that ligaments have a poor blood supply. Due to this poor supply, getting repair cells into an injured ligament and taking away the waste and injured material is more difficult, and healing is therefore slow. Also, ligaments have very few cells—which are the things that have to be stimulated in an injury to produce more fibers and fluid—and this contributes to slow healing as well. 

Those out there who have injured the ligaments at the side of the knee joint, the collateral ligaments, via sports like soccer or football, can attest to the long healing times I am referring to here. When we sprain a ligament, not only do we experience some pain and swelling, but the area also seems looser and more prone to re-injury. A ligament sprain that almost everyone has experienced at one time or another like this is the outer ankle.

It seems that one of the safest ways to stretch your tight muscles, and avoid stretching your supportive yet rigid ligaments, is via moderate intensity, slow, held stretches. Warmer muscles and ligaments seem to do this more healthily then cold ones, so I like to move slowly and mindfully in and out of a position a few times to warm up the tissues, and then follow that up with a more sustained hold. And the good news regarding safe stretching is that our nervous system warns us as we approach the kind of overstretch that could tear our ligaments (and tendons) through pain (which can have a whole range of variety and intensity), trembling or weakness. This is yet another reason to pay close attention to the sensations that arise as you perform your asanas. Also important is the location of the sensations, as those arising in the mid-length of the muscles is much more acceptable than sensations occurring right over joints. You might hang in there a bit longer in the first instance and come out of a stretch promptly in the latter!  

Next time, I’ll discuss tendons, which share some similarities with ligaments, but have some unique functions as well.

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