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Meet Antonio Capone, Jr., MD, and His Pioneering Work in Face-Down Positioning after Macular Hole Surgery

Antonio Capone, Jr., MD

Antonio Capone, Jr., M.D. is a board-certified ophthalmologist whose special interests include pediatric vitreoretinal diseases, complicated retinal detachment, ocular oncology, and macular disease.

Dr. Capone is an internationally recognized clinician, surgeon, and educator. He has authored or co-authored over 200 publications in peer-reviewed medical journals, book chapters, and publications from clinical trials. He is currently a Professor of Biomedical Sciences at Oakland University, and Professor at the European School for Advanced Studies in Ophthalmology, Lugano, Switzerland.

In addition, he is Co-Director of the Vision Research-ROPARD Foundation, overseeing the Foundation's clinical research initiative at Associated Retinal Consultants throughout Michigan. Dr. Capone has been named to America's Who's Who in Medicine, The Best Doctors in America, The Best Doctors in the Southeast, and Hour Detroit Magazine's Top Docs. He serves on the Executive Committee of the American Society of Retina Specialists and The Retina Society.

Maureen Duffy: Hello Doctor Capone. It's an honor to speak with you. To begin, can you tell us more about your background, education, and your professional specialty? How (and when) did you decide to become a retinal surgeon?

Antonio Capone: I'm honored that you asked. My parents immigrated to the states from Italy in the mid-1950s. I grew up in New England and went to undergraduate and medical school at Brown University. I did my residency in ophthalmology at the University of Pittsburgh, and a Fellowship in Vitreoretinal Diseases and Surgery at Emory University in Atlanta.

I remembered very clearly when I decided to be a doctor: I was in the third grade. My dad was a psychiatrist and someone came up to me while I was in school, speaking about my father in such glowing terms that it made a big impression on me. I aspired to be the type of man whom folks would one day see in a similar light.

I started out in a psychiatry residency, anticipating that I would finish my training and work with my father. As it happened, the work was incredibly interesting intellectually, but the day-to-day practice of psychiatry wasn't a good match for me temperamentally. The other experiences I had in medical school which were attractive to me as a specialty were surgical subspecialties. The meticulous precision of eye surgery appealed to me and proved to be a much better match for my temperament.

I did a pre-residency research fellowship in cornea, and went through my residency thinking I would want to be an orbital [i.e., having to do with the eye socket] surgeon. Once I did my retina rotation during residency, however, I found the career path I'd been looking for. On a personal level it is highly impactful and incredibly gratifying work. Intellectually, I knew the vast majority of discoveries with regard to understanding retinal disease and novel therapies were yet to be explained and analyzed; therefore, it was an endeavor that would be intellectually stimulating for my entire professional career.

MD: One of the most-visited pages on the VisionAware website is our five-part first-person series on Surviving Recovery from Macular Hole Surgery by Joy R. Efron, Ed.D., which includes Suggestions for Maintaining Face-Down Positioning. Your research, however, indicates that face-down positioning is not required for a successful outcome. Can you share the highlights of your research with our readers?

AC: Macular hole surgery has an interesting, and fairly recent, evolution and history. In the late 1980s-early 1990s, macular hole was a diagnosis for which there was no surgical intervention. Kelly and Wendel, two retinal surgeons from northern California, first sought to operate on folks with macular hole and demonstrated that they could be successfully closed in some patients with subsequent improvement in vision. Interestingly, this was a controversial topic at that time, as many patients with macular hole are affected in only one eye, and both before and after surgery the better eye is the unoperated eye.

The "pros/cons of repair" controversy was followed by a debate as to whether it was safe to remove an intrinsic inner layer of the retina known as the internal limiting membrane (ILM). Up until then, only a thin layers of scar tissue which grew on the retinal surface (epiretinal membrane, or macular "pucker") was ever removed surgically. Taking off scar tissue is something that sounds logical. Removing an intrinsic layer of the retina itself seemed counter-intuitive. This too was controversial at the time. Doing so seemed to improve outcomes (meaning the percent of eyes with successfully closed holes).

The opposing school of thought was that while macular holes may be closed more effectively by removing the ILM, removal of an inner layer of the retina itself couldn't help but be detrimental in the long run. As it turns out, this latter concern has proven unfounded. Removing ILM in most surgeons' hands improves the success rate in macular hole surgery from 70%-80% to 90-95%.

The other big controversy related to the issue of face-down positioning. In the early 1990s, some surgeons asked patients asked patients to lie face down for up to a month after surgery. Little by little, as my success rate in macular hole closure improved, I started to whittle away at the duration of face-down positioning. This was the aspect of surgery that many people hated the most and I became less and less convinced that it was imperative for success. Over the years, I went from a week of face-down positioning, to three days of face-down positioning, to overnight positioning.

MD: What was your "hunch" or "instinct" that led to your initial decision to use a one-day recovery period after macular hole surgery? You first used this technique in 2001, correct?

AC: Yes – Since 2001, I've been down to as little as overnight face-down positioning on the day of surgery only. There were two main drivers to the decision to do short-duration positioning. First, my personal results were as good as anyone else's – irrespective of duration of positioning. That led me to the notion that it wasn't the positioning that was most important, but the ILM peeling described above.

Second, data started to come to publication that macular hole closure could be demonstrated within 24 hours of surgery, using an imaging technology known as optical coherence tomography (OCT). [Editor's note: OCT is a type of medical imaging technology that produces high-resolution cross-sectional and three-dimensional images of the eye.]

We published our results on the one day of face-down positioning, entitled Surgical outcomes of idiopathic macular hole repair with limited postoperative positioning, which were as good as the results published by anyone else. Currently, I don't require face-down positioning at all for typical macular holes.

MD: I'm interested to know your thoughts about many of the great strides that have been made during the past ten years in eye care, especially with the early, yet positive, results from stem cell clinical trials for Stargardt disease and dry macular degeneration and gene therapy for retinal disease.

AC: Stem cell therapy is an interesting topic. The notion of stem cell therapy is very attractive. The idea that you can take a so-called pleuri-potential cell, which has the theoretical capacity to become any cell that is needed and be normal in structure and function, and place that cell anywhere in the body is extremely attractive.

Conversely, the scientific reality with regards to stem cell therapy is nowhere near as advanced as this notion. A good analogy would be taking a wrench and throwing it at a car with an engine problem, and hoping that the wrench is going to somehow know how to fix the car. Unsurprisingly, the early days of stem cell therapy, and I don't think we are far from that now, have been fraught with stops and starts, high expectation, and frequent disappointment.

All of that said, it is an incredibly promising therapy. However, stem cell therapy becoming a reality is something that will happen in small methodical steps, as is typically the case in scientific endeavor. While there is clearly a role for stem cell therapy in the management of hereditary and degenerative diseases, there is yet a long piece of road before that role is realized. That we are in a day and time when stem cell clinical trials are ongoing is very exciting. However, I think this work is still in its infancy.

Gene therapy has similar appeal, as our understanding of disease increasingly demonstrates a genetic/molecular basis. The notion of fixing cells with the wrong genetics by inserting the right genetics again has appeal by virtue of its simplicity. And again, the reality is a bit more daunting, but this approach has incredible promise. Also, the technology is also in the clinical trial phase, which generally means approximately 2-6 years prior to implementation in routine clinical care.

MD: What do you regard as the next great frontier in ophthalmology or vision science in general?

AC: For all of medicine, understanding the molecular basis of a disease is the linchpin for the development of effective therapeutic interventions. For example, right now we have very effective therapies directed against vascular endothelial growth factor, the overproduction of which is important in a number of clinical conditions. [Editor's note: When used in the context of ophthalmology, vascular endothelial growth factor, or VEGF, is a protein that stimulates abnormal blood vessel growth in the retina and macula.] After understanding the molecular mechanism of a disease, delivering the drug therapy in a fashion that is durable is the next big step, typically then taking 2-5 years to get to clinical trials.

Once we unravel the therapeutic riddles leading to new effective therapies, the next challenge is drug delivery. I'd expect big strides in the next 5-10 years in this area of research as well. The time when a disease with a specific molecular fix can be treated with a sustained delivery approach will be soon upon us. It's a very exciting time for research into diseases of the retina and vitreous.

We thank Dr. Antonio Capone for his support of VisionAware and for his longstanding research and practice on behalf of blind and visually persons worldwide. It has been a privilege to speak with you.

Additional Information


Topics:
Personal Reflections
Medical Updates
Macular Degeneration

A New Stem Cell Immune Rejection Discovery Shows Promise for Treating Retinal Disease

Cell Stem Cell

A joint China-United States research team has discovered that a class of stem cells derived from an individual's own cells were not rejected by the immune system when they were turned into retinal pigment epithelium cells destined for the eye.

This important discovery provides a boost for the development of human stem cell therapies to treat age-related macular degeneration (AMD). Although this research has been conducted only with laboratory mice, this concept shows great promise for developing and identifying human stem cell treatments for a variety of retinal disorders.

For more information about ongoing and projected stem cell clinical trials for AMD, you can read Adult Stem Cells for Dry AMD: Emerging Future Research from the National Eye Institute; Positive Stem Cell Clinical Trial Results for Stargardt Disease and Dry Macular Degeneration; and Newly Discovered Corneal Stem Cells Could Be a Potential Source for Treatment of Retinal Disease on the VisionAware blog.

The Stem Cell Research

The research, entitled Humanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells (explained below), has been published online ahead-of-print in the August 20, 2015 edition of Cell Stem Cell.

The authors are Tongbiao Zhao, Zhen-ning Zhang, Peter D. Westenskow; Dilyana Todorova, Zheng Hu, Tongxiang Lin, Zhili Rong, Jinchul Kim, Jingjin He, Meiyan Wang, Dennis O. Clegg, Yong-guang Yang, Kun Zhang, Martin Friedlander, and Yang Xu, who represent the following institutions: the University of California, San Diego; the Chinese Academy of Sciences, Beijing; The Scripps Research Institute, La Jolla, CA; First Hospital of Jilin University, Jilin, China; Guangzhou University of Traditional Chinese Medicine, China; Southern Medical University, Guangzhou, China; the University of California, Santa Barbara; and Columbia University Medical Center, New York.

Cell Stem Cell is affiliated with the International Society for Stem Cell Research and covers the entire spectrum of stem cell biology. The journal reports on topics that are relevant to stem cell research, including basic biological advances and ethical, policy, and funding issues.

Some Relevant Stem Cell Terminology

Here is a brief explanation of the key stem cell concepts and terms used by the researchers:

  • Pluripotent: A stem cell that has the power to develop into any type of bodily cell or tissue ("pluri" = many; "potent" = having power).
  • Induced pluripotent stem cell (iPSC): A type of pluripotent stem cell that can be generated directly from adult cells.
  • Autologous: Involving one individual as both donor and recipient
  • Retinal pigment epithelium (RPE) cells: The deepest cells of the retina. The RPE helps to maintain the health of the retinal photoreceptor cells, called rods and cones. These photoreceptor cells are triggered by light to set off a series of electrical and chemical reactions that helps brain to interpret what the eye sees. The degeneration of the RPE cells also leads to the death of the rods and cones and, ultimately, vision.
  • Immunogenic: Causing, or capable of producing, an immune response.
  • Murine: Related to mice, or using a mouse model in research.

About the Stem Cell/Immune Response Research

Excerpted from Study provides hope for some human stem cell therapies at Medical Xpress:

An international team of scientists … has discovered that an important class of stem cells known as human "induced pluripotent stem cells," or iPSCs, which are derived from an individual's own cells, can be differentiated into various types of functional cells with different fates of immune rejection.

The scientists also found that these cells may not be rejected by the immune system if iPSCs are turned into retinal pigment epithelium cells destined for the eye. Their discovery provides hope for the development of human stem cell therapies to treat macular degeneration.

The research effort was headed by Yang Xu, a biology professor at UC San Diego who discovered with colleagues in 2011 that even though iPSCs are derived from an individual's own cells, the abnormal gene expression can cause the immune system to reject certain cells derived from iPSCs.

That could have been a major impediment to the safe use of iPSCs, which are regarded as particularly attractive candidates for stem cell therapies because they can be differentiated into a wide variety of cell types, are not derived from embryonic tissue, and are not subject to restrictions that limit the use of human embryonic stem cells.

Funded by a $5.12 million grant from the California Institute for Regenerative Medicine, [study author] Xu and his colleagues earlier developed "humanized" laboratory mice with a functional human immune system capable of mounting a vigorous immune rejection of foreign cells derived human embryonic stem cells. "Human and mouse immune systems are quite different," explained Xu, "so we developed a humanized laboratory mouse that carries a functional human immune system. This provides a unique opportunity to evaluate the human immune responses to stem cells."

In their experiments, the researchers developed a variety of cell types from human iPSCs, then tested the immune responses in humanized mice with the immune system of the same individual. They discovered that smooth muscle cells were highly "immunogenic," or strongly rejected by the immune systems of the humanized mice, while retinal pigment epithelial cells were tolerated by the immune system, even when transplanted in parts of the body that provide the environment for robust immune rejection.

"Immune rejection is a major challenge for stem cell therapy," Xu said. "Our finding of the lack of immune rejection of human iPSC-derived retinal pigment epithelium cells supports the feasibility of using these cells for treating macular degeneration. However, the inflammatory environment associated with macular degeneration could be an additional hurdle to be overcome for the stem cell therapy to be successful."

More about Induced Pluripotent Stem Cells

From Wikipedia:

Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from adult cells. Pluripotent stem cells hold great promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

The most well-known type of pluripotent stem cell is the embryonic stem cell. However, since the generation of embryonic stem cells involves destruction (or at least manipulation) of the pre-implantation stage embryo, there has been much controversy surrounding their use. Further, because embryonic stem cells can only be derived from embryos, it has so far not been feasible to create patient-matched embryonic stem cell lines.

Since iPSCs can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line. These unlimited supplies of autologous cells could be used to generate transplants without the risk of immune rejection.

[Please note: Although adult/iPSC research does not use human embryos and thus sidesteps the ethical issues surrounding their use, there are still significant risks associated with the use of autologous stem cells, including teratomas, or tumor formation.]

Age-Related Macular Degeneration

NEI image of how someone with macular degeneration sees: overall blurriness with a blind spot in the center

What a person with AMD sees

Age-related macular degeneration (AMD) is gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. The fovea is located in the center of the macula and provides the sharpest detail vision.

AMD is the leading cause of vision loss for people aged 60 and older in the United States. According to the American Academy of Ophthalmology, 10-15 million individuals have AMD; approximately 10% of people who are affected have the "wet" type of AMD. For more information about vision loss from AMD, see How Does AMD Affect Vision? by Lylas G. Mogk, M.D.

Wet Macular Degeneration (AMD)

In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).

The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

Dry Macular Degeneration

The dry (also called "atrophic") type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure. "Atrophy" refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula, causing it to deteriorate or degenerate over time. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.

More about the Research from Cell Stem Cell

Excerpted from the article Summary:

The breakthrough of induced pluripotent stem cell (iPSC) technology has raised the possibility that patient-specific iPSCs may become a renewable source of autologous cells for cell therapy without the concern of immune rejection. However, the immunogenicity of autologous human iPSC (hiPSC)-derived cells is not well understood.

Using a humanized mouse model (denoted Hu-mice) reconstituted with a functional human immune system, we demonstrate that most teratomas formed by autologous integration-free hiPSCs exhibit local infiltration of antigen-specific T cells and associated tissue necrosis, indicating immune rejection of certain hiPSC-derived cells.

In this context, autologous hiPSC-derived smooth muscle cells (SMCs) appear to be highly immunogenic, while autologous hiPSC-derived retinal pigment epithelial (RPE) cells are immune tolerated even in non-ocular locations.

This differential immunogenicity is due in part to abnormal expression of immunogenic antigens in hiPSC-derived SMCs, but not in hiPSC-derived RPEs. These findings support the feasibility of developing hiPSC-derived RPEs for treating macular degeneration.

Stem Cell Research from VisionAware


Topics:
Low Vision
In the News
Medical Updates
Macular Degeneration

New Research: Faulty Immune Cells May be a Cause of Vision Loss in Macular Degeneration

Nature Communications logo

A research group from the Washington University School of Medicine has identified a faulty immune cell pathway that leads to the formation of atypical blood vessels associated with age-related macular degeneration (AMD). Although their research thus far has been conducted only with laboratory mice, this concept shows great promise for identifying potential treatments for wet AMD and increases our understanding of the ways that faulty immune cells can contribute to vision loss.

The research, entitled IL10-driven STAT3 signaling in senescent macrophages promotes pathological eye angiogenesis (translated and explained below), has been published as an open-source article in the August 11, 2015 edition of Nature Communications. The authors are Rei Nakamura, Abdoulaye Sene, Andrea Santeford, Abdelaziz Gdoura, Shunsuke Kubota, Nicole Zapata, and Rajendra S. Apte, from the Washington University School of Medicine, St. Louis, Missouri.

Nature Publishing Group (NPG) is a publisher of scientific and medical information in print and online. NPG publishes a range of journals across the life, physical, chemical, and applied sciences and clinical medicine. Nature Communications is an open access journal that publishes high-quality research from all areas of the natural sciences.

Some Terminology to Begin

Here is a brief explanation of the key scientific terms used by the researchers:

  • Interleukin-10 (IL10): A cell-signaling molecule that plays a role in the formation of blood vessels involved in the "wet" form of macular degeneration.
  • STAT3: A protein that activates and alters immune cells in the eye, which causes the formation of harmful blood vessels.
  • Macrophages: Immune cells that attack, ingest, and destroy foreign substances and infectious microbes. Normally, macrophages help limit the growth of new blood vessels in the eye, but with age, the cells lose this ability.
  • Angiogenesis: A term used to describe the growth of new blood vessels, which plays a crucial role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth) and age-related macular degeneration (retinal and macular bleeding).
  • Murine: Related to mice, or using a mouse model in research.
  • Choroidal neovascularization: Refers to new ("neo") blood vessels ("vascularization") developing in the retina. In wet age-related macular degeneration (AMD), abnormal blood vessels begin to grow under the retina. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid, damaging the retina and causing it to lift up and pull away from its base. The choroid is the part of the eye that supplies blood and nutrients to the retina.

About the Immune Cell Research

Excerpted from New clues found to vision loss in macular degeneration? at EurekAlert!:

[Study author Rajendra S. Apte] has spent years studying the immune system in the eye to distinguish changes related to aging from those related to disease. In earlier work, he found that a cell-signaling molecule, called interleukin-10 (IL10), plays a role in the formation of blood vessels involved in the "wet" form of macular degeneration.

Before vision loss occurs, IL10 levels increase in the eye, as do the number of specific immune cells, called M2 macrophages. These macrophages are known to contribute to the development of damaging blood vessel growth beneath the retina.

Until now, though, how IL10 actually contributed to the proliferation of macrophages and damaging blood vessels wasn't well understood. So Apte and his colleagues engineered mice in which various cell-signaling pathways were disabled. Those experiments led them to discover that a specific signaling pathway involving a protein called STAT3 was activating and altering immune cells in the eye, and those cells then spurred the formation of harmful blood vessels.

Further, they examined eye tissue from patients treated in the 1980s and 1990s, when surgery to remove abnormal blood vessels from underneath the retina was routinely performed on patients with the wet form of macular degeneration. There, too, the same STAT3 protein that was abundant and active in M2 macrophages in mice also was found in high levels in the human tissue.

The findings suggest that the causes of damaging blood vessel growth in people are the same as what the researchers had observed in mouse models, Apte said. In both mice and in patients, abnormal blood vessel growth was linked to macrophages with high levels of the active form of STAT3.

That a cause of significant vision loss appears to be the same in mice and people is good news, Apte explained, because some compounds can disrupt the actions of STAT3 in mice and keep the pathway from spurring blood vessel growth. Those same compounds may alter the course of macular degeneration in people with the condition.

"Now that we have a better idea of how these macrophages are activated at the molecular level, we may be able to use those drugs to halt or reverse the disease process," Apte said.

More about Age-Related Macular Degeneration

NEI image of how someone with macular degeneration sees: overall blurriness with a blind spot in the center

What a person with AMD sees

Age-related macular degeneration (AMD) is gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. The fovea is located in the center of the macula and provides the sharpest detail vision.

Damage to the macula impairs the central (or "detail") vision that helps with essential everyday activities such as reading, preparing meals, watching television, playing card and board games, and needlework and sewing.

AMD is the leading cause of vision loss for people aged 60 and older in the United States. According to the American Academy of Ophthalmology, 10-15 million individuals have AMD; approximately 10% of people who are affected have the "wet" type of AMD. For more information about vision loss from AMD, see How Does AMD Affect Vision? by Lylas G. Mogk, M.D.

Wet Macular Degeneration (AMD)

In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).

The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

Dry Macular Degeneration

The dry (also called "atrophic") type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure. "Atrophy" refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula, causing it to deteriorate or degenerate over time. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.

More about the Research from Nature Communications

Excerpted from the article Introduction:

The innate immune system plays an integral role in regulating angiogenesis during development and in age-associated diseases such as cancers, atherosclerosis and blinding eye diseases. In the eye, pathological neovascularization during disease progression is observed in patients with age-related macular degeneration (AMD).

Of significant interest is the wet (exudative or neovascular) form of AMD that is associated with the majority of the vision loss. It is characterized by the development of abnormal, leaky blood vessels underneath the retina, a process called choroidal neovascularization (CNV). Over the last two decades, numerous studies have demonstrated the essential role of innate immunity, especially macrophages, in regulating CNV in AMD.

The goal of this study was to identify the molecular signaling mechanisms that govern senescent [i.e., the process of becoming old] macrophage polarization and inflammation causing neovascular proliferation and blindness in age-associated eye diseases. Macrophages are incredibly plastic cells that can adapt their activity based on the surrounding micro-environment, confounding the precise understanding of their role in regulating angiogenesis in disease processes.

In this study, we investigated the molecular mechanism behind age-dependent modulation of macrophage polarization and angiogenic function using mice of various age and genetic backgrounds. Here we have shown that IL10 and … STAT3 signaling activity are key regulators of the senescent macrophage phenotype [i.e., the behavior of aging immune cells] in the eye. We further demonstrate that these age-related modulations in macrophage polarization and function can be rescued by targeting STAT3 activity.

Taken together, our study demonstrates the therapeutic potential of targeting STAT3 activity in senescent macrophages as an attractive avenue to restore anti-angiogenic properties of these cells to prevent vision loss. These findings may also be relevant to other disease such as atherosclerosis and cancers where alternatively activated macrophages promote disease pathophysiology.

More Macrophage Research from VisionAware


Topics:
Low Vision
In the News
Medical Updates
Macular Degeneration

Meet Doug Anzlovar and the New "Low Vision Focus @ Hadley" Program at The Hadley School for the Blind

Doug Anzlovar

Doug Anzlovar is the Vice President of Education and Training at The Hadley School for the Blind, where he serves as a member of the administrative team, oversees a 31-member faculty, is involved in curriculum decisions and policy development, and oversees the Low Vision Focus @ Hadley program.

Prior to joining Hadley, Doug worked as a teacher of the visually impaired in the Chicago Public Schools for nearly 10 years. While at Walter Payton College Preparatory High School in Chicago, Doug developed a resource program for students with visual impairments and later became chair of the special education department.

Doug holds a Master of Science degree in adult rehabilitation of the blind and a Bachelor of Science in special education with an emphasis in teaching the visually impaired, both from Northern Illinois University. In addition, Doug is a Certified Vision Rehabilitation Therapist. He is currently a member of, and serves on the Board of Directors for, the Association of Vision Rehabilitation Therapists (AVRT) and the Illinois Chapter of the Association for Education and Rehabilitation of the Blind and Visually Impaired (IAER).

Maureen Duffy: Hello Doug – it's always great to speak with you! A lot has changed since we first featured the Low Vision Focus @ Hadley Program just about a year ago. At that time, the core component of the program was 10 audio lessons on CD. They were mailed directly to an interested person with low vision after speaking with a Hadley intake coordinator to determine which lesson(s) best met his or her needs. I understand the program has been expanded and updated since then. Can you tell our readers what is new at Low Vision Focus @ Hadley?

Doug Anzlovar: Thank you, Maureen. The Low Vision Focus program continues to grow! In addition to the 10 recordings that are available in CD format, they are now available on a single Library of Congress National Library Service (NLS) cartridge. The CDs and cartridge are available free of charge by calling the Low Vision Focus @ Hadley. You can find the contact information at the end of our interview.

The audio lessons include the following topics of interest:

  • Making the Kitchen User-Friendly
  • Getting Around in the House
  • Basic Tactile Marking
  • Going Out with a Friend
  • Doing Simple Kitchen Tasks
  • Keeping Prescriptions in Order
  • Low Vision Cooking
  • Looking Your Best
  • Going Out for a Meal
  • Simple Home Modifications

We relaunched the website in early August 2015 with major upgrades. The website has been completely redesigned to be more contemporary, visually appealing, user-friendly, and functional. The 10 audio recordings are now available as free downloads directly from the Low Vision Focus @ Hadley website, following the completion of a short registration form. We have also bundled existing Hadley programming that has a low vision focus, making it available through the website. This programming includes archived webinars, courses, and our popular iFocus instructional videos, which provide the latest information on how to take advantage of the vision accessibility features built into the iPhone, iPad, and iPod Touch.

Qualified staffers are available to consult with individuals who have questions about their low vision, as well as answer questions from family members, caregivers, or other professionals. We no longer have a lengthy intake process to identify which audio recording to send to our participants. We feel individuals know the kinds of activities of daily living they struggle to perform as a result of their vision loss and can identify which audio recordings they feel will best meet their goals. Should they have questions, individuals could always speak to a qualified staff member. Our goal is always to encourage independence.

MD: Can you tell our readers more about the philosophy that underlies Low Vision Focus @ Hadley Program? I assume that hasn't changed, right?

DA: The overall philosophy of the program has not changed. As vision loss progresses, it often becomes necessary to learn new methods to perform daily activities. The resources of the Low Vision Focus @ Hadley have been developed to help those with low vision maintain independence in their home and community.

MD: Can you give us an idea of what a typical adaptive daily living skill lesson contains?

DA: The audio recordings follow a "radio show" format, in which two hosts discuss a variety of tips and techniques for managing several daily living tasks for someone with low vision. The recordings are meant to be – first and foremost – informative, but also easy and fun to listen to. The average run-time for a recording is about 30 minutes. As an example, the recording "Making the Kitchen User Friendly" offers insight into lighting and contrasting colors for kitchen work areas, the use of magnifiers for completing kitchen tasks, and a variety of safety tips for working in the kitchen.

MD: I'm interested to know more about the audience for the program. I know it is designed for older adult learners with low vision, but are there other audiences it can also apply to?

DA: While the Low Vision Focus @ Hadley program is geared toward older adults, the program is open to any individual who is experiencing vision loss or caring for someone who may be losing his or her vision. This includes, but is not limited to, adult children of seniors living with low vision, caregivers, and professionals.

MD: And finally, what are your future plans for Low Vision Focus @ Hadley?

DA: There has been much enthusiasm over the past several months from our advisory committee and program participants to grow the Low Vision Focus @ Hadley. Short videos are extremely popular in today's culture and we have had dozens of requests to develop videos geared toward those living with low vision. This summer, we began production on 15 short videos that model the tips and techniques discussed in the 10 audio recordings. A total of 25 videos is planned to round out the series. The first 15 videos should be available on the website in the spring of 2016.

In the coming year, we will offer a monthly webinar series that will focus on relevant and timely topics in low vision. Although low vision support groups can be difficult to access due to geographic location and transportation issues, they can provide invaluable information and resources to their members. Therefore, the Low Vision Focus @ Hadley program plans to begin a virtual low vision support group by phone for those who live in rural areas or otherwise cannot access a local support group. Through a partnership with the National Eye Institute's National Eye Health Education Program, we plan to make available additional educational resources and programming.

For More Information

We thank Doug Anzlovar for his longtime support of VisionAware and for his tireless (and talented) work on behalf of older adults with low vision throughout the country. For more information, or to begin taking advantage of the Low Vision Focus @ Hadley, you can visit www.lowvisionfocus.org or call toll-free: 1-855-830-5355.

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Macular Degeneration, Central Vision Loss, and Preferred Retinal Location: New Research May Enable New Approaches to Low Vision Rehabilitation

Optometry and Vision Science cover

People who have central vision loss, caused primarily by age-related macular degeneration, can sometimes adapt by developing a new fixation point in a different part of the retina, called the preferred retinal location (PRL). Recently, Canadian vision scientists developed a new method that makes it possible to identify PRLs in both eyes simultaneously.

This new "proof-of-principle" technique opens the door to an exploration of new approaches to low vision rehabilitation for people with central vision loss. As the authors note, "Understanding binocular [i.e., both eyes] vision opens up exploration of new approaches to visual rehabilitation for these individuals."

The research, entitled Identifying Absolute Preferred Retinal Locations during Binocular Viewing, has been published as an open-source article in the August 2015 edition of Optometry and Vision Science. The authors are Luminita Tarita-Nistor; Moshe Eizenman; Natalie Landon-Brace; Samuel N. Markowitz; Martin J. Steinbach; and Esther G. González, from Toronto Western Hospital and the University of Toronto, Ontario, Canada.

Optometry and Vision Science, the official publication of the American Academy of Optometry, publishes current developments in optometry, optics, and vision science, and promotes interdisciplinary exchange among optometrists and vision scientists worldwide.

About the Preferred Retinal Location Research

Excerpted from New eye-tracker method shows 'preferred retinal location' in both eyes at EurekAlert!:

Central vision loss results from degeneration of the fovea – the central pit of the retina, where visual acuity is sharpest. The most common cause is age-related macular degeneration, which is also the leading cause of blindness in older adults. Especially when present in both eyes, loss of central (reading) vision is a major intrusion on quality of life and everyday functioning.

Taking advantage of visual plasticity that persists even in old age, the brain and eye can partly compensate for loss of the fovea by developing a preferred retinal location (PRL); that is, shifting fixation to another nearby spot in the retina. Patients learn to use an area of their peripheral vision to substitute for their lost central vision.

A technique called microperimetry with eye-tracking can precisely identify the preferred retinal location (PRL), but only in one eye at a time. This may not adequately represent binocular function – vision with both eyes working together. "Understanding binocular vision is important for designing optimal rehabilitation methods for patients with central vision loss," [the authors] write.

[Editor's note: Microperimetry is a type of visual field testing and is a more accurate method to assess the visual field in individuals with central, or macular, visual field loss. Microperimetry allows the examining doctor to monitor and control the patient's central fixation activity while accurately measuring the visual field.]

They developed a method to establish the preferred retinal locations (PRLs) in both eyes, based on the relationship between microperimetry and eye-tracking measurements in healthy eyes. By enabling simultaneous identification of the PRLs in both eyes, the technique provides important information on binocular function in eyes with low central vision. At least for some patients, the results may help to guide approaches to maximizing binocular vision – for example, through relocation training to help move the PRL to the corresponding location in both eyes.

The eye-tracker method may be especially valuable for managing the large number of patients with age-related macular degeneration affecting both eyes. Such an approach not only allows a better understanding of how the eyes and brain deal with binocular central vision loss, but also opens up exploration of new approaches to visual rehabilitation for these individuals.

More about Age-Related Macular Degeneration

NEI image of how someone with macular degeneration sees: overall blurriness with a blind spot in the center

What a person with AMD sees

Age-related macular degeneration (AMD) is gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. The fovea is located in the center of the macula and provides the sharpest detail vision.

Damage to the macula impairs the central (or "detail") vision that helps with essential everyday activities such as reading, preparing meals, watching television, playing card and board games, and needlework and sewing.

AMD is the leading cause of vision loss for people aged 60 and older in the United States. According to the American Academy of Ophthalmology, 10-15 million individuals have AMD; approximately 10% of people who are affected have the "wet" type of AMD. For more information about vision loss from AMD, see How Does AMD Affect Vision? by Lylas G. Mogk, M.D.

Wet Macular Degeneration (AMD)

In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).

The macula is the part of the retina that provides the clearest central vision. Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

Dry Macular Degeneration

The dry (also called "atrophic") type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure. "Atrophy" refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula, causing it to deteriorate or degenerate over time. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.

More about the Research from Optometry and Vision Science

From the article Summary and Discussion:

The information about the locations of the preferred retinal locations (PRLs) simultaneously in the two eyes has been long sought after by researchers working in the field of low vision because the impairments in binocular vision of patients with central vision loss are not well understood.

Also, this information may be helpful in deciding the best course of action for the rehabilitation process for each patient. For example, in the case of the patient with very low vision, the monocular PRL of the left eye and that of the right eye are on opposite sides of each eye's large central scotoma [i.e., blind spot] and therefore in non-corresponding positions. During binocular viewing, however, the PRL of the slightly worse eye moves to a corresponding position with the PRL of the better eye while falling on the scotoma.

Consequently, during binocular viewing, the patient is left with the visual input from only one eye. This patient would probably benefit from PRL relocation training to the upper part of the retina of the two eyes, provided that the trained location is within the same distance from the former fovea as the original PRL to maintain the same level of resolution. This position is beneficial for reading not only because it provides a larger visual span but also because the two PRLs will fall on functional retina.

This is a "proof-of-principle" study and some limitations must be acknowledged. The eye-tracker measures eye movements based on anatomical assumptions described elsewhere and individual factors, such as corneal shape and the roundness of the pupil, affect the accuracy of the measurements.

In addition, we have not tested this eye-tracker on patients with central vision loss and high myopia [i.e., nearsightedness] or hypermetropia [i.e., farsightedness]. For these patients, the eyeball is elongated/shortened and the offset between the eye-tracker and the microperimeter would probably be different from that reported in this article.

Additional Research from Optometry and Vision Science


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