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New Research Examines the Risk of Serious Eye Infection After Eye Injection Treatments for Macular Degeneration and Diabetic Eye Disease

Photograph of a retina with wet age-related macular degeneration

Although the injectable drugs Lucentis, Eylea, or Avastin have revolutionized the treatment of wet macular degeneration and diabetic eye disease, questions persist among persons with these eye disorders about the safety and tolerability of the eye injection procedures themselves: "How painful are they?" and "Are they safe? What are the chances that I'll get a serious eye infection?"

Of particular concern to doctors and patients alike is the possibility of post-operative, post-injection endophthalmitis, an inflammation of the internal parts of the eye that can be an extremely serious complication of intraocular [i.e., within the eye] surgery.

Now, a new study designed to answer doctors' questions about (a) the rates of post-injection endophthalmitis and (b) the most effective protocols to prevent endophthalmitis has also yielded information that may provide some reassurance to patients who are undergoing injection treatments for eye disease.

Short answer: The rate of post-injection endophthalmitis is extremely low. In this particular study, only 30 cases of endophthalmitis occurred after 90,339 eye injections. The researchers also confirmed for doctors that the use of antibiotic eye drops prior to the eye injection had minimal effect on the rate of post-injection infections.

About the Research from Retina

This new research, entitled Endophthalmitis after Intravitreal Injection: the Role of Prophylactic Topical Ophthalmic Antibiotics (explained below), has been published in the July 2016 edition of Retina: The Journal of Retinal and Vitreous Diseases. Retina is a peer-reviewed journal, published monthly, that focuses exclusively on retinal disorders and provides current information on diagnostic and therapeutic techniques.

The authors are Alexa L. Li; Charles C. Wykoff, MD, PhD; Rui Wang; Eric Chen, MD; Matthew S. Benz, MD; Richard H. Fish, MD; Tien P. Wong, MD; James C. Major Jr., MD, PhD; David M. Brown, MD; Amy C. Schefler, MD; Rosa Y. Kim, MD; and Ronan E. O'Malley, MD, from Retina Consultants of Houston, Blanton Eye Institute, and Houston Methodist Hospital, all from Houston, Texas.

What Is Endophthalmitis?

Endophthalmitis is an inflammation of the internal parts of the eye that is a possible complication of all intra-ocular [i.e., within the eye] treatments and surgeries, but particularly cataract surgery. Post-operative endophthalmitis is a rare, extremely serious complication of intraocular surgery.

Endophthalmitis is usually the result of a bacterial infection. The most common bacteria found to cause this infection are the "staph" (staphylococcus) and "strep" (streptococcal) bacteria, which normally live on human skin. Endophthalmitis usually develops in the first week after surgery and causes a range of symptoms, including pain, redness, decreasing vision, eyelid redness or swelling, or a yellow/green discharge from the eye.

Should any of these symptoms develop, it is extremely important to seek medical care immediately. The sooner endophthalmitis is treated, the better the prognosis for the eye and vision. Endophthalmitis is treated either with antibiotics injected into the eye or with surgery plus antibiotics injected into the eye. Even with treatment, the vision and the eye can be permanently damaged.

About Wet Macular Degeneration, Diabetic Eye Disease, and Eye Injections

In wet macular degeneration and diabetic eye disease, abnormal blood vessels develop that can break, bleed, and leak fluid. If left untreated, these damaged blood vessels can result in a rapid and severe loss of vision. The most effective treatments to date for this blood vessel damage are the injectable drugs Lucentis, Eylea, or Avastin.

At present, these drugs are administered by injection with a very small needle directly into the eye after the surface has been numbed. This is called an "intra-vitreal" injection because the doctor injects the needle directly into the vitreous gel that fills the inside of the eye and gives the eye its shape.

The needle is very small and is inserted near the corner of the eye – not the center. During the injection procedure, the doctor will ask the patient to look in the opposite direction to expose the injection site, which also allows the patient to avoid seeing the needle.

About the Research

Excerpted from Endophthalmitis Risk Low after Intravitreal Injection at Medscape (registration required):

Intravitreal injections are a common treatment for retinal pathologies, including [wet] age-related macular degeneration, diabetic [eye disease], and retinal vein occlusion. Patients usually tolerate these procedures well, but can develop a rare but potentially disastrous infection known as endophthalmitis.

In the past, many physicians have prescribed topical antibiotics in the peri-intravitreal injection period [i.e., the time immediately before, or prior to, the eye injection], but this practice has fallen out of favor; 90.5% of 2015 respondents to the Preferences and Trends survey reported that they do not use antibiotics with these injections.

In the current study, the authors retrospectively [i.e., using past records] identified patients who underwent intravitreal injections at all offices of a large retina-only practice from January 1, 2011, to December 31, 2014.

[The doctors] used prophylactic antibiotics from January 1, 2011, through December 2011 and did not use them from January 1, 2013, to December 31, 2014. The doctors phased out use of the antibiotics during 2012, and the researchers considered this year to be the transition period. [Editor's note: "Prophylactic" describes a medicine or course of action used to prevent disease or the spread or occurrence of disease or infection.]

A total of 30 cases of clinically suspected endophthalmitis occurred post-injection and were treated, for a rate of 0.033%, or about one case for every 3,011 intravitreal injections. Per year, the number of identified and treated endophthalmitis cases was six in 2011, 13 in 2012, seven in 2013, and four in 2014.

"Owing to the nature of performing intravitreal injections, there is a risk of contamination with nasopharyngeal [i.e., affecting the nose and the pharynx, which is the tube connecting the mouth and nasal passages with the esophagus] micro-organisms, including streptococcal organisms. Masks were not a part of the standard protocol in the current series," the authors write. "Most retina specialists recommend either wearing a surgical mask or minimizing talking while preparing and administering intravitreal injections."

Endophthalmitis rates did not differ significantly during the period in which patients received prophylactic antibiotics (6 out of 16,984, or 0.035%) compared with the period in which patients did not receive prophylactic antibiotics (11 out 53,345, or 0.021%). Of the patients who developed endophthalmitis, 12 (40%) had diabetes mellitus.

More about the Study from Retina

Edited and excerpted from the study abstract:

Purpose: To determine the rate of post-intravitreal injection endophthalmitis and to assess microbiological features and outcomes with and without the use of peri-intravitreal injection topical ophthalmic antibiotics.

Methods: Consecutive series of endophthalmitis cases retrospectively identified after intravitreal injection at a multicenter, retina-only referral practice (Retina Consultants of Houston) from January 1, 2011 to December 31, 2014. Prophylactic peri-intravitreal injection topical antibiotics were routinely used during the initial 12-month period (January 1, 2011–December 31, 2011) and not used in the final 24-month period (January 1, 2013–December 31, 2014). Main outcome measures were incidence of endophthalmitis, microbiology results, treatment strategies, and visual outcomes.

Results: Of 90,339 intravitreal injections, 30 cases of endophthalmitis were identified (endophthalmitis rate = 0.033%; or approximately 1 of 3,011 intravitreal injections). The most common organisms isolated were coagulase-negative staphylococci (n = 10, 33%), followed by Streptococcus mitis (n = 2, 7%). Fourteen cases (47%) were culture negative. Peri-intravitreal injection topical antibiotic prophylaxis did not decrease the rate of endophthalmitis (0.035%) with antibiotic use versus 0.021% without antibiotic use.

Conclusion: The risk of endophthalmitis after intravitreal injection remains low, with coagulase-negative staphylococci and Streptococcus mitis the most common bacterial isolates identified. Prophylactic peri-intravitreal injection topical ophthalmic antibiotic use did not decrease the endophthalmitis rate.

Additional Information


Topics:
Avastin
Diabetes and diabetic retinopathy
Eylea
Health
Lucentis
Macular Degeneration
Medical Updates

My Journey: Coping with Dry Eye Syndrome

Holly putting in eye drops

Holly applying her eye drops

July is Dry Eye Disease Awareness Month! Dry eye disease is one of the most common eye problems affecting people today.

Although the actual prevalence of dry eye is difficult to determine, due to varying definitions of the disease, the National Eye Institute, in Facts about Dry Eye, estimates that "… five million Americans 50 years of age and older are estimated to have dry eye. Of these, more than three million are women and more than one and a half million are men. Tens of millions more have less severe symptoms."

Dealing with chronic dry eye, in conjunction with vision loss, can further complicate matters. Dry Eye Syndrome is a prevalent, chronic problem most often exhibited in older adults and, in particular, older women.

What is Dry Eye Syndrome?

Tears allow all of us to maintain proper eye health and clear vision. Dry Eye Syndrome is an ocular condition in which a person either does not make enough tears or does not create good quality tears to properly lubricate their eyes and keep the cornea hydrated. People with dry eye may experience scratchy, burning, or irritated eyes, excess watering, and blurry vision. According to the National Eye Institute, if left untreated, this condition can lead to pain, ulcers or scars on the cornea, and some loss of vision. However, permanent loss of vision from dry eye is uncommon.

How Eye Doctors Diagnose Dry Eye

A comprehensive eye exam can diagnose Dry Eye Syndrome. Your eye doctor will evaluate the quality and quantity of your tear production. By taking a detailed medical history, your doctor also can determine if any pre-existing medical conditions, environmental factors, or current medications could be causing the dryness. Your eye doctor may also perform an external examination of the eye, evaluating your eyelids, cornea, and observing your blinking patterns.

Talking to My Doctor about Possible Solutions

As someone who has suffered from Dry Eye Syndrome since 2009, having this disease is as annoying as it is painful. My dry eye diagnosis was first linked to the chemotherapy and radiation I received during my battle with breast cancer. However, even after my cancer was in remission, the dry eye persisted. I spoke with my doctor about the chronic burning sensation and ocular pain that I was experiencing. Working collaboratively, we developed several solutions to make living with my Dry Eye Syndrome more manageable.

Taming the discomfort is a delicate balancing act of conserving tears, making tears, and controlling eyelid inflammation. It is important to note that every individual's case is different and you must consult with your doctor to determine the best course of action for combating your Dry Eye Syndrome.

Treatment of Dry Eye

First you have to uncover the underlying reason for dry eye, such as medications or a medical or ocular condition. After your doctor determines the cause, here are some treatment options to consider:

Artificial Tears

For mild cases of dry eye, over-the-counter artificial tears may help alleviate some of your symptoms. Preservative-free drops in individual vials are recommended. Artificial tears with chemical preservatives can harm your eyes and actually make your eyes worse! Ask your eye doctor for a recommendation. Currently, I carry lubricating artificial tear drops with me at all times. Whether in my coat pocket or at the bottom of my diaper bag, these drops do offer minor relief for dryness.

Tear Duct or "Punctal" Plugs

Conserving your own natural tears is important when you have dry eye. Blocking your tear drainage ducts with tiny plugs can prevent the tears you have from draining. These very small silicone, collagen, or synthetic polymer plugs, called "punctal plugs," help tears evaporate naturally from your eyes, which helps the surface of your cornea to retain moisture. Each plug is no larger than a grain of rice.

Your ophthalmologist can conduct this procedure right in the office. In some cases, your doctor will numb your eyes with anesthetic eye drops; in other cases, no anesthetic is required. The doctor will use a tweezer- or forceps-like instrument to insert the sterile plugs into the tear drainage ducts, which are located in the inner corners of your upper and lower eyelids.

There are four drainage ducts in total. Each drainage duct is called a "punctum" (the plural is "puncta"). Punctal plugs can be inserted in the puncta of your lower eyelids, your upper eyelids, or both, depending upon the severity of your dry eye.

My Own Experience with Punctal Plugs

Admittedly, I was fearful when my doctor suggested this method as a way to lessen my dry eye symptoms. I didn't exactly love the idea of a foreign object being placed into my eye. However, the entire procedure takes less than five minutes per eye to complete. My ophthalmologist compares the plugs to a lollipop because they slowly melt over time within the eye.

While this treatment may not be ideal for everyone, on average the collagen plugs I have been prescribed last approximately three months before dissolving completely and needing to be replaced. Currently, I have four punctal plugs placed into my eyes every eight to twelve weeks, due to the severity of my dry eye symptoms. I have noticed a considerable decrease in pain due to this intervention.

[Editor's note: Punctal plugs can be temporary, extended-duration temporary, or longer-lasting, depending upon the severity of dry eye symptoms and each person's individual needs.]

Prescription Eye Drops: Another Option

Your eye doctor may also suggest treating your dry eye with prescription medicated eye drops to help eyelid or ocular surface inflammation. For the past several years, I have been using a prescription medication called Restasis, which helps with tear production, reduces inflammation, and lubricates the eye. It takes 60-90 days to experience the full benefit of the medication. Currently, I use Restasis twice daily. While it hasn't completely rid me of my dry eye symptoms, the medication has made it easier to cope with some of the uncomfortable side effects of this condition.

Also, on July 11, 2016, the United States Federal Drug Administration (FDA) approved Xiidra for the treatment of signs and symptoms of dry eye disease.

Implementing Self-Care to Fight Dry Eye

Over the years, I have also found it very beneficial to combine a self-care approach towards coping with dry eye. In addition to my ophthalmologist's medical recommendations, I also do the following:

  • Blink More: It sounds like such a simple thing to do, but reminding yourself to blink when staring at a computer screen or cell phone for a long period of time may help re-moisture your dry eyes.
  • Take A Technology Break: We live in an age of technology, but having dry eye sometimes requires us to put down our cell phones and shut down those laptops. Short, incremental breaks help give our eyes the rest they need to retain much-needed moisture. If I am working on a project that requires a lot of computer work, I set an audio timer to remind me when to take a tech break.
  • Wear Sunglasses: I always wear wraparound eye protection whenever my family and I are outdoors. This reduces exposure to sunlight and other seasonal elements, like wind, which can increase symptoms of dry eye.
  • Dietary Supplements: Increasing your body's own essential fatty acids may also help fight against Dry Eye Syndrome. Omega-3 fatty acids, in the form of fish, fish oil, or flaxseed oils can assist your body in maintaining its own natural form of hydration. Please note: Always consult your physician and your eye doctor before beginning any dietary supplement regimen.
  • Pay Attention to the Weather: My dry eye is always worse when the heat or air conditioning is on inside my home. During those times of the year, I make sure I increase my use of over-the-counter artificial tears to maintain moisture. I also utilize tabletop humidifiers.
  • Invest in a Humidifier: Humidifiers add moisture back into the air. These small, often inexpensive home appliances can really help relieve some of the symptoms of dry eye. Humidifiers come in all shapes, sizes and colors to coordinate with your own personal style and home décor.
  • Drink Lots of Water: It's important to keep yourself hydrated by drinking plenty of water every day. If your body has the natural hydration is needs, dry eye symptoms can become more manageable.
  • Use Warm Compresses: Placing a warm compress on my eyes has always provided me with a cooling sensation and has alleviated my dry eye pain. When symptoms are really intense, I may even choose to sleep with the warm compress over my eyes.
  • Be Careful with Eye Makeup: For women especially, makeup makes a big difference when dealing with dry eye. Always make sure you remove eye shadow, mascara, and liners from your eyes before applying drops. In addition, be proactive in replacing your eye makeup regularly to avoid any bacteria they may collect over time on brushes and applicators.

Dry Eye Syndrome can be managed with over-the-counter remedies, medical interventions, and self-care methods. Maintaining good communication with your eye care professional can help you to learn how to minimize any discomfort and maintain proper eye health.

Additional Information


Topics:
Health
Low Vision
Medical Updates
Personal Reflections

Notes on Blindness: A Remarkable Film about Professor John Hull's Experience of Blindness Receives Strong Reviews

Cover of Touching the Rock

"Vision, in ordinary circumstances, is seamless and gives no indication of the underlying processes on which it depends. It has to be decomposed, experimentally or in neurological disorders, to show the elements that compose it." ~Oliver Sacks, M.D., In the River of Consciousness

Touching the Rock: An Experience of Blindness

Touching the Rock: An Experience of Blindness, first published in 1990, is the late British theologian John M. Hull's audio diary and exploration of the many processes (physical, emotional, psychological, and metaphysical) that accompanied his steady, intractable journey through vision loss and into total blindness, where he began to "…take up residence in another world" in which human experience was transformed.

Professor Hull (1935-2015) was the Honorary Professor of Practical Theology in the Queen's Foundation for Ecumenical Theological Education, Birmingham, England and Emeritus Professor of Religious Education at the University of Birmingham.

Now, 26 years after the publication of Touching the Rock, filmmakers Peter Middleton and James Spinney have brought Professor Hull's story to a worldwide audience, via the award-winning feature film Notes on Blindness. The film premiered at the Sundance Film Festival in January, and opened in theaters throughout the United Kingdom on July 1, 2016.

About Touching the Rock

The book opens in the summer of 1983 as Professor Hull begins "sinking into darkness" and concludes in the summer of 1986 when he "touches the rock" of total, absolute, "deep" blindness. In a review in The New York Review of Books, entitled The Dark, Paradoxical Gift, the late neurologist and prolific author Dr. Oliver Sacks called Touching the Rock "a masterpiece":

There have been many autobiographies written by the blind – narratives at once poignant and inspiring – that bring out the emotional and moral effects of blindness in a life, and the qualities of will and humor and fortitude needed to transcend them. Touching the Rock, John Hull's account of his "experience of blindness," is not such a tale: it has no clear beginning, middle, or end; it lacks literary pretension; it eschews the narrative form itself – and it is, to my mind, a masterpiece.

Touching the Rock was not written at a sitting, as a narrative, but was dictated at intervals—at first daily, then occasionally—after Professor Hull, who had trouble with his eyes since he was a boy, finally lost his sight completely during the late 1970s, when he was in his forties. What he provides are observations piercing in their immediacy and clarity …

He describes how it is to cross the street; how it is to find oneself ignored or infantilized; how the memories and images of people's faces, one's own face too, no longer updated by actually seeing, become first fossilized, then faint, then disappear altogether; how relationships with one's family change …

The observation is minute, and it is also profound: everything is pondered, explored, to its limit – every experience turned this way and that until it yields its full harvest of meanings. The incisiveness of Hull's observation, the beauty of his language, make this book poetry; the depth of his reflection turns it into philosophy.

A VisionAware Interview with Professor John M. Hull

In 2013, VisionAware's Mary D'Apice spoke with Professor Hull (pictured at left) about his reactions to the then-in-progress Notes on Blindness feature film. Here's an excerpt:

head shot of John Hull

Mary: I understand a company in London is interested in turning those original audio tapes into a feature film. How did the filmmakers find you?

John: A few years ago, some filmmakers [Peter Middleton and James Spinney] were interested in making a film about how blind people travel in snow. They came across Touching the Rock and asked if they could come to my office and make a video about my experiences.

We got on so well together that they called me up later and asked if I still had those original audio tapes. I hadn't looked for them in 25 years but I did find all of them. We found out that the publisher did not have the copyright for the tapes themselves so the film company was free to go ahead with a project.

You might not know that the BBC made a 50-minute documentary based on Touching the Rock back in 1991. That was difficult because the experience was so fresh. Well, a short documentary is one thing but a feature is different. I said to the filmmakers, "But there is nothing to film! I never sailed the Atlantic as a one-man crew, hand behind my back. I never climbed Mt. Everest." They told me not to worry. They said all the drama was in those cassettes.

Mary: How are you participating in the making of the film?

John: I am frequently in touch with Peter Middleton, who comes up quite a bit with his collaborators. They like to talk through associations with the past to see if I can conjure up images they could use. I don't act in the movie, someone plays me. But it's my voiceover. You'll hear my voice from the original audio diaries. It's quite exciting really.

You can read Mary's full interview with Professor John Hull at Interview with John Hull, Author of Touching the Rock: An Experience of Blindness on the VisionAware website.

An Interview with Notes on Blindness Co-Director/Writer Peter Middleton

Also in 2013, Mary D'Apice interviewed co-director and writer Peter Middleton about his artistic vision, his passion for Professor Hull's work, and his efforts to bring Notes on Blindness to the screen. Here's an excerpt from that interview:

head shot of Peter Middleton

Filmmaker
Peter Middleton

Mary: Tell us how you came to make the film Notes on Blindness.

Peter: Back in 2010, we were researching for a short film on the blind and partially sighted experience of snow and adverse weather conditions. Initially we were interested how blind people cope in such conditions. In our search for blind subjects to interview we came across Touching the Rock.

In the book there is a really interesting passage in which he describes how snowfall distorts his world — leveling out contours of his surroundings and removing all navigational markers. Underfoot, the different textures of the ground: grass, tarmac, paving, become indistinguishable — disarming him of his ability to navigate his daily environment safely and independently.

So we contacted John Hull and things developed from there. After making the film about snow we proposed to John the idea of a longer piece using the original audio diaries that Touching the Rock had been based on. In May 2011 we collected from John this dusty box of cassette tapes — 16 hours in total, which hadn't been played for over 20 years. It's an incredible archive.

According to John, the process of keeping the diary was a way of coping with the pain of adjustment — a sort of catharsis. He said at the time he would share with the tapes with what he felt he couldn’t burden his family. This gives the recordings a real emotional rawness. We set about transcribing the material and within the first hour or so of listening we knew we had something very special on our hands that would make a really unique piece of cinema.

Mary: How do the diary entries translate into a screenplay?

Peter: Notes on Blindness has a documentary backbone in that the content is factual but we're aiming at something more cinematic, in which John's journey into blindness has the audience riding along with him. Our themes are family, his depression and the transformative experience of blindness.

head shot of James Spinney

Filmmaker
James Spinney

We will be drawing from old photos, interviews, television appearances, and the dialogues John recreates in diary entries. The audience will learn the story of how John went blind through the conversations he has with his young son, Thomas. The script gives his wife Marilyn an active voice, which takes the film out of the subjective (viewpoint) and really broadens the scope.

Mary: In John Hull's description of his loss of sight, what resonated with you?

Peter: John's recordings contain much rich, evocative imagery that resonated with us emotionally and intellectually. In particular, we were drawn to his descriptions of the neurological effects of blindness, especially where John reveals that his visual memories are beginning to fade and he is forgetting what his wife and children look like.

He discusses how the recession of the visual memory also has an impact on his sense of self — impacting on the relationship between the body image and his identity — the "horror of being faceless," of forgetting one's own appearance — a "dematerialization of his body."

You can read Mary's interview with Peter Middleton in its entirety at Interview with Peter Middleton, Producer and Director of Notes on Blindness at the VisionAware website.

2016: Notes on Blindness Opens to Strong Reviews

Following are some of the positive reviews that Peter Middleton and James Spinney's film has received:

  • The San Francisco Film Festival: "We extend a special mention to Notes on Blindness, in recognition of an audaciously ambitious, formally inventive and yet fully realized film that somehow manages to translate an intensely interior experience into compelling, even revelatory cinema, ingeniously articulating what it means to see and be seen."
  • The Guardian: "The [film] brilliantly blurs the boundary between drama and documentary, the disjuncture between authentic sound and artificial vision perfectly capturing the contradictory nature of Hull’s worldview as his eyesight is eclipsed by cataracts and retinal detachment."
  • The Arts Desk: "Notes on Blindness is an extraordinary film that wears its original genius lightly."
  • BBC News: "A beautiful and accessible work of art."
  • Read more about the nominations and awards for Notes on Blindness at the Internet Movie Database (IMDb) website.

Additional Information


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Video Description

A New, Innovative Potential Drug Therapy in Clinical Trials for the Treatment of Wet Macular Degeneration

Photograph of a retina with wet age-related macular degeneration

Although the advent of anti-VEGF therapy (explained in detail below), administered via eye injection with Lucentis, Eylea, or Avastin, has revolutionized the treatment of wet age-related macular degeneration (AMD), there are still a number of persons who do not respond to treatment. It is these "non-responders" or "reduced responders" who continue to pose significant challenges to doctors and researchers.

Despite the relative success of these drugs in treating (but not curing) wet AMD, retinal specialists acknowledge the need for additional interventions to treat wet AMD more effectively. Recent research indicates that treating AMD by inhibiting both vascular endothelial growth factor (VEGF) and platelet-derived growth factor (called PDGF, also explained below) may prove to be more beneficial. The effectiveness of this proposed "combined" or "dual" anti-VEGF and anti-PDGF therapy is the focus of several Phase 3 clinical trials with human subjects and a pre-clinical trial with animal subjects.

About Wet Age-Related Macular Degeneration (AMD)

In wet macular degeneration, the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal 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.

What Is Angiogenesis?

Angiogenesis is a term used to describe the growth of new blood vessels and 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 AMD (retinal and macular bleeding).

Substances that stop the growth of these excessive blood vessels are called anti-angiogenic (anti=against; angio=vessel; genic=development), and anti-neovascular (anti=against; neo=new; vascular=blood vessels).

Angiogenesis and Anti-VEGF Treatments

The focus of current anti-angiogenic drug treatments for wet AMD is to reduce the level of a particular protein, called vascular endothelial growth factor, or VEGF, that binds to cells on the inner lining of blood vessels (vascular endothelial cells) and promotes their abnormal growth in the retina and macula; thus, these drugs are classified as anti-VEGF treatments. At present, these drugs are administered by injection with a very small needle directly into the eye after the surface has been numbed.

Avastin

Avastin is an anti-VEGF drug that is FDA-approved since 2004 for intravenous use in colorectal cancer. It is currently used on an "off-label" basis (i.e., via eye injection) to treat wet AMD. The cost per treatment with Avastin is approximately $50.

Lucentis

Lucentis was derived from a protein similar to Avastin, specifically for injection in the eye to block blood vessel growth in AMD. In 2005, clinical trials established Lucentis as highly effective for the treatment of wet AMD. The FDA approved Lucentis in 2006. The cost per treatment with Lucentis is approximately $2,000.

Eylea

Eylea was approved by the FDA in late 2011 as an effective treatment for wet AMD. It is administered once every two months after three initial once-a-month injections. The cost per treatment with Eylea is approximately $1,800.

[Please note: The significantly higher prices of Eylea and Lucentis reflect the high cost of the FDA approval process for their intended use as a treatment for wet AMD.]

A New Approach: Angiogenesis and Anti-PDGF Treatments

In contrast with vascular endothelial growth factor (VEGF), which binds to cells on the inner lining of blood vessels (endothelial cells), platelet-derived growth factor (PDGF) binds to cells on the outer lining of blood vessels (pericytic cells or pericytes).

Thus, VEGF and PDGF play related, but separate, roles in the formation and growth of new blood vessels: While VEGF stimulates abnormal blood vessel growth in the retina and macula, PDGF stabilizes the maturing blood vessels and shields the inner/endothelial cells, keeping them alive despite anti-VEGF treatment. The result? The Lucentis, Eylea, or Avastin treatment can be rendered ineffective, as seen in persons who are "non-responders" and "reduced responders."

Researchers theorize, therefore, that a combined anti-VEGF and anti-PDGF treatment, targeting both immature and maturing blood vessels, may be more effective than anti-VEGF treatment alone (called "monotherapy"). The anti-PDGF therapy strips the pericytic/protective cells from the outer blood vessel coverings; when the outer protective cells are gone and the inner endothelial cells are exposed, the anti-VEGF therapy can eliminate them as well.

Current Research and Anti-PDGF Treatments

Fovista from Ophthotech

Fovista is an anti-PDGF drug candidate from Ophthotech. It is in development for the potential treatment of wet AMD, used in combination with anti-VEGF drugs Lucentis, Eylea, or Avastin (to be determined). Ophthotech is a United States-based biopharmaceutical company that "specializes in the development of novel therapeutics to treat diseases of the back of the eye, with a focus on developing therapeutics for age-related macular degeneration." At present, Fovista is injected into the eye via a separate needle from the anti-VEGF drugs, which requires two separate injections.

Currently, Fovista is the subject of several Phase 3 clinical trials: (a) A Phase 3 Safety and Efficacy Study of Fovista® (E10030) Intravitreous Administration in Combination With Lucentis® Compared to Lucentis® Monotherapy; (b) A Phase 3 Safety and Efficacy Study of Fovista® (E10030) Intravitreous Administration in Combination With Either Avastin® or Eylea® Compared to Avastin® or Eylea® Monotherapy; and (c) a number of active clinical trials that are no longer recruiting new subjects.

You can learn more about Fovista at the Ophthotech website.

The Durasert Insert from pSivida

Another anti-PDGF treatment in development is the Durasert Sustained-Release Insert from the biotechnology company pSivida. The company has also developed the FDA-approved injectable implant ILUVIEN for the treatment of diabetic macular edema, which you can read more about at the VisionAware blog.

The sustained-release insert is designed to deliver a repurposed cancer drug, called TKI, which is known to block the action of both VEGF and PDGF. Thus far, the insert has been used only in pre-clinical animal studies. According to pSivida, the goal of the Durasert project is to "effectively treat AMD on a sustained basis for six months with a single injection, targeting both VEGF and PDGF while avoiding the toxic systemic side effects of [cancer drugs] and the frequent injections of current AMD anti-VEGF [injections]."

About Clinical Trials

Most clinical trials are designated as Phase 1, 2, or 3, based on the questions the study is seeking to answer:

  • In Phase 1 clinical trials, researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe and effective dosage range, and identify possible side effects.
  • In Phase 2 clinical trials, the study drug or treatment is given to a larger group of people to determine if it is effective and to further evaluate its safety.
  • In Phase 3 studies, the study drug or treatment is given to even larger groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
  • In Phase 4 studies, after the United States Food and Drug Administration (FDA) has approved the drug, continuing studies will determine additional information, such as the drug's risks, side effects, benefits, and optimal use.

VisionAware will provide updates on this macular degeneration research as they become available.

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New Research Indicates Long-Term Positive Effects of Intensive Blood Sugar Control on the Progression of Diabetic Retinopathy

retina with diabetic retinopathy

New diabetes and diabetic retinopathy research indicates that people with type 2 diabetes, who intensively controlled their blood sugar levels during the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial Eye Study, cut their risk of diabetic retinopathy in half in a follow-up analysis, called the ACCORD Follow-on Eye Study (ACCORDION), which was conducted four years after stopping the intensive blood sugar control regimen required by the ACCORD Trial.

"This study sends a powerful message to people with type 2 diabetes who worry about losing vision," said Dr. Emily Chew, study co-author and deputy director of the National Eye Institute's Division of Epidemiology and Clinical Applications. "Well-controlled glycemia, or blood sugar level, has a positive, measurable, and lasting effect on eye health."

Please note, however, that there are cautionary issues and unresolved causative factors related to the blood sugar (glycemic) control group in the original ACCORD study (discussed below) that readers should evaluate carefully and discuss with their physicians.

About the Research from Diabetes Care

This new diabetic retinopathy research, entitled Persistent Effects of Intensive Glycemic Control on Retinopathy in Type 2 Diabetes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Follow-On Study, has been published in the July 2016 edition of Diabetes Care, a peer-reviewed journal published monthly by the American Diabetes Association (ADA). Diabetes Care is a journal for health care practitioners that is intended to increase knowledge, stimulate research, and promote better management of people with diabetes.

The authors are Emily Chew, MD, from the National Eye Institute; the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Eye Study Group; and the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Study Group.

Some Explanations and Terminology

The ACCORD Trial

The ACCORD Trial (2003-2009) involved 77 study sites across North America and enrolled 10,251 participants, all with type 2 diabetes. The purpose of the ACCORD Trial was to test three treatment strategies to reduce the risk of cardiovascular disease among people with longstanding type 2 diabetes: (1) maintaining near-normal blood sugar levels (intensive glycemic control); (2) improving blood lipid levels, such as lowering LDL "bad" cholesterol and triglycerides and raising HDL "good" cholesterol; and (3) lowering blood pressure.

[Editor's note: The treatment phase of the glycemic (blood sugar) control portion of ACCORD had been planned to last 5.6 years but was stopped at 3.5 years, due to an increase in death among participants in the intensive glycemic control group. Analyses thus far have not determined a specific cause for these increased deaths. However, the benefits of intensive glycemic therapy must be weighed against the potential risks – most notably the increased risk of death observed in the ACCORD Trial.]

The ACCORD Trial Eye Study analyzed a subset of 2,856 Trial participants who had not received laser photocoagulation or vitrectomy for proliferative diabetic retinopathy and who had data from the beginning through year four of the study.

ACCORD was sponsored by the National Heart, Lung, and Blood Institute, with collaborators from the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Aging; the National Eye Institute; and the Centers for Disease Control and Prevention. You can read more about the ACCORD Trial at The National Institutes of Health and Clinical Trials.gov.

The ACCORDION Follow-on Eye Study

ACCORDION (2010-2014) is a follow-up assessment of diabetic retinopathy progression in 1,310 people who participated in ACCORD. ACCORDION re-assessed diabetic retinopathy approximately four years after the intensive glycemic control portion of the study had ended, and eight years after enrollment in ACCORD.

By that time, the average A1c (see explanation below) was 7.8 percent for the intensive therapy group and 7.9 percent for the standard therapy group. However, diabetic retinopathy had advanced in only 5.8 percent of participants in the intensive therapy group since enrollment in ACCORD, compared to 12.7 percent in the standard therapy group. ACCORDION was funded through the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

Type 2 Diabetes

Type 2 diabetes (formerly called adult-onset, Type II, or non-insulin dependent) has the following characteristics:

  • It usually occurs after age 30 and affects 90%-95% of individuals with diabetes.
  • It occurs if (1) the pancreas does not produce enough insulin (insulin deficiency), (2) the body's cells are not able to use insulin correctly and efficiently (insulin resistance), or (3) both conditions are present.
  • Glucose continues to rise in the bloodstream because sufficient levels of insulin are not available to open the cells and allow glucose to enter.
  • Initially, it can be managed with weight loss, physical activity, and effective meal planning. For some individuals this suffices for a period of time; when the disease progresses, however, oral medication or insulin may also be required.
  • Primary risk factors include increasing age (45+); ethnic background (African-American, Latino, Native American, Asian); family history; and obesity. You can learn more at What Is Diabetes?.

The A1c Test

The A1c blood test, also known as glycated hemoglobin, hemoglobin A1c, and HbA1c, is the primary tool used to diagnose diabetes and pre-diabetes and to monitor blood glucose control in people with type 1 and type 2 diabetes. This test enables health care providers to diagnose diabetes and treat it before complications occur and to diagnose pre-diabetes to prevent or delay the development of type 2 diabetes. You can read more about the established A1c levels used to diagnose diabetes and pre-diabetes at Diabetes and the Significance of the A1c Test.

About the Research

Excerpted from Intense diabetes treatment prevents damage to vision at United Press International:

Intense treatment of diabetes can help prevent damage to blood vessels in the retina that often leads to blindness, according to a long-term study by the National Institutes of Health. Researchers used aggressive treatment to maintain glycemic control, blood lipid levels and blood pressure, cutting the risk for developing diabetic retinopathy in half, they reported.

The researchers stopped the portion focused on glycemic control 3.5 years into a planned 5.6-year test because of an increase in death among participants, though patients being treated for blood pressure and blood lipid levels continued for the rest of the intended test period.

Tight control of the condition improved health of patients, but did not reduce risk for cardiovascular disease. The treatment did, however, reduce the progress of retinopathy by about one-third.

For the new study, the researchers re-examined 1,310 patients who took part in the original ACCORD study to measure the progression of participants' retinopathy four years after treatment concluded. While measures of blood glucose between participants who received intensive and standard care remained similar to the end of the previous study, 5.8 percent of participants had seen advancement in their retinopathy – less than half the 12.7 percent of those receiving standard treatment whose condition progressed.

More about Diabetic Eye Disease

Diabetic Retinopathy

Although people with diabetes are more likely to develop cataracts at a younger age and are twice as likely to develop glaucoma as people who do not have diabetes, the primary vision problem caused by diabetes is diabetic retinopathy, the leading cause of new cases of blindness and low vision in adults aged 20-65:

NEI example of seeing with diabetic retinopathy: many blind spots and overall blurriness

What a person with diabetic retinopathy may see

  • "Retinopathy" is a general term that describes damage to the retina.
  • The retina is a thin, light-sensitive tissue that lines the inside surface of the eye. Nerve cells in the retina convert incoming light into electrical impulses. These electrical impulses are carried by the optic nerve to the brain, which interprets them as visual images.
  • Diabetic retinopathy occurs when there is damage to the small blood vessels that nourish tissue and nerve cells in the retina.
  • "Proliferative" is a general term that means to grow or increase at a rapid rate by producing new tissue or cells. When the term "proliferative" is used in relation to diabetic retinopathy, it describes the growth, or proliferation, of abnormal new blood vessels in the retina. "Non-proliferative" indicates that this process is not yet occurring.
  • Proliferative diabetic retinopathy affects approximately 1 in 20 individuals with the disease.

Four Stages of Diabetic Retinopathy

According to the National Eye Institute, diabetic retinopathy has four stages:

  • Mild non-proliferative retinopathy: At this early stage, small areas of balloon-like swelling occur in the retina's tiny blood vessels.
  • Moderate non-proliferative retinopathy: As the disease progresses, some blood vessels that nourish the retina become blocked.
  • Severe non-proliferative retinopathy: Many more blood vessels become blocked, which disrupts the blood supply that nourishes the retina. The damaged retina then signals the body to produce new blood vessels.
  • Proliferative retinopathy: At this advanced stage, signals sent by the retina trigger the development of new blood vessels that grow (or proliferate) in the retina and the vitreous, which is a transparent gel that fills the interior of the eye. Because these new blood vessels are abnormal, they can rupture and bleed, causing hemorrhages in the retina or vitreous. Scar tissue can develop and can tug at the retina, causing further damage or even retinal detachment.

More about the Study from Diabetes Care

Condensed and excerpted from the article summary and conclusion, with the full article available online:

Our results showed that intensive glycemic control conferred enduring protection from progression of diabetic retinopathy even though the glycated hemoglobin levels were similar 8 years after randomization and about 4 years after the cessation of the clinical trial. This is the first study in people with type 2 diabetes of about 10 years' duration and established cardiovascular disease, unlike the newly diagnosed participants in the United Kingdom Prospective Diabetes Study (UKPDS), that demonstrated this effect. This phenomenon has been called "metabolic memory" or "legacy effect" in the studies of type 1 diabetes.

The ACCORDION findings demonstrate a similar legacy effect of intensive glycemia control on the progression of retinal disease in people with established type 2 diabetes. Moreover, this effect occurred in response to a median of 3.7 years of intensive glycemic control, and was observed in people with type 2 diabetes and additional cardiovascular risk factors, whose mean diabetes duration was 10 years, and whose initial mean HbA1c was 8.2%.

These observations suggest that glucose lowering can reduce progression of retinal disease relatively late in the course of diabetes and that the retina responds to relatively short-term changes in glucose levels. Whether an even shorter period of glucose lowering could achieve a similar long-term effect on the eyes in either type 2 or type 1 diabetes remains unknown.

In summary, our study results provide evidence that intensive glycemic control is beneficial for reducing the progression of diabetic retinopathy and that the legacy effect is evident in people with type 2 diabetes. The addition of the ACCORDION retinal results to these prior findings demonstrates a posttreatment benefit of intensive glycemia control on the progression of eye, kidney, and nerve disease.

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