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Existing FDA-Approved HIV/AIDS Drugs Could Be Repurposed to Treat Macular Degeneration

A retinal photograph of dry AMD

An international research group has reported that HIV/AIDS drugs, in use for the last 30 years, could be repurposed to treat age-related macular degeneration (AMD), as well as other systemic inflammatory disorders.

Their research tested the treatment effects of nucleoside reverse transcriptase inhibitors (NRTIs) on dry AMD in laboratory mice. NRTIs are a class of drugs that were designed to treat cancer in the 1960s. They emerged again in the late 1980s and became the first FDA-approved drugs for the treatment of HIV/AIDS. In persons with HIV, NRTIs block an enzyme the virus uses to create more copies of itself.

The new research demonstrates that NRTIs prevented retinal degeneration in a mouse model of dry AMD by blocking the activity of a biological pathway that activates inflammatory processes in the body. The researchers are planning to begin human clinical trials early next year, with results about the drug's effectiveness expected in two to three years.

From the Journal Science

The research, entitled Nucleoside reverse transcriptase inhibitors [NRTIs] possess intrinsic anti-inflammatory activity was published in the November 21, 2014 edition of Science. Founded in 1880, Science is a peer-reviewed, general science journal that publishes cutting-edge international scientific research, news, commentary, and opinion. It is published by the American Association for the Advancement of Science (AAAS), the world's largest general-science society.

The research was conducted by an international group of scientists who represent the following institutions: the University of Kentucky; Institute of Genetics and Biophysics, Naples, Italy; the National Cancer Institute, National Institutes of Health, Bethesda, MD; Cardiff University, United Kingdom; the University of Calgary, Alberta, Canada; Chapman University School of Pharmacy, Irvine, CA; and Keck School of Medicine of the University of Southern California, Los Angeles, CA.

About Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. Damage to the macula impairs the central (or "detail") vision that helps with essential everyday activities such as reading, preparing meals, watching television, and playing card and board games. AMD is the leading cause of vision loss for people aged 60 and older in the United States.

About 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.

Photograph of a retina with drusen

A retina with drusen

Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina, near Bruch's membrane, 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.

Wet (Neovascular) Macular Degeneration

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.

About the Research

Excerpted from HIV drugs could treat blindness, via IOL SciTech:

HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs), including AZT and three others, blocked age-related macular degeneration in mice and worked well in experiments involving human retinal cells in the laboratory.

In HIV-infected people, NRTIs block an enzyme the virus uses to create more copies of itself. The new research shows the drugs also block the activity of a biological pathway responsible for activating inflammatory processes in the body.

It is that previously unrecognized quality that makes NRTIs promising for treating macular degeneration as well as graft-versus-host disease, a rarer ailment that can occur after a stem cell or bone marrow transplant, the researchers said.

In the new study, the NRTIs blocked a powerful collection of proteins that can kill cells in the retina, thus preserving vision in mice. Researchers are planning for clinical trials in the coming months and it could be known in as soon as two to three years whether the drugs are effective in treating macular degeneration in people.

Because these inexpensive drugs are already approved by the United States Food and Drug Administration (FDA) and have a good safety record, they could be "repurposed" rapidly to treat other illnesses, said study author Dr. Jayakrishna Ambati.

More about the Research

Excerpted from HIV/AIDS Drugs Could Be Repurposed to Treat AMD, via Drug Discovery and Development Magazine:

In their Science publication, [the authors] report that multiple FDA-approved NRTIs prevented retinal degeneration in a mouse model of dry AMD. Surprisingly, this effect of NRTIs in the eye was not due to the well-known function of these drugs to inhibit reverse transcriptase [i.e., a process that is critical for replication of HIV].

Instead, NRTIs blocked an innate immune pathway called the "inflammasome," even in experimental systems in which the NRTIs were not capable of blocking reverse transcriptase.

In their report, they also showed that NRTIs were effective in other disease models that share common signaling pathways with the dry AMD model, including the "wet" form of AMD - a disease that when treated still does not lead to substantial vision improvement in two-thirds of patients …

"Repurposing of NRTIs could be advantageous … because they are very inexpensive. Since these NRTIs are already FDA-approved, they could be rapidly and inexpensively translated into therapies for a variety of untreatable or poorly treatable conditions," said Benjamin Fowler, the lead author and a postdoctoral fellow. "We are excited at the prospect of testing whether NRTIs could be effective in halting the progression of AMD in patients."

Inflammation and Macular Degeneration

From Risk Factors for Age-Related Macular Degeneration at VisionAware.org:

Age and the environmental factors together produce an increased number of free radicals in the macula. The macula is the small sensitive area in the center of the retina that provides clear central vision. Free radicals are unstable molecules that must be neutralized to keep them from causing damage. Mother Nature has provided anti-oxidants in food to neutralize these free radicals.

However, when we have too many free radicals and not enough anti-oxidants, damage is done. The first signs of damage in the macula are small whitish or yellowish spots called drusen, which the ophthalmologist can see usually before the individual is experiencing vision loss.

This initial damage triggers inflammation, which causes more damage, exacerbated by more free radicals. This results in more inflammation and the cycle continues, eventually scarring the macula and causing central vision loss.

More about the Study from Science

From the Editor's Summary:

Nucleoside reverse transcriptase inhibitors (NRTIs) stop HIV in its tracks by blocking reverse transcription, a process critical for HIV to replicate its genome.

Fowler et al. found that in mice, these drugs also block inflammation caused by a large protein complex called the NLRP3 inflammasome. This activity is independent of the drugs' ability to block reverse transcription.

Instead, the drugs block the activity of the ion channel P2X7, which activates the NLRP3 inflammasome. NRTIs improved outcomes in several NLRP3 inflammasome-dependent mouse models of inflammation, including age-related macular degeneration and graft-versus-host disease.

Additional Information


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In the News
Medical Updates
Clinical Trials
Macular Degeneration

New Research: Uveitis, an Inflammatory Eye Disease, May Signal the Onset of Multiple Sclerosis

British Journal of Ophthalmology logo

Several research projects addressing inflammation as a source of eye disease have received attention recently.

In the genetic arena, European researchers investigating the link between inflammation and age-related macular degeneration (AMD) identified a protein, called FHL-1, that functions as a "regulator" to protect the eye from immune system attacks.

And last month, at the 2014 American Academy of Ophthalmology Annual Meeting, American and European researchers presented results from Characterization of Uveitis in Patients with Multiple Sclerosis, a large retrospective study which revealed that nearly 60 percent of persons with both uveitis, an inflammatory eye disease, and multiple sclerosis (MS) are diagnosed with each within a five-year span. In other words, uveitis may be a warning sign that could help doctors detect MS earlier in the course of the disease.

The British Journal of Ophthalmology

The supporting data and research for this retrospective study, also entitled Characterisation of uveitis in association with multiple sclerosis has been published online ahead-of-print in the British Journal of Ophthalmology (BJO). BJO is an international peer-reviewed journal for ophthalmologists and visual science specialists that publishes clinical investigations, clinical observations, and clinically relevant laboratory investigations related to ophthalmology.

[Editor's note: A retrospective study collects data from past records and does not follow up with patients in the present, which can be a limitation in some studies.]

The authors are Wyatt Messenger, Lena Hildebrandt, Friederike Mackensen, Eric Suhler, Matthias Becker, and James T. Rosenbaum, who represent the following United States and European institutions: Casey Eye Institute, Oregon Health & Science University; University of Heidelberg, Germany; Tremlispital, Zurich, Switzerland; and Legacy Devers Eye Institute, Portland, Oregon.

What is Uveitis?

An eye with anterior uveitis

According to WebMD, uveitis (pronounced you-vee-EYE-tis) is an internal inflammation of the eye (pictured left). Uveitis involves the middle layers of the eye, also called the uveal tract or uvea.

The uveal tract contains veins and arteries that transport blood to the parts of the eye that are critical for vision. It includes the following parts of the eye:

  • Iris: A tissue containing muscles that adjust the size of the pupil opening and thus regulate the amount of light that enters the eye. The iris also determines eye color.
  • Choroid: A dark brown membrane that is rich with blood vessels. It supplies blood and nutrients to the retina and nourishes all other structures within the eye.
  • Ciliary body: Contains the ciliary muscles, which change the lens shape and curvature, and the ciliary processes, which produce aqueous humor, a clear, watery fluid that provides nutrients to all parts of the eye.

Uveitis has many potential causes, including inflammatory disease affecting other parts of the body; a viral infection; bacteria; a fungal infection; a parasite, or an injury to the eye. Symptoms of uveitis include eye redness and irritation; blurred vision; eye pain; and increased sensitivity to light.

Complications of uveitis can include glaucoma; cataracts; abnormal growth of blood vessels in the eyes that interfere with vision; fluid within the retina; and vision loss. Early diagnosis and treatment is critical.

What is Multiple Sclerosis (MS)?

From A Definition of MS, via the National Multiple Sclerosis Society:

Multiple sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. The cause of MS is still unknown – scientists believe the disease is triggered by as-yet-unidentified environmental factor(s) in a person who is genetically predisposed to respond.

MS involves a process in which an abnormal response of the body's immune system is directed against the central nervous system (CNS), which is made up of the brain, spinal cord and optic nerves. The exact antigen — or target that the immune cells are sensitized to attack — remains unknown.

Within the CNS, the immune system attacks myelin — the fatty substance that surrounds and insulates the nerve fibers — as well as the nerve fibers themselves. The damaged myelin forms scar tissue (sclerosis), which gives the disease its name.

When any part of the myelin sheath or nerve fiber is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing a wide variety of symptoms. People with MS typically experience one of four disease courses, which can be mild, moderate or severe.

More about the Research

Excerpted from Research Reveals Likelihood and Onset of Multiple Sclerosis Diagnosis among Patients with Inflammatory Eye Disease, via PRNewswire:

The results of the largest retrospective study of multiple sclerosis (MS) in uveitis patients has revealed that nearly 60 percent of patients with both diseases were diagnosed with each within a five-year span. While it has long been known that there is an association between the eye condition and MS, this is the first study to provide a detailed description of the relative onset of uveitis and MS and to calculate the likelihood of an MS diagnosis among uveitis patients.

Diagnosed in approximately 38,000 Americans a year, uveitis causes swelling and irritation of the middle layer of the eye and can lead to permanent vision loss if left untreated.

It is well established in the medical community that uveitis can be a sign of MS and it is estimated that 1 to 10 percent of MS patients have uveitis. MS affects approximately 2.3 million people worldwide, causes irreversible nerve deterioration, and is notoriously difficult to diagnose.

To achieve a better understanding of the association of the two diseases, researchers from Casey Eye Institute at the Oregon Health and Science University and the University of Heidelberg, Germany conducted a database search of approximately 3,000 patients with uveitis from the Casey Eye Institute and 5,319 patients from the University of Heidelberg between 1985 and 2013.

Of these, 24 patients from the Casey Eye Institute and 89 patients from the University of Heidelberg fulfilled the inclusion criteria of diagnoses for both uveitis and MS and were included in the study.

Based on the prevalence of MS in American and European populations, the researchers found that MS is 18 times and 21 times more likely in an American and European population with uveitis, respectively, relative to the general population.

The study found that MS was diagnosed before uveitis in 28 (29 percent) of patients, simultaneously in 15 (15 percent) of patients and after uveitis diagnosis in 54 (56 percent) of patients.

"With a population size four times larger than any study to date on this topic, our study provides a wealth of clinical information to allow clinicians to make more accurate diagnoses while giving patients a better understanding of their prognosis," said Wyatt Messenger, M.D., lead researcher from the Casey Eye Institute. "Knowing more about the onset may enable patients to seek treatment earlier, therefore slowing the progression of the disease and limiting the damage done to the nervous system."

The researchers noted that a major limitation of the study is the lack of availability of brain magnetic resonance images on all of the patients or detailed neurological studies, which would have allowed correlation of the patient's uveitis with their neurological disease.

From the British Journal of Ophthalmology

From the article abstract:

Purpose: To characterise uveitis in association with multiple sclerosis (MS)

Methods: We conducted a retrospective chart review of patients with uveitis and MS at two uveitis centres (Portland, Oregon, USA and Heidelberg, Germany). Baseline characteristics and ophthalmic data were collected at the patient's first and last visits. Additionally, neurological records were obtained when possible.

Results: We identified 113 patients (196 eyes) with uveitis and MS. Of these, 53 had a diagnosis of MS confirmed by review of neurological records, 50 additional patients fulfilled the Poser criteria for MS, and 10 with MS were referred by an outside neurologist.

Among them, 83 (73%) were women and the mean age of presentation was 40.6 years (range 13-64 years). The average visual acuity in affected eyes at presentation was 20/39. There were 90 patients (80%) who presented with intermediate uveitis and 24 patients (15%) with anterior uveitis. Posterior and pan-uveitis were found in four patients (3%) and two patients (2%), respectively.

Compared with our location-matched controls with idiopathic [i.e., of uncertain or unknown origin] intermediate uveitis (n=16), patients with MS and intermediate uveitis were significantly older when diagnosed with uveitis and more likely to be female.

Conclusions: Uveitis with MS generally presents as intermediate uveitis with a minority presenting with anterior uveitis. Patients are significantly older and more likely to be women than patients with idiopathic intermediate uveitis. The visual prognosis is generally favourable.

Additional Information on Inflammatory Eye Disease

Acknowledgment

Anterior uveitis photo is a Wikimedia Commons file, used in accordance with the Creative Commons Attribution 3.0 Unported license.


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In the News
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Medical Updates

New Genetic Research Investigates the Link between Inflammation and Macular Degeneration

Photograph of a retina with wet age-related macular degeneration

European researchers investigating the link between inflammation and age-related macular degeneration (AMD) have identified a protein, called FHL-1, that functions as a type of "regulator" to protect the eye from an attack by the immune system.

According to lead author Dr. Simon Clark, this important genetic research has identified a new target for therapeutic drugs that can "reset" the immune imbalance in the eye, thus possibly preventing, or delaying the progression of, AMD.

From the Journal of Immunology

The research, entitled Identification of Factor H–like Protein 1 [explained below] as the Predominant Complement Regulator in Bruch's Membrane: Implications for Age-Related Macular Degeneration has been published online ahead-of-print in the November 5, 2014 edition of The Journal of Immunology.

The journal publishes novel, peer-reviewed findings in all areas of experimental immunology, including inflammation and autoimmunity. Immunology is a branch of biomedical science that deals with components of the immune system, immunity from disease, and the immune response.

[Editor's note: Bruch's membrane (pronounced "brooks") is the innermost layer of the choroid, the part of the eye containing blood vessels that nourish the retina. When damaged by disease or the aging process, Bruch's membrane is responsible for many bleeding disorders of the retina, such as age-related macular degeneration (AMD).]

The authors are Simon J. Clark, Christoph Q. Schmidt, Anne M. White, Svetlana Hakobyan, B. Paul Morgan, and Paul N. Bishop, who represent the following European institutions: the University of Manchester; Central Manchester University Hospitals NHS Foundation Trust; Manchester Academic Health Science Center; Cardiff University, United Kingdom, and Ulm University, Germany

About Age-Related Macular Degeneration

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. 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 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 and about 10% of people who are affected have the "wet" type of AMD.

Wet (Neovascular) Macular Degeneration

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.

About 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.

Photograph of a retina with drusen

A retina with drusen

Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina, near Bruch's membrane, 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.

About the Research

Excerpted from New insight into common cause of blindness, via The University of Manchester News:

One of the most important risk-associated genes is called complement factor H (CFH). This encodes a protein called factor H (FH) that is responsible for protecting our eyes from attack by part of our immune system, called the complement system. FH achieves this by sticking to tissues, and when it is present in sufficient quantities, it prevents the complement system from causing any damage.

Researchers … have now discovered that the protein factor H is not the main regulator of immunity in the back of the eye; instead it is a different protein that is made from the same CFH gene. This is called factor H-like protein 1 (FHL-1).

Dr. Simon Clark, who led the research, said that "FHL-1 is a smaller version of FH; about a third of the size. However, it has all the necessary components to regulate the immune system and is still subject to the genetic alterations that affect AMD risk. Research has shown that the FHL-1, because it is smaller than FH, can get into structures of the back of the eye which cannot be reached by the larger FH."

He said that this research suggests that it is FHL-1 rather than FH which protects the back of the eye from immune attack and that insufficient FHL-1 in the back of the eye may result in inflammation that eventually results in vision loss from AMD. As such, this work has identified a new target for therapeutics aimed at readdressing immune imbalance in the eye, thereby preventing or slowing down AMD.

Inflammation and Macular Degeneration

From Risk Factors for Age-Related Macular Degeneration:

Age and the environmental factors together produce an increased number of free radicals in the macula. The macula is the small sensitive area in the center of the retina that provides clear central vision. Free radicals are unstable molecules that must be neutralized to keep them from causing damage. Mother Nature has provided anti-oxidants in food to neutralize these free radicals.

However, when we have too many free radicals and not enough anti-oxidants, damage is done. The first signs of damage in the macula are small whitish or yellowish spots called drusen, which the ophthalmologist can see usually before the individual is experiencing vision loss.

This initial damage triggers inflammation, which causes more damage, exacerbated by more free radicals. This results in more inflammation and the cycle continues, eventually scarring the macula and causing central vision loss.

More about the Study from the Journal of Immunology

From the article abstract:

The tight regulation of innate immunity on extracellular matrix (ECM) is a vital part of immune homeostasis throughout the human body, and disruption to this regulation in the eye is thought to contribute directly to the progression of age-related macular degeneration (AMD).

The plasma complement regulator factor H (FH) is thought to be the main regulator that protects ECM against damaging complement activation. However, in the present study we demonstrate that a truncated form of FH, called FH-like protein 1 (FHL-1), is the main regulatory protein in the layer of ECM under human retina, called Bruch's membrane. Bruch's membrane is a major site of AMD disease pathogenesis and where drusen, the hallmark lesions of AMD, form.

We show that FHL-1 can passively diffuse through Bruch's membrane, whereas the full sized, glycosylated, FH cannot… We also show that FHL-1 is retained in drusen, whereas FH coats the periphery of the lesions, perhaps inhibiting their clearance.

Our results identify a novel mechanism of complement regulation in the human eye, which highlights potential new avenues for therapeutic strategies.

Additional Information


Topics:
Medical Updates
Macular Degeneration

Can Our Eye Movements While Watching Television Reveal the Presence of Glaucoma?

photograph of retina showing glaucomatous cupping of the optic disc

New research from City University London indicates that the sequence of specific eye movements an individual uses while watching television or films (called an "eye movement signature") could offer clues as to whether or not he or she has glaucoma.

According to the research team, these "proof of principle" findings could spur the development of an easy-to-use, non-invasive method of screening for glaucoma and additional eye conditions.

From Frontiers in Aging Neuroscience

The research, entitled What's on TV? Detecting age-related neurodegenerative eye disease using eye movement scan paths, was published in the November 11, 2014 edition of Frontiers in Aging Neuroscience. The authors are David P. Crabb, Nicholas D. Smith, and Haogang Zhu, from the Department of Optometry and Visual Science, City University London.

Frontiers is a community-driven open-access publisher and research networking platform. It is the first platform to combine open-access publishing and research networking, with the goal of increasing the reach of publications and the impact of scientific articles and authors.

About the Research

Excerpted from Eye movements while watching TV could reveal glaucoma, via Optometry Today:

How a patient watches TV and films could offer clues as to whether or not they have glaucoma. The new findings, which come from a group of London-based researchers, hint at the potential for an easy, non-invasive method of screening for eye conditions in future.

As we watch movies and TV, our eyes make large numbers of small, rapid movements [called saccades] before lingering briefly on each focal spot. Researchers have long been interested in whether neurological impairments, such as damage to the optic nerve or retinal cells, could potentially leave a trace or disease signature on these patterns of eye movements.

To investigate, a team at City University London observed 32 older adult patients with healthy vision and 44 with varying severities of clinically diagnosed glaucoma. Using eye tracking software, the researchers logged the thousands of small eye movements patients made as they watched a series of three film clips. The team generated "saccade maps," in order to analyze trends in eye movements.

Glaucoma eye movements as charted on a TV screen

Glaucoma eye movements tracked via television and film clips
(Source: Frontiers in Aging Neuroscience. Used in accordance
with the Creative Commons Attribution License)

"What we've been able to untangle, from looking at all of these maps, is that there are little departures [from healthy visual patterns] and little features that occur that are different from the [control subjects]," said study author David Crabb. Using statistical techniques normally employed … to sift through large amounts of genetic data … allowed the team to identify those with glaucoma from the control patients with healthy vision.

"There are some interesting ways in which this research could go forward," said Professor Crabb, explaining that monitoring vision over long periods could allow practitioners to look for signs of deterioration. Such a test could be done remotely in a patient's home using a tablet or computer. The team is now looking to follow up patients over a longer period to monitor vision using the technique, and there is potential to explore other areas of eye disease.

More about Glaucoma

The term "glaucoma" describes a group of eye diseases that can lead to blindness by damaging the optic nerve. It is one of the leading causes of vision loss and blindness. The human eye continuously produces a fluid, called the aqueous, that must drain from the eye to maintain healthy eye pressure.

Types of Glaucoma

In primary open-angle glaucoma, the most common type of glaucoma, the eye's drainage canals become blocked, and the fluid accumulation causes pressure to build within the eye. This increasing pressure can cause damage to the optic nerve, which transmits information from the eye to the brain. Vision loss is usually gradual and often there are no early warning signs.

In angle-closure glaucoma, also called "acute" glaucoma, the aqueous cannot drain properly because the entrance to the drainage canal is either too narrow or is closed completely. In this case, eye pressure can rise very quickly and cause an acute glaucoma attack. Symptoms can include sudden eye pain, nausea, headaches, and blurred vision. Acute glaucoma is a true ocular emergency and requires immediate treatment.

In normal-tension glaucoma, also called low-tension/low pressure glaucoma, individuals with the disease experience optic nerve damage and subsequent vision loss, despite having normal intraocular [i.e., within the eye] pressure (IOP).

Most eye care professionals define the range of normal IOP as between 10 and 21 mm Hg [i.e., millimeters of mercury, which is a pressure measurement]. Most persons with glaucoma have an IOP measurement of greater than 21 mm Hg; persons with normal-tension glaucoma, however, have an IOP measurement within the normal range.

Visual Field Loss

Glaucoma results in peripheral (or side) vision loss initially, and the effect as this field loss progresses is like looking through a tube or into a narrow tunnel. This constricted "tunnel vision" effect makes it difficult to walk without bumping into objects that are off to the side, near the head, or at foot level.

A living room viewed through a constricted visual field

A living room viewed through a constricted visual field.
Source: Making Life More Livable. Used with permission.

Glaucoma is an especially dangerous eye condition because most people do not experience any symptoms or early warning signs at the onset. Glaucoma can be treated, but it is not curable. The damage to the optic nerve from glaucoma cannot be reversed.

More about the Study from Frontiers in Aging Neuroscience

From the article abstract:

Purpose: We test the hypothesis that age-related neurodegenerative eye disease can be detected by examining patterns of eye movement recorded whilst a person naturally watches a movie.

Methods: Thirty-two elderly people with healthy vision (median age: 70) and 44 patients with a clinical diagnosis of glaucoma (median age: 69) had standard vision examinations including automated perimetry. Disease severity was measured using a standard clinical measure (visual field mean deviation).

All study participants viewed three unmodified TV and film clips on a computer setup incorporating the Eyelink 1000 eyetracker. Eye movement scanpaths were plotted using novel methods that first filtered the data and then generated saccade density maps. Maps were then subjected to a feature extraction analysis.

Results: Patients had a range of disease severity from early to advanced. Average sensitivity for correctly identifying a glaucoma patient at a fixed specificity of 90% was 79%.

Conclusions: Huge data from scanpaths of eye movements recorded whilst people freely watch TV type films can be processed into maps that contain a signature of vision loss. In this proof of principle study we have demonstrated that a group of patients with age-related neurodegenerative eye disease can be reasonably well separated from a group of healthy peers by considering these eye movement signatures alone.

Additional Information about Glaucoma Studies

Image credit: Copyright © 2014 Crabb, Smith, and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.


Topics:
Low Vision
In the News
Glaucoma

New Retinal Scan Analysis Can Predict Progression of Macular Degeneration within a Year

The ARVO logo

During the past several months, there has been much research interest focused on predicting the progression of age related macular degeneration (AMD). Last month, a new study in JAMA Ophthalmology investigated the pattern and progression of wet (also called neovascular) AMD and determined that having wet AMD in one eye was associated with an increased incidence and progression of AMD in the other eye.

More recently, researchers at Stanford University have derived a new computer algorithm [i.e., a step-by-step problem-solving procedure] that they say predicts, with high accuracy, whether an individual with mild or intermediate AMD will progress to the wet stage. The technique, which uses standard optical coherence tomography (OCT) testing, has "added on a computerized image-processing step that analyzes not only that OCT scan but any previous ones available from that same patient's earlier visits," says study author Dr. Daniel Rubin.

The Association for Research in Vision & Ophthalmology

The research, entitled Quantitative SD-OCT Imaging Biomarkers as Indicators of Age-Related Macular Degeneration Progression was published in the November 5, 2014 edition of Investigative Ophthalmology & Visual Science, the official journal of the Association for Research in Vision and Ophthalmology (ARVO). ARVO is an international organization that encourages and assists research, training, publication, and dissemination of knowledge in vision and ophthalmology, including low vision.

[Editor's note: Spectral-domain optical coherence tomography (SD-OCT) is a type of non-contact medical imaging technology similar to ultrasound and magnetic resonance imaging (MRI). OCT uses reflected light to produce detailed cross-sectional and three-dimensional images of the eye.]

The authors are Luis de Sisternes, Noah Simon, Robert Tibshirani, Theodore Leng, and Daniel L. Rubin, who represent the following institutions: Stanford University and Stanford School of Medicine, Stanford, California, and the University of Washington, Seattle, Washington.

About Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central 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 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 and about 10% of people who are affected have the "wet" type of AMD.

Wet (Neovascular) Macular Degeneration

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).

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.

About 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.

Photograph of a retina with drusen

A retina with drusen

Drusen are the hallmark of dry AMD. 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.

Risk Factors for Macular Degeneration

The primary risk factors for AMD include the following:

  1. Smoking: Current smokers have a 2-3 times higher risk for developing AMD than do people who never smoked. It's best to avoid second-hand smoke as well.
  2. Sunlight: Ultraviolet (UV) light is not visible to the human eye, but can damage the lens and retina. Blue light waves that make the sky, or any object, appear blue, are visible to the human eye and can also damage the lens and retina. Living Well with Low Vision reports on these lighting issues in Artificial Lighting and the Blue Light Hazard. Avoid UV light and blue/violet light as much as possible by wearing sunglasses with an amber, brown, or orange tint that blocks both blue and UV light.
  3. Uncontrolled hypertension: The National Eye Institute (NEI) reports that persons with hypertension were 1.5 times more likely to develop wet macular degeneration than persons without hypertension. It's important to keep your blood pressure controlled within normal limits.
  4. A diet high in packaged, processed food and low in fresh vegetables: NEI suggests that eating antioxidant-rich foods, such as fresh fruits and dark green leafy vegetables (kale, collard greens, and spinach) may delay the onset or reduce the severity of AMD. Eating at least one serving of fatty fish (salmon, tuna, or trout) per week may also delay the onset or reduce the severity of AMD.
  5. Race: According to NEI, Whites/Caucasians are more likely to have AMD than people of African descent.
  6. Family history: NEI reports that individuals with a parent or sibling with AMD have a 3-4 times higher risk of developing AMD.

You can read more about the full range of AMD risk factors at Risk Factors for Age-Related Macular Degeneration on the VisionAware website.

About the Research

Excerpted from Retinal-scan analysis can predict advance of macular degeneration, study finds, via Stanford Medical News:

Stanford University School of Medicine scientists have found a new way to forecast which patients with age-related macular degeneration (AMD) are likely to [progress to] the most debilitating form of the disease.

The formula distinguishes likely from unlikely progressors by analyzing patient data that's routinely collected by ophthalmologists and optometrists when they perform retinal scans with an imaging technique called spectral domain optical coherence tomography.

This imaging technique is analogous to ultrasound. The macula is scanned with a beam of focused laser light, and the amount of reflected light coming back at each point is measured and recorded. The resulting stream of data is … converted into an extremely high-resolution, three-dimensional image.

"Right now, a patient who goes into the ophthalmologist's office typically gets an SD-OCT scan anyway," said the study's senior author, Daniel Rubin, MD. "Our technique involves no new procedures in the doctor's office — patients get the same care they've been getting anyway.

We've simply added on a computerized image-processing step that analyzes not only that scan but any previous ones available from that same patient's earlier visits."

From this computerized analysis, the investigators are able to generate a risk score: a number that predicts a patient's likelihood of progressing to the wet stage within one year, three years or five years.

In the study, the Stanford team analyzed data from 2,146 scans of 330 eyes in 244 patients seen at Stanford Health Care over a five-year period. Patients were followed for as long as four years, and predictions of the model were compared with actual instances of progression to wet AMD.

The model accurately predicted every occurrence of progression to the wet stage within a year. About 40 percent of the time when the model did predict progression to wet AMD within a year, the prediction was not borne out.

"No test gets it right 100 percent of the time," Rubin said. "You can tweak the model to trade off the risk of telling someone they will progress when they actually won't against the risk of telling them they won't progress when they actually will. But that's nothing compared with the downside of a patient at high risk for progression's not coming in soon enough."

Rubin emphasized that this proof-of-principle study needs to be followed up by a larger study, ideally using data gathered from patients seen at other institutions. He and his associates have now embarked on such a study.

More about the Study from Investigative Ophthalmology & Visual Science

From the article abstract:

Purpose: We developed a statistical model based on quantitative characteristics of drusen to estimate the likelihood of conversion from early and intermediate age-related macular degeneration (AMD) to its advanced exudative form (AMD progression) in the short term (less than 5 years), a crucial task to enable early intervention and improve outcomes.

Methods: Image features of drusen quantifying their number, morphology [i.e., form and structure], and reflectivity properties, as well as the longitudinal evolution [i.e., development over time] in these characteristics, were automatically extracted from 2146 spectral-domain optical coherence tomography (SD-OCT) scans of 330 AMD eyes in 244 patients collected over a period of 5 years, with 36 eyes showing progression during clinical follow-up. We developed and evaluated a statistical model to predict the likelihood of progression at predetermined times using clinical and image features as predictors.

Results: Area, volume, height, and reflectivity of drusen were informative features distinguishing between progressing and nonprogressing cases. The maximum predictive performance was observed at 11 months after a patient's first early AMD diagnosis. Those eyes predicted to progress showed a much higher progression rate than those predicted not to progress at any given time from the initial visit.

Conclusions: Our results demonstrate the potential ability of our model to identify those AMD patients at risk of progressing to exudative AMD from an early or intermediate stage.

Additional Information


Topics:
Low Vision
Medical Updates
Macular Degeneration

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