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Updates from the London Project to Cure Blindness: Stem Cell Research for Wet and Dry Macular Degeneration

retina with wet AMD

The London Project to Cure Blindness was established ten years ago in the United Kingdom with the goal of developing stem cell-based treatments to cure vision loss associated with age-related macular degeneration (AMD). The Project is the result of a partnership that includes Moorfields Eye Hospital, the University College London (UCL) Institute of Ophthalmology, and the Center for Stem Cell Biology at the University of Sheffield.

Since 2015, the Project has provided updates regarding their progress in stem cell treatments and retinal transplantation for both the wet and dry types of AMD. Most recently, as detailed below, the Project has released information about their progress in developing an affordable and effective stem cell replacement for retinal damage from dry AMD.

Please note: Although this stem cell research has produced interesting results, it is in its very earliest stages and must be subjected to additional, longer-term, rigorous study and clinical trials, encompassing many more years of research. Success in this area of research is not a foregone conclusion. At present, stem cell research is fraught with numerous stops and starts, high expectations, and frequent disappointments.

First, Some Basic Stem Cell Terminology

Here is a brief explanation of some key terms that are used in many types of stem cell research:

  • Pluripotent: A stem cell that has the power to develop into any type of bodily cell or tissue ("pluri" = many; "potent" = having power)
  • Induced pluripotent stem cells (iPSCs): A type of pluripotent stem cell that can be generated or "reprogrammed" directly from adult cells. Induced pluripotent stem cells require viruses to reprogram the cells, which has the potential to cause cancerous tumors.
  • Embryonic stem cells (ESCs): Can form any cell type in the body. However, they are in limited supply, and – due to their origins – have ethical issues attached to their use.
  • Human pluripotent stem cells (hPSCs): The term includes both human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs)
  • Autologous: Involving one individual as both donor and recipient
  • Retinal ganglion cells (RGCs): Neurons, or nervous system cells. They are located near the inner surface of the retina and give rise to optic nerve fibers that transmit information from the retina to several regions in the brain.

About the London Project to Cure Blindness

Excerpted from About Us at the London Project to Cure Blindness website:

The London Project to Cure Blindness has, for the past 10 years, been developing cell-based treatments to cure blindness associated with age-related macular degeneration (AMD). The group has been culturing embryonic stem cells, which give rise to all human cell types, to grow patches of retinal cells for transplant.

 London Project to Cure Blindness logo

The project aims to bring stem cell therapy for retinal diseases, especially for AMD, to the clinic as rapidly as possible. We believe stem cell-based therapies for these conditions have the greatest chances of preventing blindness, restoring sight, and improving quality of life in the future.

The stem cell approach aims to replace cells in the eye that are either damaged or missing. In AMD the main cells that are initially affected are the retinal pigment epithelium cells (RPE). In the first of the trials developed by the London Project, we are using human embryonic stem cells (hES) that have been transformed into RPE cells. These RPE cells will then be transplanted under the patient's retina on a specially engineered patch that the London Project has developed.

[Editor's note: Retinal pigment epithelium (RPE) cells are the deepest cells of the retina. The RPE helps to maintain the health of the retinal photoreceptor cells, called rods and cones. These photoreceptor cells are triggered by light to set off a series of electrical and chemical reactions that helps brain to interpret what the eye sees. The degeneration of the RPE cells also leads to the death of the rods and cones and, ultimately, vision.]

More recently, The London Project has secured funding to examine the use of induced pluripotent stem cell (iPSC) (see explanation above) technology for transplantation. This allows the original cells to be taken from the person with the disease themselves and not from another source, such as an embryo.

Another important arm of the project is to develop the technology by which stem cells can be transformed into photoreceptors (primarily cones and rods) and transplanted into patients. It is believed that the photoreceptors are lost after the RPE cells have degenerated. [Editor's note: You can read more about the function of retinal cones and rods at Some Facts about the Retina on the VisionAware website.]

2015: Initial Report: For Wet Macular Degeneration

A pioneering clinical trial of a new treatment derived from embryonic stem cells for people with wet age-related macular degeneration (AMD) has been initiated at Moorfields Eye Hospital in London, following a successful operation on a 60-year-old woman. She is the first of 10 persons with wet AMD who will receive the stem cell treatment as part of an 18-month clinical trial to test the safety and effectiveness of this procedure.

This initial operation is a key component of the London Project to Cure Blindness. You can read more at First patient receives potential new treatment for wet age-related macular degeneration in London Project to Cure Blindness.

2016: Second Report: For Dry Macular Degeneration

Edited and excerpted from Dry AMD Treatment's "Major Achievement", via the United Kingdom-based Optometry Today:

The [Project's] first-ever treatment for dry age-related macular degeneration (AMD) has been a success, attendees of the Moorfields Eye Hospital annual general meeting heard on July 20, 2016 in London, England. Professor Pete Coffey, director of The London Project, emphasized that his team had developed an [experimental] stem cell replacement for retinal damage from dry AMD [that was implanted into two initial patients].

In the project's first stage, researchers used human embryonic stem cells to regrow retinal pigment epithelium cells on an artificial membrane, creating a specialized patch. This patch was then surgically inserted, in a 45-minute Moorfields operation, into the middle of the retina in the trial patients.

The official research results for the first two patients to receive the patch will be released shortly, but in the meantime, the research will enter the second phase. Instead of receiving an artificial membrane with just retinal pigment epithelial cells on, the next cohort of patients would receive a patch with all three layers of the retina, Professor Coffey said. "Blood cells, vascular cells, neural cells, support cells – it will rebuild the whole macula," he added.

And this would be developed from the patient's own cells, he explained, adding: "Using four genetic switches on a piece of skin, we can get the beginning cell that made you." The use of the patient's cells meant that their DNA could also be studied at the same time, potentially allowing for a personalized diagnosis of their condition, as well as an individualized treatment, Professor Coffey told the audience.

More Information about Age-Related Macular Degeneration

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

What a person with AMD sees

Age-related macular degeneration (AMD) is 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 and writing, preparing meals, watching television, and personal self-care.

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.

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. 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.

Additional Information


Topics:
Clinical Trials
In the News
Low Vision
Macular Degeneration
Medical Updates

New Research Examines the Association Between Diabetic Eye Disease and Depression: Should Eye Doctors Be More Alert to Patients' Mental Health?

retina with diabetic retinopathy

New diabetic retinopathy research from Australia and Singapore suggests that "the severity and progression of diabetic retinopathy can be a useful indicator to prompt the assessment of psychological well-being, particularly in individuals with other risk factors."

The researchers further indicate that doctors who are treating adults with chronic disabling eye disease "should be alert and sensitive to potential indicators of depression such as sad mood, poor sleep and appetite, impaired concentration, and diminished self-esteem."

In his Invited Commentary/Response to this newly-published mental health and eye care research, Peter V. Rabins, MD states the case for depression screening more forcefully: "Busy clinicians must balance their focus on the presenting disease of a patient with a duty to detect other co-morbidities [i.e., the presence of two or more chronic diseases or conditions at the same time] that the patient might be experiencing. Because depression affects 25% to 40% of individuals with significant eye pathology, it is reasonable to ask whether ophthalmologists should take specific steps to detect depression and then refer those who have symptoms for further assessment and treatment."

The Diabetes and Mental Health Research

This new diabetes and mental health research, entitled Association between Diabetes-Related Eye Complications and Symptoms of Anxiety and Depression, has been published "online first" in the July 7, 2016 edition of JAMA Ophthalmology. JAMA Ophthalmology is an international peer-reviewed journal published monthly by the American Medical Association.

The authors are Gwyneth Rees, PhD; Jing Xie, PhD; Eva K. Fenwick, PhD; Bonnie A. Sturrock, DPsych; Robert Finger, PhD; Sophie L. Rogers, MEpi; Lyndell Lim, MBBS, FRANZCO; and Ecosse L. Lamoureux, PhD, who represent the following institutions: the University of Melbourne, Australia; the National University of Singapore; and the National University of Singapore Graduate Medical School.

More about the Diabetes and Depression Research

Edited and excerpted from Diabetic Retinopathy Linked to Depression: Psychological screening may be indicated in severe cases, via MedPage Today:

Severe diabetic retinopathy [also called diabetic eye disease] was linked to depression, and its presence should prompt clinicians to inquire about a patient's mental health, according to a new study in JAMA Ophthalmology.

After controlling for socio-demographic factors and clinical characteristics, including visual acuity, severe diabetic retinopathy was independently associated with greater depressive symptoms, reported the research team.

"Our findings highlight that a simple self-report question about mental health history, which is feasible to implement in clinical practice, along with records of vision and diabetic retinopathy status can be used to identify individuals with diabetes who are at risk for poor mental health," the investigators said.

"The findings presented here highlight that the severity of diabetic retinopathy heightens the risk of depressive symptoms independent from the presence or degree of vision impairment and duration of diabetes. This association likely reflects the long-term burden of managing and coping with diabetic retinopathy in its advanced stages," [the researchers] said.

"The association between depressive symptoms, diabetes, and diabetic retinopathy is likely to be bidirectional, [meaning that] the impairment and burden of diabetes and its complications can precipitate depression and vice versa, and depression can impair diabetes control through various biological and behavioral pathways," they added.

More about Diabetic Retinopathy or Diabetic Eye Disease

Although people with diabetes are more likely to develop cataracts at a younger age and are twice as likely to develop glaucoma as are non-diabetics, 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:

  • "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.

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. 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.

In addition, fluid can leak into the macula, the small sensitive area in the center of the retina that provides detailed vision. This fluid can cause macular edema (or swelling), which can occur at any stage of diabetic retinopathy, although it is more likely to occur as the disease progresses.

Symptoms of Diabetic Eye Disease

Symptoms of diabetic retinopathy can include:

  • Blurry vision or double vision
  • Flashing lights, which can indicate a retinal detachment
  • A veil, cloud, or streaks of red in the field of vision, or dark or floating spots in one or both eyes, which can indicate bleeding
  • Blind or blank spots in the field of vision
Simulation of the effects of diabetic retinopathy

A simulation of the ocular and functional effects of diabetic retinopathy
Henry Ford Center for Vision Rehabilitation and Research

You can read more at Diabetic Eye Disease: Causes and Symptoms and Treatements for Diabetic Eye Disease on the VisionAware website.

A Response to the Research and Support for Depression Screening by Ophthalmologists

In the same July 7, 2016 edition of JAMA Ophthalmology, in an Invited Commentary/Response entitled Depressive Symptoms in Ophthalmology Patients, Peter V. Rabins, MD, MPH, from the University of Maryland, expanded on the importance of this research for adults and older adults with any eye disease:

the JAMA Network logo

Busy clinicians must balance their focus on the presenting disease of a patient with a duty to detect other co-morbidities [i.e., the presence of two or more chronic diseases or conditions at the same time] that the patient might be experiencing.

Because depression affects 25% to 40% of individuals with significant eye pathology, it is reasonable to ask whether ophthalmologists should take specific steps to detect depression and then refer those who have symptoms for further assessment and treatment.

There are several potential approaches to screening for co-morbidities of any sort. One method is to screen all individuals, a second is to screen only those at high risk, and a third is to further assess only those individuals who report the symptom or whom the [doctor] suspects might have the disorder.

This study by Reese [and colleagues] in JAMA Ophthalmology offers useful information in formulating answers to these questions. They found that individuals with moderate to severe diabetic retinopathy were at high risk of having depressive symptoms, while individuals with diabetic macular edema were not, and that it was the severity of the diabetic retinopathy, rather than the severity of the visual impairment, that correlated with depressive symptoms.

However, [because there were limitations in the way the researchers collected and analyzed the study data], their results cannot be used to decide whether universal screening is a more efficient strategy.

[Nevertheless], is it worthwhile to detect depressive symptoms in patients with eye disease? The answer is clearly yes. [Two recent studies of patients with age-related macular degeneration] suggest that clinicians treating individuals with chronic disabling eye disease should be alert and sensitive to potential indicators of depression, such as sad mood, poor sleep and appetite, impaired concentration, and diminished self-esteem. Patients reporting any of these symptoms should be asked if they have been feeling more depressed, and if so, whether they would like a referral to a counselor, social worker, psychiatrist, or psychologist.

More about the Research from JAMA Ophthalmology

Here is a helpful overview of the research, excerpted from the article abstract:

Importance: This study is needed to clarify inconsistent findings regarding the association between diabetes-related eye complications and psychological well-being.

Objective: To examine the association between severity of diabetic retinopathy and diabetic macular edema with symptoms of depression and anxiety in adults with diabetes.

Design, Setting, and Participants: A cross-sectional study was conducted in a tertiary eye hospital in Melbourne, Australia. The study comprised 519 participants with diabetes. The median duration of diabetes was 13 years. The study was conducted from March 1, 2009 to December 24, 2010.

[Editor's note: A cross-sectional study analyzes a group of subjects at one specific point in time. A prospective study, on the other hand, measures a group of individuals over time and follows up with the study subjects in the future.]

Results: Of the 519 participants in the study, 170 were female; the [average] age was 64.9 years. 80 individuals (15.4%) screened positive for depressive symptoms and 118 persons (22.7%) screened positive for symptoms of anxiety. Severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy (explained above) was … associated with greater depressive symptoms after controlling for socio-demographic factors and clinical characteristics, including visual acuity. Diabetic macular edema was not associated with depressive symptoms. No association between diabetic retinopathy and symptoms of anxiety was identified.

Conclusions: Severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy, but not diabetic macular edema, was … associated with depressive symptoms. The severity of diabetic retinopathy could be an indicator to prompt monitoring of depression in at-risk individuals with diabetes. Further work is required to replicate these findings and determine the clinical significance of the association.

Additional Information


Topics:
Diabetes and diabetic retinopathy
Low Vision

New Research Exploring Public Attitudes About Eye and Vision Health: Losing Vision Is Equal to Losing Hearing, Memory, Speech, or a Limb

the JAMA Network logo

New survey research from Johns Hopkins University and the University of Chicago that explores Americans' attitudes toward (a) the importance of eye health, (b) concerns about losing vision, (c) support for eye health research, and (d) awareness of eye diseases and risk factors has also revealed that the loss of eyesight is considered by many survey respondents to be "the worst ailment that could happen … relative to losing memory, speech, hearing, or a limb."

According to the authors, "These findings emphasize the importance of focusing on the preservation of eye health and public support for vision research across all ethnic and racial groups in the United States.

This important new research, entitled Public Attitudes about Eye and Vision Health, has been published "online first" as an open source, freely available article in the August 4, 2016 edition of JAMA Ophthalmology. JAMA Ophthalmology is an international peer-reviewed journal published monthly by the American Medical Association.

The authors are Adrienne W. Scott, MD; Neil M. Bressler, MD; Suzanne Ffolkes, BA, MA; John S. Wittenborn, BS; and James Jorkasky, MBA, who represent the following institutions: Johns Hopkins University School of Medicine, Baltimore, Maryland; Research!America, Alexandria, Virginia; the University of Chicago, Chicago, Illinois; and the Alliance for Eye and Vision Research, Washington, DC.

More about the Research from JAMA Ophthalmology

First, here is a helpful summary from the article abstract:

Importance: Understanding the importance of eye health to the US population across ethnic and racial groups helps guide strategies to preserve vision in Americans and inform policy makers regarding the priority of eye research to Americans.

Objective: To understand the importance and awareness of eye health in the US population across ethnic and racial groups.

Design, Setting, and Participants: An online nationwide [survey] created by experienced policy makers in August 2014 designed to understand the importance of eye health in the US population, although the poll was not subjected previously to formal construct-validity testing. The population survey comprised 2,044 US adults, including non-Hispanic white individuals and minority groups.

[Editor's note: "Construct validity" is a measurement used by researchers to determine whether the research design – in this case, the survey – is able to measure what the research says it is trying to measure; in this case, it is the importance and awareness of eye health to the United States population. The authors acknowledge that this is a limitation of the study, which must be considered when analyzing the survey results.]

Results: Of the 2,044 survey respondents, the mean age was 46.2 years, 48% were male, and 11% were uninsured. 63% reported wearing glasses. Most individuals surveyed (87.5%) believed that good vision is vital to overall health, while 47.4% rated losing vision as the worst possible health outcome.

Respondents ranked losing vision as equal to, or worse than, losing hearing, memory, speech, or a limb. When asked about various possible consequences of vision loss, quality of life ranked as the top concern, followed by loss of independence.

Nearly two-thirds of respondents were aware of cataracts (65.8%) or glaucoma (63.4%); only half were aware of macular degeneration; 37.3% were aware of diabetic retinopathy; and 25% were not aware of any eye conditions. Approximately 75.8% and 58.3%, respectively, identified sunlight and family heritage as risk factors for losing vision; only half were aware of smoking risks on vision loss.

Conclusions: Vision health was a priority, with high support for ongoing research for vision and eye health. Many Americans were unaware of important eye diseases and their behavioral or familial risk factors. The consistency of these findings among the varying ethnic/racial groups underscores the importance of educating the public on eye health and mobilizing public support for vision research.

More Information from the JAMA Ophthalmology Research

Next, here is more survey information from the researchers, excerpted from the article's Introduction and Discussion:

The negative impact of vision loss on quality of life has been well documented in the literature. This negative effect of vision loss on quality of life has been demonstrated in association with cataract, diabetic eye disease, and age-related macular degeneration. Consistently, a year of life with severe vision loss has been valued at a 50% to 70% [decrease] compared with a year of life in perfect health.

However, previous studies of patient attitudes and values around vision loss have not drawn from a cross-sectional, multi-ethnic sample of Americans. Additionally, while the previous literature may inform policy makers regarding resource allocation for sight-saving interventions, the literature is largely silent on the attitudes of Americans regarding resource allocation for research into the prevention of vision loss.

[Editor's note: A cross-sectional study analyzes a group of subjects at one specific point in time. A prospective study, on the other hand, measures a group of individuals over time and follows up with the study subjects in the future. This study measured the attitudes of the survey respondents at one specific point in time.]

While publications document that US ethnic minorities are affected disproportionately by chronic eye conditions, such as glaucoma, and have a greater chance of vision impairment or blindness from these, little information exists regarding attitudes and awareness of these groups toward eye diseases.

Furthermore, whereas vision loss from chronic age-related eye diseases is predicted to have a large impact on the US economy as life expectancy of Americans increases, federal funding for eye research is less than 0.5% of the $139 billion annual cost of vision disorders.

Across all ethnic and racial demographics, nearly 88% of Americans surveyed viewed eye health as critical to overall health. … 47% viewed vision loss as the worst possible health condition that might befall them. This was true of 57% of African American individuals, a group known to have a several-fold increased prevalence of severe vision loss and potentially a greater personal experience with its effects than Americans of other ethnicities. These findings underscore the importance of good eyesight to most and that having good vision is key to one’s overall sense of well-being, irrespective of ethnic or racial demographic.

Persons with greater visual impairments have been shown to have a decreased quality of life, linked to a perception of having less control over their environment, supporting our findings that respondents across all ethnic and racial backgrounds listed blindness high among most-feared ailments.

Similarly, this study showed that Hispanic adults are the ethnic group least likely to have heard of common eye conditions such as age-related macular degeneration or diabetic eye disease. This finding is particularly concerning in that older Latino adults with diabetes or self-reported eye disease had a higher incidence of vision loss when followed over a 4-year period.

What Can You Do in Your Everyday Life for the Prevention and Treatment of Eye Disorders?

1. Know the Differences Among Eye Care Professionals

  • An ophthalmologist is a medical or osteopathic physician who specializes in the medical and surgical care of the eyes and the prevention of eye disease. An ophthalmologist treats eye diseases, prescribes medications, and performs all types of surgery to improve, or prevent the worsening of, eye and vision-related conditions. An ophthalmologist will have the initials M.D. (Doctor of Medicine) or D.O. (Doctor of Osteopathy) after his or her name.
  • An optometrist is a health care professional who specializes in function and disorders of the eye, detection of eye disease, and some types of eye disease management. An optometrist is trained to examine the eyes for visual defects, diagnose problems or impairments, prescribe corrective glasses and contact lenses, and, in some states, perform certain surgical procedures. An optometrist will have the initials O.D. (Doctor of Optometry) after his or her name.
  • You can learn more at The Different Types of Eye Care Professionals on VisionAware.

2. Know the Difference between a Vision Screening and a Comprehensive Eye Examination

  • A vision screening is a relatively short examination that can indicate the presence of a vision problem or a potential vision problem. A vision screening cannot diagnose exactly what is wrong with your eyes; instead, it can indicate that you should make an appointment with an ophthalmologist or optometrist for a more comprehensive dilated eye examination.
  • A comprehensive dilated eye examination generally lasts between 30 and 60 minutes and is performed by an ophthalmologist or optometrist. It should always include the following components: (a) a health and medication history, (b) a vision history, (c) an eye health evaluation, (d) a refraction, or visual acuity testing, (e) visual field testing, and (f) a clear report and summary of your examination results.
  • You can learn more at The Difference between a Vision Screening and a Comprehensive Eye Examination on VisionAware.

3. Know the Risk Factors for Eye Disease

4. Know How to Locate an Eye Care Professional in Your Area

Additional Information


Topics:
Cataracts
Diabetes and diabetic retinopathy
Glaucoma
Health
In the News
Low Vision
Macular Degeneration

New Research: Neuroscientists Regenerate Damaged Optic Nerves in Mice, May Lead to Future Treatment for Glaucoma or Other Optic Nerve Disorders

a laboratory mouse

A group of United States-based neuroscience researchers has used a combination of gene therapy and visual stimulation to create a partial regeneration of damaged optic nerves in blind laboratory mice. Although this research is in its earliest stages and has been performed only with mice, the researchers are "cautiously optimistic" that these findings could one day be used to treat adult patients with vision loss caused by problems with the eye-brain connection – the optic nerve – such as glaucoma.

Please note: Although this regenerative cell research has produced interesting results in mice thus far, it must be subjected to additional, longer-term, rigorous study and clinical trials, encompassing many more years of research.

This new optic nerve regeneration research, entitled Neural activity promotes long-distance, target-specific regeneration of adult retinal axons, has been published in the August 2016 issue of Nature Neuroscience, a monthly scientific journal that positions itself as "the voice of the worldwide neuroscience community." Nature Neuroscience publishes original, peer-reviewed research relating specifically to neuroscience, with priority given to studies that provide insights into the functioning of the nervous system (which includes the optic nerve and the visual system).

The authors are Jung-Hwan A. Lim; Benjamin K. Stafford; Phong L. Nguyen; Brian V. Lien; Chen Wang; Katherine Zukor; Zhigang He; and Andrew D. Huberman, who represent the following institutions: the University of California, San Diego, La Jolla, CA; Harvard Medical School, Boston, MA; Utah State University, Logan, UT; and Stanford University School of Medicine, Stanford, CA.

Some Terminology Used in the Research

Here is a brief explanation of some key terms that are used in this regenerative cell research:

  • Ganglion cells: Nerve cells that are found in the retina. They are located near the inner surface of the retina and give rise to optic nerve fibers (axons) that transmit information from the retina to several regions in the brain.
  • Axons: Long, thin fibers contained within ganglion cells. They extend down the optic nerve in a bundle and then branch out to different regions of the brain, where they connect with other nerve cells to interpret visual information.
  • mTOR: The mammalian target of rapamycin. Rapamycin is a compound produced by bacteria that can suppress or prevent the immune response and has anti-tumor properties. According to Scientific American, "while many factors are responsible for adult brain cells' lack of regenerative capacity, one well-studied cause is the winding down, over time, of a growth-enhancing cascade of molecular interactions, known as the mTOR pathway, within these cells." In this case, the researchers used genetic intervention to activate, or "switch on," the regenerative mTOR pathway once again.

About the Optic Nerve Research

Edited and excerpted from First-ever restoration of vision achieved in mice, via MedicalXpress:

In experiments in mice, the scientists coaxed optic-nerve cables, responsible for conveying visual information from the eye to the brain, into regenerating after they had been completely severed, and found that they could retrace their former routes and re-establish connections with the appropriate parts of the brain. That unprecedented, if partial, restoration could pave the way to future work that enables blind people to see. The animals' condition prior to the scientists' efforts to regrow the eye-to brain-connections resembled glaucoma.

In the study, adult mice in which the optic nerve in one eye had been severed were treated with either a regimen of intensive daily exposure to high-contrast visual stimulation, in the form of constant images of a moving black-and-white grid, or biochemical manipulations that kicked the mTOR pathway (explained above) within their retinal ganglion cells back into high gear, or both.

The mice were tested three weeks later for their ability to respond to certain visual stimuli, and their brains were examined to see if any axonal regrowth had occurred.

While either visual stimulation or mTOR-pathway reactivation produced some modest axonal regrowth from retinal ganglion cells in mice's damaged eye, … when the two approaches were combined—and if the mouse's undamaged eye was temporarily obstructed in order to encourage active use of the damaged eye—substantial numbers of axons grew … and migrated to their appropriate destinations in the brain.

"Somehow these retinal ganglion cells' axons retained their own GPS systems," [study author] Huberman said. "They went to the right places, and they did not go to the wrong places." In other words, the regenerating axons, having grown back to diverse brain structures, had established functional links with these targets. The mice's once-blind eye could now see.

However, even mice whose behavior showed restored vision on some tests, failed other tests that probably required finer visual discrimination, said Huberman. Further progress, he suggested, will depend on boosting total numbers of retinal ganglion cell axons that successfully extend back to, and establish former contact with, their target structures."

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. At present, the damage to the optic nerve from glaucoma cannot be reversed.

You can learn more about the different treatments for glaucoma, including laser peripheral iridotomy (LPI), selective laser trabeculoplasty (SLT), and eye drops to lower eye pressure, on the VisionAware website.

More about the Study from Nature Neuroscience

From the study summary and abstract:

Axons in the mammalian [i.e., mammal, including mice] central nervous system (CNS) fail to regenerate after injury. Here we show that if the activity of mouse retinal ganglion cells (RGCs) is increased by visual stimulation or using chemogenetics [i.e., chemical-genetic interventions], their axons regenerate.

We also show that if enhancement of neural activity is combined with elevation of the cell-growth-promoting pathway involving mammalian target of rapamycin (mTOR), RGC axons regenerate long distances and re-innervate the brain.

Analysis of genetically labeled RGCs revealed that this regrowth can be target specific: RGC axons navigated back to their correct visual targets and avoided targets incorrect for their function. Moreover, these regenerated connections were successful in partially rescuing a subset of visual behaviors.

Our findings indicate that combining neural activity with activation of mTOR can serve as powerful tool for enhancing axon regeneration, and they highlight the remarkable capacity of CNS neurons to re-establish accurate circuit connections in adulthood.

More about Glaucoma at VisionAware


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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

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