Macular Degeneration

As the name suggests, macular degeneration involves a degeneration of tissues under the retina. The most common form of macular degeneration is age-related macular degeneration, most prevalent in the population aged 60 and older. Age-related macular degeneration is also most prevalent in Caucasians. It is particularly detrimental to quality of life because it preferentially affects the central vision. For this same reason, its only saving grace is that it will never completely blind a person in that it spares the peripheral vision. With this peripheral vision a person can be reasonably expected to get around, although at its worst macular degeneration will take our ability to read, drive, use a computer, or even recognize faces.


There are two main categories of macular degeneration, dry and wet. Ninety percent of macular degeneration is the dry form which involves a degeneration of the tissues under the retina, and ultimately the retina itself. This form is the earlier and less aggressive form of the disease. It should be understood, however, that dry macular degeneration alone can result in extreme vision loss. The earliest component of dry macular degeneration is the accumulation of deposits, called drusen, under the retina. These drusen can be visible on retinal examination and their concentration and size correlate with the severity of the disease. More advanced forms of dry macular degeneration involve entire patches of degeneration in and under the retina, visible on examination as what is called geographic atrophy. As stated above, although still a dry form of macular degeneration, this can result in markedly reduced vision.


Dry macular degeneration cannot currently be reversed by medical intervention, but to a significant degree, its progression can be slowed or abated with a number of interventions. These include the regular use of eye vitamins which include the minerals and vitamins studied in the Age Related Eye Disease Study or AREDS.  Currently the AREDS 2 formula of vitamins and minerals is recommended.


Another important intervention is cessation of smoking, which is an independent risk factor for the progression of macular degeneration to the wet or more aggressive form. Hypertension, or high blood pressure, is still another independent risk factor for the development of wet macular degeneration. Studies show less than half of Americans with hypertension have their blood pressure under control, and in practice this correlates directly with worsening macular degeneration in patients. There is almost never a reason that high blood pressure cannot be controlled, and most often it can be controlled by simply adjusting the dose of anti-hypertensive medications, resulting in a much better chance of maintenance of vision in age-related macular degeneration.


Wet macular degeneration is a more aggressive form of the disease and responsible for most of the vision loss associated with macular degeneration. Approximately 10 to 15% of eyes suffering dry macular degeneration will progress to this more aggressive form. The disease mechanisms involved in wet macular degeneration involve the tissues adjacent to the retina and include increased inflammation, leakage of blood vessels, degeneration of vital tissues, and eventually the growth of new unhealthy blood vessels under the retina. These new blood vessels unfortunately develop most often beneath the macula, which is the part of the retina responsible for fine central vision. It is for this reason the typical vision loss in macular degeneration affects the central and not the peripheral vision. These new unhealthy blood vessels are prone to leakage of fluid and frank bleeding which can lead to scar tissue and further degeneration of the retina if untreated.


In past years, no good treatments for wet macular degeneration existed. Both patients and their retinal specialists could only watch in frustration as precious sight was lost permanently over time. Eventually hot lasers were used with some success, but often with residual vision loss caused by the laser as well as the disease. Photodynamic therapy, or cold laser, eventually allowed for less residual damage and served as an effective treatment for certain lesions. This cold laser, however, still left over half of treated eyes with a loss of vision over time.


In more recent years, steroids and newer medications including VEGF inhibitors have been used more successfully to limit both the leakage and growth of the unhealthy blood vessels developing in wet macular degeneration. Combinations of these and past treatments are being used with more success than previously could be offered to patients with macular degeneration. The most commonly used class of drugs is VEGF-inhibitors. Included in this group are the drugs avastin, Lucentis, and Eylea which have allowed approximately 90% of macular degeneration patients, receiving early treatment, to maintain or gain vision. Many new treatments are in constant research, but no treatment can substitute for regular examination and early diagnosis.


Interventions such as the use of AREDS 2 supplements, cessation of smoking, aggressive control of blood pressure, diet high in vegetables and low in fats, control of cholesterol, treatment of sleep apnea, and even control of major anxiety can benefit patients with macular degeneration.

Articles

  

Patients with macular degeneration show improvement with high-dose statin treatment

Date:February 4, 2016Source:Massachusetts Eye and Ear InfirmarySummary:A phase I/II clinical trial has found that some patients taking high doses of atorvastatin (cholesterol-lowering medication) had complete resolution of lipid deposits in the dry form of age-related macular degeneration. AMD is the leading cause of blindness in the developed world, and though effective treatments are available for the wet AMD, they are currently lacking for the more-prevalent dry form.Share:     FULL STORY

Researchers at Massachusetts Eye and Ear/Harvard Medical School and the University of Crete have conducted a phase I/II clinical trial investigating the efficacy of statins (cholesterol-lowering medications) for the treatment of patients with the dry form of age-related macular degeneration (AMD) -- the leading cause of blindness in the developed world.

Although effective treatments are available for the wet form of AMD, they are currently lacking for the more prevalent dry form. The researchers found evidence that treatment with high-dose atorvastatin (80mg) is associated with regression of lipid deposits and improvement in visual acuity, without progression to advanced disease, in high-risk AMD patients. Their findings were published in EBioMedicine--a new online journal led by editors of the journals Cell and The Lancet--and not only further the connection between lipids, AMD and atherosclerosis, but also present a potential therapy for some patients with dry AMD.

"We found that intensive doses of statins carry the potential for clearing up the lipid debris that can lead to vision impairment in a subset of patients with macular degeneration," said Joan W. Miller, M.D., the Henry Willard Williams Professor and Chair of Ophthalmology at Harvard Medical School and Chief of Ophthalmology at Massachusetts Eye and Ear and Massachusetts General Hospital. "We hope that this promising preliminary clinical trial will be the foundation for an effective treatment for millions of patients afflicted with AMD."

Affecting more than 150 million patients worldwide, AMD is associated with an accumulation of drusen (deposits of lipid and fatty proteins) under the retina, and patients with AMD experience blurred vision or blindness in the center of the visual field. There are two forms of AMD: "wet" and "dry." The wet form accounts for approximately 15 percent of AMD cases and is treated using therapies previously developed at Mass. Eye and Ear/Harvard Medical School. The "dry" form is more common, accounting for approximately 85 percent of cases, and effective therapies are currently lacking.

Ophthalmologists and vision researchers have long suspected that there may be a connection between dry AMD and atherosclerosis. In dry AMD, physicians often see soft, lipid-rich drusen in the outer retina, similar to the build-up of lipid material in the inner walls of blood vessels in atherosclerosis. Statin use is widespread in middle-aged and older individuals, who also have an increased risk of AMD; however, previous studies have shown very little correlation between regular statin use and improvements in AMD. The authors of the EBioMedicine paper hypothesized that, due to the heterogeneous nature of the disease, patients with soft, lipid-rich drusen may respond better to statins prescribed at higher dosages.

"Not all cases of dry AMD are the exactly the same, and our findings suggest that if statins are going to help, they will be most effective when prescribed at high dosages in patients with an accumulation of soft, lipid material" said Demetrios Vavvas, M.D., Ph.D., a clinician scientist at Mass. Eye and Ear and Co-Director of the Ocular Regenerative Medicine Institute at Harvard Medical School. "These data suggest that it may be possible to eventually have a treatment that not only arrests the disease but also reverses its damage and improves the visual acuity in some patients."

Twenty-three patients with dry AMD marked by soft lipid deposits in the outer retina were prescribed a high dose (80mg) of atorvastatin, the generic name of the statin marketed as Lipitor® and several generic equivalents. Of the 23 patients, 10 experienced an elimination of the deposits under the retina and mild improvement in visual acuity. Other techniques that have attempted to eliminate the deposits have mostly failed with the disease continuing to progress to more advanced dry AMD or a conversion to the wet form of AMD.

As the next step for this line of research, the investigators plan to expand to a larger prospective multicenter trial to further investigate the efficacy of the treatment in a larger sample of patients with dry AMD.

"This is a very accessible, FDA-approved drug that we have tremendous experience with," said Dr. Vavvas. "Millions of patients take it for high cholesterol and heart disease, and based on our early results, we believe it offers the potential to halt progression of this disease, but possibly even to restore function in some patients with dry AMD."

This work was supported by the Yeatts Family Foundation, the Loefflers Family Foundation and the Research to Prevent Blindness Foundation.

Authors on the EBioMedicine paper include senior author Joan W. Miller, M.D., FARVO, first author Demetrios G. Vavvas, M.D., Ph.D., Anthony B. Daniels, M.D., John I. Loewenstein, M.D., Lucy H. Young, M.D., Ph.D., Evangelos S. Gragoudas, M.D., Dean Eliott, M.D., and Ivana K. Kim, M.D., of the Department of Ophthalmology at Mass. Eye and Ear/Harvard Medical School, Jeremy W. Goldfarb, M.D., of the Department of Anesthesiology at Mass. Eye and Ear/Harvard Medical School, and Zoi G. Kapsala, M.D., Emmanuel Ganotakis, M.D., and Miltiadis K. Tsilimbaris, M.D., Ph.D. of the Department of Ophthalmology at the University of Crete in Greece.

Story Source:

Materials provided by Massachusetts Eye and Ear Infirmary. Note: Content may be edited for style and length.

Journal Reference:

  1. Demetrios G. Vavvas, Anthony B. Daniels, Zoi G. Kapsala, Jeremy W. Goldfarb, Emmanuel Ganotakis, John I. Loewenstein, Lucy H. Young, Evangelos S. Gragoudas, Dean Eliott, Ivana K. Kim, Miltiadis K. Tsilimbaris, Joan W. Miller. Regression of some High-Risk Features of Age-Related Macular Degeneration (AMD) in Patients Receiving Intensive Statin Treatment. EBioMedicine, 2016; DOI: 10.1016/j.ebiom.2016.01.033

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