Macular Degeneration

Macular degeneration (or age-related macular degeneration) is the leading cause of blindness in the United States. It usually affects older patients- retirement age and above. Initial signs of macular degeneration may be picked up earlier, in the 40’s and 50’s. This is important since there is evidence that intervention with nutritional supplements and life-style changes may reduce the development of this blinding disease.

There are two forms of macular degeneration- dry and wet. The dry form is usually less severe and reading vision is often maintained. The dry forms results from degeneration of the the outer layers of the retina- the light absorbing photoreceptors and the retinal pigment epithelium (RPE). The RPE forms the blood retinal barrier between the outer retinal circulation (choriocapillaris) and the outer retina (photoreceptors). With age, the waste products of vision accumulate beneath the RPE in little mounds called drusen. These yellowish proteinaceous and fatty-like deposits impede the flow of oxygen and nutrients and result in degeneration of both the RPE cells as well as the visual cells (photoreceptors).

In the wet form of macular degeneration, abnormal blood vessles grow from the outer retinal circulation (choroid) beneath the retinal pigment epithelium (RPE) and sometimes into the retina itself. These blood vessels can leak fluid and protein and eventually form a scar. With early diagnosis of these blood vessels,injections of special medicationsinto the eye may be used toinhibit the growth ofthe blood vessels and prevent further vision loss. Fluorescein angiography, optical coherence tomography,and indocyanine green angiography may be used to image themacula and guide treatment. In addition,Retina-Vitreous Associatesparticipate in a number of clinical studies using frontier therapies for the treatment of the most blinding form of macular degeneration.
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Treatments for Macular Degeneration

Fluorescein and ICG Angiography

The abnormal blood vessels associated with macular degeneration are traditionally identified using fluorescein angiography. The dye is injected into the blood and pictures are taken with a filter to see the fluorescein filling the blood vessels. Abnormal blood vessels will leak fluorescein dye and is usually easily recognizable. Sometimes the leakage is poorly localized or blocked by blood or pigment and the source of the abnormal blood vessels cannot be found. Indocyanine green (ICG) angiography was developed to help find the source of blood vessels in such cases. The ICG dye emits infrared light that can be seen though hemorrhage and pigment. In addition, it is a larger molecule that pools in the blood vessels beneath the retina, facilitating visualizationof the source of the abnormal blood vessels within the choroid. When ICG angiography shows a "hot spot" away from the center of vision (fovea), then photodynamic therapy may be effective despite the poorly defined membrane on fluorescein angiography. Unfortunately, hot spots are uncommon.

Anti-Vascular Endothelial Growth Factor (VEGF) Agents

Anti-VEGF agents are currently the gold standard therapy for wet macular degeneration. These include both ranibizumab (Lucentis) and bevacizumab (Avastin). Lucentis has been approved by the FDA for the treatment of wet macular degeneration and has been proven to stabilize vision in greater then 90% of patients as well asimprove vision in up to 40% of patients. Both Lucentis and Avastin are given as intravitreal injections through the outside of your eye (sclera). It specifically binds to proteins known to cause the growth of abnormal blood vessels that lead to vision loss associated with wet macular degeneration. Lucentis injections are typically given every 4 weeks in the affected eye. For more information on this treatment please visit http://www.gene.com/gene/products/information/tgr/lucentis/. Avastin was not initially developed to treat macular degeneration. Based on the results of prior clinical trials Avastin was approved by the FDA to treat metastatic colorectal cancer by blocking or inhibiting a substance known as vascular endothelial growth factor (VEGF). Blocking VEGF helps prevent further growth of the blood vessels that the cancer needs to continue growing. Research has indicated that VEGF is also one of the causes for the growth of the abnormal blood vessels in wet macular degeneration.Retina specialistsare now using Avastin off label to treat wet AMD. Wehave found that many patients treated with Avastin have less fluid and more normal appearing maculas, and most importantly significant visual improvement. Avastin is also typically given every four to six weeks through an injection in the white part of the eye.

Photodynamic Therapy (PDT)

The abnormal blood vessels in the wet form of macular degeneration are typically treated with intravitreal anti-VEGF agents. However, in some refractory cases photodynamic therapy is employed to selectively destroy abnormal blood vessels without damage to surrounding tissues. The medication used in PDT, called verteporfin (Visudyne), is first infused into the vein for 10 minutes. The medication is then selectively absorbed by the abnormally proliferating blood vessels beneath the macula. When exposed to a specific wavelength of light ("non-thermal") the medication beneath the macula is activated and the abnormal blood vessels are selectively destroyed.

Pharmacologic Therapies

The goal is to develop agents that are selective for neovascular tissue- the new abnormal blood vessels in macular degeneration- with acceptable therapeutic indices and means of delivery.Many new pharmacologic therapies are currently in the pipeline in addition to anti-VEGF agents for the treatment of wet AMD, including VEGF-trap and small interfering RNA (siRNA). Retina-Vitreous Associates is a national leader in clinical trials involving many of these new treatments.

Retinal Transplantation and Stem Cells

Retinal transplantation has been attempted to treat patients with macular degeneration and other retinal degenerations (retinitis pigmentosa). The results have been disappointing to date. Transplant rejection is a major problem. Vision has been stabilized in a few cases for short periods of time but improvement has not been demonstrated.

Radiation Therapy

Radiation therapy may help the wet form of macular degeneration by inhibiting blood vessel growth. Results have been mixed with reports of improvement, no change and deterioration associated with radiation therapy. A randomized, controlled, multi-center study on radiation for age-related macular degeneration is currently underway.

Genetics

The genes causing some forms of macular degeneration have now been identified including Sorsby’s macular dystrophy, Best's macular dystrophy and Stargardt's disease. Once a gene is located, a blood test may be able to determine potential risk in family members and the population. In addition, genetic therapies may be able to bypass or compensate for the abnormal gene.

Nutrition

The Age-Related Eye Disease Study was a randomized controlled multicenter study funded by the National Eye Institute that showed a 25% decrease in the risk of developing wet macular degeneration in patients with moderate dry macular degeneration after taking high dose antioxidant nutritional supplementation. This was based on earlier studies that suggested antioxidants and carotenoids, specifically lutein, zeaxanthin, and cryptoxanthin, may reduce the risk of developing macular degeneration and may slow its progression. Leafy vegetables (spinach and collard greens) have a high concentration of the same carotenoids.