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Macular degeneration

The retina is a thin clear layer of brain tissue one-fifth of a millimeter thick.  The retina coats the inner wall of the eye and is much like the “film” in the camera; light hits the retina and the retina sends a signal to the brain, via the optic nerve.
 
If we think about how amazing our vision is in the sense of the detail, color, and motion we can see, we realize that the retina is quite an tissue to capture and convey such a rich visual signal.  To perform that job, the retina needs a tremendous amount of oxygen.  The retina has its own blood vessels but those blood vessels only supply one-third of the retina’s oxygen requirements.  The other two-thirds of the retina’s needed oxygen comes from a layer of tissue directly underneath the retina, called the RPE-choroid complex.  RPE stands for retinal pigment epithelium.  The RPE-choroid supplies two-thirds of the retina’s oxygen and also provides nutrients to the retina and removes the retina’s metabolic byproducts.
 
The macula is the “center” of the retina which accounts for our sharpest vision--our 20/20 central vision that allows us to read books and road signs, watch TV, play baseball or tennis, etc. The remainder of the retina gives us “peripheral” vision. The Amsler Grid is an easy way for patients to self-monitor their macula.
 
“Dry” macular degeneration is when the RPE-choroid complex underneath the macular “atrophies” or essentially thins out.  Sometimes the layer may almost wither away completely.  When this atrophy happens, the overlying retina does not get the oxygen and nutrients and metabolic help it needs and starts to lose some visual function.
 
Why does this atrophy in the RPE-choroid occur?  It’s not completely understood and tremendous research is going into this area, but it’s thought that oxidative damage and/or inflammation may play a role.  That’s why patients with some degree of macular degeneration may be encouraged to take antioxidant vitamins.  That’s also why patients are encouraged not to smoke or to quite smoking, as smoking causes free radicals and oxidative damage.  
 
The RPE-choroid is packed with blood vessels and is, in fact, the highest blood flow tissue in the body on a blood flow per gram weight basis.  Sometimes the oxidative/inflammatory damage to the RPE-choroid will trigger the growth of abnormal new blood vessels (“neovascularization”).  These blood vessels grow under the macula and leak fluid, blood, and cholesterol lipid.  This leakage causes the overlying retina to lose visual function. Leakage under the retina may cause "wavy lines" on the Amsler Grid. 
 
In the office we may perform a fluorescein angiogram to image the abnormal blood vessels underneath the retina.  We may also perform an OCT (optical topography of the retina) to quantify the degree of fluid that has leaked underneath and into the retina.
 
How is wet macular degeneration treated?  In the past, laser was the only treatment.  The laser burn destroyed the abnormal blood vessels.  The problem with laser is that the laser also destroys a portion on the retina, so vision is lost.  Also, over time abnormal blood vessels may grow back.  
 
In the past six years, a new class of medicines has been developed.  These medicines block a hormone made within the eye that helps new blood vessels grow.  This hormone is called VEGF, for Vascular Endothelial Growth Factor.  By blocking this hormone in the eye, the abnormal blood vessels often stop leaking and shrivel up.  
 
The two most commonly used medicines are called Avastin (Bevacizumab), Eylea (aflibercept) and Lucentis (Ranibizumab).   The medicine is injected into the eye every 4 to 8 weeks, often for several months, sometimes years.   In some patients, the abnormal blood vessels may shrivel up and not come back.  In other patients, the abnormal blood vessels may shrivel up but may return several months after the injections are stopped.  Ultimately the treatment plan is customized to each patient.

All three drugs are FDA approved. AVASTIN was designed to fight the blood vessels in colon cancer. AVASTIN is FDA-approved for colon cancer--to be injected into the blood stream of patients with colon cancer. AVASTIN is not specifically FDA-approved to be injected into the eye. In 2006, eye doctors started to inject AVASTIN into the eye “off FDA label” and see good results with macular degeneration. Eye doctors have also seen an overall good safety profile with these injections. An large scale NIH clinical trial known as the CATT study validated the use of Avastin in wet macular degeneration patients.

LUCENTIS was designed by the same company (Genentech, see www.gene.com) that makes AVASTIN. LUCENTIS was designed to fight the blood vessels in macular degeneration. The LUCENTIS molecule is very similar to the AVASTIN molecule. LUCENTIS is specifically FDA-approved for the eye.

EYLEA is a relatively new drug and is also FDA approved for the eye. All three drugs are "brothers" in that they have the same therapeutic target (VEGF) and work through a similar mechanism.

Which one is for you? The National Institutes of Health sponsored a clinical trial (CATT trial, for Complications of Age Related Macular Degeneration Treatment Trial) which compared Lucentis and Avastin head-to-head. This clinical trial showed that those two drugs have equal efficacy, and no significant safety differences between the two drugs were detected. Eylea has not been compared head-to-head with Avastin, but has been shown to produce similar results to Lucentis. In our office, we generally start out using Avastin and if needed we consider Eylea.

The injection procedure in the office is the exact same for any of the three drugs. Regardless of of the specific drug, there is a small risk (1 in 1000) of serious infection and an even smaller risk of retinal detachment and/or cataract. For more information on this risk see the consent forms referenced below.

 

Lucentis Consent Form---this is the permission slip for the injections that we will ask you to sign if you choose Lucentis.

Avastin Consent Form--this is the permission slip for the injections that we will ask you to sign if you choose Avastin.

Eylea consent form--this is the permission slip for the injections that we will ask you to sign if you choose Eylea.

 

Additional Resources:

Macular degeneration from the National Institutes of Health

Medline Plus Macular Degeneration information

AREDS eye disease clinical trial/Information on eye vitamins

Macular Degeneration Partnership--another informational web site on macular degeneration