Update on Treatments for Retinal Bleeding Caused by PXE

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AUGUST 8, 2009
by Emilie Lamb, Research Coordinator, PXE International

This article first appeared in the Summer 2009 PXE International MemberGram.

One of the changes to the retina that is a classic symptom of PXE is the presence of angioid streaks, or cracks, in the membrane under the retina, called Bruch´s membrane. The retinal bleeding caused by PXE is a result of the formation of new fragile blood vessels that grow through breaks in the membrane, a process called choroidal neovascularization (CNV). These abnormal blood vessels can leak blood and cause scarring in the eye, leading to vision loss.

Researchers have found that proteins in the blood called vascular endothelial growth factors (VEGF) encourage the development of these new blood vessels. Current treatments for CNV involve preventing VEGFs from promoting the growth of new blood vessels through injections of anti-VEGF drugs directly into the eye. As these treatments have developed, two anti-VEGF drugs have shown the most improvement in the majority of individuals, Lucentis® and Avastin®, both produced by Genentech.



Lucentis® is an anti-VEGF antibody, a small molecule that attaches to the VEGF protein and prevents it from activating the growth of new vessels in the retina. Currently, Lucentis is being used to treat the formation of fragile new blood vessels in the eye caused by Age-Related Macular Degeneration (AMD). AMD results in CNV that is similar to that seen in PXE.

In 2006, the FDA approved Lucentis for the treatment of AMD based on multiple studies looking at its effectiveness and safety. Two randomized clinical trials, called MARINA and ANCHOR, studied the effectiveness of using Lucentis to treat vision loss caused by AMD. The results of these trials showed that 40% of patients treated with monthly injections of Lucentis saw an improvement in their visual acuity and 90% maintained their vision over the two-year trial. More than 40% of the patients reported a visual acuity of 20/40 at the end of the two-year trial after receiving monthly injections of Lucentis. For a more detailed summary of these clinical trials, see Treatments for Retinal Bleeding Caused by PXE.

Following these trials, a study called PIER was conducted to look at the effectiveness of Lucentis when the injections are not given on a monthly basis. During this trial, patients with AMD were given a Lucentis injection once a month for three months and then follow-up injections every four months for 24 months. Patients on this treatment plan showed an early improvement in their vision during the first three months but returned to their initial visual acuity after 1 year.



A similar drug, called Avastin®, is approved by the FDA for the treatment of certain types of colorectal, lung, breast and brain cancer and has the same mechanism of action in the retina as it does in cancerous tumors: it blocks the formation of new blood vessels. Avastin is also an anti-VEGF antibody and is produced from the same basic antibody that is used to make Lucentis; however, Lucentis was specifically designed for use in the eye, so it is a smaller molecule. Currently, Avastin is not approved for use in the eye, but many ophthalmologists and retinologists use it ‘off-label´ (meaning they deviate from the FDA labeling) for the intraocular treatment of AMD.

A clinical study, conducted in 2004, examined the usage of Avastin injected directly into the eye (intraocular) as a treatment for CNV. While prior clinical trials reported side effects when Avastin was administered throughout the entire body for the treatment of cancer, the researchers found no serious side effects associated with intraocular injections of Avastin following three months of treatment. While this study showed positive results, it is important to remember that this was not a randomized clinical trial and more studies are needed to examine the safety of Avastin usage in the eye.

In 2007, Dr. Lawrence Yannuzzi, a member of PXE International´s Professional Advisory Board, and colleagues performed a study of the use of Avastin injected into the eye for the management of CNV in nine patients with PXE. Dr. Yannuzzi and his colleagues studied nine eyes of nine patients with angioid streaks associated with CNV and PXE. During the course of the study, either all of the patients´ vision stayed at the level it was at the start of the study or their vision improved. None of the nine patients lost visual acuity compared to his/her vision at the start of the study. Dr. Yannuzzi and his colleagues concluded that eye injections with Avastin can improve visual acuity or stabilize vision loss in patients with PXE.


How do you choose?

Currently, only Lucentis is approved by the FDA for the treatment of CNV related to AMD. However, a study comparing Avastin and Lucentis in the treatment of AMD is currently being conducted and sponsored by the National Eye Institute and the results are expected to be reported in 2010.

Injections with anti-VEGF drugs can be required as frequently as monthly or as rarely as once every six months and generally cost around $150 per injection for Avastin and $2,000 for Lucentis. In 2007, a cost benefit analysis was performed comparing Avastin and Lucentis. According to the study, the researchers found that Lucentis would have to be “2.5 times more efficacious” than Avastin to be cost effective when compared. However, studies have shown that Avastin and Lucentis have similar results.

As both of these drugs appear to be effective at treating CNV caused by AMD, and therefore likely candidates for treatment of vision loss in PXE, the question becomes, why choose one above the other?

It is very important to discuss your options with your ophthalmologist or retinologist and after considering all of the factors, make an informed decision about the best treatment plan for you.


Other Alternatives?

There are over 50 new drugs for AMD in development. For example, recently a Japanese company named OPKO created a new drug, called Bevasiranib, which also prevents the VEGF proteins from causing these leaky blood vessels to grow. However, Bevasiranib works differently from drugs like Avastin and Lucentis. While Avastin and Lucentis bind to the VEGF protein that has already been made in the eye and clear it away, Bevasiranib prevents the VEGF proteins from being produced at all.

Currently, Bevasiranib is in Phase III Clinical trials to test its safety and effectiveness for treating wet AMD, and so far it has shown an excellent safety record and has proven to be effective for treating AMD in animals and humans. While this drug has a promising future for treating AMD, it has not been tested in individuals with PXE and should not be used without consulting your physician.

Further, there are many trials using other methods of delivery, so that perhaps sometime soon time-release, and less invasive options will be available rather than intraocular injections. There are too many of these to list here, and it is not clear yet which delivery methods will be effective.

For more information on Lucentis, Avastin, and other treatment options, please visit the following websites:


Defining the Terms

Angioid streaks: Angioid streaks are cracks in Bruch´s membrane behind the retina through which new blood vessels can grow.

Choroidal Neovascularization (CNV): CNV is the formation of new blood vessels through the membrane and into the retina.

Off-label use: The term “off label” is used when a drug is used for something other than that for which it was approved. Example: Avastin was approved to treat colon cancer, and it is being used “off-label” to treat age-related macular degeneration.

Randomized clinical trials: Randomized clinical trials are trials where a group of people is randomly assigned to receive either a possible new treatment or not. This helps the researchers know that the changes they see are because of the drug and not a difference between the people.

Vascular Endothelial Growth Factors (VEGF): VEGF are chemicals in the blood stream that promote growth of new blood vessels.

Visual Acuity: Visual acuity is a measurement of how well a person can see. The “normal” visual acuity is 20/20 or 6/6 (metric). This fraction means that a person with normal vision could stand 20 feet away and read a sign clearly. If your vision was 20/40, you could read a sign from 20 feet away that someone with normal vision could read from 40 feet away.