Researchers have shown how Avastin treatments improved the visual acuity of patients with chronic wet macular degeneration.

Reporting in Retina, The Journal of Retinal and Vitreous Diseases forty-seven patients (48 eyes) aged 57 to 90 who had suffered from macular degeneration for 5 months or more were treated with one or more injections of Avastin.  These patient treated with Avastin injections had a visual acuity of 20/150 or less.  Thirty-two eyes were treated previously with photodynamic therapy.

These patients had shown a mean duration of macular degeneration symptoms for 17.9 months with the mean number of Avastin injections to treat the macular degeneration being 3.41 months.  The follow period was an average of 27 weeks.

It was shown in this research that visual acuity improved by 3 or more lines in 12 eyes (25 percent) and there was no change in 9 eyes (19 percent).  Only 4 eyes (8.3 percent) affected by macular degeneration showed a deterioration by 3 or more lines.

Visual acuity was at least 20/150 in 16 eyes (33 percent), as compared to 4 eyes (8.3 percent) before having treatment with avastin for their macular degeneration.

Because of the results shown, the researchers indicated that patients with chronic wet macular degeneration (AMD) and low vision may benefit from Avastin based therapy.

Several studies have now added some fuel to fire regarding the safety of Avastin, and the effects of using this anti-VEGF to treat eye disease are having on patients diagnosed with macular degeneration.

In one retrospective study of all patients receiving intraocular injections of Avastin (bevacizumab) at one medical centre between November 2005 and July 2006 found that retinal pigment epithelial (RPE) tears was the most common adverse condition that resulted from the injections of Avastin in patients with preexisting RPE detachments.

Other adverse conditions that were rare included retinal ischemia, subretinal hemorrhage, vitreous hemorrhage, ocular irritation or pain, worsened hypertension and headache. No deaths or blot clotting events were observed from the use of Avastin.

Another study showed that symptoms resembling endophthalmitis developed 1 day after the seventh injection of Avastin in a 76-year-old woman. The woman had extrafoveal occult chorodial neovascularization in conjuction with macular degeneration prior to receiving the injections of Avastin. This condition resolved within 5 days when the patient was treated with corticosteroids. Treatment for macular degeneration continued with macugen and no further irritation occurred.

The risk of infectious endophthalmitis resulting from intravitreal injections of Avastin is considered a small risk due to the introduction of microorganisms into the eye.

Another study provided evidence that AVastin rapidly penetrates the retina of monkeys

Genentech developed Lucentis because its scientists were concerned about how well Avastin would penetrate the retina because of its large molecule size. However, this new study shows that this may not be the case and that Avastin can penetrate the retina.

For more information on these studies you may visit the following websites:

http://www.retinajournal.com/pt/re/retina/abstract.00006982-200809000-00018.htm
http://www.ncbi.nlm.nih.gov/pubmed/18781309?dopt=Abstract
http://www.ncbi.nlm.nih.gov/pubmed/18781307?dopt=Abstract

According to Eugene de Juan, MD, “Radiation has been used for some time in the treatment of ocular neovascularization. It is an interesting option because it attacks several of the important components of the disease. It is antiangiogenic but also anti-inflammatory, which may have an important role in the recurrence of the disease, and also antifibrotic.”  While speaking at the Euretina Congress here, Doctor de Juan had stated that this treatment “can work synergistically with other therapeutic approaches. Avastin (bevacizumab, Genentech) and radiation have shown synergism in colon cancer.”

Doctor de Juan went on to indicate that studies have shown moderate effects on stabilization of vision — fairly prolonged over a couple of years but modest in terms of visual gain. From a safety standpoint, a low rate of radiation retinopathy was found.

The new retinal brachytherapy device used at the Doheny Eye Institute in Los Angeles delivers a single intraocular treatment with 24 Gy beta radiation, utilizing a strontium-90 isotope. The procedure is carried out under local anesthesia. Vitrectomy is performed, and a probe is placed into the vitreous cavity. Through this, a small radiation source is placed over the neovascular area and left in place for 3 to 4 minutes.

“The radiations are directed to the edge of the lesion, where they have a peak of power that fades toward the periphery. The exposure of surgeons and assistants to radiation is negligible,” Dr. de Juan said.

Unlike other brachytherapy methods, this device has a significant impact on vision, he said.

Radiation alone resulted in visual stability in about 90 percent of the patients over 2 years. About 50 percent of the patients gained one or more letters of vision, and 17 percent gained more than 15 letters.

Cataract was a common complication, as is expected in procedures involving vitrectomy, and a few other small complications were reported.

“Now, roughly 200 patients have been treated, many have more than 2 years of follow-up and no case of radiation retinopathy has been reported,” Dr. de Juan said.

He said he thinks this is due to the small radiation dose and to the focal character of the radiation delivered.

The brachytherapy treatment has also been found to work synergistically with anti-VEGF therapy. In a pilot study, a single radiation treatment was combined with two injections of bevacizumab. One of the injections was given immediately after the radiation procedure and the second one 30 days later.

As a result, a mean improvement of 10 letters was reported at 12 months. Seventy percent of patients improved or maintained their visual acuity, and 39 percent gained three or more letters.

One year after treatment, no adverse events associated with the exposure to radiation were found.

Dr. de Juan said that the advantage of this approach over anti-VEGF therapy alone is the fact that the radiation treatment is delivered only one time and the number of intravitreal injections is significantly reduced.

“This makes the treatment more cost-effective and certainly more advantageous for the patient’s quality of life,” he said.

As research continues in the areas of macular degeneration, patients are beginning to have many options available to them.  Macular degeneration treatments continue to develop as researchers explore and combine methods of treating the eye disease.

Wet macular degeneration is the more severe form of this eye disease.  It occurs in approximately 10 percent of all diagnosed macular degeneration cases.  However, 90 percent of the blindness caused by this eye disease is associated with wet macular degeneration.

Characterized by the development of abnormal blood vessel growth from beneath the retina, wet macular degeneration results in damage to the macula.  This damage results in scarring and results in the gradual but progressive loss of central vision.  In some cases of wet macular degeneration the loss of vision can occur very rapidly.

GenenTech developed Lucentis as a treatment for wet macular degeneration after Dr. Phillip Rosenfeld demonstrated that Avastin could be used to successful treat the eye disease.  Dr. Rosenfeld’s use of an anti-VEGF drug gave hope to both patients and researchers studying wet macular degeneration.  However, with concerns over the safety of Avastin, the drug Lucentis was created and subsequently approved as an anti-VEGF treatment for wet macular degeneration.

In clinical  testing o Lucentis, approximately 40 percent of the patients with the eye disease showed significant improvement in their vision (3 lines, 15 letters on an eye chart).  Approximately 95 percent of the patients had their vision remain the same.  Because of these results, it is even more imperative that the detection of wet macular degeneration occur early to allow treatments with Lucentis or similar drugs.  Regular eye examinations are essential if people are in high risk categories.

Lucentis is a prescription drug administered through an injection in the eye.  Lucentis is a treatment for wet macular degeneration that is classed as an anti-VEGF drug which stops the growth of abnormal blood vessels and in turn stops the scarring of the macula from occurring.

Lucentis does have some side effects.  The side effects of using Lucentis to treat the eye disease macular degeneration can include endophthalmitis, a serious eye infection and detached retinas.  Other side effects of using this macular degeneration treatment include increased pressure in the eye, redness in the eye, sensitivity to light and pain.  If these symptoms occur or if macular degeneration patients notice changes to their vision, they should immediately consult their eye care professional.

Although uncommon, conditions asscociated with eye and non-eye-related blood clots may occur when Lucentis is used to treat wet macular degeneration.

Serious side effects related to Lucentis injections were rare.  This included serious eye infections, detached retina and cataracts.  Other uncommon side effects associated with Lucentis injections included inflammation inside the eye and increased eye pressure.

The most common eye-related side effects associated with Lucentis treatments for macular degeneration included red eyes, eye pain, small specks in vision, the feeling that something is in the eye and increased tears.  The most common non-eye-related side effects were high blood pressure, nose and throat infection and headaches after the injections of Lucentis.

While Lucentis is FDA approved for wet macular degeneration treatments and it has been shown to improve vision in some patients, it is important to realize individual results may vary.

The biggest criticism against both Lucentis and GenenTech is the cost of the drug.  Lucentis costs approximately $1,600 – $2,000 per treatment when compared to $150 – $200 per treatment of Avastin.

Lucentis is currently the most effect drug used to treat wet macular degeneration.

Drugs such as Avastin, Lucentis and Macugen work by blocking the growth of problematic blood vessel growth in areas such as the eye when treating macular degeneration or in tumours when treating cancer.  The research by Dr. Ambati suggests that these anti-VEGF treatments may also harm people by blocking the growth of healthy blood vessels in healthy areas of the body.  The growth of such blood vessels is essential for things such as reproduction and healing.

Ambati has indicated that the problem occurs because these man-made molecules are created to target and “turn off” a disease causing gene that don’t function the way many scientists believe they do.  This research casts doubt on the effectiveness of Nobel Prize winning drugs that have been developed to treat both cancer and macular degeneration patients.  “This work really raises a very serious red flg,” Ambata said, when discussing his research.

Drug manufacturers have dismissed the study, even though it was published in the respected Journal of Nature.  The drug manaufacturers have indicated that patients who have taken the macular degeneration drugs and anti-VEGF cancer drugs have been followed for several years and have shown no side effects.  Many of the drug manufacturers responsible for these anti-VEGF treatments have invested billions of dollars in research and are quick to point out that clinical trials have shown no indication of what Dr. Ambati suggests in his research.

Granted that clinical trials have indicated some risks, doctors and eye care professionals should educate both themselves and their patients on the potential risks associated with these macular degeneration drugs.

According to the research there is a biological pathway that may block the development of abnormal blood vessels and leakage that is associated with wet macular degeneration.  This discovery may provide some insight into the cause of macular degeneration that could lead to alternative treatments for the eye disease.

The lead researchers Dr. Dean Li and Dr. Kang Zhang, the presence of this protein on blood vessels may provide clues as to what is causing macular degeneration.  The research team managed to mutate this protein gene in mice and then observed behaviour of cells in response to the growth factor VEGF in the presence and absence of its binding partner, another protein called SLIT2.

Normal VEGF is responsible for the growth of normal vascular materials.  It has also been shown to lead to the development of age-related macular degeneration.  “What we are saying is the cells of the blood vessels have a protein receptor, and this is called Robo4, and if you activate the Robo4 receptor by giving it a protein that binds to it, the blood vessel cells know the cells shouldn’t leak and grow,” Dr. Li stated.

This potential cause of macular degeneration and the presence of VEGF have been targeted by anti-VEGF drugs such as Avastin, Lucentis and Macugen.  These macular degeneration drugs target the production of VEGF.

This new discovery may not only unveil other potential causes of macular degeneration, but may also allow for the development of alternative drugs that may treat the eye disease.  Developing mechanisms to inhibit the role of VEGF in macular degeneration patients may prevent progression of the disease or lead to an eventual cure.