Avastin® (bevacizumab) came into the market as a drug that could reverse the damage caused by wet macular degeneration. Until the approval of Lucentis as a treatment for macular degeneration, many doctors recommended Avastin® (bevacizumab). In fact, many doctors still prescribe and use Avastin as a treatment for macular degeneration because of its relatively low cost when compared to Lucentis.

How Viable is Avastin as a Treatment for Macular Degeneration?

According to the specialists, this prescribed medication is suitable to the eyes and within short span of time; patients will regain their vision and the damage caused by abnormal blood vessels associated with wet macular degeneration is reversed.

Traditionally, Avastin was used for those macular degeneration patients who had previously shown poor results with Visudyne® or Macugen®. In actuality, comparing to Visudyne or Macugen, Avastin will perform brilliantly and accurately to add more clarity and brightness to the vision, and patients shown considerable improvement in reversing the damage caused by wet macular degeneration.

It must be noted that Avastin as a treatment for macular degeneration will have no effect on Drusen deposits generally associated with dry macular degeneration. Avastin is a treatment for wet macular degeneration only, and patients who have availed of this treatment have shown a dramatic improvement in their central vision.

However, the doctors are still uncertain whether there is any negative impact resulting from the use of Avastin when treating macular degeneration. The abnormal growth of cells associated with the eye disease is for all intensive purposed reversed, but there are still questions of safety surrounding the use of this cancer drug in the eye.

While many studies have shown that Avastin is safe to use in the eye, its use for treating macular degeneration is still considered off-label.

As a treatment for wet macular degeneration, Avastin is injected into the eye. Because Avastin is an anti-VEGF drug the series of intravenous injections stops the growth of abnormal blood vessels associated with wet macular degeneration.

The normal dosage of the Avastin is 1.2mg, the same as other macular degeneration treatments such as Macugen.

?

Avastin as an Anti-VEGF Medication

Approved by the FDA as a treatment for cancer, Avastin is classed as an anti-VEGF drug in that it shrinks the abnormal blood vessels typically associated with cancer tumours. However, because wet macular degeneration is caused by abnormal blood vessels behind the retina, Avastin has shown to improve the damaged blood vessels and at the same time enhance the flow of the nutrients through blood stream.

Wet macular degeneration can be reversed using Avastin but not in the same dosage as associated with cancer treatments. A single dose of Avastin is broken down into smaller doses for use in the eye.

Avastin is a viable treatment for wet macular degeneration, costing less than other treatments and showing similar results afterwards.

Avastin (bevacizumab) and Lucentis (ranibizumab) were compared in a double-masked, randomized controlled trial.  Lucentis is the preferred macular degeneration treatment and is approved by the FDA.  Avastin is an off-label macular degeneration treatment and was originally approved to treat colo-rectal cancer.

Until this recent study, there was no data supporting which macular degeneration drug was effective.

In this study, the Veterans Affairs Boston Healthcare System funded a study where patients were enrolled by a 2 to 1 randomization to either the Avastin or Lucentis treatment.  Patients were given intravitreal injections of either Avastin or Lucentis every month for the first three months of the trial and evaluated after the third injection to determine if subsequent macular degeneration treatments were required.

It was shown that at six months, there was no difference in those patients treated with Avastin or Lucentis.

This adds fuel to the debate over which of the two drugs should be used to treat macular degeneration.  Genentech refused to conduct any trials of Avastin as a macular degeneration treatment stating that Lucentis is the FDA approved treatment for the eye disease.

However, Avastin costs approximately $40 per treatment while Lucentis costs approximately $2000 per treatment.  With some patients requiring multiple injections to treat their macular degeneartion, the costs associated with Lucentis treatments can be enormous.

As the debate over whether Lucentis or Avastin is better for treating macular degeneration, new research recently reveals that making the choice will be much more difficult.

In a retrospective chart review published in the British Journal of Ophthalmology, it appears that Lucentis or Avastin are equally effective at decreasing macular thickness and volume.  Avastin appears to last longer than Lucentis.

Does this mean that Avastin is better than Lucentis when treating macular degeneration patients?  Not necessarily.

Another paper published in the Graefes Archive of Clinical and Experimental Ophthalmology reveals that Avastin accumulates within retinal pigment epithelial (RPE) cells.  Lucentis however, does not accumulate.  Thus, the study concluded that there are substantial differences in the pharmacokinetics of these two macular degeneration drugs.

A third study published in Investigative Ophthalmology and Vision Science reported that higher does of Avastin resulted in higher cell death of photoreceptors.  This study compared Avastin treatments with Macugen treatments.  Lucentis was not considered as part of this study.

Researchers concluded that the destruction of photoreceptors may be important for patients suffering from a variety of eye diseases, including macular degeneration and diabetic retinopathy, especially if Avastin treatments were continuing for a period of time.

Other studies in whether Lucentis or Avastin is better for treating macular degeneration are continuing.  The debate will continue especially since the cost of these two drugs is substantial.

 Tachyphylaxis, or the densensitization of the body to the drug being used, results in a loss of effectiveness of the drug over a period of time. When drugs such as Avastin have to be used over a prolongued period of time. It is thought that this desensitization will occur more frequently when drugs are used with a single target in mind. This is the case with using Avastin to treat macular degeneration. Avastin is used to target the growth of abnormal blood vessels associated with the eye disease.

The researchers reviewed a series of 59 patients whose macular degeneration was treated with the drug avastin. The study took place over a 14-month period and identified those patients that had demonstrated a loss of effectiveness of the drug avastin. Patients were treated with the drug and the effectiveness measured using an OCT.

5 patients were identified to have developed a decreased effectiveness to Avastin when it was used to treat their macular degeneration. Increased dosage did not restore the effectiveness of the drug, and it was apparent that these patients had developed some degree of resitance to Avastin.

It was noted that the median time to develop tachyphylaxis was 100 weeks and the medium number of Avastin treatments to develop the reistance was 8 treatments. This leads to great concern because typically macular degeneration patients require prolongued treatments with anti-VEGF drugs such as Avastin and Lucentis. This means an increased drug resistance over a period of time and eye specialists must ensure that injects of drugs such as Avastin are kept to an absolute minimum.

Further research into the development of a a drug resistance to Avastin when used to treat macular degeneration is ongoing. It is hoped that this desensitization can be reduced by combining Avastin with na intravitreal steroid.

However, unlike those drugs, Avastin is not approved by the FDA for intravitreal uses for macular degeneration.  Because of this, it has not been subjected to the same rigorous safety testing that both Lucentis and Macugen have gone through.  Avastin as a treatment for wet macular degeneration continues to be an off-label use of the drug.

In the most recent study, 82 patients were selected with a mean age of 67 years. These patients were divided into two groups: group A comprised patients who had hypertension and were under medication with antihypertensive drugs and group B composed of patients with normal blood pressure and therefore not on any drugs.  All subjects were graded according to their blood pressure levels before a single intravitreal dose of Avastin (0.05 ml; 1.25 mg) administered. These patients had their blood pressure measured again at day 1, as well as at 1, 3, and 6 weeks following the injection of Avastin for wet macular degeneration.

The study showed that among persons with hypertension (group A), the systolic blood pressure levels showed significant increases at weeks 1, 3, and 6 compared with baseline. Similarly, diastolic blood pressure levels were significantly higher at weeks 3 and 6.   For those patients treated with Avastin who had no blood pressure problems, (group B), the mean systolic and diastolic blood pressures showed significant elevation only at week 3. The percentages of both group A and B patients with normal blood pressure decreased at week 3 compared with baseline.

Because of this, the researchers concluded that there was a risk of elevated blood pressure or persistence of hypertension in hypertensive patients after intravitreal Avastin injection for the eye disease macular degeneration.

This should raise concerns for patients who are treated with Avastin for their macular degeneration, especially if they have a history of high blood pressure.  As with any treatment, patients must make sure they consult a physician and be full aware of the risk associated with any drug treatment.

Public health authorities are trying to draw attention to the problem with the Avastin treatments for macular degeneration in hopes of determining if this is occurring across Canada.

The problem is believed to stem from a particular lot of the drug that was distributed widely around the world but not in the United States.  According to public health authorities in Canada, the affected lot of Avastin is lot number B3002B028.

Roche, the Swiss pharmaceutical company that manufactured the drug, has been cooperating with both Health Canada and the British Columbia Centre for Disease Control.  Ophthalmologists have already been alerted of the problem with Avastin that may be used for macular degeneration treatments.

Avastin, originally developed as a cancer drug, has not been approved for use as a treatment for Macular Degeneration.  Roche has indicated that it does not recommend using Avastin to treat macular degeneration.  According to Samantha Ouimet, a spokesperson of Roche Canada, “Absolutely we do not recommend this.  They’re taking it out of its packaging, repackaging it and injecting it into people’s eyes.  This comes in a bag and it’s meant for intravenous use for people with cancer.”

Roche has resisted warning people to not use Avastin as a treatment for macular degeneration because the statement could be interpreted as promoting the off-label use of the drug to treat the eye condition.

The problem with the Avastin treatments were first detected in October 2008 when British Columbia ophthalmologists began detecting problems with people treated with Avastin for macular degeneration.  These patients began experiencing acute intra-ocular inflammation at rates much higher than was previously known.  After an investigation, it was noted that the rate was almost 10 times higher among patients treated with Avastin from the lot in question.

According to officials, there are no problems reported with using Avastin as a macular degeneration treatment in other countries and no reports of problems in cancer patients who received treatments of Avastin from the same lot.

The inflammation caused with the treatment of Avastin causes cloudy vision, but appears to clear up after a short period of time.

Roche has indicated that there have been no problems discovered in the production process used for the lot of Avastin and that there has been no problem determined with the vials of drug either.  The investigation is ongoing.

Macular degeneration is the leading cause of blindness in the elderly, and Avastin has been used for some time as an off-label treatment for wet macular degeneration.

In an uncontrolled study that examined 16 patients with wet macular degeneration that were treated with intravenous Avastin, it was shown that no serious systemic or ocular adverse events were identified.

In the study, one-half of the patients recieved a higher dose of Avastin (5 mg/kg) and the other half received a reduced dose of Avastin (2.5 mg/kg).  All the patients had received three initial intravenous infusions of Avastin at 2-week intervals.

No serious systemic or ocular adverse events were identified following the injections of Avastin.  It was also shown that there were no statistical differences between both treatments of Avastin.  Both groups of patients suffering from macular degeneration had shown significant improvement in visual acuity and reductions in macular thickness that were sustained through 6 months.

The study authors have concluded that the visual acuity, optical coherence tomography and angiographic improves shown through the course of 6 months was evidence enough to follow-up and evaluate the long term durability of using Avastin as a treatment for macular degeneration.

This study showing that Avastin is safe as a macular degeneration may help eye care professionals promote the use of this drug when treating the eye disease.

As with other drug treatments for a variety of diseases, the body tends to become desensitized to the drug, causing it to lose its effectiveness over time.  This is referred to as tachyphylaxis, and is a major problem when any drug, not just Avastin, is used for prolonged periods of time.

In this latest study of Avastin as a treatment for macular degeneration, investigators examined the records of patients who had received injections of Avastin alone, an intravitreal steroid alone, or a combination of both Avastin and the steroid.

The investigators determined that the effectiveness of Avastin treatments for macular degeneration decreased, indicating that there may be a tachyphylatic response to the drug.  Using a steroid in combination with Avastin was shown to partially alleviate this affect.

In the study, it was indicated that repeated injections of Avastin to treat macular degeneration appeared to be associated with decrease bioefficacy.  They also concluded that when using Avastin with a steroid, the effect was lessened.

With Avastin treatments for macular degeneration costing much less than the FDA approved treatment Lucentis, this may not be great news for patients who have no coverage for the more expensive drug.

A series of patients with wet macular degeneration were treated with avastin each month.  Injections of Avastin were used as long as there was evidence of activity on flourescein angiography (FA) and optical coherence tomography (OCT).  All patients in the study were followed for a period of six months during their treatment with Avastin for their wet macular degeneration.

The study showed that visual acuity changed from 0.74 logMAR to 0.68 logMAR at 6 months, but was only statistically significant in patients with macular degeneration in the early stages.  The changes in retinal thickness and total lesion size were significant in both groups (early and advanced wet macular degeneration) at all times during the follow-up after being treated with Avastin.

The study investigators concluded that Avastin treatments for macular degeneration were significant for improving vision in macular degeneration patients with newly diagnosed lesions, and not an effective treatment for advanced wet macular degeneration.

The investigators indicated that more study was required to determine which candidate of patients would benefit from anti-VEGF treatments of macular degeneration such as Avastin.

The preliminary data reported at the American Society of Retina Specialists indicate that there is a difference between Avastin (bevacizumab) and Lucentis (ranibizumab) as a treatment for Macular Degeneration.  The difference is in the short-term biological effect and in the durability of activity.  This leads to differences in remission intervals in patients treated with Avastin or Lucentis for wet macular degeneration.

In a retrospective study of 52 patients that had been treated with Lucentis and 68 patients that had been treated for macular degeneration with Avastin, it was shown that the mean remission times were 6.6 months for Avastin and 3.8 months for Lucentis.

Using optical coherence tomography (OCT) to conduct qualitative analysis, the recurrence of choroidal neovascular activity in wet macular degeneration was found after treatments of either Avastin or Lucentis.

Dr. Chang and his colleagues who completed the study indicated that the advantage of Lucentis as a treatment for macular degeneration was in its short-term biological effect.  The advantage of Avastin as a treatment for macular degeneration is in its durability of activity.