It has been noted that atherosclerosis and age-related macular degeneration (AMD) share common risk factors, such as smoking and obesity. However, it is curious that most epidemiologic studies have failed to find an association between the presence of atherosclerosis and AMD.

This month, data from the Beaver Dam Offspring Study (BOSS) reported an association between HDL cholesterol (so-called "good" cholesterol) and the risk of early AMD.

In this study, higher serum HDL cholesterol level was associated with lower prevalence of early AMD. The protective effect of serum HDL cholesterol level was an approximate 10% reduction in the odds of having AMD per 5 mg/dL increase in HDL level.

Yet, most epidemiological studies have failed to find such an association between cholesterol level and AMD. Furthermore, most studies have failed to find a protective effect of statins on AMD. (Statins are medications that lower LDL, or "bad", cholesterol.)

Nonetheless, there is convincing evidence that AMD is, at least in part, related to one's vascular health. For example, the only treatment to date with a proven ability to prevent the onset of early AMD is folic acid. The beneficial effect of folic acid is related to its ability to lower homocysteine, a chemical in the body that damages - you guessed it - blood vessels.

It is possible that the murky relationship between AMD and atherosclerosis is due to the fact that while there may be a common underlying pathology - oxidative stress - there are also many variables, including genetic makeup and environmental exposures, that determine how a given person reacts to this pathology.

Only by understanding and accounting for these many variables can we truly understand the relationship between AMD and vascular health.

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The most common genetic disease in humans may also be a cause of macular degeneration, Medical College of Georgia researchers report.

They are pursuing a link between hemochromatosis, which results in iron overload, and the wet form of AMD. They suspect that too much iron hastens normal aging of the eyes. If they are correct, donating blood a couple times annually to reduce iron levels could decrease the risk of developing neovascular AMD.

Humans, like most animals, have no means to excrete excess iron. Excess iron accumulates in tissues and organs disrupting their normal function. Hemochromatosis is most common among those of Northern European ancestry, in particular those of Celtic descent. Blood tests help make the diagnosis.

"If [hemochromatosis] is a predisposing risk for macular degeneration, we have a very useful tool for screening patients," said Dr. Julian Nussbaum, a retinal specialist.

Researchers have developed animal models for hemochromatosis. In the retina of these animals they are finding increased expression of VEGF, a key component of wet AMD.

Healthy people usually absorb about 10 percent of the iron contained in the food they eat, which meets normal dietary requirements. People with hemochromatosis absorb up to 30 percent of the iron. Over time, they absorb and retain between five to 20 times more iron than the body needs.

WHAT IT MEANS TO YOU: Research that has identified high iron levels within the retina as a contributor to the development of AMD. Iron is essential for good health, but it is a potent generator of oxidative stress. Retinal iron levels increase as part of the normal aging of the eye, and it is suspected that the increased oxidative stress of iron overload contributes to the development of AMD. One research study found that a diet high in red meat increased the risk of AMD. This would be consistent with the hypothesis that excess iron consumption contributes to the development of AMD. It is recommended that persons at risk for AMD should avoid eating a diet high in red meat, and not take iron supplements unless there is a medical need, such as iron deficiency anemia. Persons with abnormally elevated iron levels should take steps to lower their iron, such as donating blood regularly.

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Decreased levels of serum VEGF were recorded following intravitreal injection of Avastin, indicating that Avastin does enter the general circulation and may therefore affect systemic health.

There continues to be a concern regarding the long term health consequences of intravitreal anti-VEGF therapy. VEGF plays an important role in many parts of the body and is essential to good health. If sufficient amounts of intravitreally injected Avastin were to find its way into the systemic circulation, then it might be expected to have adverse health consequences.

In this study 11 eyes of 11 patients received an injection of Avastin (1.25 mg). Samples of blood were collected just before the injection, and after 1 day, 7 days and 1 month.

The serum VEGF concentration before the injection was 114.0 pg/ml. It was significantly reduced to 9.7 pg/ml after 1 day, to 11.7 pg/ml after 7 days and to 25.9 pg/ml after 1 month.

The investigators conclude that Avastin enters the general circulation after intravitreal injection.

WHAT IT MEANS TO YOU: Long-term use of any medication carries a risk of adverse health effects. For example, long-term aspirin use can contribute to the development of stomach ulcers. It is not known whether the long term use of anti-VEGF drugs leads to any significant risk of systemic adverse effects, in part because we do not know whether there is sufficient systemic exposure to the drug following intravitreal injection. A meta-analysis of data from three large clinical trials found that Lucentis (ranibizumab) is associated with a small increased risk of stroke, but other studies failed to find such a risk. The current study suggests that sufficient amounts of Avastin is reaching the systemic circulation following intravitreal injection to significantly lower serum VEGF levels. Hence, it is possible that these lower VEGF levels could result in undesirable side effects. It is expected that the large NIH-sponsored clinical trial known as CATT will uncover any significant systemic adverse effects associated with intravitreal Avastin use.

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Monthly Lucentis injections do not reduce the rate of choroidal neovascularization (CNV) development in untreated fellow eyes, according to a new study.

There are concerns regarding the risk of systemic adverse effects from the long-term use of anti-VEGF drugs in the treatment of neovascular AMD. It is known that a small amount of the drug injected into the eye will enter the general circulation. It is reasoned that among the possible effects of systemic exposure to anti-VEGF drugs would be to deter the onset of CNV in the fellow eye of patients with unilateral AMD

This study retrospectively reviewed data from randomized, controlled clinical trials to determine the rate of onset of CNV in the fellow eyes of patients with unilateral wet AMD. Patients treated with monthly Lucentis were compared with those receiving a sham injection (MARINA) or photodynamic therapy (ANCHOR).

The researchers found that differences in conversion rates at 12 and 24 months between the patients receiving Lucentis and respective controls (sham or photodynamic therapy) were not statistically significant.

The investigators conclude that monthly intravitreal Lucentis injections do not have an effect on the rate of new CNV development in the fellow eye.

WHAT IT MEANS TO YOU: This study failed to find a protective effect of monthly Lucentis therapy on fellow eyes. This means that an insufficient amount of Lucentis is reaching the systemic circulation to have a deterrent effect on the development of CNV in the fellow eye. This is good news for patients because if there is not enough Lucentis reaching the general circulation to benefit the fellow eye, then it is less likely that there is enough to cause adverse effects elsewhere in the body.

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Intravitreal injection of Avastin (bevacizumab) is associated with a low but significant risk of acute intraocular inflammation that may result in significant visual loss, according to a new study.

Acute intraocular inflammation is a well recognized and potentially severe complication of intravitreal Avastin. In previous reports its incidence has ranged from 0.14% to 1.49%. Patients typically present within the first few days postoperatively with complaints of decreased vision and floaters. Even with aggressive treatment, long-term visual outcome can be poor.

The exact cause of the inflammation is not fully understood. It is generally thought to be an immunological response to the drug or to contaminants introduced during the manufacturing or compounding process.

The investigators reviewed the records of all patients with severe anterior chamber inflammation and/or vitritis after Avastin injections that were performed by a single surgeon in Ontario, Canada.

In this series of 689 consecutive injections the incidence of post-Avastin inflammation was 1.30%, which is on the high end of the range of previously reported estimates.

The final visual acuity of all patients was worse than at the time of injection. In addition, these patients lost an average of 6 lines of visual acuity despite having only mild to moderate visual loss before injection.

The investigators state that their findings emphasize the potentially serious nature of acute inflammation following intravitreal Avastin and its potential deleterious effect on vision.

WHAT IT MEANS TO YOU: This is a very disturbing report on the potentially severe vision loss that can occur following Avastin-associated intraocular inflammation. While there are numerous reports of a toxic anterior segment syndrome (TASS)-like reaction following intravitreal Avastin injection, this is the first that we have encountered that reports such a grave prognosis for vision loss. What causes this syndrome is still a mystery, but it is believed to be a contaminant introduced during the manufacturing process. There are few reports of it following Lucentis injection.

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Choroidal thinning is a risk factor for myopic CNV (mCNV), according to a new study published in Investigative Ophthalmology and Vision Science. The mechanism of mCNV is still controversial. The incidence of mCNV does not have any consistent association with axial length. Lacquer crack is a confirmed risk factor for mCNV. They are mechanical cracks at the RPE/Bruch's membrane, indicating the presence of mechanical stress at the RPE/Bruch's membrane level. Enrolled in this study were 23 consecutive patients with bilateral high myopia and unilateral newly developed mCNV and a normal macula in the fellow eye. The parameters in the affected and fellow eyes were compared. Choroidal thickness was measured using spectral domain OCT. Choroidal thickness was significantly lower in the affected eyes. Choroidal thinning is a hallmark of high myopia. The present study found that choroidal thinning is more prominent in eyes with mCNV. It is unknown how choroidal thinning increases the risk of mCNV development.

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The U.S. Food and Drug Administration has approved Lucentis for treatment of macular edema due to retinal vein occlusion, Genentech announced in a press release. The approval is based on recently published data from the BRAVO and CRUISE trials. In the BRAVO trial, patients with branch retinal vein occlusion treated with 0.3-mg of Lucentis improved a mean 16.6 letters in visual acuity from baseline, and patients treated with a 0.5-mg dose improved a mean 18.3 letters. Patients who received a sham injection improved a mean 7.3 letters. In the CRUISE trial, 392 patients with central retinal vein occlusion received either 0.3-mg Lucentis, 0.5-mg Lucentis or sham, mean change in BCVA from baseline was 12.7 letters, 14.9 letters and 0.8 letters, respectively. "This approval provides an important new medicine for people experiencing the unexpected vision loss associated with macular edema following RVO," Hal Barron, MD, Genentech's chief medical officer, said in the release.

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The National Eye Institute has launched an ancillary study to its AREDS2 study comparing the ability of Notal Vision's ForeseeHome AMD monitor to aid the early detection of wet AMD to that of standard care, according to a joint press release from the National Eye Institute and Notal Vision. The ForeseeHome AMD monitor is the first ophthalmic device to receive U.S. Food and Drug Administration approval for the home monitoring of wet AMD. The device is programmed to transmit eye exam data to the patient's eye care physician, as well as to the Notal Vision Data Monitoring Center, the release said. AREDS2 is currently evaluating the ability of lutein, zeaxanthin and omega-3 fatty acids for slowing the progression of AMD-linked vision loss among 4,000 patients at moderate to high risk of developing AMD.

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Combination therapies generated greater visual acuity gains with fewer reinjections compared with Lucentis monotherapy in the phase 2 RADICAL study of patients with exudative AMD, according to a press release from QLT. Each combination therapy tested resulted in fewer re-treatments over 2 years compared with Lucentis monotherapy: mean 4.2 retreatments among the half-fluence triple therapy group, 5.8 retreatments among the quarter-fluence triple therapy group, 6.2 retreatments among the double therapy group (Lucentis plus PDT) and 8.9 retreatments in the monotherapy group. Visual outcomes among the groups were not significant. "Visudyne-Lucentis combination therapy significantly decreased the number of re-treatment visits required over 2 years, while patients' vision outcome was maintained within one line with an acceptable safety profile, compared with Lucentis alone," Henry Hudson, MD, one of the lead investigators in the study, said in the release.

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ThromboGenics' phase 3 trial evaluating microplasmin for the non-surgical treatment of focal vitreomacular adhesion has met its primary endpoint of resolving vitreomacular adhesion at 1 month, the company announced in a press release. Microplasmin is a vitreolytic enzyme which is currently being studied for the treatment of vitreomacular adhesion. An intravitreal injection of microplasmin may aid in releasing the posterior vitreous from the retinal surface and may yield complete posterior vitreous detachment (PVD) in some patients. "The ability to cure a significant proportion of patients with a range of retinal disorders, including macular hole, with a simple injection of microplasmin is clearly an attractive alternative to the current option of surgery," Matthew Benz, MD, said during a presentation of study results at the World Ophthalmology Congress.

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