Perhaps some of the most exciting research in the field of AMD these days is the search for an eye drop treatment for the disease.

Currently, the frontline treatment for wet AMD consists of repeated injections of drugs into the eye. While highly effective, this mode of delivery leaves alot to be desired. Not only is there the inconvenience and expense of repeatedly undergoing intravitreal injection, but also the risks inherent in getting an injection directly into the eye.

This has led scientists to search for a better way to deliver medication to the macula. For most people, an eye drop represents the most convenient way to take an eye medication. Therefore, there is great interest in developing an eye drop treatment for macular degeneration.

Currently, there are 4 eye drops undergoing phase II FDA clinical trials for the treatment of AMD. Three of the eye drops are treatments for neovascular AMD and one is a treatment for dry AMD. While these drugs are still relatively early in the development process, we may soon be able to put away the syringes and instead prescribe an eye drop to prevent vision loss caused by this potentially devastating disease.

Print version

If you could find out now whether you're likely to have a deadly disease in the future... would you want to know? That's the debate behind DNA testing. Recently, when I agreed to have my own DNA tested, I thought at first, "this is no big deal. I'll probably not go to find out I'm at risk for some incurable illness".

Then I got an e-mail stating that my results were ready and I could view them online. As I got set to enter my password, I have to admit the reality of what I was about to find out really struck me. What if I was at risk for something serious, say a form of cancer, and there was nothing I could do about it?

I went to the first category, "Aortic Aneurysm"...my risk was exactly normal...I relaxed and thought the rest of the test will go this way. I was wrong. I clicked on the very next category, "Age Related Macular Degeneration" and saw that my risk level was 20%, more than TWICE the normal rate. It couldn't have been a more chilling result for me.

Did I feel better that the results for the rest of the categories were normal? Yes, I was relieved my risk for Alzheimer's was even lower than normal, also for colorectal cancer and even heart attack.

But my mind kept focusing on the Macular Degeneration risk. I know the DNA test result doesn't adjust for family history which is a major factor, but it's still something I'm very conscious of right now. This is one of the major arguments against this type of self-testing: that you over-interpret the results and that different results don't translate directly into your actual risk of getting a serious illness.

Should you take the test? It does cost $985 although there are others that are cheaper (and some that are more expensive). Ultimately the decision comes down to whether you believe any information that can make you a more informed patient is beneficial or whether you think reading your own test results without the proper perspective just leads to needless worry. As for me, I'm glad I took the test...but I don't think I'll be doing it again soon!

Print version

The results of the AREDS study demonstrated a statistically significant benefit for their high-dose antioxidant nutritional supplement in providing a moderate reduction in the risk of developing advanced AMD. Specifically, the risk for progression was reduced by 25% for the entire study population and 34% for those patients with intermediate or advanced dry AMD.

It is now recommended that persons with intermediate AMD (bilateral large drusen) or those with advanced AMD (neovascular AMD or geographic atrophy) in one eye consider taking the AREDS-type formulation. For persons with early AMD, however, the AREDS-type supplements did not demonstrate any benefit.

During the course of AREDS, beta-carotene was demonstrated to increase the risk for lung cancer in smokers. Therefore, the AREDS formulation is not recommended for smokers.

AREDS participants were asked for details of their dietary habits on a food-frequency questionnaire. It was found that dietary lutein intake was associated with a lower rate of neovascular AMD, geographic atrophy, and large or extensive drusen. It was also found that omega-3 fatty acid consumption was associated with a decreased risk for neovascular AMD and central geographic atrophy (CGA). Omega-3 fatty acids come from fish. Persons with higher fish consumption had a lower rate of neovascular AMD. Persons with bilateral drusen who reported the highest levels of omega-3 intake had a 50% decreased likelihood of progression to CGA

Because of these findings, the AREDS2 study was designed to evaluate whether these nutrients can prevent advanced AMD. The primary objective of AREDS2 is to determine whether oral supplementation with macular xanthophylls (lutein at 10 mg/day plus zeaxanthin at 2 mg/day) and/or omega-3 fatty acids (DHA 350 mg and EPA 650 mg) will decrease the risk for progression to advanced AMD

Results from AREDS2 are not expected for at least 5 years.

Print version

Researchers have found that antioxidants disrupt a link between two processes in the retina that, in combination, contribute to macular degeneration.

The "destructive synergy" that causes macular degeneration occurs when a buildup of a compound called A2E disrupts energy production in mitochondria, the "power plants" in cells, the researchers said. The lack of energy interferes with daily cleaning and maintenance of photoreceptors and the retinal pigment epithelial cells. This leads to more buildup of A2E and a continuing cycle that results in the destruction of the vital visual cells that can't be replaced.

A2E is a constituent of lipofuscin, a toxin that is known to normally accumulate in the retina with age and is believed to play a significant role in the pathogenesis of
AMD.

Experiments using retinal cells from humans, rats and cows showed that antioxidants could completely counter the damage caused by this process, said the researchers.

"The implication is that people at risk of macular degeneration could help prevent the disease by consuming antioxidants," study author said.

Another research paper published last month reports that vitamin A supplements may accelerate lipofuscin accumulation in the retina.

Also last month, Acucela and Otsuka Pharmaceuticals announced that they have entered into an agreement to co-develop a drug called ACU-4429, that acts to prevent accumulation of A2E in the retina.

WHAT IT MEANS TO YOU: The normal aging process results in the accumulation of toxic lipofuscin (A2E) in the retina. This process may be accelerated by dietary supplementation with vitamin A. Antioxidants (lutein, fish oil, vitamins C and E, etc) help to counter the toxic properties of lipofuscin. Soon, we may have access to a drug that prevents the accumulation of lipofuscin. But until then, make sure you are getting plenty of antioxidants in your diet.

Print version

A new data analysis from the Beaver Dam Eye Study suggests a lower 5-year incidence of early AMD in patients born more recently, compared to similarly aged persons born in earlier or examined in an earlier period. These observations would suggest that there is a decreasing incidence of AMD. The reason for the observed decline of early AMD is unknown.

The investigators had collected demographic and clinical data at four examination visits in 5-year intervals, from between 1988 and 1990, 1993 and 1995, 1998 and 2000, and 2003 and 2005. Year of birth was used to categorize birth cohorts, ranging from between 1903 and 1907 to 1938 and 1942. Over 6000 persons participated in the study.

After controlling for age, smoking, blood pressure and other risk factors for the disease, the investigators identified a lower 5-year incidence of early (but not late) AMD in later birth cohorts than in earlier birth cohorts.

The investigators write "observed differences in health care changes (e.g., better control of blood pressure, use of antihypertensive agents) and lifestyle changes (e.g., less smoking) over the previous 15 years do not explain these findings. It is not clear whether other exposures earlier in life (e.g., infectious disease outbreaks such as the flu pandemic of 1918), dietary restrictions specific to a period (e.g., the Great Depression), or other unmeasured factors during later life may explain these birth cohort and period differences.

WHAT IT MEANS TO YOU: It is good news that fewer people are developing AMD today than in years past. But the reason for this apparent decline is puzzling given what we know about the disease. Smoking is the largest known modifiable risk factor for the disease, and fewer Americans smoke today than in years past. However, the investigators controlled for this and other known risk factors for the disease. Therefore, we are left with the prospect of some unknown risk factor that is less prevalent today than in the past. Identification of this unknown variable may help us better understand the disease, and help assure that the incidence of AMD continues to decline.

Print version

Patients visiting an ophthalmologist report that prayer is important to their well-being and that God plays a positive role in illness, according to a recent survey.

"Ethical medical practice includes physician behavior, beyond technical competence, that promotes healing and optimizes the patient's welfare," the authors write. "For many patients, religion and spirituality is important to their value system and may represent a unique source of motivation and coping with life events, including the experience of personal illness."

The investigators distributed a brief questionnaire to 124 patients visiting the office of a single ophthalmologist. The 14-question survey was completed by the patient and collected without any identifying information, so patients could be assured the answers would not affect their care.

Most believe either that illness is a way to make one stronger (32.3 percent) or that it is a mystery (36.3 percent) rather than a punishment from God (4 percent) or a test (22.6 percent).

69.4 percent reported that prayer was very important to their sense of well-being. 58.1 percent report that God can directly help physicians treat illness.

"The data obtained from this questionnaire suggest that patients' expressions of religion and spirituality should be assessed and acknowledged by their ophthalmologist," the authors write. "Obtaining a brief religious and spiritual history [can] add to an understanding of the patient's value system, provide the patient with a greater sense of trust in the physician and assist in the healing process, especially when a cure is not possible."

WHAT IT MEANS TO YOU: Spirtuality, prayer, and faith is a well-recognized and time-honored part of the healing process that has long held a important place in the practice of medicine. However, it is unusual to see it addressed in eye care. There is no good reason for this omission. This survey reminds ophthalmologists and optometrists that our patients rely upon their faith to help them cope with vision loss and blindness, and that by acknowledging and encouraging expressions of faith we can help patients better deal with their illness.

Print version

A new study reports that close monitoring of patients with AMD can improve the ability to detect choroidal neovascularization (CNV) while it is still outside the fovea and vision is still good.

Bilateral involvement is common in neovascular AMD, with approximately 10% of second eyes developing CNV each year through at least the first 5 years after development of CNV in the first eye. Therefore, patients with AMD are often advised to monitor their vision closely with an Amsler grid to detect the earliest symptoms of CNV.

Results of 5 or more years of follow-up data from 1052 participants in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT) were analyzed. These individuals had bilateral drusen and visual acuity of 20/40 or better at beginning of the study period.

CNV developed in 282 eyes of 225 patients during the follow-up period. Approximately 100 (35%) of the cases of CNV were detected between regularly scheduled examinations when patients reported symptoms or if their ophthalmologist wanted to see the patient more frequently than annually.

At the time of detection, 153 (54%) were subfoveal, and 157 (56%) were less than or equal to 2 disc areas in size. Visual acuity was 20/40 or better in 123 (69%) of 179 eyes with visual acuity measured at the time of detection.

The investigators conclude that when patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

The authors write "close monitoring of high-risk eyes, such as fellow eyes in patients with unilateral CNV or eyes with multiple large drusen and pigmentary changes, can lead to detection of CNV when it is more likely to be outside the fovea, relatively small, and without a large loss in visual acuity. Regular retinal examinations, optical coherence tomography, preferential hyperacuity perimetry, and use of the Amsler grid may aid in early detection of CNV."

WHAT IT MEANS TO YOU: It is extremely important that patients at risk for CNV check their vision regularly for symptoms of CNV. With currently available treatments (such as Lucentis), it is very likely that vision can be improved (or at least maintained) after CNV is found and treated. Nowadays, much of the vision lost to CNV is lost prior to the initiation of treatment. If CNV is found early, while vision is still good, the good vision can usually be maintained.

Print version

New research into the genetics behind dry macular degeneration has lead the authors of a new study to speculate that a naturally occurring virus may trigger the onset of geographic atrophy.

A team of researchers used gene-association studies to reveal links between an immune protein, toll-like receptor-3 (TLR3), and a form of dry AMD called geographic atrophy. They uncovered a protective TLR3 variant that is less active in people without the disease, suggesting activation of TLR3 may play a role in the development of geographic atrophy.

The research team found a variant of TLR3 called rs3775291 that offered protection from geographic atrophy. Subsequent experiments suggested that rs3775291 decreased TLR3 activity.

The scientists speculate that a naturally occurring virus could activate TLR3 and trigger geographic atrophy.

"If you are genetically susceptible to macular degeneration and are exposed to a virus that activates TLR3, it could lead to the death of cells in the macula," the researchers said.

WHAT IT MEANS TO YOU: We currently do not have any effective treatment for dry AMD. These findings pave the way for using TLR3 inhibitors as a potential new therapy for geographic atrophy.

Print version

Prof. Leonid Yaroslavsky, from Tel Aviv University, believes that humans may have an ability to "see" colors and shapes with their skin. His scientific model may also explain how this controversial primordial instinct, which is observable in some plants and animals, might have evolved over millions of years. "Some people have claimed that they possess the ability to see with their skin," says Prof. Yaroslavsky. Though biologists usually dismiss the possibility, there is probably a reasonable scientific explanation for "skin vision." Once understood, he believes, skin vision could lead to new therapies for helping the blind regain sight and even read. Skin vision in humans is likely a natural atavistic ability involving light-sensitive cells in our skin connected to neuro-machinery in the body and in the brain, explains Prof. Yaroslavsky.

Print version

The retrospective study published in the journal Retina analyzed 26 eyes of 26 patients with CNV secondary to pathologic myopia followed for at least 3 months following Lucentis therapy. At 1 month, 31% of the eyes had an improvement in visual acuity of 3 or more lines. A significant reduction in ocular coherence tomography central thickness was observed. No cases of severe visual acuity loss occurred, and no systemic or ocular side effects were registered during the follow-up. The authors conclude that short-term results of Lucentis therapy for myopic CNV are encouraging.

Print version

It has been suspected that crowding, the adverse spatial interaction due to the proximity of adjacent targets, may explain slow reading speeds by persons using their peripheral vision, as happens when the central vision is damaged by macular degeneration. Previously, research has shown that increased line spacing improves reading speed in normal subjects without macular degeneration. The research paper, published in Optometry and Vision Science, found that reading speeds of persons with AMD were virtually the same regardless of line spacing.

Print version

A new study finds that Avastin is able to quickly penetrate the retina of monkeys. One of the key motivations Genentech developed Lucentis was that scientists were concerned about how well Avastin, a relatively large molecule, could penetrate the retina. Lucentis, was specifically designed to penetrate the retina rapidly. *** A retrospective study of consecutive patients receiving Avastin found that retinal pigment epithelial (RPE) tears, all with preexisting RPE detachments, was the most common adverse event. Other adverse events were rare and included retinal ischemia, subretinal hemorrhage, vitreous hemorrhage, ocular irritation or pain, worsened hypertension, and headache. No death or thromboembolic events were observed. *** A case report of a patient undergoing Avastin therapy developing sterile enophthalmitis appeared in the literature. After successful treatment of the enophthalmitis with steroids the patient was able to resume treatment of their wet AMD with Macugen. *** Read more about these and other stories at myvisiontest.com.

Print version

A retrospective case series published in the journal EYE reviewed the records of 40 patients with polypoidal choroidal vasculopathy (PCV) which had photodynamic therapy (PDT) with verteporfin. Seven of 10 eyes (70%) with juxtafoveal lesions and 17 of 31 eyes (54.8%) with subfoveal lesions had stable or improved vision (loss of less than 3 lines) at the last follow-up. Thirty-three eyes (80.5%) had dry, quiescent scars at last follow-up, six eyes (14.6%) had persistent leakage, and two eyes (4.9%) had evidence of choroidal neovascularisation. The investigators conclude that a majority of patients with maculopathy secondary to PCV treated with PDT had stable or improved vision.

Print version

Last month NICE recommended NHS coverage for Lucentis for treating wet AMD in the United Kingdom. The final NICE guidance includes a reimbursement plan under which the U.K. National Health Service will subsidize the first 14 injections in each eye affected by the disease and Novartis will reimburse costs for any additional Lucentis injections. Meanwhile, there is an ongoing battle for anti-VEGF coverage in Alberta. Alberta Health says they are still reviewing information and have not made a decision about covering the cost of either Lucentis or Avastin in this Canadian province.

Print version

The designation allows the company to accelerate clinical development of its continuous, long-term release formulation of the therapeutic protein Ciliary Neurotrophic Factor (CNTF), designed to be released into the vitreous body from a proprietary Encapsulated Cell Technology (ECT) device, known as NT-501, for the treatment of dry AMD. ECT implants consist of cells that have been genetically modified to produce a desired therapeutic factor that are encapsulated in a section of semipermeable hollow fiber membrane. The hollow fiber membrane is designed to promote long-term cell survival of the implanted cells. The cells continuously produce the therapeutic protein which diffuses out of the implant into the vitreous cavity. NT-501 is designed to continually deliver a low, safe and therapeutic dose of CNTF into the vitreous cavity. The Company believes that CNTF activates dying retinal photoreceptors and protects them from degeneration.

Print version

A retrospective study found that the antiangiogenic factor vasohibin is expressed in the choroidal neovascular membranes of patients with AMD and polypoidal choroidal vasculopathy (PCV). Tissues removed from 11 patients with AMD and PCV were tested for VEGF and vasohibin. "Eyes with a lower vasohibin-to-VEGF ratio tended to have larger subretinal hemorrhages or vitreous hemorrhages, whereas eyes with higher vasohibin-to- VEGF ratio had subretinal fibrosis-like lesions," the authors said in the August issue of American Journal of Ophthalmology. The investigators speculate that vasohibin may provide an alternative target for antineovascularization therapy.

Print version