The study estimates that the National Health Service could save £84.5 million ($130 million) annually by switching from Lucentis to Avastin. Avastin is already used to treat wet AMD in some parts of the UK and extensively elsewhere in the world and also for other eye conditions.
Six hundred ten people with wet AMD were included in IVAN, which is one of the largest ever carried out in the field of eye disease in the UK. Patients received injections of the drug into the affected eye every month for the first three months. Patients were then subdivided to receive the injections at every visit (monthly group) or only if the specialist decided there was persistent disease activity (as-needed group).
The two-year results show that sight was equally well-preserved with either of the two drugs. Giving the treatment regularly every month resulted in slightly better levels of sight, which was detected through testing of near visual acuity and contrast sensitivity. The as-needed group received on average 13 injections over the two year period compared to 23 for the monthly treatment group. However, continuous treatment caused a higher proportion of eyes to develop a condition known as geographic atrophy, a thinning of the retina and its blood supply.
Professor Usha Chakravarthy of Queen’s University Belfast’s Centre for Vision and Vascular Science, who led the research study team said: “The IVAN results at the end of year two show that Lucentis and Avastin have similar functional effectiveness regardless of the drug received. With respect to monthly versus as-needed treatment, while there was marginally better eyesight in the former, the development of atrophy is a matter of concern in the longer term.”
Serious adverse events, which included death, heart attacks, strokes, and any other event that was life threatening, disabling or resulted in hospitalization, were similar for the two drugs. However, deaths occurred less frequently in the group that received monthly treatment, although there were fewer deaths overall among people taking part in the trial than were expected based on their age and gender and national death rates. When these safety results were combined with those of a similar study called the CATT trial in the United States, the findings continued to indicate fewer deaths when treatment was given monthly.
Photoreceptors Successfully Produced in Lab
For the first time, light-sensing photo-receptor cells have been grown from scratch in the lab, and then successfully transplanted into the eyes of blind mice.
The transplanted cells successfully matured and connected with nerves that transmit visual signals to the brain.
The researchers say that if the procedure can be repeated with human stem cells, they believe they can cure most forms of blindness that result from degeneration of these photoreceptor cells, due to either the effects of aging or diseases.
“We can treat a really broad range of patients,” says Robin Ali of University College London, head of the team that performed the transplant.
Another experimental stem-cell treatment, one involving a transplant of cells that support and nourish photoreceptors in the eye, has restored the sight of a man blinded by the degeneration of his retinal cells. But Ali says that this treatment will only work in people with some surviving photoreceptor cells, whereas the new therapy would work even where these cells have completely degenerated.
Dr. Ali and his colleagues made the photoreceptors using a relatively new procedure that allows embryonic stem cells to self-organize into retina-like structures within a three-dimensional glob of jelly.
Crucially for developing human treatments, they also identified the optimal stage in the cells’ development – at around 24 days – to transplant them into the eyes of mice. At that point, the photoreceptor cells are still relatively immature, but when implanted they find their own way to the correct sites in the eye where they mature fully. If the cells had already started to become fully mature photoreceptor structures called outer segments, they would not have been able to do this when transplanted, says Dr. Ali.
“We now have a route map for doing this with human embryonic stem cells,” he says. The team has already grown the precursors to human retinal photoreceptor cells. “The challenge is to get [the procedure] efficient enough for transplants,” he says.
“Until recently, photoreceptor loss was thought to be irreversible, but with this paper, there’s now enough evidence to think we might be able to reverse blindness in the future,” says Robert Lanza, medical director of Advanced Cell Technology, a company in Marlborough, Mass., that is evaluating whether implanting retinal pigment epithelial cells that nourish other types of retinal cells can prevent age-related blindness. “But it needs to be repeated using human cells, and there are lots of technical issues that need to be addressed, such as scaling up the three-dimensional culture system.”
The work was reported in Nature Biotechnology.
Evidence Lacking For General Glaucoma Screens
The U.S. Preventive Services Task Force released its final recommendation statement on screening for glaucoma, finding that there was not enough evidence to determine the accuracy and effectiveness of glaucoma screening in primary-care settings for adults who do not have vision problems. Based on this lack of clear evidence, the task force could not make a recommendation for or against screening adults for glaucoma.
“Unfortunately, we don’t have enough evidence to know how best to screen for the disease and who would benefit from screening in the primary care setting,” said task force co-vice chairman Albert Siu, MD, MSPH. The task force’s evidence review focused on primary open-angle glaucoma, which is the most common form of the disease.
It is important to note that this recommendation applies specifically to screening adults without vision problems in primary-care settings. While there are many new treatments for glaucoma, the USPSTF found that there is not enough evidence to determine how best to screen for and diagnose glaucoma in adults with no signs or symptoms of vision problems. Also, there is a lack of evidence showing that screening reduces the likelihood of vision loss and blindness. “We call on the health-care community to conduct critically needed research on effective screening tests and treatments for glaucoma,” Dr. Siu says. “Findings from new research may be able to improve the lives of many Americans and help the task force update its recommendation in the future.” The final recommendation statement is published online in the Annals of Internal Medicine and is available at uspreven tiveservicestaskforce.org.
Retinal Genes Catalogued
Investigators at Massachusetts Eye and Ear and Harvard Medical School have published the most thorough description of gene expression in the human retina reported to date. In a study published in BMC Genomics, Michael Farkas, PhD, Eric Pierce, MD, PhD, and colleagues in the Ocular Genomics Institute at Mass Eye and Ear reported a complete catalog of the genes expressed in the retina.
The investigators used a technique called RNA sequencing to identify all of the messenger RNAs (mRNAs) produced in the human retina. The resulting catalog of expressed genes, or transcriptome, demonstrates that the majority of the 20,000-plus genes in the human body are expressed in the retina. This in itself is not surprising, because the retina is a complex tissue comprising 60 cell types.
In a more surprising result, Dr. Farkas and colleagues identified almost 30,000 novel exons and more than 100 potential novel genes that had not been identified previously. Exons are the portions of the genome that are used to encode proteins or other genetic elements. The investigators validated almost 15,000 of these novel transcript features and found that more than 99 percent of them could be reproducibly detected. Several thousand of the novel exons appear to be used specifically in the retina. In total, the newly detected mRNA sequence increased the number of exons identified in the human genome by 3 percent.
“While this may not sound like a lot, it shows that there is more to discover about the human genome, and that each tissue may use distinct parts of the genome,” said Dr. Pierce, director of the OGI and the Solman and Libe Friedman associate professor of ophthalmology at Harvard Medical School.
Identifying the genetic cause of patients’ retinal degeneration has become especially important with the recent success of clinical trials of gene therapy for RPE65 Leber congenital amaurosis. As a follow-up to these initial proof-of-concept trials, clinical trials of gene therapy for four other genetic forms of inherited retinal degeneration are currently in progress. Further, studies in animal models have reported successful gene therapy for multiple additional genetic types of inherited retinal degeneration. There is thus an unprecedented opportunity to translate research progress into providing sight-preserving and/or -restoring treatment to patients with retinal degenerative disorders. REVIEW