I grew up acutely aware that good vision is precious.
In 1971, at age 46, my mother lost the sight in her right eye from a blood clot in the retina. It happened within minutes, and over the years, glaucoma and cataracts took their toll, although she continued plowing through murder mysteries with what she called her “good eye.”
Then, one night in December 2008, Mom casually mentioned that bar codes on food packages looked wavy. I knew visual distortions were a sentinel symptom of age-related macular degeneration (AMD), a leading cause of blindness, and urged her to see her ophthalmologist. Within 36 hours, a retina specialist was injecting a drug called Lucentis into her left eye to protect her central vision and ability to see detail. Since then, my 86-year-old mother has returned every six weeks for an injection of Lucentis, which has largely stabilized the so-called wet form of the disease.
As if having one parent with severe eye disease isn’t troubling enough, my 89-year-old father has been treated for glaucoma, cataracts and the so-called dry form of macular degeneration. However, his vision is so stable that he long ago stopped checking for crooked lines on what’s called an Amsler grid, which he taped inside a kitchen cabinet door more than 25 years ago.
According to the National Eye Institute, more than 1.75 million Americans 40 and older have advanced AMD. There are treatments, but there is no cure — at least not yet.
Despite my own elevated risk for the disease stemming from age and family history, this week I got a glimmer of hope that science may keep me from following in my parents’ footsteps. Researchers from UC Santa Barbara, the University of Utah and the University of Iowa reported finding 50 genes that were either overly active or less active in a comparison of donor eyes with and without macular degeneration. The findings are illuminating little-understood aspects of how macular degeneration begins and progresses, according to a study published Thursday in BioMed Central’s journal Genome Medicine.
Not only can these genes “identify people with clinically recognized AMD and distinguish between different advanced types,” some of them also appear linked to abnormal changes occurring in the eye before the disease is diagnosable, said study author Monte J. Radeke, a research scientist at UCSB’s Center for the Study of Macular Degeneration. Knowing how these genes function makes them potentially valuable targets for drug development, he said.
“That’s the most important thing about this article. It points out different pathways that could be involved in the disease progression,” said Dr. Marco Zarbin, chief of ophthalmology at the University of Medicine and Dentistry of New Jersey in Newark. “This is wonderful research because first of all, it shows a number of pathways involved in the disease process, both in the early and later stages, which creates opportunities to create treatments that might be better than what we have now.”
Eye doctors currently cannot really help someone at high risk who hasn’t yet manifested signs of the disease. In addition, the current treatment arsenal remains limited, although some of the many drugs now in clinical trials might potentially prove useful, Zarbin said.
Doctors can halt or slow the progression of wet AMD with injections of Lucentis (ranibizumab), approved in 2005; Avastin (bevacizumab), used off-label; and Eylea (aflibercept), FDA-approved last November. All three drugs, which prevent growth of abnormal and leaky vessels in the retina, appear more effective than Macugen (pegaptanib), which was approved in 2004. A few patients still receive photodynamic therapy with Visudyne (verteporfin), an intravenous drug approved in 2000 that’s activated by light shined into the eye. Patients with some manifestations of dry AMD, such as deposits called drusen, can stave off vision loss by taking a dietary supplement of minerals and vitamins.
Researchers around the globe have found some genes associated with a predisposition to AMD, but the new study “increases our knowledge of the genetic abnormalities that are associated with the different stages of AMD. You’re basically increasing the genetic fingerprint for at-risk patients,” Zarbin said. It’s still too soon to make the information the basis of a screening test, he said. “If we had perfect treatment for all stages of disease, and perfect treatments that could prevent development of disease before you get it, then genetic screening would make a lot of sense.”
By identifying genes involved in processes that damage the eye, the findings set the stage for a more sophisticated, multi-pronged approach to treatment. Doctors could develop therapies that target genes associated with inflammation, genes that control programmed cell death (apoptosis) in dry AMD, and genes that drive the formation of leaky blood vessels (angiogenesis) in wet AMD. Doctors might prescribe multiple drugs, kind of like hitting your enemy on several fronts.
Zarbin and Dr. Kang Zhang, director of the Institute for Genomic Medicine and chief of Ophthalmic Genetics at UC San Diego, said they’d like to see the study replicated in larger numbers.”What I want to see is more connections between genes which give you heightened genetic risk for AMD and the genes identified by these authors,” Zhang said.
Finally, Zhang said one of the practical limitations of the new findings was that they came from cadaver eyes. “It’s not feasible to biopsy human eyes,” Zhang said. He hopes the same kinds of genetic information might be gleaned from blood samples and eventually turned into simple blood tests.
I’m hoping that diagnostic, therapeutic and preventive advances will keep me from ever having to face a needlestick in the eye eight times a year. Unfortunately, I didn’t inherit my mother’s remarkable ability to tolerate pain and discomfort.