Scientists have gone on a fishing expedition for new genes associated with age-related macular degeneration (AMD) and they have scored big.

Researchers scanned the entire genome (a time-consuming and expensive process) of 2157 persons with AMD (cases) and 1150 people without AMD (controls) in an attempt to discover new genes associated with the presence of the disease. In addition to the genes already known to be associated with AMD, they uncovered 30 genes that seemed to increase the risk of the disease.

In an attempt to confirm this association, the researchers then examined genetic material from a number of other research projects to see whether this association held up. After examining a total of 7,749 cases and 4,625 controls the researchers confirmed an association between AMD and 5 genes that have not been previously associated with the disorder.

Their top susceptibility gene was found near TIMP3, a gene known to be associated with Sorby's fundus dystrophy, an early-onset macular degenerative disease that shares clinical features with AMD but typically presents before age 40 years.

In addition, the data revealed association signals with four genes that are associated with high-density lipoprotein (HDL) cholesterol levels in the blood. Cholesterol and lipids accumulate underneath the RPE with age and are present in the drusen that characterize early AMD.

This study strengthens the previously reported association between AMD and cardiovascular disease. It is possible that genetic variants that impact cholesterol levels in the macula and RPE might impact drusen formation and thus modulate the risk of AMD. This finding suggests that measures to improve cardiovascular health may decrease the risk of AMD.

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Patients with wet AMD that fails to respond to anti-VEGF therapy are at risk of depression, according to a new study.

Anti-VEGF treatment has dramatically reduced the risk of severe vision loss in patients with wet AMD. On average, about 30% of subjects in clinical trials gained 15 or more letters in visual acuity and 50% demonstrated improved mental health. Studies conducted prior to anti-VEGF therapy have noted that 30% of patients with AMD develop depression.

Researchers conducted telephone assessments of mood and self-reported vision function at baseline and 3 months later on a series of patients undergoing anti-VEGF therapy for wet AMD. At baseline, patients had already received a mean of 7.4 injections.

At 3 months, 10 subjects (20%) had clinically significant depressive symptoms. Compared with nondepressed subjects, depressed subjects had a greater decline in vision over 3 months. Depression was unrelated to changes in visual function scores or obstacles to treatment.

The investigators state that their findings indicate the continued need for psychiatric and rehabilitative interventions for some patients with AMD who are receiving anti-VEGF treatment.

WHAT IT MEANS TO YOU: Depression is a normal reaction to vision loss and the social changes associated with developing low vision. Thankfully, the development of effective treatments for wet AMD, such as Avastin and Lucentis, have decreased the prevalence of depression among persons with wet AMD from 30% to 20%. However, clinicians should continue to be alert for depressive symptoms, especially among patients that fail to respond to therapy.

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A British soldier who was blinded by a grenade in Iraq three years ago said his life has been transformed since he was fitted with a prototype BrainPort device that allows him to "see" with his tongue.

24-year old Lance Corporal Craig Lundberg from Liverpool, UK, told BBC News that while the device is only a prototype, it has a lot of potential to advance things for blind people: "the potential to change my life is massive," he said.

The BrainPort device looks like a square plastic lollipop that connects via a wire to a tiny video camera mounted on sunglasses worn by the user. When users want to "see" their environment, they put the "lollipop" in their mouth and the video camera images are converted to electrical impulses that users sense with their tongue when it makes contact with the lollipop.

"One of the things it has enabled me to do is pick up objects straight away, I can reach out and pick them up when before I would be fumbling around to feel for them," said Lundberg.

BrainPort is made by Wicab Inc of Middleton, Wisconsin in the United States, a company established by American neuroscientist Dr Paul Bach-y-Rita in 1998. Bach-y-Rita, who died in 2006, was a pioneer in the field of neuroplasticity, and the first scientist to introduce the idea of "sensory substitution" (feeding signals from one sense into the brain circuits of another) to treat patients with disabilities.

WHAT IT MEANS TO YOU: Sensory substitution occurs when the body uses one sense, such as touch, to provide the brain with information that is normally provided by a different sense, such as vision. Echolocation is a common example seen in bats and dolphins. It has been reported that blind persons can also develop echolocation abilities, but it seems that not everyone is equally adept at using hearing as a substitute for vision. The BrainPort device makes it possible to substitute touch for vision. The tongue is very sensitive to touch, making it idea for this purpose.

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The ability of anti-VEGF therapy to stop fluid accumulation in the macula of patients with wet AMD is well established. In an effort to reduce the number of required injections and to establish a finite treatment endpoint, researchers are now exploring combination therapy options.

"The problem with anti-VEGF is we are finding out now that more treatments are better than less, so monthly injections appear to be better than less frequent injections," Dr. Peter Kaiser said. "Even more important is, irrespective of whether monthly is better than as-needed, we're finding that in many cases the therapy may need to be continued for an extended period of time."

As a result, anti-VEGF monotherapy represents a perplexing paradigm: anything other than monthly injections compromises visual acuity and thus represents a compromise in care; however, requiring monthly injections becomes unsustainable from a practical and clinical standpoint.

"So now we are at a point where with monotherapy, all evidence points to only one way of doing this, which is to give this on a monthly basis, perhaps ad infinitum," Dr Kaiser said.

Several combination treatment protocols are being studied, including the DENALI study, which is exploring the use of both normal- and reduced-fluence photodynamic therapy (PDT) in combination with Lucentis (ranibizumab). According to Dr. Kaiser results should be available in June 2010.

"Since PDT and ranibizumab are already approved, if the DENALI study is positive in June, things could change pretty dramatically," Dr. Kaiser said.

Another combination therapy option for AMD is the use of radiation with anti-VEGF agents. An epimacular brachytherapy device using a strontium-90 isotope to deliver radiation (NeoVista) is currently being investigated in the phase 3 CABERNET study. Another radiation platform is being developed by Oraya (IRay), with phase 3 studies expected to start this summer. The IRay system delivers low dose X-rays in the three sequential beams delivered through the pars plana during a 10-minute in-office procedure.

Although both devices are early in development, they offer the potential to dramatically affect the rapidly dividing endothelial cells that are the hallmark of choroidal neovascularization, according to Dr. Kaiser.

"I'm very excited about both radiation therapies," Dr. Kaiser said. "I think both, quite frankly, will be quite successful, and the market will decide when to use the particular device. Since one requires surgery and the other doesn't, we'll see how the market plays out."

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A combination of an anterior chamber intraocular lens (IOL) and posterior chamber IOL that functions like a Galilean telescope offers reasonable visual recovery for patients with severe AMD, according to a speaker at the American Society of Cataract and Refractive Surgery meeting.

"The IOL-Vip system (LenSpecial) seems to be a promising new device for visual rehabilitation of patients suffering from an end-stage of macular degeneration, " Dr Ramin Khoramnia said.

In seven eyes of seven patients with a mean best corrected visual acuity preoperatively of 1.3 logMAR, patients had a mean improvement of 0.68 logMAR, Dr. Khoramnia said. All patients reported an improvement in quality of life after implantation.

There were no intraoperative or postoperative complications noted with the device; however, patients experienced an average of 6% endothelial cell loss after surgery and 10% during the first year after implantation.

Another device, an intraocular mirror telescopic projector may offer visual improvement in patients with severe bilateral AMD, according to another speaker at the meeting.

The device acquires an image on a mirror placed in the pupillary opening behind the iris that is reflected to a second intraocular mirror, creating a telescopic effect, Isaac Lipshitz, MD said. The new image is then projected on to a targeted area of the macula.

The current device offers 2.5-times magnification of the central visual field and preserves normal peripheral vision, although a 4-times magnification device is also in development, Dr. Lipshitz said. The device is self-contained, as it is implanted into the anterior chamber much like an IOL. Because it is intended to be a bilateral implant, aniseikonia is avoided, Dr. Lipshitz said.

In early studies of the device, patients gained an average of 3.6 ETDRS lines of distance acuity and 4.9 ETDRS lines of near acuity. In a separate study, patients gained an average of 1.0 ETDRS lines distance and 4.0 ETDRS lines near. Dr. Lipshitz said he is studying why the two cohorts had disparate results.

WHAT IT MEANS TO YOU: We have witnessed great progress in the development of computerized low vision devices in recent years. Highly sophisticated portable magnifiers, screen readers, GPS-assisted navigation aids, and more have all arisen within the past few years. The next wave of progress in low vision aids may come in the field of implantable devices, such as those mentioned here. These devices are still in the earliest stages of development, and it remains to be seen if they will truly be effective. But, they offer the hope of a permanent improvement in effective vision and freedom from reliance upon a vision aid that is conspicuous, cumbersome, and can become lost or broken.

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Combined therapy using intravitreal Avastin (bevacizumab) followed by photodynamic therapy (PDT) is safe and effective in eyes with retinal angiomatous proliferation (RAP), according to a new study.

Retinal angiomatous proliferation is a distinct form of neovascular age-related macular degeneration (AMD) associated with angiomatous proliferation that originates from the retina and extends posteriorly into the subretinal space. There is poor visual prognosis, and progression to poor vision is common and often rapid. Combination therapy of intravitreal triamcinolone plus PDT or intravitreal Avastin plus PDT has been found to be effective in patients with RAP.

The current study involved a series of consecutive patients newly diagnosed with RAP. PDT guided by indocyanine green (ICG) angiography was applied 8 days after the intravitreal Avastin injection.

In all, 21 eyes of 18 patients with RAP were enrolled. After treatment BCVA showed no statistically significant differences between each visit. Foveal thickness decreased significantly between baseline and all the follow-up visits. A mean of 1.7 injections were given per eye over the 9-month follow-up period (range 1-3 injections per eye).

The investigators conclude that a possible synergistic effect may arise from the combination of intravitreal Avastin with PDT for the treatment of RAP. These findings also suggest a possible benefit of combo therapy in the rate of intravitreal re-injections.

WHAT IT MEANS TO YOU: To know how effective our treatment is for any condition, it is helpful to know the natural course of the disease. We are lacking good information on the natural history of RAP, but most studies report a poor visual prognosis. This helps to explain the absence of vision improvement of the patients in this study; the stabilization of vision alone may represent a significant treatment benefit. However, several recent studies of Avastin monotherapy in patients with RAP found an average improvement in best-corrected vision, whereas this study did not. The real advantage of combining Avastin with PDT in patients with RAP may be to decrease the number of required injections. Unfortunately, less improvement in vision may be associated with this treatment strategy.

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Retina Implant AG, announced successful results from the company's first human clinical trial. The company is now setting up a UK trial of the implant.

The results achieved in the 11 patients involved in the preliminary study far exceeded the company's expectations. In fact, some patients were able to see objects and shapes clearly enough to read large letters and recognize words. Although other companies have developed retinal implants, until now the technology facilitated the ability to see light and outlines of objects, but did not produce a level of sight that enabled patients to read.

Retina Implant's clinical trial began in Germany in 2005 and has involved 11 patients who lost their sight due to retinitis pigmentosa (RP).

There are two main approaches to retinal implants currently being developed by scientists across the globe: epiretinal and subretinal. Both electronic implants stimulate the retina, which is a light sensitive sheet of nerve cells at the back of the eye. The 'epiretinal' approach involves sticking an electronic implant in front of the retina to stimulate the nerve cells. The surgery to do this is more straightforward, but the epiretinal implant is not itself light sensitive and needs to be connected to a camera outside the eye, often mounted on the patient's spectacles. The new 'subretinal' approach developed by Retina Implant AG involves placing the electronic device underneath the retina, which is technically challenging but stimulates the nerve cells in a more natural position. Furthermore the subretinal device is itself light sensitive, with a 1500 pixel array. This is stimulated by the natural image focused by the eye which completely does away with the need for an external camera.

Retina Implant is presenting results of this clinical trial at the Association for Research in Vision and Ophthalmology's (ARVO) annual meeting May 2 - 6 in Fort Lauderdale, Fla.

WHAT IT MEANS TO YOU: There has been a large number of very encouraging news reports over the past couple of years regarding progress on the epiretinal implant being developed by Second Sight Medical Products. This is one of the few reports we have seen regarding the subretinal implant from Retina Implant AG. It has been acknowledged that the surgery to implant a subretinal device is much more challenging than with an epiretinal device, but it seems that the superb results may warrant the extra effort. According to this press release, patients are able to achieve reading vision with the subretinal device, something that the epiretinal device cannot even come close to offering. We look forward to more details from this exciting development.

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If you're the owner of a service or therapy dog, you can get a free eye exam for your pooch, if you sign up with the American College of Veterinary Ophthalmologists National Service Dog Eye Exam Program. The American College of Veterinary Ophthalmologists is sponsoring the third annual National Service Dog Eye Exam. More than 170 veterinary ophthalmologists in the U.S. and Canada will provide free eye exams to service dogs. To qualify, dogs must be active working dogs that were certified by a formal training program or organization, or are currently enrolled in a formal training program. Owners must first register the animal online before May 16 at acvoeyeexam.org. Once registered, the owner can contact a participating veterinary ophthalmologist directly to schedule an appointment during the month of May. Appointment dates and times are filled on a first-come, first-served basis.

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Bausch + Lomb has announced the U.S. launch of PreserVision Eye Vitamin and Mineral Supplement AREDS 2 formula. This builds on the original Age-Related Eye Disease Study (AREDS) formula, replacing beta-carotene with lutein (10mg) and zeaxanthin (2mg) and adding omega-3 fatty acids (1000 mg) per daily dosage. The product will be on retail shelves in early May, 2010. The AREDS2 study, which is currently ongoing and expected to complete in 2013, is the second nationwide clinical study to determine whether a combination of vitamins and minerals can further slow the progression of vision loss from AMD. PreserVision AREDS 2 formula is one of many formulas that are being evaluated in this study.

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Intravitreal Avastin (bevacizumab) for has been associated with the onset of tonic-clonic (grand mal) seizures, according to a recent case report. An 81-year-old female was brought to the emergency room after 3 witnessed seizures. Thirty minutes earlier she had received a second injection of Avastin to the right eye for treatment of AMD. While being driven home by her daughter, approximately 20 minutes after the injection, she had a witnessed tonic-clonic seizure lasting 2-3 minutes. Her daughter immediately pulled the car over and called EMS services. After an ambulance arrival, the woman had 2 further similar episodes. Seizures have never before been reported as a side effect of intravitreal Avastin. Interestingly, there are several reports of tonic-clonic seizures associated with Avastin in cancer treatment as an entity known as "reversible posterior leukoencephalopathy syndrome" (RPLS). RPLS is characterized by headaches, seizures, visual loss, and hypertension. The pathophysiology behind Avastin-induced RPLS is poorly understood but thought to be due to either effects on the blood-brain barrier or vasospasm coupled with hypertension. In the patient described, it is possible that a small but significant absorption of Avastin may have occurred, allowing such a process to take place. The case is reported in the April 2010 edition of the Canadian Journal of Ophthalmology.

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The book, the brainchild of Lisa Murphy and called Tactile Minds, is designed to be 'enjoyed' by the blind and visually impaired - and is on sale for 150 British pounds, according to a report in The Telegraph. Among the 17 raised images include a naked woman in a 'disco pose', a woman with 'perfect breasts' and a 'male love robot'. Canadian Lisa says that she made the book to fill a gap in the market, adding: "There are no books of tactile pictures of nudes for adults. "We're breaking new ground. Playboy has an edition with Braille wording, but there are no pictures." She said that she made the book after realizing that the 'blind have been left out in a culture saturated with sexual images'. Between 1970 and 1985 Playboy printed copies of its famous magazine in Braille - but without raised pictures.

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Lucentis is effective in the treatment of punctate inner choroidopathy, according to a recently published case report. Punctate inner choroidopathy is a rare, idiopathic posterior uveitis that usually develops in young, myopic females. Choroidal neovascularization (CNV) and subretinal fibrosis are common complications. A healthy, 30-year-old female presented with 1 month of blurred central vision OD. Best-corrected visual acuity (BCVA) was counting fingers OD and 20/20 OS. Fluorescein angiography confirmed a juxtafoveal choroidal neovascular membrane. The patient's condition was diagnosed as punctate inner choroidopathy complicated by CNV. After discussion of the risks and benefits, the patient consented to an intravitreal injection of Lucentis to the right eye. One month later, the BCVA had improved to 20/400, and optical coherence tomography (OCT) revealed no subretinal fluid. Eight months after injection, the BCVA improved to 20/200 with further retraction of the macular scar. There is currently no consensus on the optimal treatment of CNV secondary to punctate inner choroidopathy. This case report demonstrates that Lucentis may be considered as a primary treatment option in the management of CNV associated with punctate inner choroidopathy. The case is reported in the June 2010 edition of the Canadian Journal of Ophthalmology.

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