Walgreens drug stores have put on hold plans to carry the Pathway Genomics genetic test kit after the FDA questioned whether the company had obtained appropriate FDA approval to market the test to consumers.

The kit, sold under the brand name Insight, comes with a vial and a shipping envelope. Buyers send a sample of their saliva to a Pathway Genomics laboratory and receive their genetic health report online.

There are currently numerous testing services available online (including the disputed Pathway Genomics test), and the Walgreens case is different only in that it would be available at a brick-and-mortar retailer.

The National Society of Genetic Counselors issued a statement saying that receiving genetic information without input from a doctor "increases the chance for misunderstanding or misinterpretation of results."

While there is no single "AMD gene", there is an abundance of evidence linking genotype with AMD risk. This risk has been quantified and algorithms constructed that can fairly precisely determine the risk of developing AMD given a genotype and information on behavioral risk factors.

People should be encouraged to be proactive about their health, and this includes, among other things, learning about what diseases we are at particular risk for based upon our genotype; and then taking steps to counter this risk by lifestyle adjustments, medication, or increased medical surveillance.

The availability of home testing will make this service much more affordable and widely used. However, the real value in knowing your genotype is in the improved (more targeted) medical care that can be provided based upon this information. Indeed, genotype not only influences risk of acquiring the disease, but also response to therapy. Genotype information will be increasing valuable to clinicians as we have more treatment options at our disposal.

Print version

Myopic choroidal neovascularization (mCNV) may develop secondary to choroidal vascular insufficiency, according to a new study.

High myopia is associated with excessive and progressive elongation of the globe, resulting in a variety of fundus changes that lead to visual impairment, including lacquer cracks in the Bruch membrane, choroidal neovascularization (CNV), and chorioretinal atrophy. The choroid is thin in highly myopic eyes and undergoes further attenuation with increasing age and increased myopia. Choroidal thinning may play a role in the pathophysiologic features of vision loss in high myopia. At some point relative ischemia of the outer retina, RPE, and the choroid itself may lead to pathologic decompensation.

This is a retrospective, consecutive, observational case series. Forty-two consecutive eyes (17 eyes with newly diagnosed mCNV and 25 eyes without CNV) were included.

Sixteen (94%) of 17 eyes with mCNV and six (24%) of 25 eyes without mCNV had well-defined hypofluorescence at the macular region on arterial phase ICGA, that is, a choroidal filling delay. The most important factors associated with mCNV, in order of importance, were the choroidal filling delay and choroidal thickness. Older age was significantly associated with both choroidal filling delay and choroidal thinning.

The investigators conclude that significant choroidal changes were observed in eyes with mCNV. Ischemia-induced growth factor expression caused by decreased choroidal perfusion may be related to the development of mCNV.

WHAT IT MEANS TO YOU: This study suggests that myopic CNV may be triggered by choroidal insufficiency that results in ischemia. It has recently been suggested that ischemia resulting from choriocapillaris atrophy may also underlie CNV in AMD. The tendency of myopic macular degeneration to worsen with increasing age may be due to the observed decline in choroidal perfusion observed in this study.

Print version

Intravitreal injection of ketorolac (Acular) into the eyes of laboratory rats significantly inhibited the growth of laser-induced choroidal neovascularization (CNV), according to a recently published report.

A growing body of scientific evidence indicates that inflammation plays a central role in the development of choroidal neovascularization. In support of this, intraocular corticosteroids have been shown to be beneficial in patients with CNV. However, their routine use is limited by numerous adverse effects (including cataract and glaucoma); thus, safer alternative anti-inflammatory agents would be beneficial.

Cyclooxygenase (COX) is an important enzyme in the inflammatory process that catalyzes the biosynthesis of prostaglandins. Prostaglandins amplify the activity of other chemical mediators, including vascular endothelial growth factor (VEGF). Research has found that COX inhibition can suppress CNV development.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are potent inhibitors of COX enzymes. These drugs also have antiproliferative and antiangiogenic effects. Most important, NSAIDs do not cause cataracts or glaucoma and thus may offer a safer alternative to steroids.

CNV was induced by applying laser burns to each eye of 18 laboratory rats. Each rat received either intravitreal injection of 30 mg/mL of ketorolac tromethamine, 40 mg/mL of triamcinolone acetonide (steroid), or balanced salt solution (control).

The researchers found that intravitreal ketorolac significantly reduced CNV leakage on fluorescein angiography compared with balanced salt solution, but intravitreal triamcinolone was a more potent inhibitor of CNV leakage than ketorolac (P < .001). Vascular budding on choroidal mounts was almost entirely suppressed with triamcinolone and significantly inhibited with ketorolac.

The investigators conclude that intravitreal ketorolac significantly inhibited CNV leakage and vascular budding in an animal model of AMD, although the effect was less than that of triamcinolone. They state that intravitreal nonsteroidal anti-inflammatory drugs may be useful in the treatment of CNV.

WHAT IT MEANS TO YOU: The use of NSAIDS to combat retinal and choroidal neovascularization is a very exciting development. A number of studies have been published about the ability of Nevanac (nepafenac) eye drops, another NSAID, to inhibit diabetic retinopathy and choroidal neovascularization. This is the first study to report on Acular's ability to combat CNV. Because the ocular penetration of Acular is inferior to that of Nevanac, Acular eye drops would not be expected to have any effect, but intravitreal injection according to this study, is effective.

Print version

Lucentis (ranibizumab) plus laser photocoagulation results in significantly better visual acuity than laser alone for patients with diabetic macular edema (DME), according to a new research study.

Macular edema is the most common cause of reduced visual acuity in diabetic retinopathy. The traditional treatment for diabetic macular edema is laser photocoagulation. Both steroids and Avastin have been reported to have beneficial effects. In a head-to-head comparison, the Diabetic Retinopathy Clinical Research Network did not find a benefit of intravitreal triamcinolone (steroid) relative to laser photocoagulation after 3-years of follow-up.

This multicenter, randomized clinical trial evaluated intravitreal Lucentis or triamcinolone (steroid) combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Eyes were randomized to one of four study groups:
1. sham injection plus prompt laser (n=293)
2. Lucentis + prompt laser (n=187)
3. Lucentis + deferred (24 weeks) laser (n=188)
4. Triamcinolone + prompt laser (n=186).

The 1-year mean change in the visual acuity letter score from baseline was significantly greater in the Lucentis + prompt laser group (+9 letter gain) and Lucentis + deferred laser group (+9 letter gain) but not in the steroid/laser group (+4 letter gain, P=0.31) compared with the sham/laser group (+3 letter gain).

Reduction in mean central macular thickness in the steroid/laser group was similar to both Lucentis groups and greater than in the sham/laser group.

Two-year visual acuity outcomes were similar to 1-year outcomes.

The investigators conclude that Lucentis plus laser is more effective than laser alone for the treatment of DME involving the central macula

WHAT IT MEANS TO YOU: This important study finds that the addition of Lucentis to standard care (laser photocoagulation) improves clinical outcomes. Vision gains were realized regardless of whether the laser was delivered immediately following Lucentis injection or delayed by several months. This study, if the results can be replicated by others, has the potential to change the current standard of care. Patients with diabetic macular edema may first receive an Lucentis injection, and if the vision does not respond satisfactorily, undergo laser photocoagulation several months later.

Print version

The inject-and-extend schedule for anti-VEGF therapy with Lucentis in AMD shows better efficacy and compatibility with patients' lifestyles than the as-needed regimen, according to a study presented at the French Society of Ophthalmology.

The inject-and-extend administration schedule entails an induction phase with three monthly injections, as suggested by landmark trials. A fourth treatment is scheduled at 6 weeks for all patients.

"The following visits are adapted to single patients, extending or shortening the interval by 2 weeks according to the presence or absence of subretinal fluid. In this way, there is no fixed interval in between visits, but at each visit we perform an injection, independent on the state of the lesion," Dr Hassiba Oubraham said.

This method was compared to the as-needed regimen employed by the PrONTO study. The inject-and-extend schedule showed better efficacy in terms of visual acuity gain, with an almost equal number of injections.

"The burden for the patients was much less. This resulted in better compliance compared to the fixed monthly appointments of the PrONTO/PRN regimen, which are often disattended," Dr. Oubraham said.

WHAT IT MEANS TO YOU: There are growing concerns about under-treatment using the as-needed (PRN) injection strategy. Recent studies have shown that vision outcomes using the PRN strategy are inferior to monthly injections. Little data exists regarding outcomes of the treat-and-extend approach, but we look forward to additional studies like the current one that compare the two approaches.

Print version

Today's aging baby boomers might be less likely to have AMD than their forebears, according to a new study presented at the Association for Research in Vision and Ophthalmology (ARVO) 2010 Annual Meeting.

"This rapid decline in age-related macular degeneration, which was 68% lower for each generation, suggests that modifiable factors play important roles in the etiology of AMD," said Dr Karen J. Cruickshanks. "Childhood exposure to environment contaminants - for instance, growing up in houses that used wood, coal, or kerosene for cooking - may contribute to the risk of AMD."

Birth cohort effects have been reported previously by other researchers. In this study, Dr. Cruickshanks sought to determine whether this trend continued for people born in the United States from 1946 to 1964 — the baby boom years.

The study looked at data on participants 45 years or older from the Beaver Dam Offspring Study and at data from the parental cohort of the Beaver Dam Eye Study and the Epidemiology of Hearing Loss Study. AMD was graded using digital-based images in the boomer cohort and film-based images in the parental cohort.

The study found that the prevalence of AMD declined with birth year, and was lower for recent generations. The age- and sex-adjusted odds ratio (OR) was 0.75 for every 5 years (P < .001), and this effect remained after adjustment for independent risk factors for AMD, such as obesity, education, and heavy drinking. However, cigarette smoking, a widely recognized risk factor, was not significantly associated with AMD in this study.

"For example, for individuals born between 1935 and 1939, the prevalence was 12%, but for individuals born between 1950 and 1954, it was 4%," Dr. Cruickshanks said.

WHAT IT MEANS TO YOU: This study suggests that the incidence of AMD is falling due to changes in behavior and environmental exposures. While these results are in line with prior research, it remains possible that the boomer generation hasn't aged enough for AMD to become very prevalent. It is very hard for researchers to adjust for age differences, and hence may underestimate the effect growing older may have on the incidence of AMD among baby boomers. It is of some significance that this study failed to find that smoking was related to AMD, something that is now widely accepted. This might suggest that there were methodological or other problems with this study that may have lead to flawed results.

Print version

Indocyanine green angiography (IA)-guided laser photocoagulation and sub-Tenon's capsule injection of triamcinolone acetonide (STTA) may be effective for treating idiopathic macular telangiectasia, according to a new study appearing in the British Journal of Ophthalmology. In the current study, 7 eyes were enrolled, (5 eyes with type 1 and 2 eyes with type 2). The mean follow-up was 10.6 months (range 7 to 19). STTA (20 mg) was injected after photocoagulation. IA identified leaky aneurysms or vessels. The final mean logMAR VA and the central macular thickness improved significantly from baseline. The VA improved by 0.3 or more logMAR unit in two eyes (29%) and stabilized in five eyes (71%). The investigators conclude that IA-guided laser photocoagulation combined with STTA might be effective for treating types 1 and 2 idiopathic macular telangiectasia.

Print version

Intravitreal injection of an anti-VEGF agent and a complement inhibitor proved safe in treating AMD, Dr Scott Cousins, said at the ARVO 2010 meeting. "Drusen contain all the different complement family of molecules, not just the effectors but also the activator and inhibitor," Dr. Cousins said. "Surprisingly, anti-VEGF is a complement pathway. So, clearly, complement plays a role in AMD." Dr. Cousins and colleagues set out to assess the safety of intravitreal injection of the aptamer ARC1905, a complement factor 5 inhibitor, combined with Lucentis. The prospective, non-controlled multicenter study included 58 patients with all clinical subtypes of subfoveal neovascular AMD. Study results showed that increased dosing was safe and tolerable for all patients. In addition, patients with less initial foveal thickness regained better vision, Dr. Cousins said. Manufacturer Ophthotech plans to proceed with a phase 1 clinical trial of ARC1905 as monotherapy in treating non-neovascular AMD. The study will involve five intravitreal injections of ARC1905 over a period of 48 weeks: three monthly doses followed by two quarterly doses.

Print version

Intravitreal injection of Lucentis does not produce a therapeutic effect in the fellow eye of patients with bilateral exudative AMD, according to a new study in the Journal of Ocular Pharmacology and Therapeutics. The current study is a prospective case series of 26 patients treated with intravitreal Lucentis injections because of bilateral exudative AMD. While mean CRT was significantly reduced in the treated first eye 2 weeks after intravitreal injection from 369.46 um to 275.04 um, mean CRT in the untreated fellow eye increased significantly: from 349.08 um to 403.46 um 2 weeks later. The investigators conclude that a therapeutic effect of Lucentis in the untreated fellow eye could not be demonstrated. This finding indicates that there is insufficient systemic absorption to produce a physiologic response to the drug in the fellow eye, and suggest a low risk of adverse systemic side effects following intravitreal administration of Lucentis.

Print version

iCo Therapeutics announced details of the company's Phase I clinical trial study employing iCo-007 in Diffuse Diabetic Macular Edema. Designed and discovered by ISIS Pharmaceuticals Inc, iCo-007 is a second-generation antisense drug targeting c-Raf kinase for the treatment of DME and diabetic retinopathy. Antisense therapy is a form of treatment for genetic disorders or infections. This synthesized nucleic acid is termed an "anti-sense" oligonucleotide because its base sequence is complementary to the gene's messenger RNA (mRNA), which is called the "sense" sequence. c-Raf is a MAP kinase kinase kinase (MAP3K). Once activated Raf-1 can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2 which in turn phosphorylate to activate the serine/threonine specific protein kinases ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. The primary endpoint of the Company's open label, dose escalating Phase I trial is safety, with visual acuity and measures of retinal thickness serving as secondary endpoints. Four U.S. clinical sites participated. iCo expects to release final results of its Phase I study later in Q2 2010.

Print version

National Institutes of Health researchers looking at data from AREDS2 of more than 4,200 seniors found that those reporting the highest intake of omega-3 fatty acids had the lowest reported rating of AMD severity. Fish oil is rich in omega-3 long-chain polyunsaturated fatty acids (LCPUFA). Docosahexaenoic acid (DHA), the major dietary and structural omega-3 LCPUFA of the retina, has the capacity to modulate processes implicated in AMD pathogenesis. Eicosapentaenoic acid (EPA), the precursor to DHA and the other major dietary omega-3 LCPUFA, can exert similar actions to DHA. At the ARVO meeting, Dr J.R. Chang reported that "dietary DHA/EPA was inversely related to AMD score in energy-adjusted comparisons of participants reporting highest vs. lowest quintile intake."

Print version

Quark Pharmaceuticals announced that researchers from Pfizer, Inc. presented data on in vivo activity of PF-04523655 at the ARVO 2010 annual meeting. The study demonstrated reduction of RTP801 mRNA levels in rat retina following intravitreal administration of PF-04523655 in a laser model of choroidal neovascularization. PF-04523655 is a chemically-modified siRNA drug candidate being co-developed by Quark and Pfizer for the treatment of wet AMD and DME. PF-04523655 is designed to inhibit the expression of Quark's proprietary target, RTP801. The ongoing Phase II prospective, randomized, multi-center, dose ranging study is designed to evaluate the efficacy and safety of PF-04523655 versus laser therapy in patients with DME. Eligible patients were randomized to receive intravitreal injections of one of three dose levels of PF-04523655 or laser. Daniel Zurr, President and Chief Executive Officer of Quark Pharmaceuticals, said, "These results on in vivo activity of PF-04523655 represent an important step forward for the field of synthetic siRNA therapeutics. Importantly, the data presented by Pfizer demonstrate that siRNAs chemically modified to improve stability are taken up by cells and elicit RNAi activity in vivo without requiring complex delivery formulations."

Print version