Quick Hits

$12.4 million awarded to “audacious goals”

The National Institutes of Health is helping to fund new treatments for blindness.

By Robert Stoneback, associate editor

The National Institutes of Health has awarded $12.4 million to six projects whose mission is to seek those factors that impact neural regeneration in the retina. These six, part of the Audacious Goals Initiative (AGI) that is sponsored by the National Eye Institute, will be funded over three years.

“The Audacious Goals Initiative is a coordinated effort led by the National Eye Institute to restore vision in people with blinding diseases such as age-related macular degeneration, glaucoma and diabetic retinopathy,” says Steven Becker, PhD, director of the AGI Office. “The six teams recently awarded funding will take different approaches to addressing biological factors that affect neural regeneration in the retina. Their objective is to identify new signals that could allow retinal cells to re-establish their connections between the eye and the visual processing system.”

According to the NIH’s website, the latest AGI projects are:

❯❯ Molecular discovery for optic nerve regeneration. Using mice with optic nerve injuries, investigators have shown they can successfully regenerate retinal ganglion cells axons, which transmit visual information from the retina to the brain. Investigators hope to identify genes and proteins that will help or hinder the ability of retinal ganglion cells to regenerate, grow axons to a target and become functional in mice.

❯❯ Screening for molecules that promote photoreceptor synaptogenesis. Investigators plan to study precursor photoreceptor cells derived from human stem cells, intending to discover what factors coax them into becoming fully developed and connected photoreceptor cells. The investigators expect to identify a list of small molecules and candidate genes that contribute to a photoreceptor cell’s ability to home in on their appropriate target cells in the retina, also known as bipolar cells.

❯❯ Evaluation of novel targets for retinal ganglion cell axon regeneration. This test will use 450 candidate genes, culled from more than 17,000, to find ones that contribute to the regeneration of axons from retinal ganglion cells. Each candidate gene will be tested in a murine optic nerve injury model, to see if it acts as a mediator of regeneration. Positive genes will be checked for further activity in the Caenorhabditis elegans worm to verify cross-species functionality.

❯❯  Novel activators of regeneration in Muller glia. Investigators will study factors with external or internal origins that contribute to the reprogramming of supportive cells in the retina. These cells, called Muller glia, have been observed in zebra fish where they have given rise to photoreceptor cells after retinal injury. Investigators will first study whether they can reprogram Muller glia in mice; if successful, they will determine which genes are turned on or off in regenerating zebra fish and murine Muller glia.

❯❯ Comparative transcriptomic and epigenomic analyses of Muller glia reprogramming. This study will examine Muller glia in chicks and zebra fish, where retinal damage can trigger Muller glia to produce neuronal progenitor cells. These cells are capable of moving to damaged retinal tissue and turning it into missing neuronal cell types. Mammalian Muller glia cannot do this; researchers will compare chick and zebra fish Muller glia to those of mice to detect differences in gene expression and to identify potential regulators that control Muller glia reprogramming. The goal is to understand why some species possess this ability and others do not.

❯❯ Novel targets to promote retinal ganglion cell axon regeneration: Insights from unique RGC cohorts. RNA sequencing in cultured murine retinal ganglion cells will be used to identify differences in gene expressions in regenerative versus non-regenerative retinal ganglion cells. Mass spectrometry will be used to determine what lipids may give subclasses of retinal ganglion cells more robust regenerative capacities. The genes found to be involved in regeneration will have further experiments conducted upon them; the most promising candidates will be used as a therapy to regenerate the optic nerve in a mouse model.

In addition, the AGI sponsored a panel in October titled “Reconnecting Neurons in the Visual System.” The panel, which featured two dozen experts on neural development and regeneration, was the basis for a recent report in the Journal of Neuroscience, titled “Reconnecting eye to brain.” OM

For more information about AGI and its projects, visit www.nei.nih.gov/audacious and http://tinyurl.com/hkylqzk.

Study calculates “global burden” of eye disease

“Sense organ disease” is one of many ailments examined by new Lancet study

By Robert Stoneback, associate editor

The Global Burden of Disease study 2015 (GBD 2015), published in October’s issue of The Lancet, analyzed 315 diseases and injuries that affect human well-being across the globe. The study measures “disability-adjusted-life-years” (DALYs), which represent the population’s years of life lived with a disability (YLD) and years of life lost (YLL) to a disease.

“Sense organ disease,” which includes vision impairments such as glaucoma, cataracts and macular degeneration, is listed as the seventh highest cause of DALYs globally, and ninth for the United States specifically. The study listed sense organ disease as the second-leading cause of YLDs specifically, resulting in 68 million DALYs over the course of 2015. While vision-related diseases made up most of the entries, the greatest single contributor to sense organ disease was hearing loss.

The chart below measures disability-adjusted-life-years for people afflicted with sense organ diseases. The data show the primarily age-related growth in DALYs, attributed to the GBD 2015, with those taken in 2005. OM

Below are the diseases responsible for the highest amount of disability-adjusted-life-years, both globally and in the United States. Exact number of DALYs are only available at the global level.

Leading causes of DALYs globally (in thousands)

1. Ischemic heart disease (164,020.4)

2. Stroke (118,626.7)

3. Lower respiratory infections (97,451.8)

4. Low back and neck pain (94,941.5)

5. Neonatal preterm birth complications (74,833.6)

6. Diarrheal diseases (71,589.5)

7. Sense organ disease (68,515.2)

8. Neonatal encephalopathy (67,856.5)

9. Road injuries (67,270.4)

10. HIV (66,689.5)

Leading causes of DALYs in the United States

1. Ischemic heart disease

2. Low back and neck pain

3. Diabetes

4. Lung, bronchus and trachea cancers

5. Depression

6. Chronic obstructive pulmonary disease

7. Drugs

8. Alzheimer’s

9. Sense organ disease

10. Other musculoskeletal disorders

New study shows good results for OSD treatment

More favorable data in for BlephEx.

By René Luthe, senior editor

A retrospective analysis of 177 OSD patients treated with the BlephEx (BlephEx LLC) procedure showed improved scores on key dry eye diagnostic measurements, reports Alice T. Epitropoulos, MD, lead investigator. Analysis of pre- and post-treatment data show that tear break-up time increased from a pretreatment average of 5.6 seconds to 9.3 seconds post-treatment — a 66% increase. SPEED scores improved following treatment as well, going from an average pretreatment of 11.5 to 5.85 post-treatment; average OSDI scores decreased from 50.60 to 32.3. Follow-up measurements were taken after just one treatment at intervals ranging from one to 16 weeks, says Dr. Epitropoulos, with ancillary treatments such as artificial tears unchanged both pre- and post-treatment.

The six-minute microblepharoexfoliation procedure treats all four eyelids using a medical-grade micro-sponge along the lid edges and lashes to remove the “scurf and biofilm that are known drivers of ocular surface inflammation, which is the most common reason patients see their eye doctor,” she explains. “I think clinicians can now take a more active role in treating blepharitis instead of relying on patients’ ability to perform semi-effective lid scrubs at home.”

Though the dry-eye market is a large one, Dr. Epitropoulos thinks the microblepharoexfoliation treatment could prove useful to another major eye-care segment: patients about to undergo cataract or glaucoma surgery. “One of the most feared complications after cataract surgery is endophthalmitis,” she notes.

“We don’t always know the source of the bacteria causing the infection, but studies show the organisms that are isolated in the vitreous of infected eyes are the same as the organisms recovered from the patient’s lids and lashes. So that’s why I think BlephEx treatment is something to consider for cataract patients, or even glaucoma patients preoperatively, to really clean those lids.” OM

CMS defends controversial reimbursement plan

Lucentis and Eylea would be most affected.

By Jerry Helzner, contributing editor

A decision on a so-called “demonstration plan” announced by CMS in March that would reward medical practitioners for administering less-costly drugs and penalize them for using more expensive therapies is expected before the end of the year.

The plan has not been withdrawn despite the fact that public comments from the medical community and lawmakers have been overwhelmingly against implementation of such an initiative.

CMS Chief Medical Officer Patrick Conway, MD, strongly defended the plan in an appearance before a hostile Senate Finance Committee this summer.¹

In an interview, Dr. Conway would only say that CMS is continuing to review the more than 1,300 public comments it has received and is considering some modifications that would ensure patients in rural communities access to the drugs they need.

Though the plan — affecting Part B Medicare physician-administered therapies — would not be initially implemented nationwide, CMS says the number of practices affected would be sizable. The greatest impact in ophthalmology would fall on retina specialists who prescribe Lucentis (Genentech) and Eylea (Regeneron).¹

Given the reimbursement formula that has been proposed by CMS, practices would most likely lose money on every injection of those two leading anti-VEGF drugs prescribed for a range of retinal diseases. The current formula of average selling price plus 6% would be reduced to average selling price plus 2.5% plus $16.80 per drug per day, which would not cover the overhead for procuring, storing, administering, tracking and applying for reimbursement. In a joint letter² to CMS disputing the merits of the plan, the AAO, ASRS, and The Retina Society asserted that Avastin (Genentech) as the lower-cost alternative anti-VEGF drug is not interchangeable with Lucentis and Eylea for efficacy, safety and — as a compounded drug — potential availability reasons.

Who’s for the demo plan? While the medical community is overwhelmingly against the demonstration plan, the major “public policy” groups, including the AARP, Public Interest and the Center for Medicare Advocacy, are all strongly backing it.

David Lipschutz, JD, managing attorney for the Center for Medicare Advocacy, says his group is for the plan because it will cut Medicare outlays as well as reduce the power of the pharmaceutical industry.

“We look at this initiative on more of a global basis and don’t get involved with the nuances that may affect each individual specialty or subspecialty,” he says. “If the ophthalmology community can cite some special factors that would make this plan a hardship, it’s up to their representatives to present them. We would be all ears.”

Meanwhile, attorneys who represent ophthalmology practices are advising that their clients prepare for a CMS decision that may not be to their liking.

“The plan may be amended and CMS may make special carve-outs to lessen the impact on certain specialties, but everyone is following this and it’s too much of a political ‘hot-button’ issue to go away,” says David Farber, of King & Spalding, Washington, D.C. OM

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