EyeNet Magazine

News in Review
A Look at Today’s Ideas and Trends
By Linda Roach, Contributing Writer

Are Your Patients Driven to Distraction?

SDF-1 Growth Factor Appears to Play a Role in Neovascularization

Who Would Be a Referee?

There’s Hope for Nipping Allergy in the Bud

Are Your Patients Driven to Distraction?

If your patients complain about difficulties with glare from those blue-tinted headlights on newer, high-priced automobiles, what should you tell them? While there’s not much practical advice you can pass along, you can update them on study findings.

About the lights. After mounting a research effort over the last few years, the National Highway Traffic Safety Administration has been able to discern the main reason that high-intensity discharge (HID) lights bother people so much: They’re brighter than conventional incandescent or halogen headlamps.1 While this news may hardly seem surprising to drivers sensitive to the lights, some researchers had hypothesized that the distinctive blue color might attract the eye or that the eye may be more sensitive to the bluish color.

One study did show that oncoming drivers fixate on the lights longer than they do conventional headlights (2 to 5 seconds, vs. 1 to 3 seconds), increasing the time it takes for their eyes to readjust to the darkened road afterward.2

However, Martin A. Mainster, PhD, MD, professor and vice chairman of ophthalmology at the University of Kansas, states in the British Journal of Ophthalmology, “an analysis of automobile headlights, intraocular stray light, glare and night driving shows that brightness rather than blueness is the primary reason for the visual problems that HID headlights can cause for older drivers who confront them.”3 (His article did not extend to younger drivers.)

The visual problems associated with these powerful lights can be exacerbated by seemingly minor details. For instance, even a one-degree vertical misalignment can cause HID headlights to shine disturbingly into the eyes of oncoming drivers, and dirt on the headlights can scatter brilliant light unpredictably down the road, and into other drivers’ eyes.4

“Although measures are taken to stabilize these systems and keep oncoming drivers from viewing HID headlights directly, the fact is that in going around curves on two-lane roads and in other situations, oncoming drivers can be directly exposed to light three times as intense as with conventional headlights,” Dr. Mainster said.

About ocular response to headlight glare. Conventional wisdom has it that the elderly are more likely to have problems with nighttime glare than younger folks. But a survey by the National Center for Statistics and Analysis showed that 35- to 54-year-olds were the most likely to complain of “disturbing” glare from auto headlights. Women were more likely to find headlight glare bothersome than men.

More than 4,600 people have complained to the NHTSA in the three-and-a-half years since the agency began an official inquiry on what to do about glare from problem headlights. In addition to the HID lights, aftermarket auxiliary lights on car bumpers and high-mounted truck and SUV lights have come in for public criticism.

To register a complaint with the NHTSA, call 1-888-327-4236.

1 National Center for Statistics and Analysis. “Drivers’ perceptions of headlight glare from oncoming and following vehicles.” Department of Transportation NHTSA Technical Report # DOT HS 809 669, January 2004. Available at: http://www-nrd.nhtsa.dot.gov/pdf/nrd-30/NCSA/Rpts/2003/809-669/images/GLARE_PERCEP.pdf.

2 Perel, M., Singh, S. “Lighting: Problems, research, countermeasures,” PowerPoint presentation at a 2003 meeting between regulators and auto engineers. Available at: http://www-nrd.nhtsa.dot.gov/pdf/nrd-01/SAE/SAE2003/Perel.pdf.

3 Br J Ophthalmol 2003;87(1): 113–117.

4 Mace, D., Garvey, P., Porter, R. J. “Countermeasures for reducing the effects of headlight glare.” Prepared for the AAA Foundation for Traffic Safety, December 2001. Available at: http://www.aaafoundation.org/pdf/HeadlightGlare.pdf.

Diabetes Update

SDF-1 Growth Factor Appears to Play a Role in Neovascularization

Maybe one way to stop retinal neovascularization in diabetics would be to block a growth factor that mobilizes the stem cells and progenitor cells that trigger production of aberrant blood vessels, a group of basic researchers has suggested.1

Their target for this approach isn’t the by-now familiar VEGF, but instead is a molecular cousin called stromal cell-derived factor-1 (SDF-1).

Earlier research by the group, based at the University of Florida, showed in mice that hematopoietic stem cells produce both blood cells and circulating endothelial progenitor cells (EPCs) that form new blood vessels.

In the current paper, the group reported that EPCs are themselves mobilized by SDF-1 to promote repair of vascular injury. Vitreous samples taken from 46 patients just before intravitreal injection of triamcinolone acetonide for diabetic macular edema showed they had elevated levels of SDF-1. The same levels of the growth factor, delivered to test mice, induced retinopathy.

Furthermore, when the researchers injected anti-SDF-1 antibodies into mouse eyes with retinal damage, neovascularization did not occur—even when high levels of VEGF were present. This indicates that SDF-1 not only is necessary in the disease process but also is sufficient by itself to cause neovascularization, they concluded.

“Though anti-VEGF treatments may be a great advancement in alleviating the effects of ocular diseases, there may be other cytokines/chemokines that, when blocked, may improve visual acuity by augmenting anti-VEGF treatments,” they write. “Our clinical data provide what we believe to be the first evidence that SDF-1 may play a major role in the pathology of both macular edema and proliferative retinopathy.”

Stromal cell-derived factor-1 is the latest growth factor implicated in neovascularization.

Caption: Move over VEGF. Stromal cell-derived factor-1 (SDF-1) is the latest growth factor implicated in neovascularization, notably in diabetics.

The researchers cautioned that the mouse model of diabetic proliferative retinopathy does not exactly parallel the human disease. However, they remain confident enough for the senior author on the paper, associate professor Edward W. Scott, PhD, to cofound a company called RegenMed Inc., to investigate stem-cell based therapies. Primate studies of SDF-1 activity are currently under way, as a prelude to a Phase 1 clinical trial in the next year to 18 months.

Dr. Scott, whose background is in microbiology and genetics, said he’s playing catchup on whether SDF-1 might also play a role in age-related macular degeneration. “I am just learning to spell AMD,” he joked. “That is the joy and bane of wonderful collaborations that take you into new areas. There are endless opportunities, but a lot to learn. We will be trying to address the AMD question this year.”

1 Butler, J.M. et al. J Clin Invest 2005;115(1):86–93.

Sports Zone

Who Would Be a Referee?

And now for something completely different: Soccer referees aren’t blind—the human eye isn’t always capable of actually seeing whether someone is offside or not.

So says a study in the British Medical Journal.1 The explanation is complicated, even convoluted, judging by reaction from British football fans on the BMJ Web site. But it will warm the hearts (or raise the hackles) of soccer fans everywhere.

Author Francisco Belda Maruenda, MD, a family practitioner at Centro Salud de Alquerías in Murcia, Spain, mined the ophthalmic literature to add up the amount of time it takes for a referee’s eyes to keep track of the five objects involved in an offside call—two players of the attacking team, the last two players of the defending team and the ball.

The referee must switch attention between objects by using saccades and accommodation, and sometimes smooth pursuit eye movements, vergence movements and vestibular movements—each with a latency of 130 to 360 milliseconds, plus the time needed for the movement itself. In the most complicated situation, it could easily take almost a second to track all five objects, and the situation wouldn’t improve much even in the best-case scenario, Dr. Belda Maruenda said.

“If all the players are within the visual field of the referee or his assistants and there is no need for accommodation, the minimum time needed to detect the three players relevant to an offside position is 160 ms because of the capacity of the central nervous system for parallel processing of different objects moving at the same time and the visual capacity to store and integrate,” he writes.

The key factor in applying this rule correctly is that the player in question must be in the offside position at the exact time when the ball is passed from a teammate, not when the player receives the ball or when the ball is en route between the players.

Indeed, a player running at a speed of 100 meters in 14 seconds will move 71 centimeters in 100 ms. If he moves in a direction opposite to the defensive player, the relative change in position between the two will be even greater—requiring a whole new set of time-consuming eye movements by the referee.

His conclusion? This sport needs video verification of offside calls because “the relative position of four players and the ball cannot be assessed simultaneously by a referee, and unavoidable errors will be made in the attempt.”

1 Belda Maruenda, F. Br Med J 2004;329(7480):1470–1472 and Br Med J 2004;330(7484):188.

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Research Report: There’s Hope for Nipping Allergy in the Bud

Prescribing mast cell inhibitors or stabilizers to treat allergic conjunctivitis isn’t unusual at this time of year. But what if, instead of blocking the release of histamine downstream, the activation of the histamine-producing mast cells could be prevented altogether?

That’s the tantalizing idea that comes from a research report showing that a chemical messenger, MIP-1α, can be blocked to prevent the acute-phase hypersensitivity reaction in conjunctival mast cells.

MIP-1α, or macrophage inflammatory protein-1α, works along with the high-affinity IgE receptor as a costimulator of the initial allergic reaction, the researchers at University College London conclude based on their studies in mice.1

They demonstrated that, if MIP-1α is prevented from binding to a specific chemokine receptor in conjunctival cells, mast cell degranulation decreases markedly and clinical symptoms of the acute allergic reaction almost disappear. This might explain the previously reported connection between MIP-1α responsiveness and the severity of a person’s allergies, the group noted.2

For the future, they say: “The data also support the emerging view that antagonizing the chemokine/chemokine receptor interaction or signaling from chemokine receptors hold[s] promise for the treatment of both acute- and late-phase reactions.”

1 Miyazaki, D. et al. J Clin Invest 2005;115(2):434–442.
2 Alam R, et al. J Exp Med 1992;176(3):781–786.




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