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February 2005

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

Lead Exposure May Lead to Cataracts

Retinopathy Is Focus of Recent Research Results

Gun-Related Eye Injury rates Still Not Low Enough

Just What the Doctor Ordered: Larger Fonts

Lead Exposure May Lead to Cataracts
Nearly half of the cataracts in men older than 60 years can be attributed in part to the level of lead they accumulated in their bones earlier in life, an analysis of a long-running men’s aging study has concluded.1

The magnitude of the added risk was surprising, even to the scientist whose idea it was to look for the link. And it could indicate that today’s young adults and children—without the chronic lead exposure from leaded gasoline, lead paint and other sources —could develop fewer or slower-progressing cataracts than their parents and grandparents did.

“Given changing levels of lead exposure, perhaps what we saw in the past in terms of rate of progression of cataracts may be changing with the cohorts coming up,” said Debra A. Schaumberg, ScD, MPH, lead author of the study and assistant professor and director of ophthalmic epidemiology in the division of preventive medicine at Boston’s Brigham and Women’s Hospital.

After adjusting for smoking and other risk factors, the researchers found that men whose shin bone level of lead was in the top quintile were about three times more likely to have cataracts as men in the lowest quintile. Risks also were elevated about 70 percent in the middle quintiles. The researchers concluded that 42 percent of the cataracts in the 642 study subjects could be attributed in part to past lead exposure. 

“Forty-two percent is a lot,” Dr. Schaumberg said. “We didn’t really know what we would find, but I thought that the hypothesis was really strong because of the strong evidence of oxidative damage that lead causes elsewhere in the body. And that oxidative damage is a key mechanism in cataractogenesis. So we were pretty sure we would find something if we had the right marker to look at lead exposure.”

X-ray fluorescence measurement of bone lead levels has emerged as a reliable marker for evaluating lead’s long-term effects and has shown that trabecular bone (e.g., patella), with its higher turnover rate, reflects more recent lead exposure while cortical bone (e.g., tibia) indicates long-term exposure.

Caption: Because lead exposure is on the decline, younger generations may have a lower risk for cataract progression.

Data from regular exams conducted during the decades-long Normative Aging Study were used in the 1990s to show that lead is associated with higher risks of hypertension and electrocardiographic conduction disturbances. But cataract results had to await further aging of the 642 study subjects to a more cataract-prone mean age, 69. 

Men in the highest quintile of mean tibia lead were 3.19 times more likely than the lowest-quintile group (P for trend = 0.01) to have cataract surgery or a cataract graded 3+ or higher during the study’s 16-year analysis period. For patellar bone, the odds ratio was 1.88, but without statistical significance.

The elimination of leaded gasoline and of lead in household paint has reduced the exposure of Americans to lead since the late 1970s. So the higher cataract risk will likely fall on adults born before that time, Dr. Schaumberg said. What will this mean for ophthalmologists? “Lead might be accelerating progression of lens opacities in the past several decades of cohorts,” she said. “But in the patients coming up now, maybe their cataracts will progress more slowly than those we saw in the past.”

The findings also suggest that ophthalmologists might want to highlight risk factors for certain patients. These include lead in household water from old plumbing and from restoring old houses. Lead solder, stained glass and indoor shooting ranges also present exposure risks. “There needs to be an awareness that even relatively low levels of exposure have measurable health effects in adults,” said Dr. Schaumberg.

1 Schaumberg, D. A. et al. JAMA 2004;292(22):2750–2754.

Retinopathy Is Focus of Recent Research Results
Preventing diabetes complications with therapies as simple as controlling blood pressure and as complicated as blocking molecules or manipulating genes has been in the research spotlight recently.

• The largest and most clinically relevant of the studies, from the long-running U.K.  Prospective Diabetes Study, concluded after nine years of follow-up that tight control of hypertension reduces the likelihood of diabetes complications such as retinal microaneurysms, hard exudates and cotton-wool spots.1 The study of 1,148 type 2 diabetics with hypertension randomized patients to tight blood pressure control (150/ 85) vs. a looser goal (180/105).

Differences in the patients’ retinal conditions appeared by 4.5 years, when 23.3 percent of the tight-control group had five or more microaneurysms compared with 33.5 percent of the other group (P = 0.003). For hard exudates at 7.5 years, the prevalence was 11.2 percent vs. 18.3 percent. At that same time point, the group with lower blood pressures had 53 percent as many hard exudates and cotton wool spots as the group with looser controls (all P < 0.001).

Caption: One study shows that by controlling blood pressure, diabetics may reduce the ocular symptioms of their disease.

The authors write that higher blood pressure may worsen diabetic retinopathy because it “increases blood flow and, thus, by increasing shear stress will damage vessel walls and will precipitate and worsen retinopathy.”

• New analysis was reported at the Academy’s 2004 Joint Meeting for data from the Phase 3 trials of Eli Lilly’s protein kinase C-beta inhibitor, ruboxistaurin (formerly known as LY333531) for diabetic macular edema. Protein kinase C-beta has been implicated as a cause of the leukocyte entrapment within the retinal microcirculation that causes blood flow disturbances in the early diabetic retina. It is thought to be upregulated in the retina by VEGF, thus playing a role in the breakdown of the blood-retinal barrier.

The ruboxistaurin study found that, when the diabetic macular edema was at the center of the macula, subjects who were taking 32 milligrams per day of ruboxistaurin had a mean ETDRS visual acuity of 71 letters. That compared with 60 letters in the placebo group (P < 0.001). The analysis also suggested that ruboxistaurin might slow the progression of peripheral edema toward the macula’s center, but the data weren’t statistically significant. The results were reported by Matthew J. Sheetz, MD, PhD.

• Researchers at the University of Pittsburgh reported success with using an inactivated herpes virus to deliver genes for neurotrophic factors to the feet of mice with diabetic neuropathy. The animals’ condition was cured, and the genes continued to produce the nerve-supporting molecules six months after inoculation. James R. Goss, PhD, research assistant professor of molecular genetics and biochemistry, reported on the study at the Society for Neuroscience’s meeting in October.

1 Matthews, David R. et al. Arch Ophthalmol 2004;122(11): 1631–1640.

Ocular Trauma
Gun-Related Eye Injury Rates Still Not Low Enough
The good news: Gun-related eye injury rates in the United States have leveled out at a relatively low rate over the last few years, after a steady decline in the mid-1990s, say researchers at the University of Alabama, Birmingham.

The bad news: There are still more than 3,000 such injuries every year, most of them unintentional.

Gerald McGwin, PhD, associate professor of epidemiology, ophthalmology and surgery at UAB, used data from the Consumer Product Safety Commission and found that the rate of eye injuries from guns was 0.97 per 100,000 in 2002, the most recent year available.

The rate rose steadily in the early 1990s, peaking at 1.5 per 100,000 in mid-decade, and has hovered around 1 per 100,000 since the late 1990s, Dr. McGwin said. “We also found that unintentional gun-related eye injuries were more common than intentional injuries,” he said.

Most commonly, the people sustaining these injuries are 10- to 19-year-olds, males and African-Americans. Paintball and BB guns are two of the major culprits, suggesting that eye protection might have prevented the injuries.

Dr. McGwin said he suspects the decline in injury rates since the late 1990s partly might reflect a lessening of the paintball fad. But paintball guns continue to account for more than a quarter of all the gun-related eye injuries seen in emergency departments, he said.

Patient’s Perspective
Just What the Doctor Ordered: Larger Fonts
It makes sense that a visually impaired patient would have trouble reading small type on the back of a bottle of eye drops. But how impaired must the patient be before this mismatch between vision and type size becomes critical?

Three Scottish physicians think they’ve found an easy tool for answering that question: the patient’s BCVA at distance.1

The cutoff point is a distance BCVA of 6/18 (roughly equivalent to 20/60), the researchers at the Tennent Institute of Ophthalmology in Glasgow concluded after testing a total of 180 patients. Most people with that level of BCVA could read the instructions on the side of a package of eye drops without magnification, they found.

But patients whose distance BCVA was 6/24 to 6/60 (roughly 20/80 to 20/200) could read instructions only if they were written in a much enlarged print, and a 22-point typeface sufficed for all. This is more than three times the size of the 6-point type commonly used on eye drop packaging.

“This has significant implications in clinical practice as it provides evidence that we need to include enlarged print instructions for patients with a visual acuity of 6/24 or less to enable them to self medicate safely and effectively,” the authors write.

Lead author Suzannah R. Drummond, MBBS, MRCOphth, specialist registrar in ophthalmology at the Tennent Institute, said this recommendation has been received positively—but also with a little sheepishness mixed in.

“Generally the feeling is that this seems such a simple and obvious idea, why has is not been done before?” she said. “People have been enthusiastic that, now the study has been completed, we can actually do something about it.”

The researchers noted in their article that physicians and their staff can assess this need without any extra testing. “As we have shown and as one would expect, the median near VA decreases as the best distance VA decreases. Therefore, to judge whether a patient will need enlarged print to read their medication instructions, the distance VA can suffice,” they write.

Their bottom line: “We would recommend that a copy of instructions, printed in enlarged print of Arial font 22, be distributed with all bottles of medication when the patient is found to have a best distance VA of 6/24 [20/80] or less, particularly if the patient is elderly.”

1 Drummond, S. R. et al. Br J Ophthalmol 2004;88:1541–1542.