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October 2004


News in Review

Wavefront’s Usefulness Expands to Cataract

Special Glasses Make Radiation More Bearable

Transplant Rejection Theory Looks Promising

New Look at How Retinoblastoma Forms

Blindness Can Lead to Exceptional Aural Skill

Wavefront’s Usefulness Expands to Cataract
A New Zealand research group has demonstrated that wavefront aberrometry can be used to document vision problems from early stage cataracts—suggesting a clinical technique that could give ophthalmologists objective means to confirm the need for surgery in these patients.

“Particularly with certain carriers in some regions, it has been difficult to document the need for cataract surgery in symptomatic patients with early opacities,” said Samuel Masket, MD, clinical professor of ophthalmology at the University of California, Los Angeles. Dr. Masket chairs the anterior segment panel within the Academy’s Preferred Practice Patterns committee.

“Some cataracts may not appear to be significant from an anatomical standpoint, and good Snellen acuity may be retained. But the Snellen test doesn’t take into account the functional visual problems of these patients,” Dr. Masket said.

Even when patients with mild to moderate cataracts complain of having to restrict their activities, such as nighttime driving, insurers want vision problems documented before authorizing surgery, Dr. Masket said. They sometimes view glare disability or contrast sensitivity testing as too subjective. “But wavefront testing is strictly an objective, not a subjective, test. Since this technology is being applied regularly for laser vision correction, we have a testing method that should give reproducible documentation of visual disability,” he said.

The study prompting Dr. Masket’s comments was conducted at the University of Auckland, where 120 patients were screened to find 20 study subjects with mild to moderate lens opacities and no other ocular pathology.1

Even though the mean BCVA for these patients was 20/30 for cortical opacities and 20/50 for nuclear cataract, they displayed statistically significant increases in higher-order aberrations compared with 20 control eyes without cataracts. In eyes with predominantly cortical cataract, coma and tetrafoil were higher. For nuclear cataract, spherical aberration and tetrafoil were increased.

“This study suggests that wavefront testing adds to the battery of tests we have available in an attempt to document visual deficits in symptomatic patients whose Snellen acuity is at a good level,” Dr. Masket said.

1 Sachdev, N. et al. J Cataract Refract Surg 2004;30(8): 1642–1648.

Special Glasses Make Radiation More Bearable
Two years ago, New York City eye cancer specialist Paul T. Finger, MD, asked himself a simple question: If nuclear manufacturing workers can wear leaded safety glasses to prevent radiation from entering their eyes, why can’t ocular melanoma patients wear the same glasses to keep radiation from exiting?

It turns out that they can, Dr. Finger discovered after trying the clear lead-coated goggles with patients who were undergoing brachytherapy for their ocular tumors. He published his findings in the June American Journal of Ophthalmology.1

Until now, brachytherapy has presented a special challenge for patients who already have lost sight in their other eye. Preventing radiation leakage into the environment has meant wearing an opaque leaded eye patch for a week at a time, said Dr. Finger, clinical professor of ophthalmology at New York University and director of ocular tumor services at the New York Eye and Ear Infirmary.

“It’s just a wonderful thing, particularly for patients who only have one eye,” he said. “They can put these leaded glasses on. And they can still live normally. At first I used them with patients who had only one eye. But then I thought, if it worked for those people, why not use them on everybody?”

Binocular patients prefer the safety glasses over the lead patch for reasons other than the patch’s visual impact, Dr. Finger said: “Because they don’t have to have tape—which gets all gooey—on their face for a week. They feel more normal.”

Dr. Finger is just happy that the idea is available for other eye cancer specialists to consider. “Sometimes the simplest things are the nicest things,” he said.

1 Am J Ophthalmol 2004;137(6): 1149–1151.

Transplant Rejection Theory Looks Promising
If the cornea can be protected from communicating with the lymphatic system, the eye’s “immune privilege” can be converted to what appears to be near-complete “protection” from the process that causes corneal transplant rejection, a recent study1 concludes.

This fundamental finding grew from the renewed observation that an inflamed corneal transplant begins growing lymphatic vessels, said the senior author on the paper, M. Reza Dana, MD, MPH, associate professor of ophthalmology at Harvard University and the Massachusetts Eye and Ear Infirmary and senior scientist at The Schepens Eye Research Institute.

“Lymphatics grow into the cornea not only in transplantation but in a variety of inflammatory corneal conditions,” Dr. Dana said. “This was observed almost 30 years ago. It was a very important observation, which many sort of forgot about because what you see more prominently is these red blood vessels. But right alongside the blood vessels you have the growth of lymphatics.”

These lymphatics drain antigen-presenting, or dendritic, cells from the cornea to the lymph nodes, he said. The dendritic cells give the T lymphocytes the information that “primes” them to attack the cornea. Blood vessels then carry the activated T cells back to the cornea, and the immune attack begins.

In an earlier paper, Dr. Dana’s group showed in mice that removing the corneal transplant recipients’ lymph nodes before transplantation resulted in no immune response occurring in the eye. In the recent study, they showed in various ways that blocking VEGFR-3 (vascular endothelial growth factor receptor-3)—important in the growth of lymphatic vessels—also prevents a corneal immune response. Together, these findings suggest that interfering with communication between the eye and lymph nodes may prevent transplant rejection in humans, he said.

“You can’t do cervical lymph node dissection in people prone to rejecting their corneal transplants,” he said. “Rather, you want to be able to neutralize VEGFR-3 at the molecular level. That is why we call this strategy ‘molecular lymphadenectomy.’”

Eventually, the goal would be to do this with an antibody or a chimeric molecule to block VEGFR-3, or a drug that would block the transcription of VEGFR-3 or its ligand, Dr. Dana said.

1 Chen L, et al. Nature advance online publication July 4, 2004.

Eye on Research
New Look at How Retinoblastoma Forms
The first mouse model for inheritable retinoblastoma has led to the surprising hypothesis that this cancer arises from an entirely different mechanism than has long been postulated.

Rather than aberrantly dividing cells that “forgot” how to undergo apoptosis, retinoblastoma cells are Rb-deficient precursor cells whose abnormal, extended growth period fails to end in terminal differentiation, a Toronto research group proposes in a paper published in the June Cancer Cell.1

“Retinoblastoma arises from a precursor [cell] that has extended, not infinite, proliferative capacity, and is intrinsically death-resistant, not death prone. We suggest that additional lesions common in retinoblastoma overcome growth arrest, not apoptosis,” they write.

In this new model for how retinoblastoma begins, a tumor would form only if another genetic mistake occurred to stop terminal differentiation of the amacrine cells. That mutation would be beyond the Rb gene defect that already has been described in the literature, said study coauthor Rod Bremner, PhD, associate professor of ophthalmology and visual sciences at the University of Toronto. The study suggests these additional defects block terminal differentiation, not death.

Dr. Bremner said this was an unanticipated conclusion from a project to breed knockout mice lacking the Rb gene, specifically in the retina. The researchers noticed that the mice’s retinas looked different than had been expected. Despite the lack of viable photoreceptors or ganglion cells, the retina’s inner nuclear layer contained healthy amacrine cells, which mediate communication between the photoreceptors and the retinal ganglion cells.

“It was a huge ‘Aha!’ moment for us,” Dr. Bremner said. “When I saw those amacrine cells forming a beautiful layer, it was like ‘Kaboom!’” 

The group now is examining which genes drive division in Rb-deficient amacrine cells and which genes keep these abnormally multiplying cells alive, while, in contrast, closely related Rb-deficient ganglion cells die. “If we can figure out the pathway that keeps Rb-deficient cells alive, then that will point us toward possible ways to disable it,” he said.

1 Chen, D. et al. Cancer Cell 2004;5(6):539–551.

Eye on Research
Blindness Can Lead to Exceptional Aural Skills
Both anecdotally and scientifically, the blind have long been known to be better than sighted people at spatial localization of sounds. But do the brain’s compensatory mechanisms also make them better at other auditory tasks, such as listening to music?

Yes—but only if the onset of blindness was very early in life, says a group of Montreal neurological researchers.

Reporting in the July 15 Nature, the University of Montreal scientists describe an experiment with 14 blind subjects, half of whom lost their sight by 2 years of age, and half with blindness after age 5.1 Along with 12 sighted controls, they were asked to listen to two pure tones in succession, then describe whether the second tone’s pitch was higher or lower. The pitch difference varied from one-eighth octave to 128th of an octave, and the tones’ duration varied from 333 milliseconds to 20.8 ms.

As expected, all subjects performed worse as the pitch difference and duration of the tones decreased. There was no difference between the late-blind and the controls. But the early blind subjects outdid the other groups in all conditions.

Indeed, when the tones were presented the most rapidly, the early blind group had a higher percentage of correct answers than did the sighted subjects under the best experimental conditions. Statistical testing showed that 42 percent of the performance variability could be attributed to the age at which loss of sight occurred, apparently because of greater cerebral plasticity at younger ages.

Say the researchers: “We conclude that compensatory auditory mechanisms following visual deprivation must extend beyond the spatial domain.”

1 Gougoux, F. et al. Nature 2004;430:309.