In 100 presentations of scientific papers and posters, scientists and physicians from the Keck School and USC’s Doheny Eye Institute described their advances in the field of ophthalmology at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO).
Thirteen of the 18 Keck School residents in ophthalmology presented, noted Alfredo Sadun, professor of ophthalmology and neurosurgery—the third highest number of residents from any medical school in the country.
At the event, held in Fort Lauderdale, Fla., April 30-May 4, almost a dozen of the presentations involved a unique cohort of Brazilian families afflicted with Leber’s Hereditary Optic Neuropathy (LHON)—a rare, hereditary condition that causes loss of central vision.
For reasons still not entirely known, not everyone who has the genes for LHON loses their sight, or even exhibits significant symptoms. The disease, which is passed from the mother through genes in the mitochondria, afflicts mostly males. The symptoms are sudden and irreversible: devastating loss of sight in one eye, followed by loss of sight in the other eye weeks or months later.
USC scientists are zeroing in on understanding more about the disease, said Sadun, thanks to this cohort of 332 individuals across seven generations living in rural Brazil. They have studied for the past six years.
“One of the many mysteries of the disease is why do people go blind instead of developing other types of problems in other parts of the body?” said Sadun. One study determined that the disease affects the smallest active neurons in the body. “It is a particular subset of the optic nerve, a very small fiber, that fails and causes the blindness,” he said.
Another study looked at an 82-year-old woman, who had the gene but had not gone blind. “The autopsy revealed that the smallest fibers had died, but the zone around them had created a buffer of protection so it did not affect the rest of the eye,” said Sadun. “That gives us some ideas for treatment.”
A third study was the application of optical coherence tomography—a newer, noninvasive imaging technology developed in part by David Huang, associate professor of ophthalmology—to visualize the smallest fibers in the back of the eye. “We brought one down to this little rural corner of Brazil and examined 158 patients with this technique, and we found even in those who are young but have not lost their vision yet the ordinarily thin fibers were very swollen. So they were still functioning, but there was subclinical disease.”
As a result of the ongoing studies, said Sadun, researchers believe LHON affected fibers undergo “a series of tinderbox effects. If the smallest fibers are considered like dry wood and the largest fibers like healthy green wood, then we’ve seen it’s not just when the dry wood is involved but when there is a critical concentration of dry over wet. In those areas where the fewest large fibers exist, there’s a conflagration, which results in blindness. Or there is a threshold of small fiber involvement that overwhelms the system.”
Sadun feels confident that these findings will lead to a clinical intervention “within the next few years.”
Another difficulty, he noted, is that LHON is seriously under-recognized worldwide, because it usually takes a neuro-ophthalmologist to diagnose it. “In most of the world it’s simply lumped in with many other diseases and called optic atrophy,” he said.