EyeWorld Asia-Pacific September 2012 Issue

46 September 2012 EWAP GLAUCOMA The ‘latitude’ - from page 45 “This says to me one of two things,” Dr. Pasquale said. “There are other genes involved, or there must be environmental risk factors for the disease. That’s how we began the search for environmental risk factors for this condition.” The latitude effect When looking at the disease burden of pseudoexfoliation glaucoma worldwide, Dr. Pasquale and colleagues noted that countries closer to the equator had a lower prevalence of the condition. “The farther away you went from the equator, heading toward the North Pole, the prevalence of the disease increased,” he said. This is what Dr. Pasquale calls the “latitude effect.” A study published in Archives of Ophthalmology (2011 Aug;129(8): 1053-60) by Dr. Pasquale et al. further examined this latitude effect in the U.S. The study assessed exfoliation syndrome by geographic latitude tier in the lower 48 states and assigned state-level climatic data such as temperature, elevation, and sun exposure according to patients’ residential location. “We looked at whether or not living in the Northern tier was associated with an increased risk of exfoliation syndrome or glaucoma after adjusting for age, race, gender, and other potential confounders,” he said. “We found on multiple occasions now that this latitude effect did hold up.” But what’s driving this? Could it be vitamin D or perhaps elevation? Maybe, but Dr. Pasquale has some other theories: solar exposure and colder ambient temperatures. “We believe it’s sun bouncing off reflective surfaces into the eye that’s the major problem,” he said. “The sun that’s bouncing off of reflective surfaces into the eye can pass through the cornea and be absorbed by the iris. That’s where there are blood vessels that are aligned with elastin. So we think that having this gene somewhat diminishes the ability for elastin to line the blood vessels over time, plus the ultraviolet (UV) damage contributes to the formation of the exfoliation material.” The temperature factor is even more compelling. The temperature inside the human body is typically a steady 98.6 degrees Fahrenheit. But there’s reason to believe the eye does not hold that heat. “The eye is more exposed to the elements than we can appreciate,” Dr. Pasquale explained. “There aren’t a lot of blood vessels inside the front of the eye. When it’s 32 degrees F outside, the temperature in the front of your eye is probably not 98.6 degrees. It’s not 32 degrees, obviously, but it’s somewhere below 98.6 degrees. The point is this exfoliation material is a heterogeneous group of large molecules that given a colder temperature will want to precipitate out a solution.” Dr. Pasquale is currently building an even stronger case to support his hypothesis. The research has yet to be published, but using a validated solar exposure questionnaire, Dr. Pasquale and colleagues found that people who previously were lifeguards during their young adult life had a three-fold risk of exfoliation syndrome. Ski instructors had an eight-fold increased risk. “This makes perfect sense with light bouncing off reflective surfaces,” he said. “Light is going to bounce more strongly off of snow than water. Both are reflective but the snow is going to be a stronger reflector.” Prevention or disease modification? If this research proves true, it would be a huge victory in the fight against glaucoma. Physicians will be able to advise the next generation of patients how to protect themselves against the disease. “The most obvious recommendation would be sunglasses,” he said. “Sunglasses not only protect your eyes from the sun, but they increase the local temperature so it is closer to 98.6 degrees. Those are the strategies I would hope down the road would be useful in reducing blindness from this condition.” He’s also looking into coffee consumption. It turns out Scandinavians are the highest consumers of coffee in the world, drinking around 10 cups a day on average. The U.S., in contrast, only consumes about 3 cups a day. “So the question is since exfoliation is hyperendemic in Scandinavian countries—1 in 5 people over the age of 60 have the condition in Norway, Sweden, and Denmark—could it be driven by coffee consumption? There is some evidence to say the answer is yes,” he said. Additional research needs to be done, but this type of approach could be the future of glaucoma treatment. “Whether it’s pseudoexfoliation or open- angle glaucoma, the future that I hope I’ll live to see and maybe help bring around is what we call disease-modifying therapy, where we understand what the disease process is and directly interrupt it,” said Douglas Rhee, MD, Massachusetts Eye and Ear Infirmary. “I think that’s what the future holds, but we’re not going to be there in 3 years, we’re not going to be there in 5. We might see the inklings of it in 7, but it’s the 10-15 year period where we hope to see that come to fruition; we’re getting there.” In the meantime, Dr. Rhee stressed that general ophthalmologists should keep pseudoexfoliation glaucoma on their radar, as the condition can be easily overlooked in early stages. “The biggest thing to me is to look for it and to be thinking about it whenever you see a patient who doesn’t dilate well,” he said. “Obviously if you see the target lesion on the lens, that’s an indication. But sometimes you don’t see that. The target lesion can be easy to miss. In early cases it can be very subtle.” Currently there is no genetic test available for the LOXL1 gene, so physicians have to diagnose pseudoexfoliation glaucoma the old-fashioned way. That, said Dr. Rhee, is probably for the best. “Even if you have a gene that predicts very high for something, it doesn’t mean that people are predestined,” he said. “Genes are very important for predicting health and disease, but it’s not the only thing. We want to make sure we accurately portray risk, but risk does not imply finality.” EWAP Editors’ note: The doctors mentioned have no financial interests related to this article. Contact information Pasquale: louis_pasquale@meei. harvard.edu Rhee: dougrhee@aol.com