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Genetics may reduce future burden of blindness from glaucoma
Novel glaucoma treatments and gene-based therapies are expected to result from recent research into the genetics of glaucoma and the latest advances in personalized medicine, according to a University of Michigan ophthalmologist.
“I anticipate that future studies will lead to the identification of a combination of predictive genetic markers that inform us which patients are at highest risk for fast progression and which treatments are optimal for the individual patient,” Sayoko E. Moroi, MD, PhD, said in an update on glaucoma genetics that she presented at Hawaiian Eye 2009.
Dr. Moroi said there is cause for increasing optimism about molecular medicine’s prospects for eventually enhancing disease detection, advancing clinical care and improving treatment outcomes for individuals with glaucoma.
Focus on common diseases
According to Dr. Moroi, for key advances to occur in glaucoma-related genetics, researchers have shifted from the simple, monogenic or “one gene = single disease” mindset, an approach that has successfully identified 70 or so known glaucoma genes or chromosomal locations for the rare Mendelian forms of glaucoma.
However, only about 10% of these identified genes are thought to relate to the common forms of glaucoma, such as open- or closed-angle glaucoma.
“Because the common forms of glaucoma are genetically heterogeneous, new basic science research is now focusing on the 1% of our genome that is different between individuals,” she said.
Applying glaucoma genetics to clinical care
Dr. Moroi discussed a clinical example of the challenges of translating genetic risk alleles, or markers, to clinical care. These challenges include identifying disease-relevant genetic risk alleles, comparing these risk alleles across different populations, validating these risk alleles and demonstrating cost-effectiveness of these validated risk alleles in diagnosis and treatment outcomes.
“To tackle these challenges, we must integrate past knowledge, current technology and well-designed studies,” she said. “It is important to take established clinical risk factors that we have learned from clinical trials and place them into context with biology and environmental risk factors.”
These clinical risk factors include age, IOP and thin corneas, and Dr. Moroi added other suspected risk factors that include blood pressure, biomechanical properties of the eye, diabetes mellitus and possibly some inflammatory markers. “We are not yet aware of environmental risk factors for glaucoma, but these will emerge in future studies,” she said.
Taken together, this makes for very complex translational challenges with diagnostic, clinical and therapeutic implications for disease treatment.
Epidemiological approach
Dr. Moroi suggested that investigators need to take more of an epidemiological approach.
“In looking at how we treat our patients, our approach is shifting from a ‘one drug fits most’ to a stratified approach based on clinical risk factors and will transition to personalized treatment based on genetic risk alleles,” she said.
In the stratified treatment approach, physicians take into account patient compliance issues, how glaucoma drugs are delivered, their toxicity and IOP lowering effect. They then observe the effect and adjust treatment accordingly. – by Susan M. Rapp
- Sayoko E. Moroi, MD, PhD, can be reached at the University of Michigan Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, 1000 Wall St., Ann Arbor, MI 48105; 734-763-3732; fax: 734-615-0542; e-mail: smoroi@umich.edu.