Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions
Condition: Glaucoma
MeSH terms: Glaucoma
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine if one of the genes that can cause glaucoma, called
      myocilin, are associated with larger eye pressure and blood pressure changes in sitting and
      lying down positions without glaucoma drug treatment and with glaucoma drug treatment with a
      combination medication called Cosopt® (Merck & Co., Inc.).
    

Detailed description: 
      Glaucoma is an important public health issue, and identifying new markers to improve
      treatment outcomes is a high priority. Progress in Mendelian genetic approaches has led to
      identifying 15 genes and 31 loci (http://www.ncbi.nlm.nih.gov/); however, since these
      monogenic forms of glaucoma are uncommon, other approaches are needed to identify genetic
      markers that contribute to common risk factors, such as elevated eye pressure, eye pressure
      fluctuation, and drug response variation.

      It is well known that eye pressure varies over a 24-hour period,1-6 but the mechanisms that
      regulate this eye pressure rhythm are not yet fully known. Drance reported that 84% of normal
      eyes (N=320 eyes) had eye pressure fluctuations of less than 5 mmHg in contrast to only 6% of
      untreated glaucomatous eyes (N=138).7 Drance clearly recognized that eye pressure factors
      were more variable in eyes with glaucoma. Attention to this eye pressure fluctuation during
      glaucoma treatment is important because fluctuation leads to progression. The variation in
      eye pressure drug response profiles measured at selected times over a 24-hour period is
      related to the mechanism of action of these drugs, endogenous circadian rhythms, and
      glaucoma. The molecular and genetic tools are now available to identify potential genetic
      markers for these variable traits.

      Advancing clinical research to the "translational" level is an important step to integrate
      our ever increasing knowledge base in genomics and proteinomics with clinical trials and
      clinical studies. Given the infrastructure at the University of Michigan with the strength in
      both glaucoma genetics and our resources in the clinic, it is possible to test for
      relationships between glaucoma genes and eye pressure. Although it is known that myocilin
      (MYOC) mutations cause the phenotype of high pressure open-angle glaucoma, the effect of
      these MYOC mutations in "pre-symptomatic" subjects and patients with early open-angle
      glaucoma on eye pressure variation is not known.
    

Intervention name(s): Cosopt (combination eyedrop of dorzolamide and timolol)
Intervention type(s): Drug
Intervention description(s): One drop in each eye every twelve hours for six weeks
Other intervention name(s): Cosopt
Intervention MeSH terms: Timolol; Dorzolamide; Ophthalmic Solutions
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Myocilin gene; Glaucoma; dorzolamide and timolol combination eyedrop