Research Opportunities Molecular Biomarkers in Glaucoma Sanjoy K. Bhattacharya, 1 Richard K. Lee, 1 Franz H. Grus, 2 and the Seventh ARVO/Pfizer Ophthalmics Research Institute Conference Working Group 3 T he seventh annual ARVO/Pfizer Ophthalmic Research Institute conference was held Friday and Saturday, April 29 and 30, 2011, at the Fort Lauderdale Hyatt Regency Pier 66, Fort Lauderdale, Florida. The conference, funded by The ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to determine the state of knowledge pertaining to molecular biomarkers associated with glaucoma, as well as the methods to identify and validate them to predict (a) those who would be susceptible to development of glaucoma; (b) markers that will enable prediction of glaucoma progression; and (c) markers that will predict efficacy of treatment of glaucoma. Identification of such biomarkers will aid in prevention of glaucoma-related vision loss and blindness. The conference focused on an evaluation of glaucoma molecular biomarkers and progress needed for future validation of glaucoma biomarkers. A working group of 21 glaucoma researchers, 7 scientists focused on diseases other than glaucoma and with expertise in areas such as proteomic biomarkers or molecular mechanisms for neurodegeneration, and 60 observers from ARVO, Pfizer, and clinical and basic ophthalmic research convened to evaluate current understanding of the molecular biomarkers of glaucoma. The meeting format emphasized discussion and concentrated on questions within areas of glaucoma molecular biomarker research: Session I: How to define a biomarker in medicine? Current knowledge about biomarkers in human health and in glaucoma Session II: Genetic biomarkers in glaucoma Session III: Proteomic biomarkers in glaucoma Session IV: Pre-immune and immune events: Immunopro- teomics and its possible applications in glaucoma Session V: From bench to bedside: How can a translational approach be successful? Each session began with a 10-minute overview by a glaucoma researcher followed by a 30-minute presentation by an outside expert, with parallels between their fields of expertise and the eye included. Invited outside experts covered several areas of research, including proteomic biomarker discovery in cancer (Emanuel Petricoin, PhD, George Mason University, Maryland; and Akhilesh Pandey, MD, PhD, Johns Hopkins University, Maryland) and astroglial cells in neurodegeneration (Stephen D. Miller, PhD, North- western University, Illinois). HOW TO DEFINE A BIOMARKER IN MEDICINE? CURRENT KNOWLEDGE ABOUT BIOMARKERS IN HUMAN HEALTH AND IN GLAUCOMA The increased sensitivity and accuracy of genomic, proteomic, and metabolomic techniques (see Figure) have brought about the potential to identify molecular entities that may serve as potentially useful markers, including (1) markers for early detection of a disease; (2) markers that will predict severity of a disease; (3) markers that will predict the rate of disease progression, and (4) markers that will serve as predictors of response to treatment. The severity of a disease may be very dissimilar in different individuals even if they are at an equivalent stage of the disease, owing to shortcomings in staging the disease process. On the other hand, the progression of the disease in different individuals, or even in different organs of the same individual, may occur at different rates. Glaucoma is an example of such asymmetric presentation. A patient with pseudoexfoliation glaucoma, often also referred to as exfoliation syndrome (ES), usually has asymmetry of involvement between the two eyes. Two-thirds of patients present unilaterally, and 50% of these develop the disease in the fellow eye within 15 years; rates of progression differ among individuals. The response to treatment also differs among individuals, and prediction of treatment outcome markers will be helpful to personalize treatment. The identification of quantitative biomarkers that reveal aspects of the disease process could especially help the clinician understand and monitor a patient’s response to treatments. Use of molecular markers in the clinical setting to meet these goals will be exciting. However, there remain limitations to be overcome, including lack of common operating procedures for proper banking of biological tissues, analytical insensitivity of underpinning technologies, lack of standards, multiplexed complicated assays, and an ever-changing regula- tory landscape. 1,2 Proteomics is at the center of a number of these activities, since proteins are either the molecular From the 1 Bascom Palmer Eye Institute, University of Miami, Miami, Florida; and 2 Experimental Ophthalmology, Department of Ophthalmology, University Medical Center of the Johannes Guten- berg University Mainz, Mainz, Germany. 3 Participants in the Seventh ARVO/Pfizer Ophthalmics Research Institute Conference Working Group are listed on page 122. The authors contributed equally to the work presented here and should therefore be regarded as equivalent authors. Supported by the ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, National Eye Institute (RKL), American Glaucoma Society (RKL), and American Health Assistance Foundation (RKL). Submitted for publication October 2, 2012; accepted October 29, 2012. Disclosure: S.K. Bhattacharya, None; R.K. Lee, None; F.H. Grus, None Corresponding author: Franz H. Grus, Experimental Ophthal- mology, Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131 Mainz, Germany; grus@eye-research.org. DOI:10.1167/iovs.12-11067 Investigative Ophthalmology & Visual Science, January 2013, Vol. 54, No. 1 Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc. 121