Glaucoma Research and Clinical Advances: 2018 to 2020

Volume 2 of our serial publication continues our desire to address glaucoma with a combination of science and speculation. As science expands, the emphasis is on data, interpretation, and dogma. We disagree; open minds open new approaches. Using methodologies that are primarily molecular and genetic, we seek to refine the causes of glaucoma as well as how it is best treated, especially incorporating thoughts and hypotheses about new methods of treatment. Glaucoma is a complex disease, and genetics proves that a variety of proteins are culpable at one level. At another level, however, there are likely final common pathways and numerous feedback loops which have defied explanations to date.

The search for answers goes on in basic science researcher’s laboratories and clinical ophthalmologist’s offices and operating rooms. We are all well-served by understanding that glaucoma is a neurodegenerative disease. Current attempts to solve the disease have focused on two strategic arenas:

• the trabecular meshwork function and its impact on intraocular pressure as a major risk factor for the disease; and
• the optic nerve dysfunction leading to visual loss.

Genetic mutations have yielded puzzling clues to the cause, but without resolution. For example, mutations in myocilin and optineurin genes are closely connected to the phenotype, but how do they cause the disease? In the next two years, priority areas of research are signaling pathway discoveries, biomarker panels, epigenetic factors, and continued genomic studies to yield answers to the common final pathways of the disease.
The final pathways are complex and redundant, such that the overlap of bio-informatics will be challenging. Current promising leads suggest the innate immune system holds important clues to both trabecular meshwork and optic nerve pathophysiology. When the primary open-angle glaucoma disease pathways are unraveled, drug discoveries and new treatment modalities will be available for better regulation of intraocular pressure and neuroprotection for the optic nerve. This volume discusses the glaucoma pipeline from several perspectives as well as future candidate classes. As always, the authors herein are urged to speculate on how the cure of glaucomatous optic nerve damage will yield to new treatments.

John R. Samples
Clinical Professor, Elson S. Floyd College of Medicine, Washington State University School of Medicine
www.glaucomaconcepts.com
Paul A. Knepper
Associate Professor of Ophthalmology, Feinberg School of Medicine, Northwestern University Medical School Research Scientist, University of Illinois at Chicago

Foreword

About the authors

Science insights

1. Do you hear me now? Mechanisms of cellular communication in the trabecular meshwork
Kate E. Keller

2. The innate immune system in primary open-angle glaucoma
Paul A. Knepper, Nicholas M. Pfahler, Kevin Carey, Indre Bielskus

3. Phagocytic activity in the trabecular meshwork
Paloma B. Liton

4. How fibronectin fibrillogenesis can regulate aqueous humor outflow
Jennifer A. Faralli, Jennifer Peotter, Donna M. Peters

5. Cell-derived matrices as a model to study ocular hypertension
VijayKrishna Raghunathan

6. Bioengineered human trabecular meshwork membrane constructs: opportunities and challenges
Karen Y. Torrejon, Matthew D. Kerr

7. Is there a final common pathway affected in POAG?
Brian S. McKay, R. Rand Allingham, W. Daniel Stamer

Clinical

8. Genetics of primary angle-closure glaucoma: genes and mechanisms
Eranga N. Vithana, Monisha E. Nongpiur, Tin Aung

9. Genetics of POAG in Greece
Anastasios G. P. Konstas, John R. Samples, Mary K. Wirtz

10. Blood flow parameters of the optic nerve
Priyanka Parekh, Alon Harris, Josh Gross, Alice C. Verticchio Vercellin, Brent Siesky

11. Systemic manifestations of microvascular disease in primary open-angle glaucoma
Nicholas M. Pfahler, Michael M. Miazga, Indre Bielskus, Elani Kaufman, Jack G. McGuire, Thomas Cronin, James Haney, Ryan McCarthy, Michael C. Giovingo, Nicholas J. Volpe, Angelo P. Tanna, Paul A. Knepper

12. Imaging of the narrow angle
Marisse Masis, Shan C. Lin

13. The link between Alzheimer’s disease and primary open-angle glaucoma
Paul A. Knepper, Nicholas M. Pfahler, Jack G. McGuire, Indre Bielskus, Michael C. Giovingo, Nicholas J. Volpe

Medications

14. Proteins in perfused and non-perfused areas of the trabecular meshwork: potential drug candidates
Julia A. Staverosky, Ted S. Acott, Janice A. Vranka

15. Modulation of intraocular pressure by ATP sensitive potassium channel openers
Uttio Roy Chowdhury, Peter I. Dosa, Michael P. Fautsch

16. Development of the nitric oxide-donating prostaglandin analog latanoprostene bunod, a novel intraocular pressure lowering drug
Megan E. Cavet, Jason L. Vittitow

17. Targeting the adenosine A1 receptor in the eye with trabodenoson, an adenosine mimetic
Cadmus C. Rich, David S. Albers, James A. Gow, Rudolf A. Baumgartner

Lasers

18. Laser trabeculoplasty renewed
Stephen S. Bylsma, Ted S. Acott, Mary J. Kelley, John R. Samples

19. Micropulse cyclophotocoagulation: an update on a novel glaucoma treatment
Michael C. Giovingo, Krishna B. Patel, Elizabeth A. Martin, Mitchell J. Greenberg, John R. Samples, Paul A. Knepper, Thomas D. Patrianakos

20. Panmacular subthreshold diode micropulse laser (SDM) as neuroprotective therapy in primary open-angle glaucoma
Jeffrey K. Luttrull, John R. Samples, David Kent, Bryant J. Lum

Surgery: Theoretical considerations

21. The development of SIBS and the InnFocus MicroShunt®
Leonard Pinchuk, Isabelle Riss, Juan F. Batlle, Yasushi P. Kato, John B. Martin, Esdras Arrieta, Paul Palmberg, Richard K. Parrish, II, Yongmoon Kwon, Jean-Marie Parel

22. What is the ideal conjunctival bleb? Learning from minimally invasive glaucoma filtration surgery
Dao-Yi Yu, Stephen John Cringle, William H. Morgan, Er-Ning Su

23. Trabecular Meshwork Study Club Abstracts 2017