Current Developments in Glaucoma

Surgery and MIGS John R. Samples

Iqbal (Editor)
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ISBN 978-90-62992-76-8

9 789062 992768
NEW CONCEPTS IN GLAUCOMA SURGERY SERIES
VOLUME 1
About the series
New Concepts in Glaucoma
and Glaucoma Surgery
These series has been conceived as a recurring project. It is neither book nor journal. Books are infrequently
edited and rarely up-to-date for more than a year or two; journals are really devoted to the standard experimental
format and no longer permit authors to wander into speculation or lengthy discussions of what might come next.
There is room for a plurality of publishing approaches. All of these formats have their place and all have different
purposes in moving a field forward.
This series is designed to allow us to consolidate new information and hold forth on speculation in glaucoma.
It does so in both the basic sciences and clinical sciences.
It is our hope that this consolidation of hypotheses and theories, along with identifying new information
and new speculation will propel us toward a more rapid cure for glaucoma.

ISSN: 2542-5595
ISSN 2589-7632 (Surgery Series)

New Concepts in Glaucoma Website

Visit our website at newconceptsinglaucoma.com for access to the videos discussed in this book, captured content
from our annual congress, and all articles published within the series.

Published by Kugler Publications

www.kuglerpublications.com
New Concepts in Glaucoma
Surgery Series:
Volume 1
Editors

John R. Samples
Iqbal Ike K. Ahmed

Kugler Publications/Amsterdam/The Netherlands

New Concepts in Glaucoma Website
Visit our website at newconceptsinglaucoma.com for access to the videos discussed in this book, captured
content from our annual congress, and clinical science and research articles published within the series.

Videos
Videos can be accessed directly through:
newconceptsinglaucoma.com/surgery1/videos/chapter-number
e.g. for chapter 10 go to to newconceptsinglaucoma.com/surgery1/videos/10)

New Concepts in Glaucoma Surgery Series - Volume 1

ISSN 2589-7632

ISBN 978-90-6299-276-8

Kugler Publications
P.O. Box 20538
1001 NM Amsterdam, The Netherlands
www.kuglerpublications.com

© 2020 Kugler Publications, Amsterdam, The Netherlands

All rights reserved. No part of this book may be translated or reproduced in any form by print, photoprint,
microfilm, or any other means without prior written permission of the publisher.

Kugler Publications is an imprint of SPB Academic Publishing bv, P.O. Box 20538, 1001 NM Amsterdam,
The Netherlands

Cover design by: Willem Driebergen, Rijnsburg, The Netherlands

Table of contents
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

About the editors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viii

About the authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x

1. Anatomy of the conventional aqueous outflow pathway . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Haiyan Gong, David L. Swain

2. Patents in an age of innovation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

William Noonan

3. Which minimally invasive glaucoma surgery should one choose for a specific patient? . . . . . . . . . . . . . . 55
Jithin Yohannan, E. Randy Craven

4. In defense of the trabeculectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

Ryan Machiele, Makena Parker, Leon W. Herndon

5. On the use of curcumin as a multimodal antifibrotic agent for glaucoma surgery . . . . . . . . . . . . . . . . . . 71

Nicholas M. Pfahler, Michael C. Giovingo, Paul A. Knepper

6. The future of MIGS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

Thiago A. Moulin, Arsham Sheybani

7. Gonioscopy-assisted transluminal trabeculotomy (GATT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .95

Ronald L. Fellman, Davinder S. Grover

8. Hydrus® microstent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107

Thiago A. Moulin, Arsham Sheybani

9. The iStent devices: iStent, iStent inject, and iStent Supra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Antonio M. Fea, Simona Scalabrin, Carlo Lavia

10. Ab interno trabecular meshwork incision, ablation, and disruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

Hamed Esfandiari, Si Chen, Ralitsa T. Loewen, Susanna Waxman, Kevin Kaplowitz, Nils A. Loewen

11. iTrack™ ab interno canal-based glaucoma surgery: the next evolution in MIGS . . . . . . . . . . . . . . . . . . . 157
Mahmoud Khaimi, David Lubeck

12. XEN: the evolution of the stent and technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167

Vanessa Vera, Daniel Lee, Natasha N. Kolomeyer, M. Reza Razeghinejad, Jonathan S. Myers

13. An ab externo minimally invasive aqueous shunt comprised of a novel biomaterial . . . . . . . . . . . . . . 181
Leonard Pinchuk, Isabelle Riss, Juan F. Batlle, Henny Beckers, Ingeborg Stalmans
vi

14. Laser trabeculoplasty and micropulse: evolution from trabecular photocoagulation,

to trabecular photothermolysis, to trabecular photostimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Giorgio Dorin, Ted S. Acott, Antonio M. Fea, John R. Samples

15. Cyclophotocoagulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211

Michael Giovingo, Shyam Patel, Shweta Chaudhary, Amar Mannina, Thomas Patrianakos

16. Excimer laser trabeculostomy: the laser-based MIGS procedure for open-angle glaucoma . . . . . . . . 231
Michael S. Berlin, Marc Töteberg-Harms, Jonathan Shakibkhou, Alyssa Francesca Ahorro, Ryan Lamrani, Antonio
Moreno Valladares, Ulrich Giers

17. Mixing and combining MIGS procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245

Steven R. Sarkisian, Jr.

18. Trabeculectomy with suprachoroidal derivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

Rodolfo A. Pérez-Grossmann, Daniel Grigera, Alan Wenger, Rodolfo A. Pérez-Simons

19. Modern retinal laser for neuroprotection in open-angle glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255

Jeffrey K. Luttrull, David Kent

20. What is the ideal conjunctival bleb and how to achieve it?
Learning from the Microfistula-XEN procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Dao-Yi Yu, Stephen John Cringle, William H. Morgan, Er-Ning Su

21. Special considerations for pediatric glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289

Peter A. Netland, John R. Samples
Foreword
Successful interventional glaucoma remains a sought-after goal for the glaucoma clinician for many reasons.
Medical costs, compliance, and adherence remain major barriers for the treatment of our patients. A truly
definitive treatment for glaucoma is most likely to be largely surgical, as it is doubtful that patients will continue to
use glaucoma drugs in the future for anything other than transient lowering of intraocular pressure. In the coming
era, it seems probable that neuroprotection and neurorestoration will be combined with MIGS to lower pressure.
Cost and access to medications, as well as cost-effectiveness are all reasons pushing towards surgery becoming
the prime method of treating adult glaucoma, as is already the case for pediatric glaucoma. However, this could
change if medications were to have a demonstrable beneficial effect upon the cells of the eye, whether corneal or
trabecular. Cytoprotection, trabecular protection, and even canaloprotection may lie ahead to join the concept
of neuroprotection. In fact, if medications were actually regenerative, it is likely that that they would become a
routine component when MIGS is performed. At present, no such beneficial cellular treatment is known, but new
medications based on neuroprotection and trabecular meshwork restoration may be on the immediate horizon. It
has been suggested that netarsudil would have beneficial effects for both the trabecular meshwork and the optic
nerve. Nitric oxide compounds may offer a similar possibility; much remains to be learned as of this writing.
Additional good news is that the different types of MIGS are increasing in proportion to their efficacy. To
date, there are no fewer than 12 choices available to glaucoma specialists. Choice of procedure depends on the
underlying anatomy as well as the patient’s individual characteristics. Truthfully, the number of available surgeries
depends upon their taxonomy. Most are based on the outflow system and the canal, as illustrated in Chapter 1 of
this book.
Since our last book on the topic, Surgical Innovations in Glaucoma, the surgical landscape has shifted consid-
erably; in only a few years, much has become obsolete, replaced by more recent findings and techniques. Due
to significant improvements, MIGS are increasingly finding their place in patient management to such a degree
that a monograph is no longer a suitable format to keep track of all the developments in this area. This collection
of articles is intended to be the first of a series of planned books on glaucoma surgery. It follows the format and
citability of another glaucoma series from Kugler Publications, Glaucoma Research and Clinical Advances, soon to
publish its third volume.
Comments and contributions to this new surgical series are very much welcome. We hope that this volume will
not only enhance the reader’s clinical care, but will also spark a dialogue that aids us all in increasing the quality
of care we render to our patients.

John R. Samples, MD
Clinical Professor, Washington State University Floyd Elson College of Medicine, Spokane, WA, USA
Director, Western Glaucoma Foundation, Sisters, OR, USA
Founder and Organizer, Trabecular Meshwork Study Club

Iqbal Ike K. Ahmed, MD, FRSC (C)

Assistant Professor, University of Toronto, Toronto, ON, Canada
Clinical Professor, Salt Lake City, University of Utah, UT, USA
Director, Glaucoma & Advanced Anterior Segment Surgery (GAASS) Fellowship, University of Toronto, Toronto,
ON, Canada
Research Director, Kensington Eye Institute, University of Toronto, Toronto, ON, Canada
Division Head, Ophthalmology, Trillium Health Partners, Mississauga, ON, Canada
Medical Director, Prism Eye Institute, ON, Canada
Co-Medical Director, TLC Oakvillle, Oakville, ON, Canada
About the editors

John R. Samples, MD

John R. Samples practices at both the Olympia Eye Clinic of Olympia, WA and the Eye
Clinic in Portland, OR, USA. He is the Chief Scientific Officer for EyeGenetix, Director of
the Western Glaucoma Foundation, and Clinical Professor at Washington State Univer-
sity’s Elson S. Floyd College of Medicine in Spokane, WA, USA.
For over thirty years, Dr. Samples has been actively involved within the professional
community including the American Academy of Ophthalmology (AAO), the American
Glaucoma Society, and the American Society for Cell Biology. He has also organized
and/or co-chaired numerous meetings since 2003, including an annual mini fellowship
in glaucoma held in Napa Valley in collaboration with the University of California San
Francisco, the Oregon Academy of Ophthalmology, the Pacific Coast Oto-Ophthalmo-
logical Society annual meeting, the International Society for Eye Research (ISER), and
a Trabecular Meshwork Study Club held annually in conjunction with the American Society for Cell Biology.
He has been active in ophthalmology research with funding from the National Eye Institute and has over
150 peer-reviewed publications to his credit, as well as numerous books on glaucoma. Dr. Samples’ research
has focused on the trabecular meshwork, cytokines, aspects of wound healing, and glaucoma genetics; he has
also worked on the development of several new glaucoma-related drugs and several new laser and surgical
procedures. He consults on new drug and device development, as well as legal intellectual property issues within
ophthalmology.

Iqbal Ike K. Ahmed, MD, FRCSC

Ike Ahmed is a fellowship-trained glaucoma, cataract, and anterior segment surgeon

with a practice focus on the surgical management of glaucoma, complex cataract and
intraocular lens complications. He is board-certified in ophthalmology in Canada and
the USA, and is an active member of numerous national and international societies.
Dr. Ahmed has become world renowned for his skills and groundbreaking work in the
diagnosis and surgical treatment of highly complex eye diseases, including glaucoma
and surgical complications. He is recognized as being one of the most experienced
complex eye surgeons in the world and has trained numerous surgeons in innovative
surgical techniques.
He is currently an Assistant Professor at the University of Toronto, and a Clinical
Professor at the University of Utah. He is the Director of the Glaucoma and Advanced
Anterior Segment Surgery (GAASS) fellowship at the University of Toronto, and Director of Research at the
Kensington Eye Institute, University of Toronto. He has trained glaucoma specialists who are now practicing in
Canada and around the world, as well as residents and medical students. Dr. Ahmed has a large tertiary glaucoma/
cataract practice at Prism Eye Institute in the Greater Toronto Area, and primarily performs surgery at Trillium
Health Partners, Mississauga, Ontario, the Kensington Eye Institute, University of Toronto, Toronto, Ontario, and
TLC Oakville.
Dr. Ahmed has a keen interest in the development of advanced microsurgical devices and techniques in
glaucoma surgery and complicated cataract extraction, and is actively involved in research and medical education
at a national and international level. He has received research grants to study glaucoma medications, glaucoma
 ix

laser and surgical devices/techniques, angle-closure glaucoma, anterior segment and retinal/optic nerve imaging
in glaucoma, cataract surgical techniques and devices, and intraocular lens designs. Dr. Ahmed has designed
innovative glaucoma diamond scalpels for surgery, microsurgical instrumentation, and devices, implants, and
techniques for the management of the dislocated cataract, iris reconstruction, and glaucoma implant devices.
He has done pioneering work in innovative glaucoma surgery, developing and coining the term “microinvasive
glaucoma surgery” (MIGS) as a new genre of surgical approaches and devices.
About the authors
Ted Acott, MD, PhD 
Dr. Acott is Research Professor of Ophthalmology and of Biochemistry & Molecular Biology
at the Casey Eye Institute, Oregon Health & Science University, OR, USA. His team’s long-term
research interests are centered on identifying therapeutic targets to treat glaucoma via
lowering intraocular pressure. They have recently identified the homeostatic mechanism
of intraocular pressure, which normally maintains the aqueous humor outflow resistance at
the appropriate levels, protecting most people from ever developing glaucoma. In addition,
they have been studying the molecular and biomechanical properties that are responsible
for this homeostatic mechanism and for maintaining the highly segmental nature of aqueous
humor outflow. Their work has recently demonstrated that the IOP homeostatic mechanism
is compromised in glaucoma, and both high and low segmental flow regions exhibit different
biomechanical and flow properties. The team has also identified individual extracellular
matrix proteins that may be important therapeutic targets in the treatment of glaucoma.

Alyssa Francesca Ahorro, BA 

Alyssa Francesca Ahorro received a Bachelor of Arts in Psychology at the University of
California, Riverside in June of 2018. Currently, she is conducting research at the Glaucoma
Institute of Beverly Hills and Cedars-Sinai Medical Center in Los Angeles, CA, USA. Her
current interests lie within the scopes of Ophthalmology and Oncology. Upon gaining further
research experience, she will pursue a medical degree.

Juan F. Batlle, MD 
Dr. Batlle is founder and President of the multi-specialty private practice Centro Laser in
Santo Domingo, Dominican Republic. He is a Distinguished Member of Vision 2020/Interna-
tional Agency for the Prevention of Blindness, Chief of Ophthalmology at the charity clinic
Elias Santana Hospital, and Medical Director of one of the most prestigious residency train-
ing programs of ophthalmology in Latin America associated with Instituto Tecnológico de
Santo Domingo. He has dedicated his professional life to the prevention of blindness in Latin
America, with an interest in cataract, glaucoma, cornea, and refractive surgery. Dr. Batlle
has more than 20 years of experience in research and collaborates with well-known oph-
thalmic companies for the development and design of ophthalmic devices and medications,
supporting submissions and approvals to world-wide regulatory agencies in his areas of
interest.
 xi

Henny J.M. Beckers, MD, PhD, FEBOphth 

Dr. Beckers is Associate Professor, Head of the Glaucoma Clinic, and Director of the Ophthal-
mology Residency Program at the University Eye Clinic of the Maastricht University Medical
Center+ in the Netherlands. She is the Secretary of the Dutch Glaucoma Group, an active
committee of Dutch ophthalmologists with a special interest in glaucoma. Her main research
interest is glaucoma surgery, with a focus on studying new glaucoma devices. Research lines
also include progression of glaucoma, prognostic factors in glaucoma, diagnosis of nar-
row-angle glaucoma, glaucoma treatment and adherence, and cost-effectiveness studies.

Michael S. Berlin, MD, MSc 

Dr. Michael Berlin is a Professor of Clinical Ophthalmology at the UCLA Stein Eye Institute.
His professional contributions are in laser surgery and in the research and treatment of
glaucoma. He is the founder and director of the Glaucoma Institute of Beverly Hills (GIBH)
in Los Angeles, CA, USA, where he has maintained a private clinical practice for over 30
years and is the director of the GIBH Research Foundation. Dr. Berlin received his bachelor’s
degree, medical degree, and his Master of Sciences degree in ophthalmology from the
University of Michigan. He completed an internship in Internal Medicine at the Harbor –
UCLA Medical Center, followed by an ophthalmology residency at the University of Michigan
and subsequent subspecialty glaucoma fellowship training at the Mount Sinai Medical
Center in New York. His research interests focus on the development of novel therapies
for the treatment of glaucoma. He holds multiple patents for innovative laser and surgical
procedures, publishes extensively and lectures internationally.

Shweta Chaudhary, MD 
Shweta Chaudhary is an ophthalmology resident at Cook County Health and Hospitals,
Chicago, IL, USA. She has completed an ophthalmology residency in India and a corneal neu-
robiology research fellowship at the University of Illinois at Chicago. Her research interests
include surgical and laser inventions in the field of glaucoma, especially mechanisms of
action of different types of glaucoma lasers and minimally invasive glaucoma surgery.

Si Chen, MD 
Si Chen is a PhD student from Central South University, Xiangya School of Medicine,
Changsha, China. She is currently a visiting international scholar in the Loewen Lab in
the Department of Ophthalmology at the University of Pittsburgh, PA, USA. Her research
interests involve the role of microincisional glaucoma surgeries in the cause, treatment, and
prevention of glaucoma. Her PhD is concerned with factors that influence outflow in the
distal outflow tract.
xii

E. Randy Craven, MD 
Dr. Craven specializes in glaucoma and complex anterior segment cases, such as iris
problems and lens issues. He is an Associate Professor at Johns Hopkins University School
of Medicine (Baltimore, MD, USA). Dr. Craven is currently also the Medical Director of the
Wilmer Eye Institute Bethesda (Bethesda, MD, USA) and serves as the Vice-Chair for the
Wilmer Eye Institute Practice Network.
From 2013 to 2016, Dr. Craven served as the Chief of Glaucoma and Glaucoma Fellowship
Director at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia. He also served
as the Residency Coordinator there.
Dr. Craven was involved with the development and implementation of risk-management
programs for ophthalmologists while serving on the Board of Directors for the Ophthalmic
Mutual Insurance Company in the USA. He participated in over 120 clinical research trials
and was the first US surgeon in the US Food and Drug Administration (FDA) trial to implant
the iStent, as well as the first US surgeon to implant the CyPass; as a result, he is active
in expanding and educating about the role of minimally invasive glaucoma surgeries
throughout Europe, the Middle East, Africa, and the USA. He has extensive experience with
optical coherence tomography for glaucoma and served as an advisor for the development
of imaging in glaucoma.

Stephen John Cringle, BSc, PhD 

Dr. Cringle is Professor of the Lions Eye Institute, Center for Ophthalmology and Visual Science
at The University of Western Australia in Nedlands, Australia. His research involves basic
studies of retinal oxygen metabolism, vascular biology, laser applications in ophthalmic
research, and the development of new diagnostic and therapeutic techniques in glaucoma
and retinal diseases. He has worked with Professor Yu and made a significant contribution
to the XEN Gel Stent technology for glaucoma filtration surgery that is now in clinical use.
Dr. Cringle has a background in physics and 35 years of experience in ophthalmic research.
 xiii

Giorgio Dorin 
Giorgio Dorin has been devoted to the development of clinical laser systems for the treatment
of glaucoma, retinal, and refractive disorders since 1969. In 1983, in recognition of his contri-
butions to the ocular applications of lasers, he was awarded with the Honorary Membership
by the Italian Society of Laser in Ophthalmology (S.I.L.O.).
During the past two decades, he has developed micropulse laser emission techniques to
master the control of the photothermal effects during ocular laser treatments, to the end of
minimizing and avoiding the treatment’s iatrogenic damage and collateral complications,
while maintaining and optimizing both clinical outcomes and therapeutic benefits.
He has pioneered the clinical use of sub-visible-threshold nondamaging micropulse laser
procedures for the treatment of retinovascular disorders and glaucoma. This has led to new
subthreshold laser micropulse photostimulation (SLMP) treatment protocols that have been
fine-tuned in pilot studies and validated in prospective randomized clinical trials, which
have provided the evidence that SLMP is at least as effective as the conventional destructive
threshold laser photocoagulation and can result in superior outcomes and unprecedented
functional benefits thanks to the absence of the treatment’s morphologic and functional
damage. This evidence is now leading a pivotal swing from laser photocoagulation to laser
photostimulation, a seminal paradigm-shift with intrinsic unprecedented safety profile and
benefit-to-risk ratio. He is now advocating the ban of destructive photocoagulation and the
use of photostimulation for the treatment of ocular chronic degenerative progressive neu-
rotrophic disorders.
He has been granted three patents on sub-threshold laser applications by the US Patent
Office, has authored/coauthored numerous publications in peer-reviewed medical journals,
has contributed with chapters in ophthalmology books, and has presented posters and given
podium presentations at ophthalmology meetings, congresses, and courses throughout the
world. He is currently serving as the Senior Development Scientist and COO for ALeyeGN
Technologies, Saratoga, CA, USA.

Hamed Esfandiari, MD 
Hamed Esfandiari is an Assistant Professor of Ophthalmology at Shahid Beheshti University
of Medical Science in Tehran, Iran. He completed a research fellowship with Dr. Loewen at
the University of Pittsburgh (PA, USA) focusing on the clinical outcomes of novel techniques
to increase conventional outflow. He is now on the Pediatric Ophthalmology service at
the Northwestern University in Chicago, IL, working extensively in the field of childhood
glaucoma. His research interests encompass success factors in traditional and new
glaucoma surgeries and how they relate to recent insights into the conventional aqueous
outflow tract. He has also conducted studies on pediatric glaucoma, optic neuropathies,
and novel glaucoma medications.
xiv

Antonio Maria Fea, MD, PhD 

Dr. Antonio Maria Fea is an Aggregate Professor at the University of Turin, Italy and an adjunct
scientist at SERI. He holds a PhD in electrophysiology. He developed and propagated the
use of several psychophysical techniques to test visual function in infants and children. Dr.
Fea was part of several humanitarian missions in Madagascar, Namibia and, India. In recent
years, he has been involved in the development and clinical evaluation of several minimally
invasive techniques for the treatment of glaucoma. He has been part of several multicenter
trials performing and teaching MIGS surgery in Armenia, India, Colombia, and Chile, and is
part of the Advisory Board of several companies involved in the development of novel and
minimally invasive methods for the treatment of glaucoma. He serves as reviewer and is part
of the editorial board of several peer-reviewed journals.

Ronald L. Fellman, MD 
Ronald Fellman is an Attending Surgeon and Clinician at Glaucoma Associates of Texas in
Dallas, Adjunct Professor of Ophthalmology at North Texas Eye Research Institute (NTERI)
University of North Texas Health Science Center Fort Worth and Associate Clinical Professor
Emeritus, Department of Ophthalmology, University of Texas Southwestern Medical Center,
Dallas (UTSWMC) in TX, USA. Dr. Fellman attained his medical degree from Tulane University,
residency at University of Texas Southwestern Medical Center, and glaucoma fellowship at
Wills Eye Hospital. He is involved in clinical research concerning the surgical management of
glaucoma including wound healing, new devices and techniques for canal surgery and the
factors associated with canalogenesis. Dr. Fellman serves on the board of Cure Glaucoma, a
foundation dedicated to translational research in glaucoma and the reduction of blindness
from glaucoma on a global level and is active in various roles for the American Glaucoma
Society.

Ulrich Giers, MD 
Dr. Ulrich Giers is the Founder, Director, and Head of the anterior segment surgery department
of the OWL Eye Clinic in Detmold, Germany. He graduated and earned his medical doctorate
degree from Marburg University. He then completed his residency and fellowship at the
University Eye Hospital in Ulm, Germany. His research interests focus on clinical outcomes
of refractive and glaucoma procedures.

Michael Giovingo, MD 
Michael Giovingo is the director of Glaucoma Service for Cook County Health and Hospital
System in Chicago, IL, USA. He is a board-certified ophthalmologist and fellowship trained
glaucoma specialist. His research interests include the pathophysiology of glaucoma,
development of new medical interventions for glaucoma, and minimally invasive glaucoma
surgery and lasers. Dr. Giovingo is also active in training medical and surgical management
of glaucoma to the Ophthalmology residents at Cook County Health and Hospital System.
 xv

Haiyan Gong, MD, PhD, FARVO 

Dr. Gong is Professor of Ophthalmology, Anatomy, and Neurobiology at Boston University
School of Medicine (MA, USA). Her research is focused on understanding the mechanisms
that regulate aqueous humor outflow resistance in normal eyes and how this resistance is
increased in eyes with primary open-angle glaucoma, using physiological and morpholog-
ical methods to provide new insights for the development of new therapeutic strategies to
treat this disease. Dr. Gong’s current research is supported by National Institutes of Health/
National Eye Institute, BrightFocus Foundation, Aerie Pharmaceuticals, Inc., and Massachu-
setts Lions Eye Research Fund.

Daniel Grigera, MD 
Dr. Grigera earned his medical degree from the University of Buenos Aires, Buenos Aires,
Argentina. He currently serves as a consultant in the Glaucoma Service at Santa Lucía Eye
Hospital and as Assistant Professor of Ophthalmology at the Faculty of Medicine of Salvador
University in Buenos Aires, Argentina.
He is a former President of the Latin American Glaucoma Society and the Pan American
Glaucoma Society, member of the World Glaucoma Association Council, and founding
member and first president of the Argentine Association of Glaucoma. Dr. Grigera has partic-
ipated as coordinator or speaker in more than 90 congresses and symposiums in Argentina,
America, and Europe. He is a reviewer of Journal of Glaucoma and has published
23 works on glaucoma in Argentinian and international peer-reviewed publications.

Davinder S. Grover, MD, MPH 

Dr. Grover is Attending Surgeon and Clinician at Glaucoma Associates of Texas, Dallas,
Adjunct Assistant Professor at North Texas Eye Research Institute (NTERI), University of
North Texas Health Science Center, Fort Worth, and Clinical Assistant Professor at University
of Texas Southwestern Medical School in Dallas, TX, USA. His interests include innovative
glaucoma surgeries, complex glaucoma, cataract, and anterior segment surgeries, as well
as clinical research outcomes in medical and surgical glaucoma. He is widely published and
has helped develop innovative surgical techniques and has designed several novel surgical
instruments.
Dr. Grover received his medical degree from the Johns Hopkins School of Medicine, residency
at the Wilmer Eye Institute, and glaucoma fellowship at the Bascom Palmer Eye Institute.
Additionally, he received a Master of Public Health degree at the Harvard University School
of Public Health. He also serves on the Board of Directors for the Cure Glaucoma Foundation,
a charitable organization with a mission to improve access to quality care, fund transforma-
tional research, and disseminate knowledge through global outreach efforts.

Leon W. Herndon, Jr., MD 

Dr. Herndon is Professor of Ophthalmology at Duke University Medical Center in Durham,
NC, USA. He currently serves as Chief of the Glaucoma Division at the Duke University Eye
Center, where he has trained 74 clinical fellows. Dr. Herndon is the recipient of the Distin-
guished Medical Alumnus Award from the UNC School of Medicine, and was the Surgery Day
Lecturer at the American Glaucoma Society Annual Meeting in 2019.
Dr. Herndon’s research interests include studying novel treatment approaches in the
diagnosis and management of glaucoma. He has ongoing research projects evaluating the
high prevalence of primary open-angle glaucoma in Ghana, West Africa.
xvi

Kevin Kaplowitz, MD 
Kevin Kaplowitz is an Associate Professor in the Department of Ophthalmology at the VA
Loma Linda with Loma Linda University, CA, USA. One of his main research interests is
evaluating the outcomes and success factors for glaucoma surgery.

David Kent, FRCOphth 

Dr. Kent is a vitreoretinal surgeon practicing in The Vision Clinic, Kilkenny, Ireland. His
research interests include the therapeutic use of light to modulate and promote repair in the
aging retina. He has been a member of ARVO since 1996 and currently serves as a director of
LIGHT: The International Retinal Laser Society.

Mahmoud A. Khaimi, MD 
Dr. Khaimi is Clinical Professor and Glaucoma Fellowship Director of the Dean McGee Eye
Institute at the University of Oklahoma in Oklahoma City, OK, USA. His clinical focus lies in
the field of glaucoma, with special emphasis in innovations in MIGS, glaucoma filtration and
drainage surgery, and complex cataracts. His research interests also include clinical phar-
macology studies and glaucoma clinical trials.

Paul A Knepper, MD, PhD 

Dr. Knepper is Associate Professor of Ophthalmology at the Feinberg School of Medicine,
Northwestern University Medical School, IL, USA, as well as a Research Scientist at the
University of Illinois at Chicago, IL, USA. His research interests focus on improved diagnostic
modalities and treatment of primary open-angle glaucoma, Alzheimer’s disease, and
age-related macular degeneration.

Natasha N. Kolomeyer, MD 
Dr. Kolomeyer is a glaucoma specialist at Wills Eye Hospital, Philadelphia, PA, USA. She has
published 20 peer-reviewed papers and has served on committees for the Association for
Research in Vision and Ophthalmology (ARVO) and The American Academy of Ophthal-
mology (AAO). Dr. Kolomeyer’s research interests include clinical outcomes, public health,
imaging, big data, and telemedicine.
 xvii

Ryan Lamrani, BS 
Ryan Lamrani started working at the Glaucoma Institute of Beverly Hills in Los Angeles, CA,
USA after graduating in May 2018 from New York University with a BS degree in Public Health
and Chemistry. He will be applying to medical school in the summer of 2019 with the intent
of becoming an ophthalmologist. His research interests include the glaucomatous eye, epi-
demiology, and stem cells.

Carlo A Lavia, MD 
Dr. Lavia completed his five-year residency at the Department of Ophthalmology of the
University of Turin, Italy in 2018. During his residency, he took part in several clinical trials
in the field of medical retina and glaucoma, with Professor Antonio Fea as main researcher.
Dr. Lavia spent six months pursuing a research fellowship in medical retina, subsequently
working for a year as a retina specialist at the Department of Ophthalmology of the Laribois-
iere Hospital in Paris, France. He is a fellow of the European Board of Ophthalmology.
Dr. Lavia has published approximately twenty original articles and reviews in peer-reviewed
journals. His current interests involve MIGS and the clinical applications of OCT angiography.
He currently works in the Department of Ophthalmology of the ASL TO5, Chieri-Carmagno-
la-Moncalieri-Nichelino, Italy.

Daniel Lee, MD 
Dr. Lee is an Assistant Professor and the Director of the Glaucoma Research Center at the
Wills Eye Hospital, Philadelphia, PA, USA. After obtaining his medical degree from Rutgers
University’s Robert Wood Johnson Medical School, ophthalmology residency at the Yale
School of Medicine, and glaucoma fellowship at the Wills Eye Hospital, Dr. Lee serves as an
assistant attending surgeon on the Glaucoma Service.
Dr. Lee has authored and coauthored numerous articles and lectured at local and national
meetings. He is actively involved in teaching residents and fellows at Wills Eye Hospital.
His current research interests include novel glaucoma treatments and the role of ocular
perfusion in glaucoma pathogenesis.

Nils A. Loewen, MD, PhD 

Nils Loewen is an Associate Professor in the Department of Ophthalmology at the University
of Pittsburgh, PA, USA. Clinically, he is specialized in glaucoma and cataract care and micro-
incisional glaucoma procedures that are bleb-free. He has comprehensive experience
with Trabectome surgery and published extensively on factors and outcomes. In his basic
research, his laboratory is focused on bioengineering of the ocular outflow system with a
particular interest in the distal outflow tract.
xviii

Ralitsa Loewen, MD 
Ralitsa Loewen is a physician-scientist who investigates aqueous humor outflow both
clinically and in the laboratory, based in the Department of Ophthalmology at the University
of Pittsburgh, PA, USA. She has developed porcine ex vivo eye models for lentiviral transduc-
tion, established methods to visualize and measure aqueous humor flow, and generated
techniques to visualize microscopic aspects of the distal outflow system at high resolution
and in 3D.

David Lubeck, MD 
David Lubeck is a founder and world-renowned surgeon at Arbor Centers for EyeCare (IL,
USA), specializing in cataract, cornea and refractive surgery. Dr. Lubeck is passionate about
surgery, teaching and innovation. Dr. Lubeck teaches cataract and refractive surgery to
ophthalmologists all over the world, focusing on new technologies and safe and efficient
eye surgery. He is regularly a first to perform complex procedures providing patients with
outstanding surgical outcomes.
In addition to a busy clinical practice, Dr. Lubeck is an Assistant Clinical Professor of Oph-
thalmology at the University of Illinois, Chicago and lectures regularly worldwide. He has
developed curricula that have been integrated into surgical teaching programs across the
USA and abroad. He has hosted and participated in live surgery programs in China, India,
Vietnam, Korea, Australia, the Philippines, and the USA.

Jeffrey K. Luttrull, MD 
Dr. Luttrull is a vitreoretinal surgeon and clinical researcher practicing in Ventura, CA, USA.
His interests and publications include medical and surgical retina, with a special interest in
retinal laser therapy. He is founder and director of LIGHT: The International Retinal Laser
Society.

Ryan Machiele 
Ryan Machiele is a 4th-year medical student at Campbell University, NC, USA. His research
interests include evidence-based treatment modalities for various types of glaucoma. Other
research interests include the relationship between intraocular pressure and systemic
illness as well as eliminating barriers to care in disease-burdened areas. He will start his
residency training in 2020.
 xix

Amar Mannina, MD 
Amar Mannina is an ophthalmology resident at Cook County Health and Hospital Systems in
Chicago, IL, USA. His research interests include treatment modalities for glaucoma, including
micropulse trans-scleral diode and minimally invasive glaucoma surgery.

William Morgan, MBBS, PhD, FRANZCO 

Dr. Morgan is Professor of the Lions Eye Institute, Center for Ophthalmology and Visual
Science at The University of Western Australia in Nedlands, Australia. His research involves
basic studies of pressure gradients in and around the optic nerve, with specific interest in the
effect of cerebrospinal fluid (CSF) pressure. Derived from this, he has been recently pursuing
a greater understanding of retinal venous pulsation and its relationship to CSF pressure and
glaucoma. Dr. Morgan was involved with Professor Yu’s team in the development of gelatin
microfistula surgery for glaucoma therapy, the XEN Gel Stent, which is currently being widely
used internationally. He has a clinical and research interest in glaucoma surgery.

Thiago A. Moulin, MD 
Dr. Moulin holds a medical degree from the University of São Paulo, Brazil. He is currently
working with Dr. Arsham Sheybani from Washington University in St. Louis, MO, USA in
the statistical modeling of glaucoma patients’ outcomes using large datasets. Since his
graduation in 2015, he has also worked with big data analyses in the Saint Louis University
Center for Outcomes Research. He is interested in advancing the specialty through data
science, which includes the implementation of sophisticated analyses and also the proper
use of machine-learning techniques in ophthalmology.

Jonathan S. Myers, MD 
Dr. Myers is the Chief of the Glaucoma Service at Wills Eye Hospital and an Associate Professor
of Ophthalmology, Sidney Kimmel Medical Center in Philadelphia, PA, USA. Dr Myers has par-
ticipated in research involving many aspects of the diagnosis and management of glaucoma,
but has particular interests in investigations involving surgical procedures, pharmaceutical
options, and perimetry.

.
xx

Peter A. Netland, MD, PhD 

Dr. Netland received his undergraduate degree at Princeton University, his PhD from
Harvard University, and his medical degree from the University of California, San Francisco.
He completed his residency in Ophthalmology, followed by a clinical fellowship in glaucoma,
at the Massachusetts Eye and Ear Infirmary, Harvard Medical School. Currently, Dr. Netland
is the Vernah Scott Moyston Professor and Chair, Department of Ophthalmology, University
of Virginia School of Medicine, Charlottesville, VA, USA. He has written numerous peer-re-
viewed publications and delivered numerous named and invited lectures on clinical and
surgical management of glaucoma. He has received the Life Achievement Honor Award from
the American Academy of Ophthalmology and was elected to the American Ophthalmolog-
ical Society.

William D. Noonan, MD, JD 

Dr. Noonan is both a physician and a patent attorney who specializes in the protection of
medical inventions. During his postgraduate training he participated in an ophthalmolo-
gy residency. He is a partner and the Chair of the Life Sciences Patent Group at Klarquist
Sparkman, LLP in Portland, OR, USA. During a 37-year career he has represented cor-
porations, research institutes, universities, and individuals in both patent litigation and
prosecution matters. For the last 20 years he has also represented the National Institutes
of Health and other government agencies, making his firm the second largest supplier of
legal services to the United States government over the last decade. He is listed in the Best
Lawyers in America (2014-2019), IAM Patent 1000 World’s Leading Patent Practitioners (2015-
2019), and Chambers USA Best Patent Practitioners (2010-2019).

Makena Parker, BA 
Makena Parker holds a BA from the University of North Carolina at Chapel Hill (NC, USA). She
is currently a second year Master of Physiology student at North Carolina State University
and works as a clinical lead technician at a retina practice. Her research interests include
ophthalmology with a focus on increased surgical success rates for glaucoma patients and
retinal diseases.

Shyam Patel, MD 
Shyam Patel is currently a cornea and external disease fellow at the Eye Consultants of
Atlanta (GA, USA). He completed medical and business school at the University of Alabama
at Birmingham (AL, USA), followed by ophthalmology residency at Cook County Health in
Chicago, IL, USA. In addition to glaucoma, his previous research interests have included
retina, oculoplastics, and pediatric ophthalmology.
 xxi

Thomas Patrianakos, DO 
Thomas D. Patrianakos is the Chair of Ophthalmology for Cook County Health and Hospitals
System in Chicago, IL, USA. He is a board-certified ophthalmologist and a fellowship-train-
ing glaucoma specialist. His research interests include optic nerve head imaging techniques,
microinvasive glaucoma surgery, and glaucoma laser surgery.

Rodolfo A. Pérez-Grossmann, MD 
Dr. Perez-Grossmann graduated in Ophthalmology from the National Institute of Oph-
thalmology (Instituto Nacional de Oftalmología) in Lima, Perú. He completed a glaucoma
fellowship at the Glaucoma Research and Education Group in San Francisco, CA, USA. He
currently serves as Medical Director of the Glaucoma and Cataract Institute (Instituto de
Glaucoma y Catarata) in Lima, Perú.
He is former President of the Pan American Glaucoma Society and the Latin American
Glaucoma Society, founding member and first president of the Peruvian Glaucoma
Society, and a member of the Steering Committee of the World Glaucoma Association. Dr.
Perez-Grossmann has participated as coordinator or speaker in numerous congresses and
symposiums worldwide. He holds a US patent involving the method and apparatus for tra-
beculectomy and suprachoroidal shunt surgery. He was one of the founders of the Hospital
de la Familia volunteer group in Guatemala.

Rodolfo A. Pérez-Simons 
Rodolfo A. Perez Simons is a medical student at the Scientific University of the South
(Universidad Científica del Sur) in Lima, Perú. He volunteers at the the Glaucoma and
Cataract Institute (Instituto de Glaucoma y Catarata) in Lima, Perú. He also took part in the
foundation of the Hospital de la Familia volunteer group in Guatemala. His research interests
involve medical and surgery treatments of glaucoma.

Nicholas M. Pfahler, BS 
Nicholas M. Pfahler holds a BS from the University of Illinois at Chicago, IL, USA and is
currently a Research Associate at the same university. His research interests include cellular
mechanisms of neurodegeneration, identification of therapeutic targets in Alzheimer’s
disease, primary open-angle glaucoma, and age-related macular degeneration, as well as
visual processing.
xxii

Leonard Pinchuk PhD, DSc (h.c.), NAE 

Dr. Pinchuk is a Distinguished Research Professor of Biomedical Engineering at the University
of Miami (FL, USA). He is also the founder, Chairman Emeritus, and Chief Scientific Officer
of InnFocus, Inc., a Santen Company (FL, USA). Dr. Pinchuk is a biomaterials scientist with
seminal patents in the area of angioplasty balloons, coronary stents, stent grafts, drug-elut-
ing stents, biomaterials (including polycarbonate urethane and SIBS), the PRESERFLO
MicroShunt, and the next-generation intraocular lens materials. He is also the 2019 Russ
Prize Laureate. His current interests involve the interpretation of clinical results of the
PRESERFLO MicroShunt, developing new methods of preserving the bleb, reinterpreting
the drainage system from the glaucomatous eye based upon new information gleaned from
MIGS and OCT, and other ocular devices.

M. Reza Razeghinejad, MD 
Dr. Razeghinejad currently serves as Associate Professor of Ophthalmology at Wills Eye
Hospital, Sidney Kimmel Medical College, Thomas Jefferson University in Philadelphia, PA,
USA, and Co-Director of glaucoma fellowship of the Glaucoma Service. Dr. Razeghinejad’s
research focuses on the medical and surgical management of glaucoma. His research has
been published in over 100 peer-reviewed publications, including major ophthalmology
journals, and several book chapters.

Isabelle Riss, MD 
Professor Riss is Director of the Ophthalmology Department at Clinique Mutualiste de Pessac
in Pessac, France. Her research interests focus on glaucoma surgical techniques, methods
of maintaining blebs, and clinical trials, as well as studies involving new glaucoma devices,
including Alcon’s ExPress Shunt and the PRESERFLO MicroShunt.

Steven R. Sarkisian, Jr., MD 

Dr. Sarkisian is founder and CEO of Oklahoma Eye Surgeons in Oklahoma City, OK,Dr.
Sarkisian is founder and CEO of Oklahoma Eye Surgeons in Oklahoma City, OK,USA. He has
an active clinical practice with a particular interest in surgical innovation for the treatment
of glaucoma and cataracts, with extensive research involvement in numerous FDA clinical
trials, particularly involving MIGS. He was part of pivotal FDA trials for the CyPass, iStent
Inject, iStent Supra, and iDose.
 xxiii

Simona Scalabrin, MD 
Dr. Scalabrin is currently a Resident in the Ophthalmology Unit at the Department of Surgical
Sciences of the City of Health and Science University Hospital of Turin (Italy).
She received her summa cum laude medical degree from the University of Turin in 2015 and
attended the Scuola di Studi Superiori “Ferdinando Rossi”, an elite Italian institution of
higher education.
Her current interests involve the etiopathogenesis of optic nerve disorders, with particular
attention to the impact of sex hormones, medical and surgical glaucoma therapy, and
stem-cell treatment of eye disease.

Jonathan Shakibkhou 
Jonathan Shakibkhou graduated from UCLA and is the research manager at the Glaucoma
Research Institute of Beverly Hills in Los Angeles, CA, USA. Mr. Shakibkhou is interested
in the development and efficacy of novel surgical methods in the treatment glaucoma.
He was worked with Dr. Michael Berlin on excimer laser trabeculectomy research, testing
the efficacy of this procedure in comparison to other surgical and non-surgical treatment
options. Further, he has been actively involved in raising awareness about glaucoma and
presenting data that is comprehensible to the general population.

Arsham Sheybani, MD 
Dr. Arsham Sheybani completed his medical degree at Washington University School
of Medicine in St. Louis, MO, USA. He then completed his residency in Ophthalmology at
Washington University in St. Louis and was selected to remain on faculty as Chief Resident.
During that year, Dr. Sheybani was responsible for ophthalmologic trauma and emergencies
as well as all adult inpatient ophthalmology consultations at Barnes Jewish Hospital. He
was the primary surgical teacher for the beginning residents and implemented a didactic
system that is still used at Washington University. He then completed a fellowship with Ike
Ahmed in Glaucoma and Advanced Anterior Segment Surgery in Toronto, Canada.
Dr. Sheybani subsequently returned to Washington University School of Medicine as faculty
in the Department of Ophthalmology and Visual Sciences where he serves as Residency
Program Director and Assistant Professor of Ophthalmology. He has presented research
internationally and is currently involved in device design aiming to make glaucoma surgery
safer amongst many other endeavors. He is an avid surgical teacher, winning the resident
selected faculty teaching award early in his career. He has also helped create one of the
highest volume surgical glaucoma fellowships in the country serving as the fellowship
director.
xxiv

Ingeborg Stalmans, MD, PhD 

Professor Dr. Ingeborg Stalmans heads the Laboratory of Ophthalmology at the Catholic
University of Leuven (KU Leuven), as well as the Glaucoma Unit of the University Hospitals in
Leuven (UZ Leuven) in Belgium. The subject of her PhD was the role of vascular endothelial
growth factor (VEGF) in retinal angiogenesis and in the pathogenesis of DiGeorge syndrome.
This work resulted in several high-impact papers published in journals such as Nature, Cell,
and PNAS, and was rewarded by the prestigious GlaxoSmithKline prize.
The current focus of her basic and clinical research work is medical glaucoma therapy,
glaucoma surgery, and retinal imaging as a biomarker for systemic diseases. She has
published in Cell, Ophthalmology, Journal of Glaucoma, IOVS, etc. Her work has been
awarded with prizes from the Funds for Research in Ophthalmology (FRO) and the Pfizer
Glaucoma Research Award. As a glaucoma specialist and researcher, she frequently lectures
both nationally and internationally, including at ARVO, WGC, ISGS, EVER, EGS, ESCRS, SOE,
and ESASO. Within the European Glaucoma society, she is a member of the Executive
Committee, treasurer, chair of the Communication Committee, as well as co-chair of the
program-planning committee. She also serves on the Board of Governors of the World
Glaucoma Association (WGA) and in the Glaucoma Expert Committee of the European Vision
Institute Clinical Research Network (EVICR.net). She is the Treasurer of the Belgian Glaucoma
Society and a member of the Royal Academy of Medicine of Belgium.

Er-Ning Su, MD, PhD 

Dr. Su is Associate Research Professor of the Lions Eye Institute, Center for Ophthalmol-
ogy and Visual Science at The University of Western Australia in Nedlands, Australia. Her
research mostly involves in vitro studies of vasoactivity of retinal arteries and veins. Dr. Su
has developed a microperfusion system that allows vasoactivity to be assessed in real time
whilst perfusing or bathing the vessels with putative vasoactive compounds. The aim is to
better understand the mechanisms of blood flow control in the eye and look for potential
vasoactive compounds that could be useful clinically. She has also developed a custom-built
system to produce a bioengineered cross-linked gelatin microfistula for experimental use in
new forms of glaucoma filtration surgery.

David L. Swain, BA 
David L. Swain holds a BA in Biology and English from Boston University (MA, USA). During
his undergraduate studies he participated in the investigation of morphological differences
in the scleral spur between normal and glaucoma eyes. Currently, he is an MD/PhD candidate
in the department of Anatomy and Neurobiology at Boston University School of Medicine,
and is completing his PhD thesis in the laboratory of Dr. Gong. His research interests include
mechanisms of increased resistance in the aqueous outflow pathway of eyes with primary
open-angle glaucoma, and the structure and function of the inner wall endothelial cells of
Schlemm’s canal.
 xxv

Marc Töteberg-Harms, MD, FEBO 

Dr. Töteberg-Harms is a glaucoma specialist and attending physician at the University Hospital
Zurich, Department of Ophthalmology and a clinical instructor and lecturer (Privatdozent)
with the University of Zurich in Switzerland. He went to Charité Medical School, Humboldt
University Berlin, Germany and to the University of Kiel, Germany, where he graduated
from. He earned his medical doctorate degree and the venia legendi at University of Zurich
Medical School. Later, he completed clinical and basic research glaucoma fellowships at the
Massachusetts Eye and Ear Infirmary, Boston, MA, and Case Western Reserve University,
Cleveland, OH, in the United States. His research interests focus on glaucoma diagnosis
(OCT, visual field testing, and different tonometry techniques) and efficacy and safety of
surgical procedures, especially MIGS procedures.

Vanessa Vera, MD 
Dr. Vera is a glaucoma specialist and a surgical consultant for Kelotec, Fs-Eye, and Allergan.
She has published numerous peer-reviewed papers and book chapters, and has over ten
patents and patent applications in the USA. Her research interests include novel medical
and laser treatments, as well as new devices and surgical options for glaucoma.

Susannah Waxman, BA 
Susannah Waxman is the Laboratory Manager of the Loewen Lab for Outflow Tract
Engineering at the Department of Ophthalmology of the University of Pittsburgh, PA, USA.
Her research interest is the conventional outflow tract. Her background in plant physiology
and food safety has led to increasingly translational research interests in human physiology.
She is set to start a PhD in the Interdisciplinary Biomedical Graduate Program at the
University of Pittsburgh.

Alan Wenger, MD 
Dr. Wenger is Chief of the Glaucoma Service at Hospital San Juan de Dios in Santiago, Chile.
He graduated in Ophthalmology from the National Institute of Ophthalmology (Instituto
Nacional de Oftalmología) in Lima, Perú and then completed a fellowship in Clinical and
Surgical Glaucoma at Hadassah University Medical Center in Jerusalem, Israel. His current
interests involve glaucoma clinical research and development of novel glaucoma surgeries.
xxvi

Jithin Yohannan, MD, MPH 

Jithin Yohannan is an Assistant Professor of Ophthalmology at the Wilmer Eye Institute,
Johns Hopkins University School of Medicine (Baltimore, MD, USA). His practice specializes
in medical, laser, and surgical treatment of glaucoma, with a focus on minimally invasive
glaucoma surgery and new glaucoma surgical devices. He also performs both routine
and complex cataract surgery. Furthermore, Dr. Yohannan specializes in the surgical
management of complex problems of the anterior segment; these problems include issues
that arise after trauma or prior surgery gone wrong, such as dislocated intraocular lenses, or
iris and pupil defects.
Dr. Yohannan earned his bachelor’s degree in biochemistry from New York University, where
he graduated summa cum laude. He then received his medical and Master of Public Health
degrees from Johns Hopkins University and completed an ophthalmology residency at the
Wilmer Eye Institute, Johns Hopkins University School of Medicine. From there, he served as
a fellow in glaucoma and advanced anterior-segment surgery at the University of Toronto,
Canada, with Ike Ahmed. Subsequently, he returned to serve as Assistant Chief of Service at
the Wilmer Eye Institute.
Dr. Yohannan’s research focuses on using artificial-intelligence algorithms to improve the
tests that are used to diagnose and monitor glaucoma. His background in biostatistics,
epidemiology, and mathematics enables this effort. The ultimate goal of this research is
to detect glaucoma and determine when it is worsening more accurately. The results of
this work will ultimately help guide doctors who are managing glaucoma to make better
treatment decisions. Dr. Yohannan also has a clinical and research interest in novel surgical
devices used to treat glaucoma. These devices hold the promise of making glaucoma surgery
safer and easier to recover from.

Dao-Yi Yu, MD, PhD 

Dr. Yu is Professor of the Lions Eye Institute, Center for Ophthalmology and Visual Science
at The University of Western Australia in Nedlands, Australia. His research interests cover
many fields in ophthalmology, including glaucoma, retinal diseases, vascular biology, and
retinal metabolism. He leads a highly innovative team and has established more than ten
laboratories performing experimental research and transferring to clinical therapeutics
and diagnostics. As lead inventor, he has worked with his team to develop a new glaucoma
surgery including a crossed-linked gelatin microfistula, an ab interno implantation and
needle type implanter to perform MIGS, now in clinical use under the name XEN Gel Stent.
Currently, the team is interested in further improving the outcomes of glaucoma filtration
surgery.
1. Anatomy of the conventional aqueous outflow
pathway
Haiyan Gong, David L. Swain
Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA
Abstract
A better understanding of the anatomy of the outflow
pathways can be useful in knowing how each class of
minimally invasive glaucoma surgery (MIGS) devices
works. This article reviews the anatomy of the aqueous
drainage pathways, emphasizing the trabecular
meshwork. Experimental evidence of the location of
the major sources of outflow resistance in this pathway
and their contribution to glaucoma pathogenesis are
discussed. The segmental outflow pattern around the
circumference of the eye, structural differences in high-
and non-flow areas, and morphological changes that
are responsible for the reduction of effective filtration
area (EFA) with increased intraocular pressure (IOP)
and glaucoma are also discussed. Lowering IOP can be
achieved by medical and surgical treatments, through
increasing EFAs in the trabecular meshwork and in the
episcleral veins. Anatomically, much more remains to
be investigated to better understand how structural
changes along this pathway contribute to the regulation
of segmental outflow, how anatomical structures distal
to Schlemm’s canal, including the collector channels
and their ostia and scleral venous plexus, contribute
to the regulation of distal outflow resistance. Further
development of in vivo assessment of the segmental
outflow pattern with optical coherence tomography
and aqueous angiography could provide better, indi-
vidualized treatment plans and outcomes for MIGS
surgery.
Correspondence: Haiyan Gong, M.D., Ph.D., Department of Ophthalmology, Boston University School of Medicine, 72 East Concord
Street, L-905, Boston, MA 02118, USA.
E-mail: hgong@bu.edu
New Concepts in Glaucoma Surgery Series: Volume 1, pp. 1-38
Edited by John R. Samples and Iqbal Ike K. Ahmed
© 2020 Kugler Publications, Amsterdam, The Netherlands
Keywords: aqueous outflow pathway, collector channel,
Schlemm’s canal, segmental outflow, trabecular
meshwork
1. Introduction
Intraocular pressure (IOP) is maintained within a normal
range from a dynamic balance between aqueous
humor formation and drainage. Dysfunctional aqueous
drainage results in elevated IOP, which is a causative
risk factor for the development and progression of
primary open-angle glaucoma (POAG).1 An under-
standing of how to lower IOP using minimally invasive
glaucoma surgery (MIGS) begins with an understanding
of the normal anatomy of the structures related to the
drainage of aqueous humor and changes in POAG.
Aqueous humor is secreted by the ciliary body, enters
the posterior chamber, flows anteriorly through the
pupil, circulates around the anterior chamber by con-
vective flow, and exits through two pathways, the con-
ventional or trabecular outflow pathway and the uve-
oscleral outflow pathway. The conventional outflow
pathway is the major drainage pathway (80-90%), which
is comprised of the uveal and corneoscleral portions
of the trabecular meshwork (TM), the juxtacanalicular
connective tissue (JCT), Schlemm’s canal (SC), the col-
lector channels (CCs), the scleral venous plexus, and
the aqueous veins (AVs). Most aqueous humor drains
from the anterior chamber through ­ progressively
2 H. Gong and D.L. Swain
smaller channels of the TM into a circumferentially
oriented channel called SC. From this canal, aqueous
humor drains from external CCs, through the circuitous
scleral venous plexus, ultimately joining the episcleral
vasculature into the venous system. Flow through this
system is driven by a bulk-flow pressure gradient, and
active transport is not involved, as neither metabol-
ic poisons nor temperature affect this system to any
significant degree.2,3 The remaining 10-20% of total
aqueous outflow has been reported to leave the normal
eye via the uveoscleral pathway,4,5 which has become
a primary target for medical intervention in glaucoma.
However, this chapter will only focus on the conven-
tional trabecular outflow pathway.
2. Normal anatomy of the conventional
aqueous outflow pathway
2.1. Trabecular meshwork
The TM is a triangular-shaped band of tissue encircling
the anterior chamber angle (Fig. 1a). The apex of the
triangle is attached to the terminal edge of Descemet’s
membrane of the cornea, which is termed Schwalbe’s
line. From this point of origin, the TM expands as it
bridges the iridocorneal angle, and ends posteriorly by
blending with the scleral spur, ciliary body, and stroma
of the iris. The scleral spur projects like a shelf onto the
base of this triangle, and its posterior surface serves as
a point of insertion for the longitudinal bundle of the
ciliary muscle. The length of the TM from Schwalbe’s
line to the scleral spur is 694.9 ± 109 µm in men and
713.2 ± 107 µm in women by histological assessment.6
Using optical coherence tomography (OCT), the mean
length of the TM was found to be 466.9 ± 60.7 µm in
vivo.7 An imaginary line drawn from Schwalbe’s line to
the tip of the scleral spur separates the TM into two
major parts; the portions of the TM closer to the sclera
in relation to this imaginary line include the corneo-
scleral meshwork, the juxtacanalicular tissue, and SC.
The portion of the TM closer to the anterior chamber
internal to this imaginary line is termed the uveal
meshwork, because it extends from Schwalbe’s line
to the stromata of the ciliary body and iris (Fig. 1). The
uveal meshwork is readily viewed gonioscopically.
It is important to understand the relationship among
the anterior chamber angle structures by comparing
the views from two perspectives — the view obtained
from meridional sections (Fig. 2), and the en face and
gonioscopic views obtained of the anterior chamber
angle (Fig. 3). In Figure 3a, the light reflection from
Schwalbe’s line and the TM below it, overlying the
blood-filled SC, can be clearly seen. Below SC, the lighter
coloration from the scleral spur is evident and finally,
below the scleral spur, the very dark coloration given
by the pigment in the ciliary body stroma is seen. This
lowest layer of the meshwork, seen from the gonioscopic
perspective, is referred to as the ciliary body band
(Fig. 3b). For comparison, these same structures are
depicted in a goniophotograph of a normal open angle
in Figure 3c and 3d. A series of alternating dark and light
bands is evident, corresponding to the areas shown in
Figure 4. The uppermost dark band is Schwalbe’s line,
which is commonly decorated with various amounts of
pigment, even in the normal eye. The lighter line below
that represents the anterior or nonfiltering meshwork.
This portion of the meshwork is not adjacent to SC and
no aqueous humor drains out of this region. The amount
of pigment phagocytosed by the trabecular cells in
this region is low and results in minimal pigmentation.
Below this lighter line is a darker line corresponding
to the posterior or filtering meshwork. This portion of
the meshwork leads most directly to SC. Here, both
the flow and the amount of phagocytosed pigment is
greater compared to the nonfiltering meshwork (Fig.
5), resulting in a darker appearance on gonioscopy (Fig.
3c). Below this dark line is another lighter line corre-
sponding to the scleral spur. Finally, just below this, the
lowest dark line corresponds to the ciliary body band.8,9
2.1.1. The uveal and corneoscleral meshwork
The uveal and corneoscleral meshwork are composed
of a series of trabecular lamellae or beams that delimit
a system of aqueous flow channels (Figs. 1 and 4). The
corneoscleral and outer uveal trabecular beams are
flattened, perforated sheets that are orientated circum-
ferentially, parallel to the surface of the limbus. However,
the inner one to two layers of uveal sheets closest to the
anterior chamber have a round, cord-like profile and
are oriented in a radial, net-like fashion, enclosing large
open spaces for aqueous outflow. The spaces become
progressively smaller from the uveal to the corneo-
scleral meshwork (Figs. 1 and 4). After surgical removal
of uveal meshwork from the TM, outflow facility was
Anatomy of the conventional aqueous outflow pathway 3

Fig. 1. Normal trabecular outflow pathway. (a) A light micrograph of the anterior chamber angle is shown. Trabecular meshwork (TM),
Schlemm’s canal (SC), collector channel (CC), intrascleral plexus (ISP), episcleral vessels (ESV), scleral spur (SS), ciliary muscle (CM), and iris
are labeled. The white arrowhead demarcates the terminus of Descemet’s membrane, also known as Schwalbe’s line. Reproduced from
Gong et al.18 (b) The trabecular meshwork is shown at higher magnification. From proximal to distal, the uveal trabecular meshwork (U),
the corneoscleral trabecular meshwork (CS), and the juxtacanalicular tissue (JCT) are labeled. The anterior chamber (AC) and Schlemm’s
canal (SC) are also labeled. Adapted from Gong et al.148
4 H. Gong and D.L. Swain

Fig. 2. (a) Macroscopic photograph and (b) corresponding sketch identifying structures visible in a meridional section of the normal
anterior chamber angle of a monkey eye. The anterior chamber is artificially deepened because of posterior sagging of the iris following
removal of the crystalline lens. The heavily pigmented region corresponds to the posterior or filtering meshwork. Schwalbe’s line (SL),
Schlemm’s canal (SC), trabecular meshwork (TM), scleral spur (SS), and ciliary body band (CBB). Reproduced from Freddo.8

Fig. 3. The anterior chamber angle viewed with both microscopy and gonioscopy. (a) Macroscopic photograph of angle structures viewed
from the gonioscopic perspective. Schlemm’s canal is filled with blood in this specimen, demonstrating its relationship to the other angle
structures. An iris process (IP) is also shown. (b) A corresponding sketch of (a) (black box). (c) Goniophotograph of a normal open angle
and (d) corresponding sketch representing a view analogous to that in (c). Five alternating dark and light bands are evident in the angle.
The uppermost dark band corresponds to Schwalbe’s line (SL). The uppermost light band corresponds to the anterior or nonfiltering
meshwork. The next dark band corresponds to the posterior or filtering meshwork (TM). The next light band corresponds to the scleral
spur (SS). The final dark band, just above the peripheral iris, corresponds to the ciliary body band (CBB). Reproduced from Freddo.8
Anatomy of the conventional aqueous outflow pathway 5

Fig. 4. Drawing of the aqueous outflow pathway and

adjacent tissue. (a) Schlemm’s canal; (b) an internal
collector channel opens into the posterior part
of Schlemm’s canal; (c) corneoscleral meshwork
beams; (d) scleral spur; (e) limbus; (f) uveal beams; (g)
Schwalbe’s line (peripheral terminus of Descemet’s
membrane); (h) an iris process extends from the root
of the iris to merge with the uveal meshwork; (i) the
longitudinal ciliary muscle is attached to the scleral
spur but has a portion which joins the corneoscleral
meshwork; and (j) the corneal endothelium becomes
continuous with the deep limbus. Double-headed
arrows represent a broad transition zone that begins
near the termination of Descemet’s membrane and
ends where the uveal meshwork joins the deep
limbus. CB: ciliary body. Adapted from Hogan et al.61

Fig. 5. Light micrograph of the trabecular meshwork

demonstrates phagocytosis of melanin by trabecular
endothelial cells in the posterior meshwork. Note
the abrupt reduction in the amount of pigmentation
in the anterior meshwork beyond the anterior edge
of Schlemm’s canal (SC) (black line). This difference
in pigmentation is evident clinically. Reproduced
from Freddo et al.149
6 H. Gong and D.L. Swain

Fig. 6. Transmission electron micrographs of normal trabecular meshwork. (a) The trabecular meshwork from a 61-year-old donor eye,
perfusion-fixed at 15 mmHg. Most beams are covered with a single layer of endothelial cells (arrowheads). Giant vacuoles (V) are seen
along the inner wall of Schlemm’s canal (SC). ITS: intertrabecular spaces. Reproduced from Gong et al.18 (b) Each trabecular beam is
covered by a single layer of trabecular endothelial cells (TEC) that rest on the basal lamina (BL), which surrounds a central connective
tissue core. Collagen (C), elastic fiber (EL), sheath material of elastic fiber (SM), and intertrabecular spaces (ITS). Reproduced from Gong
et al.150
Anatomy of the conventional aqueous outflow pathway 7

Fig. 7. Transmission electron micrographs of the juxtacanalicular region (JCT). The JCT region is composed of the JCT cells and matrix.
The JCT cells are devoid of a basal lamina; their cell processes (arrowheads) connect to endothelial cells of the inner wall of Schlemm’s
canal (SC) and other JCT cells. The matrix is composed of collagen (C) and elastin (E). Reproduced from Gong et al.151
8 H. Gong and D.L. Swain

found not to be significantly influenced.10 Ultrastruc-
turally, the uveal and corneoscleral beams consist of
a central connective tissue core that is enveloped in
a continuous wrapping of thin endothelial cells and a
subcellular basal lamina (Fig. 6). Trabecular cells are
phagocytic11 and capable of removing endogenous12,13
and exogenous14,15 particles to keep the trabecular
outflow channels free of potentially obstructive debris.
A progressive, age-related loss of trabecular cells has
been reported in normal eyes, and additional cell
loss was reported in the TM of POAG eyes, compared
to normal subjects.14,16,17 Fusion of trabecular beams
observed in POAG eyes may result from adhesions
between denuded portions of adjacent trabecular
beams.18
2.1.2. The juxtacanalicular region
The portion of the TM between the outermost corneo-
scleral beam and the inner wall of SC has a fundamen-
tally different structure. Instead of connective tissue
beams confined within endothelial wrappings, the JCT
region is an open connective tissue matrix in which
fibroblast-like cells, lacking a basal lamina, are located.
The cells in the JCT form long processes by which they
attach to each other, to an extracellular matrix (ECM),
and to the inner wall endothelial cells of SC (Figs. 6a
and 7). In addition, studies have documented that
tendons from the longitudinal bundle of the ciliary
muscle extend into the meshwork, culminating in a
system of elastic fibers that connect to the inner wall
of SC, which has been termed the cribriform plexus
(Fig. 8).19,20 The majority of the resistance to aqueous
outflow is believed to reside in the JCT region near SC
and is modulated by the inner wall of SC,10,21-27 but the
actual source of this resistance has remained elusive.
The balance between ECM synthesis and degradation
plays an important role in the regulation of aqueous
outflow resistance and IOP.28 Abnormal accumula-
tions of ECM in the JCT region have been reported in
both primary and secondary open-angle glaucoma,29-32
including POAG patients with no medical treatment.29
Thus, this accumulation of ECM appears to be a primary
pathophysiologic event in POAG.
2.1.3. Schlemm’s canal
SC is a continuous channel oriented circumferential-
ly, deep within the internal scleral sulcus. Its lumen is
directly continuous with the venous system of the eye.
Despite this connection, blood is not usually seen in
the canal unless IOP falls below the episcleral venous
pressure or when the limbal vessels are compressed, as
occurs with the use of a flanged gonioscope. When cut
in cross-section, the canal has an elliptical appearance
with its major length varying from 264 ± 55 µm by his-

Fig. 8. (a) Anterior ciliary muscle tendons (T) and their connections with the trabecular meshwork (TR). Tendons from the longitudinal
bundle of the ciliary muscle (CM) extend to the scleral spur (SP), into the outermost corneoscleral trabeculae, and into the juxtacanalicu-
lar region contributing to the cribriform plexus. Connecting fibrils (CF) extend from the plexus toward the endothelial cells (E) lining the
inner wall of Schlemm’s canal (Sc). EL: elastin. Reproduced from Rohen.19 (b) Immunoelectron micrograph shows a single connecting fibril
(C) attaching to the endothelium (E) of the inner wall of Schlemm’s canal (SC). Scattered small black dots represent colloidal gold staining
for elastin, confirming that these connecting fibrils contain this protein. Reproduced from Gong et al.20
Anatomy of the conventional aqueous outflow pathway
tological assessments33 to 347.2 ± 42.3 µm as measured
with OCT.7 The mean height of SC (at the widest distance
between the inner and outer wall of the canal) is 31 ±
2 µm in normal human eyes by histology.34
The canal usually appears slit-like (Fig. 1a), and at
some points around the circumference of the eye it
can be divided into two parallel channels that rejoin
after a short distance. One side of the canal directly
abuts the sclera, which is termed the outer wall of SC.
The opposite side is connected to the JCT region of
the meshwork and is termed the inner wall of SC. The
endothelial lining of SC is composed of a single layer of
cells that rest on a discontinuous basal lamina (Figs. 6a
and 7). The endothelial lining cells are elongated,
generally oriented parallel to the longitudinal axis of
the canal (Fig. 9). The cells are 71.8-90.2 µm in length
and 9.7-13.3 µm in width in the central nuclear region,
and narrower (3.9-8.0 µm) in non-nuclear regions.35
Adjacent endothelial cells are overlapping and
connected to each other by tight junctions (Fig. 10).36
Decreased cell overlap and tight junction strands were
found with increasing pressure experimentally.37 The
inner wall endothelial cells connect to the underlying
JCT cells and matrix through their cellular processes.35,38
There are seven types of cellular connections between
the inner wall cells and JCT cells and matrix based on
serial block-face scanning electron microscopy and 3D
reconstructions (Fig. 11).35 A characteristic aspect of the
inner wall endothelium of SC is the formation of cellular
outpouchings that are termed giant vacuoles (GVs; Figs.
9 and 12). The GVs form when aqueous humor pushes
against the basal side of the inner wall endothelium.39
They appear to be pressure-dependent and are
observed easily when the inner wall is fixed under
conditions of active flow.40 There are often multiple GVs
within each inner wall cell, and usually one large GV near
the cell nucleus accompanied by a few smaller GVs along
the length of the cell (Fig. 9b).35 Aqueous humor enters
into SC from the JCT and is believed to exit through the
GVs and small openings or pores (Fig. 9).41 There are two
types of pores that are termed intracellular and para-
cellular pores (Fig. 12).42 Intracellular pores (I-pores) are
often associated with GVs with a mean diameter around
1 µm.43 Paracellular pores are located at the border
between two adjacent endothelial cells (B-pores), where
overlap between two cells does not exist (Fig. 13).35 The
mean diameter of B-pores is 1.64 µm, slightly larger
9
than I-pores.42 Previous tracer studies showed an
increased pore density with increased accumulation of
fluorescent tracers along the inner wall44 and near the
pores on both basal and apical sides of the inner wall
endothelium of SC (Fig. 14).45 Although an earlier study
reported that pores were responsible for about 10%
of total outflow resistance in normal eyes,43 a hydro-
dynamic interaction between the pores of the inner
wall of SC and the underlying JCT may greatly increase
outflow resistance in this region through a funneling
effect, by confining the flow to the JCT regions near the
inner wall pores, forcing a funneling pattern of aqueous
outflow; thus, pores may modulate the resistance in
this region.26 Decreased pore density was found in
POAG eyes compared to normal eyes,25,46 suggesting
that loss of the ability to form pores may contribute to
increased outflow resistance in eyes with POAG. A layer
of nonuniform glycocalyx lines the wall of SC and fills
most of the pores through which aqueous humor flows
into SC (Fig. 15).47 Glycocalyx in SC may play a role in
transduction of shear stress and regulation of aqueous
outflow resistance, since a glycocalyx-filled pore has a
far higher flow resistance than an empty pore.47
Increasing IOP leads to progressive collapse of the
canal.39,48 As SC collapses, the outflow resistance
increases and IOP rises further.49,50 Collapse of SC was
also associated with a shorter scleral spur (Fig. 16),
which may compromise the ciliary muscle/scleral spur/
TM network that maintains the patency of SC.34 The
dimensions of SC in eyes with POAG were reported to
be significantly smaller than in the normal eye.33,34 This
reduction in the dimensions of SC may account for
nearly half of the decrease in outflow facility observed
in POAG eyes.33
2.2. The ciliary muscle and trabecular outflow
Attached to the posterior surface of the scleral spur
are tendons of the longitudinal bundle of the ciliary
muscle, which are continuous with the ECM of the TM
(Figs. 8 and 16).51 Contraction of these longitudinal
muscles pulls the scleral spur posteriorly and separates
the layers of the corneoscleral meshwork attached to
the anterior surface of this structure. This appears to
facilitate aqueous drainage and is the basis for the use
of miotics in increasing aqueous outflow to reduce IOP
in glaucoma. Surgical disinsertion of the ciliary muscle
has been shown to eliminate the outflow-enhancing
10 H. Gong and D.L. Swain

Fig. 9. The inner wall endothelial cells of Schlemm’s canal. (a) A scanning electron micrograph of the luminal surface of the inner wall of
Schlemm’s canal demonstrating numerous bulging giant vacuoles. Several pores are evident (arrowheads), shown at higher magnifica-
tion in the inset. Reproduced from Allingham et al.46 Inset reproduced from Gong et al.151 (b) 3D scene of an inner wall endothelial cell with
two giant vacuoles (GV) and a pore. An inner wall cell (blue) with an I-pore (circled) associated with one of two GVs (green) near the nucleus
(dark red) was 3D reconstructed based on serial, ultrathin scanning electron microscopy (EM) images. (c) A higher magnification snapshot
of the reconstructed I-pore encircled in (b). Reproduced from Lai et al.35

Fig. 10. Junctions between the adjacent inner wall cells of Schlemm’s canal (SC). Two adjacent endothelial cells are overlapping and
connected by tight junctions, which appear as fusion points between the plasma membranes of two adjacent cells (arrows).
Anatomy of the conventional aqueous outflow pathway 11

Fig. 11. Types of connections between inner wall (IW) endothelium (red) of Schlemm’s canal (SC), underlying juxtacanalicular connective
tissue (JCT) cells (green), and extracellular matrix (ECM). Cell-to-cell (arrows) and cell-to-ECM (arrowheads) connections between the IW
endothelium and JCT cells or ECM were categorized into seven types based on serial block-face scanning electron microscopy images
and 3D reconstructions. Type 1 shows the IW cell extending a cytoplasmic process to underlying ECM (and not to any cell bodies of JCT);
Type 1: IW process-to-JCT ECM. Types 2-7 are between an IW and JCT cell; Type 2: IW process-to-JCT cell body, type 3: IW tongue-in-JCT
groove, type 4: IW process-to-JCT process, type 5: JCT process-to-IW body, type 6: JCT tongue-in-IW groove, and type 7: IW body-to-JCT
body. Reproduced from Lai et al.35

Fig. 12. Two types of pores: I- and B-pores. (a) Transmission electron micrograph of the juxtacanalicular tissue (JCT) region with elastic
fibers (EL) and inner wall endothelium of Schlemm’s canal (SC) showing giant vacuole (V) and an intracellular pore leading into SC
(arrowhead). Reproduced from Gong et al.150 (b) An opening from the juxtacanalicular tissue (JCT) to Schlemm’s canal (SC) (arrows)
between two inner-wall cells. Adapted from Ye et al.37
12 H. Gong and D.L. Swain

Fig. 13. B-pores and overlapping cell margins between two inner wall (IW) endothelial cells of Schlemm’s canal (SC). (a) 3D reconstructions
of two adjacent IW cells (green and orange) were made semi-transparent to show overlapping cell margins (dark green region indicated
by arrows) and a B-pore (encircled). GV: giant vacuole. (b) Higher magnification snapshot of reconstructed pore encircled in (a). (c) Three
serial block-face scanning electron micrographs from which the B-pore (arrow) was identified and reconstructed. Reproduced from Lai
et al.35
Anatomy of the conventional aqueous outflow pathway 13

Fig. 14. Analysis of tracers crossing the inner wall. (a) Tracers (arrows) were observed across the inner wall of Schlemm’s canal (SC) at
various regions. (b) At a higher magnification, fluorescent tracers were observed on both the basal and apical side of a cell-cell junction in
the inner wall endothelium of SC. (c) Serial sections were cut in the same cell-cell junction region as shown in (b). A paracellular pore was
seen with tracers on both the basal and apical sides. Adapted from Yang et al.45

Fig. 15. Pores filled with glycocalyx. (a) A glycocalyx layer coats the luminal surface of Schlemm’s canal (SC) of a human eye. A pore in a
giant vacuole (GV) (arrow; insert at a higher magnification) is filled with glycocalyx, but the inner membrane of the GV is not coated with
glycocalyx; note the membranous material apparently in the passage through the GV. (b) Glycocalyx was seen filling a pore not associated
with the GV (arrow; insert at a higher magnification). Significant Alcian blue staining was also seen in the extracellular matrix of the basal
side of the inner wall endothelium (*). Adapted from Yang et al.47
14 H. Gong and D.L. Swain

Fig. 16. Shorter scleral spur in eyes with primary open-angle glaucoma (POAG). (a) A light micrograph from a normal eye, the red line
indicates the length of the scleral spur. (b) A light micrograph from a POAG eye; the scleral spur is shorter compared to that in the normal
eye (a). Schlemm’s canal (SC) is collapsed (arrows). TM: trabecular meshwork; CM: ciliary muscle. Adapted from Swain et al.34

effects of pilocarpine.52 In addition, the elastic fibers of
the scleral spur are continuous with the elastic fibers
in the trabecular beams and the cribriform plexus in
the JCT19 (Fig. 8) and extend to the basal lamina of the
inner wall endothelial cells of SC.20 These tendons are
thought to put tension on the inner wall of SC, resisting
the pressure-related collapse of SC when pressure is
elevated.53
2.3. Aqueous outflow pathways distal to SC
2.3.1. Collector channels
From SC, aqueous humor enters the CCs. Histologically,
25-30 CCs are found randomly distributed circumferen-
tially around SC in the human eye, with a higher distri-
bution on the inferior-nasal side than on the temporal
side of the eye.54,55 This has been confirmed by studies
using three-dimensional microcomputed tomography
(3D micro-CT) (Fig. 17).56 There is great variability in
the orifice size of CCs, with a range between 5-50 µm
to as high as 70 µm, depending on the study design.54-56
Examined by scanning electron microscopy, two classes
of CC orifices were identified. Simple, oval orifices (54 ±
4.6 µm diameter) often occurred in a planar region of
the outer wall of SC, and complex orifices (62.7 ± 3.4 µm
diameter) were usually associated with septal columns
and bridges.57 A previous study reported that smooth
muscle actin was found near the CC ostia regions, 58 but
further study is needed to understand whether these
vessels are capable of contraction and thus contribute
to regulating aqueous outflow.
A light microscopic study has shown that CC ostia
Anatomy of the conventional aqueous outflow pathway
Fig. 17. Distribution of collector channels in a normal eye. (a)
Up to 30 collector channels (black arrows) were found unevenly
distributed around Schlemm’s canal (magenta). Asterisks denote
two adjacent collector channels. Reproduced from Hann et al.56 (b)
A light micrograph of the frontal section showing the trabecular
meshwork, Schlemm’s canal (SC) and collector channel (CC) ostia.
Reproduced from Gong et al.152
were significantly narrower in POAG compared to
normal eyes.59 A study examined the anatomy of CCs
in enucleated normal and POAG eyes under normal
(10 mmHg) and high (20 mmHg) perfusion pressure
using 3D micro-CT.60 CC orifice area (8049.2 vs 6468.4
µm2) and CC diameter (36.2 ± 19.1 vs 29.0 ± 13.8 µm)
were found to be larger in 10 mmHg compared to 20
mmHg perfusion pressure in POAG eyes. In normal
human eyes, CC orifice area was larger (9962.8 vs
8825.2 µm2), but a similar CC diameter (34.3 ± 17.8 vs
32.7 ± 13.0 µm) was found at 10 mmHg compared to
20 mmHg, suggesting that compensatory mechanisms
for transient and short periods of increased pressure
are diminished in POAG eyes.60 Partial and total CC
occlusions or partial and complete herniations into CC
ostia were present in normal and POAG eyes, with an
increase in total occlusions or complete herniations
15
Fig. 18. Diagrammatic representation of the distal portion of
the aqueous outflow pathways from Schlemm’s canal. External
collector channels (lower right), deep and intrascleral plexi (upper
right), aqueous veins (1 and 2; upper left), and arterial circle (lower
left). Reproduced from Hogan et al.61
into CCs in POAG compared to normal eyes.59,60
2.3.2. Scleral venous plexus
From the CCs, aqueous humor passes through a tortuous
system of passages, including the deep, midlimbal, and
superficial intrascleral venous plexuses that lead in turn
to the episcleral veins (Fig. 18).61 The intrascleral venous
plexus is composed of a series of small, interconnected
venules 10 to 50 µm in diameter with many interconnect-
ing branch points forming a dense vascular network.
The venous plexus is drained posteriorly by several
larger veins forming a series of radial arcades. These
vessels are 50 to 100 µm in diameter and progressively
converge into larger vessels moving posteriorly away
from SC. These vessels eventually converge with larger
episcleral veins. Visualization of these vessels has been
reported using OCT,62,63 fluorescent microsphere tracer
studies,63 and 3D micro-CT.56
2.3.3. Aqueous veins
The human eye contains a small number of unique
vessels termed AVs (of Ascher), which are of great
importance to normal aqueous outflow. AVs bypass
the deep and intrascleral venous plexus and directly
communicate from SC to episcleral veins that return
16 H. Gong and D.L. Swain

Fig. 19. Neoprene cast of Schlemm’s canal and limbal vessels

showing sector containing marked aqueous vein. The tantalum
wire loop is still to be seen in situ. Reproduced from Ashton.153

Fig. 20. Pulsatile flow changes in the normal eye. Illustration of characteristic pulsatile flow changes caused by increasing IOP or addition
of medications. Still frames and illustrations derived from video images of a 59-year-old male subject. (a) Baseline IOP: velocity (V) is low
and aqueous pulse-wave travel (D) with each stroke is small. A standing transverse interface of aqueous and blood oscillates, resulting
in systolic discharge of aqueous into a small venous tributary (ST). (b) Slightly increased IOP: The oscillatory aqueous fluid wave travels
an increased distance. (c) Highest IOP: increased velocity and travel of the aqueous fluid wave. At each systole a lamina of clear aqueous
discharges into an episcleral vein. (d) Decreasing IOP: velocity and travel of the fluid wave increase further. Continuous, oscillating laminar
flow is present in a more distal episcleral vein. Two hours after drinking water, IOP was again 10 mmHg and stroke volume returned to the
appearance seen in image (a). Reproduced from Johnstone et al.76
Anatomy of the conventional aqueous outflow pathway 17

blood to the general circulation64-66 (Fig. 19). AVs
contain clear aqueous at their origins but anastomose
with episcleral vessels that contain blood. Transition-
al zones are often identified in AVs on the conjuncti-
val surface as a large vessel with a clear central lumen
bordered on either side by dark blood. With changes in
IOP, these transitional zones vary in their composition
of aqueous and blood. Direct observation of these
changes is a reliable method to gauge the efficacy of
medical and surgical treatments aimed at reducing IOP
in glaucoma.67
AVs vary in their position, size, and anatomical
arrangements. On slit-lamp examination, two to three
AVs are typically visible with up to a maximum of six
occasionally observed.68 AVs have unequal distributions
and are present most abundantly in the inferior-nasal
quadrant, with the remainder in the inferior-temporal
quadrant.68 Their size varies from 20-100 µm, with an
average of 50 µm.68-70 Histologically, AVs are indistin-
guishable from conjunctival and episcleral veins.
A dynamic equilibrium exists in AVs based on the
current understanding of pulsatile flow driving aqueous
outflow (Fig. 20).71-73 Pulsatile flow occurs from an
oscillatory, compressive force provided by the cardiac
pulse and blinking, inlet channels from the JCT and
the inner wall endothelium to SC, and outlet channels
via CCs and AVs. Glaucoma patients show a decrease
in pulsatile flow compared to normal subjects.74,75 The
reduction of pulsatile flow in glaucoma patients can be
accounted for by physiologic changes in the elasticity
of the TM. The TM must be deformable to dynamic
pressure and volume changes in inflow and outflow
for normal aqueous outflow to occur from the anterior
chamber to SC.76
The major source of aqueous humor outflow
resistance is located in the JCT, within 7-14 µm of the
inner wall of SC by microcannula pressure measure-
ments,24 and is modified by the inner wall endothelium
of SC through its pores.10,21-23,25-27 Structures distal to SC,
including the CCs, intrascleral venous plexuses, and AVs,
are assumed to contribute less to outflow resistance.77,78
An early study reported that 75% of aqueous outflow
resistance was localized to the TM and SC with 25%
occurring from the structures distal to SC21 when eyes
were perfused at 25 mmHg. Following complete trabec-
ulotomy, 49% of outflow resistance was eliminated at
a perfusion pressure of 7 mmHg (corresponding to the
normal IOP in enucleated human eyes with no episcleral
venous pressure),79 and 71% of outflow resistance was
eliminated at a perfusion pressure of 25 mmHg.10 This
suggests that pressure-dependent changes in outflow
resistance are present in the TM and SC with additional
resistance distal to SC. Another study using excimer
laser to ablate one clock hour of tissue from the outer
wall of SC and distal sclera eliminated 35% of outflow
resistance at a perfusion pressure of 10 mmHg.80 These
studies indicate that one-third to half of the outflow
resistance lies distal to the inner wall of SC.

Fig. 21. Segmental aqueous flow pattern in normal human eyes. (a) Posterior view of the tracer distribution in the trabecular meshwork
(TM) in a global image. Segmental tracer distribution is seen. S: superior; N: nasal; I: inferior; T: temporal. (b) Segmental tracer distribution
is seen in the scleral veins in the anterior view of a global image. (c) A confocal microscopic image showing tracer distribution in the TM is
segmental, and more tracer (green) is near the collector channel (CC) ostia region, leading away from Schlemm’s canal (SC). (d) A confocal
microscopic image showing no tracer in this region of the TM, nor near a CC. Reproduced from Gong et al.152
18 H. Gong and D.L. Swain

Fig. 22. Pigmentation near the collector channel ostia region of the trabecular meshwork (TM). Light micrograph of the TM demonstrates
phagocytosis of melanin by trabecular endothelial cells. More pigmentation is observed in the TM near the collector channel (CC) ostia,
which is open to Schlemm’s canal (SC) obliquely. Reproduced from Gong et al.152

Fig. 23. Trabecular meshwork (TM) thickness in areas of active and inactive outflow. (a) In areas of active outflow, more fluorescent green
tracers were observed within the TM and along the inner wall of Schlemm’s canal (SC), and a thicker trabecular meshwork was noted (red
double arrows). CC: collector channel. (b) Inactive areas of outflow showed little to no green fluorescent tracers within the TM and along
SC inner wall, as well as a thinner TM (red double arrows). (c) TM thickness was significantly larger in areas of active outflow compared to
areas of inactive outflow (*P ≤ 0.01). Reproduced from Cha et al.82

3. Aqueous outflow patterns
3.1. Aqueous outflow is nonuniform (segmental) in
normal eyes
Aqueous humor outflow is nonuniform or segmental
circumferentially as observed from the distribution of
pigment in the TM81 and fluorescent tracer perfused
into the anterior chamber.48,82-84 At any given time, only
a fraction of the outflow pathways is actively involved
in aqueous humor drainage (Fig. 21a and 21b). This
active area is termed the effective filtration area (EFA).
Segmental outflow has been reported in n ­ onhuman48,83-86
and human eyes.45,81,82 A greater concentration of tracer
was observed in the TM adjacent to CC ostia where more
pigment was also observed in human eyes (Figs. 21c, 22,
and 23a), suggesting that preferential flow pathways are
present and that pigment may serve as a useful internal
marker to identify the area with active flow. However,
active flow is not observed in some TM regions near CC
ostia, especially in the superior and temporal regions
of the eye45,82 (Fig. 23b), suggesting higher outflow
resistance near these CC ostia. The factors that regulate
regional outflow resistance remain unclear. A segmental
nature of outflow is observed along the trabecular
outflow pathway in the TM, near the inner wall of SC,
and in the episcleral veins (Fig. 21). Similar EFA was
found in the inner wall of SC and episcleral veins. Pref-
erential active outflow was observed in the nasal and
inferior quadrants of the eye, where a higher number
of CCs was found.82 The TM and JCT in the active flow
region appear more expanded compared to inactive
flow regions (Figs. 23 and 24).
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At length Livingston agreed to stand provided both Clinton and Gates
would run. Straightway, Burr rushed to Gates. It was a hard struggle. Burr
pleaded, cajoled, flattered, appealed to party pride. Finally Gates agreed to
run if Clinton would make the race. And there Burr almost met his
Waterloo. The rugged old war-horse was prejudiced against Jefferson. He
had ambitions for the Presidency himself, and they had been passed over.
Burr left the matter open, smiled, flattered, bowed, departed. Then, out from
his office committees began to make their way to Clinton with
importunities to stand. The personal friends of the stubborn old man were
sent to persuade him. He was adamant. A scene at Burr’s home at
Richmond Hill: Present, the nominating committee and Clinton. A mass
movement on Clinton—he would not budge. Then Burr’s master-stroke. A
community had a right to draft a man in a crisis—the crisis was at hand.
Without his consent they would nominate him. The rebellious veteran,
flattered, agreed not to repudiate the nomination. The victory was Burr’s—
and Jefferson’s.
A little later, the press announced that a meeting of the Democrats had
been held at the home of J. Adams, Jr., at 68 William Street, where the
Assembly ticket had been put up. Spirited resolutions were adopted. The
enthusiasm of the Jeffersonians reached fever heat. Hamilton and the
Federalists were paralyzed with amazement. The impossible had happened.
Against Hamilton’s mediocre tools—this ticket, composed of commanding
figures of national repute![1729] Immediately the frantic fears of the
Federalists were manifest in the efforts of ‘Portius’ in the ‘Commercial
Advertiser’ to frighten the party into action. Jefferson had become a
possibility—the author of the Mazzei letter! Clinton and Gates candidates
for the Assembly! Old men laden with honors who had retired, in harness
again! Clearly no office lured them—it must be the magnitude of the issue.
And who were Clinton, Gates, and Osgood? Enemies of the Constitution!
To your tents, O Federalists![1730] A few days later the merchants met at the
Tontine Coffee-House to endorse the Hamiltonian ticket because ‘the
election is peculiarly important to the mercantile interests.’[1731] In the ‘Pig
Pen’ the Tammanyites read of the action of the merchants, clicked their
glasses, and rejoiced. Hamilton, now thoroughly alarmed, redoubled his
efforts. The Federalist press began to teem with hysterical attacks on
Jefferson, Madison, and Clinton—men who were planning the destruction
of the Government.[1732]
Meanwhile, Burr, calm, confident, suave, silent, was giving New York
City its first example of practical politics. Money was needed—he formed a
finance committee to collect funds. Solicitors went forth to wealthy
members of the party to demand certain amounts—determined upon by
Burr. It was a master psychologist who scanned the subscription lists. One
parsimonious rich man was down for one hundred dollars.
‘Strike his name off,’ said Burr. ‘You will not get the money and ... his
exertions will cease and you will not see him at the polls.’
Another name—that of a lazy man liberal with donations. ‘Double the
amount and tell him no labor will be expected of him.’
With infinite care Burr card-indexed every voter in the city, his political
history, his present disposition, his temperament, his habits, his state of
health, the exertions probably necessary to get him to the polls. The people
had to be aroused—Burr organized precinct and ward meetings, sent
speakers, addressed them himself. And while Burr was working, the
lowliest too were working on the lowliest. One evening ‘a large corpulent
person with something of the appearance of Sir John Falstaff’ was seen in
the lobby of a theater ‘haranguing an old black man who sells peanuts and
apples to come forward and vote the Republican ticket.’
‘You pay heavy taxes this year.’
‘Yes, Massa, me pay ten dollars.’
‘Well, if you vote the Republican ticket you will have little or no taxes to
pay next year; for if we Republicans succeed, the standing army will be
disbanded, which cost us almost a million of money last year.’
The peanut vendor promised to appear at the polls ‘with six more free-
born sons of the African race.’[1733] Whereupon the campaigner had a tale
to tell to the boys at the Wigwam that night.
The polls opened on April 29th and closed at sunset on May 2d. Days of
intense ceaseless activity. Hamilton and Burr took the field. From one
polling-place to another they rushed to harangue the voters. When they met,
they treated each other with courtly courtesy. Handbills were put out,
flooding the city during the voting. In the midst of the fight Matthew L.
Davis found time at midnight to send a hasty report to Gallatin in
Philadelphia. ‘This day he [Burr] has remained at the polls of the Seventh
ward ten hours without intermission. Pardon this hasty scrawl. I have not
ate for fifteen hours.’[1734] The result was a sweeping triumph for the
Democrats. When the news reached the Senate at Philadelphia, the
Federalists were so depressed and the Democrats so jubilant that the
transaction of business was impossible, and it adjourned.[1735]
Hamilton was stunned, and ready for trickery to retrieve the lost battle.
The next night he was presiding over a secret meeting of Federalists where
it was agreed to ask Governor Jay to call an extra session of the Legislature
to deprive that body of the power to choose electors. Hamilton approached
Jay in a letter. ‘In times like these,’ he wrote, ‘it will not do to be over-
scrupulous.’ There should be no objections to ‘taking of legal and
constitutional steps to prevent an atheist in religion and a fanatic in politics
from getting possession of the helm of state.’[1736] Jay read the letter with
astonishment, made a notation that it was a plan to serve a party purpose,
and buried it in the archives. It was the blackest blot on Hamilton’s record.
That victory elected Jefferson.
It destroyed Hamilton—and it made Burr Vice-President.
Scarcely had the polls closed when Burr’s friends, giving him the whole
credit, as he deserved, began to urge on the leaders in Philadelphia his
selection for the Vice-Presidency. Davis wrote Gallatin that the Democrats
of New York were bent on Burr.[1737] Admiral James Nicholas, the father-
in-law of Gallatin, wrote that the triumph was a miraculous ‘intervention of
Supreme Power and our friend Burr, the agent.’ It was his ‘generalship,
perseverance, industry, and execution’ that did it, and he deserved ‘anything
and everything of his country.’ He had won ‘at the risk of his life.’[1738] On
May 12th Gallatin wrote his wife: ‘We had last night a very large meeting
of Republicans, in which it was unanimously agreed to support Burr for
Vice-President.’
That was a bitter month for the Federalists. In the gubernatorial contests
in New Hampshire and Massachusetts the Democrats had polled an
astonishing vote. Painfully labored were the efforts of the Federalist press to
explain these remarkable accessions. The ‘Centinel’ in Boston had
previously sounded a note of warning under the caption, ‘Americans, Why
Sleep Ye?’ The Democrats, it said, were ‘organized, officered, accoutered,
provided, and regularly paid.’ They were ‘systematized in all points.’ In
Pennsylvania a Jeffersonian Governor had thrown Federalist office-holders
‘headlong from their posts.’ In New Hampshire the Democrats were
fighting ‘under cover of an ambuscade.’ In all States new Jeffersonian
presses were established, ‘from Portsmouth in New Hampshire to Savannah
in Georgia,’ through which ‘the orders of Generals of the faction are
transmitted with professional punctuality; which presses serve as a
sounding board to the notes that issue through that great speaking trumpet
of the Devil, the Philadelphia Aurora.’ Did not Duane get the enormous
salary of eight hundred dollars a year? ‘Why Sleep Ye?’
Dismayed, disgruntled with Adams, but afraid to reject him openly, the
Federalist caucus convened in Philadelphia and selected Charles
Cotesworth Pinckney as his running mate with the idea of electing him to
the Presidency through treachery to Adams.

When Adams learned of the Federalist defeat in New York, he

momentarily went to pieces. His suspicious mind instantly saw in his
humiliation the hand of Hamilton and his supporters. He had long been
cognizant of the treachery about him, in his official household. On the
morning of May 5th, McHenry received a note from the house on Market
Street: ‘The President requests Mr. McHenry’s company for one minute.’
As the poet-politician walked up Market Street in response that spring
morning, he could not have conceived of any other issue than a brief
discussion of some departmental matter. Only a few weeks before he had,
with Adams’s knowledge, arranged for a house at Georgetown, and for the
removal of his family thither.[1739] As he had surmised, the subject which
had summoned him to the conference was a minor matter relating to the
appointment of a purveyor. This was satisfactorily disposed of. Was there
something smug or offensive in the manner of Hamilton’s messenger that
suddenly enraged the old man, smarting under the sting of the defeat in
New York? Suddenly he began to talk of McHenry’s derelictions, his anger
rising, his color mounting, his voice ringing with unrepressed rage.
McHenry thought him ‘mad.’ Washington, said Adams, had saddled him
with three Secretaries, Pickering, Wolcott, and McHenry. The latter had
refused to give a commission to the only elector in North Carolina who had
voted for Adams. He had influenced Washington to insist on giving
Hamilton the preference over Knox—which was true. In a report to
Congress, McHenry had eulogized Washington and sought to praise
Hamilton—the President’s enemy. He had urged the suspension of the
mission to France. The old man was spluttering with fury, and his disloyal
Secretary was dumb with amazement. It was time for him to resign.
McHenry beat a hasty retreat, returned to his office, prepared his
resignation, which in decency should have been voluntarily submitted long
before, and sent it in the next morning.[1740]
Having set himself to the task of ridding his household of his enemies,
Adams bethought himself of Pickering. Five days after the stormy scene
with McHenry, the austere Secretary of State received a note from the
President inviting a resignation. This was on Saturday. On Monday
morning, Pickering went to his office as usual, having been long
accustomed to ignoring or thwarting the wishes of his chief, and sent a
letter dealing, strangely enough, with his pecuniary embarrassments, and
refusing to resign.[1741] The letter had not been sent an hour before an
answer was in his hands. It was curt and comprehensive. ‘Divers causes and
considerations essential to the administration of the government, in my
judgment requiring a change in the department of state, you are hereby
discharged from any further service as Secretary of State.’[1742]
Hamilton, enraged at the dismissal of his servitors, hastened an
astonishing letter of instructions to Pickering. He should ‘take copies and
extracts of all such documents as will enable you to explain both Jefferson
and Adams.’ No doubt Pickering was ‘aware of a very curious journal of
the latter when he was in Europe—a tissue of weakness and vanity.’ The
time was coming when ‘men of real integrity and energy must write against
all empirics.’[1743] To McHenry he wrote that ‘a new and more dangerous
era has commenced’; that ‘Revolution and a new order of things are
avowed in this quarter’; and, with something of Adams’s hysteria, that
‘property, liberty, and even life are at stake.’[1744]
The news that Adams had rid himself of his betrayers, and found in John
Marshall and Samuel Dexter as successors men incapable of treachery,
made a profound impression. To Duane of ‘The Aurora’ it was a
vindication. Two months before he had divided the Cabinet into
Hamiltonians and Adamsites, with Pickering and McHenry bearing the
brand of Hamilton.[1745] Announcing the dismissals under the caption, ‘The
Hydra Dying,’ he described Pickering as ‘an uncommon instance of the
mischiefs that may be done in a country by small and contemptible talents
and a narrow mind when set on fire by malignity.’[1746] The Federalist
papers were hard put to sugar-coat the pill. The ‘Centinel’ cautiously said
that ‘the best men here have variant opinions on the measure’ of Pickering’s
dismissal.[1747] Three days later, it rushed to the defense of the humiliated
representative of the Essex Junto with the comment that the best eulogy on
his official conduct was ‘the chuckling of the Jacobins over his removal’
and the assurance that he carried into retirement ‘the regrets of all good
men.’[1748] The Essex Junto made no attempt to conceal their disgust.
Cabot, Ames, Gore, and Pickering were soon sending their versions to
Rufus King in London. ‘You are so well acquainted with the sort of
sensibility for which our chief is remarkable, that you will be less surprised
than most men,’ wrote Cabot.[1749] Gore wrote that the dismissal ‘produces
general discontent.’[1750] The delicate moral sensibilities of all these
politicians were much hurt because Adams had fallen into the habit of
swearing and using ‘billingsgate.’[1751] He was even speaking with
bitterness of the Essex Junto and the British faction, quite in the manner of
Jefferson. It was even ‘understood’ among the Hamiltonians that the
dismissals were the price of the alliance which had been formed between
Jefferson and Adams.[1752]
But Adams knew what he was about. He knew that a plan had been
made to trick him out of his reëlection. The scheme was bald, bold, stupid.
All the Federalist electors in the North would be urged to vote for Adams
and Pinckney; in the South enough would be asked to vote for Pinckney,
and not Adams, to bring the Hamiltonian Carolinian in ahead. Hamilton
was writing frankly to his friends in this vein, ready to ‘pursue Pinckney as
my single object’;[1753] while Gore was writing King that ‘the intention of
the Federalists is to run General Pinckney and Mr. Adams as President and
Vice-President.’[1754] When, in July, Adams appeared in Boston at a dinner
and toasted Sam Adams and John Hancock, the much-abused Jeffersonians,
as ‘the proscribed patriots,’ the Hamiltonians groaned their disgust and the
Democrats shouted with glee. ‘This was well understood by the Jacobins
whom it will not gain,’ wrote Ames.[1755] ‘The Aurora’ observed that ‘he
did not give the great orb [Franklin] around which he moved as a
satellite.’[1756] The rupture was now complete. When Adams was permitted
to leave Philadelphia without a demonstration the latter part of May, ‘The
Aurora’ was unseemly in its mirth. ‘Did the Blues parade? No? What—not
parade to salute him “whom the people delight to honor”—“the rock on
which the storm beats”—the “chief who now commands”? Did not the
officers of the standing army or the marines parade? The new army officers
are not fond of the President; he has dismissed Timothy.’[1757]
Meanwhile, the most consummate of the betrayers, Wolcott, unsuspected
still, remained within the fort to signal to Hamilton.

VI

It was common knowledge early in the spring that Hamilton would exert
his ingenuity to defeat Adams by hook or crook. ‘The Aurora’ declared,
March 12th, that ‘the party with Alexander Hamilton at their head have
determined to defeat Adams in the approaching elections.’ The watchful
eye of the suspicious Adams, who felt the treachery, unquestionably read
the article and heard the gossip. When, after the death of Washington, the
Cincinnati met in New York to select Hamilton as the head of the order,
Adams was informed that his enemy had electioneered against him among
the members. He heard particularly of the action of ‘the learned and pious
Doctors Dwight and Babcock, who ... were attending as two reverend
knights of the order, with their blue ribbons and bright eagles at their sable
button-holes,’ in saying repeatedly in the room where the society met, ‘We
must sacrifice Adams,’ ‘We must sacrifice Adams.’
Thus, when in June, Hamilton, under the pretext of disbanding the army
in person, fared forth in his carriage on a tour of the New England States,
no one doubted the political character of his mission. His purpose was to
prevail upon the leaders to give unanimous support to Pinckney and to drop
a few Adams votes, or, that impossible, to give Pinckney the same support
as Adams. The records of this dramatic journey are meager enough. It is
known that in New Hampshire he talked with Governor Gilman, who was
the popular leader, and ‘took pains’ to impress upon him ‘the errors and the
defects of Mr. Adams and of the danger that candidate cannot prevail by
mere Federal strength.’ He urged support of Pinckney on the ground that in
the South he would get some anti-Federal votes.[1758] In Rhode Island he
evidently encountered a spirited protest from Governor Fenner. The
Governor expressed the hope that all the electors would be Federalists, but
clearly gave no encouragement to the Pinckney candidacy, according to
Hamilton’s own version of the conference.[1759] There were other versions,
however, indicative of a stormy interview. The ‘Albany Register’ advised
Hamilton, in giving the story of his tour to the ‘Anglo-Federal party which
wishes to make Charles C. Pinckney President,’ to ‘forget his interview
with the Governor of Rhode Island.’[1760] ‘The Aurora’ followed in a few
days with a more circumstantial story. Hamilton had ‘warmly pressed
Governor Fenner to support Pinckney’ and ‘the old Governor’s eyes were
opened and he literally drove the gallant Alexander out of the door.’[1761] 3
But in Massachusetts, albeit the home of Adams, Hamilton could count
upon a cordial reception for his views, since it was also the home of the
Essex Junto. This was composed of the Big-Wigs of the party in that State,
all ardently devoted to Hamilton, sharing in his hate of democracy and
doubt of the Republic. For years these men had met at one another’s homes
and directed the politics of Massachusetts. They were men of intellect and
social prestige, intimately allied with commerce and the law. There was
George Cabot, the greatest and wisest of them all, and one of the few men
who dared tell Hamilton his faults. He was a man of fine appearance, tall,
well-moulded, elegant in his manners, aristocratic in his bearing, earnest but
never vehement in conversation; a man of wealth, and a merchant.[1762]
There was Fisher Ames, brilliant, vivacious, smiling, cynical, eloquent,
exclusive in his social tastes, and wealthy. There was Theophilus Parsons,
learned in the law, contemptuous of public opinion and democracy,
reactionary beyond most of his conservative contemporaries, more
concerned with property than with human rights. Tall, slender, cold in his
manner, colder in his reasoning, he stood out among the other members of
the Junto because of his slovenliness in dress. Among his friends, at the
dinner table, he was a brilliant conversationalist, for he liked nothing better
than to eat and drink, talk and laugh, unless it was to smoke, chew tobacco,
and use snuff.[1763] He was the personification of the political intolerance
of his class. There, too, was Stephen Higginson, one of the wealthiest and
most cultured merchants of his day, a handsome figure of a man who took
infinite pains with his toilet and always carried a gold-headed cane. Given
to writing for the press, he made ferocious attacks on John Hancock under
the nom-de-plume of ‘Laco,’ and the truckmen on State Street whom he
passed on his way to business taught a parrot to cry, ‘Hurrah for Hancock;
damn Laco.’ So intolerant and bigoted was his household that a child,
hearing a visitor suggest that a Democrat might be honest, was shocked.
[1764] There also was John Lowell, able lawyer, cultured, ultra-conservative,
disdainful of democracy; and there was Christopher Gore, who amassed a
fortune in speculation, and held a brilliant position at the Bar. A striking
figure he was, when he appeared at the unconventional meetings of the
group, tall, stout, with black eyes and florid complexion, his hair tied
behind and dressed with powder, courtly in his manners, eloquent in speech,
utterly intolerant in his Federalism, and completely devoted to Hamilton’s
policies.[1765] These and their satellites were Hamilton’s Boston friends;
more, they were the backbone of his personal organization, his shock
troops. Thus, when he crossed into Massachusetts on his tour, he was going
to his own with the knowledge that they would receive him gladly—and
they did.
Reaching Boston on Saturday evening, he conferred with his friends, and
on Sunday ‘attended divine services at the Rev. Mr. Kirkland’s.’ On
Monday a dinner was given in his honor, where, the party paper insisted,
‘the company was the most respectable ever assembled in the town on a
similar occasion.’ General Lincoln presided. Higginson and Major Russell
of the ‘Centinel’ were vice-presidents. Governor Strong, the Lieutenant-
Governor, the Speaker of the House, Chief Justice Dana, Ames, Cabot,
several members of Congress, and members of ‘the Reverend Clergy’ sat
about the boards. ‘The tables were loaded with every dainty the season
affords and every luxury which could be procured.’[1766] It appears that
some Adamsites or Jeffersonians declined to do homage, for we find the
‘Centinel’ commenting that ‘had a certain citizen known that General
Hamilton resembled his demi-god, Bonaparte, instead of refusing a ticket to
the dinner he would have solicited the honor of kissing—his hand.’[1767]
The Hamiltonians were clearly delighted with the occasion; Hamilton
himself expanded and talked with freedom in the friendly atmosphere. He
talked for Pinckney and against Adams; and in an especially expansive
moment, dwelling on the sinister presumption of democracy, said that
within four years ‘he would either lose his head or be the leader of a
triumphant army.’ The dinner over, the conference concluded, he made an
inspection of Fort Independence on Castle Island, and was on his way,
accompanied ‘as far as Lynn by a cavalcade of citizens.’[1768] Everything
had been carried off with becoming éclat, for had he not stayed at ‘the
elegant boarding house of Mrs. Carter?’[1769] Unhappily the carriage in
which he rode with the ‘cavalcade’ broke down in the middle of the street,
[1770] to the delight of the Jacobins, but his composure gave his followers
much satisfaction.
Had not the Adamsites implied that he had received the cold shoulder
elsewhere in Massachusetts we might never have known his activities
beyond Lynn. He was ‘everywhere welcomed with unequivocable marks of
respect, cordiality, and friendship.’ He dined in Salem with Mr. Pickman,
‘drank tea at Ipswich,’ arrived at Davenport’s late in the evening, departed
early in the morning for Portsmouth, and reached Newburyport on Sunday.
That is the reason there was no demonstration there. But there in the
evening he stayed with Parsons ‘in company with some of the most
respectable gentlemen of the town.’[1771]
But Hamilton and the Junto were not soon to hear the last of that tour.
The Democrats harped incessantly on the promise to lose his head or be the
leader of a triumphant army. ‘We have often heard of a French gasconade,’
said ‘The Aurora,’ ‘but we have now to place alongside of it a Creole
gasconade in America. Alexander Hamilton leading an army to effect a
Revolution! Why, the very idea is as pregnant with laughter as if we were to
be told of Sir John Falstaff’s military achievements.’[1772] ‘Manlius’ rushed
to the attack, ostensibly in behalf of Adams, in the ‘Chronicle.’ Why this
trip to ‘disband the army’? Had Hamilton ever been in the camp before?
Had he appeared ‘to plant the seed of distrust in the bosom of the troops?
against Adams?’ And what a painful effect upon the great men of Boston!
‘Your personal appearance threw poor Cabot into the shade. Even what had
been deemed eloquence in the smiling Ames was soon reduced to
commentary; and so petrifying was your power that our District Judge has
scarcely since dared to report an assertion from his Magnus Apollo of
Brookline, either on politics or banking.’ And lose his head or lead a
triumphant army if Pinckney were not elected? ‘Your vanity was more gross
than even your ignorance of the characters of the people of the eastern
States.’[1773] Two months later, the echoes were still heard. The Reverend
Mr. Kirkland, flattered by Hamilton’s cultivation and ingratiation, and
young, not content with indiscreetly repeating Hamilton’s observations
made in company, rushed into the papers with an attack on Adams and a
glorification of Hamilton. What a disgrace to the clergy, wrote ‘No
Politician,’ for this flattered youth ‘to vindicate the character of a confessed
adulterer, and artfully to sap the well-earned reputation of President
Adams.’[1774] Even King heard from a Bostonian that Hamilton ‘in his
mode of handling [political themes] did not appear to be the great General
which his great talents designate him.’[1775] But Hamilton made his
observations and reached his conclusions—that the leaders of the first order
were in a mood to repudiate Adams, but that those of the second order,
more numerous, were almost solidly for him. He merely changed his
tactics.
 CHAPTER XX

HAMILTON’S RAMPAGE

F INDING that persuasion had failed to shake the fidelity of the second-
class leaders, Hamilton bethought himself of coercion. The moment he
returned to New York, he wrote Charles Carroll of Carrollton proposing
to ‘oppose their fears to their prejudices,’ by having the Middle States
declare that they would not support Adams at all. Thus they might be
‘driven to support Pinckney.’ Both New Jersey and Connecticut, he thought,
might agree to the plan, since in both places Adams’s popularity was on the
wane. In any event, it was not ‘advisable that Maryland should be too
deeply pledged to the support of Mr. Adams.’[1776] The effect on Carroll
was all that could have been desired. Two months later, an emissary of
McHenry’s, sent to interview the venerable patriot, found that he considered
Adams ‘totally unfit for the office of President, and would support ... the
election of General Pinckney.’[1777] Throughout the summer the leaders in
the inner circle of the Hamiltonian conspirators were busy with their pens.
Richard Stockton urged on Wolcott the wisdom of making a secret fight.
‘Prudent silence ... get in our tickets of electors ... they will be men who
will do right in the vote ... and Mr. Pinckney will be the man of their
choice.’[1778]
No one was deeper in the business than Wolcott, who, holding on to his
position, and presenting a suave, unblushing front to his chief, was writing
feverishly to the leaders of the conspiracy. While Hamilton was receiving
the homage of his New England idolaters in June, Wolcott was writing
Cabot that ‘if General Pinckney is not elected all good men will have cause
to regret the inactivity of the Federal party.’[1779] In July he was writing
McHenry that if ‘you will but do your part, we shall probably secure Mr.
Pinckney’s election,’[1780] and to Chauncey Goodrich that good men
thought Mr. ‘Adams ought not to be supported.’[1781] He was receiving
letters from Benjamin Goodhue, presumably Adams’s friend, concerning
‘Mr. Adams’ insufferable madness and vanity,’[1782] and from McHenry
that ‘Mr. Harper is now clearly of opinion that General Pinckney ought to
be preferred.’[1783] In August he was assuring Ames that ‘Adams ought not
to be supported,’[1784] and in September ‘The Aurora’ was charging that
during that month he had declared in Washington ‘that Mr. Adams did not
deserve a vote for President.’[1785] Clasping Adams’s hand with one of his,
this consummate master of intrigue was using the other to wig-wag
messages to Hamilton from the window of the fortress.
But Hamilton found much to disconcert him. Albeit Cabot rather boasted
that in July he had not yet paid a visit of courtesy to Braintree, and probably
would not,[1786] he was writing Hamilton that to discard Adams at that
juncture would mean defeat in Massachusetts.[1787] He was opposed,
however, only to an open rupture. Noah Webster, having made a New
England tour of his own, and lingered a moment under the trees at
Braintree, went over to Adams bag and baggage.[1788] All but two of the
Federalist papers were supporting Adams with spirit. To prod him more, the
Jeffersonian press was pouncing upon Hamilton ferociously. ‘Dictator of
the aristocratical party!’ ‘Father of the funding system!’ Working
desperately for Pinckney, ‘continually flying through the continent rousing
his partisans by the presence of their chief, prescribing and regulating every
plan,’ was Hamilton, charged a Jeffersonian editor. Author of ‘a little book’
in which he ‘endeavors to give an elegant and pleasant history of his
adulteries,’ he added.[1789] Hamilton began to meditate a sensational stroke.

II

Meanwhile, the Jeffersonians, united, enthusiastic, thoroughly organized,

confident, were waging war along the whole line. The mechanics who could
vote, the small farmers, the liberals and Democrats, the private soldiers of
the Revolution who felt they had been tricked, the small merchants, the
Germans because of taxes and the proscription of Muhlenberg, the Irish
because the Federalists abused them and passed the Alien Law, were almost
a unit behind their chief. All the cost of the army and navy, and the frequent
outrages of soldiers with nothing to do, brought support. In North Carolina,
Gales, in ‘The Register,’ was using the camp near Raleigh as a veritable
recruiting point for Democrats. The eight per cent loan of that day and the
Excise Law of the day before were bringing great accessions to the ranks.
The growing indebtedness of the Nation, and Wolcott’s admission that
another eight per cent loan would be necessary, was making converts. The
scandals in administration were creating havoc in Administration circles
and driving Wolcott to distraction. The scandal of Jonathan Dayton,
Federalist leader of New Jersey, broke, and the hailstones beat upon the
head of Wolcott, who was the victim of his credulity alone. While Speaker,
Dayton had made written application at the end of the session of 1798 for
thirty-three thousand dollars as compensation for the House. That amount
was not needed. Wolcott’s plea that he did not know he had given Dayton
more than necessary was greeted with jeers. His assertion that he had the
right to expect the unexpended balance to be immediately refunded only
met derisive laughter. Not until the winter of 1799 was the discovery made
that Dayton had retained more than eighteen thousand dollars since July,
1798. Wolcott, discovering this fraud, summoned Dayton, wrote him a
sharp letter, and recovered the money—but not the interest.[1790]
Meanwhile, Duane, in ‘The Aurora,’ was devoting pages to affidavits
concerning Dayton’s notorious land frauds.[1791] Defalcations were
numerous, due, according to the apologists of the Administration, to ‘the
difficulty of procuring men of standing and character ... to execute their
duties.’[1792]
Then, to darken the picture for the Federalists, stories were afloat
corroborative of the Jeffersonian charge that they favored aristocracy and
monarchy. Again Adams appeared as the champion of kingly government.
Senator John Langdon, a reputable man, personally vouched in a signed
letter to the truth of the charge that, in the presence of himself and John
Taylor of Caroline, Adams had said that ‘he expected to see the day when
Mr. Taylor and his friend, Mr. Giles, would be convinced that the people of
America would not be happy without an hereditary chief and Senate—or at
least for life.’[1793] This was greatly strengthened from Federalist sources.
‘The observations of the President when he went through town [New
Haven] last, made more Democrats than any other thing beside,’ wrote
Timothy Phelps to Wolcott. ‘He told Dr. Dana he did not believe the United
States could exist as a nation unless the Executive was hereditary.’[1794]
The lesser lights among the Federalists were likewise contributing to the
Jeffersonian cause. Noah Webster was being vigorously assailed in the
‘American Mercury’ for saying that reading and observation had convinced
him that republicanism was impossible unless the poorer classes were
excluded from the vote.[1795] But the climax came with the publication of
the stupid pamphlet of John Ward Fenno, who, with his father, had been
editor of the Federalist organ for years. In ‘Desultory Reflections on the
New Political Aspect of Public Affairs,’ he clearly reflected the views of
Hamilton, to whom he referred as having been pitched ‘down the Tarpeian
rock of oblivion, not for subsequent apostacy, but for the very deed of
greatness itself.’ It was a slashing assault on Adams for making peace with
France. Glorious prospects had been opening ‘the doors of the temple of
Janus,’ but Adams had acted in a ‘puerile’ fashion. The masses were
denounced as ‘the stupid populace, too abject in ignorance to think rightly,
and too depraved to draw honest deductions.’ The patriotic Federalists
were, by Adams’s action, ‘by one sudden stroke in one short hour, beaten
off their ground, overwhelmed with confusion, and left abandoned to all the
ridicule and all the rage of their antagonists ... and nauseating nonsense,
meanness, abject servility, and the effeminacy of Sybaris now reign with a
pomposity undisturbed even by any casual exertions of genius or common
sense.’ Pickering had been dismissed because he ‘approached too near to
holding a divided empire with [Adams] in the hearts of the people.’ The
time had come to ‘repudiate the author of our evils.’
More: the form of government should be changed. ‘The continent
[should be] divided into ten, fifteen, or twenty counties, to be governed by a
Lieutenant or Prefect appointed by the Executive; certain subaltern
appointments should be in his gift. These Prefects would constitute as
proper an upper House for one branch of the Legislature as could be
devised.’ The franchise should be ‘cut off from all paupers, vagabonds, and
outlaws’—the poor, the democrats—and ‘placed in those hands to which it
belongs, the proprietors of the country.’[1796] This from the man who had
edited the Hamilton Federalist organ in Philadelphia. Copies were carried
about in the pockets of the Jeffersonians and worn out by readings in the
taverns.
On top of this, Federalist leaders, writers, and papers began to hint at
secession in the event of Jefferson’s election. It had become a habit. There
had been talk of secession among them if the State debts were not assumed:
talk again if the Jay Treaty was not ratified. Wolcott’s father had written his
son, long before, of its desirability if Jefferson should be elected. Four years
previously the ‘Hartford Courant,’ the strongest Federalist paper in New
England, began to publish letters by ‘Pelham,’ paving the way for the
secession of the North. The South was bitterly assailed. There were more
interesting objects than the Union, thought ‘Pelham.’ The time had come to
secede. A year later, ‘Gustavus’ began writing in the same paper on the
same theme. Jefferson was denounced as an atheist and traitor.[1797] In
1800, ‘Burleigh’ took up his pen to advocate secession in the event of
Jefferson’s election. In this case the author was known—it was the fanatic
John Allen, who, as a member of Congress, had charged Livingston with
sedition because of his attack in the House on the Alien Law. In his initial
letter he urged all Federalist papers to copy, and some did. The election of
Jefferson would destroy the Constitution, result in anarchy, expel
Federalists from office, wreck the financial system, and lead to Revolution,
for ‘there is scarcely a possibility that we shall escape a civil war.’ This
would be bad, but ‘less, far less, than anarchy or slavery.’ Secession would
be almost certain. Where would the boundary be? At the Potomac?—the
Delaware?—the Hudson? New England might have trouble if New York
and Pennsylvania were included in the Northern Confederacy. ‘They are
large, wealthy, powerful. They have many men of intrigue and talent among
them, desperate in their fortunes, ambitious and unprincipled.’ It would be
hard to get them to join a peaceful body and keep them quiet.
These were the leading political articles in the leading Federalist paper in
the most uncompromising Federalist State through the campaign of 1800.
[1798] In the ‘American Mercury,’ ‘Rodolphus’ replied with a stinging
rebuke. ‘He tells us,’ wrote ‘Rodolphus,’ ‘that if Mr. Jefferson is elected our
towns will be pillaged, our inhabitants rendered miserable and our soil dyed
in blood; that we shall have a Jacobin government, that the Constitution ...
will fall a sacrifice, and finally if the man of his choice is not elected, the
Federal Union must be destroyed and that the Northern States must form a
separate Government. The writer is a Federalist indeed.’[1799]
The Jeffersonians made the most of ‘Burleigh’s’ secession articles.

III

Nowhere were the Jeffersonian activities more annoying to the

Federalists than in New England where Federalism thought itself
permanently entrenched. It had reached its peak in 1798 during the war
hysteria, and the next two years were marked by a notable decline. The
activities of the defiant Democrats were intensified. Denunciations of the
‘aristocracy’ that governed, of the political meddling of the clergy, brought
the fight personally home to the leaders. In Vermont, where Lyon had been
persecuted and his followers aroused, the stamp tax and the extravagance in
government made a deep impression on the small farmers. It was a scandal
in the best regulated households that ‘Matthew Lyon and his cubs’ were
prowling about the highways.[1800] In Massachusetts, where Gerry had
made a remarkable race for Governor in the spring, the fight was being
made in every quarter, and Ames was wailing that ‘on the whole the rabies
canina of Jacobinism has gradually passed of late years from the cities,
where it was confined to the docks and the mob, to the country.’[1801] In
New Hampshire, the Jeffersonians had made an astonishing showing in the
gubernatorial contest in the spring, carrying a number of the towns,
including Concord and Portsmouth. There, under the leadership of John
Langdon, they had capitalized the refusal of the Federalist Legislature to
grant a charter to a bank which proposed to loan money in small sums, and
place credit within the reach of the farmers and the poor.[1802] Their defeat,
notwithstanding their heavy vote, encouraged them to persevere in their
attacks on corporations and the ‘privileged few.’
But it was in Connecticut that the Jeffersonians gave the Federalists their
greatest shock by the audacity of their attacks. There the Democrats, though
few, made up in zeal and ability for what they lacked in numbers. In the
home of Pierrepont Edwards, a Federal Judge and a foremost citizen, they
perfected their plans for the campaign. Aaron Burr spent some time in the
State assisting in the creation of a militant organization. A Federalist
complained in a letter to Wolcott that ‘the Democrats spent all their time
and talents for eight weeks endeavoring to persuade the ignorant part of the
community that the Administration was endeavoring to establish a
monarchy; and even good Mr. Edwards told them he had held an important
office under government, but that he had found them so vile and corrupt, he
was determined to resign the office.’[1803] Nothing could have been more
distressing to the aristocratic and clerical oligarchy which had long lorded it
over the people. The ‘Courant’ piously prayed that Connecticut would not
‘exhibit the distressing spectacle of two parties rending the State with their
reproaches and whetting their swords for civic combat,’ and held up ‘the
awful condition in Pennsylvania and Virginia’ as a warning.[1804] The ‘New
York Commercial Advertiser,’ founded by a son of Connecticut, was
disheartened at the effrontery of the Democrats. ‘Jacobinism in
Connecticut,’ it said, ‘has heretofore been confined to back streets and dark
recesses; but in consequence of the successes in other States it begins to
creep forth and show its hideous front in good company.’[1805] In
September the ‘American Mercury’ of Hartford was boasting through
‘Gracchus’ that ‘in many towns where there was not a man who a few
months ago avowed the cause of republicanism, the friends of liberty and
the Constitution have now a majority,’ although ‘in most towns there was a
fight.’[1806]
To Abraham Bishop, the fighting leader of the Jeffersonians, was left the
congenial task of whipping the Federalists to a frenzy. A graduate of Yale,
of which Dwight, popularly known as ‘the Pope of Federalism,’ and a man
of scholarly attainments, was President, he was invited to deliver the Phi
Beta Kappa oration at the commencement. It was assumed that he would
speak on some literary or scientific subject, but nothing was more remote
from his intentions. Very carefully, and with malice aforethought, he
prepared a scathing arraignment of Federalist principles and policies. At the
last moment the clergy discovered the nature of the discourse and
recommended its rejection. One indignant partisan wrote Wolcott that ‘the
Society discovered the cheat before it was delivered and destroyed its effect
so far as was within their power.’[1807] The ‘Courant’ explained that when
the invitation was extended, the members of the fraternity were ‘ignorant of
his sentiments,’ and of the fact that ‘he had been once desired by a
committee of the society to resign the presidency because of profanity.’ The
moment it was found that the wicked man had written ‘a seditious and
inflammatory libel on the religion and government of the country,’ it was
decided to dispense with the oration.[1808] But the seditious and irreligious
Bishop had no notion of being robbed of an audience. The ‘Courant’
reported that ‘with an impudence and effrontery known only to weak or
wicked men,’ Bishop ‘proceeded at seven o’clock to palm off on the public
the production.’[1809] More than fifteen hundred men, women, and children,
including some members of the clergy, heard him,[1810] but the ‘Courant,’
looking over the assemblage, solemnly declared it as ‘a singular fact that
every open reviler of religion was there and highly gratified,’ but that the
young ladies of New Haven ‘refused to grace an audience thus collected
and consisting of such characters.’[1811]
No more slashing attack was heard during the campaign. The audience
was sympathetic, jubilant. The orator in fine fettle, the subject to his taste.
He attacked the extravagance in government, sneered at the ceremonious
launching of war vessels, ridiculed the military pretensions of Hamilton.
The army had not fought, but had ‘stood their ground bravely in their
cantonments.’ The funding system had ‘ruined thousands, but ... has also
led up to an aristocracy more numerous than the farmers-general in France,
more powerful than all others because it combined the men of wealth.’
But it was for the political preachers of Connecticut that Bishop reserved
his heaviest fire. ‘How much, think you, has religion been benefited by
sermons intended to show that Satan and Cain were Jacobins?’ Then a
contemptuous fling at ‘Pope’ Dwight—‘Would Paul of Tarsus have
preached to an anxious, listening audience on the propriety of sending
envoys?’ After all, ‘the Captain of Salvation is not so weak as to require an
army and navy and a majority in Congress to support His cause.’ Then,
falling into satire: ‘Let no one imagine that I would represent the clergy as
acting out of their sphere ... for is it not said unto them, “Go ye into all the
world and preach politics to every creature. When men oppose ye, call them
enemies of God and trample them under your feet.” ... When the people are
assembled, say to them that the Lord reigneth on the earth in the midst of
men of power and wealth; that he delighteth in the proud, even in those who
are lofty; that he will exalt the vain, and lay in the dust they who are humble
in his sight; that the great are gods; but that the little men are like the chaff
which he driveth before the wind; that in the day of his power he will shine
mightily on those who are in power, and that he will make the people under
them like the hay and the stubble and the sweepings of the threshing floor.’
Immediately the speech was published in pamphlet form and sent
broadcast over the country. Editions were printed in numerous towns and
States.[1812] Within a week an answer had been published in a pamphlet, ‘A
Rod for a Fool’s Back,’[1813] but it failed to affect the popularity of
Bishop’s ‘Oration on the Extent and Power of Political Delusions,’ and two
months later, when he was at Lancaster during a session of the Legislature,
he repeated the speech on invitation of Governor M’Kean.[1814] It was a
palpable hit.
 IV

And it was a hit, primarily because it was an assault on the part the
clergy was playing in the campaign. All over New England, and in New
York and Philadelphia, ministers were preaching politics with an
intemperance of denunciation and a recklessness of truth that seems
incredible to-day. The game of the politicians to picture Jefferson as an
atheist, a scoffer at religion who despised the Church and laughed at the
Bible, was entrusted to the Ministerial Corps, which did the best it could. It
was a line of slander that had followed Jefferson from the moment he
forced religious liberty and toleration into the laws of Virginia. The only
campaign canard of which Jefferson took cognizance was set afloat by the
Reverend Cotton Smith, who proclaimed that the man of Monticello had
accumulated his property by robbing a widow and fatherless children of
their estate while acting as their executor. ‘If Mr. Smith thinks that the
precepts of the Gospel are intended for those who preach them as well as
for others,’ wrote Jefferson, ‘he will some day feel the duties of repentance
and acknowledgment in such forms as to correct the wrong he has done. All
this is left to his own conscience.’[1815] But if Jefferson was content to
leave to their consciences clergymen bearing false witness, his followers
were not. When the Reverend Dr. Abercrombie of Philadelphia gravely
warned his congregation against voting for an atheist, Duane made a biting
reply. ‘He is the man who opposed reading the Declaration of Independence
on 4th of July last,’ he wrote. ‘Need we wonder at his hatred of Mr.
Jefferson?’[1816] When the clergyman, stung by the attack, made a weak
reply, Duane asked: ‘During the prevalence of yellow fever ... in 1798 on a
day in the house of Mr. Richard Potter in Germantown did you not provoke
an argument in which you supported monarchical doctrines and assert that
the country would never be happy until it had a king?’[1817] To another
minister, fortunately ‘the late Rev. Dr. J. B. Smith of Virginia,’ was ascribed
one of the most amazing stories of the campaign, that Jefferson on passing a
dilapidated church had sneeringly said that ‘it was good enough for Him
Who was born in a manger.’[1818]
When the Reverend John M. Mason published a political pamphlet under
the cover of religion,[1819] accusing Jefferson of being a Deist, and the
Reverend Dr. Lynn of New York, actively electioneering for Pinckney
against both Adams and Jefferson at the instance of Hamilton, printed