Cornea 2011 Syllabus

Subspecialty Day
2011
Orlando
October 21 – 22
CORNEA
Cornea 2011:
Controversies and Consensus
Cornea 2011
Controversies and
Consensus
Program Directors
Christopher J Rapuano MD, Natalie A Afshari MD, Anthony J Aldave MD
In conjunction with the Cornea Society
Orange County Convention Center

Orlando, Florida
Saturday, October 22, 2011
Presented by:
The American Academy of Ophthalmology
2011 Cornea Planning Group 2008 Michael W Belin MD Staff

Christopher J Rapuano MD David B Glasser MD Melanie R Rafaty CMP, Director,
Program Director Mark J Mannis MD Scientific Meetings
2007 Michael W Belin MD Ann L’Estrange, Scientific Meetings
Natalie A Afshari MD David B Glasser MD Coordinator
Program Director R Doyle Stulting MD PhD Debra Rosencrance CMP CAE, Vice
Anthony J Aldave MD President, Meetings & Exhibits
Program Director Subspecialty Day Advisory Committee Patricia Heinicke Jr, Editor
William F Mieler MD Mark Ong, Designer
Michael W Belin MD Associate Secretary Gina Comaduran, Cover Design
David B Glasser MD
Donald Tan MD MBBS Donald L Budenz MD MPH
Daniel S Durrie MD
Former Program Directors Robert S Feder MD
2010 Michael W Belin MD Leah Levi MBBS
David B Glasser MD R Michael Siatkowski MD
Christopher J Rapuano MD Jonathan B Rubenstein MD
Secretary for Annual Meeting
©2011 American Academy of Ophthalmology. All rights reserved. No portion may be reproduced without express written consent of the American Academy of Ophthalmology.
ii 2011 Subspecialty Day | Cornea
Dear Colleague:
On behalf of the American Academy of Ophthalmology and the Cornea Society, it is our great plea-
sure to welcome you to Orlando and to Cornea 2011: Controversies and Consensus.
As co-chairs of the Cornea Subspecialty Day Program Planning Group, we are honored to plan this
year’s meeting. We have assembled an outstanding faculty of nationally and internationally recog-
nized experts and anticipate that this will be an extraordinary educational event. Our faculty have
spent innumerable hours preparing their presentations and course materials to provide the most
up-to-date and comprehensive review of their topics. We thank them for all of their efforts and for
sharing their expertise.
The day is divided into six sections. The morning will start off with a discussion of ocular surface
diseases, focusing on replacement versus regeneration. We begin with the most popular keratopros-
thesis, the Boston KPro, and proceed to a much less commonly used keratoprosthesis, but one with
a very long track record, the osteo-odonto-keratoprosthesis. Biosynthetic, oral mucosal epithelial,
limbal epithelial and dental pulp cell tranplantation will also be discussed. Session 2 will cover infec-
tious keratitis, including the pros and cons of adjunctive therapy with topical steroids, the use of
collagen crosslinking in infectious keratitis, and an examination of the evidence-based use of periop-
erative antibiotics. The morning ends with a session on lamellar corneal transplantation, including
tips on transitioning to Descemet-stripping endothelial keratoplasty (DSEK), Descemet membrane
endothelial keratoplasty, and deep anterior lamellar keratoplasty, and for the more experienced
lamellar corneal surgeon, how to achieve success in “extreme DSEK.”
After lunch, we continue with keratoplasty, focusing on how to choose between penetrating kerato-
plasty, endothelial keratoplasty, and KPros in the adult population, and then proceed with a discus-
sion on optimizing outcomes in pediatric PK and the utility of KPros as an alternative to PK in the
pediatric population. The next session is on therapeutics: the controversial role of VEGF-inhibitors
in managing corneal neovascularization, uses and abuses of amniotic membrane transplantation,
the role for scleral contact lenses in the management of ocular surface disease, and what’s new in the
management of dry eye syndrome. The final session of the day is a potpourri of topics, including the
best uses of corneal topography and other anterior segment imaging techniques, the pros and cons
of using autologous serum, and future therapies for corneal endothelial disease. After each session
there will be a panel discussion to address outstanding issues.
In an effort to provide the most innovative and interesting Subspecialty Day Meetings, we request that
you assist us by completing the evaluation form. We carefully review all comments to better under-
stand your needs, so please candidly indicate the strengths and shortcomings of today’s program.
Again, we welcome you to Cornea 2011: Controversies and Consensus. We hope you find it educa-
tional and enjoyable.
Sincerely,

Christopher J Rapuano MD Natalie A Afshari MD Anthony J Aldave MD
Program Director Program Director Program Director
2011 Subspecialty Day | Cornea iii
Cornea 2011 Contents
Program Directors’ Welcome Letter ii
CME iv
Faculty Listing v
Program Schedule x
Section I: Ocular Surface Disease—Replacement vs. Regeneration 1
Section II: Infectious Keratitis 26
Section III: Corneal Transplantation—Lamellar Keratoplasty 35
Section IV: Corneal Transplantation—Penetrating Keratoplasty and Pediatric Keratoplasty 49
Section V: Ocular Surface Disease—Therapeutics 58
Surgery by Surgeons Update 64
Section VI: Cornea Potpourri 65
Faculty Financial Disclosure 81
Presenter Index 85
iv 2011 Subspecialty Day | Cornea
CME Credit
Academy’s CME Mission Statement has mechanisms in place to resolve all conflicts of interest prior
to an educational activity being delivered to the learners.
The purpose of the American Academy of Ophthalmology’s
Continuing Medical Education (CME) program is to pres-
Attendance Verification for CME Reporting
ent ophthalmologists with the highest quality lifelong learning
opportunities that promote improvement and change in physi- Before processing your requests for CME credit, the Academy
cian practices, performance or competence, thus enabling such must verify your attendance at Subspecialty Day and/or the
physicians to maintain or improve the competence and profes- Annual Meeting. In order to be verified for CME or auditing
sional performance needed to provide the best possible eye care purposes, you must either:
for their patients.
• Register in advance, receive materials in the mail and turn
in the Final Program and/or Subspecialty Day Syllabus
2011 Cornea Subspecialty Day Meeting Learning
exchange voucher(s) onsite;
Objectives
• Register in advance and pick up your badge onsite if mate-
Upon completion of this activity, participants should be able to: rials did not arrive before you traveled to the meeting;
• Register onsite; or
• Compare the patient selection criteria, surgical technique
• Use your ExpoCard at the meeting.
and outcomes of two types of keratoprostheses for manag-
ing advanced ocular surface disease
CME Credit Reporting
• Recognize developments in new and innovative methods
of ocular surface cell transplantation Level 2, Lobby B; Academy Resource Center, Hall A4,
• Identify the relative merits and complications associated Booth 1359
with the different techniques for corneal replacement (e.g.,
Attendees whose attendance has been verified (see above) at the
penetrating keratoplasty, Descemet-stripping endothelial
2011 Annual Meeting can claim their CME credit online during
keratoplasty, Descemet membrane endothelial kerato-
the meeting. Registrants will receive an e-mail during the meeting
plasty, deep anterior lamellar keratoplasty)
with the link and instructions on how to claim credit.
• Identify issues important to appropriate patient selection
Onsite, you may report credits earned during Subspecialty Day
for pediatric corneal transplantation
and/or the Annual Meeting at the CME Credit Reporting booth.
• Identify and initiate appropriate management of bacterial
Academy Members: The CME credit reporting receipt is not
and fungal corneal ulcers
a CME transcript. CME transcripts that include 2011 Annual
Meeting credits entered onsite will be available to Academy
2011 Cornea Subspecialty Day Meeting Target
members on the Academy’s website beginning Nov. 16, 2011.
Audience
NOTE: CME credits must be reported by Jan. 18, 2012. After
The intended audience for this program is cornea surgeons, com- the 2011 Annual Meeting, credits can be claimed at www.aao.org.
prehensive ophthalmologists with an interest in anterior segment The Academy transcript cannot list individual course atten-
and allied health personnel who are performing or assisting with dance. It will list only the overall credits spent in educational
cornea surgery. activities at Subspecialty Day and/or the Annual Meeting.
Nonmembers: The Academy will provide nonmembers with
2011 Cornea Subspecialty Day CME Credit verification of credits earned and reported for a single Academy-
sponsored CME activity, but it does not provide CME credit tran-
The American Academy of Ophthalmology is accredited by the
scripts. To obtain a printed record of your credits, you must report
Accreditation Council for Continuing Medical Education to pro-
your CME credits onsite at the CME Credit Reporting booths.
vide continuing medical education for physicians.
The American Academy of Ophthalmology designates this live
Proof of Attendance
activity for a maximum of 7 AMA PRA Category 1 Credits™.
Physicians should claim only the credit commensurate with the The following types of attendance verification will be available
extent of their participation in the activity. during the Annual Meeting and Subspecialty Day for those who
need it for reimbursement or hospital privileges, or for nonmem-
Scientific Integrity and Disclosure of Relevant bers who need it to report CME credit:
Financial Interest
• CME credit reporting/proof-of-attendance letters
The American Academy of Ophthalmology is committed to • Onsite Registration Form
ensuring that all continuing medical education (CME) informa- • Instruction Course Verification Form
tion is based on the application of research findings and the
Visit the Academy’s website for detailed CME reporting
implementation of evidence-based medicine. It seeks to promote
information.
balance, objectivity and absence of commercial bias in its con-
tent. All persons in a position to control the content of this activ-
ity must disclose any relevant financial interest. The Academy
2011 Subspecialty Day | Cornea v
Faculty
No photo
available
Natalie A Afshari MD Penny A Asbell MD FACS Stuart I Brown MD

Durham, NC New York, NY La Jolla, CA
Associate Professor of Ophthalmology Professor of Ophthalmology
and Director of Cornea and Mount Sinai School of Medicine
Refractive Surgery Fellowship
Duke University Eye Center
No photo
available
Alan N Carlson MD
Durham, NC
Dimitri T Azar MD Professor of Ophthalmology
Chicago, IL Duke Eye Center
Anthony J Aldave MD Interim Dean
Los Angeles, CA College of Medicine
Associate Professor of Ophthalmology Professor, Field Chair, and Head
The Jules Stein Eye Institute Department of Ophthalmology and
Visual Sciences
University of Illinois at Chicago
James Chodosh MD MPH

Boston, MA
Professor of Ophthalmology
Massachusetts Eye and Ear Infirmary
James V Aquavella MD Harvard Medical School
Rochester, NY
Professor of Ophthalmology Keith Hugh Baratz MD
Flaum Eye Institute Rochester, MN
University of Rochester Professor of Ophthalmology
Mayo Clinic
vi Faculty Listing 2011 Subspecialty Day | Cornea
Roy S Chuck MD PhD Per Fagerholm MD Jose Gomes MD

Bronx, NY Stockholm, Sweden Sao Paulo, SP, Brazil
Professor and Chairman of Professor of Ophthalmology Professor of Ophthalmology
Ophthalmology University of Linköping Federal University of Sao Paulo
Albert Einstein College of Medicine Director of the Cornea and External
Professor and Chairman of Disease Service
Ophthalmology Federal University of Sao Paulo
Montefiore Medical Center
Marjan Farid MD
Huntington Beach, CA
Assistant Professor of Ophthalmology
University of California, Irvine Kristin M Hammersmith MD
Reza Dana MD MSc MPH Director of Cornea, Cataract, and Philadelphia, PA
Boston, MA Refractive Surgery
Professor and Director of Cornea & Gavin Herbert Eye Institute
Refractive Surgery
Massachusetts Eye and Ear Infirmary
Department of Ophthalmology
Harvard Medical School
Senior Scientist and W Clement Stone
Scholar
Schepens Eye Research Institute
Andrew J W Huang MD MPH

St Louis, MO
Kenneth M Goins MD Professor of Ophthalmology
Iowa City, IA Washington University School of
Professor, Clinical Ophthalmology Medicine in St Louis
University of Iowa
Randy J Epstein MD
Highland Park, IL
Rush University Medical Center
2011 Subspecialty Day | Cornea Faculty Listing vii
Bennie H Jeng MD Anna S Kitzmann MD Christopher Liu FRCOphth

San Francisco, CA Iowa City, IA Brighton, England
Associate Professor of Ophthalmology Assistant Professor of Ophthalmology Ophthalmology
University of California, San Francisco University of Iowa Sussex Eye Hospital, Brighton
Ophthalmology
Tongdean Eye Clinic (Hove, England)
A John Kanellopoulos MD Friedrich E Kruse MD

Athens, Greece Erlangen, Germany
Professor of Ophthalmology Professor of Ophthalmology Francis S Mah MD
New York University Medical College University of Erlangen Sewickley, PA
Associate Professor of Ophthalmology
and Pathology
University of Pittsburgh School of
Medicine
Medical Director
No photo Charles T Campbell Ocular
available Microbiology Laboratory
Shigeru Kinoshita MD Thomas M Lietman MD

Kyoto, Japan San Francisco, CA
Kyoto Prefectural University of Medicine
Todd P Margolis MD PhD

San Francisco, CA
Professor of Ophthalmology and
Director, F I Proctor Foundation
University of California, San Francisco
viii Faculty Listing 2011 Subspecialty Day | Cornea
Stephanie Jones Marioneaux MD Rudy Nuijts MD Christopher J Rapuano MD

Chesapeake, VA Maastricht, Limburg, Netherlands Philadelphia, PA
American Academy of Ophthalmology Associate Professor of Ophthalmology Chief, Cornea Service
Assistant Professor of Ophthalmology Department of Ophthalmology Wills Eye Institute
Eastern Medical of Virginia Academic Hospital Maastricht Professor of Ophthalmology
Jefferson Medical College
Thomas Jefferson University
No photo
available
Majid Moshirfar MD N Venkatesh Prajna MD

Salt Lake City, UT Tamilnadu, India
Professor of Ophthalmology George O D Rosenwasser MD
Aravind Eye Hospital Hershey, PA
Director, Central Pennsylvania Eye
Institute
Medical Director, Gift of Life Donor
Program Eye Bank
Kohji Nishida MD
Osaka, Japan
Professor and Chairman of Francis W Price Jr MD
Ophthalmology Indianapolis, IN
Osaka University Graduate School of Medical Director
Medicine Price Vision Group
President of the Board Virender S Sangwan MBBS
Cornea Research Foundation of America Hyderabad, Andhra Pradesh, India
Ophthalmologist
L V Prasad Eye Institute
2011 Subspecialty Day | Cornea Faculty Listing ix
Geoffrey C Tabin MD Mark A Terry MD

Salt Lake City, UT Portland, OR
Professor of Ophthalmology and Visual Director, Corneal Services
Science and Director, International Devers Eye Institute
Division Professor, Clinical Ophthalmology
The John A Moran Center Oregon Health Sciences University
University of Utah
Codirector, Himalayan Cataract Project
x 2011 Subspecialty Day | Cornea
Cornea 2011: Controversies and Consensus

In Conjunction With The Cornea Society
Saturday, October 22, 2011

6:30 AM REGISTRATION/ MATERIAL PICKUP/ CONTINENTAL BREAKFAST
8:00 AM Welcome and Introductions Christopher J Rapuano MD*
Anthony J Aldave MD*
Natalie A Afshari MD*
Section I: Ocular Surface Disease—Replacement vs. Regeneration

Moderator: Anthony J Aldave MD*
Panelists: James Chodosh MD MPH*, Per Fagerholm MD, Jose Gomes MD*, Christopher Liu FRCOphth,
Kohji Nishida MD, Virender S Sangwan MBBS
8:05 AM The Boston Keratoprosthesis in the Management of Limbal Stem Cell
Failure James Chodosh MD MPH* 1
8:15 AM The Osteo-Odonto-Keratoprosthesis for Management of Severe Ocular
Surface Disease Christopher Liu FRCOphth 3
8:25 AM A Biosynthetic Alternative to Human Donor Tissue Per Fagerholm MD 18
8:35 AM Oral Mucosal Epithelial Transplantation for the Management of Ocular
Surface Disease Kohji Nishida MD 20
8:45 AM Cultivated Limbal Epithelial Transplantation for the Management of
Ocular Surface Disease Virender S Sangwan MBBS 21
8:55 AM Ocular Surface Reconstruction With Immature Dental Pulp Stem Cell
Transplantation Jose Gomes MD* 24
9:05 AM Panel
Section II: Infectious Keratitis

Moderator: Natalie A Afshari MD*
Panelists: A John Kanellopoulos MD*, Thomas M Lietman MD, Francis S Mah MD*,
Todd P Margolis MD PhD, N Venkatesh Prajna MD*
9:20 AM Bacterial Keratitis: Synergy, Steroids, and Other Treatment Controversies Thomas M Lietman MD 26
9:30 AM An Evidence-Based Approach to Managing Fungal Keratitis N Venkatesh Prajna MD* 28
9:40 AM Corneal Collagen Crosslinking: Does It Have a Role in Managing
Infectious Keratitis? A John Kanellopoulos MD* 30
9:50 AM Now That We Have Topical Ganciclovir, What Is the Role of
Oral Antivirals? Todd P Margolis MD PhD 33
10:00 AM Perioperative Antibiotics: Looking for a Consensus Amid the Chaos Francis S Mah MD* 34
10:10 AM Panel
10:25 AM REFRESHMENT BREAK and ANNUAL MEETING EXHIBITS
* Indicates that the presenter has financial interest.

No asterisk indicates that the presenter has no financial interest.
2011 Subspecialty Day | Cornea Program Schedule xi
Section III: Corneal Transplantation—Lamellar Keratoplasty

Moderator: Christopher J Rapuano MD*
Panelists: Marjan Farid MD, Friedrich E Kruse MD*, Rudy Nuijts MD*, Francis W Price Jr MD*,
George O D Rosenwasser MD*, Geoffrey C Tabin MD, Mark A Terry MD*
10:55 AM A Decade of Endothelial Keratoplasty: What Has the Literature Taught Us? Mark A Terry MD* 35
11:05 AM Ten Tips to Avoid Trouble When Transitioning to Descemet-Stripping
Endothelial Keratoplasty Friedrich E Kruse MD* 38
11:15 AM Extreme Descemet-Stripping Endothelial Keratoplasty: When You Think
DSEK Is the Best Option for the Cornea, but Not for Your Coronaries George O D Rosenwasser MD* 41
11:25 AM Descemet Membrane Endothelial Keratoplasty: Is It Time for You to
Convert From Descemet- Stripping Endothelial Keratoplasty? Francis W Price Jr MD* 42
11:35 AM Deep Anterior Lamellar Keratoplasty: Is It Time for You to Convert
From PK? Rudy Nuijts MD* 44
11:45 AM Deep Anterior Lamellar Keratoplasty: Tips for the Transitioning Surgeon Geoffrey C Tabin MD 46
11:55 AM Deep Anterior Lamellar Keratoplasty: Why You Should Be Performing It
With a Femtosecond Laser Marjan Farid MD 47
12:05 PM Panel
12:20 PM LUNCH and ANNUAL MEETING EXHIBITS
Section IV: Corneal Transplantation—Penetrating Keratoplasty and Pediatric Keratoplasty

Moderator: Anthony J Aldave MD*
Panelists: James V Aquavella MD*, Stuart I Brown MD, Alan N Carlson MD*, Kenneth M Goins MD,
Kristin M Hammersmith MD
1:30 PM PK: When I Choose PK Instead of Descemet-Stripping Endothelial
Keratoplasty Kenneth M Goins MD 49
1:40 PM Failed PK: How I Choose Between Repeat PK and Descemet-Stripping
Endothelial Keratoplasty Alan N Carlson MD* 51
1:50 PM Failed PK: How I Choose Between Repeat PK and a Keratoprosthesis Kristin M Hammersmith MD 53
2:00 PM Transplantation of Congenitally Opaque Corneas: Pearls and Pitfalls Stuart I Brown MD 55
2:10 PM Pediatric Keratoprosthesis: Are We There Yet? James V Aquavella MD* 56
2:20 PM Panel
Section V: Ocular Surface Disease—Therapeutics

Moderator: Natalie A Afshari MD*
Panelists: Penny A Asbell MD FACS*, Roy S Chuck MD PhD*, Reza Dana MD MSc MPH*,
Andrew J W Huang MD MPH*
2:35 PM What to Do for Corneal Neovascularization Reza Dana MD MSc MPH* 58
2:45 PM Amniotic Membrane Grafts: Uses and Controversial Uses Roy S Chuck MD PhD* 60
2:55 PM Scleral Contact Lens: Resolving Ocular Surface Issues? Andrew J W Huang MD MPH* 61
3:05 PM Dry Eye: A Burning Issue Revisited Penny A Asbell MD FACS* 63
3:15 PM Panel
3:30 PM REFRESHMENT BREAK and ANNUAL MEETING EXHIBITS

xii Program Schedule 2011 Subspecialty Day | Cornea
Section VI: Cornea Potpourri

Moderator: Christopher J Rapuano MD*
Panelists: Dimitri T Azar MD*, Keith Hugh Baratz MD*, Randy J Epstein MD*, Bennie H Jeng MD*,
Shigeru Kinoshita MD*, Anna S Kitzmann MD, Majid Moshirfar MD
4:00 PM Surgery by Surgeons Stephanie Jones Marioneaux
MD64
4:05 PM Straighten Up and Listen: Ergonomics for Your Aching Back Anna S Kitzmann MD 65
4:15 PM Corneal Imaging: Confocal, OCT, and Ultrasound Biomicroscopy—
What Are They Good For? Majid Moshirfar MD 66
4:25 PM Corneal Topography and Tomography Interpretation for the Cataract
Surgeon—Implications for Premium and Toric IOLs Randy J Epstein MD* 69
4:35 PM Autologous Serum: Is It Worth the Hassle? Bennie H Jeng MD* 71
4:45 PM What Is New in the Genetics of Fuchs Dystrophy? Keith Hugh Baratz MD* 74
4:55 PM Future Therapies for Corneal Endothelial Disease Shigeru Kinoshita MD* 77
5:05 PM How the Cornea Remains Clear in Health and Disease Dimitri T Azar MD* 79
5:15 PM Panel
5:30 PM Closing Remarks Christopher J Rapuano MD*
Anthony J Aldave MD*
Natalie A Afshari MD*

2011 Subspecialty Day | Cornea Section I: Ocular Surface Disease — Replacement vs. Regeneration 1
The Boston Keratoprosthesis in the Management of

Limbal Stem Cell Failure
James Chodosh MD MPH
I. History of the Boston Keratoprosthesis corneal allograft rejection (Boston Keratopros-

thesis Type I)
A. The predicted survival of a corneal allograft (reten-
tion of corneal clarity) performed for routine 2. Deep and extensive corneal neovascularization
indications is approximately 50% at 15 years after (Type I)
surgery, but essentially zero at 5 years after a third
3. Aniridia (Type I)
keratoplasty. The Boston Keratoprosthesis has
become a widely utilized option for patients with 4. Stevens Johnson syndrome / toxic epidermal
corneal allograft failure, and it is the now most necrolysis (Type I or II, depending on severity of
utilized keratoprosthesis in the United States, the ocular surface disease)
Americas, and Western Europe, with over 1200
5. Mucous membrane pemphigoid (Type I or II,
devices placed annually worldwide. The Boston
depending on severity of ocular surface disease)
Keratoprosthesis is one of many similar through-
and-through collar-button designs; the current Bos- 6. Post-chemical burn (Type I or II, depending on
ton design is the product of many years of dedicated severity of ocular surface disease)
work by Claes H Dohlman MD PhD.
7. Other autoimmune conditions (Type I or II,
B. FDA approved for marketing in 1992 depending on severity of ocular surface disease)
C. Continual improvement and innovation since incep- 8. Severe tear film deficiency (Type II)
tion
B. Pediatric patients with poor prognosis for conven-
1. Contact lens to improve hydration of corneal tis- tional allograft (Type I): Still controversial, but
sue adjacent to keratoprosthesis stem; prevents avoids astigmatism of allograft and allows immedi-
dellen formation at edge of frontplate ate amblyopia therapy
2. Holes in backplate allow aqueous contact with 1. Bilateral Peters anomaly
posterior cornea and appear to reduce tissue
2. Other congenital or acquired corneal disorders
necrosis
of infancy
3. Postoperative topical vancomycin (14 mg/ml
IV. Limbal Stem Cell Failure and the Boston Keratopros-
with BAK): In a retrospective study, topical
thesis
vancomycin reduced rate of postoperative endo-
phthalmitis due to Gram-positive bacteria to A. Status of the ocular surface determines choice of
nearly zero. Boston keratoprosthesis type.
II. Design Types of Boston Keratoprosthesis Patients with severe tear deficiency, keratinization,
symblepharon, eyelid abnormalities that would pre-
A. Type I
clude stable tear film but cannot be corrected with
1. Implanted in corneal donor graft tissue or in surgery, and/or severe limbal stem cell deficiency
patient’s own cornea (autograft) and prone to spontaneous corneal necrosis (melt)
should be considered for a Boston Keratoprosthesis
2. Used for patients with normal or near normal
Type II.
tear film and eyelid anatomy and function
B. Decision making: Boston Keratoprosthesis Type I or
B. Type II
II. Examples to be presented.
1. Similar to Type I, but with extra stem/optic ante-
V. General Complications of the Boston Keratoprosthesis
rior to corneal plane to extend between/through
surgically closed eyelids A. Stromal necrosis and extrusion
2. Used in patients with end-stage cicatricial ocular B. Infectious keratitis
surface disease, severe aqueous tear deficiency,
C. Infectious endophthalmitis
and/or ocular surface keratinization
D. Sterile vitritis
III. General Indications for Implantation of a Boston Kera-
toprosthesis E. Retroprosthetic membrane
A. Any patient with corneal blindness not amenable to F. Retinal detachment
corneal allograft surgery
G. Glaucoma
1. Failed corneal graft when a subsequent corneal
allograft is also expected to fail, as in repeated
2 Section I: Ocular Surface Disease — Replacement vs. Regeneration 2011 Subspecialty Day | Cornea
VI. Complications of the Boston Keratoprosthesis Specific F. Glaucoma, particularly in alkali burns, is the great-
to Limbal Stem Cell Failure est obstacle to long-term success in keratoprosthesis
patients.
A. Limbal stem cell failure is in no way a contraindica-
tion to implantation of the Boston Keratoprosthesis 1. Glaucoma is particularly difficult to treat in
and may be an indication for keratoprosthesis when patients with Boston Keratoprosthesis Type II.
corneal clarity is compromised and the likelihood of
a. Topical medications do not penetrate closed
successful corneal allograft is low.
lids, even around keratoprosthesis stem.
B. After Boston Keratoprosthesis Type I, when tear
b. Oral agents may be contraindicated or not
film is of poor quality and/or quantity, contact lens
sufficiently effective.
may develop deposits that interfere with vision.
Consider hybrid lens alternatives. c. Glaucoma drainage valves have high failure
rate without conjunctival mucosa as covering.
C. Difficulty with contact lens retention after Boston
Keratoprosthesis Type I due to existent or progres- 2. Any IOP elevation should be treated aggressively
sive foreshortening of fornices and symblepharon in any patient with a Boston Keratoprosthesis,
even before any evidence of optic neuropathy
D. Severe trichiasis
develops.
E. Stromal necrosis can occur even in patients with
3. IOP should be targeted lower in patients after
Boston Keratoprosthesis Type II despite complete
alkali burn than in other patient groups.
eyelid coverage, particularly around keratoprosthe-
sis stem.
The Osteo-Odonto-Keratoprosthesis for Management

of Severe Ocular Surface Disease
Christopher Liu FRCOphth
Osteo-odonto-keratoprosthesis (OOKP) surgery is a technique to whether the eye is phakic, pseudophakic, or aphakic. A- and
used to replace damaged cornea in blind patients for whom B-scans are used for biometry to determine the axial length,
cadaveric corneal transplantation is doomed to failure. Devel- exclude prephthisis, confirm the lens status and exclude retinal
oped some 40 years ago by Strampelli, it uses the patient’s own detachment, and detect gross glaucomatous cupping.
tooth root and alveolar bone to support an optical cylinder. Assessment of a patient for OOKP also involves an assess-
After a long interval, the technique is finally gaining widespread ment of the general medical and psychological status of the
recognition by corneal surgeons worldwide as the treatment of patient. The patient must be fully informed of the procedures
choice for patients with end-stage corneal disease. In the case of a and risks. The “side effects” and possible complications are
dry eye, no other device will work nearly as well. described below.
Oral assessment
Referral Guidelines for OOKP Surgery
The oral assessment must take into account both the buccal
Indications mucosal graft donor site and a selection of an appropriate tooth
to form a dentine/bone lamina.
Patients with bilateral corneal blindness resulting from severe
Stevens-Johnson syndrome, ocular cicatricial pemphigoid, chemi- Buccal mucosal assessment
cal burns, trachoma, dry eyes, or multiple corneal graft failure
Since a number of patients will need an OOKP due to mucocuta-
may be considered for OOKP surgery. The better, or only, eye
neous diseases, the oral mucosa may be damaged. The extent of
should have poor vision such as PL, HM, or at best CF. One eye
damage has never, in our experience, affected the harvesting of a
only will be rehabilitated. In suitable cases, there would be no
graft, but this must still be borne in mind; severe scarring of the
need to go through unsuccessful penetrating keratoplasty with or
oral mucosa may compromise the successful harvest. Those who
without limbal stem cell transplantation and amniotic membrane
smoke should be advised to stop smoking to improve the chance
grafting beforehand.
of graft revascularization. Betel nut chewing will compromise tis-
Contraindications sue quality.
Patients who are happy and managing with their level of vision, Dental assessment
children under the age of 17, eyes that have no perception of
The procedure involves harvesting a tooth and its associated
light or that have evidence of phthisis, advanced glaucoma, or
alveolar bone for fashioning a “lamina.” The assessment aims
irreparable retinal detachment should be excluded. Suitable can-
to select a healthy tooth (root) with the best shape and size and
didates have to understand that the surgery can be prolonged—
good covering of alveolar bone. The surrounding anatomy is
they may require multiple procedures—and that there is a sig-
assessed to avoid possible complications and to reduce the cos-
nificant risk of serious complications, including loss of the eye.
metic defect to a minimum. There also needs to be adequate
The patient must be able to commit to lifelong follow-up and not
space between the teeth to harvest the tooth without damage to
have unreasonable expectations of outcome and cosmesis.
its neighbor. There is sometimes a compromise.
The assessment therefore involves methods of assessing these
Patient Assessment factors. The overall oral health, with particular reference to oral
hygiene and periodontal bone loss, must be assessed. Gingival
Ophthalmic assessment disease with no bone loss can be easily reversed. Clinical assess-
In Brighton, patients referred for possible OOKP surgery attend ment of bone loss can be useful, but radiographs are essential.
a joint clinic headed by an ophthalmologist and a maxillofacial The ideal tooth in size and shape with the best surrounding
surgeon. In the preoperative assessment we take a detailed his- bone is usually the canine tooth. There is usually little to choose
tory and determine the primary diagnosis and previous surgical in these parameters between the upper or lower canine. Other
interventions, especially regarding ocular perforation, glaucoma, single-rooted teeth can be used in the absence of a canine.
or a history of amblyopia. Preoperative examination involves The assessment of suitability of the tooth depends on clinical
determining an intact and functioning retina and optic nerve. examination but mainly on radiological assessment. The main-
This can be by relatively accurate light projection in all quad- stay views are orthopantomograms (OPT) and intraoral periapi-
rants and a normal B-scan. In some cases a flash electroretino- cal radiographs (IOPAs). These views are essential. They give
gram and visual evoked potential (VEP) can be useful. enough information in the majority of cases. CT scans can be
The lids and fornices are examined, and the degree of dry eye useful to get more detail and are advocated by some operators.
is noted, although a severe dry eye is not a contraindicated (as it All other things being equal, the choice of upper or lower
is with other forms of KPros). The conjunctiva and cornea are canine depends on the proximity of the maxillary sinus in the
examined, and evidence of stem cell failure, metaplasia, or dys- upper and, although this is rarely a problem, the proximity of
plasia is noted. Thinning of the cornea and evidence of previous the mental foramen in the lower. The lower canine harvesting is
corneal perforation, iris adhesion, and degree of vascularization straightforward, but the buccal plate is occasionally a little thin
are also noted. The depth of the anterior chamber, if visible, is and the lingual mucoperiosteum is more difficult to preserve.
noted. The IOP is determined digitally and a record is made as The upper canine occasionally gives too much bone palatally and
there is the risk of violation of the antrum; however, technically, duced under the mucosa to free the graft from the underlying tis-
the harvesting is easier. sue. The graft can then be delivered.
The patient must be given full information at this stage to Hemostasis is achieved. There is usually no need for any
give adequate consent. Complications will be dealt with later, sutures, although in Japan, surgeons have been using artificial
but side effects of the dental part of the procedure, such as the mucous membrane to cover the harvest site.
inevitable gap left in the dentition and the possible methods of
management, should be mentioned at this stage. The patient’s Fine details of harvesting tooth, root, and surrounding
regular dental practitioner should be informed at this stage so jaw bone
that preparation to replace the missing tooth may be made and The harvest of the alveolar/dental complex involves the section-
so the oral hygiene and periodontal condition can be optimized ing of bone on either sides and apical to the chosen tooth and
preoperatively. removing the tooth and its surrounding alveolar bone, together
Occasionally, there is no tooth suitable because of deficient with the associated mucoperiosteum. An incision is made to the
surrounding tissues, and in this circumstance an allograft may be bone and mucoperiosteum elevated from adjacent teeth. The
considered. bone cuts are made between the teeth and below the chosen
tooth with a fine saw, under constant irrigation to minimize any
thermal injury to the lamina. The complex is then removed from
Surgical Technique
the mouth in readiness to prepare the lamina.
Stage I The resulting alveolar defect is covered as best as possible
with adjacent mucosa, but the exposed bone epithelializes very
OOKP surgery is usually carried out in two stages. In the
rapidly. In Japan, surgeons have been covering the defect with
first stage a monoradicular tooth is harvested to prepare an
artificial mucous membrane grafting to accelerate wound heal-
osteoodonto-lamina. The root and surrounding jaw bone is
ing. The patient is advised regarding oral hygiene and diet; hard
sliced sagittally, while the crown is grasped with extraction for-
food should be avoided for some time. Antibiotics and analgesics
ceps to expose pulp, which is removed. A hole is drilled through
are prescribed.
dentine, through which the anterior part of a PMMA optical cyl-
inder is cemented in place. The crown is removed prior to drying When not to do ocular surface reconstruction and tooth
with filtered oxygen and cementing of the optical cylinder. The harvesting together
saw, flywheel and drill, and bur tips are constantly irrigated with
If the eye is very dry or there is a risk of the mucous membrane
balanced salt solution to provide cooling. Where periosteum has
graft not taking, it may be better to perform Stage I surgery in 2
been detached, it is glued back with fibrin glue. The KPro is then
steps. The mucous membrane graft to the eye is done first, and
implanted into a submuscular pouch (often the lower eyelid of
it is only when the graft has been shown to be well established
the fellow eye) for a period of 2 to 4 months.
that the patient is readmitted for tooth harvesting and prepar-
A buccal mucous membrane graft is used to cover the OOKP
ing an OOKP lamina. Otherwise, if there is a significant delay
lamina: it is more physiological than other coverings (ie, fascia
in mucous membrane healing or if further partial or full repeat
lata, donor sclera, etc.), there are stem cells present, it has prolif-
mucosal grafting proves necessary, the lamina may be resorbed
erating capability, and it is adapted to high bacterial load. It will
while buried in the lid for an excessively long time.
be vascularized by the time of Stage 2 surgery and will provide
the blood supply to the bone part of the OOKP lamina. Once Stage II
harvested, the fat from the buccal mucous membrane graft is
Stage II surgery is carried out 2 to 4 months after Stage I in order
removed with curved scissors and the graft soaked in an anti-
for soft tissue to invest into the bone pores of the lamina. The
biotic solution until required. The eye is prepared by isolating
interval also allows the lamina to recover from thermal damage,
the recti with stay sutures, a 360-degree peritomy is performed,
and any infection introduced from the oral cavity can be treated
and the conjunctiva and tenons are separated from underlying
while the lamina is submuscular rather than on the eye. If the
sclera. Corneal epithelium and Bowman membrane are removed.
lamina is implanted submuscularly for a longer period of time,
The buccal mucosa is then trimmed to obtain an oval piece of
there may be significant resorption of the lamina. The first step
adequate size to fit snugly on the front of the eye. The mucous
in Stage II surgery is to retrieve the buried lamina for inspection.
membrane graft is sutured onto the side of the insertion of the
Only if this is of adequate size does the surgeon proceed to pre-
4 recti muscles and to the sclera with interrupted 6-0 vicryl. If
paring the eye for receiving the device. After the OOKP lamina is
possible, the cut edge of the graft should also be sutured to the
retrieved from its submuscular pocket, soft tissue is excised from
conjunctiva.
the posterior surface and trimmed from the anterior. A template
Fine details of harvesting buccal mucous membrane graft is made of the lamina in order to plan placement of a Flieringa
ring, and sutures are preplaced for securing the lamina. The
The buccal graft must be full-thickness mucosa and of an area
lamina is temporarily returned to its submuscular pocket until
large enough to extend from medial to lateral canthi and from
the cornea is about to be trephined.
upper to lower lid fornices. This usually means harvesting a graft
Traction sutures are applied to the lids for access to the eye.
of 3 cm in diameter. The mouth is opened with a speculum, the
A superior rectus stay suture is placed and a buccal graft flap
parotid duct is identified, and local anesthetic with adrenaline is
is fashioned by making an arcuate incision from 3 o’clock to 9
injected.
o’clock under constant irrigation with BSS and adrenaline. The
A compression type retractor with the inner holder having a
flap is reflected and the cornea exposed. The buccal mucous
minimum internal diameter of 3 cm can be used. The outline of
flap is then reflected and a Flieringa ring sutured in place, with
the graft is marked, taking into account the parotid duct; this can
sutures left long at 3 and 9 o’clock for traction. The center of
usually be accommodated by going below the duct opening. The
the cornea is marked and the template placed on the cornea, and
mucosa is incised along its circumference, and scissors are intro-
cardinal sutures are preplaced. Intravenous mannitol has by then
been administered to reduce the IOP before trephination. The Postoperative Care
cornea is partially trephined, the size depending on the diameter
The immediate postoperative period requires pain relief, pred-
of the posterior part of the optical cylinder. This is completed
nisolone 20 mg and lansoprazole 30 mg for 5 days, and oral
with scissors or a blade. The iris is then completely removed
antibiotics. After Stage I, a conformer is often in place over the
using forceps. If the patient is phakic, the lens is removed by
buccal mucous membrane and daily glass rodding is carried out
extracapsular cataract extraction (ECCE) (Falcinelli advocates
to the fornices to keep them open. The patient uses chlorhexidine
an ICCE). A posterior capsulotomy is made and an anterior
and nystatin mouth washes. Post Stage II, Diamox, steroids, and
vitrectomy is performed, with adequate traction provided by the
antibiotics are continued. The optic is cleaned and the health of
surgical assistant on the two Flieringa ring sutures. The lamina is
the buccal mucous membrane monitored. The skin sutures are
then sutured to the cornea with the posterior part of the optical
removed after 5 days, and the patient is admitted for 1 week for
cylinder traversing the corneal opening. Sterile air is then injected
each stage.
to reinflate the eye, and indirect funduscopy is performed to
ascertain adequate centration and to take note of the appear- Follow-up visits
ance of the posterior pole of the eye and any presence of blood
The follow-up is lifelong: at weekly intervals for 1 month, then
in the vitreous. Further interrupted sutures are applied to secure
monthly for 3 months, then every 2 months for 6 months, then
the lamina onto the sclera. The Flieringa ring is then removed
every 4 months. If stable, then follow-up can be at longer inter-
and the buccal mucous membrane is repositioned and sutured in
vals, possibly shared with the referring ophthalmologist. At the
place, with a hole cut through the membrane to allow the ante-
follow-up visits, the vision is checked, unaided and with correc-
rior part of the optical cylinder to protrude (see Figures 1 and 2).
tion and pinhole, and a refraction performed. The IOP is checked
digitally, the lids are examined, and the buccal mucous mem-
brane is assessed, including color, dryness, and the presence of
any areas of thinning or ulceration. The optical cylinder is exam-
ined, specifically looking at the cement to see if there is tilting or
lengthening and to check for the presence of a retroprosthetic
membrane. The stability of the optical cylinder is also tested by
prodding with a cotton-tipped stick. Funduscopy is carried out to
check the optic disk and macula; B-scans are done to detect early
peripheral detachments; and visual field assessments are made
every 6 months for diagnosis and to monitor glaucoma. Resorp-
tion of the bone may be assessed clinically by palpating the mass
and dimensions of the lamina and radiologically using spiral CT,
MRI, or electron beam tomography.
If the patient has had an allograft, cyclosporin will be in use.
An empirical serum level of between 100 and 200 ng/ml is aimed
for, and after baseline investigations the urea and electrolytes,
Figure 1. Slitlamp photograph of an OOKP eye. creatinine, and cyclosporin levels are monitored at 3 days, 7
days, fortnightly for 2 months, every month for 4 months, then
every 2 months if stable.
Selected Reading
1. Liu C, Paul B, Tandon R, et al. The osteo-odonto-keratoprosthesis

(OOKP). Semin Ophthalmol. 2005; 20:113-128.
Figure 2. Schematic diagram of cross-section anatomy of an OOKP eye.

Appendix
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Reviewed: August 2011
A Biosynthetic Alternative to Human Donor Tissue

Per Fagerholm MD, May Griffith PhD, Neil Lagali PhD
Introduction 9 out of 10 patients in the human tissue group (6 male, 3 female,

age 56 ± 17 years at surgery). Indication for transplantation in
Biosynthetic corneal replacements can potentially address two
the human tissue group was keratoconus (5 cases), endothelial
main problems: (1) the short supply of high-quality transplant
decompensation (2 cases), a deep, central scar (1 case), and pseu-
tissue to meet the need, where 10 million people are estimated
dophakic bullous keratopathy (1 case). One patient underwent
to require transplantation and (2) the use of acellular implants
successful cataract surgery at 12 months, while another exhibited
reduced inflammation, and biosynthetics may minimize/eliminate
rejection at 12 months, which resolved after topical dexametha-
the risk of rejection, which for PK is 10% within 2 years. The use
sone treatment. A tenth patient from the human tissue group was
of recombinant collagen also eliminates transmission of diseases
removed from the study after a retinal detachment occurred a
such as those caused by viruses and prions.
few months postoperatively.
The biosynthetic implants mimic the extracellular matrix of
Additionally, a group of 20 healthy volunteers was examined
the corneal stroma and guide the recipient cells in a healing pro-
to establish a reference for normal corneal morphology (healthy
cess that leaves the cornea transparent, with appropriate refrac-
group).
tive properties after the healing process.
Results
Background Observations
Three years after surgery, the gross appearance of human donor
Implants were made from human recombinant collagen type III
and biosynthetic tissue was similar (see Figure 1). In all patients,
(RHCIII), crosslinked using water soluble carbodiimide (WSC).
areas of reduced transparency were observed. In the human
After extensive animal workup in several species, we conducted
donor group, prominent haze was observed at the peripheral
a human Phase 1 study where the material was implanted into
host-graft interface, while all central corneas were transparent. In
10 eyes following approvals from the Swedish Medical Products
the biosynthetic group, all corneas had peripheral host-implant
Agency and the Regional Ethical Review Board in Linköping.
interface haze, but with a less discernible implant-host border.
The patients’ 2-year data have been published,6 and the 3-year
An additional posterior lamellar interface haze was also present,
follow-up is presented here.
and 8 out of 10 biosynthetic implants also had focal areas of
haze in the midperipheral to central cornea.
Materials and Methods We believe the haze within the central cornea was due to the
disruption of re-epithelialization by the tight overlying sutures, as
Details of materials and methods were previously reported.6
the pattern of haze corresponded to the position of earlier over-
Briefly, 10 consecutive patients, aged 18-75 years (8 male,
lying sutures. These areas were first noted at the time of suture
2 female) from a waiting list for a first corneal transplantation
removal and persisted to 36 months. The corneal thickness is
were enrolled. Inclusion criteria included a clear posterior stroma
indicated in Figure 2.
and normal endothelium. Nine of 10 eyes had a diagnosis of
The BCVA was not impressive, but the patients improved
advanced keratoconus. The tenth eye had a permanent midstro-
considerably when fitted with contact lenses (see Figure 3).
mal scar in the visual axis secondary to bacterial keratitis. Ten
longitudinally followed PKP patients served as controls.
Anterior lamellar keratoplasty (ALK) was performed under
either local or general anesthesia. The cornea was trephined to
6.0- to 6.5-mm diameter to a depth of 200 µm, and deepened
manually with a diamond knife to 370-400 µm. Manual lamellar
dissection was then used to remove the corneal tissue. A punch
trephine (Baron, Katena, New Jersey, USA) cut the biosynthetic
implant 500 µm thick, 0.25 mm larger in diameter than the
recipient bed. The implant was anchored with overlying 10-0
nylon mattress sutures. A bandage contact lens was placed. Post-
operatively, patients received 1 drop each of chloramphenicol
and Opnol topical steroid drops (0.1% dexamethasone, Clean Figure 1. Corneal appearance by slitlamp biomicroscopy 36 months
after surgery. Top row: human donor corneas; bottom row: biosynthetic
Chemical Sweden, Borlänge, Sweden) 3 times daily for a mean corneas. Peripheral to midperipheral haze is evident at the graft border in
of 6.5 ± 3 weeks, at which time the contact lens and sutures were human tissue (A-C, arrows), with some grafts exhibiting good transpar-
removed. One patient underwent successful cataract surgery at ency throughout (D). In biosynthetic tissue, posterior lamellar interface
10 months. No episodes of rejection were observed. haze (E, arrowhead) and central foci of haze (E-G, arrows) were evident,
while some implants remained substantially transparent (H).
All control patients underwent PKP with human donor cor-
neas from Swedish cornea banks. PKP was performed under gen-
eral or local anesthesia. The 3-year follow-up was completed for
Conclusions
The results from the Phase 1 study was reasonably success-
ful. We also have identified problems that will be addressed
in a Phase 2 study. We have increased the collagen content of
the construct in order to make the material mechanically more
robust, allowing for use of peripheral interrupted sutures that
will leave the central cornea undisturbed. We also aim to evalu-
ate the anti-inflammatory effect of using an amniotic membrane.
Likewise, a keratoconus group will be compared to a nonkera-
toconus group (dystrophies, scars, etc). Part of this concept has
been successfully tested in minipigs.
References
1. Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a

global perspective. Bull World Health Organ. 2001; 79:214-221.
Figure 2. Corneal thickness in the central 2 mm of cornea in operated
groups and in a healthy group of volunteers, measured by anterior seg- 2. Claesson M, Armitage WJ, Fagerholm P, Stenevi U. Visual outcome
ment OCT (AS-OCT). Markers indicate mean thickness values in the in corneal grafts: a preliminary analysis of the Swedish Corneal
group, while error bars represent 1 standard deviation. Mean corneal Transplant Register. Br J Ophthalmol. 2002; 86:174-180.
thickness was assessed by AS-OCT. In the human donor group, a signifi-
cant thickness increase occurred from 12 to 24 months (Wilcoxon signed 3. Merrett K, Fagerholm P, McLaughlin CR, et al. Tissue engineered
rank test, P = .008) but stabilized thereafter. At 36 months, they were recombinant human collagen-based corneal substitutes for implan-
significantly thicker than healthy corneas (t test, P = .021). No change tation: performance of type I versus type III collagen. Invest Oph-
in central thickness could be detected in the biosynthetic group (1-way thalmol Vis Sci. 2008; 49:3887-3894.
ANOVA, P = .98). They were significantly thinner than human donor
corneas and healthy groups (Mann-Whitney, P < .001). 4. Lagali N, Griffith M, Fagerholm P, Merrett K, Huynh M, Munger
R. Innervation of tissue-engineered recombinant human collagen-
based corneal substitutes: a comparative in-vivo confocal micros-
copy study. Invest Ophthalmol Vis Sci. 2008; 49:3895-3902.
5. Liu W, Merrett K, Griffith M, et al. Recombinant human colla-
gen for tissue engineered corneal substitutes. Biomaterials 2008;
29(9):1147-1158.
6. Fagerholm P, Lagali NS, Merrett K, et al. A biosynthetic alternative
to human donor tissue for inducing corneal regeneration: 24-month
follow-up of a phase 1 clinical study. Sci Transl Med. 2010;
2(46):46ra61.
Figure 3. The mean BSCVA in logMAR units over time. There is some
improvement over the first 18 months. The BCLVA, however, is consid-
erably better, as depicted after 24 months.
Oral Mucosal Epithelial Transplantation for the

Management of Ocular Surface Disease
Corneal Reconstruction With Autologous Oral Mucosal Epithelial Cell Sheets
Kohji Nishida MD
Drastic progress of the understanding of stem cell biology II. Introduction of Cultivated Corneal Epithelial Cell
occurred in the 1990s, and the clinical usage of stem cells seems Transplantation
to be promising. Recently, a novel therapeutics utilizing tissue
A. Several approaches for cultivated corneal epithelial
engineering and stem cell technology, called regenerative medi-
cell transplantation
cine, has been emphasized. As regenerative medicine for corneal
epithelial diseases, transplantation of cultivated corneal epithelial B. Disadvantage of cultivated corneal epithelial cell
cell sheets fabricated from corneal epithelial stem cells expanded transplantation
ex vivo has been developed and has already entered the clinical
III. A Novel Tissue Engineering Approach: Cell Sheet
realm.
Engineering
In this presentation, I will talk on corneal reconstruction
with autologous oral mucosal epithelial cell sheets. We have A. What is cell sheet engineering?
developed this technique and performed a clinical application
B. How to manipulate epithelial stem cells in vitro
for patients who suffered from severe limbal stem cell deficiency.
The outline of my talk is described below. C. Advantage of cell sheet engineering
I. Corneal Stem Cells and Diseases With Stem Cell IV. Corneal Epithelial Reconstruction With Cell Sheets
Deficiency
A. Cell source and basic data
A. Concept of corneal epithelial stem cell
B. Advantage of cell sheet engineering for corneal epi-
B. Limbal stem cell deficiency thelial reconstruction
C. Corneal epithelial stem cell transplantation C. Surgical procedure
D. Indication and clinical data
Cultivated Limbal Epithelial Transplantation for the

Management of Ocular Surface Disease
Virender S Sangwan MBBS
Background legrini et al in 1997.17 Since then, many modifications of this

original technique using different culture systems and carriers
The corneal surface is maintained by a steady supply of epithelial
have been reported in the literature.18,19
cells from the limbus that surrounds it.1 There is now enough
clinical and scientific evidence to suggest that adult corneal epi-
thelial stem cells reside at that location.2,3 Ocular trauma or sur- LVP Technique and Outcomes
face disease can damage the limbus, leading to a functional loss
We have developed novel and successful modifications in the
of these stem cells and consequently inducing corneal epithelial
procedure, namely, a feeder-free explant culture system, use of
instability.4,5 This condition, termed limbal stem cell deficiency
human autologous (rather than animal based) serum, and human
(LSCD), is clinically characterized by the loss of corneal epithe-
recombinant growth factors (see Figure 1). Over the course of
lial clarity, loss of vision, and recurrent or persistent epithelial
the last decade we have characterized the cultured cells,20 stan-
defects.4,5 Conventional corneal transplantation is not successful
dardized our cultivation technique,21 and reported encouraging
in such eyes as there is insufficient supply of endogenous recipi-
early results of clinical transplantation.22,23 Earlier we reported
ent limbus-derived epithelium to maintain the graft.6,7
our short-term results in 88 eyes with a success rate of 73%,23
which is comparable to other large studies by Rama et al (107
Origin of Stem Cell–Based Therapy for LSCD eyes, 68%)24 and Di Ioro et al (166 eyes, 80%).25 Successful
outcome was noted in 279 of 444 eyes (62.8%), and probability
Kenyon and Tseng provided proof-of-principle that transplanta-
of survival for autologous cultivated limbal epithelium transplan-
tion of stem cell–bearing limbal tissue could cure LSCD.8 Since
tation (CLET) was 65% at 1 year, with median survival of 4.3
then, direct limbal transplantation from the unaffected fellow eye
years (our unpublished data).
(autologous) or from donors (allogenic) has become standard of
care for LSCD.8-16 However, direct transplantation requires at
least 4 clock hours (3x10 mm) of donor limbal tissue,8-16 which Outcomes of Autologous Cultivated Limbal
can lead to donor site iatrogenic LSCD.9,15,16 Epithelial Transplantation
This study included 444 eyes of 435 patients who underwent
Current Status of Stem Cell–Based Therapy for autologous CLET for clinically diagnosed LSCD due to ocular
LSCD burns between April 2001 and November 2010. The primary
outcome measure was clinical success of the transplantation,
Ex vivo expansion of the limbal epithelium is a novel therapeutic
defined as the achievement of a stable corneal surface. Failure
approach to treat LSCD. This requires relatively smaller (2x1
was defined as superficial corneal vascularization, conjuncti-
mm) donor tissue, thus eliminating the risk of inducing iatro-
valization, and/or recurrent epithelial breakdown. Results were
genic LSCD in the donor eye. The first report of the culture of
analyzed using Kaplan Meier survival analysis. The secondary
corneal epithelial cells with murine feeder cells came from Pel-
Figure 1.
outcome measure was improvement in best spectacle corrected was 76.9% ± 11.7% at 12 months, with median survival of 40
visual acuity (BSCVA). Most patients were young (median age: months. No donor or recipient eyes developed serious ocular
20 years) males (75.6%) with ocular chemical burns (88.5%), complications. Visual acuity improved to 20/60 or better in 7
unilateral LSCD (92.2%), and severe visual loss (76.6%). The eyes after allo-CLET alone, and in 11 other eyes following PK.
median postsurgical follow-up was 1.2 years, with a maximum Ocular surface stability and visual restoration can be success-
follow-up of 7.2 years. fully achieved in eyes of patients with bilateral total LSCD by
CLET was successful in 279 of 444 eyes (62.8%; median performing allo-CLET followed by PK.
survival of 4.3 years). Most (76.9%) failures occurred within the
first 8 months. Subgroup analysis showed that success of CLET
Outcomes of Penetrating Keratoplasty After
was significantly better (81.5%, P = .012) in eyes without previ-
Autologous Cultivated Limbal Epithelial
ous corneal surgeries, poor preoperative BSCVA (< 20/200),
Transplantation
and simultaneous keratoplasty. Among 279 successful cases, a
2-line improvement of BSCVA was seen in 183 eyes (65.6%; P < This study included 47 patients with unilateral limbal stem cell
.0001) and 124 eyes (44.4%) achieved BSCVA of 20/60 or bet- deficiency (LSCD) due to ocular surface burns, treated by autolo-
ter. No serious ocular complications were noted in transplanted gous cultivated limbal epithelial transplantation and PK between
or donor eyes. In this large series, autologous CLET was effective 2001 and 2010. PK was performed either along with (single-
in restoring ocular surface stability and improving vision in eyes stage, n = 12) or at least 6 weeks after (2-stage, n = 35) limbal
with LSCD caused by ocular surface burns (see Figure 2). transplantation. Primary outcome measure was corneal allograft
survival, and failure was clinically defined as loss of central graft
clarity. Secondary outcomes were postoperative Snellen visual
acuity and complications. Most patients were young (mean age:
18 ± 11.4 years) males (76.6%) with LSCD due to alkali burns
(78.7%) and vision less than 20/200 (91.5%). The mean follow-
up was 4.2 ± 1.9 years.
Kaplan-Meier corneal allograft survival rate at 1 year was sig-
nificantly greater in eyes undergoing 2-stage (80% ± 6%, median
survival: 4 years) as compared to single-stage (25% ± 13%,
median survival: 6 months) limbal and corneal transplantation (P
= .0003). Visual acuity of 20/40 or better was attained by 71.4%
of eyes with clear corneal grafts. Allograft failure occurred in
26 eyes (60.5%) due to graft rejection (57.7%), graft infiltrate
(26.9%), or persistent epithelial defects (15.4%). Recurrence of
LSCD was more common after single-stage (58.3%) than 2-stage
(14.3%) surgery (P = .008).
Two-stage approach of autologous cultivated limbal epithe-
lial transplantation followed by PK successfully restores ocular
surface stability and vision in eyes with unilateral LSCD due to
Figure 2. Survival curve for outcome of CLET. ocular burns. Single-stage approach is associated with poorer
clinical outcomes and should be avoided.
Outcomes of Allogenic Cultivated Limbal Epithelial

Transplantation
This study included 28 eyes of 21 patients with bilateral clini-
cally diagnosed total LSCD who were treated between January
1, 2001, and January 1, 2010. All patients developed corneal
blindness after the age of 8 years and had at least 6 weeks of
postsurgical follow-up. The primary outcome was maintenance
of a clinically stable ocular surface, and failure was defined as
the formation of a persistent epithelial defect, diffuse fluorescein
staining, or central corneal neovascularization. Secondary out-
comes were visual acuity, complications, and survival of subse-
quent corneal allografts. The mean age at the time of allo-CLET
was 27.9 ± 14.7 years, with male-to-female ratio of 4.25:1. The
median time between the initial injury and allo-CLET was 38
months (range: 3-432). Most eyes (61%, n = 17) had history of
chemical or thermal injury, and preoperative vision ranged from
20/100 to light perception.
The Kaplan-Meier allo-CLET survival rate at 12 months was Figure 3. Survival curve for PK after CLET.
76.4% ± 8.7%, with mean follow-up of 58 ± 33 months. At
last follow-up, 20 eyes (71.4%) had either maintained a healthy
corneal surface or underwent penetrating keratoplasty (PK).
The corneal allograft survival rate following allo-CLET (n = 13)
Outcomes of Repeat Autologous Cultivated Limbal 7. Brown SI, Bloomfield SE, Pearce DB. Follow-up report on trans-
Epithelial Transplantation plantation of the alkali burned cornea. Am J Ophthalmol. 1974;
77:538-542.
To evaluate the outcomes of repeat autologous cultivated limbal
8. Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular
epithelial transplantation (CLET) after failed primary CLET for
surface disorders. Ophthalmology 1989; 96:709-722.
limbal stem cell deficiency (LSCD). This study was a retrospec-
tive chart review of 68 eyes of 68 patients who underwent repeat 9. Miri A, Said DG, Dua HS. Donor site complications in autolimbal
autologous CLET for unilateral LSCD due to ocular surface and living-related allolimbal transplantation. Ophthalmology.
burns between 2001 and 2009. A limbal biopsy was obtained Epub ahead of print 30 Mar 2011.
from the healthy contralateral eye. The limbal epithelial cells 10. Miri A, Al-Deiri B, Dua HS. Long-term outcomes of autolimbal and
were expanded ex vivo on human amniotic membrane using a allolimbal transplants. Ophthalmology 2010; 117(6):1207-1213.
xeno-free and feeder-free culture system. The resulting cultured 11. Santos MS, Gomes JA, Hofling-Lima AL, Rizzo LV, Romano AC,
monolayer sheet was transplanted on the patient’s affected eye Belfort R Jr. Survival analysis of conjunctival limbal grafts and
after surgical preparation. All patients underwent a comprehen- amniotic membrane transplantation in eyes with total limbal stem
sive ophthalmic examination of both eyes at every visit. Primary cell deficiency. Am J Ophthalmol. 2005; 140(2):223-230.
outcome measure was success of repeat CLET, clinically defined
12. Ozdemir O, Tekeli O, Ornek K, Arslanpençe A, Yalçindağ NF.
as stable ocular surface with absence of conjunctivalization or Limbal autograft and allograft transplantations in patients with
peripheral corneal neovascularization at 1 year postoperatively. corneal burns. Eye (Lond). 2004; 18(3):241-248.
Most patients were young (mean age: 17.3 ± 12.3 years) males
13. Dua HS, Azuara-Blanco A. Autologous limbal transplantation in
(72.1%) with history of alkali burns (83.8%) and median fol-
patients with unilateral corneal stem cell deficiency. Br J Ophthal-
low-up of 19 (range: 12 to 90) months.
mol. 2000; 84:273-278.
Kaplan Meier survival probability of repeat autologous CLET
was 46.3% ± 0.07% at 1 year (median survival: 10 months). 14. Rao SK, Rajagopal R, Sitalakshmi G, Padmanabhan P. Limbal allo-
Subgroup analysis showed that success of CLET was signifi- grafting from related live donors for corneal surface reconstruction.
Ophthalmology 1999; 106:822-828.
cantly better (80.4%, P = .0004) in eyes without symblepharon
(hazard ratio: 4.6) and simultaneous keratoplasty (hazard ratio: 15. Basti S, Mathur U. Unusual intermediate-term outcome in three
2.6). In 82% of successful cases vision improved to 20/40 or bet- cases of limbal autograft transplantation. Ophthalmology 1999;
ter postoperatively (P < .0001). All donor eyes had normal ocu- 106(5):958-963.
lar surface postoperatively. 16. Tan DT, Ficker LA, Buckley RJ. Limbal transplantation. Ophthal-
Autologous CLET is safely repeatable and is effective in mology 1996; 103(1):29-36.
treating eyes with failed primary CLET and LSCD due to ocular
17. Pellegrini G, Traverso CE, Franzi AT, Zingirian M, Cancedda R,
surface burns. De Luca M. Long-term restoration of damaged corneal surfaces
with autologous cultivated corneal epithelium. Lancet 1997;
Conclusions 349:990-993.
18. Shortt AJ, Secker GA, Notara MD, et al. Transplantation of ex
Cultivated limbal epithelial transplantation (CLET) is safe and
vivo cultured limbal epithelial stem cells: a review of techniques and
effective procedure for total or partial LSCD. Significant percent- clinical results. Surv Ophthalmol. 2007; 52:483-502.
ages of patients show improved ocular surface and vision on a
long-term basis. 19. Baylis O, Figueiredo F, Henein C, Lako M, Ahmad S. 13 years of
cultured limbal epithelial cell therapy: a review of the outcomes.
J Cell Biochem. 2011; 112:993-1002.
References 20. Polisetti N, Agarwal P, Khan I, et al. Gene expression profiles of
epithelial cells and mesenchymal cells derived from limbal explant
1. Shapiro MS, Friend J, Thoft RA. Corneal re-epithelialization from culture. Mol Vis. 2010; 16:1227- 1240.
the conjunctiva. Invest Ophthalmol Vis Sci. 1981; 21:135-142.
21. Mariappan I, Maddileti S, Savy S, et al. In vitro culture and expan-
2. Schermer A, Galvin S, Sun T-T. Differentiation-related expression of human limbal epithelial cells. Nat Protoc. 2010; 5:1470-
sion of a major 64K corneal keratin in vivo and in culture suggests 1479.
limbal location of corneal epithelial stem cells. J Cell Biol. 1986;
103:49-62. 22. Sangwan VS, Matalia HP, Vemuganti GK, et al. Early results of
penetrating keratoplasty after cultivated limbal epithelium trans-
3. Shanmuganathan VA, Foster T, Kulkarni BB, et al. Morphologi- plantation. Arch Ophthalmol. 2005; 123:334-340.
cal characteristics of the limbal epithelial crypt. Br J Ophthalmol.
2007; 91:514-519. 23. Sangwan VS, Matalia HP, Vemuganti GK, et al. Clinical outcome
of autologous cultivated limbal epithelium transplantation. Indian J
4. Dua HS, Azuara-Blanco A. Limbal stem cells of the corneal epithe- Ophthalmol. 2006; 54:29-34.
lium. Surv Ophthalmol. 2000; 44:415-425.
24. Rama P, Matuska S, Paganoni G, et al. Limbal stem-cell therapy
5. Tseng SC. Concept and application of limbal stem cells. Eye 1989; and long-term corneal regeneration. N Engl J Med. 2010; 363:147-
3:141-157. 155.
6. Maguire MG, Stark WJ, Gottsch JD, et al; Collaborative Corneal 25. Di Iorio E, Ferrari S, Fasolo A, et al. Techniques for culture and
Transplantation Studies Research Group. Risk factors for corneal assessment of limbal stem cell grafts. Ocul Surf. 2010; 8:146-153.
graft failure and rejection in the collaborative corneal transplanta-
tion studies. Ophthalmology 1994; 101(9):1536-1547.
Ocular Surface Reconstruction With Immature Dental

Pulp Stem Cell Transplantation
José AP Gomes MD
Introduction: Challenges in the Treatment of Other autologous epithelia such as the conjunctiva have also
Bilateral Limbal Stem Cell Deficiency been successfully cultivated and transplanted experimentally for
the same purpose.14-16
Limbal epithelial stem cells (LSC), which reside in the transition
Searching for another alternative stem cell source that could
area between the cornea and the sclera, are capable of promoting
be potentially used in corneal reconstruction, we turned our
constant renewal of the corneal epithelium and its regeneration
attention to a population of stem cells isolated by our group
in case of injury.1-3
from deciduous teeth, which were named human immature den-
A variety of diseases, such as Stevens-Johnson syndrome,
tal pulp stem cells (hIDPSC).
chemical burn, and ocular cicatricial pemphigoid, may cause par-
tial or total limbal stem cell deficiency (TLSCD).1 As a result of
such deficiency, the conjunctival epithelium invades the cornea Background Observations: hIDPSC
in a process known as conjunctivalization, which predisposes to
hIDPSC exhibit all characteristics of multipotent adult stem cells,
corneal neovascularization and opacification.2,3 In TLSCD, con-
expressing mesenchymal stem cell and several human embryonic
junctivalization usually compromises the visual axis, leading to a
stem (ES) cell markers.17-20 Additionally, hIDPSC have a normal
significant loss of visual acuity.2,3
karyotype and show the capacity for multilineage differentia-
When TLSCD is unilateral, limbal epithelial cell transplan-
tion into neurons, smooth and skeletal muscle, cartilage, bone,
tation (CLAU) from the contralateral healthy eye can restore
and other cell types in vitro and in vivo.20 We verified LSC gene
normal corneal epithelium and decrease neovascularization
expression profile in undifferentiated hIDPSC.21 These undif-
and inflammation, leading to improvement of corneal trans-
ferentiated cells continuously expressed markers of LSC such as
parency.2-4 This procedure cannot be applied to patients with
ABCG2, ß1-integrin, vimentin, p63, connexin 43, and keratin
bilateral LSCD. In this case, transplant is obtained from a living
12, but they were negative for the corneal cell marker keratin K3
related (lr-CLAL) or cadaveric eye (KLAL).5,6 The success of
when cultured in vitro.21
such grafts is limited by microenvironmental factors as found in
In order to determine the outcome of the use of a tissue-
severe dry eyes and by immunologic rejection for the allogeneic
engineered cell sheet composed of hIDPSC for ocular surface
transplanted cells.5,6
reconstruction, we established two different models of TLSCD
induced by chemical injury with 0.5 M NaOH in rabbit eyes.22
After 1 month of injury, a superficial keratectomy was per-
formed to remove the fibrovascular pannus that covered the
animals’ burned corneas, and a tissue-engineered hIDPSC sheet
was transplanted onto the corneal bed and then covered with
de-epithelialized human amniotic membrane (AM).22 In the
respective control groups, the denuded cornea was covered with
AM only. After 3 months, a detailed analysis of the rabbit eyes
was performed with regard to clinical aspect, histology, electron
microscopy, and immunohistochemistry.22
Figure 1. Survival curve of eyes with TLSCD after conjunctival limbal

graft and amniotic membrane transplantation according to HLA com-
patibility of the recipient and the donor of the conjunctival/limbal graft.6
Advances in tissue culture and bioengineering have allowed

the ex vivo expansion of limbal epithelial cells using different
scaffolds, including amniotic membrane, fibrin gel, or collagen
contact lenses.7-10 Functional reconstruction of cornea in TLSCD Figure 2. Transplantation of tissue-engineered cell sheet made from
undifferentiated hIDPSC. A, Morphology of hIDPSC (phase contrast,
by limbal epithelial autograft transplantation has been success- PC). B, Three days after reaching confluence, cells form a cell sheet (PC).
fully achieved.7-10 Encouraging outcomes with ex vivo allogeneic C, The viable cell sheet is harvested by reducing the temperature to 20
LSC transplantation in TLSCD eyes have been reported; how- degrees C for 30 minutes. D, Sheet of tissue-engineered hIDPSC (arrow)
ever, the problem of graft rejection needs to be overcome.7-10 In is harvested with the use of a doughnut-shaped supporter (white). E,
Conjunctival tissue over the cornea is surgically removed to expose trans-
an attempt to avoid rejection, autologous oral mucosal epithelial parent corneal stroma. F, Sheet of tissue-engineered hIDPSC is placed on
cells have been successfully transplanted in LSCD by Nishida et the stromal bed. G, The sheet adheres to the corneal stroma and the sup-
al using an elegant technique of epithelial cell cultivation on tem- porter is removed. H, Amniotic membrane is placed over cell sheet and
perature-responsive polymer poly(N-isopropylacrylamide).11-13 sutured.22 Scale bar (A-B) = 5 µm.
Corneal transparency of the rabbit eyes that underwent in eyes with total limbal stem cell deficiency. Am J Ophthalmol.
hIDPSC transplantation was improved throughout the follow- 2005; 140:223-230.
up, while the control corneas developed total conjunctivaliza- 7. Pellegrini G, Traverso CE, Franzi AT, et al. Long term restoration
tion and opacification.22 The clinical data were confirmed by of damaged corneal surface with autologous cultivated corneal epi-
histologic analysis that showed healthy uniform corneal epithe- thelium. Lancet 1997; 349:990-993; comment: 1556.
lia, especially in the mild chemical burn group.22 The presence 8. Tsai RJ-F, Li LM, Chen J-K. Reconstruction of damaged corneas by
of hIDPSC was detected using an anti-hIDPSC antibody. The transplantation of autologous limbal epithelial cells. N Engl J Med.
corneal tissue also showed positive immunostaining with anti- 2000; 343(2):86-93.
human antibodies. In the control corneas, none of these antigens
9. Koizumi N, Inatomi T, Suzuki T, et al. Cultivated corneal epithelial
were detected.22
stem cell transplantation in ocular surface disorders. Ophthalmol-
ogy 2001; 108:1569-1574.
10. Du Y, Chen J, Funderburgh JL, et al. Functional reconstruction of
rabbit corneal epithelium by human limbal cells cultured on amni-
otic membrane. Mol Vis. 2003; 9:635-643.
11. Nishida K, Yamato M, Hayashida Y, et al. Functional bioen-
gineered corneal epithelial sheet grafts from corneal stem cells
expanded ex vivo on a temperature-responsive cell culture surface.
Transplantation 2004; 77:379-385.
12. Nishida K, Yamato M, Hayashida Y, et al. Corneal reconstruction
with tissue-engineered cell sheets composed of autologous oral
mucosal epithelium. N Engl J Med. 2004; 351(12):1187-1196.
Figure 3. Representative figures of rabbit eyes 1 month after ocular sur- 13. Kinoshita S, Koizumi N, Nakamura T. Transplantable cultivated
face damage and 3 months after transplantation of a tissue-engineered
mucosal epithelial sheet for ocular surface reconstruction. Exp Eye
hIDPSC sheet.22
Res. 2004; 78(3):483-491.
14. Tan D, Ang L, Beuerman R. Reconstruction of the ocular surface
Preliminary Results: Clinical Experience With by transplantation of a serum-free derived cultivated conjunctival
hIDPSC Transplantation for Total Stem Cell equivalent. Transplantation 2004; 77(11):1729-1734.
Deficiency 15. Kinoshita S, Tanioka H, Kawasaki S, et al. Establishment of culti-
vated human conjunctival epithelium as an alternative tissue source
In 2010, we obtained the approval of the Institutional Review for autologous corneal epithelial transplantation. Invest Ophthal-
Board and the Brazilian Committee for Ethics in Research to mol Vis Sci. 2006; 47(9):3820-3827.
start the first cases of hIDPSC transplantation for ocular surface
16. Ang LP, Tanioka H, Kawasaki S, et al. Cultivated human conjunc-
reconstruction in TLSCD. The preliminary results will be pre-
tival epithelial transplantation for total limbal stem cell deficiency.
sented in this session.
Invest Ophthalmol Vis Sci. 2010; 51(2):758-764.
17. Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem
Conclusion cells suppress lymphocyte proliferation in vitro and prolong skin
graft survival in vivo. Exp Hematol. 2002; 30:42-48.
Overall, these data suggest that transplantation of a tissue-
engineered hIDPSC sheet may represent a potential option for 18. Rasmusson I, Ringdén O, Sundberg B, Le Blanc K. Mesenchymal
reconstruction of the corneal epithelium in TLSCD. stem cells inhibit the formation of cytotoxic T lymphocytes, but not
activated cytotoxic T lymphocytes or natural killer cells. Transplan-
tation 2003; 76:1208-1213.
References
19. Ma Y, Xu Y, Xiao Z, et al. Reconstruction of chemically burned rat
corneal surface by bone marrow derived human mesenchymal stem
1. Kruse FE. Classification of ocular surface disease. In: Holland EJ,
cells. Stem Cells 2006; 24:315-321.
Mannis MJ, eds., Ocular Surface Disease: Medical and Surgical
Management. New York: Springer-Verlag; 2001:16-36. 20. Kerkis I, Kerkis A, Dozortsev D, et al. Isolation and characteriza-
tion of a population of immature dental pulp stem cells expressing
2. Tsubota K. Ocular surface management in corneal transplantation,
Oct-4 and other embryonic stem cell markers. Cells Tissues Organs.
a review. Jpn J Ophthalmol. 1999; 43(6):502-508.
2006; 184(3-4):105-116.
3. Dua HS, Azuara-Blanco A. Autologous limbal transplantation in
21. Monteiro BG, Serafim RC, Melo GB, et al. Human immature den-
patients with unilateral corneal stem cells deficiency. Br J Ophthal-
tal pulp stem cells share key characteristic features with limbal stem
mol. 2000; 84:273-278.
cells. Cell Prolif. 2009; 42(5):587-594.
4. Kenyon KR, Tseng SCG. Limbal autograft transplantation for ocu-
22. Gomes JA, Geraldes Monteiro B, Melo GB, et al. Corneal recon-
lar surface disorder. Ophthalmology 1989; 96:709-722; discussion:
struction with tissue-engineered cell sheets composed of human
722-723.
immature dental pulp stem cells. Invest Ophthalmol Vis Sci. 2010;
5. Tseng SC, Prabhasawat P, Barton K. Amniotic membrane trans- 51(3):1408-1414.
plantation with or without limbal allografts for corneal surface
reconstruction in patients with LSCs cell deficiency. Arch Ophthal-
mol. 1998; 116:431-441.
6. Santos MS, Gomes JAP, Höfling-Lima AL, et al. Survival analysis of
conjunctival limbal grafts and amniotic membrane transplantation
26 Section II: Infectious Keratitis 2011 Subspecialty Day | Cornea
Bacterial Keratitis: Susceptibility Testing, Steroids, and

Other Treatment Controversies
Thomas M Lietman MD
The Importance of Bacterial Keratitis for corticosteroids in the treatment of bacterial corneal ulcers,
there is insufficient evidence to make an official recommenda-
Corneal opacity has been reported as the fourth leading cause of
tion.18 To date, the only evidence available to guide decisions are
blindness globally.1 Much of this is due to infectious ulcers. The
animal and retrospective studies, and 2 small clinical trials that
annual occurrence of infectious keratitis has been estimated at
were too underpowered to definitively answer the question.19,20
1.5-2 million cases globally, and the true incidence may be much
higher.2 Bacteria such as Streptococcus pneumoniae and Pseu-
domonas aeruginosa are common etiologic agents of infectious Therapeutic Exploratory Study for SCUT
keratitis, responsible for as much as half of the corneal ulceration
The primary objective of the Steroids for Corneal Ulcers Trial
in South India, and typically far larger proportions in the United
(SCUT) is to assess the impact of adjunctive topical corticoste-
States and Europe.3-7 Treatment of bacterial keratitis is difficult
roids on clinical outcomes in patients with bacterial corneal
and can lead to poor visual outcomes and blindness, and antimi-
ulcers. Forty-two patients were enrolled, treated with moxi-
crobial-resistant bacteria are increasingly found.8
floxacin, and treated with either 1% prednisolone phosphate or
Major issues in treatment of bacterial ulcers include the
placebo (in a masked manner). Acuity and scar size were slightly
importance of susceptibility testing and antibiotic choice, and the
better in the steroid-treated cases, although not significantly
use of adjunctive steroid treatment.
so. Re-epithelialization was significantly delayed in the steroid-
treated cases. There was no increase in adverse outcomes (such
Susceptibility Testing as perforation) in the steroid arm.20
In systemic bacterial infections, in vitro susceptibility is thought
to predict clinical outcomes.9,10 In ocular infections, since a large Therapeutic Confirmatory SCUT
concentration of antibiotic is delivered directly to the site of
In 2006, the Proctor Foundation at the University of California,
infection with application of topical antibiotics, it is possible that
San Francisco, Dartmouth Medical School, and the Aravind Eye
in vitro susceptibility does not play as large a role in determining
Care System started an NEI-sponsored randomized controlled
clinical outcome.11 Recent studies have suggested that in vitro
trial evaluating the effect of prednisolone phosphate on outcome
susceptibility may predict clinical outcome in bacterial keratitis;
in bacterial keratitis. As with the therapeutic exploratory trial, all
however, the role of organism in this relationship is not clear.12-14
cases were treated with topical moxifloxacin. Enrollment of 500
As part of the National Eye Institute–funded Steroids for
cases was completed in February 2010, and 12-month follow-up
Corneal Ulcers Trial (SCUT), we collected minimum inhibitory
was completed in early 2011. Results of this study will be pre-
concentration (MIC) information for all isolates to moxifloxacin,
sented as allowed by NEI regulations.
the antibiotic used per protocol. Specific clinical outcomes, such
as visual acuity or infiltrate/scar size, were measured precisely,
allowing correction for baseline measurements for each clinical References
outcome. This allowed assessment of the MIC’s effect during the
course of treatment, an analysis that can be difficult to perform 1. Resnikoff S, Pascolini D, Etya’ale D, et al. Global data on visual
in other disease settings. Here, we will present the relationship impairment in the year 2002. Bull World Health Organ. 2004;
between MIC to moxifloxacin and clinical outcomes (acuity, 82(11):844-850.
scar size, and time to re-epithelialization), while controlling for 2. Whitcher J, Srinivasan M, Upadhyay M. Corneal blindness: a
organism as well as baseline clinical measurements. A higher global perspective. Bull World Health Organ. 2001; 79:214-221.
MIC was significantly associated with poorer outcomes, includ- 3. Bourcier T, Thomas F, Borderie V, Chaumeil C, Laroche L. Bacte-
ing worse acuity (~1 letter per 2-fold dilution in MIC), worse rial keratitis: predisposing factors, clinical and microbiological
scar (0.03 mm larger in diameter), and longer re-epithelialization review of 300 cases. Br J Ophthalmol. 2003; 87:834-838.
(hazard ratio = 0.92). These results indicate that while in vitro
4. Srinivasan M, Gonzales C, George C, et al. Epidemiology and aetio-
susceptibility testing correlates with clinical outcome, MIC itself
logical diagnosis of corneal ulceration in Madurai, South India. Br J
explains only a small portion of the overall variance in outcome Ophthalmol. 1997; 81:965-971.
(estimated with mediation analysis as 13% of total outcome
variance). 5. Varaprasathan G, Miller K, Lietman T, et al. Trends in the etiology
of infectious corneal ulcers at the F.I. Proctor Foundation. Cornea
2004; 23:360-364.
Corticosteroid Use in Bacterial Keratitis 6. Bharathi MJ, Ramakrishnan R, Meenakshi R, Padmavathy S,
The use of topical corticosteroids as adjunctive therapy in the Shivakumar C, Srinivasan M. Microbial keratitis in South India:
treatment of bacterial corneal ulcers has been debated extensively influence of risk factors, climate, and geographical variation. Oph-
thalmic Epidemiol. 2007; 14(2):61-69.
over the past few decades. Corticosteroids are thought to reduce
immune-mediated damage and have been shown to be beneficial 7. Leck A, Thomas P, Hagan M, et al. Aetiology of suppurative cor-
in some systemic bacterial infections.15-17 The American Acad- neal ulcers in Ghana and south India, and epidemiology of fungal
emy of Ophthalmology suggests that while there may be a role keratitis. Br J Ophthalmol. 2002; 86:1211-1215.
2011 Subspecialty Day | Cornea Section II: Infectious Keratitis 27
8. Alexandrakis G, Alfonso E, Miller D. Shifting trends in bacterial 15. Schoeman J, Van Zyl L, Laubscher J, Donald P. Effect of cortico-
keratitis in south Florida and emerging resistance to fluoroquino- steroids on intracranial pressure, computed tomographic findings,
lones. Ophthalmology 2000; 107(8):1497-1502. and clinical outcome in young children with tuberculous meningitis.
Pediatrics 1997; 99(2):226-231.
9. Rex J, Pfaller M. Has antifungal susceptibility testing come of age?
Clin Infect Dis. 2002; 35:982-989. 16. Girgis N, Farid Z, Mikhail I, Farrag I, Sultan Y, Kilpatrick M.
Dexamethasone treatment for bacterial meningitis in children and
10. Weinstein M, Reller L, Murphy J, Lichtenstein K. The clinical sig-
adults. Pediatr Infect Dis J. 1989; 8(12):848-851.
nificance of positive blood cultures: a comprehensive analysis of
500 episodes of bacteremia and fungemia in adults. I. Laboratory 17. Lebel M, Freji B, Syrogiannopoulos G, et al. Dexamethasone ther-
and epidemiologic observations. Rev Infect Dis. 1983; 5(1):35-53. apy for bacterial meningitis. New Engl J Med. 1988; 319:964-971.
11. Baum J, Barza M. The evolution of antibiotic therapy for bacterial 18. American Academy of Ophthalmology Cornea/External Disease
conjunctivitis and keratitis: 1970-2000. Cornea 2000; 19(5):659- Panel. Preferred Practice Pattern Guidelines: Bacterial Keratitis. San
672. Francisco, CA: American Academy of Ophthalmology; 2008.
12. Chen A, Prajna L, Srinivasan M, et al. Does in vitro susceptibility 19. Carmichael T, Gelfand Y, Welsh N. Topical steroids in the treat-
predict clinical outcome in bacterial keratitis? Am J Ophthalmol. ment of central and paracentral corneal ulcers. Br J Ophthalmol.
2008; 145:409-415. 1990; 74:528-531.
13. Kaye S, Tuft S, Neal T, et al. Bacterial susceptibility to topical anti- 20. Srinivasan M, Lalitha P, Mahalakshmi R, et al. Corticosteroids for
microbials and clinical outcome in bacterial keratitis. Invest Oph- bacterial corneal ulcers. Br J Ophthalmol. 2009; 93(2):198-202.
thalmol Vis Sci. 2010; 51(1):362-368.
14. Wilhelmus K. Evaluation and prediction of fluoroquinolone phar-
macodynamics in bacterial keratitis. J Ocul Pharmacol Ther. 2003;
19:493-439.
An Evidence-Based Approach to Managing

Fungal Keratitis
N Venkatesh Prajna MD
Introduction and Magnitude of Fungal Corneal Ulcers The Role of Antifungal Susceptibility on Clinical
Outcome
In some geographic regions, fungus is responsible for as much as
half of all corneal ulcers and the incidence may be increasing.1-4 The role of antifungal susceptibility on clinical outcomes is not
While the incidence of fungal keratitis historically is lower in clear for fungal keratitis. There is some evidence that in systemic
temperate climates,5,6 a recent outbreak of Fusarium keratitis in fungal infections, resistant fungal strains may have worse clinical
the United States and Asia heightened global awareness of fungal outcomes than susceptible strains.10 In ocular fungal infections,
keratitis and underscored the need to find evidence-based treat- reports indicate that minimum inhibitory concentration (MIC)
ment practices for these patients.7 Fungal keratitis frequently may be associated with clinical outcome.11 In a prespecified sec-
leads to poor outcomes, so the need for early, effective treatment ondary analysis of the Mycotic Ulcer Treatment Trial therapeutic
is great. In this presentation, I will discuss the evidence to date exploratory study, we analyzed the association between MIC
for treating fungal keratitis, and where we are going from here. and clinical outcome. We found that a higher MIC was associ-
ated with an increased likelihood of perforation, demonstrat-
ing that resistant strains of fungus lead to poor outcomes. This
Dearth of New Antifungals and Few Randomized,
emphasizes the need the development and study of new antifun-
Controlled Trials
gal strategies.
No new antifungals have been approved for ocular fungal infec-
tions since the approval of natamycin in the 1960s. Voricon-
Gender Differences in Healing Rates for Fungal
azole, a newer triazole, has been shown to have good in vitro
Keratitis
efficacy against certain filamentous fungi8; however, it remains
unclear whether voriconazole is as good as the commercially We also found that there appear to be gender differences in
available natamycin in treating fungal corneal ulcers. To date, re-epithelialization after a fungal corneal ulcer. Women re-epi-
there have been only 2 published, randomized, controlled trials thelialized twice as slowly as men in a model controlling for age,
of antifungal therapy for fungal keratitis.5,9 While the results of baseline epithelial defect size, and treatment arm. There may be
these studies have provided some evidence for best treatment differences in re-epithelialization because of androgens mediating
practices, a larger randomized, controlled trial is needed to pro- the lacrimal and meibomian glands, and recently we have dem-
vide definitive evidence for the best treatment practices for fungal onstrated that there are differences in the tear protein makeup
keratitis. between men and women.12 Gender may play a role in determin-
ing clinical outcomes, and responses to treatment between men
and women may differ. Analyzing clinical responses in men and
Therapeutic Exploratory Study for Mycotic Ulcer
women remains important in the study of fungal keratitis.
Treatment Trial
In 2008, we completed a therapeutic exploratory study for a
Future Directions
larger clinical trial comparing clinical outcomes in patients with
smear-positive fungal keratitis treated with either topical vori- While the number of rigorous studies in fungal keratitis is
conazole or topical natamycin.5 This study was a randomized, increasing, there is a need for larger sample size confirmatory
double-masked, controlled trial, in which 120 patients were clinical trials. We are currently enrolling patients in 2 large
randomized to receive either topical voriconazole or topical National Eye Institute–funded fungal corneal ulcer clinical trials.
natamycin, and to receive repeat scraping or not. The primary The first is comparing topical voriconazole and topical natamy-
outcome was best spectacle-corrected visual acuity at 3 months cin in patients with enrollment visual acuity between 20/40 and
from enrollment. 20/400. 368 patients are being enrolled in this trial. We are cur-
Overall, there was no significant difference in 3-month visual rently more than halfway done with enrollment. The second trial
acuity with topical voriconazole treatment compared to nata- is evaluating the addition of oral voriconazole in the treatment
mycin. In a subanalysis of patients who were able to read some of severe fungal keratitis. These patients have enrollment acu-
letters on the eye chart (acuity between 20/40 and 20/400), there ity of worse than 20/400, and 240 patients are being enrolled in
was a trend toward a 2-line benefit with topical voriconazole. this trial. Patients are randomized to receive topical voriconazole
In addition, there was a trend toward scraping being associated with oral voriconazole, or topical voriconazole with placebo.
with worse clinical outcomes. While it had been thought that Currently we are approximately 25% through with enrollment.
rescraping of the cornea may be beneficial to help penetration of We expect the results of these trials not only to provide definitive
antifungal medications, this trial demonstrated that there does evidence on the use of natamycin and voriconazole, and the use
not seem to be a benefit with rescraping of the cornea in fungal of an oral antifungal agent, but also to provide a large database
keratitis. This trial also provided some preliminary evidence that to answer a host of secondary questions in the treatment and
the use of voriconazole may result in better visual outcomes in a clinical response of fungal keratitis.
subset of patients, but this result must be confirmed in a larger,
confirmatory trial.
References
1. Chowdhary A, Singh K. Spectrum of fungal keratitis in north India. 8. Lalitha P, Shapiro B, Srinivasan M, Prajna N, et al. Antimicrobial
Cornea 2005; 24:8-15. susceptibility of Fusarium, Aspergillus, and other filamentous fungi
isolated from keratitis. Arch Ophthalmol. 2007; 125:789-793.
2. Laspina F, Samudio M, Cibils D, et al. Epidemiological character-
istics of microbiological results on patients with infectious corneal 9. Prajna N, John R, Nirmalan P, Lalitha P, Srinivasan M. A random-
ulcers: a 13-year survey in Paraguay. Graefes Arch Clin Exp Oph- ized clinical trial comparing 2% econazole and 5% natamycin for
thalmol. 2004; 242:204-209. the treatment of fungal keratitis Br J Ophthalmol. 2003; 87:1235-
1237.
3. Leck A, Thomas P, Hagan M, et al. Aetiology of suppurative cor-
neal ulcers in Ghana and south India, and epidemiology of fungal 10. Rex J, Pfaller M. Has antifungal susceptibility testing come of age?
keratitis. Br J Ophthalmol. 2002; 86:1211-1215. Clin Infect Dis. 2002; 35:982-989.
4. Srinivasan M, Gonzales C, George C, et al. Epidemiology and aetio- 11. Shapiro B, Lalitha P, Loh A, Fothergill A, Prajna N, et al. Suscepti-
logical diagnosis of corneal ulceration in Madurai, south India. Br J bility testing and clinical outcome in fungal keratitis. Br J Ophthal-
Ophthalmol. 1997; 81:965-971. mol. 2010; 94(3):384-385.
5. Prajna N, Mascarenhas J, Krishnan T, et al. Comparison of nata- 12. Ananthi S, Santhosh R, Nila M, Prajna N, Lalitha P, Dharmalin-
mycin and voriconazole for the treatment of fungal keratitis. Arch gam K. Comparative proteomics of human male and female tears
Ophthalmol. 2010; 128(6):672-678. by two-dimensional electrophoresis. Exp Eye Res. 2011; 92:454-
463.
6. Varaprasathan G, Miller K, Lietman T, et al. Trends in the etiology
of infectious corneal ulcers at the F.I. Proctor Foundation. Cornea
2004; 23:360-364.
7. Alfonso E, Cantu-Dibildox J, Munir W, et al. Insurgence of Fusar-
ium keratitis associated with contact lens wear. Arch Ophthalmol.
2006; 124:E1-E7.
Corneal Collagen Crosslinking: Does It Have a Role in

Managing Infectious Keratitis?
The Athens Protocol: The Management of Keratoconus and Post-LASIK
Ectasia With Combined, Same-Day Partial Topography-Guided PRK and
Collagen Crosslinking
A John Kanellopoulos MD
Cornea collagen crosslinking (CXL) has been well established to Our theoretical and clinical evidence supports the use of the
halt the progression of ectasia and keratoconus (KCN). A second Athens protocol where CXL and topography-guided surface abla-
procedure for visual rehabilitation may sometimes be needed tion are performed in the same session rather than sequentially.
after CXL for treatment of progressive KCN or post-LASIK ecta- It is our experience that surface ablation using the topogra-
sia. Following many years of employing CXL for ectasia cases, phy-guided excimer laser platform (Allegretto, Alcon/Wave-
we introduced the “Athens Protocol”: same-day topography- Light) effectively and predictably normalizes the corneal surface
guided partial PRK and CXL. and improves functional vision, and we believe there is a syn-
ergistic effect when this procedure is performed simultaneously
with CXL.
Safety with our combination approach has been favorable as
well. Although postoperative haze and delayed epithelial healing
have occurred, these have been minor complications in a small
number of eyes within a very large series.
Figure 1. The basic steps of the Athens Protocol: Upper left, the PTK
treatment plan on the Alcon/WaveLight platform. Upper right, following
PTK, areas of the Bowman have been ablated by PTK, confirming evi-
dence that the epithelium over the cone is thinner. Lower left, The treat- Figure 2. The clinical picture of the O.D. of a 27-year-old male with
ment plan of the topography-guided partial PRK that is the core concept advanced KCN. His preop BSCVA was 20/50 with -2.5, 5 @ 80. He
of this platform. Lower right, MMC application prior to the riboflavin underwent the Athens Protocol and his UCVA is now 20/30; BSCVA is
and CXL. 20/20 with -1, -1.5 @ 85. The slitlamp photo shows the cornea clarity
and the ground-glass appearance typical of CXL.
Our scientific findings support the conclusion that simultane-

ous topography-guided partial PRK with CXL offers a safe and
effective approach for normalizing the cornea and enhancing
visual function in eyes with ectatic conditions. The core impor-
tance of combining CXL in this technique is that it addresses
highly irregular astigmatism in the management of eyes with
keratoconus and post-LASIK ectasia.
Meeting Visual Rehabilitation Needs Results from a comparison of two large, consecutive series of
eyes treated at the same session or with CXL first followed 1 year
later by a topography-guided surface ablation showed statisti-
cally significant differences in a number of outcome parameters
favoring the same day procedure. The study, which has been
published (J Refract Surg. 2009; 25:S812-818), included 127
eyes in the sequential group and 198 eyes treated with the Athens
Protocol.
Figure 3. Cornea OCT of the same eye 7 months following the Athens
Protocol. One can appreciate the anterior cornea hyper-reflectivity con-
sistent with CXL and the demarcation line at about 300 microns depth
depicting (as we have introduced and published) the depth of effective
CXL. Those clinicians familiar with these findings following CXL alone
they may appreciate the enhanced depth and diameter of the CXL effect
noted on OCT, supporting the advantage of the Athens Protocol.
Although the efficacy of CXL for stabilizing keratectasia is well

established and the procedure also causes some corneal flatten-
ing, significant residual astigmatism limiting contact lens wear
may be a persistent problem for some patients. This situation
creates an indication to perform the topography-guided partial Figure 4. Pentacam comparison of preop with 7-month postop, showing
PRK. The ablation removes no more than 50 microns of stroma the significant normalization of the cone, keratometric flattening, and
and at most treats 2 to 2.5 D of astigmatism and up to 1 D of better symmetry.
myopia.
The protocol begins with a 6.5-mm phototherapeutic kera- CASE
tectomy (PTK) to remove 50 microns of epithelium. Then,
the topography-guided partial PRK is performed, followed by
mitomycin C application (0.02% for 20 seconds) and the CXL A 57-year-old man had severe corneal blindness from scarring
procedure. The excimer laser ablation resembles part of a hyper- at the age of 12 following firework explosion. Uncorrected
opic treatment. It is performed using a 5.5-mm effective optical distance visual acuity (UDVA) was 20/400 O.U. in 2009; pin-
zone and targets steepening of the area adjacent to the cone in an hole to 20/100 in the right and 20/70 in the left. There was no
attempt to regularize the corneal surface. improvement to his visual function with spectacle refraction or
In discussing our rationale for performing the two procedures soft contact lenses, and there was intolerance to gas-permeable
simultaneously with the ablation first, we have reported data contact lenses. There was no possible endothelial cell count in the
showing that the corneal epithelium and Bowman membrane can right and 2000 cells/mm2 in the left eye. Slitlamp biomicroscopy
act as barriers to UVA light penetration into the stroma. As these revealed a severe horizontal central corneal scar O.U. Dilated
tissues are removed with the PTK/PRK procedure, it seems intui- fundus examination revealed no cataract, normal disc, macula
tive that the efficacy of the CXL procedure would be increased. and retina vessels.
This concept is supported by clinical findings. CDVA was 20/100 O.U. with refraction: +4.00, -4.50 @ 135
For example, in a patient who had CXL alone in one eye and O.D. and O.S: +3.50, -1.00 @ 55. Respective keratometries were
the Athens protocol in the other, inspection of OCT maps for 42.3, 60.4 @ 17 and 35.8, 39.1 @ 151.3.
hyper-reflectivity, which we recently described as a sign of the Tomographic evaluation (Oculyzer II, WaveLight, Erlagen,
extent of crosslinking, shows the area of crosslinking is much Germany) showed thinnest pachymetry of 467 μm and 448 μm
broader and denser in the latter eye. O.D. and O.S., respectively. Considering the options of lamel-
We additionally introduced the theory that the PRK-treated lar and penetrating keratoplasty, we discussed and employed
eye represents a better biomechanical model for performing the the Athens Protocol (combined topography-guided partial PRK
CXL procedure. In theory, an eye with a more regularized sur- and CXL) O.D. in February 2010 and O.S. in September 2010.
face as opposed to one where there is ongoing strain from IOP We have previously reported on this technique1-5 for the man-
and eye rubbing localized over the cone peak would be better agement of cornea ectasia. The treatment plan—pivotal to the
strengthened by CXL and more likely to remain stable after the application of the Athens Protocol—combines a myopic abla-
procedure. tion over the elevated cornea and a partial hyperopic applica-
We believe redistribution of corneal strain by remodeling tion peripheral to the flattened-by-scarring inferior cornea. This
the cornea with the surface ablation is a significant factor in the combination treatment enhances the normalization of the severe
synergistic effect achieved when performing the two procedures irregularity with small ablation (35 μm) over the thinnest cornea.
together. The simultaneous procedure also avoids removing Fifteen months after the O.D. treatment, the cornea had cleared
crosslinked cornea, which occurs when performing CXL first fol- and was topographically stable, with UDVA 20/50 and CDVA
lowed by the laser treatment. 20/40 and refraction +0.50, -2.00 @ 5. We noted a similar out-
come 8 months after the O.S. treatment, with UDVA 20/50 and
CDVA 20/40, -0.50, -2.00 @ 170.
Patient’s tomographic keratometry O.D. has improved to References

44.3, 59.0 @ 13.7 and O.S., 35.4, 38.4 @ 166.3 O.S. Endothelial
1. Kanellopoulos AJ, Skouteris VS. Secondary ectasia due to forceps
cell counts are 1600 cells/mm2 and 2010 cells/mm2, respectively. injury at childbirth. management with combined topography-
The patient has recently obtained a driver’s license and has guided partial PRK and collagen cross-linking (the Athens Pro-
assumed a more independent lifestyle. tocol), followed by the implantation of a phakic intraocular lens
In this particular patient, the therapeutic aim of the topogra- (IOL). J Refract Surg. 2011. In print.
phy-guided PRK was to normalize the corneal surface, and the 2. Kanellopoulos AJ, Binder PS. Management of corneal ectasia after
employment of the CXL was two-fold: to reduce corneal scarring LASIK with combined, same-day, topography-guided partial tran-
by eliminating keratocytes and to stabilize the thinner cornea sepithelial PRK and collagen cross-linking: the Athens Protocol.
produced by the removal of corneal tissue with the therapeutic J Refract Surg. 2011; 27(5):323-331.
topography-guided ablation. 3. Kruger RR, Kanellopoulos AJ. Stability of simultaneous topogra-
We feel that the introduction of this successful management phy-guided photorefractive keratectomy and riboflavin/UVA cross-
of severe corneal abnormalities and scarring with the Athens linking for progressive keratoconus: case reports. J Refract Surg.
Protocol may provide an effective alternative to other surgical or 2010; 26(10):S827-832.
medical options. 4. Kanellopoulos AJ. Comparison of sequential vs same-day simulta-
neous collagen cross-linking and topography-guided PRK for treat-
ment of keratoconus. J Refract Surg. 2009; 25(9):S812-818.
5. Kanellopoulos AJ, Binder PS. Collagen cross-linking (CCL) with
sequential topography-guided PRK: a temporizing alternative for
keratoconus to penetrating keratoplasty. Cornea 2007; 26(7):891-
895.
LEGEND, Figure 1.
Image A: Slit lamp of the OD at presentation,
showing the significant horizontal cornea scar.
Image B: Slit lamp picture of the OS. The cor-
nea scar similar to the OS.
Image C: The treatment plan on the Wave-
light excimer platform for topography-guided
partial PRK employed for the OD treatment.
The treatment plan—pivotal to the application
of the Athens Protocol—combines a myopic
ablation over the elevated cornea and a partial
hyperopic application peripheral to the flat-
tened by scarring inferior cornea. This combi-
nation treatment enhances the normalization
of the severe irregularity with small ablation
(35um) over the thinnest cornea.
Image D: Tomography maps (Oculyzer, Wave-
light, Erlagen, Germany) of the OD and OS
pre-operative to the Athens Protocol.
Image E: Tomography maps of the OD and
OS post-operative to the Athens Protocol. 15
months following the OD and 8 months fol-
lowing the OS
Image F: Slit lamp Picture of the OD, 15
months following treatment, cornea regularity
and improvement in translucency is evident
(when compared to Image A).
Image G: Slit lamp Picture of the OS, 8 months
following treatment, cornea regularity and
improvement in translucency is evident (when
compared to image B).
Image H: The treatment plan on the Wavelight
excimer platform employed for topography-
guided partial PRK of the OS.
Now That We Have Topical Ganciclovir, What Is the

Role of Oral Antivirals?
Todd P Margolis MD PhD
Since the days of the ancient Egyptians, corneal epithelial (400 mg PO b.i.d.) reduced overall recurrence rates of ocular
debridement has been used as a treatment option for herpes sim- HSV by about 50%. Many clinicians have noted even lower
plex virus (HSV) epithelial keratitis. Whereas the average heal- recurrence rates when patients were treated prophylactically
ing time of an untreated HSV epithelial dendrite is 9-10 days, with higher doses of antivirals, and a recent retrospective study
treatment with debridement and patching reduces healing time carried out by the Mayo Clinic reported an 85%-95% reduction
to 2.5 days. in ocular HSV in patients receiving oral antiviral prophylaxis
Several thousand years later, topical antivirals were intro- (varying drugs and doses). Generic forms of oral acyclovir, vala-
duced for the treatment of HSV epithelial keratitis. The first of cyclovir, and famciclovir are all widely available. All 3 of these
these antivirals was idoxuridine, followed by vidarabine, tri- drugs are easy to take, have a long shelf life, and are extremely
fluorothymidine, acyclovir, and most recently ganciclovir. The well tolerated, even when taken for years. After oral administra-
healing time of HSV epithelial keratitis treated with any of these tion all 3 drugs also reach therapeutic levels in the tear film and
topical antivirals is about 7 days. Over the years these agents aqueous.
have also been widely used by ophthalmologists as part of thera- At this point topical ganciclovir has been approved by the
peutic regimens for the treatment of HSV stromal disease and FDA for the treatment of HSV epithelial keratitis, and the clini-
iritis, but their role in the management of these immunologically cal data suggest that it is non-inferior to topical acyclovir in
mediated diseases is not completely clear, and they are gener- the treatment of this form of HSV ocular disease. There is no
ally used as prophylaxis against recurrent infectious epithelial published evidence at this time that topical ganciclovir is effec-
disease in the face of treatment of the immunological disease tive for the treatment of HSV stromal keratitis or iritis, or for
with topical corticosteroids. Over the years these antiviral agents the prophylaxis of recurrent ocular disease. Topical ganciclovir
have also been widely used by ophthalmologists for prophylaxis is more expensive than oral antiviral medications. It is preserved
against recurrent infectious epithelial keratitis when treating with benzalkonium chloride, and anecdotal reports note that it
HSV stromal keratitis and iritis (immune-mediated diseases) is better tolerated than trifluorothymidine, which is preserved
with a topical corticosteroid. with thimerosal. Sixty percent of patients using topical ganciclo-
Despite the introduction of topical antivirals in the 1970s, vir report blurred vision, 20% report irritation, and 5% develop
the rates of corneal transplantation for HSV keratitis remained punctate keratitis. At this point in time topical ganciclovir is a
high until the 1990s, corresponding with the increased use of reasonable alternative to the use of trifluorothymidine or oral
oral acyclovir in the management of HSV ocular disease. The acyclovir for the treatment of HSV epithelial keratitis. However,
average healing time of HSV epithelial keratitis treated with topical ganciclovir is significantly more expensive than oral
oral acyclovir is also about 7 days. And in a landmark study antivirals, and patients have more rapid healing times following
published in the New England Journal of Medicine as part of the corneal debridement.
HEDS, investigators demonstrated that acyclovir prophylaxis
Perioperative Antibiotics: Looking for a Consensus

Amid the Chaos
Prophylaxis for Intraocular Surgery
Francis S Mah MD
Prophylactic strategies for intraocular surgery include using topi- use of a 5% solution of povidone iodine in the conjunctival cul-
cal antibiotic eye drops before surgery, applying 5% povidone de-sac to prevent infection. Given the absence of clear evidence
iodine solution to the conjunctival cul-de-sac, preparing the peri- about the benefit of other prophylactic measures, the Academy
ocular skin with 10% povidone iodine scrub, careful sterile drap- also notes that it is up to the ophthalmologist to decide on the
ing of the eyelid margins and eyelashes, adding antibiotics to the use of any particular strategy in addition to povidone iodine in
irrigating solution, injecting intracameral antibiotics at the close the perioperative period.12
of surgery, injecting subconjunctival antibiotics, collagen shield Evidence-based recommendations and a review of the litera-
mediated antibiotic delivery, and applying topical antibiotic eye ture will be presented to allow participants all of the information
drops after surgery. A nonrandomized, controlled trial provided needed to develop reasonable strategies for prophylaxis.
evidence that using topical 5% povidone iodine solution in the
conjunctival cul-de-sac reduces the incidence of postoperative
References
infection.1,2
Lower concentrations of povidone iodine are less effective in 1. Ciulla TA, Starr MB, Masket S. Bacterial endophthalmitis prophy-
reducing conjunctival bacterial colony counts.3 Systemic anti- laxis for cataract surgery: an evidence-based update. Ophthalmol-
biotics are rarely used; however, it has been shown that certain ogy 2002; 109:13-24.
fluoroquinolone antibiotics penetrate the blood/ocular barrier
2. Speaker MG, Menikoff JA. Prophylaxis of endophthalmitis with
adequately to reach levels above the minimum inhibitory concen-
topical povidone-iodine. Ophthalmology 1991; 98:1769-1775.
trations for many organisms inside the eye.4-6
Although still controversial in the United States, there is some 3. Ferguson AW, Scott JA, McGavigan J, et al. Comparison of 5%
evidence that supports the use of intraocular antibiotics to reduce povidone-iodine solution against 1% povidone-iodine solution in
the risk of endophthalmitis. The European Society of Cataract preoperative cataract surgery antisepsis: a prospective randomised
double blind study. Br J Ophthalmol. 2003; 87:163-167.
and Refractive Surgeons (ESCRS) study,7 a partially masked,
randomized, placebo-controlled multinational trial of the pro- 4. Hariprasad SM, Shah GK, Mieler WF, et al. Vitreous and aqueous
phylactic effect of intracameral cefuroxime injection at the con- penetration of orally administered moxifloxacin in humans. Arch
clusion of the procedure and/or perioperative levofloxacin eye Ophthalmol. 2006; 124:178-182.
drops on the incidence of endophthalmitis after phacoemulsifica- 5. Kampougeris G, Antoniadou A, Kavouklis E, et al. Penetration of
tion, was halted early because of results of a beneficial effect of moxifloxacin into the human aqueous humour after oral adminis-
intracameral cefuroxime. With data from 13,698 patients with tration. Br J Ophthalmol. 2005; 89:628-631.
complete follow-up records, investigators found that the odds 6. Garcia-Saenz MC, Arias-Puente A, Fresnadillo-Martinez MJ,
ratio for developing endophthalmitis was 4.59 (95% CI, 1.74- Carrasco-Font C. Human aqueous humor levels of oral ciprofloxa-
12.08; P = .002) in the group not receiving intracameral injection cin, levofloxacin, and moxifloxacin. J Cataract Refract Surg. 2001;
of cefuroxime, a second-generation cephalosporin. However, the 27:1969-1974.
incidence of endophthalmitis in the control group was approxi- 7. Barry P, Seal DV, Gettinby G, et al. ESCRS study of prophylaxis of
mately 3 times higher than that reported in most other studies postoperative endophthalmitis after cataract surgery: preliminary
from U.S. centers. This raises the question of whether the results report of principal results from a European multicenter study.
can be generalized to a U.S. population. It is important to note J Cataract Refract Surg. 2006; 32:407-410.
that in the ESCRS prophylaxis study, all patients received pre-
8. Montan PG, Wejde G, Koranyi G, Rylander M. Prophylactic intra-
operative povidone-iodine 5% solution in the conjunctival cul- cameral cefuroxime: efficacy in preventing endophthalmitis after
de-sac, and a postoperative topical fluoroquinolone started 18 cataract surgery. J Cataract Refract Surg. 2002; 28:977-981.
hours following the conclusion of surgery. It was felt that these
two maneuvers were standard of care surrounding cataract sur- 9. Garat M, Moser CL, Alonso-Tarres C, et al. Intracameral cefazolin
to prevent endophthalmitis in cataract surgery: 3-year retrospective
gery. An earlier retrospective study in Sweden reported efficacy
study. J Cataract Refract Surg. 2005; 31:2230-2234.
of intracameral cefuroxime in reducing postcataract endophthal-
mitis.8 Two retrospective studies in Spain have reported that 10. Romero P, Mendez I, Salvat M, et al. Intracameral cefazolin as
intracameral injection of cefazolin, a first-generation cephalospo- prophylaxis against endophthalmitis in cataract surgery. J Cataract
rin, reduced postcataract endophthalmitis.9,10 Refract Surg. 2006; 32:438-441.
Evidence of the benefit of injecting subconjunctival antibiotics 11. Brown GC, Eagle RC, Shakin EP, et al. Retinal toxicity of intravit-
at the close of surgery is inconclusive and is associated with risks real gentamicin. Arch Ophthalmol. 1990; 108:1740-1744.
that include intraocular toxicity with the potential for macular 12. American Academy of Ophthalmology. Cataract in the Adult Eye,
infarction if aminoglycosides are used and inadvertently injected Preferred Practice Pattern. San Francisco: American Academy of
into the eye.11 In the Cataract in the Adult Eye Preferred Practice Ophthalmology, 2006. Available at: www.aao.org/ppp. Accessed
Pattern, the America Academy of Ophthalmology recommends May 20, 2009
2011 Subspecialty Day | Cornea Section III: Corneal Transplantation — Lamellar Keratoplasty 35
A Decade of Endothelial Keratoplasty: What Has the

Literature Taught Us?
Mark A Terry MD
I. Endothelial keratoplasty (EK) has now replaced pen- 3. Bubble size, bubble time, IOP pressure: Common
etrating keratoplasty (PK) as the standard of care for practice prejudices, but there is nothing in litera-
endothelial dysfunction.1 ture to support one method over another.
A. Eye Bank Association of America 2010 statistical B. Iatrogenic primary graft failure11-14
report shows EK to represent 45% of all transplants
1. Minimize endothelial trauma by minimizing
performed in the United States.
donor manipulations.
B. Most common indication for EK in the United
2. Use larger diameter wounds for insertion or use
States is Fuchs dystrophy.
tissue inserter.
C. EK can be performed in cases of pseudophakic
C. Pupillary block glaucoma
bullous keratopathy, ABK, congenital hereditary
endothelial dystrophy, iridocorneal endothelial 1. Leave a small, freely mobile air bubble in eye at
syndrome, and in the presence of anterior chamber end of surgery: Lowest rate of pupillary block,
lenses, tubes, trabeculectomy blebs, etc. highest rate of donor attachment.3,4
II. Established Benefits of EK2-5 2. Place an inferior peripheral iridectomy/iri-
dotomy: Not always effective15 and can result in
A. Better quality of vision than PK: Less aberrations,
bleeding.
smoother surface
D. Eccentric donor trephination16,17
B. Astigmatically neutral when a scleral incision is used
1. Can result in primary graft failure (PGF) and epi-
C. Induced refractive hyperopic shift that averages 1.0
thelial ingrowth to interface
to 1.5 D—likely primarily from posterior curvature
changes of the hourglass donor 2. Completely avoided by using the microscope to
trephinate donor tissue; never use the naked eye
D. Stronger eye with substantial resistance to postop-
to assess edge clearance within a tolerance of
erative trauma
only 0.25 mm.
E. More predictable “triple procedure” than PK
V. Methods of Insertion: Benefits and Risks
III. Most Common Complications of EK4
A. Forceps insertion with “taco” folding: Most estab-
A. Dislocation: Rates from 1% to 82% reported in lit- lished method, most surgeon dependent3,4,7
erature.
B. Busin glide pull through: Popular but sparse litera-
B. Iatrogenic primary graft failure: Rates from 0% to ture data; appears similar to forceps insertion by
29% reported in literature. experienced surgeons18
C. Pupillary block glaucoma: Rates from 0.1% to C. Cartridge loaded pull through: Appears comparable
9.5% reported in literature. to forceps19
D. Eccentric donor trephination: Rates from 0% to D. All others (sheets glide push in, Healon on sclera, or
10% reported. sheets glide push in, pull in, etc.): No literature on
complication rates or endothelial survival20,21
IV. Methods of Avoiding Dislocation and other Complica-
tions6: Benefits and Risks E. Tissue inserters (see below)
A. Dislocation VI. Endothelial Survival After EK3,4,14,8,21-23
1. Minimize endothelial trauma by minimizing A. Worse than PK at 1 year; better than PK at 5 years
donor manipulations
B. Technique dependent: Smaller incisions for insertion
2. Evacuate interface fluid cause more endothelial damage, higher dislocation
rates, and higher PGF rates.14,22,23
a. Surface sweeping with IOP increased with air
filling chamber: Fully effective but epithelial VII. Donor Tissue: “Common knowledge” is often wrong,
damage can occur.7 and the truth is . . .
b. “Venting” full-thickness corneal incisions: A. Higher preoperative endothelial cell counts of a
Effective, but eye is put at risk for postop- donor do not yield higher postoperative cell counts
erative epithelial ingrowth and infections in and do not protect against dislocation or primary
interface, and late corneal melting.8-10 graft failure.24
36 Section III: Corneal Transplantation — Lamellar Keratoplasty 2011 Subspecialty Day | Cornea
B. Larger diameter donor discs that theoretically trans- 8. Price MO, Price FW. Endothelial cell loss after Descemet stripping
plant more total endothelial cells do not result in with endothelial keratoplasty: influencing factors and 2 year trend.
higher postoperative cell counts and do not protect Ophthalmology 2008; 115:857-865.
against dislocation or primary graft failure.25 9. Bansal R, Ramasubramanian A, Das P, Sukhija J, Jain AK. Intra-
corneal epithelial ingrowth after Descemet stripping endothelial
C. Longer storage time of donor tissue does not result
keratoplasty and stromal puncture. Cornea 2009; 28(3):334-337.
in worse postoperative cell counts and does not
increase dislocation or PFG rates.26 10. Hannush SB, Chew HF, Eagle RC. Late-onset deep infectious kera-
titis after Descemet stripping endothelial keratoplasty with vent
D. The thickness of the donor tissue does not influence incisions. Cornea 2011; 30:229-232.
the postoperative visual acuity level: thinner Des-
11. Terry MA, Shamie N, Chen ES, Phillips PM, Hoar KL, Friend DJ.
cemet-stripping automated endothelial keratoplasty Pre-cut tissue for Descemet’s stripping endothelial keratoplasty:
(DSAEK) grafts do not yield better vision than vision, astigmatism, and endothelial survival. Ophthalmology
thicker grafts.27,28 2009; 116:248-256.
VIII. DSAEK Tissue Inserters: Very Little Data Currently 12. O’Brien PD, Lake DB, Saw VP, Rostron CK, Dart JK, Allan BD.
Available in Literature29 Endothelial keratoplasty: case selection in the learning curve. Cor-
nea 2008; 27:1114-1118.
A. Platform inserters: NCI and Endoserter
13. Suh LH, Yoo SH, Deobhakta A, et al. Complications of Descemet’s
B. Glide inserters: Tan endoglide stripping with automated endothelial keratoplasty: survey of 118
eyes at one institute. Ophthalmology 2008; 115:1517-1524.
C. Cartridge inserter: InJEk technique
14. Foster JB, Vasan R, Walter KA. Three-millimeter incision Des-
IX. Descemet-Membrane Endothelial Keratoplasty cemet stripping endothelial keratoplasty using sodium hyaluronate
(DMEK) and Descemet Membrane Automated (Healon): a survey of 105 eyes. Cornea 2011; 30:150-153.
Endothelial Keratoplasty (DMAEK)30-32
15. Koenig SB, Covert DJ. Early results of small-incision Descemet’s
A. Better (and faster) visual acuities postop than stripping and automated endothelial keratoplasty. Ophthalmology
DSAEK 2007; 114:221-226.
B. Steep learning curve 16. Oster SF, Ebrahimi KB, Eberhart CG, Schein OD, Stark WJ, Jun
AS. A clinicopathologic series of primary graft failure after Des-
C. Higher rate of re-bubbling: 25% (DMAEK) to cemet’s stripping and automated endothelial keratoplasty. Ophthal-
60% (DMEK) in U.S. studies (5% in Melles’ recent mology 2009; 116:609-614.
DMEK series) 17. Terry MA, Shamie N. Avoiding eccentric trephination [letter]. Oph-
D. Higher rate of primary graft failure: 5% to 8% thalmology 2009; 116:2481-2482.
E. Higher rate of tissue wastage: 5% to 16% 18. Busin M, Bhatt PR, Scorcia V. A modified technique for Descemet
membrane stripping automated endothelial keratoplasty to mini-
mize endothelial cell loss. Arch Ophthalmol. 2008; 126:1133-1137.
References 19. Kaiserman I, Bahar I, McAllum P, Slomovic AR, Rootman DS.
Suture-assisted vs forceps-assisted insertion of the donor lenticula
1. Medical Advisory Board, eds. Annual Statistical Report of the during Descemet stripping automated endothelial keratoplasty. Am
EBAA. Washington, DC: Eye Bank Association of America; 2010. J Ophthalmol. 2008; 145:986-990.
2. Terry MA. Endothelial keratoplasty: clinical outcomes in the two 20. Balachandran C, Ham L, Birbal RS, Wong TH, van der Wees J,
years following deep lamellar endothelial keratoplasty (an Ameri- Melles GR. Simple technique for graft insertion in Descemet-strip-
can Ophthalmological Society thesis). Trans Am Ophthalmol Soc. ping (automated) endothelial keratoplasty using a 30-gauge needle.
2007; 105: 530-563. J Cataract Refract Surg. 2009; 35(4):625-628.
3. Terry MA, Shamie N, Chen ES, et al. Endothelial keratoplasty for 21. Price MO, Fairchild KM, Price DA, Price FW. Descemet’s stripping
Fuchs’ dystrophy with cataract: complications and clinical results endothelial keratoplasty: five year graft survival and endothelial cell
with the new triple procedure. Ophthalmology 2009; 116:631-639. loss. Ophthalmology 2011; 118(4):725-729.
4. Lee WB, Jacobs DS, Musch DC, Kaufman SC, Reinhart WJ, Shtein 22. Terry MA, Saad HA, Shamie N, et al. Endothelial keratoplasty: the
RM. Descemet’s stripping endothelial keratoplasty: safety and influence of insertion techniques and incision size on donor endo-
outcomes—a report by the American Academy of Ophthalmology. thelial survival. Cornea 2009; 28:24-31.
Ophthalmology 2009; 116:1818-1830.
23. Price MO, Bidros M, Gorovoy M, et al. Effect of incision width
5. Jun B, Kuo AN, Afshari NA, Carlson AN, Kim T. Refractive on graft survival and endothelial cell loss after Descemet stripping
change after Descemet stripping automated endothelial keratoplasty automated endothelial keratoplasty. Cornea 2010; 29:523-527.
surgery and its correlation with graft thickness and diameter. Cor-
nea 2009; 28(1):19-23. 24. Terry MA, Shamie N, Chen ES, Hoar KL, Phillips PM, Friend DJ.
Endothelial keratoplasty: the influence of pre-operative donor
6. Terry MA. Ten tips for successful DSAEK surgery. Tech Ophthal- endothelial densities on dislocations, primary graft failure, and one
mol. 2011; 9(1):10-14. year cell counts. Cornea 2008; 27:1131-1137.
7. Terry MA, Shamie N, Chen ES, Hoar KL, Friend DF. Endothelial 25. Terry MA, Li J, Goshe J, Davis-Boozer D. Endothelial keratoplasty:
keratoplasty: a simplified technique to minimize graft dislocation, the relationship between donor tissue size and donor endothelial
iatrogenic graft failure and pupillary block. Ophthalmology 2008; survival. Ophthalmology. Epub before print 6 Jun 2011.
115:1179-1186.
26. Terry MA, Shamie N, Straiko MD, Friend DJ, Davis-Boozer D.
Endothelial keratoplasty: the relationship between donor tissue
storage time and donor endothelial survival. Ophthalmology 2011;

118:36-40.
27. Ahmed KA, McLaren JW, Baratz KH, et al. Host and graft thick-
ness after Descemet stripping endothelial keratoplasty for Fuchs’
endothelial dystrophy. Am J Ophthalmol. 2010; 150:490-497.
28. Nieuwendaal CP, van Velthoven ME, Biallosterski C, et al. Thick-
ness measurements of donor posterior disks after Descemet strip-
ping endothelial keratoplasty with anterior segment optical coher-
ence tomography. Cornea 2009; 28:298-303.
29. Foster JB, Swan KR, Vasan RA, Greven MA, Walter KA. Small
incision DSAEK: a comparison of a small incision tissue injector
and forcep techniques. Cornea. In press.
30. Price MO, Giebel AW, Fairchild KM, Price FW. Descemet’s mem-
brane endothelial keratoplasty: prospective multi-center study of
visual and refractive outcomes and endothelial survival. Ophthal-
mology 2009; 116:2361-2368.
31. Ham L, Dapena I, van der Wees J, Melles GRJ. Endothelial cell
density after Descemet membrane endothelial keratoplasty: 1- to
3-year follow-up. Am J Ophthalmol. 2010; 149(6):1016-1017.
32. McCauley MB, Price MO, Fairchild KM, Price DA, Price FW Jr.
Prospective study of visual outcomes and endothelial survival with
Descemet membrane automated endothelial keratoplasty. Cornea
2011; 30(3):315-319.
Ten Tips to Avoid Trouble When Transitioning to

Descemet-Stripping Endothelial Keratoplasty
Friedrich E Kruse MD FEBO, Björn Bachmann MD FEBO, Kathrin Laaser MD FEBO,
Ursula Schlötzer-Schrehardt PhD, Claus Cursiefen MD FEBO
1. Select an appropriate patient. graft, it seems to be best to start with DASEK. This technique
is in widespread use and offers the advantage of an established
Patient selection is of utmost importance for all variants of
surgery with a step-wise surgical approach and renders excellent
Descemet-stripping endothelial keratoplasty. The success of the
visual results.
procedure is largely dependent on the amount of endothelial cells
Removal of the Descemet membrane, which might not be
that are lost during insertion, unfolding, and attachment of the
necessary in all cases, may be performed under fluid or viscoelas-
graft. Endothelial loss is dependent on the ease of the manipula-
tic, however the use of air facilitates the visualization of small
tion of the donor tissue in the anterior chamber, which is influ-
remnants of Descemet membrane and therefore aids complete
enced by two factors: the dimensions of the anterior chamber
removal of donor tissue.
and the pressure in the eye during surgery (vis a tergo). While a
Donor preparation should be performed by use of a micro-
soft eye is easiest to maintain during general surgery, the dimen-
keratome whenever possible because of the optical properties of
sions of the anterior chamber need to be taken into account dur-
the resultant graft lenticule. Price and co-workers have shown
ing patient selection:
that the use of manually dissected grafts can also render excellent
The beginning surgeon should seek to operate patients with:
visual results and that the use of precut tissue might be superior
• Deep anterior chamber to the use of manually dissected grafts.2 The use of precut tissue
• Emetropia or myopia is suggested for the beginning surgeon because it eliminates tech-
• Pseudophakia (with uneventful history) nical problems associated with microkeratome handling as well
• Normal or slightly larger corneal diameter as investment in costly equipment.
The beginning surgeon should not operate on patients with:
4. Select an appropriate injection technique for
• Shallow anterior chamber
DSAEK grafts.
• Significant hyperopia
• Thick crystalline lens In all forms of posterior lamellar surgery, the endothelial cell loss
during surgery is largely determined by the insertion technique.
Furthermore, all situations that impair the stability of the
In DSAEK there are 3 types of insertion techniques:
iris diaphragm should be avoided initially because the use of air
bubbles required for unfolding the graft is greatly impaired in 1. Forceps: Folding the graft like a “taco” with 60/40 over-
situations such as: fold, trifold, 40/60 underfold
2. Glides: Busin glide, Sheets glide, Tan Endoglide
• Aphacia
3. Inserters: Mechanical, closed chamber injector systems
• Status post vitrectomy
with a variety of mechanisms
• Large iris defects
Although the use of the taco technique may render excellent
Since the ease of the removal of the patient’s Descemet mem-
results in the hands of a very experienced surgeon, it is generally
brane depends on the underlying pathology, we would suggest
agreed that the use of a glide or a inserter reduces endothelial
to start with patients with Fuchs dystrophy before moving to
cell loss.3 For the beginning surgeon the use of a glide is highly
patients with pseudophakic bullous keratopathy and finally to
recommended: both the Busin glide4 and the Tan Endoglide,5 as
patients with keratopathy after 5-fluorouracil treatment or graft
well as other devices on the market, may be used with very good
dysfunction due to endothelial decompensation.
success.
2. Select appropriate donor.

5. Convert to Descemet membrane endothelial
Experience with DSAEK has shown that both tissue from cold keratoplasty (DMEK) or ultrathin DSAEK.
storage (4°C) and organ culture can be used and that younger
Although results with DSAEK are very good and tend to improve
donors may have an advantage because of higher cell counts.
over time, DMEK, developed by Melles, renders still better visual
In DMEK donors under 60 years of age have proven to be not
acuity, which might be due to the unsurpassed quality of the pos-
suitable because of the increased elasticity of the Descemet mem-
terior corneal surface resulting from this technique.1,6 Similarly,
brane. Thus Descemet membranes from younger donors are dif-
ultrathin DSAEK using donor tissue of less than 100 µm thick-
ficult to unroll. In addition organ-cultured donor tissue seems to
ness renders favorable results. Until now problems with donor
have a slight advantage concerning graft adhesion.
preparation leading to tissue loss, problems manipulating the iso-
lated Descemet membrane, and a lack of standardization of the
3. Gain initial experience with Descemet-stripping procedure, as well as the need for rebubbling, have precluded the
automated endothelial keratoplasty (DSAEK). widespread use of this technique. We will therefore offer 4 steps
to avoid trouble with DMEK:
To gain experience with removal of the recipient’s Descemet
membrane as well as insertion and manipulation of a lamellar
6. Donor Preparation for DMEK With Minimal

Tissue Loss
In contrast to DSAEK, where preparation is based on a micro-
keratome cut, preparation of Descemet membrane in DMEK
does not require special instrumentation. The fundamental
problem is to gain access to the margin of the membrane and to
remove it without creating tears. The latter problem is addressed
by the recent development of a 2-forceps approach, which
reduces the tension exerted on a particular stretch of Descemet
membrane while pulling it apart from the underlying stoma.7
Also the surgeon or eye bank technician has to apply the same
principles as during capsulorrhexis by creating an outer margin
of the membrane that is free of tears. The principle of this tech-
nique is explained in a recent publication in the journal Cornea.7
The reader is referred to this article for details of preparation as
well as practical hints. In essence the technique consists of the
following steps:
• Removal of a small, curvilinear strip of Descemet mem-
brane in the periphery of the corneoscleral button by very
careful use of a razor blade, which is used to drag Des- Figure 1.
cemet membrane rather than to cut it
• Lifting the central edge of Descemet membrane by careful
undermining with round blade 9. Control donor unfolding and attachment in DMEK.
• Subtotal removal of Descemet membrane by simultaneous Unfolding of Descemet membrane in the anterior chamber
pulling with two forceps (The use of two forceps reduces proves to be the most critical step in DMEK. Prolonged manipu-
tension on the margin.) lation in the anterior chamber leads to loss of endothelial cells.
• Trephination with a 8-mm trephine According to our experience,7 unfolding of the graft is made
• Staining with Trypan blue and complete removal relatively easy by using a small air bubble inside the Descemet
In our hands this technique enabled the successful removal of roll. In conjunction with the maneuver of controlled graft inser-
392 of 400 preparations. In 1%-2% of donor corneal buttons, tion, the roll can be delivered into the anterior chamber with the
central invaginations of Descemet membrane preclude complete air bubble already inside the roll. Thus the surgeon should aim at
removal (see Tip #8 for further details of the anatomy of the injecting the roll in the right direction with an air bubble already
cleavage plane). in place. Unfolding of the graft is achieved by lateral movement
of the air bubble and simultaneous enlargement of the bubble.
When the graft is unfolded and centered, the bubble is removed
7. Control graft orientation in DMEK. while the anterior chamber becomes shallow. Now a bubble is
Upon release from the corneal stroma, the Descemet membrane placed underneath the graft and the anterior chamber is filled
forms a roll with endothelial cells on the outside. Trypan blue with air. We recommend filling the anterior chamber with air for
applied to the isolated roll for 1 minute can help to visualize the 60 minutes and removing 50% of the air at the end of the first
roll in the anterior chamber. However, a surgeon who is tran- hour.
sitioning to endothelial keratoplasty might have difficulties in
maintaining orientation in the anterior chamber. Indeed, even 10. Rebubbling: Compliance
gifted surgeons have reported on inverted grafts resulting in
graft failure. We have therefore suggested a very easy technique While DMEK renders unsurpassed visual results along with fast
to ensure orientation of DMEK grafts.9 This technique is based visual recovery, the procedure requires excellent and faithful
on 3 circular marks, which are set in an identifiable order at the interaction between the surgeon and the patient. The patient has
outer margin of the graft by use of a 1-mm trephine (see Figure to spend the first 2 days in bed looking at the ceiling. Thereaf-
1). This technique allows complete control over the orientation ter graft detachment might occur, requiring rebubbling. Thus
of the graft. more exact knowledge of the procedure on the patient’s side is
required than with any other type of corneal surgery. At present,
rebubbling is more frequent in DMEK than in DSAEK surgery;
8. Control graft insertion in DMEK. however, the rate of graft detachment is significantly reduced by
There are several suggestions for how to insert a Descemet roll the advent of improved insertion techniques (see above).
into the anterior chamber. Melles and co-workers suggest using a
glass pipette, which implies loss of control over the orientation of Selected Readings
the graft during injection.10 Along with Price and co-workers,11
we1,7 prefer an IOL shooter. The use of a small air bubble inside 1. Laaser K, Bachmann BO, Horn FK, et al. Donor tissue culture con-
the Descemet roll offers additional stability because it precludes ditions and outcome after Descemet membrane endothelial kerato-
lateral movement of the graft. Thus a reproducible insertion plasty. Am J Ophthalmol. 2011; 151(6):1007-1018.
becomes possible. 2. Price MO, Price FW Jr. Descemet’s stripping with endothelial
keratoplasty: comparative outcomes with microkeratome-dissected
and manually dissected donor tissue. Ophthalmology 2006;

113(11):1936-1942.
3. Lee WB, Jacobs DS, Musch DC, et al. Descemet’s stripping endo-
thelial keratoplasty: safety and outcomes: a report by the American
Academy of Ophthalmology. Ophthalmology 2009; 116(9):1818-
1830.
4. Bahar I, Kaiserman I, Sansanayudh W, et al. Busin guide vs for-
ceps for the insertion of the donor lenticule in Descemet stripping
automated endothelial keratoplasty. Am J Ophthalmol. 2009;
147(2):220-226.
5. Khor WB, Mehta JS, Tan DT. Descemet stripping automated endo-
thelial keratoplasty with a graft insertion device: surgical technique
and early clinical results. Am J Ophthalmol. 2011; 151(2):223-232.
6. Ham L, Balachandran C, Verschoor CA, et al. Visual rehabilitation
rate after isolated Descemet membrane transplantation: Descemet
membrane endothelial keratoplasty. Arch Ophthalmol. 2009;
127(3):252-255.
7. Kruse FE, Laaser K, Cursiefen C, et al. A stepwise approach to
donor preparation and insertion increases safety and outcome
of Descemet membrane endothelial keratoplasty. Cornea 2011;
30(5):580-587.
8. Schlötzer-Schrehardt U, Bachmann BO, Laaser K, Cursiefen C,
Kruse FE. Characterization of the Cleavage plane in Descemet’s
membrane endothelial keratoplasty. Ophthalmology. E-pub before
print 25 June 2011.
9. Bachmann BO, Laaser K, Cursiefen C, Kruse FE. A method to con-
firm correct orientation of Descemet membrane during Descemet
membrane endothelial keratoplasty. Am J Ophthalmol. 2010;
149(6):922-925.
10. Dapena I, Moutsouris K, Droutsas K, Ham L, van Dijk K, Melles
GR. Standardized “no-touch” technique for Descemet membrane
endothelial keratoplasty Arch Ophthalmol. 2011; 129(1):88-94.
11. Price MO, Giebel AW, Fairchild KM, Price FW Jr. Descemet’s
membrane endothelial keratoplasty: prospective multicenter study
of visual and refractive outcomes and endothelial survival. Oph-
thalmology 2009; 116(12):2361-2368.
Extreme Descemet-Stripping Automated Endothelial

Keratoplasty: When You Think DSEK Is the Best
Option for the Cornea, but Not for Your Coronaries
George O D Rosenwasser MD
I. Feeling Detached? Attachment Issues

A. Tubing
B. Pressure
C. Aphakia
D. Posture
E. Dementia
F. Technique
1. Retention suture technique
2. Parallel and cloverleaf technique
II. Short on Space?
A. Anterior chamber (AC) IOLs
B. Hyperopia/shallow AC
III. Feel Like You’ve Been Scarred? Do you need the whole
thing?
IV. I’m Gonna Cut You: Eccentric Cuts and Recuts
V. This Will Make You Flip: Disk Inversion
Descemet Membrane Endothelial Keratoplasty: Is It

Time for You to Convert From Descemet-Stripping
Endothelial Keratoplasty?
Francis W Price Jr MD
To make this decision you need to ask 3 relevant questions: Looking at same-center studies is very important as they would
be expected to use the same methods of measuring visual acuity
1. Does the thickness of an endothelial keratoplasty (EK)
and same criteria for excluding cases with poor visual potential
graft affect vision?
such as macular degeneration, amblyopia, etc. The induction of
2. Does the thickness of an EK graft affect the refractive
higher-order aberrations and irregular astigmatism from the pos-
results?
terior surface of the cornea is the cause of poorer vision in DSEK.
3. Currently what is the thinnest EK donor graft?
Let’s look at what we know about the induction of lower-
Current evidence shows that very thin EK grafts provide bet- order aberrations in DSEK. BJ Dupps et al showed very nicely
ter visual results and fewer refractive surprises.1-3 Currently the that the variable thickness from center to periphery in the donor
thinnest EK graft available is Descemet membrane endothelial tissue explains much of the hyperopic shift in DSEK eyes.7 They
keratoplasty (DMEK), consisting of only endothelium and the also showed that thicker donor tissue caused more induced
Descemet membrane. DMEK donor grafts will be the thinnest hyperopia. However, what is rarely discussed is that microkera-
grafts available until we are able to transplant just endothelial tomes do not cut a planar dissection. The Moria CB is an ideal
cells or do away with the need for donor tissue by stimulating the microkeratome for DSEK because it cuts thicker in the periphery
patient’s own endothelial cells to regenerate. Work is being done than the center and helps to offset the normal thickness gradi-
in these areas, but I suspect it will be a number of years before ent increase present in most corneas from center to periphery.
they become available. However, even that microkeratome does not cut uniformly at the
Currently no eye bank in the world that I know of screens same thickness from one side to the other. Any irregularity in the
donor corneas for the curvature or Ks. Both living recipients and microkeratome cut induces some low- or higher-order aberration
donors all have a range of Ks from the mid-30s to low 50s. The to the optical system when the donor is placed in the eye. The
most common Ks in the typical bell-shaped curve will be in the thinner the graft, the less chance of inducing these aberrations, so
mid-40s, and usually when we place a donor EK graft there is why not just get rid of the stroma altogether?
only mild folding of the tissue that occurs to allow it to conform What we don’t know is whether leaving just 50 to 75 microns
to the posterior surface of the recipient cornea. Bear in mind of stromal tissue with DSEK will provide vision comparable to
that even if the donor and recipient Ks are the same, there will that provided by DMEK. This is an area we are investigating.
still be some folding that has to take place when the donor graft I will also add that so far there have been no published reports
is placed on the recipient because we are inherently decreasing showing good visual results with any femtosecond laser for
the radius of curvature of the inner posterior surface as we add DSEK. All of these lasers tend to produce a reasonably good sur-
thickness to the patient’s cornea with the graft. The degree of face appearance by electron microscopy but poor visual results
folding and distortion of the donor tissue increases as the thick- due to gross irregularities in the tissue induced by the compres-
ness of the donor tissue increases.4 The folding of the corneal sion of the cornea during applanation or an inability of the laser
lamellae and gross distortion of the surfaces of the donor tissue to provide smooth cuts through the posterior portion of the
lead to degradation of the optics of the cornea, leading to poorer cornea, where the collagen lamellae are less dense than in the
vision and visual quality.5 anterior cornea.
Compared to penetrating keratoplasty (PK), Descemet- The final hurdle for most surgeons performing DMEK is the
stripping endothelial keratoplasty (DSEK) surgery represented increased difficulty in doing the surgery and in the postoperative
a dramatic improvement in visual results and safety for patients care. I began my ophthalmology training in 1978. At that time,
because it eliminated the irregular astigmatism induced by all the cataracts at my university were performed as intra-caps.
imperfectly aligning the anterior surfaces of the donor and recipi- We began doing extra-caps while I was a resident. I learned
ent corneas with sutures as well as the need for a full-thickness phaco on my own after going into practice. Each of these steps
360-degree corneal incision. DMEK further helps eliminate the was hard, and I noticed that with each increase in surgical com-
induction of higher-order aberrations that have been shown to plexity, some surgeons would simply stop doing cataract surgery.
occur in DSEK surgery.6 I also vividly recall a doctor in our town who openly told every-
Why do we have less than perfect vision after EK? Why one he would not start using an operating microscope because he
doesn’t everyone see 20/20? Some eyes have irregularities on got good results with his loops. (He was also the one who told
the anterior surface or subepithelial haze as a result of the prior everyone to stand firm and not sign up with an HMO but on the
corneal edema, especially if bullous changes have occurred. That side contracted the whole job for himself.) Be careful of those
is common to all EK, and I will not discuss this further as treat- who say you should not do something because it is hard and not
ment of those issues improves the visual results for all types of worth the effort. Use your own deductive reasoning to look at
EK. However, in same-center studies like ours and those of Ger- the results and the methods, and decide what is best for you and
ritt Melles, why has DMEK led to dramatic improvements in best for your patients!
the rates of 20/20 and 20/25 vision compared to DSEK cases?1-3
References
1. Ham L, Balachandran C, Verschoor CA, van der Wees J, Melles

GRJ. Visual rehabilitation rate after isolated Descemet membrane
transplantation. Arch Ophthalmol. 2009; 127:252-255.
2. Price MO, Giebel AW, Fairchild KM, Price FW. Descemet mem-
brane endothelial keratoplasty: prospective multicenter study of
visual and refractive outcomes and endothelial survival. Ophthal-
mology 2009; 116:2361-2368.
3. McCauley MB, Price MO, Fairchild KM, Price DA, Price FW.
Prospective study of visual outcomes and endothelial survival after
Descemet stripping automated endothelial keratoplasty. Cornea
2011; 30:315-319.
4. Patel SV, va der Meulen IJ, van den Berg TJ, McLaren JW. Quality
of vision in Fuchs endothelial dystrophy before and after Descemet-
stripping endothelial keratoplasty. Program and abstracts of the
Association for Research in Vision and Ophthalmology (ARVO);
May 2, 2011; Ft. Lauderdale, Florida.
5. Letko E, Price DA, Lindoso EM, Price MO, Price FW. Secondary
graft failure and repeat endothelial keratoplasty after Descemet
stripping automated endothelial keratoplasty (DSAEK). Ophthal-
mology 2011; 118:310-314.
6. Chamberlain W, Omid N, Lin A, Farid M, Gaster RN, Steinert RF.
Comparison of corneal surface higher-order aberrations after endo-
thelial keratoplasty, femtosecond laser-assisted keratoplasty, and
conventional penetrating keratoplasty. Cornea. In press.
7. Dupps WJ, Qian Y, Meisler DM. Multivariate model of refractive
shift in Descemet-stripping automated endothelial keratoplasty.
J Cataract Refract Surg. 2008; 34:578-584.
Deep Anterior Lamellar Keratoplasty: Is It Time for

You to Convert From PK?
Rudy MMA Nuijts MD, Yanny YY Cheng MD, and the Dutch Lamellar Corneal Transplantation Study
(DLCTS) Group
Introduction 0.31 ± 0.3 logMAR in PK. This indicates that Anwar’s big-
bubble technique achieves a deep dissection up to the level of the
Deep anterior lamellar keratoplasty (DALK) can be performed
Descemet membrane and does not lead to substantial interface
in patients with corneal stroma pathologies not affecting the
hazing. Although a significantly better BCVA following DALK
endothelium. Main advantages of DALK are prevention of long-
has been reported,4 the majority of the studies report similar val-
term endothelial cell (EC) loss and reduction of immunological
ues in DALK eyes, compared to PK eyes.6-11
rejection.
Visual outcomes of DALK might be limited compared to PK
if baring of the Descemet membrane is incomplete and interface
haze occurs. Deep dissection at the level of the Descemet mem-
brane is thought to lead to better visual outcomes due to the
absence of stromal scarring at the graft-host stromal interface.1,2
Various techniques have been used to accomplish baring of the
Descemet membrane, and Anwar and Teichmann introduced
the so-called “big-bubble” technique, in which partial thickness
trephination is followed by stromal air injection to form an air
bubble to dissect the Descemet membrane from the posterior
stroma.3 This facilitates a safer exposure of the Descemet mem-
brane and produces a smooth surface for high-quality vision (see
Figure 1). However, this big-bubble technique is technically chal-
lenging and may result in perforations of the Descemet membrane
in up to 57% of the cases.4 Recently, the Dutch Lamellar Corneal
Transplantation Study (DLCTS) was designed as a randomized,
controlled trial (RCT) to compare EC loss, visual and refractive
outcomes, quality of vision and complication profile after DALK
and PK.5 The outcomes of this study can probably answer the Figure 2.
question: DALK: Is It Time for You to Convert From PK?
Refractive astigmatism values after DALK were comparable
to PK with an average refractive astigmatism of -3.37 D and
-3.76 D, respectively, after 12 months follow-up. This is in com-
parison with previous studies.6-11
The high preoperative topographic astigmatism values in both
the DALK and PK eyes (6.61 ± 4.9 D and 6.90 ± 6.4 D, respec-
tively) may be caused by corneal irregularities due to epithelial
irregularities, corneal scars or keratoconus. Postoperative topo-
graphic astigmatism in the DALK group did not differ from the
PK group. Another study has shown similar astigmatism in both
groups after suture removal.2
Endothelial Cell (EC) Loss

EC loss was significantly higher following PK, compared to
DALK procedures performed without perforation of the Des-
cemet membrane (12 months: 27.7 ± 11.1% vs. 12.9 ± 17.6%).
Three months after DALK surgery, EC loss was 6.6%, compared
to the preoperative situation. Surgically induced EC loss in
Figure 1.
DALK treated eyes has been reported to be around 10%.12 Other
studies show an EC loss ranging from 6% to 20% in the first
Visual and Refractive Outcomes After DALK and PK year after DALK surgery.13-15 Shimazaki et al performed a RCT
comparing DALK and PK and found a stabilization of EC loss 6
Initial postoperative visual outcomes were significantly better in months after a DALK procedure.16 Longer follow-up RCTs are
the PK group, compared to the DALK group. However, 6 to 12 needed to evaluate this further.
months after surgery, both the UCVA and BSCVA in the DALK A sufficiently high ECD is one of the major factors contribut-
group reached the same level as in the PK group (see Figure 2). ing to long-term graft survival. The higher EC loss in PK treated
BSCVA at 12 months was 0.39 ± 0.3 logMAR in DALK and eyes is in accordance with previous studies. A large cohort study
with a 15-year follow-up showed that the endothelial cell den- 2. Ardjomand N, Hau S, McAlister JC, et al. Quality of vision and
sity continues to decrease following a PK, until it stabilizes about graft thickness in deep anterior lamellar and penetrating corneal
10 years after surgery.17 At this time, total EC loss is estimated allografts. Am J Ophthalmol. 2007; 143:228-235.
at 70%. 3. Anwar M, Teichmann KD. Big-bubble technique to bare Des-
cemet’s membrane in anterior lamellar keratoplasty. J Cataract
Refract Surg. 2002; 28:398-403.
Complications
4. Anshu A, Parthasarathy A, Mehta JS, et al. Outcomes of thera-
The main complication of a DALK procedure is intraoperative peutic deep lamellar keratoplasty and penetrating keratoplasty for
perforation of the Descemet membrane. A recent overview of advanced infectious keratitis: a comparative study. Ophthalmology
comparable deep-dissection techniques reports a perforation 2009; 116:615-623.
rate ranging from 6% to 57%.4,18 However, the reported per- 5. Cheng YY, Visser N, Schouten JS, Wijdh RJ, Pels E, van Cleynen-
foration rates also depend on whether discrimination is made breugel H, Eggink CA, Zaal MJ, Rijneveld WJ, Nuijts RM. Endo-
between microperforations and larger perforations that require thelial cell loss and visual outcome of deep anterior lamellar kera-
a conversion. In the DLCTS a total perforation (microperfora- toplasty versus penetrating keratoplasty: a randomized multicenter
tions and larger perforations) rate of 32% was noted, and 18% clinical trial. Ophthalmology 2011; 118:302-309.
of the patients required conversion to PK. This might be partially 6. Panda A, Bageshwar LM, Ray M, et al. Deep lamellar keratoplasty
explained by a learning curve of the surgeons. An additional versus penetrating keratoplasty for corneal lesions. Cornea 1999;
explanation is that 6 out of 9 patients with Descemet membrane 18:172-175.
perforations in our study had been diagnosed with severe stro-
7. Shimazaki J, Shimmura S, Ishioka M, Tsubota K. Randomized clin-
mal scarring due to herpes simplex virus keratitis. We advise
ical trial of deep lamellar keratoplasty vs penetrating keratoplasty.
caution when using the big bubble technique in eyes with stro- Am J Ophthalmol. 2002; 134:159-165.
mal scarring.
In the DLCTS endothelial rejection occurred in 3 PK patients, 8. Bahar I, Kaiserman I, Srinivasan S, et al. Comparison of three dif-
but did not occur in any DALK patient. ferent techniques of corneal transplantation for keratoconus. Am J
Ophthalmol. 2008; 146:905-912 e1.
9. Krumeich JH, Knulle A, Krumeich BM. [Deep anterior lamellar
Cost-Effectiveness (DALK) vs. penetrating keratoplasty (PKP): a clinical and statistical
The DLCTS also showed that DALK is more costly and more analysis]. Klin Monatsbl Augenheilkd. 2008; 225:637-648.
effective than PK.19 Results on the National Eye Institute Visual 10. Watson SL, Ramsay A, Dart JK, et al. Comparison of deep lamellar
Function Questionnaire (NEI-VFQ 25) were in favor of DALK, keratoplasty and penetrating keratoplasty in patients with kerato-
and endothelial cell loss in DALK patients remained stable conus. Ophthalmology 2004; 111:1676-1682.
after 6 months postoperatively, whereas cell loss in PK patients 11. Han DC, Mehta JS, Por YM, et al. Comparison of outcomes of
continued. Furthermore, it is shown that DALK procedures lamellar keratoplasty and penetrating keratoplasty in keratoconus.
performed without perforation of the Descemet membrane were Am J Ophthalmol. 2009; 148:744-751 e1.
more effective. However, as it is unknown what society is willing
12. van Dooren BT, Mulder PG, Nieuwendaal CP, et al. Endothelial
to pay for an additional improved patient, cost-effectiveness of cell density after deep anterior lamellar keratoplasty (Melles tech-
DALK within a limited follow-up period of 12 months is unclear. nique). Am J Ophthalmol. 2004; 137:397-400.
In addition, the cost-effectiveness of DALK may improve over
time due to lower graft failure. 13. Fontana L, Parente G, Tassinari G. Clinical outcomes after deep
anterior lamellar keratoplasty using the big-bubble technique in
patients with keratoconus. Am J Ophthalmol. 2007; 143:117-124.
Conclusion 14. Morris E, Kirwan JF, Sujatha S, Rostron CK. Corneal endothelial
DALK procedures performed without perforation of the Des- specular microscopy following deep lamellar keratoplasty with
cemet membrane result in a significantly lower EC loss, while lyophilised tissue. Eye 1998; 12(pt 4):619-622.
at the same time achieving equally good visual outcomes as a 15. Bahar I, Kaiserman I, Srinivasan S, et al. Comparison of three dif-
PK procedure. Therefore, in 2 of 3 patients a DALK procedure ferent techniques of corneal transplantation for keratoconus. Am J
is highly beneficial for the patient since the host endothelium is Ophthalmol. 2008; 146:905-912 e1.
saved. However, in the occurrence of intraoperative perforation 16. Shimazaki J, Shimmura S, Ishioka M, Tsubota K. Randomized clin-
of Descemet membrane this advantage is lost. Since complete ical trial of deep lamellar keratoplasty vs penetrating keratoplasty.
suture removal in the DLCTS was only performed in the minor- Am J Ophthalmol. 2002; 134:159-165.
ity of DALK and PK patients, a final comparison in postopera- 17. Patel SV, Hodge DO, Bourne WM. Corneal endothelium and post-
tive visual outcomes, astigmatism differences, and suture-related operative outcomes 15 years after penetrating keratoplasty. Am J
problems will only be possible after all sutures have been Ophthalmol. 2005; 139:311-319.
removed. Given the obvious “endothelium saving advantages”
18. Reinhart WJ, Musch DC, Jacobs DS, Lee WB, Kaufman SC, Shtein
of DALK we believe it is time to convert. However, surgical
RM. Deep anterior lamellar keratoplasty as an alternative to pen-
improvements are needed to standardize the big-bubble tech- etrating keratoplasty a report by the American Academy of Oph-
nique in order to reduce the perforation rate. thalmology. Ophthalmology 2011; 118(1):209-218.
19. van den Biggelaar FJ, Cheng YY, Nuijts RM, et al. Economic evalu-
References ation of deep anterior lamellar keratoplasty versus penetrating kera-
toplasty in The Netherlands. Am J Ophthalmol. 2011; 151:449-
1. Sugita J, Kondo J. Deep lamellar keratoplasty with complete 459.
removal of pathological stroma for vision improvement. Br J Oph-
thalmol. 1997; 81:184-188.
Deep Anterior Lamellar Keratoplasty: Tips for the

Transitioning Surgeon
Geoffrey Tabin MD
I. Converting to Deep Anterior Lamellar Keratoplasty G. Safe dissection; decompress eye, cut into quadrants,
use rounded scissors, continue plane beyond edge of
A. Equal results to PKP but preserves patient’s endo-
trephination
thelium
H. Stripping Descemet from donor; under BSS, under
B. DALK procedures: Big bubble or manual dissection
microscope, use Trypan blue
II. Big Bubble: Anwar and Beyond
I. Sew safely, align epithelial edges, avoid needle per-
A. Getting started: Try for all cases with anterior foration
pathology; you can always convert.
III. Manage Complications
B. Step-by-step big bubble DALK by video
A. No bubble? Try again in another place.
C. Getting the big bubble tips and tricks: central 8-mm
B. Still no bubble? Manual dissection: soften eye,
trephination to 2/3 depth, remove anterior stroma
rounded blade without fixation of globe, hydro or
D. Use rounded cannula, deep dissection; air follows visco dissection tricks
path of least resistance; use 5 cc syringe.
C. Microperforation: Can usually continue
E. Gentle pressure, past initial resistance until you see
D. Double chamber POD 1: May have microperfora-
stromal air expand to silvery round big bubble of
tion from dissection or suture; try air injection
Descemet separation
E. Macroperforation: Convert to PKP
F. Confirming the bubble and tricks for opening, use
viscoelastic
Deep Anterior Lamellar Keratoplasty: Why You

Should Be Performing It With a Femtosecond Laser
Marjan Farid MD
I. Deep Anterior Lamellar Keratoplasty (DALK) D. Procedure

A. Definition 1. First step: Standard nonpenetrating femtosecond
laser zigzag incision (leave about 70 microns post
B. Replace entire corneal stroma while retaining the
bridge uncut)
patient’s Descemet membrane and endothelium
2. Second step: Baring of Descemet membrane
C. Disease targeted lamellar surgery
using “big bubble” technique: Femtosecond laser
D. Anwar “big bubble” technique can create a track for blunt tip cannula insertion;
decreases risk of perforation with a needle.
1. Baring of Descemet membrane from stroma
3. Third step: Remove entire stroma and discard.
2. Discard all of the stroma
4. Fourth step
3. Full-thickness donor minus endothelium
sutured on a. Wipe off donor endothelium and suture on
the donor graft.
II. Femtosecond Laser Technology
b. If Descemet membrane was perforated, pro-
A. Photodisruption
ceed with full-thickness transplant.
B. Creates precise cuts at specified depths
V. Visante OCT
C. Infinite custom trephination possibilities
A. Excellent apposition of native Descemet membrane
1. Mushroom to donor
2. Top-hat B. Results
3. Zigzag 1. Retrospective comparison of keratoconus eyes
status post zigzag corneal transplantation: DALK
4. Christmas tree
(14 eyes) vs. PKP (46 eyes)
III. Femtosecond Laser Zigzag Incision
2. No statistically significant difference in:
A. Angled smooth anterior edge
a. Best spectacle-corrected visual acuity
B. Better donor-host transition (BSCVA): logMAR 0.15 vs. 0.19 at 6 months
C. Hermetic wound seal b. Topographical astigmatism: 3.07 D vs. 3.87
D at 6 months
IV. Zigzag DALK
c. Manifest astigmatism: 2.5 D vs. 3.01 D at 6
A. Combined “big-bubble” DALK technique with fem-
months
tosecond laser zigzag incision
VI. Conclusion
B. Indications
A. Femtosecond laser zigzag incision guides needle
1. Keratoconus (KC)
insertion into posterior stroma, allowing baring of
2. Corneal ectasia Descemet membrane.
3. Stromal scarring or dystrophies B. In cases of Descemet rupture, convert to a full-
thickness transplant, retaining the benefits of the
C. Benefits
zigzag trephination.
1. No risk of endothelial rejection. Especially good
C. Zigzag DALK results in excellent recovery of
in the young KC patient (stromal rejection still
BSCVA and astigmatism, comparable to full-
possible).
thickness zigzag transplants.
2. Rapid wound healing with custom trephination
3. Extraocular surgery
4. Easily converted to full-thickness penetrating
keratoplasty in case of Descemet perforation
References
1. Farid M, Steinert RF. Deep anterior lamellar keratoplasty per-

formed with the femtosecond laser zigzag incision for the treatment
of stromal corneal pathology and ectatic disease. J Cataract Refract
Surg. 2009; 35(5):809-813.
2. Price FW Jr, Price MO, Grandin JC, Kwon R. Deep anterior lamel-
lar keratoplasty with femtosecond-laser zigzag incisions. J Cataract
Refract Surg. 2009; 35(5):804-808; erratum in: J Cataract Refract
Surg. 2009; 35(7):1325.
3. Chan CC, Ritenour RJ, Kumar NL, Sansanayudh W, Rootman DS.
Femtosecond laser-assisted mushroom configuration deep anterior
lamellar keratoplasty. Cornea 2010; 29(3):290-295.
4. Buzzonetti L, Laborante A, Petrocelli G. Refractive outcome of
keratoconus treated by combined femtosecond laser and big-
bubble deep anterior lamellar keratoplasty. J Refract Surg. 2011;
27(3):189-194.
5. Mosca L, Fasciani R, Mosca L, et al. Graft rejection after femtosec-
ond laser-assisted deep anterior lamellar keratoplasty: report of 3
cases. Cornea. Epub ahead of print 3 Jun 2011.
2011 Subspecialty Day | Cornea Section IV: Corneal Transplantation — Penetrating and Pediatric Keratoplasty 49
PK: When I Choose PK Instead of Descemet-Stripping

Endothelial Keratoplasty
Patient Selection in Keratoplasty: When Is Penetrating Keratoplasty Preferred
to Lamellar Keratoplasty?
Kenneth Mark Goins MD
Purpose able to recognize those situations where the clinical benefits of

PK still outweigh the negative attributes (ie, 1, 2, and 3).
To review those clinical situations where, for the “average cor-
It should be noted that PK is not fairly judged in comparison
neal surgeon” who performs penetrating keratoplasty (PK), deep
to its LK counterparts. For example, the reported average visual
anterior lamellar keratoplasty (DALK), and Descemet-stripping
results after PK are quite varied, and in the scientific literature
endothelial keratoplasty (DSEK), the patient may be better
they are often influenced by nonexcluded comorbidities, such as
served by PK.
glaucoma, AMD, cystoid macular edema, and other factors. PK
has a major advantage over LK surgery of all types, by providing
Introduction: A Paradigm Shift an optically pure corneal window that is devoid of an interface
that could be susceptible to haze, scarring, wrinkles, and infec-
In the 21st century, there is a paradigm shift from penetrating to
tious organisms (ie, as reported with DALK and DSAEK).
lamellar keratoplasty (LK). DALK, which preserves the recipient
endothelium and eliminates immune-mediated endothelial rejec-
tion, has been introduced as an alternative to PK in eyes with Surgeon Factors in the Selection Process
keratoconus and stromal opacities attributable to dystrophies,
Surgeon training and experience are perhaps the most important
degenerations, trauma, and microbial keratitis. Conversely,
factors in the selection process, for if a procedure is so difficult
endothelial keratoplasty offers the advantage of preservation of
that it can only be performed by a few surgeons, that particular
normal corneal stroma and provides rapid visual rehabilitation,
procedure is less likely to become mainstream. The Eye Bank
thereby replacing PK as the surgical treatment of choice in most
Association of America (EBAA) 2010 donor statistical data
cases of endothelial dysfunction.
suggest that this may be true for DALK in the United States (ie,
It is generally accepted that the benefits of LK of all types
there has been a slow increase in procedures over time), whereas
include a decreased risk for allograft rejection, reduced astigma-
the opposite is true for endothelial keratoplasty (EK), which has
tism, improved wound integrity and less susceptibility to blunt
become widely accepted.
trauma, decreased incidence from intraoperative suprachoroidal
Similar to PK in the 20th century, the technology and tech-
hemorrhage, and better maintenance of the anterior chamber
niques of EK have advanced dramatically over the past 10 years,
angle, with reduced glaucoma development. In essence, LK
making the procedure easier to perform with a secondary benefit
exchanges only the pathologically defective tissue layers, reduces
of transfer of surgical skills to resident and fellowship training
the chance for adverse events, and provides faster visual recov-
programs. The same cannot be said for DALK; however, it is
ery. With the ascension of LK, PK is being used less often. Nev-
anticipated that a similar transformation will occur in the future.
ertheless, there are certain indications for which PK will remain.
It can also be said that the excellent outcomes seen with PK for
The purpose of this paper is to evaluate those situations in which
keratoconus and anterior corneal scars may be responsible for
LK may be a less desirable option.
the slow transition to DALK in the United States.
How does PK fare as a keratoplasty procedure? In 2011, the
goal of keratoplasty surgery of all types is six-fold, as stated by
Terry et al.7 Patient Factors in the Selection Process
1. A consistent and smooth surface topography with little to Monocular vs. binocular vision status
no change in preoperative astigmatism
In general, the patient with monocular vision status should have
2. Predictable and stable corneal power after transplantation
the best procedure that allows a rapid return to average daily liv-
3. Tectonically stable globe that is safe from injury or infec-
ing activities. If concomitant procedures such as triamcinolone-
tion
assisted vitrectomy, IOL exchange, iris reconstruction, and/or
4. Successful transfer and maintenance of corneal endothe-
seton placement are necessary, the corneal surgeon may want to
lium
consider a full-thickness graft to have better visualization so as
5. An optically pure cornea devoid of interface opacity
to reduce the chance for intraoperative complications. Similarly,
6. Last but not least, a procedure that is easily and quickly
the monocular patient with severe bullous keratopathy and ante-
adopted into clinical practice (ie, easily performed by sur-
rior corneal scarring may have faster vision recovery with a PK
geons of various backgrounds and experiences)
instead of EK.
Despite the advances in suture techniques, tissue adhesives,
and wound construction (ie, femtosecond laser), PK does not Age and longevity
consistently achieve the first 3 goals of keratoplasty surgery. In the elderly patient who suffers from systemic complications
However, PK does fulfill the last 3 goals of keratoplasty surgery (ie, COPD, coronary artery disease, malignancy, etc.), restora-
(ie, 4, 5, and 6). It is very important that the corneal surgeon be tion of vision with one surgery may be more beneficial than that
seen with multiple-stage procedures. In this situation, the full-
50 Section IV: Corneal Transplantation — Penetrating and Pediatric Keratoplasty 2011 Subspecialty Day | Cornea
thickness surgery is more likely to be completed, without further edema may preclude accurate endothelial cell assessment. Persis-
enhancement procedures (ie, re-bubble or repositioning of the tent epithelial defect (PED) may prevent adequate assessment of
DSAEK button, excimer laser phototherapeutic keratectomy, the posterior cornea due to corneal haze and swelling. Anterior
etc.), at the expense of slower visual return. Surgeon experience, segment imaging with confocal microscopy is important in the
of course, is an interrelated function in this decision-making decision process to rule out atypical pathogens and to determine
process. endothelial cell morphology. As a rule of thumb, if the patient
is young, the cornea stroma is compact, and there is no history
of hydrops, herpes simplex, or varicella zoster endotheliitis, it
Specific Situations to Consider
would be most appropriate to proceed with DALK. The ben-
Long-term corneal edema efits of DALK include a better posterior corneal curvature with
reduced wavefront aberrations, less peripheral anterior synechiae
In patients with endothelial dysfunction who have long-standing
formation and glaucoma, the potential for longer graft survival,
disease that is associated with collagen disruption and subepi-
and the ability to use older donor tissue. If there is a question as
thelial scar formation, PK may offer a more rapid and better
to whether the disease process has affected the endothelium, a
final visual acuity because it provides an optically pure cornea. It
traditional PK should be considered.
may take months to years before anterior corneal haze resolves
over time after DSAEK, which may hinder patient functioning,
depending upon individual need. In the monocular patient, who Conclusion
needs rapid visual recovery, the full-thickness graft may actually
The purpose of this presentation is to determine when is it appro-
be preferred.
priate to use PK in the setting of LK of all types. With proper pre-
Anterior segment reconstruction operative evaluation using anterior segment imaging techniques
and patient/physician discussion, the proper treatment modality
The patient with endothelial dysfunction (namely, pseudophakic
may be determined in these difficult cases. PK is a procedure that
bullous keratopathy) with an anterior chamber (AC) IOL and
can be performed very well by most corneal specialists, and it
vitreous incarceration into the anterior segment may actually
still has a great role in the management of our patients.
be better served by PK, IOL exchange, and anterior vitrectomy.
This procedure can be done in one setting as apposed to a staged
vitrectomy and IOL exchange, followed by DSAEK, which is References
commonly done by many corneal surgeons today. There are,
however, short-term outcome studies that suggest that reten- 1. Anshu A, Parthasarathy A, Mehta JS, Htoon HM, Tan DTH.
tion of fixed AC IOLs in the setting of EK can be successful and Outcomes of therapeutic deep lamellar keratoplasty and penetrat-
appropriate. At the current time, findings within our practice ing keratoplasty for advanced infectious keratitis. Ophthalmology
2009; 116:615-623.
at Iowa suggest that 5-year EK graft survival in the setting of
AC IOL retention may be less than desirable. Regardless of the 2. Tan DTH, Anshi A, Mehta JS. Paradigm shifts in corneal transplan-
procedure performed, these patients are at high risk for cystoid tation. Ann Acad Med Singapore. 2009; 38:332-339.
macular edema, glaucoma, and allograft rejection. The Boston 3. Sutphin JE, Goins KM, Wagoner MD. Deep anterior lamellar kera-
keratoprosthesis, an alternative type of PK, should be considered toplasty: when should it replace penetrating keratoplasty? Am J
if multiple allograft rejections have occurred in this particular Ophthalmol. 2009; 148:629-631.
setting.
4. Goins KM. Surgical alternatives to penetrating keratoplasty II:
endothelial keratoplasty. Int Ophthalmol. 2008; 28:233-246.
Previous failed keratoplasty
In the setting of a failed PK, the surgeon has the option of repeat 5. Pramanik S, Musch DC, Sutphin JE, Farjo AA. Extended long-term
outcomes of penetrating keratoplasty for keratoconus. Ophthal-
PK or EK. EK ensures a very rapid recovery of vision in most
mology 2006; 113:1633-1638.
cases; however, if the patient is contact lens intolerant with
disabling astigmatism that is not amenable to laser vision correc- 6. Tan DTH, Anshu A. Anterior lamellar keratoplasty: ‘back to the
tion, a PK would be preferred. future’—a review. Clin Exp Ophthalmol. 2010; 38:118-127.
7. Terry MA. Endothelial keratoplasty: clinical outcomes in the two
Previous or active keratitis years following deep lamellar endothelial keratoplasty (an Ameri-
The decision to perform DALK over PK may be difficult to can Ophthalmological Society thesis). Trans Am Ophthalmol Soc.
discern in the setting of ocular infection, for inflammation and 2007; 105:530-563.
Failed PK: How I Choose Between Repeat PK and

Descemet-Stripping Endothelial Keratoplasty
Alan N Carlson MD
I. Background toward high degrees of astigmatism and refractive

instability.
Roles of the ideal cornea guide surgical principles and
decision making: D. Intraoperative considerations
A. Structural goals: Maintaining or restoring structural DSAEK may be more technically challenging in
integrity as part of the “wall” of the eye some cases that have, for example, synechiae or
anterior chamber IOLs; however, there is the
B. Optical transmission: Maintaining or restoring opti-
advantage of having a “closed” system should you
cal clarity for transmission of light
encounter hemorrhage or vitreous prolapse.
C. Refractive contribution: Contributing to the focus-
E. Infection
ing power of the optical system
The long-term risk of infection is much less with
D. Cosmetic: Maintaining or restoring normal corneal
DSAEK, as suture exposure and breakage contrib-
physiology to help preserve the appearance of a nor-
utes to this late in post-PK patients. There is a grow-
mal eye
ing sense that the closed system offered by DSAEK,
II. Reasons for PK Failure along with the transplantation of less tissue, may
result in a lower risk of serious early infections than
A. Immunologic: Rejection
is seen with PK.
B. Surface disease: Multifactorial
V. When is DSAEK after failed PK a “bad” idea?
C. Infection
A. Return to basic principles: When IA, IB, IC, ID are
D. Trauma compromised or not restored with surgery.
E. Neurotrophism B. Structural integrity issues, such as a severely com-
promised graft-host junction (GHJ), tissue over-ride,
F. Glaucoma
or severe ectasia peripheral to the previous graft.
G. Ectasia These cases are often better handled with a repeat
PK with special attention to wound maintenance
H. Poor wound healing
than with DSAEK, which would not repair the
III. Connect the Dots problem. There are some cases where a GHJ wound
revision would help restore structural integrity and
How did the patient get from point A (PK) to point B
surface contour and can be combined with DSAEK.
(failed PK)?
C. Optical transmission may be compromised by a scar
IV. Advantages of Proceeding With DSAEK to Treat a
from previous infection or ulceration, and if this is
Failed PK
visually significant, it needs to be factored into con-
A. Structural integrity sideration favoring PK rather than DSAEK surgery.
Relying on previous graft-host junction healing D. Refractive considerations may lead to repeat PK if
rather than repeating a process that requires suture tissue distribution mismatch or previous healing
supported healing for 12-24 months resulted in large amounts of irregular astigmatism.
Unless the patient was a successful rigid contact lens
B. Surface disease
wearer, repeat PK would be the better choice from
A complex multifactorial insult on the corneal sur- an optical standpoint.
face related to neurotrophism, medication toxicity,
E. Cosmetic considerations are usually a lower prior-
lid margin disease, evaporative dry eye, etc.—all fac-
ity, but in general DSAEK offers the advantage
tors that are typically worse with patients undergo-
of having less swelling, redness, and ptosis after
ing full repeat PK in comparison to DSAEK.
surgery. However, there are also those cases where
C. Recovery stromal scarring from infection, inflammation, or
chronic edema is better treated with repeat PK than
Typically much faster with DSAEK than with PK,
with DSAEK.
allowing for a faster taper of medications, includ-
ing steroids. Also, recovery is more predictable VI. Special Cases and Other Considerations
with DSAEK than with PK in terms of astigmatism,
A. Traumatic aphakia and aniridia can make DSAEK
refractive stability, and a reasonably predictable
problematic, as poor donor attachment can lead to
small hyperopic shift; PK is much more prone
posterior dislocation of the donor tissue.
B. Hypotony, particularly if severe, requires special VIII. Summary

attention to make DSAEK a viable option when
Eyes with a failed PK are usually complex, result-
repeating a graft. Some of these cases are better
ing from a variety of issues. It is important whenever
managed with PK.
possible to understand the reasons behind the donor
C. Retinal considerations: Combination surgical pro- tissue failure. There is great incentive to take advan-
cedures that include extensive vitreoretinal surgery tage of the newer DSAEK techniques that offer more
often require a temporary keratoprosthesis for bet- rapid healing; better structural integrity, refractive
ter visibility and are therefore better treated with PK stability, and predictability; reduced medications; and
than with DSAEK. decreased infection risk long term. Unfortunately, not
every patient with a failed PK can be reduced to purely
D. Failed PK in combination with an anterior chamber
endothelial dysfunction. Additional considerations may
IOL and shallow chamber are typically poor candi-
require PK to re-establish both optical and structural
dates for DSAEK unless the chamber is deepened,
considerations.
and the IOL may need to be exchanged for a poste-
rior IOL, sutured if there is no capsular support.
References
E. End-stage glaucoma patients may be considered at
unacceptable risk from the elevated IOP created to 1. Jun B, Kuo AN, Afshari NA, Carlson AN, Kim T. Refractive
attach the donor tissue with DSAEK. change after Descemet stripping automated endothelial keratoplasty
F. Patients with previous glaucoma filtering surgery surgery and its correlation with graft thickness and diameter. Cor-
nea 2009; 28(1):19-23.
including tube shunts require attention relative to
their proximity to DSAEK donor tissue and also air 2. Kharod BV, Carlson AN. Corneal transplantation using the Des-
bubble evacuation and the risk for potential hypot- cemet’s stripping endothelial keratoplasty technique. Expert Rev
ony, and therefore some of these patients are better Pharmacoecon Outcomes Res. 2007; 7(2):137-142.
treated with PK. 3. Caldwell MC, Perfect JR, Carlson AN, Proia AD. Candida glabrata
endophthalmitis following penetrating keratoplasty. J Cataract
VII. Clinical Examples
Refract Surg. 2009; 35(3):598-602.
A. Patient DD 4. Patel M, Challa P, Afshari NA. Descemet’s stripping automated
Failed PK O.S. resulting from severe trauma. Trau- endothelial keratoplasty in a patient with four glaucoma tubes. Ann
matic aniridia and aphakia along with vitreous Ophthalmol (Skokie). 2010; 42 Spec No: 20-23.
prolapse into anterior chamber and poor visibility. 5. Duarte MC, Herndon LW, Gupta PK, Afshari NA. DSEK in eyes
High-risk patient better suited for repeat PK than with double glaucoma tubes. Ophthalmology 2008; 115(8):1435.
for DSEK. Tissue dislocation would be difficult to e1.
manage. 6. Clements, JL, Bouchard CS, Lee WB, et al. Retrospective review of
graft dislocation rate associated with Descemet stripping automated
B. Patient MV
endothelial keratoplasty after primary failed penetrating kerato-
Neisseria meningitidis endophthalmitis requiring plasty. Cornea 2011; 30(4):414-418.
extensive vitrectomy, so decision for PK was made 7. Hwang RY, Gauthier DJ, Wallace D, Afshari NA. Refractive
to allow for intraoperative temporary keratopros- changes after Descemet stripping endothelial keratoplasty: a sim-
thesis for better visibility for extensive PPV. plified mathematical model. Invest Ophthalmol Vis Sci. 2011;
52:1043-1054.
Failed PK: How I Choose Between Repeat PK and

a Keratoprosthesis
Kristin M Hammersmith MD
I. Outcomes and Complications of Boston procedures and corneal neovascularization were

Keratoprosthesis (KPro, Type 1) statistically significant risk factors for failure of a
third graft.
A. Outcomes
B. Visual acuity
1. Retention rate of 80%-100% (range of
follow-up: 8.5-33.6 months) Forty percent of patients with a third graft had a
visual acuity of 20/100 or better at postoperative
2. Visual acuity
year 1, 33% at postoperative year 2 and 3, and 20%
a. 1-year: 23%-43% with vision greater than or had better than 20/100 at last follow (mean: 4.3
equal to 20/40 or 20/50, and 59%-77% of years).
patients with greater than or equal to 20/100-
C. Reference
20/200
1. Yildiz EH, Hoskins E, Fram N, et al. Third or
b. 5-year: 29%-100% with vision greater than
greater penetrating keratoplasties: indications,
or equal to 20/200 at 5 years (n = 10 patients)
survival and visual outcomes. Cornea 2010;
B. Complications 29:254-259.
1. Retroprosthetic membrane III. Questions That Help Guide Decision Between Repeat
PK and KPro
2. Corneal melt
A. Who is the patient?
3. Progression of glaucoma
1. Age
4. Endophthalmitis
Boston KPro affords more rapid visual recovery
C. References
in amblyogenic age, but it takes a long time
1. Zerbe BL, Belin MW, Ciolino JB; Boston Type to develop complications (RPM, glaucoma,
1 Keratoprosthesis Study Group. Results from endophthalmitis).
the multicenter Boston Type 1 Keratoprosthesis
a. Nallasamy S, Colby K. Keratoprosthesis:
Study. Ophthalmology 2006; 113:1779-1784.
procedure of choice for corneal opacities in
2. Chew HF, Ayres BD, Hammersmith KM, et children? Semin Ophthalmol. 2010; 25:24-
al. Boston keratoprosthesis outcomes and 28.
complications. Cornea 2009; 28:989-996.
b. Aquavella JV, Gearinger MD, Akpek EK, et
3. Aldave AJ, Kamal KM, Vo RC, Yu F. The al. Pediatric keratoprosthesis. Ophthalmology
Boston type I keratoprosthesis: improving 2007; 114:989-994.
outcomes and expanding indications.
2. Status of fellow eye
Ophthalmology 2009; 116:640-651.
3. Compliance
4. Greiner MA, Li JY, Mannis MJ. Longer-
term complications with the Boston type I B. Why did the graft(s) fail? Are these factors
keratoprosthesis at the University of California, modifiable in the future?
Davis. Ophthalmology. Epub ahead of print 12
1. Limbal stem cell deficiency. Not modifiable
Mar 2011.
without limbal stem cell transplant. Favor KPro.
II. Outcomes for Repeat Penetrating Keratoplasty (PK)
a. Chemical injury
A. Graft survival
b. Aniridia
Six years of Wills Eye Institute cornea records were
c. Autoimmune disorders (TENS, MMP) still
recently reviewed to identify all patients who had
suffer high complication rates from KPro.
undergone 3 or more PKs. Of 45 patients identified,
A titanium KPro backplate and adjunctive
third grafts had an 89% 1-year survival; 78%,
immunomodulation may enhance outcomes.
2-year survival; and 53%, survival at last follow-up
(median 4.3 years). The median survival time for the 2. Recurrent herpetic keratitis
third graft was 12.8 years for Fuchs dystrophy, 5.2
a. Did patient receive postoperative prophylactic
years for herpetic keratitis, 4.0 years in keratoconus,
oral antivirals?
3 years for pseudophakic bullous keratopathy, 2.3
years for iridocorneal endothelial syndrome, and Prophylactic oral acyclovir has been shown
2 years in stromal dystrophies. Previous glaucoma to decrease herpes-related recurrences and
episodes of rejection and improve graft 4. Endothelial failure

survival. (Garcia DD, Farjo Q, Musch DC,
a. Following rejection: If not treated with
et al. Effect of prophylactic oral acyclovir
adequate steroids or if poor compliance with
after penetrating keratoplasty. Cornea 2007;
steroid therapy in past, favor repeat PK. If
26:930-934. van Rooij J, Rijneveld WJ,
treated with aggressive steroids in past, favor
Remeijer L, et al. Effect of oral acyclovir
KPro.
after penetrating keratoplasty for herpetic
keratitis). If patient did not receive oral b. Following subsequent surgery (cataract,
prophylaxis, favor repeat PK with antiviral glaucoma): If current status of the eye is now
therapy. pseudophakic and/or with better controlled
IOP, favor repeat PK.
b. Very promising results of improved vision
and a low complication rate in 14 patients c. Late endothelial failure: If patient had many
with history of failed graft and herpetic dis- years of clear graft but now with late failure,
ease who underwent Boston KPro. (Khan BF, favor repeat PK.
Harissi-Dagher M, Pavan-Langston D, et al.
The Boston keratoprosthesis in herpetic kera-
Additional Selected Readings
titis. Arch Ophthalmol. 2007; 125:745-749.)
If received adequate oral prophylaxis, favor 1. Colby KA, Koo EB. Expanding indications for the Boston kerato-
KPro. prosthesis. Curr Opin Ophthalmol. 2011; 22(4):267-273.
3. Neurotrophic complications 2. Traish AS, Chodosh J. Expanding application of the Boston type
1 keratoprosthesis due to advances in design and improved post-
a. Depends on level of neurotrophia. (Pavan
operative therapeutic strategies. Semin Ophthalmol. 2010; 25:239-
Langston D, Dohlman CH. Boston 243.
keratoprosthesis treatment of herpes zoster
neurotrophic keratitis. Arch Ophthalmol. 3. Ament JD, Todani A, Pineda R, et al. Global corneal blindness
2008; 115:S21-S23.) and the Boston keratoprosthesis type I. Am J Ophthalmol. 2010;
149:537-539.
b. If had PK without tarsorrphaphy, favor
4. Ament JD, Stryjewski TP, Ciolino JB, et al. Cost-effectiveness of the
repeat PK and tarsorrhaphy. If had PK Boston keratoprosthesis. Am J Ophthalmol. 2010; 149:221-228.
with temporary tarsorrhaphy, still with
neurotrophic complications, favor KPro.
Transplantation of Congenitally Opaque Corneas:

Pearls and Pitfalls
Stuart I Brown MD
The experiences of pediatric keratoplasty (PKP) in 72 infant’s Key Factors Toward Success
eyes with congenitally opaque corneas (COC) performed
• Most successes had a relatively normal anatomy (ie, pres-
between 23 and 10 years ago were reviewed and evaluated
ence of lens and majority of iris).
toward determining factors important in achieving transparent
• Intact donor epithelium, which needs protection during
grafts for at least 10 years. All surgeries were performed before 4
surgery in eyes with PSC or SC
months of age.
• Glaucoma, especially the treatment, was associated with
two-thirds of failures.
Classification • Operative identification and location of pupil, iris defects,
and chamber dimensions by transillumination facilitates
Congenitally opaque corneas were classified as follows:
sizing of graft, locating initial incision, and maintaining
• Peters anomaly or central corneal opacities with or with- integrity of lens capsule.
out PAS: Nineteen of the 22 corneal grafts remained trans- • Large donors (of at least 30%) relative to excised host.
parent more than 10 years. Glaucoma occurred in 2 eyes This requires accurate deep placement of sutures, espe-
of the 3 failures. cially when dealing with irregularities in host corneal
• Partial sclerocornea (PSC) or central corneal opacities thickness.
extending to part but not all of the limbus: Eight of 15 • Suture removal between 1 and 2 weeks postoperatively in
grafts remained transparent more than 10 years. Glau- vascularized and between 3 and 6 weeks in nonvascular-
coma only occurred in 5 of the 7 failures. ized corneas
• Sclerocornea (SC)—totally opaque corneas: Three of 7 • Frequent topical corticosteroids for at least 6 months
grafts remained transparent more than 10 years. Glau- • Amblyopia therapy for second eye is critical, but compli-
coma occurred in 3 of the 4 failures. ance is difficult.
• Congenital glaucoma: Two of 2 eyes remained transparent • Transplantation of unilateral congenital corneal opacifica-
more than 10 years. tion provides excellent vision if carried out in the first 3
• Forceps rupture of Descemet membrane: One eye months.
remained transparent more than 10 years. • Corticosteroid-induced pressure elevations occur in infants
as well as adults.
Exclusions The above was important toward our achieving long-term
success: 85% in Peters, 66% in PSC, and 40% in SC.
• Twelve eyes with a mixture of classifications had transpar-
ent grafts but were lost to follow-up between 8 months
and 8 years after surgery.
• Thirteen eyes were excluded because of extreme altera-
tions requiring multiple procedures: corneal keloid (4
eyes), corneal ectasia (3 eyes), microphthalmos < 15 mil-
limeters (3 eyes), and buphthalmos (3 eyes).
Pediatric Keratoprosthesis: Are We There Yet?

James V Aquavella MD
Introduction 360 degree direct inspection of the peripheral retina. An aphakic

powered device is always implanted. In the presence of ocular
Neonatal cornea opacity may be acquired from forceps injury,
surface irregularities, an amniotic membrane may be considered
birth canal infection, or trauma, but it is most frequently congen-
in addition. All cases receive a hydrophilic bandage lens and are
ital as a result of Peters anomaly, glaucoma, nondescript dysgen-
placed on a prophylactic antibiotic regimen with appropriate
esis, or more rarely congenital hereditary endothelial dystrophy.
doses of steroids to control inflammation.
Traditional management involves patching with dilatation to
enable light to enter the eye beyond the confines of the cornea
scarring, optical iridectomy in more severe cases, and cornea Advantages
transplantation. These are not just small eyes with cloudy cor-
Advantages include a rapid progression to best potential acuity,
neas; they are subject to a variety of ophthalmic pathology as a
absence of discomfort, ease of amblyopia treatment, and excel-
result of associated glaucoma, inflammation, and vitreoretinal
lent optics without astigmatism or anisometropia. Direct and
disease. The treating ophthalmologist is aware of the potential
facile observation of the posterior pole is possible from the first
for amblyopia, and parental concerns increase the pressure for
day, and of course graft rejection will not occur.
early diagnosis and therapy.
Disadvantages
Controversies
Disadvantages include the operative team approach with multi-
In monocular cases some feel that no therapy is warranted since
specialty follow-up, long-term antibiotic prophylaxis, maintain-
a reasonably normal development is possible with one eye. There
ing a bandage lens, and the fact that retroprosthetic membranes
is considerable disagreement in the literature as to the results of
occur in 30% of cases.
penetrating keratoplasty. Published reports often differ in the cri-
teria for success or failure: graft clarity, graft survival, and visual
acuity, as well as the length of follow-up. In any event, we are Anticipated Improvements
aware of the significantly elevated incidence of allograft rejection
As with all forms of therapy, improvements will occur over time.
in infants compared with adults.
Management of the ocular surface, new methods for measuring
IOP, and perhaps systemic measures to combat the ever-present
Keratoprosthesis potential for inflammation will be welcome.
Following the reintroduction of the modified Boston type I
device, our team has advocated keratoprosthesis as a primary Conclusions
procedure and most definitely when a standard cornea transplant
For some groups such as ours infant keratoprosthesis is the best
has failed. While a cornea transplant is often performed by a
option to afford the development of useful vision. The inherent
single cornea surgeon, we feel strongly that the combination of
difficulties in dealing with multifactorial pathology as well as the
comorbidity and propensity for inflammation in these infants
related logistical complexities must not be allowed to cloud the
demands a team approach. Thirty percent of our cases are asso-
value of the surgical procedure. Others will be more comfortable
ciated with some form of vitreoretinal disease, glaucoma is not
in awaiting a broader dissemination prior to adopting the tech-
infrequent, and the prospects of amblyopia are ever present.
nology.
Logistical Considerations
Video Summary
A multispecialty team consists of cornea, pediatrics, glaucoma,
The cornea opacification is varied and compounded by previ-
and retina subspecialties. Medical records must be reviewed, and
ous failed keratoplasty. Dysgenesis combined with conjunctiva
a dedicated postoperative management system developed in con-
overgrowth make recognition of the central cornea difficult. A
junction with the referring ophthalmologist, who likely resides in
Flieringa ring precedes a nonpenetrating outline deepened with
a distant location. Prior authorization and insurance issues can-
a diamond blade. Hemostasis is important. Severing adherent
not be avoided. At the very least, exams under anesthesia as well
synechiae and iris dysgenesis can have a variety of presentations.
as the actual surgery will involve both cornea and retina services,
Shunts may be preexisting. Lensectomy and anterior vitrectomy
so coordination and scheduling will be important.
precede placement of the assembled KPro, followed by the ban-
dage lens. Pars plana vitrectomy is the final step in all cases.
Procedural Options
Removal of the clear or opaque natural lens is performed in all
cases. Elevated pressure can be addressed prior to, during, or fol-
lowing the placement of a keratoprosthesis. We feel strongly that
all cases should have the benefit of a pars plana vitrectomy with
Selected Readings
1. Dana MR, Schaumberg DA, Moyes AL, Gomes JA. Corneal trans-
plantation in children with Peters anomaly and mesenchymal dys-
genesis. Ophthalmology 1997; 104(10):1580-1586.
2. Rao KV, Fernandes M, Gangopadhyay N, Vemuganti GK, Krish-
naiah S, Sangwan VS. Outcome of penetrating keratoplasty for
Peters anomaly. Cornea 2008; 27(7):749-753.
3. Yang LL, Lambert SR, Drews-Botsch C, Stulting RD. Long-term
visual outcome of penetrating keratoplasty in infants and children
with Peters anomaly. J AAPOS. 2009; 13(2):175-180.
4. Aquavella JV, Gearinger MD, Akpek EK, McCormick GJ. Pediatric
keratoprosthesis. Ophthalmology 2007; 114(5):989-994.
5. Aquavella JV. Keratoprosthesis in the treatment of congenital cor-
neal opacity. Contemp Ophthalmol. 2008; 7(8):1-6.
58 Section V: Ocular Surface Disease —Therapeutics 2011 Subspecialty Day | Cornea
What to Do for Corneal Neovascularization

Reza Dana MD MSc MPH
I. Background 2. Pterygium
Corneal neovascularization (NV) is the “common E. Limbal stem cell insufficiency states
denominator” of a vast number of corneal and ocular
F. Autoimmune disorders: PUK
surface pathologies. As such, it is associated with the
second most frequent cause of blindness worldwide, G. Meibomian gland dysfunction
cornea scarring. Not only is the invasion of the nor-
H. Neurotrophic disorders
mally avascular and transparent cornea by blood ves-
sels a consequence of many pathologies, but it can also I. Corneal transplant
cause or amplify corneal pathologies by promoting
J. Contact lens–related (hypoxia)
leaky vessels that lead to lipid deposition and ampli-
fied immune responses (eg, as seen in the setting of IV. Therapeutic Approaches
corneal transplantation). For all these reasons, a better
A. Optimize treatment of underlying etiology or
understanding of the pathophysiologic mechanisms of
offending agent
corneal NV and effective therapeutic measures is an
integral part of corneal and external disease manage- 1. Infection
ment.
2. Contact lens
II. Pathogenic Mechanisms of Corneal NV
B. Surgical
A. Molecular and cellular bases of corneal avascularity
1. Excision of lesion (pterygium)
1. Soluble vascular endothelial growth factor
2. Superficial keratectomy ± amniotic membrane
(VEGF) receptors
grafting
2. Ectopic expression of epithelial VEGF receptor
3. Limbal stem cell grafting
(“VEGF sink”)
C. Laser
3. Pigment epithelium-derived factor (PEDF)
D. Photodynamic therapy
4. Other antiangiogenic factors
E. Diathermy/cautery
B. Molecular and cellular bases of corneal NV
F. Pharmacologic
1. Vascular endothelial cell proliferation and migra-
tion 1. “Conventional” drugs
2. Stromal matrix degradation and role of matrix Efficacy: Corticosteroids > NSAIDs >
metalloproteinases (MMPs) cyclosporin A
3. Proangiogenic factors 2. Biologic or small molecule approaches
a. Inflammatory cytokines a. Directed at one or more pathogenic factors
b. VEGFs b. Anti-VEGFs
c. Platelet-derived growth factor i. bevacizumab (Avastin)
d. Fibroblast growth factor ii. ranibizumab (Lucentis)
III. Principal Clinical Etiologies of Corneal NV iii. others
A. Infections c. Others
1. Herpetic
References
2. Bacterial
3. Chlamydial 1. Clements JL, Dana R. Inflammatory corneal neovascularization:
etiopathogenesis. Semin Ophthalmol. 2011. In press.
B. Chemical burns: Alkali > acid
2. Cursiefen C, Chen L, Saint-Geniez M, Hamrah P, Jin Y, Rashid S,
C. Penetrating trauma Pytowski B, Persaud K, Wu Y, Streilein JW, Dana R. Nonvascular
VEGFR-3 expression by corneal epithelium maintains avascularity
D. Degenerations and vision. Proc Nat Acad Sci U S A. 2006; 103:11405-11410.
1. Terrien’s
2011 Subspecialty Day | Cornea Section V: Ocular Surface Disease —Therapeutics 59
3. Gupta D, Illingworth C. Treatments for corneal neovasculariza-

tion: a review. Cornea. Epub ahead of print 11 Mar 2011. PMID:
21403519.
4. Dastjerdi M, Saban DR, Okanobo A, Nallasamy N, Sadrai Z,
Chauhan SK, Hajrasouliha A, Dana R. Effects of topical and sub-
conjunctival bevacizumab (Avastin) in high-risk corneal transplant
survival. Invest Ophthalmol Vis Sci. 2010; 51:2411-2417.
5. Dastjerdi MH, Al-Arfaj KM, Nallasamy N, Hamrah P, Jurkunas
U, Pineda R, Pavan-Langston D, Dana R. Topical bevacizumab in
the treatment of corneal neovascularization: results of a prospec-
tive open-label, non-comparative study. Arch Ophthalmol. 2009;
127:381-389.
Amniotic Membrane Grafts:

Uses and Controversial Uses
Roy S Chuck MD PhD
Pterygium Surgery With Amniotic Membrane Controversies and Limitations of Amniotic

Membrane
An ideal pterygium surgery should achieve three principal goals:
low recurrence rate, lack of complications, and satisfactory cos- The various inhibitory and proinflammatory cytokines and other
metic appearance. A number of methods for surgical excision molecules identified in amniotic membrane may have contradic-
and prevention of recurrence have been reported, with widely tory actions. For example, IL-6 and IL-8 are proinflammatory,
variable results. Although conjunctival autografts have shown and, conversely, IL-10 and IL-1ra are anti-inflammatory, yet
success and are considered the gold standard, they are oftentimes both are present in amniotic membrane. Similarly, the presence
not able to cover large defects created in double-head primary of various growth factors such as epithelial growth factor (EGF)
or large recurrent pterygia. Furthermore, concerns have been can support epithelial growth and transforming growth factor
raised for those in whom there exist free conjunctival shortages (TGF) wound healing. However, under some circumstances TGF
or who may require future glaucoma-filtering surgeries. In addi- can also promote scar tissue formation and counter the “anti-
tion, because of graft suturing, this method has the disadvantage adhesive or scar suppressing action” proposed for the membrane
of a relatively longer surgery time when compared with the bare in preventing corneal and conjunctival cicatrization.
sclera technique. Also, it carries the risk of complications such as A likely mechanism by which amniotic membrane delivers its
granuloma formation and giant papillary conjunctivitis, as well beneficial effect is as a substrate or basement membrane trans-
as significant patient discomfort after surgery. In recent years, a plant for new epithelial cells to migrate on, expand, and adhere
better understanding of the role of limbal stem cells and wide- to. Use of membrane as a bandage to cover inflamed or exposed
spread use of amniotic membrane in pterygium surgery have led areas, due to injury or surgery, not only favorably influences the
to the development of new surgical techniques, especially involv- healing process but also has a dramatic favorable effect on the
ing fibrin glue, for this disease. Some of these techniques will be symptoms of pain or discomfort.
presented and reviewed in this talk. Many differences can also exist between amniotic membranes
Although not without its limitations, amniotic membrane obtained from different donors. Even for the same donor, it is
transplantation has proven successful in reducing recurrence general practice to obtain numerous pieces of amnion for use in
rates in both primary and recurrent pterygia, with minimal com- multiple operations. Therefore, some pieces could be from loca-
plications and good cosmetic results. This is accomplished by tions closer to the placenta and others distant to it. The thick-
thoroughly removing the abnormal pterygium tissue, by restor- ness of these locations can vary, as can the morphology of the
ing the matrix in the excision area through the use of the amni- amniotic epithelium. Age, race, parity, gravidity, and duration
otic membrane, which provides a new basement membrane for of gestation may all contribute to variability of specimens. It is
rapid re-epithelialization and a stromal matrix for suppressing important to keep in mind that membranes used in transplanta-
scarring, and by decreasing inflammation with postoperative use tion are far from standardized across donors and even within the
of topical corticosteroids. The main advantage of using amniotic same donor.
membrane resides in its ability to restore large excised areas (eg, Finally, several differences may exist between different mem-
in double-head or large recurrent pterygia), where a conjuncti- branes depending on whether they are used fresh or preserved
val autograft is not possible. It is also advantageous in cases in and, in the case of the latter, depending on the mode and dura-
which the conjunctiva is already scarred from previous surgery tion of preservation. Most methods employed in the preservation
or has to be reserved for a possible glaucoma-filtering surgery. of the membrane affect it in some manner. The weight of the
However, further randomized, controlled studies are required to evidence available supports the notion that the viability of the
scientifically evaluate the efficacy of the membrane in general, as tissue components of amniotic membrane is not essential for its
well as different membrane preparations. Perhaps the generation biological effectiveness. Until the effect of different methods of
of a “synthetic membrane,” in which collagen or polymers are preservation and storage has been fully evaluated and standard-
used as matrices to incorporate growth factors, cytokines, anti- ized, success or failure of the membrane should be qualified by
microbial peptides, and other substances tailored toward specific the method of preservation employed.
clinical applications, will be possible in the future. This could
pave the way to a standardized product with known quantities
of desired ingredients with hopefully even more predictable out-
comes.
Scleral Contact Lenses: Resolving Ocular

Surface Issues?
Andrew J W Huang MD MPH
I. Definition of Scleral Contact Lenses IV. Indications for Scleral Contact Lenses
Scleral contact lenses are large-diameter rigid gas-per- A. Corneal irregularity
meable lenses ranging from 15 to 24 mm in diameter
1. Primary corneal ectasias: Keratoconus, kerato-
(vs. hybrid lens or large silicone lens).
globus, pellucid marginal degeneration, Terrien
II. Lens Types marginal degeneration
III. History of Scleral Contact Lenses: Old Concept, but 2. Secondary/postsurgical corneal ectasias: Post-
New Tool LASIK and post-PRK, irregular corneas due to
trauma or corneal graft
A. 1500s: Leonardo da Vinci first described contact
lenses B. Protection of ocular surface
B. 1880s: Glass contact lenses first produced 1. Severe ocular surface disease: Sjögren syndrome,
Stevens-Johnson syndrome, mucous membrane
1. FE Muller: Blown glass scleral lenses for his own
pemphigoid, graft vs. host disease, persistent
severe myopia (1887)
epithelial corneal defects, neurotrophic ulcers,
2. AE Fick: Filling the glass lens shells with a thick corneal anesthesia (herpes simples virus, herpes
grape sugar solution to promote movement of zoster ophthalmicus, trigeminal ablation)
the lens on the cornea (1888).
2. Limbal stem cell deficiency: Aniridia, radiation,
3. E Kalt: Glass contact shell for keratoconus (1888) chemical burns
C. 1920s: First preformed ground glass scleral shell fit- 3. Lagophthalmos: Facial palsies, ectropion, exoph-
ting sets thalmos, eyelid coloboma
D. 1930s: Polymethylmethacrylate (PMMA) with C. Cosmesis: Corneal opacities, ptosis
impression molding
V. Pros and Cons of Scleral Contact Lenses
E. 1950s: Smaller PMMA corneal lens vs. larger scleral
A. Advantages
lens
1. Larger size (up to 25 mm , ~ the size of a quarter)
F. 1960s: More flexible and oxygen permeable “soft”
for excellent protection of the ocular surface
hydrogel materials
2. Vaulting the cornea without limbal bearing
G. 1980s: “Breathable” rigid gas permeable (RGP)
materials 3. Masking surface irregularity and independent of
the corneal contour
H. 1990s: Silicone hydrogels and newer, high-oxygen
permeable polymers with new design concepts to 4. May preserve large tear reservoir
manufacture scleral lenses
5. More physiological and comfortable with less
I. Today decentration
1. Pullum scleral lens (Kenneth Pullum) extensively B. Disadvantages
used overseas
1. Poor surface wetting with reduced oxygen per-
2. Boston scleral lens (aka Prosthetic Replacement meability to cornea
of the Ocular Surface Ecosystem [PROSE], Perry
2. Challenging and time-consuming to fit
Rosenthal) primarily in the United States
3. Relatively prohibitive costs
4. Difficulty of lens insertion and removal
Table 1. Types of Scleral Contact Lenses
Lens Type Alternative Name Diameter Bearing Tear Reservoir

Corneal Up to 12.5 mm On cornea None
Corneoscleral Semi-scleral; Limbal 12.5 to 15 mm On limbosclera Limited
Mini-scleral (Mini) Haptic 15 to 18 mm On sclera Slightly limited
(Full) Scleral Haptic 18 to 24 mm On sclera Ample
VI. Designs and Costs of Scleral Contact Lenses VII. Special Applications of Scleral Contact Lenses
A. Designs A. As therapeutic reservoirs
1. Traditional: Serial conics (optical, transition, and 1. Autologous serum
landing zones) with fenestration
2. Growth factors (EGF, NGF)
2. Newer: Custom-lathe, spline functions, fluid ven-
3. Bevacizumab (Avastin)
tilation
B. As surgical adjuncts
B. Costs
1. Post-LASIK keratoneuralgia
1. Custom fit and manufactured for specific pathol-
ogy and patient needs 2. Corneal collagen crosslinking
2. Considerable chair and fitting time 3. Ocular surface reconstruction or limbal stem cell
transplantation
3. Approximately $4000 per lens (PROSE; $5000
one eye and $7600 both eyes, EyeWorld, 2011)
4. Lens maintenance and replacement costs
Dry Eye: A Burning Issue Revisited

Penny A Asbell MD FACS
Definition of Dry Eye Disease MGD Report: (Meibomian Gland Dysfunction Workshop)
Chronic pain syndrome associated with fluctuating vision. 9. Nichols KK. The International Workshop on Meibomian Gland
Dysfunction: introduction. Inv Ophthalmol Vis Sci. 2011; 52:1917-
1921.
Selected Readings
10. Nichols KK, Foulks GN, Bron AJ, et al. The International Work-
1. Asbell PA, Lemp M, eds. Current Treatment and Diagnosis in Dry shop on Meibomian Gland Dysfunction: executive summary. Inv
Eye Disease. New York: Thieme Medical Publishers; 2006. Ophthalmol Vis Sci. 2011; 52:1922-1929.
11. Nelson JD, Shimazaki J, Benitez-del-Castillo JM, et al. The Interna-
DEWS (Dry Eye WorkShop): www.tearfilm.org/dewsreport/ tional Workshop on Meibomian Gland Dysfunction: report of the
Definition and Classification Subcommittee. Inv Ophthalmol Vis
2. Introduction to the Report of the 2007 International Dry Eye Sci. 2011; 52:1930-1937.
WorkShop (DEWS). Ocul Surf. 2007; 5(2):69-70.
12. Knop E, Knop N, Millar T, Obata H, Foulks GN. The International
3. The definition and classification of dry eye disease: report of the Workshop on Meibomian Gland Dysfunction: report of the Sub-
Definition and Classification Subcommittee of the International committee on Anatomy, Physiology, and Pathophysiology of the
Dry Eye WorkShop (2007). Ocul Surf. 2007; 5(2):75-92. Meibomian Gland. Inv Ophthalmol Vis Sci. 2011; 52:1938-1978.
4. The epidemiology of dry eye disease: report of the Epidemiology 13. Green-Church KB, Butovich I, Willcox M, et al. The International
Subcommittee of the International Dry Eye WorkShop (2007). Workshop on Meibomian Gland Dysfunction: report of the Sub-
Ocul Surf. 2007; 5(2):93-107. committee on Tear Film Lipids and Lipid-Protein Interactions in
5. Methodologies to diagnose and monitor dry eye disease: report of Health and Disease. Inv Ophthalmol Vis Sci. 2011; 52:1979-1993.
the Diagnostic Methodology Subcommittee of the International Dry 14. Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols
Eye WorkShop (2007). Ocul Surf. 2007; 5(2):108-152. KK. The International Workshop on Meibomian Gland Dysfunc-
6. Design and conduct of clinical trials: report of the Clinical Trials tion: report of the Subcommittee on the Epidemiology of, and
Subcommittee of the International Dry Eye WorkShop (2007). Associated Risk Factors for, MGD. Inv Ophthalmol Vis Sci. 2011;
Ocul Surf. 2007; 5(2):153-162. 52:1994-2005.
7. Management and therapy of dry eye disease: report of the Man- 15. Tomlinson A, Bron AJ, Korb DR, et al. The International Work-
agement and Therapy Subcommittee of the International Dry Eye shop on Meibomian Gland Dysfunction: report of the Diagnosis
WorkShop (2007). Ocul Surf. 2007; 5(2):163-178. Subcommittee. Inv Ophthalmol Vis Sci. 2011; 52:2006-2049.
8. Research in dry eye: report of the Research Subcommittee of 16. Geerling G, Tauber J, Baudouin C, et al. The International Work-
the International Dry Eye WorkShop (2007). Ocul Surf. 2007; shop on Meibomian Gland Dysfunction: report of the Subcommit-
5(2):179-193. tee on Management and Treatment of Meibomian Gland Dysfunc-
tion. Inv Ophthalmol Vis Sci. 2011; 52:2050-2064.
17. Asbell PA, Stapleton FJ, Wickström K, et al. The International
Workshop on Meibomian Gland Dysfunction: report of the Clini-
cal Trials Subcommittee. Inv Ophthalmol Vis Sci. 2011; 52:2065-
2085.
64 Surgery by Surgeons 2011 Subspecialty Day | Cornea
2011 Surgery by Surgeons Update

Stephanie J Marioneaux MD
With this year’s passage of legislation in Kentucky that allows the Washington DC area to provide critical input and to discuss
optometrists to perform laser surgery, the American Academy and collaborate on the American Academy’s advocacy agenda.
of Ophthalmology’s partnership with ophthalmic subspecialty The Cornea Society remains a crucial partner to the Academy
and state societies on the Surgery by Surgeons campaign becomes in its ongoing federal and state advocacy initiatives. As a 2011
even more important in protecting quality patient eye care across Congressional Advocacy Day (CAD) partner, The Cornea Soci-
the country. ety ensured a strong presence of cornea specialists to support
In 2009-2010, the Eye M.D.s serving on the Academy’s Secre- ophthalmology’s priorities as over 350 Eye M.D.s had scheduled
tariat for State Affairs collaborated with the leadership of many CAD visits to members of Congress in conjunction with the
state ophthalmology societies on legislative battles in which Academy’s 2011 Mid-Year Forum in Washington DC.
optometry continued to push for expanded scope of practice. At the state level, the Academy’s Surgery by Surgeons cam-
Leadership of subspecialty societies provided essential support paign has demonstrated a proven track record. Kentucky was an
in some of these battles. Success was reached with surgery pro- outlier; the Academy’s SSF has helped 31 state ophthalmology
visions removed and/or bills defeated in Idaho, Maine, Missis- societies reject optometric surgery language.
sippi, Nebraska, South Carolina, Texas, Washington and West Help us help you protect our patients and quality eye care.
Virginia. The Academy’s Surgical Scope Fund remains a critical tool in the
In 2011, the stakes were raised with the disappointing out- Surgery by Surgeons campaign. The Academy’s Surgical Scope
come in Kentucky. The Kentucky legislation also includes the Fund Committee works hard on your behalf to ensure the ongo-
creation of an independent optometric board; no other board or ing strength and viability of the SSF.
state agency has the authority to question what constitutes the
practice of optometry. The Secretariat for State Affairs continues Thomas Graul MD (Nebraska): Chair
to work diligently with state society leaders in South Carolina, Arezio Amirikia MD (Michigan)
Nebraska, Tennessee and Texas to ensure that a Kentucky out- Kenneth P Cheng MD (Pennsylvania)
come is not repeated. For example, following the passage of leg-
Bryan S Lee MD PhD (Maryland): Consultant
islation in Kentucky, fundraising material by organized optom-
etry in Tennessee made it clear that they would like to replicate Richard G Shugarman MD (Florida)
optometry’s outcome in Kentucky and have begun discussions Stephanie J Marioneaux MD (Virginia)
with state legislators. Bryan S Sires MD PhD (Washington)
The Surgical Scope Fund (SSF) is a critical tool of the Surgery
Andrew Tharp MD (Indiana)
by Surgeons campaign to protect patient quality of care. The
Academy relies not only on the financial contributions via the Ex-officio members:
SSF by individual Eye M.D.s but also on the contributions made Cynthia A Bradford MD
by ophthalmic state, subspecialty and specialized interest societ- Daniel J Briceland MD
ies. The Cornea Society contributed to the SSF in 2010, and the The SSF is our collective fund to ensure that optometry does not
Academy counts on its contribution in 2011. legislate the right to perform surgery. Do not forget about Con-
The results in Kentucky should be viewed as a failure neither gress, where ophthalmology’s influence is through OPHTHPAC.
of the SSF nor of the Academy’s Secretariat for State Affairs, Just as a strong state presence is needed, so do we need to remain
which geared up immediately to strategize with Kentucky strong in the federal arena. While OPHTHPAC is the third larg-
Academy physician leadership. In a period of 15 days, with no est medical PAC, a mere 15% of the Academy’s membership
advanced warning, optometry was able to introduce and pass a contribute.
bill in the Kentucky state legislature and secure its passage into The Kentucky legislation is not in the best interests of patient
law. A SSF disbursement actually assisted with critical media safety and quality patient care. Ophthalmology needs the active
buys and powerful public messaging favoring ophthalmology support of every member—and this includes contributions to the
and quality patient eye care for the citizens of Kentucky. This Surgical Scope Fund, state eye PACs and OPHTHPAC.
should be a lesson to each Eye M.D. in the country about the Please respond to your SSF Committee and OPHTHPAC
importance of contributions to your state eyePAC and to the Committee colleagues when they call on you and your subspe-
SSF. cialty society to contribute. There are some decisions that require
Leaders of The Cornea Society are part of the American thought, but donating $500 to the SSF and OPHTHPAC is the
Academy of Ophthalmology’s Ophthalmology Advocacy Lead- easy answer for you and your patients. Do it today. Do it now.
ership Group (OALG), which has met for the past four years in
2011 Subspecialty Day | Cornea Section VI: Cornea Potpourri 65
Straighten Up and Listen: Ergonomics for Your

Aching Back
Anna Kitzmann MD
It’s been a long day; you’ve seen 40 patients and performed many Recommendations for Decreasing Risks for MSDs4
laser vision correction procedures. You leave work, and driv-
ing home you note stiffness in your lower back and neck. You In the operating room
turn on your heated seat despite the 90 degree outside tempera- • Adjust seat, table, and scope to accommodate a neutral
ture and soon feel relief from your back and neck discomfort. posture.
However, a disturbing thought runs through your mind: is the • Use seats with padded lumbar support and adjustable
stiffness related to all the awkward positioning and static muscle height features to maintain a neutral pelvis.
contractions throughout the day? Will this stiffness and/or pain • Keep the lumbar spine in contact with the back support.
become chronic? You are not alone, as many of your colleagues • Rest elbows at sides and wrists on a padded support.
also have had musculoskeletal symptoms and pain. • Do not elevate/abduct the arms.
The prevalence of musculoskeletal disorders (MSDs) has been
reported over the past decade in the ophthalmic literature and at At the slitlamp and laser
various meetings. While the survey instruments and populations • Adjust equipment and patient position to maintain neutral
studied are variable, an approximate prevalence of neck pain is posture.
33%-69%; lower back pain, 38%-80%; and both neck and back • Use seats with height and anterior tilt features to accom-
pain, 52%-54%.1 In a recent survey conducted by the Academy modate sitting postures.
in 2009 during its biennial random survey of its members, 951 • Tilt the pelvis anteriorly to maintain the lumbar lordosis.
members responded, with 30% experiencing current neck prob- • Rest elbows only on a foam-padded or viscoelastic surface.
lems and 20% experiencing current upper or lower back, hand,
Will any of this advice translate to reduced MSDs in oph-
or arm problems related to working.2
thalmologists? In the Netherlands, 50% of dentists adopted all
However, none of these surveys had a control group of non-
or most and an additional 40% adopted some of their dental
ophthalmologists to determine if the prevalence of MSD symp-
profession’s ergonomic recommendations, with a resulting 72%
toms in ophthalmologists is higher. At the University of Iowa
reduction or disappearance of their main MSD complaint.5
and Mayo Clinic, we used a standard survey instrument to deter-
Perhaps we should follow the advice of baseball player Dante
mine MSD symptoms in eye care physicians and family medicine
Bichette Jr: “Keep your head up and don’t let anything get to
physicians. In this study, eye care physicians had a statistically
you. Always keep good posture.”
significantly higher prevalence of neck, hand/wrist, and low back
Optimal positioning during examinations and in the operat-
pain compared to family medicine physicians.3
ing room will be shown with photographic representation of
In response to published reports and data from the recent
incorrect and improved positioning. A noon-time symposium on
Academy membership survey, the Academy Board of Trustees
Ergonomics in Ophthalmology will be presented on Monday,
has commissioned a task force composed of 6 ophthalmologists,
October 24.
a group of ergonomics specialists, and Academy leadership. Our
goals are (1) to inform academy members about common occu-
pational musculoskeletal disorders and how to prevent them References
and (2) to develop ergonomic guidelines/standards for oph-
1. Dhimitri KC, McGwin G Jr, McNeal SF, et al. Symptoms of muscu-
thalmic equipment and encourage their adoption by the device
loskeletal disorders in ophthalmologists. Am J Ophthalmol. 2005;
industry.
139:179-181.
While the task force works with ergonomics specialists, what
can we do now to help members? We can educate members 2. AAO Biennial Survey of Members. 2009. Unpublished.
about ergonomic postures in the office and operating room and 3. Kitzmann AS, Fethke NB, Baratz KH, et al. A survey study of mus-
share advice on preventative exercises. culoskeletal disorders among eye care physicians compared to fam-
ily medicine physicians. Ophthalmology. In press.
4. Mark JL, Wertz FD, Dhimitri KC. Work-related musculoskeletal
disorders in ophthalmologists. Tech Ophthalmol. 2005; 3:54-61.
5. Droeze EF, Jonsson H. Evaluation of ergonomic interventions to
reduce musculoskeletal disorders of dentists in the Netherlands.
Work 2005; 25:211-220.
66 Section VI: Cornea Potpourri 2011 Subspecialty Day | Cornea
Corneal Imaging: Confocal, OCT, and Ultrasound

Biomicroscopy —What Are They Good For?
Majid Moshirfar MD, Brent Betts BS
I. Evolution of Corneal Imaging methods of flap creation, but returned to

normal levels 36 months following sur-
A. Corneal imaging has grown from traditional kera-
gery.
tometry to advanced imaging modalities capable of
3-dimensional analysis of the cornea. iii. Femtosecond flap creation was not associ-
ated with faster corneal reinnervation.
B. These new imaging modalities have uses in refrac-
tive surgery, the diagnosis of corneal pathology, and b. Corneal haze assessment
accurate assessment of anterior chamber measure-
i. McLaren et al assessed corneal haze in 35
ments.
post-LASIK eyes and 36 untreated eyes via
II. Cornea Imaging Today: In vivo confocal microscopy SSCM.3
(IVCM)1
ii. Image intensity was 30% lower in the
A. How does it work? stroma of LASIK treated eyes (P < .001).
Brightness was not significantly different
1. Light focuses on tissue through an objective lens
between the groups
and is reflected back to through objective lens
and into a detection apparatus. c. Flap healing
2. Takes information from tissue without the need i. Petroll et al assessed corneal keratocyte
for physical sectioning response following flap creation with the
IntraLase FS60 Laser.4
B. Types of IVCM
ii. Keratocyte activation was found in 10 of
1. Tandem scanning-based confocal microscopy
30 eyes, but interface haze was trace. The
(TSCM)
authors recommended a higher steroid
a. Simple design, but low intensity of illumina- dose to decrease keratocyte activation.
tion
2. Cell density measurements
b. Inefficient illumination causes it to appear
a. Analysis in LASIK/PRK
bright to the patient and causes patient dis-
comfort. i. Amoozadeh et al examined stroma and
endothelial cell counts following LASIK
2. Slit-scanning confocal microscopy (SSCM)
and PRK.5
a. Slit aperture allows increased light through-
ii. Anterior stromal keratocyte count sig-
put, which improves field brightness and con-
nificantly decreased 6 months following
trast vs. TSCM
LASIK/PRK.
b. Lower illumination is more comfortable for
iii. Stromal and endothelial cell counts were
patients.
not significantly different after surgery
3. Laser scanning confocal microscopy (LSCM) between the groups.
a. Provides faster scanning of the tissue plane via b. Analysis in Fuchs dystrophy
laser technology
i. Hecker et al examined anterior keratocyte
b. High-depth resolution and high contrast populations in corneas that required PKP
allow for more detailed view of tissue vs. for Fuchs dystrophy.6
SSCM and TSCM
ii. Anterior keratocytes decreased 54%-63%
C. Clinical applications in Fuchs dystrophy.
1. LASIK iii. The authors felt anterior stromal changes
may contribute to degrading vision follow-
a. Corneal sub-basal nerve layer assessment
ing an endothelial keratoplasty.
i. Patel et al fellow eye study comparing
3. Infectious keratitis
sub-basal nerve density with SSCM in fem-
tosecond laser and microkeratome created a.
Acanthamoeba: Shirashi et al used LSCM to
flaps2 monitor tissue response to treatment against
Acanthamoeba and adjust the treatment regi-
ii. Nerve density was significantly decreased
men as needed.7
(P < .001) following surgery with both
b. Fungal keratitis: Takezawa et al found LSCM C. Clinical applications

to be an effective tool in quick diagnosis of
1. LASIK
fungal keratitis and monitoring the effect of
therapy in FK.8 a. Postoperative analysis of LASIK flaps created
with femtosecond laser can be accurately
c. Vaddavalli et al found SSCM had 88.3%
assessed with FD-OCT.15
sensitivity and 91.1% specificity in identifying
fungal filaments and Acanthamoeba cysts.9 b. SD-OCT provides more consistent flap thick-
ness estimates than TD-OCT 1 month follow-
d. Curzat et al has recently shown increased cor-
ing LASIK.16
neal epithelial dendritic cell density correlates
with decreased sub-basal nerve density in 2. Anterior segment pathology detection
infectious keratitis.10
SD-OCT has recently been shown to be useful in
e. Acanthamoeba, fungal, and bacterial keratitis the detection of Salzmann nodular degeneration,
all cause temporary neurotrophic keratopa- corneal dystrophy of Bowman layer type II, and
thy. granular dystrophy, among others.17
f. Loss of nerve plexus more severe in Acan- 3. Wound healing assessment
thamoeba keratitis.
AS-OCT has recently been shown to help assess
III. Cornea Imaging Today: Ultrasound Biomicroscopy quality of epithelial wound healing in patients
(USBM) who are wearing therapeutic contact lenses.18
A. Cost effective real-time imaging 4. Anterior chamber (AC) dimensions
B. Clinical applications Doors et al analyzed AC dimensions with
TD-OCT before and after implantation of iris-
1. Corneal layer imaging: Corneal thickness
fixated phakic IOLs (pIOL). The authors found
Reinstein et al showed USBM generates highly most measurements did not differ significantly
repeatable corneal layer readings and suggest this from preop to postop, with a range of agreement
may have application in keratoconus screening between preop and postop measurements to be
and assessing candidacy for LASIK.11 between 0.24 mm and 0.29 mm. There was a
significant difference between preop and postop
2. Keratoconus: Javadi et al used USBM to confirm
distance from the nasal edge of the pIOL to the
acute hydrops following DALK in a patient with
endothelium and the distance from the pIOL to
keratoconus.12
the crystalline lens.19
3. Phakic IOL implantation: Choi et al found using
III. Future Directions
USBM to measure sulcus-to-sulcus horizontal
diameter for an implantable contact lens to be A. Confocal microscopy: Multiphoton fluorescence
more accurate in creating an ideal ICL vault than and second harmonic generation microscopy
traditional white-to-white horizontal corneal
1. Tan et al used this technology ex vivo to monitor
diameter.13
corneal structural changes in infectious keratitis.
IV. Cornea Imaging Today: Optical Coherence Tomogra-
2. Furthermore, this imaging modality may increase
phy (OCT)14
the ability to diagnose the cause of infectious
A. How does it work? keratitis.20
Measurement is based on the delay of light reflected B. Ultrasound biomicroscopy: Acoustic radiation force
from the tissue back to the detection apparatus. imaging
B. Types of OCT 1. May have application in measuring the elastic
qualities of the cornea
1. Time domain (TD-OCT)
2. Hollman et al used radiation force imaging to
a. Tissue depth is detected serially, but image
measure lens elasticity in vivo.21
acquisition is slower than newer technologies
due to mechanical parts. C. Optical coherence tomography
b. Penetrates deeper through sclera and iris due 1. Applications in determining IOL power calcula-
to longer wavelength tions in patients who have had laser vision cor-
rection
2. Fourier domain (FD-OCT) or spectral domain
OCT (SD-OCT) 2. Tang et al found OCT was statistically similar to
established formulas in determining IOL power
a. Tissue depth detected as a spectrum
for cataract surgery and have an ongoing study
b. Higher definition and faster than TD-OCT looking at OCT’s application in IOL power
determination following laser refractive sur-
gery.22
References
1. Guthoff RF, Zhivov A, Stachs O. In vivoconfocal microscopy, an 13. Choi KH, Chung SE, Chung TY, Chung ES. Ultrasound biomi-
inner vision of the cornea—a major review. Clin Experiment Oph- croscopy for determining Visian implantable contact lens length in
thalmol. 2009; 37(1):100-117. phakic IOL implantation. J Refract Surg. 2007; 23(4):362-367.
2. Patel SV, McLaren JW, Kittleson KM, Bourne WM. Subbasal nerve 14. Konstantopoulos A, Yadegarfar G, Fievez M, Anderson DF,
density and corneal sensitivity after laser in situ keratomileusis: fem- Hossain P. In vivo quantification of bacterial keratitis with opti-
tosecond laser vs mechanical microkeratome. Arch Ophthalmol. cal coherence tomography. Invest Ophthalmol Vis Sci. 2011;
2010; 128(11):1413-1419. 52(2):1093-1097.
3. McLaren JW, Bourne WM, Patel SV. Standardization of corneal 15. Rosas Salaroli CH, Li Y, Zhang X, et al. Repeatability of laser in
haze measurement in confocal microscopy. Invest Ophthalmol Vis situ keratomileusis flap thickness measurement by Fourier-domain
Sci. 2010; 51(11):5610-5616. optical coherence tomography. J Cataract Refract Surg. 2011;
37(4):649-654.
4. Petroll WM, Bowman RW, Cavanagh DH, Verity SM, Mootha V,
McCulley JP. Assessment of keratocyte activation following LASIK 16. Hall RC, Mohamed FK, Htoon HM, Tan DT, Mehta JS. Laser in
with flap creation using the IntraLase FS60 Laser. J Refract Surg. situ keratomileusis flap measurements: comparison between observ-
2008; 24(8):847. ers and between spectral-domain and time-domain anterior seg-
ment optical coherence tomography. J Cataract Refract Surg. 2011;
5. Amoozadeh J, Aliakbari S, Behesht-Nejad AH, et al. Confocal
37(3):544-551.
microscopy of corneal stroma and endothelium after LASIK and
PRK. J Refract Surg. 2009; 25(suppl):S963-S967. 17. Vajzovic LM, Karp CL, Haft P, et al. Ultra high-resolution anterior
segment optical coherence tomography in the evaluation of ante-
6. Hecker LA, McLaren JW, Bachman LA, Patel SV. Anterior kerato-
rior corneal dystrophies and degenerations. Ophthalmology 2011;
cyte depletion in Fuchs endothelial dystrophy. Arch Ophthalmol.
118(7):1291-1296.
2011; 129(5):555-561.
18. Pang CE, Vanathi M, Tan DTH, Mehta JS. Evaluation of corneal
7. Shiraishi A, Uno T, Oka N, et al. In vivo and in vitro laser confo-
epithelial healing under contact lens with spectral-domain anterior
cal microscopy to diagnose acanthamoeba keratitis. Cornea 2010;
segment optical coherence tomography (SD-OCT). Open Ophthal-
29(8):861-865.
mol J. 2011;5:51.
8. Takezawa Y, Shiraishi A, Noda E, et al. Effectiveness of in vivo
19. Doors M, Berendschot TT, Hendrikse F, Webers CA, Nuijts RM.
confocal microscopy in detecting filamentous fungi during clinical
Value of preoperative phakic intraocular lens simulation using
course of fungal keratitis. Cornea 2010; 29(12):1346-1352.
optical coherence tomography. J Cataract Refract Surg. 2009;
9. Vaddavalli PK, Garg P, Sharma S, et al. Role of confocal micros- 35(3):438-443.
copy in the diagnosis of fungal and Acanthamoeba keratitis. Oph-
20. Tan HY, Sun Y, Lo W, et al. Multiphoton fluorescence and second
thalmology 2011; 118(1):29-35.
harmonic generation microscopy for imaging infectious keratitis. J
10. Cruzat A, Witkin D, Baniasadi N, et al. Inflammation and the ner- Biomed Opt. 2007; 12(2):024013.
vous system: the connection in the cornea in patients with infectious
21. Hollman KW, O’Donnell M, Erpelding TN. Mapping elasticity in
keratitis. Invest Ophthalmol Vis Sci. 2011; 52(8):5136-5143.
human lenses using bubble-based acoustic radiation force. Exp Eye
11. Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. Res. 2007; 85(6):890-893.
Repeatability of layered corneal pachymetry with the Artemis very
22. Tang M, Li Y, Huang D. An intraocular lens power calculation
high-frequency digital ultrasound arc-scanner. J Refract Surg. 2009;
formula based on optical coherence tomography: a pilot study. J
26(9):646-659.
Refract Surg. 2010; 26(6):430.
12. Javadi MA, Feizi S, Kanavi MR, et al. Acute hydrops after deep
anterior lamellar keratoplasty in a patient with keratoconus. Cor-
nea 2011; 30(5):591-594.
Corneal Topography and Tomography Interpretation

for the Cataract Surgeon: Implications for Premium
and Toric IOLs
Randy J Epstein MD
I. Cataract surgeons should, at this point, perform preop B. Macular pathology (epiretinal membranes, drusen):
topography on every patient We frequently check macular OCT preop
A. Even if you don’t use any premium IOLs C. Abnormal corneas
B. Cataract surgery is refractive surgery! 1. Keratoconus, prior cornea and/or refractive sur-
gery
II. The Role of Topography and Tomography
2. Severe ocular surface disease (EBMD, keratocon-
A. Preoperative
junctivitis sicca)
1. Defining preop astigmatism
D. Glasses-wearing low myopes
2. Assessment of ocular surface disease
VI. Presbyopia-Correcting IOLs: Complications
a. Dry eyes
A. IOL power errors
b. Epithelial basement membrane dystrophy
B. Miscommunication with patients (mono-vision, etc.)
(EBMD)
C. Surgical complications
3. Detecting occult keratoconus
1. Backup IOLs need to be available: 3-piece multi-
4. Staging of the cataract
focals with PMMA haptics
B. Intraoperative
2. No backup for toric IOL, so prepare for LRIs
1. Placement of incision (preferably in steep axis) (another reason for topography)
2. Placement of the IOL VII. Presbyopia-Correcting IOLs: Postop Issues
C. Postoperative A. Younger patients may have issues with contrast sen-
sitivity, etc. when used for RLE.
1. Dealing with the “unhappy patient”
B. Failure to underpromise/overdeliver
2. Planning for “enhancements”
C. Use -2.50 D glasses for demo of what near visual
III. “Upgrades” for Premium IOLs
acuity would have been like without multifocal IOL.
Should include postop enhancements: limbal relaxing
D. Use topography to illustrate residual astigmatism
incisions (LRIs), PRK, LASIK. If you don’t do corneal
(which is usually the issue).
refractive surgery/IOL XC, establish a relationship with
a refractive surgeon who does. E. Have a low threshold for offering no charge PRK/
LASIK touch-ups.
IV. Refractive Lens Exchange (RLE)
F. Dissatisfaction after implantation of multi-focal
A. My preferred procedure for patients > 60 years old
IOL’s: De Vries, et al. J Cataract Refract Surg. 2011.
who are interested in refractive surgery
1. Ametropia and/or astigmatism was the main
B. Azar study: LASIK is “OK” for older (presbyopic)
cause of blurred vision.
patients.
2. 84% successfully treated: brimonidine, refractive
C. RLE with a multifocal IOL addresses both distance
correction, refractive surgery, YAG.
and near issues most effectively.
3. Only 4% required IOL exchange.
1. Treats lens (“cataract”)-induced higher-order
aberrations and “lenticular astigmatism” VIII. Toric IOLs
2. Avoids dissatisfaction with “quality” of vision A. Astigmatism correction always takes precedence
over presbyopia Rx!
3. Eliminates “post-LASIK IOL calculation hassle”
for inevitable cataract surgery 1. I rarely use multifocal IOLs if over +1.5D corneal
cylinder.
V. Objective Exclusion Criteria for Presbyopia-Correcting
IOLs 2. My comment: “You have 3 problems (cataract,
astigmatism, and presbyopia), and we can only
A. Astigmats (> 1.5 D of corneal astigmatism)
fix 2 at the present time.”
3. Otherwise patients may wind up with inadequate IX. The Use of Corneal Tomography for Cataract Surgery
uncorrected distance and near vision.
A. Pentacam Comprehensive Eye Scanner
B. Toric/multifocal IOLs
1. Most popular example of this technology in the
1. Currently investigational but in use in Europe United States at present (Oculus GmbH, Wetzlar
Germany)
2. May enable us to treat all 3 problems simultane-
ously 2. Scheimpflug camera: rotates around a meridian
point, captures thin slices of tissue
C. Contraindications to the use of toric IOLs: Not too
many! 3. Uses in cataract surgery planning:
1. Fewer ocular issues: OK to use with GLC, AMD, a. Holladay Report
postops, etc.
b. Nuclear Grading System (PNS) software
2. KC +/- May change with Orange (WaveTec
c. Accurate white-to-white measurements
Vision Systems, Aliso Viejo CA), etc.
B. Pentacam Holladay Report
3. ? Ocular surface disease (EBMD, dry eyes)
1. “True corneal power”: equivalent “K” reading
D. Toric IOLs with or without LRIs: Preop consider-
(EKR) at 4.5 mm o.z.
ations
2. “Power spread” graphs provide a measure of
1. LRIs: online calculator = ASCRS calculator
accuracy (or at least the range).
(www.ascrs.org)
3. Tangential and pachymetry maps, plus axial
2. Surgical planning
power and standard topography
3. Incision placement: Online “toric IOL calcula-
4. Can demonstrate degree of post–refractive sur-
tor” takes into account your surgically induced
gery power spread
astigmatism (SIA) = (www.acrysoftoriccalculator
.com) C. Pentacam Nucleus grading System (PNS) software
E. Choice of toric IOL is facilitated by careful study of 1. Can determine density and volume of nucleus
topography preop
1. Calculate how much corneal astigmatism you 2. Useful for OR phaco parameter presets
want to correct when choosing IOL power.
3. Objective and reproducible
2. Higher powers are now available.
4. Improves efficiency and safety
3. Factor in “lenticular astigmatism”: Ignore it!
5. Documentation
4. Use other measurements (like interferometer,
D. IOL exchange techniques: Critical to master with
etc.) to corroborate cylinder axis as glasses and
premium IOLs
refraction not reliable with cataract
F. Toric IOL positioning
References
1. Bring topography to the OR.
1. deVries NE, Webers CAB, Wouter RH. Dissatisfaction after
2. Put axis marks on the eye, using topography as a implantation of multifocal intraocular lenses. J Cat Ref Surg. 2011;
guide. 37:859-865.
3. Initial partial alignment: Allow for clockwise 2. Ghanem RC, de la Cruz, J, Tobaigy FM, Ang LPK, Azar DT.
rotation. LASIK in the presbyopic age group. Ophthalmology 2007;
114:1303-1310.
G. What if there is more astigmatism than a toric IOL
can correct? 3. Wolffsohn JS, Bhogal G, Shah S. Effect of uncorrected astigmatism
on vision. J Cataract Refract Surg. 2011; 37:454-460.
1. Not likely with extended power range now avail-
4. Rao S, Konowal A, Murchison AE, Epstein RJ. Enlargement of the
able
temporal clear corneal incision to treat pre-existing astigmatism.
2. Make incision in steep axis and extend it (Epstein J Refract Surg. 2002; 18:463-467.
study)
Feel free to contact me at: repstein@chicagocornea.com
3. Add LRIs in addition
4. Leave patient with undercorrected astigmatism
5. Augment with later refractive surgery if neces-
sary
Autologous Serum: Is It Worth the Hassle?

Bennie H Jeng MD
Introduction Dry eyes

The use of autologous serum in ophthalmology has a long his- One of the other major indications for the use of autologous
tory that dates back at least to the 1970s, when autologous serum is that of dry eyes. Dry eyes can be caused by various eti-
serum was used via a mobile perfusion pump to treat dry eyes. ologies, and the use of autologous serum has been explored in
Subsequently, a report in the rheumatologic literature in 1984 a number of these. The use of autologous serum has been dem-
further suggested that autologous serum could be used as a tear onstrated to have success in the treatment of dry eyes associated
substitute. In the last 15 years or so, the use of autologous serum with Sjögren syndrome in terms of both clinical response and
has become increasingly popular, and the indications for its patient symptoms. A number of smaller studies have demon-
use have expanded rapidly. Many investigators throughout the strated the efficacy of autologous serum in patients with dry eyes
world are using autologous serum for the treatment of various secondary to chronic graft vs. host disease. Dry eyes that occur
ocular surface disorders. However, despite the reported suc- after various types of keratorefractive surgery have also been
cesses of the use of this product, there are clinical and nonclinical treated with autologous serum, with demonstrated benefits both
concerns regarding this therapy that must be addressed. In this in clinical objective findings and in subjective patient symptoms.
presentation, I will discuss the current indications for the use of Anecdotally, many refractive surgeons will even plan to start
autologous serum for the treatment of ocular surface disorders, autologous serum at the time of surgery to help maximize healing
and I will also discuss potential barriers to the use of this ther- response. With a mixed population of different etiologies causing
apy, as well as whether or not this therapy is “worth the hassle.” dry eye syndrome in my own practice, I have found that 90% of
patients achieve symptomatic improvement in their symptoms,
and nearly 100% of patients achieve clinical improvement as
Current Indications measured by rose bengal staining of the ocular surface.
Since the revival of the use of autologous serum for the treat-
Neurotrophic keratopathy
ment of various conditions of the ocular surface approximately
a decade and a half ago, many indications for its use have been Because of the neurotrophic factors that autologous serum is
proposed. Some of the most common uses of autologous serum noted to harbor, including substance P and nerve growth factor,
include the treatment of dry eyes and of persistent epithelial autologous serum has been used in the treatment of neurotrophic
defects. In addition, autologous serum has also been demon- keratopathy of various etiologies. In one larger study of 14 eyes
strated to be effective in the treatment of neurotrophic keratopa- of 11 patients, corneal sensitivity as measured by the Cochet-
thy, recurrent erosion syndrome, and superior limbic keratocon- Bonnet esthesiometer improved significantly after treatment with
junctivitis. autologous serum.
Persistent epithelial defects Recurrent erosion syndrome

In 1999, Dr. Kazuo Tsubota and colleagues published an excel- Recurrent erosions effectively occur because of the lack of abil-
lent prospective study describing the use of autologous serum in ity of the corneal epithelium to heal appropriately in the specific
the treatment of persistent epithelial defects. In this study, 62.5% setting of an irregular basement membrane and/or poor epithelial
of 16 patients with persistent epithelial defects healed with the adhesion. Thus, it would make sense that autologous serum
use of 20% autologous serum within 1 month. Since the publica- could be effective in treating this condition, as it is effective in
tion of this study, a number of studies have also described the treating persistent epithelial defects. Although the serum does not
successful use of autologous serum in the treatment of this condi- treat the underlying basement membrane irregularity, basement
tion. Authors have used concentrations of serum ranging from membrane polishing in conjunction with the immediate use of
20% to 100% and have demonstrated a healing rate of defects autologous serum eye drops may prove to be beneficial for the
between 20% to 60% at 2 weeks, and between 47% to 83% long-term treatment of this debilitating condition.
at 4 weeks. In our own recent study, we found similar results Indeed the use of autologous serum for the treatment of
using 50% autologous serum. In addition, we also found that recurrent erosion syndrome has been shown to be effective in
the length of time required for healing is directly correlated with reducing the number of recurrences experienced by patients. In
the length of time a persistent epithelial defect has been present. my own practice, I always plan to have patients with recalcitrant
Thus, consideration should likely be given to earlier treatment recurrent erosions (after failing an invasive procedure such as
of an epithelial defect with autologous serum in cases that are epithelial debridement with basement membrane polishing or
at high risk of being nonhealing. Indeed, in line with this idea, phototherapeutic keratectomy) treated with further basement
autologous serum has been used in eyes immediately following membrane polishing followed by immediate use of autologous
surgery (ie, following diabetic vitrectomy surgery in which the serum eye drops. This has proven to be exceptionally effective at
corneal epithelium was debrided and in post–penetrating kerato- preventing future recurrences.
plasty eyes), demonstrating superior efficacy in healing compared
Superior limbic keratoconjunctivitis
to controls.
Expanding the use of autologous serum treatment to superior
limbic keratoconjunctivitis has been suggested by some inves-
tigators. In one report, 9 of 11 patients responded well to this considered concurrently. In 2005 Liu and colleagues proposed
therapy, with a decrease in rose bengal and fluorescein staining an optimized protocol for the production of autologous serum
as well as an improvement in subjective symptoms. that they showed to be effective at yielding the highest amounts
of these growth factors and vitamins in the serum. While this
protocol has not yet been confirmed by other groups, it could be
Potential Barriers to Widespread Use
a starting block from which government agencies could work to
approve the production of autologous serum more freely.
Potential complications
Although there are very few reports of complications associated Patient inconvenience and cost
with the use of autologous serum, potential problems such as Patients who need to use autologous serum eye drops often have
deposition of immunoglobulins have been reported. In addition, to do so for an extended period of time, and thus they will need
the possibility exists for microbial contamination, and indeed, to have blood drawn at least every 3 months. Not only is this
anecdotal reports of this have been seen. Furthermore, sample- inconvenient, but in some cases, patients may not even be medi-
swapping in the laboratory could result in transmission of viral cally able to use their own blood for production into autologous
infections such as hepatitis and HIV from one patient to another. serum. In these cases, allogeneic serum, donated by a family
Laboratory personnel are also at risk for transmission because member, could be considered, but there are ethical consider-
they are handling the serum. Thus, it may be advisable that prep- ations with this practice as well. In addition to the inconvenience,
aration of autologous serum be undertaken only after screening autologous serum can be also expensive; patients in the United
for transmissible viral infections is done, and that it should be States generally have to pay out-of-pocket for the serum as the
performed only by trained technicians in controlled laboratory vast majority of insurance carriers do not cover this treatment.
settings. Very recently, however, the Northern California Kaiser Perma-
nente Health Care System (which serves 30% of the population
Serum preparation of northern California) has made autologous serum a covered
One of the major roadblocks to the widespread use of autolo- benefit, and to date, more than 100 patients have benefited from
gous serum is the limited availability of laboratories authorized this therapy. With any luck, other insurance carriers will also fol-
to process whole blood to produce the serum for ocular use. In low suit.
the United States, it is particularly difficult to find laboratories
that are willing to perform this processing. This may explain the
Is it worth the hassle?
relative paucity of published articles coming from the United
States on the topic of autologous serum. Even worldwide, the In most circumstances, patients who are prescribed autolo-
protocol for the production of serum also runs into regulatory gous serum eye drops have already been treated with all other
and legislative restrictions. Especially in light of the potential standard medical treatment modalities. As such, many of these
contamination and infection risks associated with production patients are facing some sort of an intervention for their next
of the autologous serum, it may be prudent to have regulatory treatment step: tarsorrhaphy or amniotic membrane graft for
guidelines in place for the preparation of this product. Perhaps persistent epithelial defects or phototherapeutic keratectomy for
a standardized protocol for the production of autologous serum recurrent erosion syndrome, for example. Or, they may be con-
would also aid in overcoming some of these regulatory restric- sidering prosthetic replacement of the ocular surface ecosystem
tions. (formerly Boston Scleral Lens) for severe dry eyes, which may
require travel to a center that fits these specialty lenses. Thus,
Lack of an optimized protocol if faced with these alternatives and given the reported efficacy
At this point, there is much evidence in the literature regarding of autologous serum eye drop therapy, then even in spite of the
the success in the treatment of various types of ocular surface inconveniences and the expense to the patient, I believe that
disorders with the use of autologous serum eye drops. However, autologous serum eye drops is “worth the hassle”!
most of these studies are retrospective in nature and run the
gamut in terms of the protocol for the production of the serum:
Future Directions
not only do the concentrations of serum in these studies vary
(from 20% to 100%), but the actual processing of the serum var- While it would be very interesting to know exactly which factors
ies as well. are the most efficacious at healing various types of ocular surface
The key steps in the production of serum that can result in disorders, the greatest challenge that will face ophthalmolo-
differing yields of various growth factors in the product include gists using autologous serum eye drops in the near future is the
the clotting time after drawing blood, as well as the time and ability to attain the production of serum in a standardized yet
speed of centrifugation of the blood. Variations in these steps efficient, feasible, and cost-effective manner that adheres to local
have been demonstrated to yield differing amounts of factors and regulatory guidelines. Well-designed and appropriately powered
vitamins in the blood, and these differing levels can have differ- prospective clinical trials to test the safety and efficacy of this
ing effects on the rate of healing of the ocular surface. The key therapy (at varying concentrations, with different preparation
components in serum that are likely involved in ocular surface methods, and for various indications) would be able to guide
health and repair include epidermal growth factor, transforming the development of appropriate therapeutic guidelines for use of
growth factor, fibroblast growth factor, platelet derived growth autologous serum eyedrops and to allow for an evidence-based
factor, hepatocyte growth factor, nerve growth factor, vitamin method of creating a standardized protocol for autologous serum
A, vitamin E, fibronectin, and substance P. production. If the results of these studies also demonstrate the
Thus, in order to develop regulatory guidelines for the pro- benefit of autologous serum, then in the words of Dr. Stephen
duction of autologous serum, the development of a standard- Pflugfelder, autologous serum really would be “a tonic for the
ized protocol for the manufacture of these drops should also be ailing corneal epithelium.”
References
1. Chen YM, Hu FR, Huang JY, et al. The effect of topical autologous 14. Noda-Tsuruya T, Asano-Kato N, Toda I, Tsubota K. Autologous
serum on graft re-eptihelialization after penetrating keratoplasty. serum eye drops for dry eye after LASIK. J Refract Surg. 2006;
Am J Ophthalmol. 2010; 150:352-359. 22:61-66.
2. Chiang CC, Chen WL, Lin JM, et al. Allogeneic serum eye drops 15. Ogawa Y, Okamoto S, Mori T, et al. Autologous serum eye drops
for the treatment of persistent corneal epithelial defect. Eye 2009; for the treatment of severe dry eyes in patients with chronic graft-
23:290-293. versus-host disease. Bone Marrow Transplant 2003; 31:579-583.
3. Esquenazi S, He J, Bazan HE, Bazan NG. Use of autologous serum 16. Pflugfelder SC. Is autologous serum a tonic for the ailing corneal
in corneal epithelial defects post-lamellar surgery. Cornea 2005; epithelium? Am J Ophthalmol. 2007; 142:316-317.
24:992-997.
17. Poon AC, Geerling G, Dart JKG, et al. Autologous serum eyedrops
4. Fox R, Chan R, Michelson J, et al. Beneficial effect of artificial tears for dry eyes and epithelial defects: clinical and in vitro toxicity stud-
made with autologous serum in patients with keratoconjunctivitis ies. Br J Ophthalmol. 2001; 85:1188-1197.
sicca. Arthritis Rheum. 1984; 27:459-461.
18. Ralph RA, Doane MG, Dohlman CH. Clinical experience with a
5. Geerling G, MacLennan S, Hartwig D. Autologous serum eyedrops mobile ocular perfusion pump. Arch Ophthalmol. 1975; 93:1039-
for ocular surface disorders. Br J Ophthalmol. 2004; 88:1467- 1043.
1474.
19. Schulze SD, Sekundo W, Kroll P. Autologous serum for the treat-
6. Goto E, Shimmura S, Shimazaki J, et al. Treatment of superior ment of corneal epithelial abrasions in diabetic patients undergoing
limbic keratoconjunctivitis by application of autologous serum. vitrectomy. Am J Ophthalmol. 2006; 142:207-211.
Cornea 2001; 20:807-810.
20. Tsubota K, Goto E, Fujita H, et al. Treatment of dry eye by autolo-
7. Jeng BH, Dupps WD. Autologous serum 50% eyedrops in the treat- gous serum application in Sjögren’s syndrome. Br J Ophthalmol.
ment of persistent corneal epithelial defects. Cornea 2009; 28:1104- 1999; 83:390-395.
1108.
21. Tsubota K, Goto E, Shimmura S, et al. Treatment of persistent
8. Kojima T, Ishida R, Dogru M, et al. The effect of autologous serum corneal epithelial defect by autologous serum application. Ophthal-
eyedrops in the treatment of severe dry eye disease: a prospective mology 1999; 106:1984-1989.
randomized case-control study. Am J Ophthalmol. 2005; 139:242-
22. Weisbach V, Dietrich T, Kruse FE, et al. HIV and hepatitis B/C
246.
infections in patients donating blood for use as autologous serum
9. Lee GA, Chen SX. Autologous serum in the management of recalci- eye drops. Br J Ophthalmol. 2007; 91:1724-1725.
trant dry eye syndrome. Clin Exp Ophthalmol. 2008; 36:119-122.
23. Yoon KC, Heo H, Im SK, et al. Comparison of autologous serum
10. Liu L, Hartwig D, Harloff S, et al. An optimized protocol for the and umbilical cord serum eye drops for dry eye syndrome. Am J
production of autolgous serum eyedrops. Graefes Arch Clin Exp Ophthalmol. 2007; 144:86-92.
Ophthalmol. 2005; 243:706-714.
24. Young AL, Cheng ACO, Ng HK, et al. The use of autologous
11. Matsumoto Y, Dogru M, Goto E, et al. Autologous serum applica- serum in persistent corneal epithelial defects. Eye 2004; 18:609-
tion in the treatment of neurotrophic keratopathy. Ophthalmology 614.
2004; 111:1115-1120.
25. Ziakas NG, Boboridis KG, Terzidou C, et al. Long-term follow up
12. McDonnell PJ, Schanzlin DJ, Rao NA. Immunoglobulin deposition of autologous serum treatment for recurrent corneal erosions. Clin
in the cornea after application of autologous serum. Arch Ophthal- Exp Ophthalmol. 2010; 38:683-687.
mol. 1988; 106:1423-1425.
13. Noble BA, Loh RSK, MacLennan S, et al. Comparison of autolo-
gous serum eye drops with conventional therapy in a randomised
controlled crossover trial for ocular surface disease. Br J Ophthal-
mol. 2004; 88:647-652.
What’s New in the Genetics of Fuchs Dystrophy?

Keith Hugh Baratz MD
I. Introduction 2. Specific genes

Fuchs endothelial corneal dystrophy (FCD) is a com- a. Transcription factor 4 (TCF4)8
mon condition. The hallmark of the disease, cornea
b. Transcription factor 8 (ZEB1)6
guttata, is present in about 5% of the population over
age 40 in the United States.1 According to the Eye SLC4A113
c.
Bank Association of America, corneal edema due to
IV. Proteins and Pathways
FCD was the most common indication among the
approximately 42,000 corneal transplants performed A. Antioxidant pathways
in the United States in 2009, accounting for over 9900
1. Oxidative stress as a mechanism of FCD makes
grafts.2 FCD also may have been a contributing fac-
sense.
tor among many of the 12,800 additional procedures
performed for post–cataract surgery corneal edema or a. Interpalpebral cornea (which has greatest
repeat transplants for failed grafts. exposure to UV light) more involved than
periphery.
Despite the frequency of the disease and our extensive
knowledge of the natural history and surgical treatment b. Aqueous very high in citrate, an antioxidant
of FCD, our understanding of the causes of FCD is lim- endothelium from FCD corneas more suscep-
ited. Prior investigators have identified proteins, genes, tible to oxidative stress
genetic loci, and microstructural findings that implicate
2. Proteins implicated
biochemical pathways and mechanisms of disease,
but a unifying theory of disease pathogenesis is lack- a. Peroxiredoxins: Decreased in FCD9
ing. Without further understanding of the root causes
b. DJ-1 (Jurkunas et al, abstract #6469, ARVO
of FCD, discovering treatments other than surgical
2011)
replacement of diseased endothelial tissue will remain
elusive. i. a cofactor in the production of antioxi-
dants
The purpose of this presentation is to provide a review
of our current knowledge of the possible causes of ii. decreased in FCD
FCD, with a focus upon recent genetic discoveries.
B. Glycolysis
II. Understanding the Mechanisms of Disease
Decreased levels of glycolytic enzymes (Hecker et al,
A. Genetics abstract #6599, ARVO 2011)
B. Proteins α-enolase
1.
C. Biochemical pathways 2. PGK-1
D. Cellular microstructure C. Transcription factors
E. Environmental associations / modifiable risk factors 1. E2-2 protein (TCF4 gene)
III. Genetics 2.
ZEB1 (aka zinc finger E-box binding homeobox
1, transcription factor 8)
A. Early-onset FCD
D. Other proteins
1. Distinct from common older-onset FCD
1. Clusterin
2. Mutations in col8A23: alpha 2 chain of collagen
8 a. Elevated in FCD
B. Older onset FCD b. Nonspecific stress protein
1. Chromosomal loci 2. SLC4A11
a. Chr. 5q33.1-q35.24 a. Sodium – boron cotransporter
b. Chr. 13pTel-13q12.135 b. Unknown mechanism of action
c. Chr. 96 c. Implicated in small percentage of FCD fami-
lies
d. Chr. 18q21.2-q21.327: May be most com-
mon association
V. Microstructural Abnormalities 4. Paradox of replication studies of TCF4/

Fuchs11,12
A. Guttae: May implicate abnormal collagen produc-
tion a. Fuchs associated with SNP rs613872 in TCF4
gene.
B. Endoplasmic reticulum stress10
b.
TCF4 variant not predictive of affected vs.
1. Unfolded protein response
unaffected within families.
2. May lead to apoptosis
c. Linkage studies map to chr. 18 region sepa-
VI.
TCF4 gene (E2-2 protein) rate from TCF4.
A. General information VII.
ZEB1
β helix-loop-helix proteins: Dimerize to serve as
1. A. Recognized role in cornea disease
promoters or inhibitors of DNA transcription
1. Posterior polymorphous dystrophy
2. Ubiquitous proteins that serve numerous func-
2. Congenital hereditary endothelial dystrophy
tions: Important in differentiation and develop-
ment as well as ongoing cellular processes 3. One family with FCD6
3. Corresponds to chromosome 18 locus B. General information
B. E2-2 in various tissues 1. aka Zinc finger e-box homeobox 1, transcription
factor 8, TCF8
1. Responsible for Pitt-Hopkins syndrome
2. A transcription factor
a. Mental retardation
3. Plays integral role in EMT
b. Periodic hyperventilation / apnea
a. Transcription factor
c. Seizures
b. Implicated in other dystrophies
2. Tumor suppressor effect: Inhibitor of cyclin
dependent kinase pathway via p21cip1 i. posterior polymorphous dystrophy
3. Tumor promoter via epithelial to mesenchymal ii. congenital hereditary endothelial dystro-
transition (EMT) phy
C. E2-2 and EMT SLC4A113
VIII.
1. EMT A. Na+-borate co-transporter protein: Cellular func-
tion uncertain
EMT is a complex pathway controlling the bal-
ance between cells expressing epithelial vs. mes- B. Mutations of SLC4A11
enchymal characteristics.
1. Likely an uncommon cause of FCD
a. Epithelial characteristics: cell polarity, base-
2. FCD mechanism may be accumulation of mis-
ment membrane, intercellular adhesion, non-
folded protein.
invasive
b. Mesenchymal characteristics: loss of polarity,
References
loss of adhesion, invasive nature
c. E-cadherin is marker and regulator of EMT. 1. Lorenzetti DW, Uotila MH, Parikh N, Kaufman HE. Central cor-
nea guttata: incidence in the general population. Am J Ophthalmol.
2. E2-2 represses e-cadherin. 1967; 64:1155-1158.
D. E2-2 and Fuchs 2. America EBAo. 2009 Eye Banking Statistical Report. Washington,
DC.
1. Found by genome-wide association study and
confirmed in replication8,11,12 3. Vithana EN, Morgan PE, Ramprasad V, et al. SLC4A11 mutations
in Fuchs endothelial corneal dystrophy. Hum Mol Genet. 2008;
2. Role in FCD is unknown. 17:656-666.
3. Possible roles 4. Riazuddin SA, Eghrari AO, Al Saif A, et al. Linkage of a mild late-
onset phenotype of Fuchs corneal dystrophy to a novel locus at
a. Regulation of gene transcription and thus 5q33.1-q35.2. Invest Ophthalmol Vis Sci. 2009; 50:5667-5671.
expression of proteins such as antioxidants
5. Sundin OH, Jun AS, Broman KW, et al. Linkage of late-onset Fuchs
b. Maintenance of tissue phenotype via EMT corneal dystrophy to a novel locus at 13pTel-13q12.13. Invest
Ophthalmol Vis Sci. 2006; 47:140-145.
c. Numerous other possibilities
6. Riazuddin SA, Zaghloul NA, Al-Saif A, et al. Missense mutations
in TCF8 cause late-onset fuchs corneal dystrophy and interact with
FCD4 on chromosome 9p. Am J Hum Genet. 2010; 86:45-53.
7. Sundin OH, Broman KW, Chang HH, Vito EC, Stark WJ, Gottsch
JD. A common locus for late-onset Fuchs corneal dystrophy maps
to 18q21.2-q21.32. Invest Ophthalmol Vis Sci. 2006; 47:3919-
3926.
8. Baratz KH, Tosakulwong N, Ryu E, et al. E2-2 protein and Fuchs’s
corneal dystrophy. N Engl J Med. 2010; 363:1016-1024.
9. Jurkunas UV, Rawe I, Bitar MS, et al. Decreased expression of
peroxiredoxins in Fuchs’ endothelial dystrophy. Invest Ophthalmol
Vis Sci. 2008; 49:2956-2963.
10. Engler C, Kelliher C, Spitze AR, Speck CL, Eberhart CG, Jun AS.
Unfolded protein response in Fuchs endothelial corneal dystrophy:
a unifying pathogenic pathway? Am J Ophthalmol. 2010; 149:194-
202.
11. Li YJ, Minear MA, Rimmler J, et al. Replication of TCF4 through
association and linkage studies in late-onset Fuchs endothelial cor-
neal dystrophy. PLoS One. 2011; 6:e18044.
12. Riazuddin SA, McGlumphy EJ, Yeo WS, Wang J, Katsanis N,
Gottsch JD. Replication of the TCF4 intronic variant in late-onset
Fuchs corneal dystrophy and evidence of independence from the
FCD2 locus. Invest Ophthalmol Vis Sci. 2011; 52:2825-2829.
Future Therapies for Corneal Endothelial Disease

Shigeru Kinoshita MD
The corneal endothelium, which is located at the innermost lial dysfunction. A “corneal endothelial cell sheet transplanta-
layer of the cornea, plays a crucial role in maintaining corneal tion” with cells grown on a type I collagen carrier was successful
transparency via its barrier and pump functions. The human to some extent, but a good material for the cell carrier has to be
corneal endothelium is generally nonregenerative in vivo; thus developed.
the corneal endothelial cell loss due to Fuchs corneal endothelial
dystrophy, corneal trauma, and surgical intervention such as
cataract surgery, etc. is followed by an enlargement of the adja-
cent endothelial cells. However, if corneal endothelial cell loss
is too severe, the cornea develops an irreversible corneal endo-
thelial dysfunction. Although either penetrating keratoplasty,
Descemet-stripping automated endothelial keratoplasty, or Des-
cemet membrane endothelial keratoplasty has been the choice of
surgery for recovering visual loss due to corneal endothelial dys-
function, a massive corneal endothelial cell loss postoperatively
can be a long-term problem following the procedures described
above.
To overcome these problems and to achieve a sophisticated
treatment, we must develop new surgical and medical therapeu-
tic modalities for corneal endothelial disease, which provide a
healthy corneal endothelium with high cell density. To achieve
this we have been currently focusing on the basic understanding Figure 2. Cultivated human corneal endothelium.
and clinical application of cell proliferation and migration pro-
cess of human corneal endothelial cells both in vitro and in vivo.
Cultivated Corneal Endothelial Cell Injection
Therapy3
A recent report described that the Rho-kinase (ROCK) inhibitor,
Y-27632, promotes cell adhesion and proliferation and inhibits
the apoptosis of primate corneal endothelial cells in culture.
When cultivated corneal endothelial cells in rabbits and monkeys
were injected into the anterior chamber in the presence of ROCK
inhibitor, endothelial cell adhesion was enormously promoted,
resulting in the achievement of a high cell density with a normal-
looking morphology. Therefore, a “cell-injection therapy” com-
bined with the application of ROCK inhibitor may be a promis-
Figure 1. Future therapies for corneal endothelial disease. ing procedure in the future.
Our recent attempts to develop new therapeutic modalities Eye Drops4

for corneal endothelial disease are divided into 3 approaches as
follows: We are also trying to develop a novel medical treatment for the
early phase of corneal endothelial disease by the use of ROCK
1. Cultivated corneal endothelial cell sheet transplantation inhibitor eye drops. In rabbit and monkey experiments using par-
2. Cultivated corneal endothelial cell injection therapy tial endothelial dysfunction models, corneal endothelial wound
3. Eye drops healing was accelerated by the topical application of ROCK
Generally, the proliferative ability of corneal endothelial cells inhibitor to the eye, resulting in the regeneration of a corneal
in primates and humans is severely limited; we have been devel- endothelial monolayer with a high endothelial cell density. We
oping a new cultivating method of promoting cell proliferation are now trying to establish 1 clinical trial for patients with partial
with good physiological function. This procedure is applicable to corneal endothelial dysfunction.
the human corneal endothelium as well.
References
Cultivated Corneal Endothelial Cell Sheet 1. Koizumi N, Sakamoto Y, Okumura N, Okahara N, Tsuchiya H,
Transplantation1,2 Torii R, Cooper LJ, Tanioka H, Kinoshita S. Cultivated corneal
We described the results of cultivated corneal endothelial cell endothelial cell sheet transplantation in a primate model. Invest
sheet transplantation in primates for advanced corneal endothe- Ophthalmol Vis Sci. 2007; 48:4519-4526.
2. Koizumi N, Sakamoto Y, Okumura N, Tsuchiya H, Torii R, Coo-

per LJ, Ban Y, Tanioka H, Kinoshita S. Cultivated corneal endo-
thelial transplantation in a primate: possible future clinical applica-
tion in corneal endothelial regenerative medicine. Cornea 2008;
suppl.:48-55.
3. Okumura N, Ueno M, Koizumi N, Sakamoto Y, Hirata K, Hamuro
J, Kinoshita S. A ROCK inhibitor enhances survival of primate
corneal endothelial cells in vitro. Invest Ophthalmol Vis Sci. 2009;
50:3680-3687.
4. Okumura N, Koizumi N, Ueno M, Sakamoto Y, Takahashi H,
Hirata K, Torii R, Hamuro J, Kinoshita S. Enhancement of corneal
endothelium wound healing by a Rho-associated kinase (ROCK)
inhibitor eye drop. Br J Ophthalmol. 2011; 95:1006-1009.
How the Cornea Remains Clear in Health and Disease

Dimitri T Azar MD
Outline invade the cornea, which maintains corneal avascularity. This

can be attributed to the upregulation of anti-angiogenic factors
I. Corneal Clarity
and/or to a decrease in angiogenic factors, resulting in a shift
A. Corneal endothelium as a barrier to aqueous humor toward vessel regression. While not much research has been pub-
lished on this topic, vessel regression following corneal wound
B. Corneal endothelium as a metabolic pump
healing is likely due to a combination of anti-angiogenic factor
II. Corneal Avascularity upregulation and angiogenic factor downregulation.
A. The balance of angiogenic and anti-angiogenic fac-
tors in the cornea The Limbus and the Limbal Barrier
B. The limbus and the limbal barrier: Questionable The limbus is believed to play an integral role in preventing cor-
role in corneal angiogenic privilege neal NV and maintaining corneal avascularity. The limbal bar-
rier hypothesis is one of the most well-accepted explanations for
III. Loss of Corneal Clarity
the mechanism behind the limbal anti-angiogenic effect and the
A. Diseases associated with loss of corneal clarity severe NV seen in limbal deficiency and damage. This hypothesis
describes the constant renewal (proliferation, migration, and dif-
B. Pathophysiology
ferentiation) of corneal epithelial cells by the limbus as acting as
C. Treatment options a physical barrier to prevent conjunctival and vessel outgrowth
in the cornea. However, the concept of the limbus acting as a
IV. Loss of Corneal Avascularity
physical barrier to prevent corneal NV has been recently ques-
A. Diseases associated with corneal neovascularization tioned.
In our laboratory, we have used a bFGF pellet corneal NV
B. Pathophysiology
model to demonstrate that the limbus may not necessarily func-
C. Treatment Options tion as a true physical barrier to NV. Our results showed that
removal of half of the limbus (hemilimbal deficiency) leads to
corneal NV from the opposite side of the cornea where the lim-
Corneal Clarity and Avascularity
bus was intact; this observation questions the role of the limbus
Corneal clarity and corneal avascularity are important for the and whether it truly acts as a physical barrier to corneal NV.
proper optical performance of the cornea. Approximately 1 mm Since it has long been believed that the role of the limbus in
thick peripherally and 0.5 mm centrally, the cornea comprises an corneal NV was to act as a true physical barrier, inhibiting the
outer stratified squamous nonkeratinized epithelium, an inner growth of vessels, additional studies in this area are required to
connective tissue stroma with resident keratocytes, and border- elucidate the role of the limbus in corneal angiogenic privilege.
ing the anterior chamber, a low cuboidal endothelium. Corneal
avascularity is an active process involving the production of anti-
Diseases Associated With Loss of Corneal Clarity
angiogenic factors, which counterbalance the proangiogenic/lym-
phangiogenic factors that are upregulated during wound healing. Corneal edema
The corneal endothelium maintains corneal clarity through 2
Balance of Angiogenic and Anti-angiogenic Factors in functions: by acting as a barrier to the aqueous humor and by
the Cornea providing a metabolic pump. Alteration of either function by
damage or maldevelopment leads to corneal edema, a condition
Corneal neovascularization (NV) in response to tissue injury,
of abnormal homeostasis resulting in excess fluid within the cor-
resulting from trauma, infection, and inflammatory or degenera-
neal stroma and/or epithelium.
tive disorders, involves the dual invasion of blood (hemangio-
Various traumatic, inflammatory, and dystrophic mecha-
genesis) and lymphatic (lymphangiogenesis) vessels. More often,
nisms can produce corneal edema, such as trauma, inflamma-
corneal wound healing occurs in the absence of NV. In this situ-
tion, hypoxia, hydrops from ruptured Descemet membrane,
ation, the balance between angiogenic factors, such as fibroblast
increased IOP, Fuchs dystrophy, posterior polymorphous dys-
growth factor-2 (FGF-2) and vascular endothelial growth factor
trophy, iridocorneal endothelial syndrome, and retained lens
(VEGF), and anti-angiogenic molecules, such as angiostatin,
fragment.
endostatin, or pigment epithelium-derived factor (PEDF), is
tilted toward anti-angiogenesis. Corneal angiogenic privilege and
maintenance of corneal avascularity occur not only as a result Diseases Associated With Corneal NV
of the upregulation of anti-angiogenic factors but also from the
A wide variety of insults can tip the balance between angiogenic
downregulation of pro-angiogenic factors.
and anti-angiogenic factors in favor of angiogenesis and cause
In healthy corneas after minor injury, the upregulation of
various patterns of NV. Processes of corneal NV can be caused
anti-angiogenic factors tilts the balance toward vessel regression.
by inflammatory disorders, corneal graft rejection, infectious
Following corneal wound healing, newly formed vessels do not
keratitis, contact lens–related hypoxia, alkali burns, neuro-

trophic ulceration, aniridia, and limbal stem cell deficiency. NV
patterns can generally be grouped into 3 clinical entities: (1)
deep NV overlying the Descemet membrane, as seen in herpetic
and luetic interstitial keratitis, (2) stromal NV, which is mainly
associated with stromal keratitis, and (3) vascular pannus com-
posed of connective tissue proliferating in the superficial corneal
periphery and mainly associated with ocular surface disorders.
References
1. Ellenberg D, Azar DT, Hallak JA, et a.. Novel aspects of corneal

angiogenic and lymphangiogenic privilege. Prog Retin Eye Res.
2010; 29(3):208-248.
2. American Academy of Ophthalmology. Basic and Clinical Science
Course Section 8: External Disease and Cornea. Chapter 1: Struc-
ture and function of the external eye and cornea. San Francisco:
AAO; 2011-2012, p. 3.
2011 Subspecialty Day | Cornea 81
Financial Disclosure
The Academy’s Board of Trustees has determined that a Category Code Description
financial relationship should not restrict expert scientific,
Consultant / Advisor C Consultant fee, paid advisory
clinical, or nonclinical presentation or publication, provided
boards or fees for attending a
that appropriate disclosure of such relationship is made. As
meeting (for the past one year)
an Accreditation Council for Continuing Medical Education
(ACCME) accredited provider of CME, the Academy seeks to Employee E Employed by a commercial
ensure balance, independence, objectivity, and scientific rigor in entity
all individual or jointly sponsored CME activities.
Lecture fees L Lecture fees (honoraria), travel
All contributors to Academy educational activities must dis-
fees or reimbursements when
close any and all financial relationships (defined below) to the
speaking at the invitation of a
Academy annually. The ACCME requires the Academy to dis-
commercial entity (for the past
close the following to participants prior to the activity:
one year)
• any known financial relationships a meeting presenter,
Equity owner O Equity ownership/stock options
author, contributor, or reviewer has reported with any
of publicly or privately traded
manufacturers of commercial products or providers of
firms (excluding mutual funds)
commercial services within the past 12 months
with manufacturers of com-
• any meeting presenter, author, contributor, or reviewer
mercial ophthalmic products or
(hereafter referred to as “the Contributor”) who report
commercial ophthalmic services
they have no known financial relationships to disclose
Patents / Royalty P Patents and/or royalties that
For purposes of this disclosure, a known financial relation-
might be viewed as creating a
ship is defined as any financial gain or expectancy of financial
potential conflict of interest
gain brought to the Contributor or the Contributor’s family,
business partners, or employer by: Grant support S Grant support for the past one
year (all sources) and all sources
• direct or indirect commission;
used for this project if this form
• ownership of stock in the producing company;
is an update for a specific talk
• stock options and/or warrants in the producing company,
or manuscript with no time
even if they have not been exercised or they are not
limitation
currently exercisable;
• financial support or funding from third parties, including
research support from government agencies (e.g., NIH),
device manufacturers, and/or pharmaceutical companies;
or
• involvement in any for-profit corporation where the
Contributor or the Contributor’s family is a director or
recipient of a grant from said entity, including consultant
fees, honoraria, and funded travel.
The term “family” as used above shall mean a spouse,
domestic partner, parent, child or spouse of a child, or a brother,
sister, or spouse of a brother or sister, of the Contributor.
82 2011 Subspecialty Day | Cornea
2011 Cornea Planning Group Financial Disclosures
Christopher J Rapuano MD AAO Staff

Alcon Laboratories, Inc.: L
Allergan, Inc.: C,L Ann L’Estrange
Bausch + Lomb Surgical: L None
EyeGate Pharma: C
Inspire Pharmaceuticals, Inc.: C,L Melanie Rafaty
Rapid Pathogen Screening: O None
Vistakon Johnson & Johnson Visioncare, Inc.: L
Debra Rosencrance
Natalie A Afshari MD None
National Eye Institute: S
Research to Prevent Blindness: S
Anthony J Aldave MD
Allergan, Inc.: C
Inspire Pharmaceuticals, Inc.: C,L
National Eye Institute: S
Michael W Belin MD
Alcon Laboratories, Inc.: L
Allergan, Inc.: L
Oculus, Inc.: C,L
David B Glasser MD
None
Donald Tan MD FRCS FRCOphth

Bausch + Lomb Surgical: C
Carl Zeiss Meditec: L
NetWork Medical Products: P
Santen, Inc.: L
Faculty Financial Disclosures
Natalie A Afshari MD Roy S Chuck MD PhD Shigeru Kinoshita MD

National Eye Institute: S Alcon Laboratories, Inc.: C Abbott Medical Optics: C,L
Research to Prevent Blindness: S IOP: C Alcon Laboratories, Inc.: C,L
University of California: P Hoya Corp.: C,L
Anthony J Aldave MD Otsuka Pharmaceutical Co.: C,L
Allergan, Inc.: C Reza Dana MD MSc MPH Pfizer, Inc.: C,L
Inspire Pharmaceuticals, Inc.: C,L Alcon Laboratories, Inc.: C Santen, Inc. C,L
National Eye Institute: S Allergan, Inc.: C,S Senju Paharmaceutical Co.: C,L
Bausch + Lomb Surgical: C,S
James V Aquavella MD Eleven Biotherapeutics: C,O Anna S Kitzmann MD
Bausch + Lomb Surgical: S InSite Vision, Inc.: C None
Johnson & Johnson Consumer & Pfizer, Inc.: C,S
Personal Products Worldwide: S Rigel: C Friedrich E Kruse MD
Research to Prevent Blindness: S Sirtris/GSK: C,S Cell Seed: C
Santen, Inc.: C
Penny A Asbell MD FACS Randy J Epstein MD
Addition Technology: C,L,S Alcon Laboratories, Inc.: L Thomas M Lietman MD
Alcon Laboratories, Inc.: C,L,S Tear Sciences, Inc.: C None
Allergan, Inc.: C,L,S
Aton, Inc.: C,L,S Per Fagerholm MD Christopher Liu FRCOphth
Bausch + Lomb Surgical: C,L,S None None
Johnson & Johnson Consumer &
Personal Products Worldwide: L Marjan Farid MD Francis S Mah MD
Novartis Pharmaceuticals Corp.: C,L,S None Alcon Laboratories, Inc.: C,S
Paragon Vision Sciences: C,L,S Allergan, Inc.: C,S
Pfizer, Inc.: C,L,S Kenneth M Goins MD Foresight Biotherapeutics: C
Santen, Inc.: C,L,S None Inspire Pharmaceuticals, Inc.: C,S
Vistakon Johnson & Johnson Ista Pharmacuticals: C
Visioncare, Inc.: C,L,S Jose Gomes MD Ocular Therapeutix: C
Alcon Laboratories, Inc.: L Ox-danthia: C,S
Dimitri T Azar MD Allergan, Inc.: C,L
Alcon Laboratories, Inc.: L Fapesp, Brazil: S Todd P Margolis MD PhD
Allergan, Inc.: C,L Natura, Inc.: C None
Bausch + Lomb Surgical: C
ForSight Labs: C Kristin M Hammersmith MD Stephanie Jones Marioneaux MD
Prism Ventures: C None None
Sarentis: C
Andrew J W Huang MD MPH Majid Moshirfar MD
Keith Hugh Baratz MD Allergan, Inc.: C,L None
National Eye Institute: S National Eye Institute: S
Research to Prevent Blindness, Inc.,: S Research to Prevent Blindness: S Kohji Nishida MD
None
Stuart I Brown MD Bennie H Jeng MD
None Santen, Inc.: C Rudy Nuijts MD
Alcon Laboratories, Inc.: L,S
Alan N Carlson MD A John Kanellopoulos MD Asico: P
Inspire Pharmaceuticals, Inc.: L Alcon Laboratories, Inc.: L
Tear Science: O KeraMed, Inc.: L N Venkatesh Prajna MD
Ocular Therapeutix, Inc.: L National Eye Institute: S
James Chodosh MD MPH Revision Optics: L
Alcon Laboratories, Inc.: C Seros Medical, USA: L
Allergan, Inc.: C WaveLight AG: L
National Eye Institute: C,S
84 Faculty Financial Disclosures 2011 Subspecialty Day | Cornea
Francis W Price Jr MD Christopher J Rapuano MD Virender S Sangwan MBBS

Abbott Medical Optics: C,L Alcon Laboratories, Inc.: L None
Addition Technology: C Allergan, Inc.: C,L
Alcon Laboratories, Inc.: C Bausch + Lomb Surgical: L Geoffrey C Tabin MD
Allergan, Inc.: C,L EyeGate Pharma: C None
Calhoun Vision, Inc.: O Inspire Pharmaceuticals, Inc.: C,L
Cellular Bioengineering, Inc.: C Rapid Pathogen Screening: O Mark A Terry MD
Forsight Vision: C Vistakon Johnson & Johnson Alcon Laboratories, Inc.: L
Inspire Pharmaceuticals, Inc.: C Visioncare, Inc.: L Bausch + Lomb Surgical: P
Ista Pharmacuticals: C Optovue: O
Moria: L George O D Rosenwasser MD
Oculus, Inc.: C Accutome: C
OPHTEC, BV: C,L Allergan, Inc.: C,L,
ReVital Vision: O Inspire Pharmaceuticals, Inc.: L
TearLab: O Katena Products, Inc.: C
Voisin Consulting: C Konan: C
Sharppoint/Angiotech: S
Vistakon Johnson & Johnson
Visioncare, Inc.: L
Presenter Index
Aquavella*, James V 56

Asbell*, Penny A 63
Azar*, Dimitri T 79
Baratz*, Keith Hugh 74
Brown, Stuart I 55
Carlson*, Alan N 51
Chodosh*, James 1
Chuck*, Roy S 60
Dana*, Reza 58
Epstein*, Randy J 69
Fagerholm, Per 18
Farid, Marjan 47
Goins, Kenneth M 49
Gomes*, Jose 24
Hammersmith, Kristin M 53
Huang*, Andrew J W 61
Jeng*, Bennie H 71
Kanellopoulos*, A John 30
Kinoshita*, Shigeru 77
Kitzmann, Anna S 65
Kruse*, Friedrich E 38
Lietman, Thomas M 26
Liu, Christopher 3
Mah*, Francis S 34
Margolis, Todd P 33
Marioneaux, Stephanie Jones 64
Moshirfar, Majid 66
Nishida, Kohji 20
Nuijts*, Rudy 44
Prajna*, N Venkatesh 28
Price*, Francis W 42
Rosenwasser*, George O D 41
Sangwan, Virender S 21
Tabin, Geoffrey C 46
Terry*, Mark A 35


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Subspecialty Day

In conjunction with the Cornea Society

Orange County Convention Center

2011 Cornea Planning Group 2008 Michael W Belin MD Staff

Cornea 2011 Contents

Program Directors’ Welcome Letter ii

Section I: Ocular Surface Disease—Replacement vs. Regeneration 1

Section II: Infectious Keratitis 26

Section III: Corneal Transplantation—Lamellar Keratoplasty 35

Section IV: Corneal Transplantation—Penetrating Keratoplasty and Pediatric Keratoplasty 49

Section V: Ocular Surface Disease—Therapeutics 58

Surgery by Surgeons Update 64

Section VI: Cornea Potpourri 65

Faculty Financial Disclosure 81

Natalie A Afshari MD Penny A Asbell MD FACS Stuart I Brown MD

James Chodosh MD MPH

Roy S Chuck MD PhD Per Fagerholm MD Jose Gomes MD

Andrew J W Huang MD MPH

Bennie H Jeng MD Anna S Kitzmann MD Christopher Liu FRCOphth

A John Kanellopoulos MD Friedrich E Kruse MD

Shigeru Kinoshita MD Thomas M Lietman MD

Todd P Margolis MD PhD

Stephanie Jones Marioneaux MD Rudy Nuijts MD Christopher J Rapuano MD

Majid Moshirfar MD N Venkatesh Prajna MD

Geoffrey C Tabin MD Mark A Terry MD

Cornea 2011: Controversies and Consensus

Saturday, October 22, 2011

Section I: Ocular Surface Disease—Replacement vs. Regeneration

Section II: Infectious Keratitis

* Indicates that the presenter has financial interest.

Section III: Corneal Transplantation—Lamellar Keratoplasty

Section IV: Corneal Transplantation—Penetrating Keratoplasty and Pediatric Keratoplasty

Section V: Ocular Surface Disease—Therapeutics

* Indicates that the presenter has financial interest.

Section VI: Cornea Potpourri

* Indicates that the presenter has financial interest.

The Boston Keratoprosthesis in the Management of

I. History of the Boston Keratoprosthesis corneal allograft rejection (Boston Keratopros-

The Osteo-Odonto-Keratoprosthesis for Management

1. Liu C, Paul B, Tandon R, et al. The osteo-odonto-keratoprosthesis

Figure 2. Schematic diagram of cross-section anatomy of an OOKP eye.

A Biosynthetic Alternative to Human Donor Tissue

Introduction 9 out of 10 patients in the human tissue group (6 male, 3 female,

1. Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a

Oral Mucosal Epithelial Transplantation for the

Cultivated Limbal Epithelial Transplantation for the

Background legrini et al in 1997.17 Since then, many modifications of this

Outcomes of Allogenic Cultivated Limbal Epithelial

Ocular Surface Reconstruction With Immature Dental

Figure 1. Survival curve of eyes with TLSCD after conjunctival limbal

Advances in tissue culture and bioengineering have allowed

Bacterial Keratitis: Susceptibility Testing, Steroids, and

An Evidence-Based Approach to Managing

Corneal Collagen Crosslinking: Does It Have a Role in

Our scientific findings support the conclusion that simultane-

Although the efficacy of CXL for stabilizing keratectasia is well

Patient’s tomographic keratometry O.D. has improved to References

Now That We Have Topical Ganciclovir, What Is the

Perioperative Antibiotics: Looking for a Consensus

A Decade of Endothelial Keratoplasty: What Has the

storage time and donor endothelial survival. Ophthalmology 2011;

Ten Tips to Avoid Trouble When Transitioning to

2. Select appropriate donor.

6. Donor Preparation for DMEK With Minimal