Management of Early Progressive Corneal Ectasia: Accelerated Crosslinking Principles

222 Pages·2017·11.62 MB·English

by  Cosimo Mazzotta et al.

Management of
Early Progressive
Corneal Ectasia
Accelerated
Crosslinking Principles
Cosimo Mazzotta
Frederik Raiskup
Stefano Baiocchi
Giuliano Scarcelli
Marc D. Friedman
Claudio Traversi
123
Management of Early Progressive
Corneal Ectasia
Cosimo Mazzotta • Frederik Raiskup
Stefano Baiocchi • Giuliano Scarcelli
Marc D. Friedman • Claudio Traversi
Management of Early
Progressive Corneal
Ectasia
Accelerated Crosslinking Principles
Cosimo Mazzotta Frederik Raiskup
Ophthalmology Speciality School Siena Department of Ophthalmology
University and Siena Crosslinking Center Carl Gustav Carus University
Siena Dresden
Italy Germany
Stefano Baiocchi Giuliano Scarcelli
Ophthalmology Speciality School Department of Bioengineering
Siena University University of Maryland
Siena College Park, Maryland
Italy USA
Marc D. Friedman Claudio Traversi
Avedro Ophthalmology Speciality School
Waltham, Massachusetts Siena University
USA Siena
Italy
ISBN 978-3-319-61136-5 ISBN 978-3-319-61137-2 (eBook)
DOI 10.1007/978-3-319-61137-2
Library of Congress Control Number: 2017952041
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To Paola, Martina, Giulia and Lucia and to
all Authors’ Families
Preface
For the last 10 years the advent of Riboflavin-UV-A-induced crosslinking (CXL)
has drastically modified the natural history of Keratoconus and secondary corneal
ectasia therapy. The number of corneal transplants for Keratoconus has notably
reduced over a 30% drop in the last 5 years. Potentially correct and early use of
CXL, at an early stage, can lead to its annulment in the next 5–10 years with notable
savings for the health care system, of expenses for patients, and above all, radically
improving patient quality of life which for years had been the “sword of Damocles”
of surgery. This ambitious goal is possible if ophthalmologists pay ever more atten-
tion to timely diagnosis and early treatment, especially in the paediatric age. Early
identification of Keratoconus is the fundamental stage in this “ideal path”. The
Scheimpflug cameras and new partial optical coherence light-based (OCT) tomog-
raphers available in the clinical practice allow us to “surprise” the illness at its
onset. One can, at this point, hypothesize a treatment that immediately stabilizes the
pathological process, impeding its evolution, and most importantly stabilizing the
cornea when the refractive defect is still modest and correctable, without difficulties
with spectacles or contact lenses. Over 10 years have passed since the effective
introduction of corneal CXL therapy, and the Dresden protocol remains the most
important point of reference because it is the most studied and the most used, as
well as the protocol with the most valued clinical results and longest follow-up. The
fields of application have rapidly stretched from keratoconus to iatrogenic second-
ary ectasias, especially post-Lasik, with excellent results and more recently extended
to the treatment of therapy-resistant infectious keratitis. Nonetheless, the conven-
tional CXL (C-CXL) protocol has shown some limits: the excessive duration (1 h),
the need to remove the epithelium, post-operative pain, risk of infection, haze devel-
opment (stromal wound healing complications), endothelial risks for thin corneas
and long waiting lists. Recently, thanks to the principles articulated in the Bunsen-
Roscoe law, accelerated crosslinking treatments (A-CXL) have emerged with the
objective of shortening the procedure, maintaining efficiency. Some of these pro-
posals are proving to be valid alternatives of the conventional CXL protocol, while
other techniques such as super-fast A-CXL, trans-epithelial and iontophoresis-
assisted CXL (I-CXL) have shown notable limits and are thus to be modified and
evaluated in the long term, large number of cases and different age groups. Another
challenging chapter is the attempt to combine treatments of improving the aberro-
metric and refractive defect induced by Keratoconus. This is a dream for all patients
vii
viii Preface
who are intolerant of contact lenses: stopping Keratoconus progression and simul-
taneously improving the visual acuity without the necessity of resorting to corneal
transplants. The so-called “Crosslinking plus” is already a reality for selected cases,
reserved for patients with scarce visual acuity and intolerant to contact lenses, who
are usually candidates for lamellar keratoplasty. The existence of clinical and instru-
mental parameters permits these people to attempt a stabilizing approach associated
with contemporary refractive empowerment or postponement before thinking about
replacement surgery. The ball is rolling, but adjustments are necessary for patient
ease and repetitive, satisfying results. Crosslinking is a therapy that has changed the
story of Keratoconus all over the world, and it is in continuous evolution. Accelerated
CXL procedures illustrated in the book will be the leading part of the future cross-
linking revolution.
Acknowledgements
Special Thanks To
Prof. Gian Marco Tosi, Head of the Ophthalmology Unit, Department of Medicine,
Surgery and Neurosciences of Siena University, IT
Prof. Ennio Polito, Head of the Post-Graduate Ophthalmology School of Siena
University, IT
and to
Prof. Eberhard Spoerl, Ph.D., Dresden Technical University, GE
Dr. Joshua N. Webb, Ph.D., University of Maryland, USA
Dr. Robert Herber, Dresden Technical University, GE
Dr. Janine Lenk, Dresden Technical University, GE
Dr. Miguel Rechichi, M.D., Ph.D., Eye Center, Catanzaro, IT
Dr. Mario Fruschelli, Ophthalmology Unit, Siena University, IT
Dr. Maria Margherita De Santi, Dept. Human Pathology, Siena University, IT
Dr. Pietro Rosetta, Humanitas University, Milan, IT
*Dr. Yulia Litasova, Siena University, IT
*Dr. Fiorella Fusco, Siena University, IT
*Dr. Pierfrancesco Mellace, Siena University, IT
*Dr. Simone Alex Bagaglia, Siena University, IT
*Dr. Maria Eugenia Latronico, Siena University, IT
*Dr. Gennaro Chimenti, Siena University, IT
*Dr. Marco Capozzoli, Siena University, IT
*Dr. Francesco Rana, Siena University, IT
*Dr. Stefano Fazio, Siena University, IT
*Dr. Tommaso Bacci, Siena University, IT
*Dr. Francesco Martino, Siena University, IT
*Dr. Giulia Esposti, Siena University, IT
*Dr. Maria Sole Polito, Post-Graduate Ophthalmology School, Turin University, IT
*Dr. Antonio Tarantello, Siena University, IT
*Dr. Pietro Mittica, Siena University, IT
*Dr. Giulia Cratocci, Siena University, IT
+Dr. Giovanni Neri, Siena University, IT
*Post-Graduate Ophthalmology School, Siena University, IT
Mrs. Jennifer Berkeley for English editing of the Book
ix
Contents
1 Principles of Accelerated Corneal Collagen Cross-Linking . . . . . . . . . 1
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Corneal Structure and Ectasia Pathophysiology . . . . . . . . . . . . . . . . 1
1.2.1 Keratoconic Microstructure . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2.2 Corneal Cross-Links . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.2.3 Standard Crosslinking and the “Dresden Protocol” . . . . . . . . 6
1.3 Accelerated Crosslinking, Photochemical Kinetic Principles . . . . . . 7
1.3.1 Laboratory Methods for Quantifying Crosslinking . . . . . . . . 8
1.3.2 Photochemical Kinetics of Corneal Crosslinking
with Riboflavin and UVA Light . . . . . . . . . . . . . . . . . . . . . . . . 11
1.4 Clinical Correlation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.5 Accelerated Crosslinking Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
1.6 Accelerated Crosslinking Applications . . . . . . . . . . . . . . . . . . . . . . . . 25
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2 Crosslinking Results and Literature Overview . . . . . . . . . . . . . . . . . . . . 33
2.1 Conventional Crosslinking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.1.1 The Standard “Dresden Protocol” . . . . . . . . . . . . . . . . . . . . . . 33
2.1.2 Medical History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.1.3 Evidence of Progression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
2.1.4 Clinical Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
2.1.5 Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.1.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
2.2 T ransepithelial Crosslinking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
2.3 Accelerated Crosslinking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
2.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
2.3.2 The 9 mW/cm2 Accelerated CXL . . . . . . . . . . . . . . . . . . . . . . 43
2.3.3 The 18 mW/cm2 Accelerated CXL . . . . . . . . . . . . . . . . . . . . . 45
2.3.4 The 30 mW/cm2 Accelerated CXL . . . . . . . . . . . . . . . . . . . . . 46
2.3.5 The 45 mW/cm2 Accelerated CXL . . . . . . . . . . . . . . . . . . . . . 49
2.3.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
2.4 Crosslinking for Paediatric Keratoconus: 10 Years-Follow-Up . . . . . . 50
2.4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
2.4.2 Demographic Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
xi
xii Contents
2.4.3 Surgical Procedure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2.4.4 Clinical Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
2.4.5 Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
2.4.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
3 Crosslinking Evidences In-Vitro and In-Vivo . . . . . . . . . . . . . . . . . . . . 63
3.1 H istology After Accelerated Cross-Linking (ACXL) . . . . . . . . . . . . 63
3.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3.1.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
3.1.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
3.1.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
3.1.5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
3.2 In Vivo Confocal Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
3.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
3.2.2 Stromal Healing After CXL . . . . . . . . . . . . . . . . . . . . . . . . . . 80
3.2.3 Epithelium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
3.2.4 Nerves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
3.2.5 Endothelium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.2.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.3 Biomechanical Measurement: Brillouin Microscopy . . . . . . . . . . . . 87
3.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
3.3.2 Measuring Corneal Biomechanics . . . . . . . . . . . . . . . . . . . . . 88
3.3.3 Brillouin Microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
3.3.4 Brillouin Microscopy to Assess CXL Mechanical
Outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
3.3.5 The Future of Brillouin Technology . . . . . . . . . . . . . . . . . . . 93
3.3.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
4 A ccelerated Crosslinking Protocols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
4.1 Dresden Accelerated CXL Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
4.2 Siena Crosslinking Center® Accelerated CXL Protocol . . . . . . . . . . 104
4.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
4.2.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
4.2.3 Surgical Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
4.2.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
4.2.5 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
4.3 Transepithelial ACXL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
4.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
4.3.2 Iontophoresis-CXL (I-CXL) . . . . . . . . . . . . . . . . . . . . . . . . . 112
4.4 Thin Corneas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
4.4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
4.4.2 Hypo-osmolar Riboflavin Solution . . . . . . . . . . . . . . . . . . . . 117
4.4.3 Transepithelial CXL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
4.4.4 Customized Pachymetry Guided Epithelial Debridement . . . 118