Mastering endothelial keratoplasty vol 1

Soosan Jacob has been at the forefront of these advances with multiple innovations to her credit including the endo-illuminator assisted Descemet’s membrane endothelial kerato-plasty dev

Volume I

123

Editor

Mastering Endothelial Keratoplasty

DSAEK, DMEK, E-DMEK, PDEK, Air pump-assisted PDEK and others Volume I

ISBN 978-81-322-2816-5 ISBN 978-81-322-2818-9 (eBook)

The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use

The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors

or omissions that may have been made

Printed on acid-free paper

This Springer imprint is published by Springer Nature

The registered company is Springer (India) Pvt Ltd

Soosan Jacob

Director and Chief

Dr Agarwal’s Refractive and Cornea Foundation

Dr Agarwal’s Group of Eye Hospitals

Chennai

India

For Ashwin and Riya – you are the reason

for me!

“The strongest and sweetest songs yet

remain to be sung.”

-Walt Whitman

We are now witnessing the natural progression of the management of corneal thelial disease from full thickness penetrating keratoplasty to endothelial transplan-tation With any new disruptive surgical technique there are pioneers who provide the leadership and direction to take an innovative idea and create the transformation that will change the future of our specialty Dr Soosan Jacob is one of these indi-viduals She is an undisputed innovator, educator and international leader in anterior segment surgery who constantly looks at surgical dilemmas and discovers solutions

endo-to the most diffi cult problems facing anterior segment surgeons endo-today Her surgical techniques have changed the face of ophthalmology and have been adapted world-wide to the betterment of our patients Her videos, often in collaboration with her mentor Dr Amar Agarwal, are masterpieces of innovation that have helped educate

an entire generation of ophthalmologists and have won numerous international awards In addition she is a prolifi c writer editing 15 textbooks, writing 200 book chapters and authoring 80 peer-reviewed publications She is a superb surgeon with many innovative instrumentations and surgical techniques to her credit, but most remarkably she possesses the rarest of all personal attributes, she is an original thinker Dr Jacob is creative, analytical, pioneering, and her advances are built on the foundation that no matter what we do, our patients come fi rst and we should do everything to maximize their visual outcome No case is too complex for Dr Jacob

In addition, Dr Jacob, despite all of her accomplishments, is humble and ing, always giving credit to anyone who has in anyway been associated with her success There is a small group of surgeons around the world that I call on for advice

self-effac-in managself-effac-ing my most demandself-effac-ing surgical cases and Dr Jacob is at the pself-effac-innacle of this elite group

Over little more than a decade there has been a revolution in advancing our agement of corneal endothelial disease Just a few short years ago penetrating kera-toplasty was the routine management of bullous keratopathy, pseudophakic bullous keratopathy and Fuchs’ dystrophy The visual rehabilitation was painfully slow with high postoperative astigmatism, surgically induced glaucoma and a lifetime risk of even mild ocular trauma resulting in a vision threatening wound dehiscence Endothelial keratoplasty has changed the course of the most common causes of

man-corneal transplantation Beginning with DSAEK and advancing to DMEK and now PDEK, visual rehabilitation for endothelial disease has now become safer with more rapid visual rehabilitation and incredible improvement in quality of vision and quality of life over full thickness penetrating keratoplasty Dr Soosan Jacob has been at the forefront of these advances with multiple innovations to her credit including the endo-illuminator assisted Descemet’s membrane endothelial kerato-plasty devised to enhance visualization and three-dimensional depth perception dur-ing DMEK and air-pump assisted pre-Descemet’s endothelial keratoplasty (PDEK) that makes PDEK surgery easier and more adoptable by surgeons

Dr Jacob’s new book, Mastering Endothelial Keratoplasty , is a comprehensive

tour de force of the surgical management of endothelial disease beginning with the history and anatomy, advancing through corneal transplantation, Descemet’s strip-ping automated endothelial keratoplasty (DSAEK), ultrathin DSAEK, Descemet’s membrane endothelial keratoplasty (DMEK) and fi nally pre-Descemet’s endothe-lial keratoplasty (PDEK) The book is a comprehensive analysis of the management

of endothelial disease and summarizes all of the best and most useful and practical pearls that she and her authors have developed Dr Jacob has brought together an extraordinary internationally recognized group of authors who have changed the face of endothelial management This book will be widely read by anterior segment surgeons who wish to add to their surgical skill and will be an important contribu-tion to ophthalmology

Eric Donnenfeld, MD Clinical Professor of Ophthalmology, NYU Trustee Dartmouth Medical School

Past President, ASCRS Editor-in-Chief, EyeWorld

The landscape of cornea as a sub-speciality has changed signifi cantly from the past Technology has improved by leaps and bounds and new techniques are constantly evolving Interlinking of technology, newer surgical techniques, and basic research has brought about rapid shifts in our approach to corneal surgery, especially kerato-plasty Lamellar keratoplasty, both anterior and posterior, have shown such improved results that they have become the standard of care The last two decades have seen the introduction of posterior lamellar keratoplasty as well as many changes in the way it has been performed Endothelial keratoplasty has today become the most popular of choices for endothelial dysfunction requiring surgery In 2011, about half the corneal transplants performed in the USA were Descemet stripping automated endothelial keratoplasty (DSAEK), and in 2012 it overtook penetrating keratoplasty

in terms of the number of corneas being used The acceptance is similar in many other parts of the world The reason DSAEK is fi nding favor with both surgeons and patients is because of the improved recovery times and visual outcomes as well as the numerous intra-operative advantages However, despite the even greater per-ceived advantages of the two more recent forms of endothelial keratoplasty – Descemet membrane endothelial keratoplasty (DMEK) and Pre-Descemet endothelial keratoplasty (PDEK) – there is still hesitancy on the part of many cor-neal surgeons to the inclusion of these into their surgical armamentarium This is because these are perceived as more challenging techniques with a greater learning curve

This two-volume book on endothelial keratoplasty (EK) serves to fi ll up a uum in this space as there is at present no book that covers all kinds of EK including DSAEK, ultra-thin DSAEK (UT-DSAEK), DMEK, and PDEK It has been aimed

vac-to serve as an excellent guide for DSAEK vac-to both the beginning surgeon as well as those who need a refresher to sharpen their skills further It also at the same time serves as a stepping stone for successfully, and with minimal heartburn, mastering the more challenging newer endothelial keratoplasties, viz., DMEK and PDEK The various minute steps that are essential for these as well as for newer ancillary tech-niques which help make surgery easy such as endoilluminator assisted DMEK (E-DMEK) and the air-pump assisted PDEK have been described in detail The

original pioneers for the various techniques as well as eminent specialists in this area have contributed their knowledge as well as given their tips and tricks for increasing surgical success The two volumes have been designed to comprehen-sively cover the pre-, intra-, and post-operative period The presence of numerous high-quality photographs, illustrations, and linked videos help make understanding easier and make this two volume book a must-have for all corneal surgeons Despite the amount of educational material in it, the size and format has been kept to allow easy reading The electronic format of the book helps carry it around for easy and quick reference at any place or time

I would like to thank many people for making this labor of love possible My co-authors who have contributed so much of their valuable time and effort to writing excellent chapters and have become dear friends; my friends and colleagues for their constant support in innumerable ways, and Saijimol AI for helping me with everyday work that otherwise would have overwhelmed me I would also like to thank Naren Aggarwal and Teena Bedi from Springer for encouraging me to take on this task, for being immensely helpful at every step and for keeping this book to such high standards I would like to thank all my patients from whom I have learnt

so much and all the teachers in my life who have taught me so much I would like

to especially thank my two mentors, Drs Amar and Athiya Agarwal who have pushed me ever forwards and always encouraged me to keep raising the bar further and further, always more than I would think possible for myself I would also like to thank my parents – Mary Jacob and Lt Col Jacob Mathai – for guiding me and molding me into what I am and my brother Alex Jacob and my sister Asha Jacob for always being there for me Finally, I would like to thank Dr Abraham Oomman, my husband, my best friend, my confi dante, and my sounding board for his unfl inching support and constant love, for making me keep at it and complete it, and lastly my children, Ashwin and Riya, who tolerated me throughout and kept me smiling through all the long hours spent

Finally, as Oliver Wendell Holmes said, “Great things in this world depends not

so much on where we stand but which direction we are moving.” This book is an attempt to throw a light to illuminate the path and make it easier to travel I hope you the reader will enjoy this book and glean from it pearls that you will be able to incorporate into your practice

Dr Soosan Jacob, MS, FRCS, DNB, MNAMS is Director & Chief; Dr Agarwal’s Refractive and Cornea Foundation (DARCF) and Senior Consultant, Cataract and Glaucoma Services, Dr Agarwal’s Group of Eye Hospitals, Chennai, India She is a noted speaker widely respected for her innovative techniques and management of complex surgical scenarios She conducts courses and delivers lectures in numerous national and international conferences; has been the recipient of IIRSI Special Gold medal, Innovator’s award (Connecticut Society of Eye Physicians), ESCRS John Henahan award for Young Ophthalmologist, AAO Achievement award and two time recipient of ASCRS Golden Apple award She has special interest in cutting-edge cataract, cornea, glaucoma, and refractive surgery and has won more than 40 international awards for videos on her surgeries, innovations and challenging cases

at prestigious international conferences in United States and Europe Her tions, many of which have won international awards, include anterior segment trans-plantation, where cornea, sclera, artifi cal iris, pupil and IOL are transplanted enbloc for anterior staphyloma; suprabrow single stab incision ptosis surgery to enhance postoperative cosmesis; turnaround techniques for false channel dissection during Intacs implantation; Glued Endo-Capsular Ring and Glued Capsular Hook for sub-luxated cataracts; Stab Incision Glaucoma Surgery (SIGS) as a guarded fi ltration surgery technique; Contact lens assisted crosslinking (CACXL) for safely cross-linking thin keratoconic corneas; Endo-illuminator assisted DMEK (E-DMEK) and Air Pump Assisted PDEK for easier and better surgical results; and the PrEsbyopic Allogenic Refractive Lenticule (PEARL) Inlay for treating presbyopia She has pro-posed a new classifi cation of Descemet’s membrane detachments into rhegmatoge-nous, tractional, bullous and complex detachments with a suitable treatment algorithm and a new technique of relaxing descemetotomy for tractional Descemet’s detachment Her surgeries and surgical techniques have often been Editor’s Choice

innova-in prestigious International Ophthalmic websites (AAO/ ONE network, ISRS, Eyetube etc) Her video blog “Journey into the Eye - A surgeon’s Video blog” in the prestigious Ocular Surgery News, USA features her surgical videos She also has her own surgical educational YouTube channel: Dr Soosan Jacob with more than

2500 subscribers Dr Jacob is senior faculty for training postgraduate, fellowship

and overseas doctors She has authored more than 80 peer reviewed articles, ous chapters in more than 30 textbooks by international publishers, is editor for 15 textbooks in ophthalmology and reviewer for many prestigious journals She has two popular columns, “Eye on Technology” and “Everything you want to know about” in the prestigious Eurotimes magazine published by ESCRS She is a com-mittee member of ISRS/AAO Multimedia Library and is on the editorial board of the Ocular Surgery News–Asia Pacifi c Edition, Cataract and Refractive Surgery Today- Europe, Glaucoma Today and the EuroTimes Magazines Her life and work have been featured on the Ocular Surgery News cover page, “5Q” interview (presti-gious Cataract and Refractive Surgery Today), “Sound off” column (CRST) and is the fi rst researcher internationally to be interviewed in the prestigious CRST

numer-“Researcher’s Column.” She can be contacted at dr_soosanj@hotmail.com

1 Anatomy of the Cornea 1

Soosan Jacob and Preethi Naveen

2 History of Endothelial Keratoplasty 13

Bishoy Said and Natalie Afshari

3 Penetrating and Endothelial Keratoplasty: An Overview 29

Prafulla K Maharana , Rajesh Pattebahadur , and Namrata Sharma

4 Endothelial Keratoplasty Versus Penetrating Keratoplasty 57

Soosan Jacob and A Sumathi

5 Evaluation of the Graft and Tissue Preparation

for Modern Endothelial Keratoplasty 75

Ian R Gorovoy , Maanasa Indaram , and Mark S Gorovoy

6 Role of Optical Coherence Tomography

in Endothelial Keratoplasty 89

Matthew Wade , Marjan Farid , Sumit Garg , and Roger Steinert

7 Descemet’s Stripping Automated Endothelial Keratoplasty 107

Robert A Copeland Jr , Usiwoma Abugo , and Young-Joo Lee

8 Ultrathin DSAEK 133

Yoav Nahum and Massimo Busin

9 Descemet Membrane Endothelial Keratoplasty (DMEK)

Surgery with a Standardized Technique 143

Christopher S Sáles , Zachary M Mayko , Mark A Terry ,

and Michael D Straiko

10 Unfolding Techniques for the DMEK Graft 173

Ester Fernández , Jack Parker , Isabel Dapena , Lamis Baydoun ,

Vasilios S Liarakos , and Gerrit R J Melles

11 The PDEK Bubble 189

Soosan Jacob

12 Pre-Descemet’s Endothelial Keratoplasty 205

Soosan Jacob and Amar Agarwal

13 Techniques for Graft Visualization and Identification

of Graft Orientation: Endoilluminator-Assisted Descemet’s

Membrane Endothelial Keratoplasty (E-DMEK) and Others 217

Soosan Jacob

14 Air-Pump-Assisted Pre-Descemet’s Endothelial Keratoplasty 227

Soosan Jacob

15 Descemet Membrane Endothelial Transfer (DMET) 239

María Satué , Fook Chang Lam , Isabel Dapena , Marieke Bruinsma ,

and Gerrit R.J Melles

Melles Cornea Clinic Rotterdam , Rotterdam , The Netherlands

Marieke Bruinsma, PhD Netherlands Institute for Innovative Ocular Surgery , Rotterdam , The Netherlands

Melles Cornea Clinic Rotterdam , Rotterdam , The Netherlands

Massimo Busin , MD Department of Ophthalmology , “Villa Igea” Hospital , Forlì , Italy

Istituto internazionale per la Ricerca e Formazione in Oftalmologia (IRFO) , Forlì , Italy

Robert A Copeland Jr , MD Department of Ophthalmology , Howard University Hospital , Washington , DC , USA

Isabel Dapena Netherlands Institute for Innovative Ocular Surgery , Rotterdam , The Netherlands

Melles Cornea Clinic Rotterdam , Rotterdam , The Netherlands

Marjan Farid , MD Department of Ophthalmology , Gavin Herbert Eye Institute, University of California , Irvine , CA , USA

Ester Fernández Netherlands Institute for Innovative Ocular Surgery , Rotterdam , The Netherlands

Melles Cornea Clinic Rotterdam , Rotterdam , The Netherlands

Sumit Garg , MD Department of Ophthalmology , Gavin Herbert Eye Institute, University of California , Irvine , CA , USA

Ian R Gorovoy Gorovoy Eye Specialists , Fort Myers , FL , USA

Department of Ophthalmology , University of California, San Francisco ,

San Francisco , CA , USA

Mark S Gorovoy Gorovoy Eye Specialists , Fort Myers , FL , USA

Maanasa Indaram Department of Ophthalmology , University of California, San Francisco , San Francisco , CA , USA

Soosan Jacob , MS, FRCS, DNB Director and Chief, Dr Agarwal’s Refractive and Cornea Foundation , Dr Agarwal’s Group of Eye Hospitals , Chennai ,

TN , India

Fook Chang Lam Netherlands Institute for Innovative Ocular Surgery ,

Rotterdam , The Netherlands

Melles Cornea Clinic Rotterdam , Rotterdam , The Netherlands

Young-Joo Lee , MA, MS Louis Stokes Health Sciences Library , Howard University , Washington , DC , USA

Vasilios S Liarakos Netherlands Institute for Innovative Ocular Surgery , Rotterdam , The Netherlands

Melles Cornea Clinic Rotterdam , Rotterdam , The Netherlands

Prafulla K Maharana , MD Department of Ophthalmology , All India Institute

of Medical Sciences , Bhopal , India

Zach M Mayko , MS Lions VisionGift , Portland , OR , USA

Gerrit R J Melles , MD, PhD Netherlands Institute for Innovative Ocular Surgery , Rotterdam , The Netherlands

Melles Cornea Clinic Rotterdam , Rotterdam , The Netherlands

Amnitrans EyeBank Rotterdam , Rotterdam , The Netherlands

Yoav Nahum , MD Department of Ophthalmology , “Villa Igea” Hospital ,

Preethi Naveen , MBBS, MS, FMRF (Cornea) Dr Agarwal’s Refractive

and Cornea Foundation , Dr Agarwal’s Eye Hospital , Chennai , TN , India

Jack Parker Netherlands Institute for Innovative Ocular Surgery , Rotterdam , The Netherlands

UAB Callahan Eye Hospital , Birmingham , AL , USA

Rajesh Pattebahadur , MD Department of Ophthalmology , All India Institute

of Medical Sciences , Bhopal , India

Christopher S Sáles , MD MPH Devers Eye Institute , Portland , OR , USA Weill Cornell Medicine , New York , NY , USA

Bishoy Said , MD Sharp Rees-Stealy Medical Group , San Diego , CA , USA

María Satué Netherlands Institute for Innovative Ocular Surgery , Rotterdam , The Netherlands

Melles Cornea Clinic Rotterdam , Rotterdam , The Netherlands

Namrata Sharma , MD Cornea & Refractive Surgery Services , Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences , New Delhi , India

Roger Steinert , MD Department of Ophthalmology , Gavin Herbert Eye Institute, University of California , Irvine , CA , USA

Michael D Straiko , MD Devers Eye Institute , Portland , OR , USA

A Sumathi , DNB Dr Agarwal’s Refractive and Cornea Foundation ,

Dr Agarwal’s Eye Hospital , Chennai , TN , India

Mark A Terry , MD Devers Eye Institute , Portland , OR , USA

Matthew Wade , MD Department of Ophthalmology , Gavin Herbert Eye

Institute, University of California , Irvine , CA , USA

© Springer India 2016

S Jacob (ed.), Mastering Endothelial Keratoplasty,

DOI 10.1007/978-81-322-2818-9_1

Anatomy of the Cornea

Soosan Jacob and Preethi Naveen

References 11

S Jacob , MS, FRCS, DNB ( * )

Director and Chief, Dr Agarwal’s Refractive and Cornea Foundation ,

Dr Agarwal’s Group of Eye Hospitals ,

19, Cathedral Road , Chennai 600086 , TN , India

e-mail: dr_soosanj@hotmail.com

P Naveen , MBBS, MS, FMRF (Cornea)

Dr Agarwal’s Refractive and Cornea Foundation ,

Dr Agarwal’s Group of Eye Hospitals ,

19, Cathedral Road , Chennai 600086 , TN , India

1.1 Introduction

The cornea is a transparent dome-shaped structure covering the iris, lens, and anterior chamber (AC) of the eye It accounts for nearly two-thirds of the total refractive power of the eye (Fig 1.1a, b ) The adult cornea measures 11–12 mm horizontally and 9–11 mm vertically The thickness varies from 0.5 mm in the central cornea and gradually increases to around 1 mm near the limbus [ 1 ] The periphery is more aspheric as the curvature decreases from the center toward the periphery Refractive index of the cornea is 1.376 The radius of curvature anteriorly is 7.8 mm and poste-riorly 6.5 mm The refractive power of the cornea is +48D on the anterior surface and

−5D on the posterior surface accounting for a net power of +43 D The normal tometric value for the cornea is within the range of 42–45 D Transparency, avascu-larity, and immunological privilege are unique properties of the cornea It derives its nutrition from tears, aqueous, and the perilimbal vasculature Oxygen supply is from the atmosphere through the tear fi lm and also from the perilimbal capillaries Aqueous humor is the main source of glucose for all layers of the cornea, while amino acids required for protein synthesis are acquired by passive diffusion from the aqueous

kera-1.2 Embryology

Corneal development begins from the 22nd day of gestation The layers of the cornea develop from different cell lineages The epithelium is derived from surface ecto-derm The corneal stroma, Bowman’s layer, and endothelium are derived from the mesenchymal cells of neural crest origin The Descemet’s membrane is laid down by the endothelial cells of neural crest origin from the 6th month onward The cornea starts becoming transparent around this time Cell migration occurs in three waves between the ectoderm and lens vesicle [ 2 ] The fi rst wave gives rise to corneal endo-thelium The second wave of cells is between the epithelium and endothelium giving rise to keratocytes which form the stroma The third wave of cells migrates between endothelium and lens giving rise to stroma of the iris The corneal epithelium

Fig 1.1 ( a ) The human cornea is a six-layered structure which is transparent and optically clear

It contributes to majority of the refractive power of the eye ( b ) The normal cornea seen in slit view

develops during the 6th week when the ectoderm detaches from lens vesicle The junctional complexes in the epithelium also form by the 6th week The cornea is well developed by the 7th month of gestation when the epithelium has clearly demarcated basal, wing, and superfi cial cells and stroma is almost fully developed with accumu-lation of keratan sulfate among collagen fi bers [ 3 ] The glycosaminoglycan chains bind to core protein from the proteoglycans which occupy the space between the collagen fi bers At birth the corneal epithelium has only two layers which gradually keeps increasing to reach adult thickness of fi ve to seven layers Anterior segment anomalies arise due to defective migration of neural crest derived cells

1.3 Layers of Cornea

The cornea has six layers and the Dua’s layer or the pre-Descemet’s layer (PDL) which is present between the stroma and Descemet’s membrane is a new addition to the traditional classifi cation of corneal layers into fi ve (Fig 1.2 )

This is the outermost layer of the cornea and is derived from the surface ectoderm It’s

a non-keratinized stratifi ed squamous epithelium measuring 50 μm in thickness posed of fi ve to seven layers of cells [ 3 ] The epithelium plays a crucial role in main-taining a smooth refractive surface along with the tear fi lm It also provides a mechanical

Fig 1.2 Layers of the cornea (not to scale): ( a ) epithelium, ( b ) Bowman’s layer, ( c ) stroma, ( d )

Dua’s layer, ( e ) Descemet’s membrane, ( f ) endothelium

barrier to all external pathogens The superfi cial cells are two to three layers, fl at, polygonal with numerous microvilli and microplicae on their surface that secrete gly-cocalyx which play a role in maintaining stability of the tear fi lm These cells are well differentiated (Fig 1.3A ) The next layer-the wing cell layer, so named because of the typical wing shape of the cells, consists of two to three layers, and these cells are in an intermediate state of differentiation (Fig 1.3B ) The basal layer is the only layer where the cells have mitotic activity and differentiate into wing and superfi cial cells The basal layer is attached by hemidesmosomes to the basal lamina (Fig 1.3C ).

There are different types of intercellular junctions between the epithelium The superfi cial cells have desmosomes and tight junctions (zonula occludens) which are mostly present along the apical surface of the superfi cial cells providing an effective barrier to penetration of tears The wing cells and basal cells have desmosomes, gap junctions, and hemidesmosomes [ 3 ]

The epithelium regenerates every 7–14 days The daughter cells differentiate into wing cells and migrate toward the surface as superfi cial cells Thoft and Friend postulated the X,Y,Z hypothesis where X-mitosis, Y-cellular migration, and Z-shedding of superfi cial cells suggests that there exists an equilibrium between these three factors which play a major role in epithelial regeneration [ 2 ] The epithe-lial stem cells are found in the palisades of Vogt which form a 1 mm zone around the limbus The stem cells give rise to transient amplifying cells which later migrate and form well-differentiated epithelial cells The limbal stem cells have a high pro-liferative capacity but are poorly differentiated

Diabetes causes the corneal epithelium to show reduced corneal sensitivity with increased susceptibility to delayed healing of epithelial defects There is a decrease

in the density of the subbasal nerve plexus which is noted to be related to the ity of diabetic retinopathy There is also increased permeability of the epithelium which could be due to abnormality in the tight junctions

sever-1.3.2 Bowman’s Layer

This is an acellular, tough membrane measuring 10 μm situated between the lium and stroma [ 3 ] It is not a true basement membrane unlike the Descemet’s membrane It is composed of randomly arranged collagen fi bers which are continu-ous with that of the anterior stroma This layer primarily contains collagen types 1

Fig 1.3 Normal epithelial

cells of the cornea ( A

superfi cial cells, B wing

cells, C basal cells)

and 3 The Bowman’s layer helps maintain the shape and is also resistant to trauma Unlike epithelium, it does not have the property to regenerate once destroyed and can form a fi brous scar following injury

Melles et al have recently come up with a novel technique for treatment of eyes with advanced keratoconus [ 4] In keratoconus, there is fragmentation of the Bowman’s layer, and hence Bowman’s layer transplantation into the mid-stromal region could cause fl attening of the anterior corneal surface and also an increase in the tensile strength The fl attening of the cone post-surgery was due to fi brosis and stromal compression Their study has shown an average reduction of 6–7 D in cor-neal power post-surgery As there are theoretically lesser risks of allograft rejection

as compared to a PK/DALK, this procedure offers promising results in the treatment

of advanced keratoconus which might require a transplant

1.3.3 Stroma

This layer contributes to almost 90 % of corneal thickness [ 2 ] It is derived from the mesenchyme There are approximately 200–250 lamellae of collagen fi bers arranged parallel to one another which run from limbus to limbus The stroma may be divided into anterior one-third and posterior two-thirds both of which have distinct features that play a role in the biomechanical strength of the cornea The prominent collagens are type 1 with smaller amounts of types 3, 5, and 6 [ 3 ] The proteoglycans in the stroma are dermatan sulfate, keratan sulfate and chondroitin sulfate Most abundant among them is keratan sulfate In the anterior one-third, the lamellar arrangement is oblique to each other and interlacing providing more strength It contains less water, glucose, and more dermatan sulfate The posterior two-thirds of the stroma has collagen fi bers which are parallel to one another and contain more keratan sulfate Posterior stroma has poor interlamellar connections This difference in fi ber arrangement offers more tensile strength to the anterior one-third of stroma as compared to the posterior stroma The keratocytes are highly metabolically active cells which are spindle shaped and lie scattered among the lamellae They synthesize collagen and proteoglycans

of the stroma The anterior stroma has a higher density of keratocytes as compared

to posterior stroma

1.3.4 Pre-Descemet’s Layer (PDL) or Dua’s Layer

The recent discovery of the pre-Descemet’s layer or the Dua’s layer has changed the understanding of lamellar corneal surgeries This previously unrecognized distinct layer of cornea is located between the posterior stroma and the Descemet’s mem-brane (Fig 1.4 )

The Dua’s layer is a tough, acellular layer measuring between 6 and 15 μm in thickness and composed of 5–8 thin lamellae of tightly packed collagen bundles

which run in longitudinal, transverse, and oblique directions [ 5 ] The fi brils are much thicker in this layer The collagen bundles on the anterior surface of the Dua’s layer are more regularly arranged and parallel The posterior surface has coarse bands of collagen arranged in a pleated pattern This layer is impervious to air which can be attributed to the tightly packed lamellae and greater space between

fi brils possible accommodating greater amounts of proteoglycan

The type 1 bubble in lamellar surgery is well circumscribed and dome shaped and starts from the center of the cornea and expands toward the periphery It typically forms between the stroma and PDL The type 2 bubble occurs when air enters the space between the posterior surface of Dua’s layer and the Descemet’s membrane This occurs because the PDL ends before the Descemet’s membrane and air escap-ing beyond the edge of the PDL into the periphery gains access to this plane [ 5 ] This plane between the Dua’s and stroma can be used to generate tissue for endo-thelial transplant This layer may also be involved in posterior corneal pathologies like acute hydrops and descemetocele

Recent studies [ 6 ] have also postulated that the collagen matrix of the trabecular meshwork (TBM) is an extension of the Dua’s layer and that the broad beams of the TBM take origin from the peripheral termination of the collagen lamellae of the Dua’s layer The presence of collagen 6 in both TBM and Dua’s layer as well as trabecular cells in the Dua’s layer has been presented by the authors as lending sup-port to the theory that formation of TBM commences in the peripheral part of Dua’s layer anterior to termination of DM

1.3.5 Descemet’s Membrane

This is secreted by the endothelial cells which are derived from the neural crest It

is composed primarily of collagen types 4 and 8 and laminin The membrane is divided into an anterior banded zone which is laid during fetal development and a posterior non-banded zone which is laid throughout life Thickness is around 8–10

Fig 1.4 Figure showing

schematic cross section of

the cornea Inset is the

zoomed view of the

microscopic structure

Arrow points to the

pre-Descemet’s layer

μm It is a true basement membrane and not a continuation of stroma like the Bowman’s layer [ 2 ] The peripheral termination of the DM forms the Schwalbe’s line The natural excrescences found in the periphery of the membrane are called Hassall-Henle bodies which do not interfere with vision The elasticity of this layer

is due to particular arrangement of collagen fi bers and glycoproteins (fi bronectin, laminin, thrombospondin) It is a tough layer which resists enzymatic degradation The DM has strong attachments to post surface of stroma In corneal ulcers as a result of high IOP, it herniates forming a descemetocele

1.3.6 Endothelium

This is a single layer of hexagonal cells arranged in a mosaic pattern around 5 μm thick with a density of 3000–4000 cells/mm 2 at birth which gradually keeps decreasing with age Average cell count for adults is between 1500 and 3500 cells/

mm 2 Primary function of the endothelium is to maintain corneal transparency by keeping the stroma in a dehydrated state Normal cornea has 70–80 % of hexagonal cells [ 2 ] The coeffi cient of variation (CV) normally is 0.25 The CV is the most sensitive index of endothelial dysfunction It is the standard deviation of cell area/mean cell area Polymegathism refers to increased variability in cell area and pleo-morphism is the deviation from hexagonality Loss of endothelial cells due to an insult is compensated for by enlargement and spreading of adjacent cells A fall in the endothelial cell count below a critical value results in corneal decompensation (Figs 1.5 and 1.6 )

1.3.6.1 Endothelial Pump

The endothelial pump plays a major role in corneal transparency There exists a pump-leak mechanism in the endothelium Passive movement of solutes from aqueous occurs through gap junctions in the endothelial layer The endothelium

Fig 1.5 Specular

microscopic picture of

corneal endothelium

has a Na+ and K+ dependent ATPase and a sodium/hydrogen exchange pump in its basolateral membrane [ 3 ] These cells contain numerous mitochondria and cyto-plasmic organelles as they are very metabolically active There exists an osmotic gradient between the aqueous and the stroma allowing sodium movement from the aqueous to stroma and potassium in the opposite direction Carbon dioxide diffuses into the cytoplasm of these cells along with water and generates bicarbonate This reaction is catalyzed by carbonic anhydrase enzyme The movement of bicarbonate into aqueous is coupled with water entry across the endothelial cells This pump mechanism is partly dependent on cellular energy Cooling of cornea causes swell-ing and opaque cornea which reverts back to normal once body temperature is normal known as the temperature reversal phenomenon When there is a failure in this pump mechanism, there is entry of aqueous into the stroma resulting in corneal edema, widening of space between collagen fi bers and loss of transparency (Table 1.1 ).

Fig 1.6 Pseudophakic

bullous keratopathy

Table 1.1 Causes of

corneal edema Fuchs endothelial dystrophy

Aphakic and pseudophakic bullous keratopathy Cornea guttata

Other endothelial dystrophies Trauma

ICE syndrome Glaucoma Advanced age Uveitis Contact lens wear

1.3.6.2 Specular Microscopy

It is a noninvasive method to evaluate the endothelial status It captures images which are refl ected from the optical interface between the endothelium and aqueous humor [ 3 ] The parameters analyzed are endothelial cell density, mean cell area, coeffi cient

of variation, and hexagonality There are two methods of analyzing the cells – the

fi xed frame and the variable frame analysis, with the latter being more reliable Donor corneas should have a count of at least 2000 cells/mm 2 for optimal functioning

1.4 Nerve Supply of the Cornea

The cornea is a highly innervated tissue Sensory nerves are derived from the long ciliary nerve which is a branch of the ophthalmic division of the trigeminal nerve [ 1 ] The long ciliary nerves run in the suprachoroidal space and pierce the sclera a little away from the limbus, where they branch and along with the conjunctival nerves form the pericorneal plexus of nerves From the perilimbal plexus, the nerves penetrate the cornea in the deep peripheral stroma The bulk of the corneal nerves enter at 3 and 9 o’clock positions They ascend upward in the stroma losing their myelin sheath and form three plexuses of nerves, namely, stromal plexus in the mid- stroma, the subbasal plexus, and the intraepithelial plexus The nerves penetrate the Bowman’s layer and terminate at wing cell level The sensitivity is maximum at the apex and minimum at periphery and further drops at the limbus Loss of corneal epithelium leads to increased pain sensitivity due to exposed nerve endings Amongst other causes, post Lasik dry eye symptoms are also directly related to the transection of corneal nerves during fl ap creation It is a temporary phenomenon

as the nerves regenerate within a period of 3–6 months The superiorly hinged fl ap

is found to sever more nerves as compared to a nasally or a temporally hinged fl ap

as the bulk of corneal nerves enter at 3 and 9 o’clock positions

1.5 Vascular Supply of the Cornea

The cornea is an avascular structure Anterior ciliary artery from the ophthalmic artery forms a vascular arcade and anastomoses with vessels from facial branch of the external carotid artery to form the perilimbal plexus of blood vessels [ 3 ] In normal corneas, there are no blood vessels because of the compact arrangement of

fi bers, whereas in pathological conditions when the cornea swells and creates space, vessels grow in between In conditions of infection or infl ammation there is growth

of new vessels which aid in repair Corneal hypoxia is also a stimulus for larization In superfi cial vascularization, vessels arise from the conjunctival plexus and can be traced beyond the limbus Deep vessels arise from anterior ciliary arter-ies and traverse deep in the stroma Once the infl ammatory stimulus is lost, these

neovascu-vessels regress leaving them as ghost neovascu-vessels The corneal epithelium has high expression of VEGFR-3 receptor which has an anti-angiogenic effect [ 2 ]

The success of corneal transplants is largely attributed to the avascular nature of cornea which offers it an immune privilege The presence of vascularization is one

of the main factors which interfere with graft survival The presence of more than two quadrants of deep vascularization poses a high risk of graft rejection Subconjunctival bevacizumab may be useful for regression of neovascularization prior to transplant

1.6 Transparency of the Cornea

Corneal transparency is contributed to by various factors both anatomical and physiological

These include the smooth surface of epithelium along with tear fi lm, regular arrangement of collagen fi bers, the absence of blood vessels, and the presence of nonmyelinated nerve fi bers Physiological factors like the role of stromal swelling pressure, endothelial pump mechanism, and the barrier function of corneal epithe-lium all play a key role in maintaining a dehydrated state of the cornea

The arrangement of collagen fi bers in the stroma plays a major role in ing corneal transparency The lattice theory of Maurice (1957) [ 3 ] postulates that the collagen fi bers are equal in diameter and the space between each fi ber is less than half the wavelength of light This arrangement causes destructive interference

maintain-of scattered light rays thereby maintaining transparency (Fig 1.7 ) The Goldman

a

b

Fig 1.7 Lattice theory ( a ) Cross-sectional view showing regular arrangement of collagen fi bers

in corneal stroma ( b ) Picture showing irregular arrangement of collagen fi bers in sclera

theory states that fi ber diameter less than one-third of the wavelength of light is enough to maintain transparency When there is fi brosis or edema, there is an increase in fi ber spacing leading to a loss in transparency.

Following any insult to corneal stroma, the keratocytes transform into myofi blasts [ 3 ] and produce extracellular matrix, collagen-degrading enzyme, matrix metalloproteases, and cytokines for tissue repair leading to wound closure

Stromal swelling pressure plays a role in maintaining the dehydrated state of the cornea The tendency of the stroma to swell is called swelling pressure (SP) Imbibition pressure is the property of collagen lamella to draw in fl uid This is also due to the repulsive forces between the negative charges on keratin and chondroitin sulfate The correlation between the imbibition pressure, swelling pressure, and intraocular pressure (IOP) is expressed as IP = IOP − SP [ 3 ] The IP is lower than swelling pressure due to the compressive effect of IOP In an excised cornea, the imbibition pressure is equal to swelling pressure

4 van Dijk K, Liarakos VS, Parker J, Ham L, Lie JT, Groeneveld-van Beek EA, Melles

GR Bowman layer transplantation to reduce and stabilize progressive, advanced keratoconus Ophthalmology 2015;122(5):909–17

5 Dua HS, Faraj LA, Said DG, Gray T, Lowe J Human corneal anatomy redefi ned: a novel pre- Descemet’s layer (Dua’s layer) Ophthalmology 2013;120(9):1778–85

6 Dua HS, Faraj LA, Branch MJ, Yeung AM, Elalfy MS, Said DG, Gray T, Lowe J The collagen matrix of the human trabecular meshwork is an extension of the novel pre-Descemet’s layer (Dua’s layer) Br J Ophthalmol 2014;98(5):691–7

© Springer India 2016

S Jacob (ed.), Mastering Endothelial Keratoplasty,

DOI 10.1007/978-81-322-2818-9_2

History of Endothelial Keratoplasty

Bishoy Said and Natalie Afshari

Contents

2.2 Penetrating Keratoplasty Versus Endothelial Keratoplasty 16

Table 2.1 Major milestones

Am J Ophthalmol 1964; 57:

67–78

1984 Barrquer Posterior keratoplasty w/sutures

Barraquer J The technique for penetrating keratoplasty In: Barraquer J,

Rutlan J, eds Microsurgery of the

Cornea 1998;17:618–26

2000 Terry DLEK

Terry MA, Ousley PJ Deep lamellar endothelial keratoplasty in the fi rst United States patients: early clinical results

Cornea 2001; 20: 239–243

2004 Melles Descemetorhexis

Melles GR, Wijdh RH, Nieuwendaal

CP A technique to excise the Descemet’s membrane from a recipient cornea (descemetorhexis)

Cornea 2004; 23: 286–288

2005 Price DSEK

(Cases started 2003, reported 2005) Price FW, Jr, Price MO Descemet’s stripping with endothelial keratoplasty in

50 eyes: A refractive neutral corneal transplant

2006 Busin Ultrathin DSAEK

Busin M, Bhatt PR, Scorcia V A modifi ed technique for Descemet membrane stripping automated endothelial keratoplasty to minimize endothelial cell loss

Cornea 2006; 25: 987–90

Table 2.1 (continued)

2012 Jacob S E - DMEK/E - PDEK

Jacob S, Agarwal A et al

Endoilluminator-assisted transcorneal illumination for Descemet membrane endothelial keratoplasty: enhanced intraoperative visualization of the graft in corneal decompensation secondary to pseudophakic bullous keratopathy

J Cataract Refract Surg

2014;40(8):1332–6

Jacob S, Agarwal A, Kumar

DA Endoilluminator- assisted Descemet membrane endothelial keratoplasty and endoilluminator-assisted pre-Descemet endothelial keratoplasty

Clin Ophthalmol 2015 Nov

16;9:2123–2125

2014 Agarwal,

Dua

PDEK

Agarwal A, Dua HS, Jacob S et al

Pre- Descemet’s Endothelial Keratoplasty (PDEK)

Br J Ophthalmol 2014

Sep;98(9):1181–5

2014 Jacob S Jacob S Air pump assisted PDEK https://www.youtube.com/

watch?v=lcIHrzdbDd4 Accessed on 26.6.16

Czech Eduard Zirm performed the world’s fi rst successful human corneal plant in 1905 He transplanted a donor cornea from the enucleated eye of an 11-year- old into a recipient who had sustained severe alkali burns [ 1 ] Several advances allowed for more successful transplantation during these cases including the intro-duction of antibiotics in the 1940s, development of microsurgical techniques and instruments in the 1950s, use of steroids in the 1970s, and advances in corneal preservation and eye banking [ 2 ]

The concept of selective replacement of diseased posterior tissue was introduced

by CW Tillet In 1956 he described the fi rst case of posterior lamellar keratoplasty [ 3 ] He performed a lamellar dissection of the posterior recipient cornea, excised the dissected central cornea, and then inserted the donor into the anterior chamber and sutured it into position

Air was injected into the anterior chamber for better positioning of the donor sue on the host The cornea failed to clear however, developing synechial angle closure and endothelial damage In 1964, Polack described endokeratoplasty where

tis-he created an anterior corneal fl ap that was retracted to trephine ttis-he recipient rior stroma, and then positioned a posterior lamellar donor corneal button He then repositioned the anterior fl ap and sutured it into place [ 4 ]

Subsequently, Jose Barraquer described a method of partial transplantation using

an anterior approach via a LASIK fl ap A partial-thickness fl ap was cut with a microkeratome; the posterior cornea (including posterior stroma, Descemet mem-brane, and endothelium) was trephined and replaced with a donor graft that was sutured in place The fl ap was then replaced and sutured into place [ 5 ] In 1980 he

presented a modifi cation of this technique Using a microkeratome, he created a hinged anterior fl ap, followed by trephination of the posterior stromal bed and suturing of a posterior donor lenticule [ 6 ]

Each of these original techniques and modifi cations had signifi cant drawbacks including being technically diffi cult and with limited clinical success It wasn’t until recent developments in the past two decades that has heralded the dramatic popular-ization of endothelial keratoplasty (EK) as discussed in detail below

2.2 Penetrating Keratoplasty Versus Endothelial

Keratoplasty

Penetrating keratoplasty (PK) certainly still plays a vital role for the cornea ist There are many indications where partial transplantation simply does not address the needs of the patient However, the two most common indications for corneal transplantation in the United States are Fuchs dystrophy and pseudophakic bullous keratopathy [ 7 ] Although both of these diseases have been successfully treated with PK for many years in the past, selective corneal transplantation of component tissue has revolutionized the treatment of these diseases resulting in improved recovery times and visual outcomes [ 8 ] 2012 was the fi rst year where more corneas were used for EK than for PK [ 9 ]

Traditional PK is a tried and proven procedure; however, it has disadvantages

and limitations Intraoperative need for removal of host tissue results in a period of

“open sky” which exposes ocular content and increases risk of choroidal hemorrhage and effusion during surgery [ 10 ] A large issue with PK is the fundamental struc-tural problems causing astigmatism and perpetually weak wounds given its full-thickness nature [ 11 ] (Fig 2.1 ) EK essentially eliminates this issue due to the minimal sutures and partial-thickness nature [ 6 ] The unpredictable astigmatism produced by circumferential sutures in PK is avoided in EK as well resulting in bet-ter visual outcomes with faster recovery [ 12 , 13 ] Since there is no full-thickness incision, the susceptible risk of rupture from minor trauma is also minimized [ 13 ] Since PK creates an anesthetic cornea, problems arise with epithelial breakdown which is aggravated by use of topical medications and presence of sutures This is avoided in EK since the normal corneal innervation is preserved [ 11 ]

Fig 2.1 Penetrating keratoplasty with full-thickness replacement of graft (Image Courtesy Dr

Soosan Jacob, Dr Agarwal’s Eye Hospital, Chennai, India)

Endothelial keratoplasty represents a paradigm shift in corneal transplant

sur-gery similar to phacoemulsifi cation in cataract sursur-gery [ 6 ] EK minimizes recovery period by limiting the number of sutures which subsequently induces less astigma-tism Fewer sutures also result in less vascularization which can also suggest less risk of ingrowth and graft rejection A smaller graft is used which means less for-eign antigen is introduced to the donor The absence of a full-thickness graft also lowers the risk of dehiscence Overall, EK allows for treatment of damaged endo-thelial disease with a lower risk of rejection, improved globe stability, and faster visual recovery [ 8 ]

2.3 Road Mapping of Endothelial Keratoplasty

2.3.1 PLK/DLEK

The foundation of the modern endothelial keratoplasty was laid by Dr Gerrit Melles

in 1998 [ 14 ] Melles was the fi rst to suggest that a posterior graft could be placed onto recipient stroma without the need for sutures; this should allow for better

vision Melles called this procedure posterior lamellar keratoplasty ( PLK ) This

procedure involved leaving the anterior stroma intact and creation of a deep stromal pocket of approximately 50 % depth across the cornea though a 9.0 mm superior scleral incision Donor tissue consisting of posterior stroma, Descemet membrane, and healthy endothelium was then inserted and held in place using an air bubble [ 15 ] (Fig 2.2a, b ) He later modifi ed the technique by using a 5.0 mm incision and folding the donor tissue to allow for insertion [ 16 ]

Melles also slightly modifi ed his original technique by using a 7.0 or 7.5 mm diameter transplant rather than the original 6.0 mm diameter disk fi rst described in the animal study In addition, the dissection was performed at 80 % depth instead of

50 % to allow for easier excision, less interface scarring, and leaving more of the original anterior stroma intact Early results showed all transplants were clear and in position 6–12 months after surgery Best-corrected visual acuity varied from 20/20 to 20/80 with average astigmatism of 1.54 diopters, average pachymetry of 490 um, and average endothelial cell density of 2520 cells/mm 2 [ 17 ] A 3-year follow-up study reported that in PLK, the donor corneal endothelium showed a decrease in cell den-sity similar to that after conventional full-thickness penetrating keratoplasty [ 18 ]

Mark Terry et al later presented a variation on PLK which they called deep lar endothelial keratoplasty ( DLEK ) [ 19 ] Modifi cations to PLK that Terry and Ousley introduced included using an artifi cial anterior chamber for manual preparation of the donor tissue Also, they dissected the recipient lamellar bed under viscoelastic rather than air The dissection on the recipient cornea extended beyond the area to be excised, but they used a donor lenticule that matched the diameter of the excised tissue This allowed for tucking of the edges of the donor tissue into the lamellar pocket of the recipient tissue [ 20 ] Terry also adopted the 5.0 mm incision that Melles introduced in

lamel-2002 and used the folding technique as well to perform the DLEK procedure

Terry showed stability in visual acuity, astigmatism, and endothelial cell count in 2-year outcomes using the original 9.0 mm or 9.5 mm scleral incision [ 21 ] Terry later showed promising results in a prospective study that included both large inci-sion and small incision (5.0 mm) DLEK Results showed improved vision to 20/46, astigmatism of 1.34 diopters, and a mean cell loss of 25 % [ 22 ]

Results from PLK and DLEK were both encouraging in that they showed rapid visual recovery with minimal astigmatic change compared to conventional full- thickness penetrating keratoplasty However, PLK and DLEK were two techniques that gained little popularity for a couple of reasons Firstly, few surgeons adopted the techniques because the procedure was so complicated and diffi cult to reproduce [ 6 ] In addition, the visual results were not predictable because of the double lamel-lar dissection causing irregular astigmatism [ 11 ]

2.3.2 DSEK/DSAEK

Endothelial keratoplasty truly gained momentum with the advent of Descemet

strip-ping endothelial keratoplasty (DSEK) In 2004, Melles described the rhexis (Fig 2.3 ) This technique involved removing only the Descemet membrane and the dysfunctional endothelium from the recipient eye, leaving the posterior lamella intact [ 23 ] This simplifi ed preparation no longer required the diffi cult

descemeto-a

b

Fig 2.2 Posterior lamellar keratoplasty (PLK) ( a ) Posterior 50 % stroma; the Descemet

mem-brane and endothelium are removed ( b ) Donor tissue consisting of posterior stroma, Descemet

membrane, and healthy endothelium is inserted and held in place with air (Image Courtesy Dr Soosan Jacob, Dr Agarwal’s Eye Hospital, Chennai, India)

lamellar dissection and excision procedure on the recipient cornea This technique

was adopted, modifi ed, and popularized by Price et al who termed it Descemet stripping endothelial keratoplasty ( DSEK ) [ 24 ] In this procedure, they utilized Melles’ technique to remove the host Descemet membrane and place a donor lenti-cule consisting of posterior stroma, Descemet membrane, and healthy endothelium This lenticule is folded and inserted through a 5 mm incision into the anterior cham-ber As previously described with PLK and DLEK, the graft is held in place with an air bubble

In a series of 50 eyes, Price et al showed that 76 % of eyes treated with DSEK corrected to 20/50 or better and 62 % of eyes corrected to 20/40 or better The post-operative manifest cylinder was unchanged from preoperative cylinder [ 25 ]

Although this showed a marked improvement in visual outcomes, it was still diffi cult to achieve 20/20 results, and this was believed to be caused by the haze

at the graft-host interface Also the depth of the dissection was inconsistent and the technique remained challenging [ 6 ] To address this issue, Gorovoy was the

fi rst to introduce the use of a microkeratome for donor tissue dissection which

he termed Descemet stripping automated endothelial keratoplasty ( DSAEK )

[ 26 ] (Fig 2.4 ) DSAEK gained even more popularity and acceptance once eye banks started providing precut donor tissue, eliminating the need for surgeons to perform a two-step procedure [ 27 ] (Note: for the remainder of this section, DSEK will be the term used but will refer to both DSEK and DSAEK interchangeably.)

Price recognized that interface fl uid needed to be eliminated to minimize risk of dislocation Accordingly, he introduced compressing and sweeping the corneal sur-face while a large air bubble was present in the anterior chamber to squeeze out

fl uid trapped in the interface He also introduced venting incisions to remove face fl uid [ 28 ] Terry introduced the surgical technique of peripheral recipient bed scraping to enhance physical attachment of donor tissue and minimize risk of dislocation [ 29 ]

The adoption of DSEK surgery has been extremely rapid and accounted for approximately half of the corneal transplant surgeries performed in the United States in 2011 compared to only 4.5 % of cases in 2005 [ 30 , 31 ]

DSEK provides rapid and predictable visual recovery The procedure has gained such popularity for a number of reasons: (1) it avoids an open-sky procedure, (2) there are fewer sutures which minimize astigmatism, (3) it promotes better tectonic stability because of a smaller beveled incision rather than a full-thickness vertical incision in PK, (4) it avoids an anesthetic donor cornea, (5) it results in reduced graft failure from ocular surface disease, and (6) it allows an earlier return of refractivity stability and good visual acuity [ 32 ] It is essentially a refraction neutral transplant procedure that results in earlier visual recovery than PK with better uncorrected and best corrected visual acuity [ 6 ] The American Academy of Ophthalmology prepared

an Ophthalmic Technology Assessment report on DSEK and reviewed published

lit-erature on safety and outcomes The average best corrected Snellen visual acuity ranged from 20/34 to 20/66 (mean 9 months; range, 3–21 months) The review showed postoperative refractive induced hyperopia ranging from 0.7 to 1.5 diopters (D; mean 1.1D), with minimal induced astigmatism ranging from −0.4 to 0.6 D and

a mean refractive shift of 0.11D [ 32 ] The percentage of patients seeing 20/40 or ter ranges from 38 to 100 % [ 6 ] Visual outcomes are better in younger patients and

bet-in eyes without long-standbet-ing edema and associated stromal scarrbet-ing [ 33 , 34 ]

The Cornea Donor Study showed that overall graft success was comparable for

DSEK and PK procedures, and endothelial cell loss was higher with DSEK The regraft rate within 15 months was 2.3 % in DSEK group and 1.3 % in PK group At 12 months, percent endothelial cell loss was 38 + −22 % for DSEK and 20 + −23 % in PK group [ 35 ] Complications from DSEK include graft dislocation, endothelial rejec-tion, primary graft failure, iatrogenic glaucoma, and infection Dislocations are the most common complication of this procedure The AAO report found that rates var-

Fig 2.4 Descemet

stripping automated

endothelial keratoplasty:

microkeratome is used for

donor tissue preparation

for transplanting stroma,

Descemet membrane, and

endothelium after host

descemetorhexis

ied from 0 to 82 %, with an average dislocation rate of 14.5 % Endothelial rejection

is defi ned as failed grafts that were previously clear after initial DSEK surgery These rates varied from 0 to 45.5 %, with average rejection rate of 10 % in studies with fol-lowing from 3 to 24 months Primary graft failure is linked to poor surgical technique and surgeon inexperience The report showed rates from 0 to 29 % with an average primary graft failure rate of 5 % Postoperative glaucoma can be caused by pupil block from the air bubble or induced by topical corticosteroids Rates of glaucoma have been reported from 0 to 15 %, with an average of 3 % Endophthalmitis has never been reported with DSEK although it certainly is a potential complication

DSEK has become the standard of care for EK in the United States [ 6 ] The high safety profi le, reproducible and manageable surgical technique, rapid visual recov-ery, and predictable visual outcomes have certainly contributed to this trend and its popularization

2.3.3 Ultrathin DSAEK

One of the largest issues with DSEK is the postoperative hyperopic shift Studies have shown that thicker grafts induce more hyperopia [ 36 , 37 ] Accordingly, thin DSEK techniques have been introduced and are becoming increasingly popular to address this issue [ 38 ] Neff et al showed that grafts thinner than 131 um had better visual outcomes [ 39 ] Busin et al showed promising results in a series of 285 eyes with a mean graft thickness of 78.28 + −28.89 um with 2-year outcomes He showed visual outcomes with ultrathin DSEK to be comparable with those published for DMEK and better than those reported after DSEK in terms of speed of visual recov-ery and percentage of patients with 20/20 fi nal visual acuity [ 40 ] Another study that reviewed 460 eyes showed that there was no difference in visual acuity based on graft thickness [ 41 ] The ideal DSEK graft thickness for optimum results remains to

be determined

2.3.4 DMEK/DMAEK

In 2006, Melles et al described a procedure they termed Descemet membrane thelial keratoplasty (DMEK) [ 42 ] (Fig 2.5 ) DMEK allows transplantation of an isolated endothelium and Descemet membrane (DM) layer without adherent cor-neal stroma The donor DM was stripped from the corneoscleral rim and injected into the host anterior segment via a clear corneal incision The membrane was unrolled using pneumatic and fl uidic manipulations and apposed to the recipient posterior stroma using the same air bubble technique used in DSEK The early results from this group showed much promise [ 43 ] Price and Giebel et al described

endo-a modifi cendo-ation for prependo-arendo-ation of the donor tissue termed the SCUBA technique In

this technique, the peripheral DM is gently scored and under immersion; the scored

edge of DM is grasped with a non-toothed forceps and slowly stripped away from the stroma about half way to the center for 360° A central partial-thickness trephi-nation is then performed on the endothelial side of the donor tissue, and then the separation of the central punched DM is completed [ 44 ] Kymionis et al have

described Descemet membrane automated endothelial keratoplasty ( DMAEK ) with

the use of an epikeratome for automated lamellar dissection of the tissue similar to DSAEK [ 45 ]

The host tissue is prepared similar to the process of DSEK where a central ent descemetorhexis is performed under air, fl uid, or viscoelastic The donor tissue

recipi-is then inserted into the eye using one of the several methods Melles originally described donor insertion using a glass pipette with an attached bulb to draw up the donor and then inject it into the anterior chamber [ 46 ] IOL injectors or Jones tube with BSS or viscoelastic have also been used [ 44 , 47 ]

Once in the eye, the donor tissue is then unfolded by one of several described techniques After the tissue is unfolded and in correct orientation, air is injected beneath the graft to attach it to the recipient cornea [ 6 ]

Visual recovery with DMEK occurs fast Price et al showed that mean CDVA

was 20/30 at 1 month At 3 months, 26 % of patients had 20/20 vision, 63 % of patients had 20/25 vision or better, and 94 % of patients had 20/40 vision or better Refractive cylinder remained unchanged at 0.9 D, but there was a statistically sig-nifi cant hyperopic shift of 0.5 D [ 44 ] Similar results were reported in several other studies [ 47 – 50 ] Initial endothelial cell counts have been comparable to PK and DSEK The Melles group reported an average endothelial cell density of 1850 cells/

mm 2 at 6 months after surgery and 1680 cells/mm 2 at 12 months [ 51 ]

A more recent multicenter study of DMEK looking at the fi rst case series of 18 surgeons in 11 countries showed promising results as well Of 275 eyes, 78.9 % had best corrected visual acuity of at least 20/40, 42.5 % at least 20/25, and 22.2 % at least 20/20 [ 52 ]

DMEK is a surgically challenging procedure with a high learning curve It requires high surgical dexterity and has been used with limitation recently [ 53 ] Despite these challenges, however, there is faster recovery, better visual outcomes, lower higher-order aberrations, and less refractive changes [ 54 ] DMEK is still evolving, and as modifi cations and technique alterations make the procedure more feasible, there will likely be further adoption of the surgery as we similarly wit-nessed with DSEK in the past decade

2.3.5 E-DMEK or Endoilluminator-Assisted DMEK

This was described by Jacob et al as a technique to facilitate easier surgery [ 55 ] It utilizes the endoilluminator to enhance visualization and 3-dimensional perception

of the DMEK graft This helps in easier comprehension of graft position, tion, morphology, and dynamics, all of which leads to easier and faster surgery It avoids unnecessary maneuvers that might otherwise be required to analyze graft position and thereby decreases potential graft damage (Fig 2.6 )

orienta-2.3.6 PDEK/E-PDEK or Endoilluminator-Assisted PDEK

In 2014, Agarwal et al in collaboration with Dua et al described pre-Descemet thelial keratoplasty (PDEK) [ 56 ] This involves transplantation of the newly described pre-Descemet layer along with the Descemet membrane and the endothelium (Fig 2.7 ) This gives the advantage of being able to use young grafts of any age, thus allowing transfer of a greater number of endothelial cells The PDEK graft is also more tough and robust and less likely to tear than the DMEK graft E-PDEK refers to the technique

endo-of using the endoilluminator in PDEK to allow far greater ease endo-of surgery

perception of the DMEK

graft within the AC This

helps in easier

comprehension of graft

position, orientation,

morphology, and

dynamics, all of which

leads to easier and faster

surgery