.1016j.ajo.2013.10.001 [605314]

Intraoperative Anterior Segment Optical Coherence
Tomography: A Novel Assessment Tool during Deep
Anterior Lamellar Keratoplasty
LAURA DE BENITO-LLOPIS, JODHBIR S. MEHTA, ROMESH I. ANGUNAWELA, MARCUS ANG, AND
DONALD T.H. TAN
/C15PURPOSE: To describe the use of high-resolution ante-
rior segment optical coherence tomography (AS-OCT)during deep anterior lamellar keratoplasty (DALK).
/C15DESIGN: Prospective case series.
/C15METHODS: At the Singapore National Eye Centre we
performed sequential intraoperative AS-OCT scans usingiVue 100-2 (Optovue, Fremont, CA, USA) duringvarious DALK techniques.
/C15RESULTS: In case 1 (corneal scarring) the OCT images
helped to guide manual dissection, showed the depth ofthe needle track before air injection, and identified thelocation of a small bubble when the big bubble failed. Incases 2 (macular dystrophy) and 3 (lattice), viscodissec-tion was undertaken, but in case 2 the OCT showed theviscoelastic trapped intrastromally, compared to case 3,in which the viscobubble dissection was successful. In
case 4 (irregular corneal thinning and scarring), AS-
OCT enabled accurate decision on initial trephinationand guided dissection. In case 5 (keratoconus), theOCT showed the achieved big-bubble and detachedDescemet membrane. Case 6 was a repeat DALK; theOCT guided the manual dissection of the residual stromaunderlying the failed graft. In case 7, the OCT showed anintrastromal retention of fluid that was not detectable by
the operating microscope due to diffuse scarring following
alkaline injury. The OCT helped to assess the location ofthe Descemet membrane and guided the manual dissec-tion.
/C15CONCLUSIONS: Intraoperative high-definition AS-OCT
obtained good-quality images of the cornea duringDALK and proved useful in various cases of DALK tohelp the surgeon decide on a number of surgicalsteps. (Am J Ophthalmol 2014;157:334–341. /C2112014
by Elsevier Inc. All rights reserved.)
RECENT IMPROVEMENTS IN SURGICAL TECHNIQUES
and technology have led to the resurgence of deepanterior lamellar keratoplasty (DALK) as an alterna-
tive to penetrating keratoplasty (PK) for the treatment of
corneal stromal diseases for a variety of optical, tectonic andtherapeutic indications.
1A recent review has established
that DALK is superior to PK in preserving corneal endothe-lium and is therefore the preferred option for patients experi-encing corneal stromal disease that does not affect theendothelium.
2Even while taking into consideration the
differing complications and outcomes of DALK and PK,
D A L Kh a sb e e ns h o w nt ob eam o r ec o s t – e f f e c t i v ep r o c e d u r e .3
Visual acuity results of DALK have been shown to be better
if a bare Descemet membrane is achieved or if there is mini-mal residual stroma, as in a predescemetic DALK.
2,4,5
Variations of the big-bubble technique first introduced byAnwar
6have been described.7–9In our centre, we use a
modified technique in which an anterior stromal layer isremoved before attem pting the big-bubble.
10,11The depth
of the initial trephination is routinely decided based on the
ultrasound pachymetry, aiming to leave a residual stroma ofapproximately 150 mm to allow for the safe placement of
the 27-gauge needle closer to the Descemet membrane. Inour technique, a needle is first used to create the initial tunnelin the stroma advancing for 2–3mm. A blunt cannula (TanDALK cannula 27 gauge, AE-7803; Asico, Westmont, IL,USA) attached to a 3 or 5 mL air-filled syringe is then intro-
duced through that initial opening. It is advanced 1 mm
farther toward the Descemet membrane before injection ofa i ri sc o m m e n c e d .
The initial manual dissection and the use of a blunt can-
nula allows for a safer air-injection with reduced risk forperforation. However, in cases of marked irregular thin-ning, the ultrasound pachymetry can provide only an esti-mate of the corneal thickness and the location of the
thinning, which can lead to an inadequate depth of treph-
ination and manual dissection, increasing the risk forobtaining too thin a residual stroma for the safe introduc-tion of the needle/cannula, or even an undesired perfora-tion. Also, in cases where the injection of air does notachieve the desired Descemet membrane separation, the
Supplemental material available at AJO.com .
Accepted for publication Oct 2, 2013.
From the Singapore National Eye Centre, Singapore (L.B.-L., J.S.M.,
R.I.A., M.A., D.T.H.T.); the Singapore Eye Research Institute,Singapore (J.S.M., M.A., D.T.H.T.); the Department ofOphthalmology, National University Health System, Singapore (J.S.M.,D.T.H.T.); and the Duke-NUS Graduate Medical School, Singapore(J.S.M.).
Laura de Benito-Llopis is currently at St Thomas’ Hospital, London,
UK. Romesh I. Angunawela is currently at Moorfields Eye Hospital,London, UK.
Inquiries to Laura de Benito-Llopis, Singapore National Eye Centre, 11
Third Hospital Avenue, Singapore 168751; e-mail: lauradeb@hotmail.
com
334 0002-9394/$36.00
http://dx.doi.org/10.1016/j.ajo.2013.10.001/C2112014 BY ELSEVIER INC.ALL RIGHTS RESERVED .

surgeon is left with an emphysematous whitened cornea,9
in which visualization is impaired and ultrasound pachyme-
try may not obtain reliable measurements.12The surgeon
may then try a viscodissection or continue with anotherlayer of manual dissection without knowing the real depthand evenness of the dissection. This increases the risk forperforation and for irregular residual stroma that may affectthe final postoperative visual acuity.
Anterior segment optical coherence tomography
(AS-OCT) allows for rapid, noncontact, high-resolutionimaging of the anterior segment.
13Intraoperative AS-
OCT imaging has been shown to be useful during Descemet
FIGURE 1. Intraoperative anterior segment optical coherence tomography (AS-OCT) images obtained in a case of deep anterior
lamellar keratoplasty performed with manual dissection. Top left: corneal scarring secondary to neurotrophic keratopathy; theAS-OCT provided a precise measurement of the corneal thickness. Top right: partial trephination and initial manual dissection. Sec-
ond line, left: residual stromal thickness following 2 layers of manual dissection, measured by the OCT. Second line, right: intrao-
perative image of the manual dissection of the second layer. Third line, left: track created by the 27 gauge needle. Third line, center:cannula inserted into the stromal track. Third line, right: the metallic cannula prevented imaging of the underlying stroma with the
OCT. Bottom left: partial detachment of the Descemet membrane following air injection. Some air bubbles can be seen in the anterior
chamber with the OCT. Bottom right: final manual dissection.
VOL.157,NO.2 335 INTRAOPERATIVE ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY

stripping automated endothelial keratoplasty (DSAEK) to
detect the presence of interface fluid and assess the effect ofthe procedure and air tamponade on graft thickness.
14In
this study, we assessed the utility of intraoperative AS-
OCT during DALK surgery: whether it could help reduce
the risk for perforation and for uneven residual stromaand guide the surgeon intraoperatively in various surgicalsteps in cases where the surgery is more complicated.
METHODS
WE CONDUCTED A PROSPECTIVE STUDY OF PATIENTS
undergoing DALK for a variety of corneal diseases at theSingapore National Eye Center between November 2011and March 2012. Informed consent was obtained from allsubjects to participate in this prospective study, whichfollowed the principles of the Declaration of Helsinki,and ethics approval was obtained from the SingaporeHealth Services Institutional Review Board in accordancewith their guidelines.
Depending on the condition of each eye, either a modi-
fied big-bubble technique, as described in the introduction,
or a manual dissection was planned.
11Surgeries were
performed by 2 experienced corneal surgeons (J.S.M. andD.TH.T). Intraoperative AS-OCT imaging was performedduring several steps of the surgery, using the spectral domainOCT (iVue 100-2; Optovue, Fremont, CA, USA) in thedark operating theater. All scans were performed by 1 inde-pendent observer (LBL), who optimized each scan for the
best image quality. We used the standard anterior segment
single-scan protocol with multiple horizontal scans, ie,26,000 axial scans per second, scanning width of 6 mmand 5 mm image resolution. We have previously described
the use of this device in DSAEK surgery; however, thisdevice is now supported by a microscope arm, and a pedalallows it to be aligned in the X, Y, and Z axes.
14
FIGURE 2. Intraoperative anterior segment optical coherence tomography (AS-OCT) images obtained during deep anterior lamellar
keratoplasty in a case of irregular corneal thinning. Top: bilateral corneal scarring and irregular thinning after corneal infectionsfollowing epipolis laser in situ keratomileusis (epi-LASIK) surgery. Center: intraoperative AS-OCT revealed 312 mm of stroma
at the thinnest point (under epithelium). Bottom: bare Descemet membrane after successful big bubble and removal of corneal stroma.
336 FEBRUARY 2014 AMERICAN JOURNAL OF OPHTHALMOLOGY

RESULTS
INCLUDED IN THE STUDY WERE 7 EYES OF 7 ASIAN PATIENTS;
their mean age was 31.5 616.5 years.
/C15CASE 1, MANUAL DISSECTION: A 9-year-old male with
corneal scarring secondary to neurotrophic keratopathyunderwent DALK ( Fig. 1 , top left). The described modified
big-bubble technique was used, starting with partial treph-
ination and dissection ( Fig. 1 , top right). In this case, the
residual thickness shown by the OCT was 250 mm, so a
further manual dissection was undertaken, leaving a poste-rior residual stroma of approximately 150 mm(Fig. 1 ,
second line). A 27-gauge needle was used to create theinitial opening, and the depth of the track was assessedwith the AS-OCT imaging ( Fig. 1 , third line, left). A blunt
cannula was introduced through that initial opening in the
stroma, attached to an air-filled syringe ( Fig. 1 , third
line, center); the OCT image, however, could not showthe underlying structures beneath the metallic cannula(Fig. 1 , third line, right). After air injection, the surgeon
suspected that only a small, localized air bubble had beenattained, but visualization under the operating microscopecould not confirm it. The OCT confirmed its presence and
location ( Fig. 1 , bottom left). However, in view of his
young age, the surgeon decided to avoid any risk for perfo-ration and did not dissect the small bubble, undertakinginstead an OCT-guided predescemetic manual dissection(Fig. 1 , bottom right). The surgery was successfully
completed, leaving 50 mm of residual stroma and leaving
the area of the bubble to reabsorb.
/C15CASE 2, FAILED VISCODISSECTION: A 57-year-old male
with lattice dystrophy underwent DALK with initial succes-ful trephination and dissection, but a big bubble was notachieved. A dispersive ophthalmic viscosurgical device(Viscoat; Alcon Laboratories, Hu ¨nenberg, Switzerland)
was used to perform a viscodissection. With this, a bubblewas achieved, but due to the difficult visualization under
the surgical microscope through the viscohydrated cornea,
the surgeon could not identify whether it was intrastromalor whether dissection at the Descemet plane had beenachieved. The OCT image at this stage showed that theviscoelastic had created an intrastromal separation of thecorneal lamellae, with no Descemet membrane separation(Supplemental Fig. 1 ). Further manual dissection was there-
fore undertaken, with the help of the intraoperative OCT to
guide the depth of dissection. Finally, the Descemet plane
was reached, and a descemetic dissection successfullyachieved.
/C15CASE 3, SUCCESSFUL VISCODISSECTION: In this case of
macular dystrophy in a 38-year-old male, a DALK wasscheduled because endothelial function was still preserved.
FIGURE 3. Intraoperative anterior segment optical coherence tomography (AS-OCT) images of a successful big bubble before
removal of residual stroma, obtained during deep anterior lamellar keratoplasty. Short thick arrows indicate the detached Descemetmembrane. Long thin arrows indicate the image artifact created by the reflection of the overlying stroma. Top: AS-OCT image from
the center of the cornea. Bottom: AS-OCT image from the peripheral cornea.
VOL.157,NO.2 337 INTRAOPERATIVE ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY

However, a big bubble was not achieved, and multiple
small air bubbles could be detected separating thestroma from the Descemet membrane on AS-OCT(Supplemental Fig. 2 ). The surgeon decided to attempt
viscodissection, which proved successful and, although
the OCT could not show the viscobubble, it did not
show any intrastromal accumulation of the viscoelastic,and the surgeon could complete the baring of the Descemetmembrane without complications.
/C15CASE 4, IRREGULAR CORNEAL THINNING: A 41-year-
old male suffered bilateral corneal scarring and irregularthinning after corneal infections following epipolis laser
in situ keratomileusis (epi-LASIK) surgery ( Fig. 2 , top).
Intraoperative AS-OCT revealed 312 mm of stroma in
the thinnest point (under the epithelium) in contrast toultrasound pachymetry of 450 mm (with epithelium)
(Fig. 2 , middle). Based on this, the surgeon decided to
trephine initially only up to 200 microns, to avoid perfora-tion. Manual dissection was then undertaken, guided byrepeated OCT images, until it showed a residual stroma
of 200 to 300 mm in different parts of the cornea. A big bub-
ble was then attempted and achieved, and the residualstroma was removed, leaving a bare Descemet membrane(Fig. 2 , bottom)./C15CASE 5, BIG BUBBLE: In this 30-year-old male with kera-
toconus and no previous history of hydrops, the big bubblewas achieved and imaged with the AS-OCT ( Fig. 3 ). The
air bubble could be seen close to the iris and the anteriorcapsule of the lens, but because the scan had to be focusedmuch deeper to detect the bubble, and the depth of theimage obtained with the OCT was limited, we could not
get a single image that included both the cornea and the
big bubble together. Surgeons desiring to detect the bubblewith the OCT need to be aware that the scan has to befocused significantly posteriorly to detect the bubble andDescemet membrane separation.
/C15CASE 6, MANUAL DISSECTION: In this 22-year-old
female with a previous failed DALK, intraoperative AS-
OCT revealed 80 mm of posterior lamella underneath the
failed DALK ( Fig. 4 , top left). Careful manual dissection
was performed ( Fig. 4 , top right) until the interface sepa-
rating the failed graft and the recipient’s cornea wasreached ( Fig. 4 , middle), and the graft was safely removed.
The residual layer of the recipient’s cornea had becomevascularized following rejection of the graft. Furthermanual dissection was then undertaken, guided by OCT,
to remove the vascularized stroma, leaving a clear residual
stromal thickness of 40 mm(Fig. 4 , bottom).
FIGURE 4. Intraoperative anterior segment optical coherence tomography (AS-OCT) images obtained during manual dissection of a
previously failed deep anterior lamellar keratoplasty (DALK). Top left: the AS-OCT image shows 80 mm of posterior lamella under-
neath the failed DALK. Top right: initial lamellar dissection. Center: AS-OCT-guided manual dissection to remove the previous graft
and part of the underlying recipient’s posterior stroma. Bottom left: the AS-OCT shows residual stromal thickness of 40 mm at the
end of the dissection. Bottom right: surgical image at the end of the dissection.
338 FEBRUARY 2014 AMERICAN JOURNAL OF OPHTHALMOLOGY

/C15CASE 7, DECREASED VISUALIZATION: A 30-year-old
male suffered bilateral alkaline injury resulting in diffuse,severe corneal scarring that decreased visualization of theunderlying stroma both with the operating microscopeand with the AS-OCT ( Fig. 5 , top). Intraoperative AS-
OCT revealed an intrastromal pocket of fluid during initialmanual dissection, which was not clinically evident underthe operating microscope ( Fig. 5 , second line, left). When
the manual dissection reached that fluid collection, the
leaking fluid made the surgeon suspect a possible perfora-tion into the anterior chamber ( Fig. 5 , second line, right).
The AS-OCT could identify an intrastromal layer ofscarred/coagulated tissue forming a ‘‘cyst’’ where the fluidhad been accumulating, and it helped to locate the intactDescemet membrane further posteriorly ( Fig. 5 , thirdline, left). Dissection up to the Descemet plane was
achieved in that area ( Fig. 5 , third line, right), but later a
small perforation in the superior cornea was noted. Toavoid extension of the perforation, a stromal patch wasleft to cover the perforation, as previously described,
10
and the donor cornea was dissected to fit the remanent stro-
mal patch ( Fig. 5 , bottom).
DISCUSSION
AN OPTIMAL BIG BUBBLE IS NOT ALWAYS ACHIEVED DURING
DALK,15and visualization may make it difficult to decide
how to proceed thereafter.9Although reasonably good
FIGURE 5. Intraoperative anterior segment optical coherence tomography (AS-OCT) images obtained during deep anterior lamellar
keratoplasty performed with manual dissection in a case of decreased visualization. Top: diffuse, severe corneal scarring resultingfrom alkaline injury impairs visualization of deeper layers by AS-OCT and the operating microscope. Second line, left: intrastromal
pocket of fluid revealed by intraoperative AS-OCT. Second line, right: manual dissection of that pocket. Third line, left: intrastromal
layer of scarred/coagulated tissue where the fluid had been accumulating (short thick arrows). The intact Descemet membrane islocated farther posteriorly in the AS-OCT image (long thin arrow). Third line, right: intrasurgical image showing dissection up to
the Descemet membrane. Bottom left: AS-OCT image showing the residual stroma, left, as a patch in an area of microperforation,
with the overlying graft in place. Bottom right: intrasurgical image of the residual stroma left as a patch in an area of perforation beforeplacing the donor cornea.
VOL.157,NO.2 339 INTRAOPERATIVE ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY

outcomes are achieved even if residual stroma is left in
place,4,9better contrast sensitivity and visual acuity are
obtained if the Descemet membrane is exposed.16
In this case series, our surgeons found that intraoperative
AS-OCT was useful in several steps of the surgery and in avariety of therapeutic, optical and tectonic cases. Pre- and
postoperative use of AS-OCT in other forms of kerato-
plasty has been described,
17,18but we could find only 1
recent study using intraoperative AS-OCT duringDALK.
19The purpose of that study was to assess the depth
of the cannula placed before the air injection and toanalyze the relationship between that depth and the suc-cess rate in obtaining the big bubble. As in our case series,they found the AS-OCT to be very useful in determining
the depth of the cannula, and they suggest the possibility
of obtaining an OCT image before attempting the air injec-tion, in case repositioning the cannula is considered neces-sary. We agree, based on our series, that the intraoperativeAS-OCT images can be used as a basis for surgical deci-sions, increasing the safety and success of the surgery.
The AS-OCT has been shown to be useful in aiding
decision making during other corneal procedures, such
as LASIK, DSAEK and implantation of intracorneal
rings.
20–23In our case series, the AS-OCT was useful in
guiding manual dissection in cases of failed big bubble,ensuring a thin and even residual stromal bed in order toimprove visual outcomes.
16In cases with irregular corneal
scarring and thinning, the AS-OCT can help to determinethe initial trephination depth so as to avoid a perforationand reach an adequate depth to achieve a big bubble.
19,24
In our case series, the AS-OCT was especially useful incases of decreased visualization under the operating micro-scope, where the image obtained with the OCT providedinvaluable information to the surgeon.
We found, however, 2 drawbacks. First, the surgery had
to be interrupted every time an image was taken becausethe operating microscope had to be moved away to allowfor the AS-OCT device to be placed over the eye. Thisdelayed the surgery and made it necessary to have anunscrubbed assistant to take all the images and measure-ments. Ideally, development of a real-time AS-OCT thatcould image every intraoperative step during surgery,
attached to the operating microscope, would have a greater
impact on surgical practice during DALK.
Second, metallic instruments obstruct image acquisition.
The depth of the needle could be obtained only byremoving the needle and assessing the tunnel created(Fig. 1 , third line, left). The image obtained with the
needle or cannula in position showed only the superiorborder of the metallic instrument ( Fig. 1 , third line, right)
and obscured any deeper structures.
In conclusion, intraoperative AS-OCT was useful during
DALK to guide in several steps of the surgery and toachieve an optimal descemetic or predescemetic dissec-tion, although the assembly of the machine could improveto make its use more time-efficient during surgery.
THE AS-OCT WAS ON LOAN FROM OPTOVUE (IVUE; OPTOVUE, FREMONT, CA, USA). GRANT FROM THE NATIONAL MEDICAL
Research Council of the Singapore government (JSM, DT); consultancy by Carl Zeiss Meditec (JSM); royalties from UK Network Medical (JSM). Designand conduct of study (L.B.L., J.S.M., R.A., D.T.); Collection, management, analysis, and interpretation of data (L.B.L., J.S.M., R.A., M.A., D.T.) ; Prep-
aration of manuscript (L.B.L., M.A.); and Review and final approval of manuscript (L.B.L., J.S.M., R.A., M.A., D.T.).
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Biosketch
Dr Laura de Benito-Llopis did her ophthalmology residency in Madrid, Spain, and her corneal fellowship at Moorfields Eye
Hospital, London. She obtained her PhD in laser surface ablation surgery with cum laude at the Universidad Complutense
of Madrid. She worked as a consultant at the Cornea and Refractive Surgery department at Vissum Madrid, and as senior
clinical associate at the Singapore National Eye Centre, Singapore. She is now a consultant at St Thomas’ Hospital,
London.
341.e1 FEBRUARY 2014 AMERICAN JOURNAL OF OPHTHALMOLOGY

Biosketch
Assoc Prof. Jod S. Mehta is Head of the Tissue Engineering and Stem Cell Group at the Singapore Eye Research Institute
and Head of the Corneal Service and Senior Consultant in the Refractive Service at Singapore National Eye Centre.
His corneal interests lie in corneal transplantation – penetrating keratoplasty, lamellar keratoplasty and endothelial
keratoplasty, femtosecond laser technology, corneal imaging, corneal infections, corneal refractive surgery,
keratoprosthesis surgery, ocular drug delivery systems and corneal genetics.
VOL.157,NO.2 341.e2 INTRAOPERATIVE ANTERIOR SEGMENT OPTICAL COHERENCE TOMOGRAPHY

SUPPLEMENTAL FIGURE 1. Intraoperative anterior segment optical coherence tomography (AS-OCT) images obtained during
deep anterior lamellar keratoplasty in a case of failed viscodissection that was followed by manual dissection. (Top): intrastromal sep-aration of the corneal lamellae by the viscoelastic following failed viscobubble attempt. (Bottom): AS-OCT–guided manual dissection
of the residual stroma.
SUPPLEMENTAL FIGURE 2. Intraoperative anterior segment-optical coherence tomography images obtained during deep anteriorlamellar keratoplasty in a case of successful viscodissection. (Top): multiple small air bubbles detected separating stroma from Desce-
met membrane after failed big-bubble attempt. (Bottom left): viscodissection achieved successful viscobubble. (Bottom right):removal of residual stroma shows underlying bare Descemet membrane.
341.e3 FEBRUARY 2014 AMERICAN JOURNAL OF OPHTHALMOLOGY