Download ARVO 2016 Annual Meeting Abstracts 311 Keratoconus and

ARVO 2016 Annual Meeting Abstracts
311 Keratoconus and Collagen Crosslinking
Tuesday, May 03, 2016 8:30 AM–10:15 AM
Exhibit/Poster Hall Poster Session
Program #/Board # Range: 2883–2922/A0143–A0182
Organizing Section: Cornea
Program Number: 2883 Poster Board Number: A0143
Presentation Time: 8:30 AM–10:15 AM
Same Day vs. Sequential CK+CXL in the Treatment of Ectasia
Olivia Dryjski1, Roy Rubinfeld2, 1, Richard Lindstrom6,
Deborah Kim2, Michael Choi2, Sirikishan Shetty3, Renato Ambrosio5,
Arthur Cummings4. 1Ophthalmology, Medstar Georgetown
University Hospital/Washington Hospital Center, Washington,
DC; 2Ophthalmology, Re:Vision Private Practice, Washington,
DC; 3Ophthalmology, Weill Cornell Medical College, New York
Presbyterian Hospital, New York, NY; 4Wellington Eye Clinic,
Beacon Hospital, Dublin, Ireland; 5Instituto de Olhos Renato
Ambrosio, Rio de Janeiro, Brazil; 6Ophthalmology, Minnesota Eye
Consultants, University of Minnesota, Minneapolis, MN.
Purpose: Corneal crosslinking (CXL) is often combined with
procedures to improve vision and corneal shape in patients
with advanced ectasia; however, studies combining conductive
keratoplasty (CK) with CXL have demonstrated marked regression
by 3 months. We performed a non-randomized, prospective, noncomparative case series to evaluate Logmar improvement in vision
using CK followed by same day CXL compared to CK 1 day before
CXL in patients with ectasia. The goal of our study is to find a
sustainable method for stabilizing the cornea and ultimately improve
vision in patients with advanced ectasia.
Methods: Our study includes 209 eyes from 149 patients, 65%
are male and 35% female. The mean age is 34 years. 17% of eyes
were treated for post LASIK ectasia and 81% for keratoconus.
Exclusion criteria includes corneal apex thickness less than
325 microns, rigid contact lens use within 4 weeks of CK and
postoperatively, and patients with adequate corrected distance
visual acuity (CDVA). CK was performed using intraoperative
keratometry and/or serial Pentacam tomography measurements;
CXL, using a novel, proprietary riboflavin loading system was
performed the same day or 1 day following CK. CDVA was
analyzed preoperatively and at postop month (POM)1, 2-4.5, 4.510, 10-15 using 2-tailed paired Ttest.
Results: For all patients at POM10-15, mean improvement in
LogMAR UDVA is 0.083 (p=0.132) and LogMAR CDVA is 0.106
(p=0.001). Mean improvements in LogMAR CDVA is 0.08(p=0.03)
at POM10-15 for same day eyes, 0.16 (p=0.01) at POM10-15 for
eyes with CXL 1 day after CK. For patients with a preop CDVA of
20/40 or worse, mean improvements in LogMAR CDVA is 0.17
(p=0.02) at POM10-15 for CK followed by same day CXL and
0.41(p<0.001) at POM10-15 for eyes with CXL 1day after CK.
Conclusions: CK plus proprietary Epi-On CXL for ectasia is a safe,
effective, non-invasive method to improve vision in select patients.
Statistically significant improvement in CDVA is noted up to 15
months postop. Improvement in uncorrected distance visual acuity
(UDVA) is noted, but is not statically significant at POM10-15.
Superior improvement in vision is observed with CXL 1day after
CK compared to eyes with same day CK and CXL. These results
are more pronounced at 10-15 months, as there was markedly more
regression in patients with same day CK + CXL by 10-15 months
postoperatively. As expected, greater results are visible in patients
with a preoperative CDVA of 20/40 or worse.
Commercial Relationships: Olivia Dryjski, None; Roy Rubinfeld;
Richard Lindstrom, Refractec CXLO (I), Refractec;
Deborah Kim, None; Michael Choi, None; Sirikishan Shetty,
None; Renato Ambrosio, Alcon (I), Zeiss (I), Oculus Gmb (I);
Arthur Cummings, None
Clinical Trial: NCT01024322
Program Number: 2884 Poster Board Number: A0144
Presentation Time: 8:30 AM–10:15 AM
Monitoring of O2 concentrations during Corneal Cross-Linking
(CXL) by Phosphorescence Lifetime Imaging Microscopy (PLIM)
Rebecca M. McQuaid1, Michael C. Mrochen3, Ruslan Dmitriev2,
Dmitri Papkovski2, Brian Vohnsen1. 1Ophthalmology, Univ Coll
Dublin/IROC Innocross, Dublin, Ireland; 2School of Biochemistry
and Cell Biology, University College Cork, Cork, Ireland;
3
Ophthalmology, IROC Science AG, Zurich, Switzerland.
Purpose: The diffusion of riboflavin and oxygen is vital for efficient
corneal cross-linking (CXL) with UV light. Previous studies
found the biomechanical effect of CXL to be oxygen dependent.
The purpose of this study is to investigate the role of O2 and its
distribution across the stroma before and during CXL through the use
of phosphorescence based probes and imaging.
Methods: Porcine eyes were obtained from the local slaughterhouse
4 hours post mortem and kept at a temperature of 4oC. The epithelium
was removed and the cornea was stained with a solution containing
0.5% riboflavin and infra-red emitting nanoparticles O2 probe for 30
min to allow diffusion. The globe was then analysed at 37° C and
21% ambient O2 on the confocal upright PLIM microscope (Zeiss,
Becker & Hickl GmbH) using 5x/0.25 Fluar objective, excitation
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ARVO 2016 Annual Meeting Abstracts
at 488 nm and emission collected at 750-810 nm. The cornea was
imaged over 10 minutes at depths of 0, 50, 100, 150 and 200 µm.
The cross-linking was achieved through periodic 20-30 cycles
illumination of cornea with UV-A LED light (7 mW/cm2) whilst
imaging. Photon distributions and phosphorescence decay curves
were analysed after measurement, from which lifetime values and O2
concentrations were calculated and presented as 2D and 3D maps.
Results: We optimised staining with the O2 probe and measurement
conditions for the cornea, and performed proof-of-principle PLIM
experiments before and after CXL. We observed efficient and
uniform in-depth staining of the cornea allowing us to generate highresolution O2 maps and monitor O2 dynamics during CXL. Previous
PLIM results scanning in the Z-direction revealed little to no change
in lifetime decays during UV illumination, suggesting axial scanning
may be a quicker and more efficient method in quantifying O2
lifetimes during the CXL process.
Conclusions: The use of phosphorescent O2 probes allows for
efficient and a minimally-invasive method in measuring O2 prior to,
and during CXL. 2D and 3D maps of O2 concentrations across the
stroma during CXL will enable us to better understand the role of
oxygen during CXL. Future work will focus on measurements under
different O2 environments to verify the CXL effect with O2 probes,
and to investigate the suitability of O2 PLIM method for future invivo use.
Nanoparticle staining of the cornea at depths up to 250µm (ambient
conditions only)
Commercial Relationships: Rebecca M. McQuaid, None;
Michael C. Mrochen, None; Ruslan Dmitriev, None;
Dmitri Papkovski, None; Brian Vohnsen, None
Support: IRCSS EPSPG/2013/598
Program Number: 2885 Poster Board Number: A0145
Presentation Time: 8:30 AM–10:15 AM
Corneal Collagen Crosslinking and Intracorneal Ring Segments:
Simultaneous vs Sequential Surgery
Reda Issa1, Peter S. Hersh1, Steven Greenstein2. 1Ophthalmology,
Rutgers University - New Jersey Medical School, Newark, NJ;
2
Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA.
Purpose: Intacs® (implantable intracorneal ring segments (ICRS))
and corneal collagen crosslinking (CXL) are used for the treatment of
keratoconus and corneal ectasia. In previous work, using symmetric
350µm segments, we found no clinical difference between sequential
and simultaneous treatment. In this prospective randomized
controlled clinical trial, we compare the 6-months clinical outcomes
of eyes with one 450µm Intacs® segment placed, CXL performed
simultaneously or 3 months later.
Methods: 26 eyes of 18 patients (19 eyes in the simultaneous group,
and 7 eyes in the sequential group) received one 450µm segment of
Intacs® (Addition Technology Inc, Illinois, USA) followed by CXL.
The first group had Intacs® placed followed by CXL on the same
day (simultaneous group), and the second group received Intacs®
followed by CXL 3 months later (sequential group). Principal
outcomes included uncorrected distance visual acuity (UCDVA)
and best-corrected distance visual acuity (BCDVA), maximum and
average keratometry (K), inferior-superior (I-S) ratio, and point of
maximum flattening, as measured by the Pentacam (Oculus Inc,
Wetzlar, Germany).
Results: UCDVA improved by -0.28 ± 0.28 LogMAR (P < 0.01) and
-0.2 ± 0.43 LogMAR (P = 0.41) in the simultaneous and sequential
group, respectively. BCDVA improved by -0.07 ± 0.12 LogMAR (P
= 0.065) and -0.16 ± 0.12 LogMAR (P = 0.056) in the simultaneous
and sequential group, respectively. With regards to topography,
average K flattened by -1.67 ± 1.07D (P < 0.01) and -3.72 ± 3.33D (P
= 0.054), and maximum K flattened by -3.01 ± 2.09D (P < 0.01) and
-5.78 ± 4.45D (P = 0.034) in the simultaneous and sequential group,
respectively. The I-S ratio improved by -4.9 ± 2.24D (P < 0.01) in the
simultaneous group, and by -6.05 ± 4.47D (P = 0.03) in the sequential
group. The point of maximum flattening flattened by -8.0 ± 2.64D
compared to -11.68 ± 5.65D. There was no statistically significant
difference between the simultaneous and sequential group with
regards to all of the primary outcomes (PUCDVA = 0.66, PBCDVA =0.18,
Paverage K = 0.24, Pmaximum K = 0.2, PI-S = 0.60, Pmax flattening = 0.18).
Conclusions: Intacs®, with a single 450µm segment, followed
by corneal collagen crosslinking, performed sequentially or
simultaneously, appear to have similar efficacy.
Commercial Relationships: Reda Issa, None; Peter S. Hersh,
None; Steven Greenstein, None
Clinical Trial: NCT01112072
Program Number: 2886 Poster Board Number: A0146
Presentation Time: 8:30 AM–10:15 AM
CORNEAL CROSS-LINKING BEFORE INTRASTROMAL
RING SEGMENT IMPLANTATION DECREASES THE
EFFECTIVENESS OF THE RINGS
Lucia Ibares-Frias1, 2, Patricia Gallego1, 3, Roberto Cantalapiedra3,
Gisele Cristina G. Gonçalves de Almeida Cunha3,
Jesus Merayo-Lloves1, 4, María Carmen Martínez-García1, 3.
1
Group of Optical Diagnostic Techniques, University of Valladolid,
Valladolid, Spain; 2Ophthalmology, Hospital Clínico Universitario
de Valladolid, Valladolid, Spain; 3Cellular Biology, Histology and
Pharmacology Department, Faculty of Medicine, University of
Valladolid, Valladolid, Spain; 4Instituto Universitario Oftalmológico
Fernandez-Vega, Oviedo, Spain.
Purpose: To compare the clinical and histological response after
intracorneal ring segment (ICRS) implantation with previous and
posterior corneal crosslinking (CXL) in an experimental animal
model (hen).
Methods: We performed surgery for this study on 16 hens (32 eyes)
which were randomly divided into three groups. In the first group,
epi-off CXL was performed before ICRS implantation by a manual
Technique (Ferrara Technique). In the second group implantation
of ICRS was performed before epi-off collagen CXL. After ICRS
implantation, hens were followed clinically for 4 months, when they
were euthanized for histological analysis and immunofluorescency
studies. Quantitative measurements of the histological preparations
were also performed. Direct transmittance of the central cornea was
also measured in each group. Values of the measured variables were
analyzed by calculating the mean and standard deviation. SPSS 19
Statistical software was used. An independent T Student Test was
used for comparisons between the two groups. A p value less than
0.05 was considered to be statistically significant.
Results: In the first group 83% of the eyes had good clinical follow
up. Complications described were, superficial neovascularization
and intrasurgically segment break. In the second group 71% had
good follow up and complications were ;neovascularization and
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ARVO 2016 Annual Meeting Abstracts
spontaneous extrusion. Clinically, in both groups fewer deposits were
found with lower intensity than in ICRS implantation without CXL.
Histologically, statistically significant differences were found in
corneal thickness and segment rotation. All these values were lower
in the first group. Direct transmittance in both groups 4 months after
treatment was similar to no treated corneas.
Conclusions: Cross linking in combination with ICRS implantation
in an experimental animal model is related to some complications
that must be considered in daily practice. Corneal crosslinking before
implantation of ICRS leads to less clinical and histopathological
wound healing response than cross linking after implantation.
Commercial Relationships: Lucia Ibares-Frias, None;
Patricia Gallego, None; Roberto Cantalapiedra, None; Gisele
Cristina G. Gonçalves de Almeida Cunha, None; Jesus MerayoLloves, None; María Carmen Martínez-García, None
Program Number: 2887 Poster Board Number: A0147
Presentation Time: 8:30 AM–10:15 AM
Corneal endothelial loss after corneal crosslinking for
keratoconus
Naoko Kato1, 2, Megumi Shinzawa2, Kenji Konomi2, Kozue Kasai2, 3,
Jun Shimazaki2. 1Department of Ophthalmology, Saitama Medical
University, Saitama, Japan; 2Ophthalmology, Tokyo Dental
College Ichikawa General Hospital, Chiba, Japan; 3Department of
Ophthalmology, Jikei University, Tokyo, Japan.
Purpose: Corneal crosslinking (CXL) is known as a procedure that
halts the progression of keratoconus using riboflavin and ultraviolet-A
(UVA) light. To avoid endothelial cell density (ECD) loss due to
UVA, we should swell the corneal stroma with a hypotonic solution
to obtain a 400µm thickness during UVA irradiation. However,
reaching 400µm is difficult in some cases. We retrospectively
investigated the effect of CXL on the ECD comparing the corneal
stromal thickness before and during the CXL procedure.
Methods: Sixty-three eyes of 49 patients with progressing
keratoconus (38 males and 11 females, 21.7 ± 6.3 years-old) were
investigated. CXL was performed using the epithelial off method.
Following 0.1% riboflavin instillation for 20 minutes, the thinnest
corneal thickness was measured by pachymetry around the apex
of the corneal cone. When the thickness was less than 400µm, a
hypotonic solution was instilled until the corneal stroma swelled to
400 µm or more. UVA was irradiated at 3.0 mW/mm2 for 30 minutes
or 18.0 mW/mm2 for 5 minutes. The eyes were divided into 2 groups;
eyes with no ECD decrease, and eyes with a decrease of 10% or
more at 1 month after CXL compared to their preoperative value.
Patients’ age, sex, pattern of ultraviolet-A irradiation, preoperative
keratometric readings, thinnest corneal thickness (TCT), and ECD
were analyzed.
Results: The average ECD count for all of the eyes was 2,664.9 ±
368.7 cells/mm2 preoperatively and decreased to 2,632.0 ± 497.0
cells/mm2(p=0.0147)at 1 month after CXL, however, this returned to
the preoperative value at 3 months and thereafter. Twenty-nine eyes
(46.3%)revealed an ECD decrease at 1 month after CXL. Between
the eyes with and without ECD decrease, the preoperative TCT was
not significantly different (406.5 ± 46.0 μm vs 406.2 ± 69.4 μm),
however, the TCT just before the ultraviolet-A irradiation was 419.4
± 49.0 μm in eyes with an ECD decrease and 434.1 ± 51.6 μm in
eyes without an ECD decrease (P=0.0427). Other factors were not
significantly different between the groups.
Conclusions: More than 40% of eyes showed transient ECD
decrease after CXL. Obtaining enough corneal thickness by swelling
the corneal stroma just prior to the UVA irradiation seemed to be
necessary in order to avoid ECD loss after CXL using riboflavin and
ultraviolet-A.
Commercial Relationships: Naoko Kato, Eye Lens Lte Ptd. (F);
Megumi Shinzawa; Kenji Konomi, None; Kozue Kasai, None;
Jun Shimazaki, Eye Lens Lte Ptd (F)
Clinical Trial: http://www.umin.ac.jp/ctr/index-j.htm,
UMIN000014719
Program Number: 2888 Poster Board Number: A0148
Presentation Time: 8:30 AM–10:15 AM
Biocompatible Chondroitin sulfate-based cross-linker restores
corneal mechanics and collagen alignment
Xiaokun Wang, Jeeyeon Sohn, Garret Ma, Samuel C. Yiu,
Jennifer Elisseeff. ophthalmology, Johns Hopkins University,
Baltimore, MD.
Purpose: Collagen crosslinking initiated by riboflavin and UVA
irradiation has recently been developed as a clinical treatment
to slow the corneal ectasia progression. However, there are
clinical complications of the UVA crosslinking, such as corneal
scarring, and corneal tissue thinning ect., indicating a safer and
more biocompatible method to reinforce the cornea is in demand.
Chondroitin sulfate is a biological polymer that is abundant in the
extracellular matrix of tissues throughout the body, including corneas.
In this study we developed a functionalized chondroitin sulfate
N-hydroxysuccinimide (CS-NHS) as a biocompatible, non-UVA
initiated crosslinker to crosslink ectatic corneas.
Methods: Cadaver rabbit eyes were crosslinked in 2, 5, 10mg/ml
CS-NHS in PBS buffer for 30 and 60 min respectively. CS-NHS
penetration, swelling ratio and ultrastructural change were evaluated
to optimize the crosslinking time and crosslinker concentration.
As for crosslinking of ectatic corneas, rabbit eyes were treated with
collagenase and chondroitinase enzymes to generate the ectatic
models, and then crosslinked in 5mg/ml CS-NHS solution for 60 min.
Corneal mechanics, ultrastructure, thermal stability, and inflammatory
gene expression were evaluated before and after crosslinking.
Results: The enzyme treatment significantly decreased the
corneal mechanics and also damaged collagen fibril. The CS-NHS
crosslinker was able to effectively penetrate into corneal stroma,
restored corneal strength by 20~30%, decreased swelling ratio
by 60%, and significantly increased collagen fibril thickness and
density. Furthermore, qPCR results demonstrated that conventional
UVA crosslinking significantly up-regulated TNFa and MMP9
gene expression, which raised the risk of complications such as
corneal scarring and melting, whereas CS-NHS did not trigger
any inflammatory response, and exhibited a protective potential of
keratocytes during crosslinking, as it up-regulated keratocan and
biglican gene expression.
Conclusions: In this study, we generated an ex vivo corneal ectatic
model that simulates the structural disorder of keratoconus. CS-NHS
crosslinking effectively stabilized the corneas without triggering
inflammatory response. These findings indicate CS-NHS will benefit
the ectatic corneas not only in the conventional structural stabilizing
way, but also in a more versatile, non-invasive and potentially
protective way.
Commercial Relationships: Xiaokun Wang; Jeeyeon Sohn, None;
Garret Ma, None; Samuel C. Yiu, None; Jennifer Elisseeff, None
Support: KKESH grant
Program Number: 2889 Poster Board Number: A0149
Presentation Time: 8:30 AM–10:15 AM
Effect of Epithelial Removal on the Corneal Curvature in
Keratoconic Eyes prior to Crosslinking
Michael W. Belin1, Jimena C. Siordia2. 1Ophthalmology, University of
Arizona, MARANA, AZ; 2University of Arizona, Tucson, AZ.
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ARVO 2016 Annual Meeting Abstracts
Purpose: To evaluate epithelial masking on keratoconic corneas and
determine how anterior and posterior curvature is altered by epithelial
thinning.
Methods: 22 eyes of 22 patients with mild to moderate keratoconus
scheduled for corneal collagen crosslinking were imaged with the
Pentacam HR prior to and immediately following epithelial removal.
Pre and post epithelial removal anterior and posterior radius of
curvature (ARC, PRC respectively) from the central 6.0 mm zone and
corneal thickness at the thinnest point were recorded.
Results: Pre-operative ARC averaged 7.55 +/- 0.33 mm. Post
removal values were 7.42 +/- 0.39, representing a significant change
of -0.12 +/- 0.10 mm (p < .001). Pre-operative PRC averaged 6.03 +/0.24 mm. Post removal values were 6.02 +/- 0.24 mm, representing
a non significant change of -0.01 +/- 0.04 (p=0.28). Pre-operative
pachymetry at the thinnest point averaged 510 +/- 37 um and post
removal 483 +/- 34 um. The change in corneal thickness at the
thinnest point was significant with an average of 24.5 +/- 11/6 um
(p<.001). A larger change in ARC was associated with a smaller
pachymetric changes (r=0.50, p=0.018).
Conclusions: Epithelial thickness varies in mild to moderate
keratoconus eyes with more thinning being correlated with disease
severity. ARC changes were inversely related to corneal thickness
change suggesting a greater masking effect. the degree of posterior
ectasia greatly exceeded anterior ectasia with or without the effect of
the corneal epithial masking.
Commercial Relationships: Michael W. Belin, OCULUS GmbH
(C); Jimena C. Siordia
Program Number: 2890 Poster Board Number: A0150
Presentation Time: 8:30 AM–10:15 AM
One-year outcomes of changes in corneal densitometry after
accelerated (45mW/cm2) transepithelial corneal collagen crosslinking for keratoconus
Yang Shen, Weijun Jian, Ling Sun, Meng Li, Tian Han, Mi Tian,
Xingtao Zhou. Eye and ENT Hospital of Fudan University, Shanghai,
China.
Purpose: The conventional CXL (C-CXL) procedure removes
corneal epithelium and increases corneal densitometry. Accelerated
transepithelial corneal collagen cross-linking (ATE-CXL) is a newly
developed CXL technique, which maintains the integrity of corneal
epithelium layer. We investigated the changes in corneal densitometry
after ATE-CXL for progressive keratoconus by using an automatic
Scheimpflug Densitometry Program.
Methods: Forty eyes of 40 participants including 20 eyes of 20
patients (24.9±6.5 years, 13 male and 7 female) diagnosed with
progressive KC (KC group) and 20 eyes of 20 myopic patients
(24.9±6.5 years, 13 male and 7 female, Control group) were
recruited. Corneal topography and corneal densitometry were
evaluated before ATE-CXL and at the 1-, 6-, and 12-month follow-up
visits. Manifest refraction spherical equivalent (MRSE) and bestcorrected distant visual acuity (BCDVA) were assessed before and at
12-month after the procedure.
Results: MRSE remained stable (t=0.458, P=0.652) but BCDVA
improved significantly (Z=-2.857, P=0.004) at 12 months after
ATE-CXL. The densitometry values (annulus 0 to 6mm in
diameter) of the anterior layer, central layer, posterior layer
and the total thickness of the corneas in the KC group were
all significantly higher than those in the control group (All P
values <0.01). After ATE-CXL procedure, the densitometry
values (over the annulus 0 to 2mm area) of the anterior layer
(F=4.729, P=0.005), central layer (F=7.960, P<0.001), posterior
layer (F=6.622, P=0.001) and total thickness (F=6.551, P=0.001)
decreased significantly, as well as over the annulus 2 to 6mm
area (F=3.961, P=0.012; F=9.739, P<0.001; F=7.130, P<0.001
and F=6.415, P<0.001, respectively). Although the densitometry
values all decreased in the 12 months postoperatively, they were
still statistically higher than those of the control group (All P
values <0.01).
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ARVO 2016 Annual Meeting Abstracts
Conclusions: The densitometry values of progressive KC patients
were higher than those of the myopic ones. The main topographic
parameters remain stable, but the densitometry values decreased
steadily during the first year after ATE-CXL. At 12 months
postoperatively, the densitometry values of progressive KC patients
remains higher than those of the myopic population.
Corneal densitometry analysis
Riboflavin was saturating the total thickness of the corneal tissue
Commercial Relationships: Yang Shen, None; Weijun Jian, None;
Ling Sun, None; Meng Li, None; Tian Han, None; Mi Tian, None;
Xingtao Zhou, None
Support: National Natural Science Foundation of China(Grant
No.81570879); Outstanding Academic Leaders Program of Shanghai
Health System (Grant No. XBR2013098)
Program Number: 2891 Poster Board Number: A0151
Presentation Time: 8:30 AM–10:15 AM
Freiburg keratoconus registry: Implementation and first findings
of a monocentric keratoconus registry
Stefan J. Lang, Daniel Boehringer, Thomas Reinhard. Eye Center,
Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Purpose: Keratoconus is a progressive corneal disease with thinning
and scarring of the cornea. Diagnostic and treatment options have
changed dramatically over the recent years. The benefits from
these improvements are poorly investigated to date. We report the
monocentric keratoconus registry of one of the largest tertiary care
eye hospitals in Germany. Purpose of this registry is to enable further
analyses that help to characterize the course of the disease.
Methods: We evaluated all our computerized charts from 2007
to present for the key words keratoconus, corneal ectasia and
keratoglobus. We manually excluded all false positives. At the
time of first presentation, each eye was classified into one out of
four categories: suspect, early disease, late disease, state following
keratoplasty. Suspects included patients with a suspicious topography
but not enough proof for the diagnosis of keratoconus. Early disease
classification was used for patients with keratometric evidence of
keratoconus but no signs of a late disease like corneal scarring, visual
impairment or pronounced thinning of the cornea. All eyes that had
already undergone any form of keratoplasty were classified as state
following keratoplasty.
Results: We included 3681 eyes from 1841 patients. Longest followup was up to 40 years. 378 eyes were classified as suspects. Here,
median follow up was 6 months and median patient age was 34 years,
44% of the suspects were females. 1930 eyes were classified as early
disease. Median follow up was 0.45 years and median patient age 35
years, 29% of these patients were females. 968 eyes were classified
as late disease. Here, median follow up was 1.3 years and median
patient age 39 years, 30% of the patients were females. 405 eyes
already had undergone keratoplasty at the first visit. In this group
mean follow up was 2.1 years; median patient age was 51 years, 28%
of these patients were females. Patient age and male to female ratios
differed statistically significantly between all groups (p<0.001).
Conclusions: Our registry reveals strong associations between a high
patient age and a further progression of keratoconus. There are fewer
female patients in the groups with proven keratoconus. Our registry
has the potential to improve the understanding of the natural course
of keratoconus. Further cross sectional and longitudinal analyses will
help to characterize risk factors for progression.
Commercial Relationships: Stefan J. Lang, None;
Daniel Boehringer, None; Thomas Reinhard, None
Program Number: 2892 Poster Board Number: A0152
Presentation Time: 8:30 AM–10:15 AM
PRELIMINARY RESULTS OF A RANDOMIZED
CONTROLLED TRIAL COMPARING TRANSEPITHELIAL
CORNEAL CROSS-LINKING WITH IONTOPHORESIS
AND STANDARD CROSS-LINKING IN PATIENTS WITH
PROGRESSIVE KERATOCONUS
Sebastiano Serrao1, Giuseppe Lombardo2, Marianna Rosati1,
Domenico Schiano lomoriello1, Marco Lombardo1. 1Fondazione Bietti
Roma, Rome, Italy; 2Consiglio Nazionale delle Ricerche, Istituto per
i Processi Chimico-Fisici, Messina, Italy.
Purpose: To report the clinical outcomes 3 months after
transepithelial corneal cross-linking (CL) using iontophoresis
(T-ionto CL) in comparison with standard corneal cross-linking in
eyes with progressive keratoconus.
Methods: Transepithelial CL using iontophoresis was performed
using hypotonic ethylenediaminetetraacetic acid and trometamol
enriched dextran-free 0.1% riboflavin solution and UV-A irradiation
with 10 mW/cm2 UV-A device for 9 minutes. Standard CL was
performed according to the “Dresden protocol” using 20% dextran
enriched 0.1% riboflavin solution and UV-A irradiation with 3 mW/
cm2 UV-A device for 30 minutes. The primary outcome measure was
the maximum simulated keratometry value (Kmax). Other outcome
measures were best spectacle corrected visual acuity (BSCVA;
logMAR units), manifest refraction, central corneal thickness (CCT;
using AS-OCT) and endothelial cell density (ECD; no-contact
specular microscopy). Follow-up visits were scheduled at 3 and 7
days, 1- and 3-months.
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ARVO 2016 Annual Meeting Abstracts
Results: Thirty-four eyes with progressive keratoconus were
recruited in the study and randomized in two groups: T-ionto CL (22
eyes) and standard CL (12 eyes). At 3 months, Kmax decreased from
54.7±4.0 D to 54.2±3.9 D (P=0.11) and from 54.7±4.2 D to 54.3±4.7
D (P=0.33) in the study and in control group respectively. At 3
months, BSCVA improved from 0.12±0.20 LogMAR to 0.04±0.10
LogMAR (P=0.01) after T-ionto CL; no change in BSCVA was found
after standard CL (from 0.03±0.09 LogMAR to 0.06±0.09 LogMAR;
P=0.26). The manifest spherical equivalent refraction changed
averagely by +0.57 D (P=0.02) and +0.22 D (P=0.26) in the T-ionto
CL and standard CL groups respectively at 3 months. CCT ranged
from 484±37 µm to 486±28 µm (P=0.72) and from 494±34 µm to
484±38 µm (P=0.15) in the study and control group respectively
from preoperatively to 3 months. ECD count did not change during
3 months, except for a drop at day 3 in the control group, due to
posterior stromal edema in 60% of cases. There was 1 eye in the
control group with peripheral corneal infiltrates that did not affect the
3 months visual acuity.
Conclusions: The 3-months results are demonstrating that T-ionto CL
is safe with comparable efficacy to conventional treatment for halting
keratoconus progression in the short term period.
Commercial Relationships: sebastiano serrao, None;
Giuseppe Lombardo, None; Marianna Rosati, None;
domenico schiano lomoriello, None; Marco Lombardo, None
Support: PON_0100110
Clinical Trial: NCT02117999
Program Number: 2893 Poster Board Number: A0153
Presentation Time: 8:30 AM–10:15 AM
Non invasive label free hyperspectral method to assess corneal
cross-linking efficacy
Giuseppe Lombardo1, Valentina Villari1, Norberto Liborio Micali1,
Nancy Leone1, Marco Lombardo2. 1IPCF, CNR, Messina, Italy;
2
IRCCS Fondazione G.B. Bietti, Rome, Italy.
Purpose: To present a novel, non invasive, optical method for
assessing the concentration of stromal riboflavin in riboflavin/UV-A
corneal cross-linking in order to determine treatment efficacy.
Methods: Eight human donor corneas were de-epithelialized and
soaked with 20% dextran-enriched 0.1% riboflavin. Four tissues were
then irradiated using 3 mW/cm2 UV-A device for 30 minutes and
the other four using 10 mW/cm2 UV-A device for 9 minutes. During
treatment, corneal specimens were imaged using a novel optical
method in order to collect their hyperspectral response in real time.
A calibrated RGB camera recorded the fluorescence and the diffuse
reflectance images from each tissue and a processor elaborated the
information in order to evaluate the stromal riboflavin concentration
both during stromal soaking and UV-A irradiation of the cornea.
Immediately after treatment, the elastic modulus of the anterior
stroma in each specimen was probed by means of atomic force
microscopy.
Results: After stromal soaking, the concentration of riboflavin in the
stroma showed consistent results between tissues (0.016% ± 0.003%).
During UV-A irradiation, the stromal riboflavin concentration
decreased non linearly over time, then reaching the minimum value
of 0.006% ± 0.002% at the end of treatment. A regression model was
developed to correlate the stromal riboflavin consumption with the
increase of corneal stiffness. The results of the model were highly
significant (R = 0.79; P = 0.03).
Conclusions: The present label-free optical method shows to be
reliable for the assessment of stromal riboflavin concentration during
corneal cross-linking. The method is an active monitoring solution of
the stromal riboflavin consumption during corneal UV-A irradiation,
which provides an estimation of treatment efficacy in real-time.
During corneal cross-linking, the corneal tissue is imaged by a
RGB camera. The hyperspectral response of the cornea is evaluated
in a region of interest (green circle) in order to assess the stromal
riboflavin concentration and the induced stiffness.
Commercial Relationships: Giuseppe Lombardo, Vision
Engineering Italy srl (P); Valentina Villari, Vision Engineering Italy
srl (P); Norberto Liborio Micali, Vision Engineering Italy srl (P);
Nancy Leone, None; Marco Lombardo, Vision Engineering Italy
srl (P)
Program Number: 2894 Poster Board Number: A0154
Presentation Time: 8:30 AM–10:15 AM
CORRELATION BETWEEN EYE RUBBING AND
KERATOCONUS SEVERITY IN A TREATMENT-NAIVE
KERATOCONIC POPULATION
Mohamed Zaidi, Louis Lhuillier, Nadia OUAMARA,
Christophe GOETZ, Naïla Houmad, SOT Maxime, Alix Ehrhardt,
Jean-Marc Perone, Oualid Guechi, Adina Agapie, Piotr Krawczyk.
OPHTALMOLOGY, Regional Hospital of Metz Thionville
(FRANCE), METZ, France.
Purpose: We tried to determine if, within a keratoconic population,
strong eye rubbing was correlated with visual acuity, spherical
equivalent value, biomicroscopic signs, corneal pachymetry,
keratometry, and tomography classification determinating
keratoconus stage.
Methods: A retrospective study was performed between november
2014 and october 2015 in the Metz Hospital Center. Were included
33 patients presenting with treatment-naive keratoconus. Patients
responded to a questionnaire that assessed eye rubbing habits, family
history of keratoconus, history of atopy. 2 groups were separated:
group 1 constituted by 15 eyes with no eye rubbing, and group 2
constituted by 18 eyes with moderate or severe eye rubbing. The
following informations were collected: best visual corrected acuity
(BCVA), spherical equivalent value (SEV), corneal opacities or Vogt
striae. For each eye were performed an anterior segment OCT (ASOCT) to determine the OCT stage for keratoconus (Fourrier domain
OCT classification, 2013), and a Scheimpflug camera imaging to
determine the maximal keratometry (Kmax) and the minimal corneal
thickness (MCT).
Results: 15 eyes were included in group 1 and 18 in group 2; the
average age was respectively 28 and 30 years old (p=0.77). Women
represented 20% in group 1 and 44% in group 2 (p=0.27). In group
1, 1 patient had family history of keratoconus, versus (vs) 2 in group
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ARVO 2016 Annual Meeting Abstracts
2 (p=1). In group 1, 2 patients had history of atopy vs 12 in group
2 (p=0.004). Mean BVCA was 0.33 logMAR in group 1 and 0.58
logMAR in group 2 (p=0.005). Only 1 eye presented corneal opacity
in each group (p=1). In group 1, 2 eyes presented Vogt striae vs 9
eyes in group 2 (p=0.034). Mean MCT was 444μm (+/-37μm) in
group 1 vs 431μm (+/- 55μm) in group 2 (p=0.39). Mean Kmax
was 55.9D(+/-3.3D) in group 1 versus 64.4D(+/-11.9D) in group 2
(p=0.02). Mean SEV was -4.3D(+/-4.4D) in group 1 vs -7.5D(+/4.8D) in group 2 (p=0.07). In group 1 and 2, AS-OCT respectively
showed 14 (93%) and 14(78%) stage 1 keratoconus (p=0.35) ;1 (7%)
and 2 (11%) stage 2 (p=1); 0 and 1 (6%) stage 3 (p=1); no stage 4 and
5.
Conclusions: In our study, eye rubbing is significantly associated
with atopic status, decreased visual acuity, more frequent Vogt striae,
and increased maximal keratometry. It tends to induce highest spheric
equivalent value by increasing astigmatism. We found no difference
in minimal pachymetry and OCT stage between the 2 groups.
Commercial Relationships: Mohamed Zaidi, None;
Louis Lhuillier, None; Nadia OUAMARA, None;
Christophe GOETZ, None; Naïla Houmad, None; SOT Maxime,
None; alix ehrhardt, None; Jean-Marc Perone, None;
Oualid Guechi; adina agapie, None; piotr krawczyk, None
Program Number: 2895 Poster Board Number: A0155
Presentation Time: 8:30 AM–10:15 AM
Ultrastructural Study of lamellar organization of Peripheral and
Central Stroma of Keratoconus Cornea
Aljoharah Alkanaan2, 1, Omar Kirat3, Robert Barsotti2,
Turki Almubrad1, Adnan Khan1, Saeed Akhtar1. 1King Saud
University, Riyadh, Saudi Arabia; 2Salus University, Philadelphia,
PA; 3King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
Purpose: Keratoconus (KC) is a progressive bilateral asymmetrical
corneal disorder characterized by localized corneal thinning and
conical protrusion, leading to high myopia, irregular astigmatism,
corneal scarring and visual impairment. In this study we assess the
lamellar organization of the peripheral and central stroma of the KC
and normal cornea.
Methods: Three normal and three keratoconus corneas were fixed
in 2.5% glutaraldehyde and post fixed in the osmium tetroxide. The
tissue were dehydrated in a graded series of ethanol and processed
for electron microscopy. The Ultrathin sections were observed
under JOEL 1400 TEM and digital images were taken with a bottom
mounted 11 megapixel Quamisa camera, using iTEM software.
Measurement of lamellae were carried out with iTEM software.
Statistics were performed using the SPSS programme.
Results: In the central part of the KC cornea, undulation of the
lamellae was observed in the anterior, middle and posterior stroma
whereas in the peripheral part, the undulation was observed in middle
and the posterior stroma. Collagen fibrils were disorganized and of
variable size in the undulating lamellae. Electron dense granular
material was present among the collagen fibrils.
Mean lamellar thickness of the peripheral (752.79±31.98nm) and
central (828.76±25.75nm) stroma of KC cornea was significantly
(P〈 0.001) thinner than the peripheral (1928.90±108.13nm) and
central (1330.10±85.07 nm) stroma of the normal cornea. Among
the KC cornea, the mean lamellar thickness of the peripheral
middle (1030.32±86.25nm) and posterior (615.68±30.94nm) stroma
were also significantly (P〈0.05) different from the central middle
(1151.1±65.48nm) and posterior 783.57±31.10nm) stroma. However
the mean lamellar thickness of the anterior stroma did not differ
significantly between the periphery (686.84±46.47nm) and center
(600.84±25.10 nm) of KC cornea (P=0.558).
In both the normal and KC cornea, the number of lamellae in the
central stroma (296,241) was consistently less than that in the
peripheral stroma (360 in both normal and KC corneas).
Conclusions: The results of this study shows that KC pathological
changes to the lamellar organization is not limited to the central
stroma but rather extends to affect the lamellae within the peripheral
stroma.
Commercial Relationships: Aljoharah Alkanaan, None;
Omar Kirat, None; Robert Barsotti, None; Turki Almubrad,
None; Adnan Khan, None; Saeed Akhtar, None
Program Number: 2896 Poster Board Number: A0156
Presentation Time: 8:30 AM–10:15 AM
A pilot study of corneal sensitivity and its associations in
keratoconus
Preeji S. Mandathara1, Fiona Stapleton1, Jim Kokkinakis1, 2,
Mark D. Willcox1. 1School of Optometry and Vision Science,
University of New South Wales, Randwick, NSW, Australia; 2The
Eye Practice, Sydney, NSW, Australia.
Purpose: To examine changes in corneal sensitivity and its
association with other clinical parameters in keratoconus.
Methods: 24 keratoconus subjects aged 18-65 years were recruited.
Ocular symptoms using validated questionnaires (ocular surface
disease index and contact lens dry eye questionnaire 8), corneal
topography, tear osmolarity, tear meniscus height measurement,
tear volume, ocular surface staining with fluorescein and lissamine
green dye, corneal sensitivity threshold using Cochet-Bonnet
aesthesiometer and corneal nerve mapping using HRT II confocal
microscopy were obtained. Correlations were sought by determining
either the Spearman’s or Pearson’s coefficient. Partial correlation was
performed to control the effect of confounding factors.
Results: Based on the maximum simulated keratometry (K max)
reading, subjects were graded as having mild (N=11; K max ≤52D)
or severe (N=13; K max >52D) keratoconus. Only data from the most
severe eye of each subject were included in the analyses. Central
corneal sensitivity was lower (i.e. increased corneal sensitivity
threshold) in the severe keratoconus group compared to the mild
keratoconus group (Median, range: 1.09, 0.42-19.66 vs 0.51, 0.393.74 g/mm2, p=0.035). In bivariate correlations, decreased corneal
sensitivity in keratoconus was associated with severity (ρ = 0.43;
p=0.032), lower central nerve fibre density (r=-0.68, p=0.014),
contact lens wear (ρ=0.44; p= 0.025), and contact lens tolerance
(ρ=0.455; p=0.033), and the age of the patient (r=0.414; p=0.036)
and duration of the disease (r=0.467; p=0.016). There was no
association between corneal sensitivity and symptom scores and
the tear variables of osmolarity, volume or meniscus height. After
adjusting for contact lens wear, there was no association between
corneal sensitivity and severity or nerve fibre density, but there was a
trend (p<0.1) where age and duration of the disease were associated
with decreased corneal sensitivity. Contact lens intolerants had a
higher corneal sensitivity compared to tolerant people. (Median,
range: 0.56, 0.39-2.17 vs 1.51, 0.39-19.66 g/mm2, p=0.026).
Conclusions: Decreased corneal sensitivity was associated with
age and duration of disease. Reduced tolerance to contact lenses in
keratoconus was associated with increased corneal sensitivity.
Commercial Relationships: Preeji S. Mandathara, None;
Fiona Stapleton, None; Jim Kokkinakis, None; Mark D. Willcox,
None
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ARVO 2016 Annual Meeting Abstracts
Program Number: 2897 Poster Board Number: A0157
Presentation Time: 8:30 AM–10:15 AM
Determining the Efficacy of Corneal Cross-linking (CXL)
Protocols for Different Corneal Thicknesses: Theoretical Model
and Experimental Validation
Sabine Kling1, 2, Farhad Hafezi2, 3. 1Laboratory of Ocular Cell
Biology, University of Zurich, Zurich, Switzerland; 2University of
Geneva, Geneva, Switzerland; 3ELZA Institute, Dietikon/Zurich,
Switzerland.
Purpose: A theoretical model was developed to predict the stiffening
effect of CXL for different corneal thicknesses and UV irradiation
protocols. Ex vivo experiments were performed to verify the
accuracy.
Methods: The theoretical model considered the reaction kinetics
of riboflavin diffusion, photo-degradation, UV intensity, oxygen
availability, production of singlet oxygen and extracellular matrix
oxidation. For the experiments, freshly-enucleated porcine (n=66),
murine (n=55) and rabbit (n=2) corneas were de-epithelialized and
riboflavin was instilled for 30 minutes, prior to UV-irradiation.
Different UV irradiation protocols (continuous, accelerated, pulsed),
UV fluences (0.09 to 5.4 J/cm2) and irradiation times (30s to 30min)
were analyzed. Stress-relaxation tests at 0.6 MPa were performed to
measure the increase in corneal stiffness.
Results: The theoretical concentration of newly induced cross-links
matched well with the experimental stress resistance in all groups
(Figure 1). Standard CXL was more effective in thinner than in
thicker corneas. The remaining stress after 120s of relaxation was:
322kPa (riboflavin) / 456kPa (CXL) in murine, 168kPa (riboflavin) /
213kPa (CXL) in rabbit and 9.3kPa (riboflavin) / 10.4kPa (CXL) in
porcine corneas. The corresponding theoretical increase in cross-link
concentration was: 1.03mol/m3 in murine, 0.63mol/m3 in rabbit and
0.28mol/m3 in porcine corneas. Murine corneas could be effectively
cross-linked with only 1/60 of the standard UV fluence used in
humans. Pulsed CXL was significantly less effective than standard
continuous CXL (p<=0.017).
Conclusions: The proposed theoretical model predicts correctly the
stiffening effect after CXL under different conditions. Increasing
CXL efficacy in a clinical setting would require prolonged UV
irradiation at reduced irradiances, or a higher oxygen tension in
the environment. Pulsed CXL does not allow to speed up CXL or
to increase its efficacy compared to continuous CXL of the same
irradiation time.
Scatter plot comparing the theoretical concentration of induced crosslinks during CXL with the experimental stiffness increase directly
after treatment.
Commercial Relationships: Sabine Kling, None; Farhad Hafezi,
None
Program Number: 2898 Poster Board Number: A0158
Presentation Time: 8:30 AM–10:15 AM
Four-year results of riboflavin ultraviolet-A corneal collagen
cross-linking for progressive corneal ectasia in 129 eyes
Samar A. Al-Swailem, Salem Al Zaid. King Khaled Eye Specialist
Hosp, Riyadh, Saudi Arabia.
Purpose: To report the clinical course of conventional corneal
collagen cross-linking (CXL) with up to 4.7 years of follow-up, for
the treatment of progressive corneal ectasia. At the baseline and all
follow-up examinations, Snellen uncorrected visual acuity (UCVA),
Snellen best corrected visual acuity (BCVA), keratometry, central
corneal thickness (CCT), and complications were analysed.
Methods: The records of 129 eyes (keratoconus = 114; post-excimer
ectasia=15) which underwent CXL using Dresden’s protocol, were
reviewed retrospectively.
Results: The mean age of the 83 men and 46 women was 24.73±
5.5 (Range 14-42) years, and 68.2% were in the age range of 21-30
years. The CCT almost resumed its baseline reading at 9-months
postoperatively (460.5 vs. 479.7um), and stabilized until the last
follow-up (465.3um) (p<0.086). At last follow-up, median simulated
mean keratometry decreased from 45.1±3.6D (range 37.9-66.9D) to
44.5±3.6D (range 37.6-60.5D) (p<0.008). At last follow-up, median
UCVA and BCVA changed from 20/60 to 20/40 and 20/25 to 20/25,
respectively. The UCVA of ≥20/40 was recorded in 38.8% and 53.3%
before and after CXL, respectively. At last follow-up, mean UCVA
improved and worsened by ≥ 1 Snellen line in 27.1% and 10.8%,
respectively. Complications included: transient corneal haze in first 3
months (n=9) and sterile infiltrate (n=3).
Conclusions: Our study not only demonstrated a halt in ectasia
progression, but also showed a significant improvement in visual
acuity at 4-year of follow-up. Conventional CXL is safe in
stabilization of progressive ectasia. Given the simplicities, minimal
costs of CXL and likelihood of reducing the need of keratoplasty, it
might also be well-suited for developing countries.
Commercial Relationships: Samar A. Al-Swailem, None; Salem Al
Zaid, None
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ARVO 2016 Annual Meeting Abstracts
Program Number: 2899 Poster Board Number: A0159
Presentation Time: 8:30 AM–10:15 AM
Relationship between repeatability in corneal topography
parameters and increased disease severity in keratoconic eyes
Ciara Bergin, Francois Majo, Kattayoon Hashemi, Ivo Guber.
Ophthalmology, Jules-Gonin Eye Hosptial, Lausanne, Switzerland.
Purpose: Good repeatability of topographic measurements has been
demonstrated in normal eyes but a clinically significant reduction in
repeatability has been recently identified in keratoconic eyes. The aim
of this study was to evaluate the relationship between repeatability
and disease severity in keratoconic eyes measured by the Pentacam
HR® device and to identify the best performing parameters in each
disease stage.
Methods: This is an intra-instrument repeatability assessment
study. Two hundred and forty eight keratoconic eyes of 197 patients
were identified. All available images were exported automatically
from the Pentacam HR device. Two good quality images taken
on the same day within the same sitting were extracted and the
repeatability between these two measures was assessed. The limits
of repeatability (r) at each stage of keratoconus (KCN) to determine
those limits significantly different than r in healthy eyes. The r were
also compared with the length of the respective range to determine
the relative utilty (RU) of each parameter at each stage of KCN. High
RU values indicate a parameters best positioned to detect disease
progression.
Results: Mean age was 35.3 years, average maximal corneal
curvature (Kmax) was 55.3D, mean minimum pachymetry was
458mm. Mean r of K-max was 0.7D, 1.3D, 1.8D and 2.4D for
topographic keratoconus classification (TKC) grade 1, 2, 3 and 4
respectively. A highly significant relationship between K-max and
repeatability was observed, p<0.001, significantly increasing with
each stage of KCN. Astigmatism and Belin Ambrosia score had
high RU values in new cases of KCN (TKC1), while the anterior
corneal curvature parameters are best placed to distinguish disease
progression (TKC 2-4).
Conclusions: The results of the present study suggest that
progression will be more difficult to detect accurately using
topographic measures in patients with high corneal curvature and/or
more advanced KCN. The RU gives a systematic approach to detect
parameters best positioned to detect change at each stage of disease.
In this study those parameters with high RU values were isolated for
each stage of KCN and appropriate limits of repeatability for each
parameter in each stage of KCN were provided. This information
should help the clinician more accurately assess KCN progression
with topography images.
Commercial Relationships: Ciara Bergin; Francois Majo, None;
Kattayoon Hashemi, None; Ivo Guber, None
Program Number: 2900 Poster Board Number: A0160
Presentation Time: 8:30 AM–10:15 AM
Keratoconus is not attributable to eye rubbing in a young Down’s
syndrome cohort
Stephanie Campbell, Joy Margaret Woodhouse, Keith Meek. Cardiff
Centre for Vision Sciences, Cardiff University, Cardiff, United
Kingdom.
Purpose: The onset and progression of keratoconus is considered
to be a complex interplay of genetic and environmental factors,
with the ‘cause or effect’ role of eye rubbing remaining particularly
elusive. Keratoconus has much greater prevelence in the Down’s
syndrome (DS) population, and is largely attributed to eye-rubbing in
scientific literature, but has not yet been investigated experimentally.
This prospective, case-control observational study explored the
associations of eye rubbing, atopy and keratoconus in DS. We
hypothesise that significant eye rubbing corresponds to a higher level
of atopy and keratoconus in DS.
Methods: Forty-six subjects were recruited from the Cardiff
University Down’s syndrome cohort (range 7.5 - 27.8 years, 28 male,
18 female). A diagnosis of keratoconus was made using Scheimflug
tomography (Pentacam, Oculus, Germany) in combination with
clinical indicators of visual function and slit lamp biomicroscopy.
Eyes with previous ocular surgery or co-morbidity were excluded
from analysis. Structured questionnaires with graded responses were
used to elicit the history of atopy and eye rubbing from family or care
team members over a two-week period. Statistical analysis of the
correlation between variables was carried out using the Chi-squared
test (with Yates’ correction where appropriate) in SPSS (Version 20.0,
IBM Corp.).
Results: In contrast to the hypothesis, and in contrast to what
is observed in the non-DS population, there was no significant
associations between the prescence of keratoconus and eye
rubbing (p = 0.786), keratoconus and atopic dermatitis (p = 0.876)
or keratoconus and atopy as a whole (p = 0.734). Of forty-six
subjects, two had blepharitis that required intervention, neither had
keratoconus nor were observed to rub their eyes.
Conclusions: These results do not support the hypothesis that
keratoconus is associated with eye rubbing nor atopy in this cohort.
Keratoconus in the DS cohort may be attributable to an underlying
biomechanical weakness or collagen abnormality, and such a
group may represent a useful model for further targeted genetic
investigations of keratoconus. The majority of subjects with DS were
observed not to rub their eyes significantly. Therefore, presumed
eye rubbing due to intellectual disability alone should not be a
contraindication to contact lenses, collagen cross-linking or corneal
grafting in DS.
Commercial Relationships: Stephanie Campbell, None; Joy
Margaret Woodhouse, None; Keith Meek, None
Support: Cardiff School of Optometry and Vision Sciences,
EPSRC (UK)
Program Number: 2901 Poster Board Number: A0161
Presentation Time: 8:30 AM–10:15 AM
Stromal demarcation line: is it predictive for Cross-Linking
efficiency?
Louis Lhuillier1, Naïla Houmad1, Mohamed Zaidi1, SOT Maxime1,
Alix EHRHARDT1, Adina Agapie1, Oualid Guechi1, Piotr Krawczyk1,
Huong Duong Nguyen Viet2, 1, Jean-Marc Perone1. 1Ophthalmology,
CHR Metz, Metz, France; 2Hoang Quoc Hung Hospital, Hô Chi Minh
ville, Viet Nam.
Purpose: To assess the association between stromal demarcation
line after collagen crosslinking (CXL) for progressive keratoconus
and mid-term (6 month) refractive, topographic and clinical
outcomes of CXL.
Methods: All consecutive patients treated with CXL between March
2014 and March 2015 were included. They all underwent the same
procedure: accelerated-CXL protocol (10 minutes UVA irradiation
with 9 mW/cm2 intensity), irradiation device (IROC UV-X™ 2000,
Medeuronet). One month after the procedure, AS-OCT examination
was performed in all patients (RS-3000, NIDEK). The visibility of
the stromal demarcation line was scored (0: not visible line; 1: visible
line, but measurement not clearly defined; 2: clearly visible line) and
its depth was measured centrally at anytime it was possible. Changes
in best corrected visual acuity (BCVA), spherical equivalent (SE),
Kmax and thinnest pachymetry, were studied preoperatively and at 6
months.
Results: 36 eyes (29 patients) with progressive keratoconus were
included mean age was 26.1 ± 10.4 years.
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ARVO 2016 Annual Meeting Abstracts
One month after CXL, a stromal demarcation line was visible for
28 patients (77.8%) (grade 2 : 15, 41.7% and grade 1 : 13, 36.1%)
and not visible (grade 0) for 8 (22.2%) patients. Mean depth of the
corneal stromal demarcation line was 342.3 ± 58.5 μm (range 226440μm).
Six month after CXL, the study showed : a significant improvement
in BCVA (preoperative : 0.5LogMar ±0.2 vs postoperative
0.39LogMar ±0.2, p = 0.031) and SE (preoperative -6.46 D ±2.1
vs postoperative 5.42D± 2.1, p = 0.027); a significant decrease in
thinnest pachymetry (preoperative : 451.6 µm ± 30.8 vs postoperative
421µm ± 46.9, p = 0.043). No significant change for Kmax
(preoperative: 58.1 D ± 5.4 vs postoperative 57.8 ± 4.5, p=0.35).
Neither the visibility of the stromal line nor its depth was
significantly associated with post-operative changes in Kmax, SE,
BVCA or pachymetry (p>0.05).
This study tends to show that preoperatively stepper and thinner
corneas were associated with a more visible line: Kmax = 58.3 ±
5.5D (visible) vs 54.5 ± 5.8D (not visible line) p=0.051; thinnest
pachymetry = 451.2 ±34.9µm vs 477.1 ± 26.2µm, p= 0.059.
Conclusions: In our study neither the visibility of the stromal
line nor its depth was significantly associated with post-operative
changes in Kmax, SE, BVCA or pachymetry (p>0.05). The stromal
demarcation line was not predictive for CXL efficiency 6 month after
the procedure.
Commercial Relationships: Louis Lhuillier, None; Naïla Houmad,
None; Mohamed Zaidi, None; SOT Maxime, None;
Alix EHRHARDT, None; adina agapie, None; Oualid Guechi,
None; Piotr Krawczyk, None; Huong Duong Nguyen Viet, None;
Jean-Marc Perone, None
Program Number: 2902 Poster Board Number: A0162
Presentation Time: 8:30 AM–10:15 AM
Correlation of Anterior and Posterior Corneal Shape in Clinical
Keratoconus
Jaime Larrea Gonzalez1, Arturo J. Ramirez-Miranda1,
Alejandro Navas1, Enrique O. Graue-Hernandez1, Aida JimenezCorona2. 1Cornea and Refractive Surgery, Instituto de Oftalmología
Conde de Valenciana, Mexico City, Mexico; 2Research & Evaluation,
Instituto de Oftalmología Conde de Valenciana, Mexico City,
Mexico.
Purpose: To evaluate the corneal volume, pachymetry, and
correlation of anterior and posterior corneal shape in subclinical and
clinical keratoconus.
Methods: Eyes were placed into 3 groups: keratoconus grade I,
grade II, subclinical and a control group. All eyes undewent corneal
curvature evaluation by Scheimpflug imaging (Sirius). The posterioranterior corneal power ratio was also calculated.
Results: 172 eyes (92 patients) were evaluated. Astigmatism and
keratometry of both surfaces were significantly higher in the 3 groups
(P=<0.05). Posterior astigmatism was significantly higher in the
subclinical group. A correlation in astigmatism between the anterior
and posterior surface was found in all groups.
Conclusions: The correlation between both surfaces was low, and
the correlation between anterior and posterior astigmatism was
maintained
Commercial Relationships: Jaime Larrea Gonzalez, None;
Arturo J. Ramirez-Miranda, None; Alejandro Navas, None;
Enrique O. Graue-Hernandez, None; Aida Jimenez-Corona, None
Program Number: 2903 Poster Board Number: A0163
Presentation Time: 8:30 AM–10:15 AM
To differentiating keratoconus and contact lens-related corneal
warpage by combining pattern analysis of focal changes in
anterior corneal topography, pachymetry, and epithelial
thickness maps
Maolong Tang, Yan Li, David Huang. Oregon Health and Science
University, Portland, OR.
Purpose: To differentiating keratoconus and contact lens-related
corneal warpage by combining pattern analysis of focal changes in
anterior corneal topography, pachymetry, and epithelial thickness
maps.
Methods: All keratoconic eyes had abnormal topography and bestcorrected visual acuity of 20/25 or worse. Contact lens warpage was
defined as contact lens wearers with topographic inferior-superior
asymmetry greater than 1.4 D or 5-mm zone irregularity index >1.5
D on slit-scanning topographer (Orbscan). Pachymetry and epithelial
thickness maps were obtained from a commercial Fourier-domain
OCT system (RTVue). Warpage Index was calculated by the crosscorrelation of Pattern deviation (PD) maps of anterior topography
and epithelial thickness. Positive correlation indicates warpage,
and negative correlation indicates keratoconus. Anterior Ectasia
Index was based on Gaussian fitting of PD maps of anterior corneal
topography and pachymetry. Its magnitude represented the coincident
focal topographic steepening and epithelial thinning. Epithelial
Patterns Standard Deviation (PSD) was also computed.
Results: The study included 36 keratoconic eyes and 11 eyes with
contact lens warpage. The Epithelial PSD was normal (0.021±0.0075;
threshold=0.035) for all normal eyes, and abnormal for all
keratoconic (0.083 ± 0.034) and warpage (0.055 ± 0.023) eyes. The
average Anterior Ectasia Index was normal (threshold=6.7) for all
normal (1.66 ± 0.74) and warpage (2.76 ± 1.45) eyes, and abnormal
(17.5 ± 7.18) in all keratoconic eyes. The Warpage Index was
positive in all warpage eyes (0.12 ± 0.089) and all except one normal
eyes, (0.065 ± 0.050) and negative (-0.58 ± 0.52) for all except one
keratoconus eyes. The one keratoconus eye with positive Warpage
Index was a wearer of rigid gas-permeable contact lens.
Conclusions: The Epithelial PSD was able to perfectly distinguish
normal eyes from those having either keratoconus or warpage, but do
not distinguish the 2 pathologies. The novel Anterior Ectasia Index
is abnormal in keratoconic eyes but not warpage eyes. The novel
Warpage Index is positive for all warpage eyes and negative for all
keratoconus eyes, except in some cases where both keratoconus and
warpage co-exist. Together, the 3 OCT-based parameters are strong
tripartite discriminators of normal, keratoconus, and warpage.
Commercial Relationships: Maolong Tang, Optovue Inc. (P),
Optovue Inc. (F); Yan Li, Optovue Inc. (P), Optovue Inc. (F);
David Huang, Optovue Inc. (P), Optovue Inc. (I), Carl Zeiss Meditec
Inc. (P), Optovue Inc. (F)
Support: This study was supported by NIH grants R01 EY018184,
a grant from Optovue Inc. a NIH Core grant (P30 EY010572) and an
unrestricted grant from Research to Prevent Blindness.
Program Number: 2904 Poster Board Number: A0164
Presentation Time: 8:30 AM–10:15 AM
OUTCOME OF IMPLANTABLE COLLAMER LENS IN
KERATOCONUS
Salem G. Almalki. OPHATHALMOLOGY, KING KHALID EYE
SPECIALIST HOSPITAL, RIAYDH, Saudi Arabia.
Purpose: To assess the safety and efficacy of collamer lens (ICL) in
the posterior chamber for correction of myopia and astigmatism in
patients with keratoconus
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ARVO 2016 Annual Meeting Abstracts
Methods: A retrospective chart review was conducted of 27 patients
diagnosed as keratoconus underwent ICL (Model V4) insertion,
performed by different surgeons. All ICL surgeries and preoperative
evaluations were performed at tertiary hospital
Results: There was a statistically significant increase in mean UCVA
from 20/200(range: 20/80 - count fingure) preoperatively to 20/30
(range: 20/20 – 20/100) at the last postoperative visit (P < 0.0001).
There was statistically significant decrease in mean MRSE (Manifest
refractive spherical equivalent) from - 8.36 ± 3.67 D (range, -2 to - 16
D) preoperatively to -0.56 ± 1.00 D (range, -2 to 1 D) postoperatively
(P < 0.0001). Mean improvement in postoperative BCVA was 1 line
compared to preoperatively. At the last postoperative visit, 28.6%
of eyes had a BCVA of 20/20 or better compared with only 17.85%
preoperatively. No intraoperative or postoperative complications
occurred
Conclusions: Our study yielded favorable results compared to other
studies in the literature. However, a larger number of patients and a
longer follow-up period are needed to truly assess the efficacy of ICL
in the management of keratoconus with high myopia and moderateto-high myopic astigmatism
Commercial Relationships: salem G. almalki, None
Program Number: 2905 Poster Board Number: A0165
Presentation Time: 8:30 AM–10:15 AM
Is keratoconus risk associated with genetic variation of aldehyde
dehydrogenase ALDH3A1 gene?
Piotr Krawczyk1, 2, Jean-Marc Perone1, Anna Ambroziak2,
Joanna Giebultowicz2, Oualid Guechi1, Adina Agapie1,
Nadia OUAMARA1, Louis Lhuillier1, Naïla Houmad1,
Huong Duong Nguyen Viet3, Jacek Szaflik2. 1ophthalmology,
Regional hospital center, Mercy hospital, METZ cedex 03, France;
2
ophthalmology, Medical University of Warsaw, Warsaw, Poland;
3
University of Medicine and Pharmacy of Ho Chi Minh City, Ho Chi
Minh City, Viet Nam.
Purpose: To evaluate the influence of the genetic variation of the
ALDH3A1 gene region on the risk of keratoconus in the European
population. ALDH3A1 is a structural and enzymatic protein
representing up to 50% of the corneal water-soluble proteins in
mammalian species, which may be involved in the pathogenesis of
keratoconus.
Methods: The study, conducted at the Department of Ophtalmology
at the Medical Universitity of Warsaw, consisted of sequencing of
promotor regions, 10 exons and intronic sequences flanking each
exon of the ALDH3A1 gene. A total of 300 keratoconus patients
were examined (EDTA blood samples). Patients with any metabolic
defects were excluded. DNA isolation was performed with the kit
method followed by a polymerase chain reaction (PCR). A direct
sequencing of all exons ALDH3A1 and/or analysis of important
gene rearrangements were performed. Direct fluorescent sequencing
(Applied Biosystems 3130 Genetic Analyzer) was applied to screen
any gene mutations in patients DNA. The frequencies of selected
SNPs in the control group were checked using high resolution
melt technique (HRM) or TaqMan technique (StepOne Plus RealTime PCR System AppliedBiosystem). Programs like SNPSplicer,
EuSplice, GeneSplicer and ESE Finder were used to verify and
analyze a potential impact of sequence variation on pre-mRNA
splicing.
Results: Our results were compared with data from the European
population genomic base (phase 1 of the 1000 Genomes Projects).
According to our analysis, three single nucleotide polymorphisms
SNPs are in linkage disequilibrium (D’= 0,916-1, r2=0,727-0,93)
and are organized in haplotype block. The study did not show
any punctual mutations in the analyzed aldehyde dehodrogenase
ALDH3A1 region, however our analysis confirmed the existence of
ten already known single nucleotide polymorphisms (SNPs) in the
examined area.
Conclusions: The study results show that keratoconus does not seem
to be associated with any mutation in the ALDH3A1 gene region.
However, the proven presence of single nucleotide polymorhisms
SNPs in the analyzed zone requires further attention and probably
plays a considerable role in the risk and prevalence of this pathology.
Commercial Relationships: Piotr Krawczyk; Jean-Marc Perone,
None; anna ambroziak, None; joanna giebultowicz, None;
Oualid Guechi, None; adina agapie, None; Nadia OUAMARA,
None; Louis Lhuillier, None; Naïla Houmad, None; Huong Duong
Nguyen Viet, None; jacek szaflik, None
Program Number: 2906 Poster Board Number: A0166
Presentation Time: 8:30 AM–10:15 AM
Hair cortisol analysis in progressive and stable keratoconus
patients
Janine Lenk, Eberhard Spoerl, Lutz E. Pillunat, Frederik Raiskup.
Department of Ophthalmology, Univ. Hospital Carl Gustav Carus,
TU Dresden, Dresden, Germany.
Purpose: To investigate hair cortisol concentration as a biochemical
correlate of chronical psychological stress as a risk factor for
keratoconus progression.
Methods: 70 participants were included in this prospective
observational study (28 progressive keratoconus (KCp) patients, 27
stable keratoconus (KCs) patients and 15 healthy (H) participants).
Hair strands of keratoconus patients and healthy subjects were
analyzed in order to compare their hair cortisol concentration as a
biomarker of stress. Based on an average hair growth rate of 1 cm/
month, hair cortisol of a hair segment of 3 cm length is supposed to
represent the stress profile of the last three months. We investigated
hair strands of a diameter of approximately 3 mm which were taken
scalp-near from a posterior vertex position. Cortisol concentrations
were determined from the 3 cm hair segment most proximal to the
scalp. Cortisol levels were determined in Institute of Biopsychology
of the TU Dresden using a commercially available immunoassay with
chemoluminescence detection (CLIA, IBL-Hamburg, Germany).
Relevant sociodemographic variables were recorded. An objective
standardized questionnaire for chronic stress had to be answered
using the Trierer Inventar of chronic stress (TICS) screening scale.
Statistical analysis was performed using SPSS: Chi-square-test and
ANOVA were used to determine which parameters differed between
the two groups.
Results: In patients with progressive keratoconus was hair cortisol
concentration higher compared to the patients with stable disease
and healthy subjects (27.54 (CI 95% 19.31…39.28) vs. 18.2
(14.61…22.66) pg/mg P=0.043). There was no difference between
healthy subjects and patients with stable keratoconus (16.33 (CI 95%
10.69 …24.95) vs. 19.28 (14.06 … 26.42) P=0.900). Normal hair
cortisol ranges from 5-25 pg/mg. Increased values were found in
the group with progressive keratoconus than in the group of healthy
participatns and patients with stable keratoconus (50% vs. 33%
vs. 13%; P=0.05). The BMI was slightly higher in KCp compared
to healthy group and KCs (27.06±7.5 vs. 24.5±4.5 P= 0.086). No
difference was found in age, gender, TICS.
Conclusions: This study showed that increased hair cortisol
concentration seemed to be a risk factor for progression of
keratoconus and these patients might benefit from avoiding chronical
stress.
Commercial Relationships: Janine Lenk, None; Eberhard Spoerl,
None; Lutz E. Pillunat, None; Frederik Raiskup, None
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ARVO 2016 Annual Meeting Abstracts
Program Number: 2907 Poster Board Number: A0167
Presentation Time: 8:30 AM–10:15 AM
Collagen arrangement from Second Harmonic Microscopy in
corneas following cross-linking
James Germann, Eduardo Martinez-Enriquez, Susana Marcos.
Instituto de Óptica, CSIC, Madrid, Spain.
Purpose: Cross-linking (CXL) is a treatment for keratoconus that
counteracts the weakening of the cornea by promoting the formation
of links between the collagen fibers of the corneal stroma. How CXL
affects the physical structure of the stroma and the organization of
the collagen lamella is still precisely unknown. This study compares
the orientation of collagen lamella of both cross-linked and untreated
eyes and compares the average variance of lamella orientation to
provide a quantitative measure of the changes induced by CXL.
Methods: Three freshly enucleated porcine eyes were obtained
from a local abatoir and separated into 3 groups; untreated eyes,
Riboflavin-UV (UVX) cross-linked eyes, and Rose Bengal-Green
Light (RGX) cross-linked eyes. CXL treatments involved deepithelization, photosensitizer instillation (0.125% Riboflavin/20%
Dextran solution every 5 min for 30 min in UVX; Rose Bengal at
0.1% in PBS for 2 min and 30 s for RGX) and light irradiation (370
nm, 3 W/cm2, 30 min, in UVAX; 532 nm, 0.25 W/cm2, 400 s, in
RGX). The corneas from the eyes were excised and placed under a
custom built two-photon laser scanning microscope. A z-scan was
performed with each sample, in 5 μm steps. The images were 2D
Fourier transformed and the resulting magnitude and direction of the
collagen lamella were calculated. The number of lamella was counted
in angular sections and the variance between the numbers of lamella
in each angular section was calculated.
Results: The average orientation variance for the collagen lamella
bundles within the 450 um anterior cornea was calculated to be
0.0462 ± 0.0136 for the untreated eyes, 0.0425± 0.0123 for the
UVX treated eyes, and 0.0376 ± 0.083 for the RGX treated eyes.
The Fourier transform of the images showed 17.6% of the untreated
cornea had a random orientation while the cross-linked eyes had
26.3% for the UVX and 25.3% for the RGX. Of the random slices,
approximately half were found within the first 100 um of the anterior
surface for the untreated eye and the UVX eye. For the RGX eye, half
of the random slices were located with the first 200 um.
Conclusions: The more random arrangement of collagen fibers in
the stroma of the CXL-treated cornea, particularly within the treated
volume, indicates microscopic changes introduced by the procedure,
which should relate to mechanical and optical effects post-CXL.
Commercial Relationships: James Germann, None;
Eduardo Martinez-Enriquez, None; Susana Marcos
Support: ERC-2011-AdG-294099, FIS2014-56643
Program Number: 2908 Poster Board Number: A0168
Presentation Time: 8:30 AM–10:15 AM
An ex vivo investigation into the effect of accelerated crosslinking
using pulsed and continuous UVA irradiation modes on corneal
enzymatic resistance
Nada H. Aldahlawi1, Sally Hayes1, David P. O’Brart2,
Alina Akhbanbetova1, Stacy L. Littlechild1, Keith M. Meek1. 1School
of Optometry and Vision Sciences, Cardiff University, Cardiff,
United Kingdom; 2Department of Ophthalmology, Keratoconus
Research Institute St Thomas Hospital, London, United Kingdom.
Purpose: Riboflavin-UVA crosslinking (CXL) has become a
ubiquitous treatment for halting progressive corneal ectasia. This
study examines the increase of corneal enzymatic resistance
following the standard CXL protocol (SCXL), and higher UVA
intensity CXL protocols, using continuous (HCXL) or pulsed
(p-HCXL) UVA irradiation modes.
Methods: Sixty-six enucleated porcine eyes, with corneal epithelium
removed, were divided into 6 groups. Group 1 was untreated
controls, groups 2-6 received riboflavin/dextran for 30 minutes, group
3 underwent SCXL with 3mW/cm2 UVA for 30 minutes (total energy
dose 5.4 J/cm2), group 4 underwent HCXL with 30mW/cm2 UVA
for 3 minutes (5.4 J/cm2), group 5 received high energy dose HCXL
with 30mW/cm2 UVA for 4 minutes (7.2 J/cm2) and group 6 received
high energy dose p-HCXL using 30mW/cm2 UVA for 8 min with
1 s on/1 s off (7.2 J/cm2). A pepsin digestion assay was performed
on central corneal disks trephined from each treated and untreated
cornea. Statistical analysis of corneal disk dry weight after 13 days of
digestion (n= 5 per group) and the time required for complete tissue
digestion (n = 6 per group), was performed using ANOVA.
Results: The time required for complete digestion was significantly
longer for the CXL-treated corneas than the non-irradiated corneas
(P < 0.0001). Significant differences in digestion time were also
observed between the cross-linked groups such that HCXL (5.4 J/
cm2) < SCXL (5.4 J/cm2) < HCXL (7.2 J/cm2) < p-HCXL (7.2 J/cm2)
(P < 0.0001). The average dry weight of SCXL (5.4 J/cm2) treated
corneas after 13 days of digestion was significantly higher than that
of the HCXL (5.4 J/cm2 and 7.2 J/cm2) treated corneas (P < 0.0001)
and the p-HCXL 7.2 J/cm2 treated corneas (P <0.03). No difference in
dry weight was detected between the HCXL 7.2 J/cm2 and p-HCXL
7.2 J/cm2 treatment groups.
Conclusions: Differences in the enzymatic resistance of SCXL and
HCXL corneas suggest that there are variations in the intensity and
distribution of the cross-links formed within the corneal tissue with
different UVA protocols. The precise location and amount of crosslinking needed to prevent disease progression is unknown.
Commercial Relationships: Nada H. Aldahlawi, None;
Sally Hayes, None; David P. O’Brart, None; Alina Akhbanbetova,
None; Stacy L. Littlechild, None; Keith M. Meek, None
Support: King Saud University Scholarship
Program Number: 2909 Poster Board Number: A0169
Presentation Time: 8:30 AM–10:15 AM
Is topography guided crosslinking the next stage in the evolution
of crosslinking: Refractive, keratometric and biomechanical
outcomes
Aarti Agrawal1, Natasha Pahuja1, Rohit Shetty1, Arkasubhra Ghosh2,
Abhijit Sinha Roy2. 1Cataract and refracrive surgery, Narayana
Nethralaya, Mumbai, India; 2Narayana Netharalaya, Bangalore, India.
Purpose: We conducted a prospective, longitudinal study to evaluate
the refractive, keractometric and biomechical outcomes of the newly
developed topography guided crosslinking.
Methods: 17 keratoconic eyes underwent topography guided
crosslinking (Avedro Inc., USA). The topography was used to
design a patient specific UV beam, which was centered and had peak
intensity at the location of the cone. The delivered energy varied
from 10 at the center to 3 J/cm2 at the periphery of the UV beam. The
maximum treated diameter was 8 mm. Topography was measured
with Pentacam (OCULUS Optikgeräte Gmbh, Germany). Corneal
deformation was measured with Corvis-ST (OCULUS Optikgeräte
Gmbh, Germany). Refractive, keratometric and deformation was
measured pre and post (6 months) surgery.
Results: Mean MRSE reduced by 0.53 ± 0.35D (p = 0.15). Flat and
steep axis keratometry, mean keratometry and maximum keratometry
also reduced without statistical significance [-0.39 ± 0.21D (p =
0.08), -0.11 ± 0.26D (p = 0.69), -0.25 ± 0.23D (p = 0.30), -0.59 ±
0.59 (p = 0.34), respectively]. Root mean square (RMS) of anterior
lower order aberration, higher order aberration and total aberration
was -0.67 ± 0.32 (p = 0.06), -0.09 ± 0.07 (p = 0.22), -0.67 ± 0.33 (p
= 0.06) was relatively unchanged at 6 months. Similar results were
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ARVO 2016 Annual Meeting Abstracts
obtained with the RMS of posterior corneal surface. However, mean
deformation amplitude reduced significantly by -0.04 ± 0.02 (p =
0.025).
Conclusions: Clinical outcomes of topography guided crosslinking
were similar to published short term outcomes of conventional
crosslinking, which is not centered on the cone location. Further
study with larger sample size and longer follow-up is needed.
Planning of differential energy delivery profile for a keratoconic
cornea.
Commercial Relationships: Aarti Agrawal, None;
Natasha Pahuja, None; rohit shetty, None; Arkasubhra Ghosh,
None; Abhijit Sinha Roy
Program Number: 2910 Poster Board Number: A0170
Presentation Time: 8:30 AM–10:15 AM
Corneal Collagen Crosslinking for progressive keratoconus: a
prognosis factor analysis
Everardo Hernandez-Quintela, María Costa-González,
Nallely Ramos Betancourt, Manuel Ramirez, Jaime D. Martinez,
Valeria Sánchez-Huerta. Cornea and Refractive Surgery, Asociación
para Evitar la Ceguera en México, Hospital “Dr. Luis Sánchez
Bulnes”, Mexico City, Mexico.
Purpose: To identify factors associated with uncorrected distance
visual acuity (UDVA) outcome 1 year after corneal collagen
crosslinking (CXL) treatment in patients with progressive
keratoconus.
Methods: A retrospective cohort study was carried out in a high
referral ophthalmology centre in Mexico City. Data was collected
from medical charts of patients who attended the Cornea Service
from 2010 to 2015 with a diagnosis of progressive keratoconus
and had undergone crosslinking. Basic demographic information,
topographic and refractive data, visual acuity outcomes and,
complications were obtained. A total of 191 eyes were included.
Predictive factors for analysis included: age, sex, preoperative
uncorrected visual acuity, best-corrected visual acuity, steep
keratometry, corneal central pachymetry, refractive sphere and,
cylinder.
Results: Thirty eyes (50.7 %) have a change of less than 1 line of
UDVA, 22 eyes (32.8%) gained 1 line or more and, 11 eyes (16.4%)
lost 1 line or more. After a multivariable analysis no factor was found
to be associated with postoperative UDVA after 1 year of CXL.
Complications reported were pain in 22 cases (15.7%) and haze in 5
eyes (2,6%). No other complications were reported.
Conclusions: No preoperative factors associated with UDVA
outcome were found in this study after 1 year of CXL. Other factors
that might be involved in the visual prognosis of CXL need to be
analyzed
Commercial Relationships: Everardo Hernandez-Quintela, None;
María Costa-González, None; Nallely Ramos Betancourt, None;
Manuel Ramirez, None; Jaime D. Martinez; Valeria SánchezHuerta, None
Program Number: 2911 Poster Board Number: A0171
Presentation Time: 8:30 AM–10:15 AM
NC-1059 peptide-assisted transepithelial riboflavin penetration in
an ex-vivo rabbit corneal model
Daniel M. Gore3, Paul French1, David O’Brart2, Chris Dunsby1,
Bruce D. Allan3. 1Physics Department, Imperial College, London,
United Kingdom; 2Ophthalmology, St. Thomas’ Hospital, London,
United Kingdom; 3External Disease Service, Moorfields Eye
Hospital, London, United Kingdom.
Purpose: NC-1059 is a synthetic non-selective ion channel-forming
peptide. This study measured NC-1059-assisted riboflavin penetration
through an intact epithelium in an animal model, compared to
standard epithelium-off riboflavin delivery.
Methods: Rabbit heads transported in phosphate buffered saline
were received within 5 hours post-mortem. Intact globes were
enucleated and warmed to room temperature in balanced salt
solution. A 200 µM NC-1059 peptide solution (sequence KKKKAARVGLGITTVLVTTIGLGVRAA) was prepared by dissolving it
in either 0.25 % or 0.1 % w/v riboflavin 5’-monophosphate solution.
A 9 mm vacuum well secured on the cornea was filled with
approximately 0.5 ml of 200 µM NC-1059 peptide in 0.1 % w/v
riboflavin solution (n=3) or 0.25 % w/v riboflavin solution for 30
minutes (n=3). Riboflavin then was rinsed from the cornea for 1
minute. Epithelial-debrided globes soaked with peptide-free 0.1%
w/v riboflavin solution served as controls (n=3).
At the end of the soak, the globes were immediately frozen in liquid
nitrogen. 35 µm corneal cross-sections were cut on a cryostat,
mounted on a slide and imaged by two-photon fluorescence (TPF)
microscopy. Riboflavin was excited by two-photon light of 890 nm
wavelength, with fluorescence signal detected between 525-650 nm.
TPF signals were converted to riboflavin concentration by use of a
calibration curve which we produced by measuring the TPF signal
within known concentrations of riboflavin on a well slide.
Results: Mean (± SD) peak riboflavin concentration of 0.09 %
(± 0.01) was observed within the anterior stroma in epitheliumoff controls. The maximum stromal riboflavin concentration in
the presence of 200 µM NC-1059 peptide solution and 0.1 % w/v
riboflavin was 0.012 (± 0.005) %. The maximum stromal riboflavin
concentration in the presence of 200 µM NC-1059 peptide solution
and 0.25 % w/v riboflavin was 0.041 (± 0.01) %.
Conclusions: NC-1059 peptide enhances riboflavin penetration
through an intact corneal epithelium, but does not match stromal
concentrations achieved ‘epithelium-off’.
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ARVO 2016 Annual Meeting Abstracts
Colour photographs of corneas soaked with NC-1059 peptide and
riboflavin showing riboflavin penetration through the cornea into the
anterior chamber. Upper row: Sagittal sections of globes mounted
on a cryostat during section preparation. Lower row: 35 μm corneal
sections laid on paper
Two-photon fluorescence images of tissue sections (grey scale). e,
epithelium
Commercial Relationships: Daniel M. Gore; Paul French, None;
David O'Brart, None; Chris Dunsby, None; Bruce D. Allan, None
Support: DMG is supported by Fight for Sight (1348/9), the
Rosetrees Trust (JS16/M282), the Ian Collins Rayner Fellowship
(Rayner Intraocular Lenses Ltd, United Kingdom and Ireland Society
of Cataract and Refractive Surgeons), and the Special Trustees of
Moorfields Eye Hospital (ST1415A).
Program Number: 2912 Poster Board Number: A0172
Presentation Time: 8:30 AM–10:15 AM
Alterations to Bowman’s layer and local molecular deregulation
driving focal corneal weakening: new evidence towards
Keratoconus etiopathogenesis
Natasha Pahuja1, Nimisha R. Kumar2, RUSHAD SHROFF1,
Rohit Shetty1, Abhijit Sinha Roy2, Arkasubhra Ghosh2. 1CorneaRefractive, Narayana Nethralaya, Pune, India; 2Narayana Nethralaya,
Bangalore, India.
Purpose: To elucidate local factors in ectatic cones of
Keratoconus(KC) patients which may reveal a functional cause for
focal corneal weakening characteristic of the disease.
Methods: Samples were collected after informed written consent and
with Institutional Ethics committee approval. The Bowman’s layer
in KC patients as imaged by high resolution anterior segment optical
coherence tomography(ASOCT) was segmented using combination
of Graph search and Djikstra’s algorithm. In patients (n=70)
undergoing corneal crosslinking, corneal epithelium over 4.5mm
cornea, centered on the cone (located by corneal topography) was
trephine marked and debrided whereas the surrounding periphery was
debrided separately. Non-ectatic refractive surgery patients (n=26)
served as controls. Gene expression levels were estimated separately
in cone and periphery samples of each eye and ratio of the values
used to correlate differential expression for each molecular factor
with clinical parameters and biomechanical data.
Results: ASOCT revealed local aberrations and focal loss of
Bowman’s layer in some KC cones. Epithelium from the cone
apex of these particular patients had highly elevated MMP9, TNFα
and IL6 but reduced IL10, TIMP1, Collagen IV and Collagen I
expression relative to peripheral epithelium indicating a cone-specific
local effect. Data across the cohort revealed significant loss of LOX
(p=0.002) Collagen IV (p=0.008) and Collagen I (p=0.01) expression
in the cone of KC patients compared to controls. MMP9 levels
(p=0.009) were significantly elevated in the cone while its inhibitor
TIMP1 showed a reducing trend in KC patients. Inflammatory genes
TNFα and IL6 were elevated in the cone in KC patients while IL10
showed slight reduction. The same results were validated in matched
cone vs periphery samples of corneal stroma as well as epithelium
from 4 KC patients undergoing keratoplasty.
Conclusions: Our study uncovers the first evidence in KC patients
that local alterations to Bowman’s layer due to injury, eye rubbing,
structural defects, etc may trigger a focal, cone specific degenerative
process. Consequently deregulated local epithelial molecular factors
drive changes that could cause the focal thinning and protrusion.
This data also suggests that functional correction using collagen
crosslinking should be concentrated at the cone rather than entire KC
cornea
Commercial Relationships: Natasha Pahuja, None;
Nimisha R. Kumar; RUSHAD SHROFF, None; rohit shetty,
None; Abhijit Sinha Roy, Carl Zeiss (F), Bioptigen (F), Avedro (F),
Topcon (F), Cleveland Clinic Innovations (P), Narayana Nethralaya
(P); Arkasubhra Ghosh, None
Clinical Trial: NCT01746823
Program Number: 2913 Poster Board Number: A0173
Presentation Time: 8:30 AM–10:15 AM
Characteristics of corneal astigmatism of anterior and posterior
surface in healthy individuals and keratoconus patients
Ingo Schmack, Gabriel Shajari, Miad PourSadeghian,
Matthias Remy, Fritz Hengerer, Thomas Kohnen. Ophthalmology,
Goethe-University, Frankfurt, Germany.
Purpose: To evaluate and compare power and axis orientation
of anterior and posterior astigmatism in eyes with keratoconus to
healthy eyes.
Methods: This retrospective study examined 861 eyes of 494 patients
diagnosed with keratoconus with a mean age of 35±11 years and 500
eyes of 500 healthy individuals serving as a control group. Using
a Scheimpflug device we measured magnitude and axis orientation
of anterior and posterior corneal astigmatism, as well as, corneal
thickness and conus location. The results were compared between
the different stages of the disease according to Amsler Krumeich
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ARVO 2016 Annual Meeting Abstracts
classification (124 subclinical; 233 Stage1; 327 Stage2; 146 Stage3;
31 Stage4) and to eyes of healthy individuals.
Results: Magnitude of corneal astigmatism was 3.47±2.10 D on
anterior surface and 0.69±0.40 on posterior surface in eyes with
keratoconus. We found significant increase of anterior and posterior
corneal astigmatism with progression of disease (p<0.01, one-way
ANOVA) and significant correlation between anterior and posterior
corneal astigmatism (r=0.77, p<0.01). In contrast to eyes of healthy
individuals where posterior corneal axis alignment is vertical in
majority of cases independent of anterior alignment, we found,
in eyes with keratoconus, a match between anterior and posterior
alignment when alignment was vertical in 97% of eyes, 46% when
oblique and 61% when horizontal (Cohen kappa coefficient κ =
0.55, p=0.00). With progression of the disease, alignment of anterior
and posterior corneal astigmatism became increasingly vertical.
Logistic regression analysis showed a significant increase in vertical
alignment with decrease in corneal pachymetry (p=0.02 for anterior
surface and p=0.01 for posterior surface). Vertical alignment was
found significantly more often if cone was central compared to
paracentral location (p<0.01 for anterior and posterior surface).
Conclusions: In difference to healthy individuals in eyes with
keratoconus posterior axis alignment of corneal astigmatism is in
line with alignment of anterior surface in majority of cases. With
progression of the disease and decrease in pachymetry corneal
resistance to vertical forces, most probably by eyelids, decrease and
axis orientation becomes increasing vertical. Axis alignment can be
used in algorithm to support diagnosis and staging of keratoconus.
Commercial Relationships: Ingo Schmack, None;
Gabriel Shajari, None; Miad PourSadeghian, None;
Matthias Remy, None; Fritz Hengerer, None; Thomas Kohnen,
None
Program Number: 2914 Poster Board Number: A0174
Presentation Time: 8:30 AM–10:15 AM
The role of Transforming growth factor beta 2 (TGF-beta 2) in
the pathogenesis of keratoconus
Omer Iqbal, Wells Brambl, Charles Bouchard. Ophthalmology,
Loyola University Chicago, Maywood, IL.
Purpose: We sought out to test the hypothesis that TNF-alpha and/
or gentle mechanical stimulation of Human Corneal Endothelial Cells
(HCEC) induces the expression of activated TGF-beta2.
Methods: HCEC’s were obtained courtesy of Dr. Monika Valtink
and cultured in Basal F99 medium as per Dr. Valtink’s protocol. Cells
were trypsinized and plated at a concentration of a 12k cells/mL in
a 24 well plate and allowed to grow to 100% confluency. Cells were
washed and media replaced with DMEM and 10% FBS. Cells were
exposed to sham, 1 ng/mL, 10 ng/mL, or 100 ng/mL of TNF-alpha.
Half of those cells were exposed to gentle mechanical stimulation.
After 16 hours of incubation supernatants were collected and stored
at -80C. TGF-beta2 concentration in supernatants was assayed using
eBioscience TGF-beta2 platinum ELISA, which were then subjected
to one-way ANOVA compared to control sample.
Results: When compared to control samples, HCEC cells exposed
to 10 ng/mL TNF-alpha expressed more TGF beta 2, 346.7
vs. 512.2 ng/mL respectively (p=0.0096). When compared to
control samples, HCEC cells exposed to 100 ng/mL TNF-alpha
expressed increased TGF beta 2, measuring 346.7 vs 505.1 ng/
mL respectively (p=0.0435). However there was no significant
effect of gentle mechanical stimulation of cells in the presence or
absence of TNF-alpha.
Conclusions: TNF-alpha exposed cells at concentrations greater
than or equal to 10 ng/mL had increased secretion of TGF-beta2.
These data suggest that an initial inflammatory response may trigger
increased secretion of TGF-beta 2 by HCEC’s, therefore possibly
increasing fibrosis of the stroma as seen in Keratoconus. Interestingly,
this effect was not enhanced by gentle mechanical stimulation.
However, this study is limited by the short time course of the
experiment, which obviates the lack of applicability to chronic eye
rubbing. Future testing will evaluate Human Corneal Epithelial Cells
and their response to TNF-alpha and whether inhibition of Smad3
rescues increased TGF-beta 2 secretion in response to TNF-alpha.
Clinical studies are warranted to validate these results.
HCEC secretion of TGF-Beta 2 in sham, mechanical stimulation
alone, 1 ng/mL TNF-alpha, 1 ng/mL TNF-alpha + mechanical
stimulation, 10 ng/mL TNF-alpha, 10 ng/mL TNF-alpha +
mechanical stimulation, 100 ng/mL TNF-alpha, and 100 ng/mL TNFalpha + mechanical stimulation.
Commercial Relationships: Omer Iqbal, None; Wells Brambl,
None; Charles Bouchard, None
Support: Illinois society for the prevention of blindness
Program Number: 2915 Poster Board Number: A0175
Presentation Time: 8:30 AM–10:15 AM
In-vivo Penetration of WST11 to the Corneal Stroma using
Dextran with Various Molecular Weights
Arie Marcovich1, 2, Alexander Brandis1, Ilan Samish1, Iddo Pinkas1,
Ilan Feine1, Alexandra Goz1, 2, Yoram Salomon3, Avigdor Scherz1.
1
Plant and Environmental Sciences, Weizmann Institute of Science,
Rehovot, Israel; 2Ophthalmology, Kaplan Medical Center, Rehovot,
Israel; 3Biological Regulation, Weizmann Institute of Science,
Rehovot, Israel.
Purpose: To evaluate the in-vivo corneal penetration depth of the
photosensitizer WST11 in saline and with dextran of different
molecular weights following different impregnation times. We have
demonstrated previously that WST11 followed by near infrared (NIR)
light can induce ex-vivo and in-vivo corneal stiffening. Its penetration
in the cornea determines its tissue effect and safety.
Methods: Eyes of anesthetized rabbits were incubated after
corneal deepithelization with 2.5 mg/mL WST11 in saline or in
20% dextran of 6kD, 70kDa and 500kDa molecular weight for 10
and 30 minutes. After euthanization, corneal sagittal slices were
prepared using cryomicrotome. Fluorescence microscopy detected
corneal stromal WST11 penetration depth. In eyes incubated with
WST11 in 20% dextran 500kDa (WST11-D500) anterior chamber
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ARVO 2016 Annual Meeting Abstracts
humor was drawn after incubation and WST11 concentration was
assessed spectroscopically and by Inductively coupled plasma mass
spectrometry (ICP-MS).
Results: WST11 in saline crossed ~0.7 of the corneal stromal depth
within 10 minutes of incubation and the entire stromal depth after 30
minutes of incubation. The addition of dextran attenuated the stromal
penetration according to dextran’s molecular weight. The 10 minutes
penetration of WST11 formulated with 6kD, 70kDa and 500kDa
dextran was ~0.7, ~0.5 and ~0.5 of stromal depth, respectively. After
30 minutes of incubation with WST11 formulated with 6kD, 70kDa
and 500kDa dextran the stromal penetration reached ~0.85, ~0.7 and
~0.7 respectively. With the heavier 500kDa dextran, even after 30
minutes of incubation, there was a sharp decline in the intensity of
the fluorescence levels at 0.5-0.6 of the corneal stromal depth. No
detectable levels of WST11 were observed in the anterior chamber by
spectroscopy and ICP-MS.
Conclusions: We demonstrated in-vivo that the addition of high
molecular weight dextran to WST11 limits its penetration into the
deepithelized corneal stroma. This feature increases the safety of the
treatment by confinement of the photodynamic effect away from the
endothelium. This newly described phenomenon may be applied to
other drugs or tissues.
Commercial Relationships: Arie Marcovich, Yeda Weizmann
institute of Science (P); Alexander Brandis, Yeda Weizmann
institute of Science (P); Ilan Samish, None; Iddo Pinkas, None;
Ilan Feine, None; Alexandra Goz, None; Yoram Salomon, Yeda
Weizmann institute of Science (P); Avigdor Scherz, Yeda Weizmann
institute of Science (P)
Program Number: 2916 Poster Board Number: A0176
Presentation Time: 8:30 AM–10:15 AM
Functional And Anatomical Modifications In A Six-Month
Follow-up Of Patients Treated With Collagen Cross-linking
Riccardo Scotto, Donatella Musetti, Fabio Licata, Carlo E. Traverso.
DiNOGMI, University of Genoa, Genova, Italy.
Purpose: To analyze functional and anatomical corneal changes after
corneal collagen cross-linking.
Methods: 41 eyes of 35 patients (25 male and 10 female) mean age
24 ±7 years affected by mono or bilateral progressive keratoconus
were enrolled. All patients underwent corneal collagen cross-linking
using epithelium-off technique. Corneal topography, anterior segment
OCT and in-vivo confocal microscopy were used for the evaluation
of corneal changes.
Results: Compared to pre-treatment values, corneal curvature and
corneal apex decreased (p>0,05), Best Corrected Visual Acuity
(BCVA) improved from 20/32 to 20/25 (p<0,05), while Central
Corneal Thickness (CCT) was unchanged at 6-month follow-up visit
(p=0,9557). In-vivo confocal microscopy showed anatomical changes
during follow-up.
Conclusions: Our study highlights that corneal anatomical changes
have led to improved visual function. This confirms the efficacy
and safety of collagen cross-linking in patients with progressive
keratoconus.
Commercial Relationships: Riccardo Scotto, None;
Donatella Musetti, None; Fabio Licata, None; Carlo E. Traverso,
None
Program Number: 2917 Poster Board Number: A0177
Presentation Time: 8:30 AM–10:15 AM
Trans-Epithelial Accelerated Corneal Cross-linking for
Keratoconus in Children: 18 month follow-up
Alejandro Navas, Andrew Olivo-Payne, Alexandra Abdala,
Erick Hernandez-Bogantes, Arturo J. Ramirez-Miranda,
Enrique O. Graue-Hernandez. Instituto de Oftalmologia - Catarata,
Institute of Ophthalmology “Conde de Valenciana”, Mexico City,
Mexico.
Purpose: To evaluate the safety and efficacy of trans-epithelial
accelerated corneal cross-linking (TE-ACXL) in children with
progressive keratoconus.
Methods: Prospective, consecutive, case-series of 23 eyes of 14
children who underwent TE-ACXL. Tomographic and refractive
changes were analyzed at baseline and 1, 3, 6, 12 and 18 months
postoperatively.
Results: Follow-up ranged from 18 to 30 months with a mean
follow-up time of 23.82 months ±3.15. Mean age was 13.7 years
±1.4 (range 11-16). Mean preoperative UDVA from 0.92 ± 0.45
logMAR (20/160) to 0.71 ± 0.40 logMAR (20/100) (p=0.001).
Mean keratometry (Km) changed from 53.87 ± 6.03 to 53.00 ± 5.81
(p=0.001). Pachymetry was 433.64±38.09 microns before treatment
and 430.09 ± 54.26 microns at last follow-up (p=0.30). The mean
preoperative sphere was -5.58±2.48 D and -4.89±4.66 (p=0.11) at
last follow-up; refractive cylinder and spherical equivalent from
-5.58±2.48 to -5.02±2.23 (p=0.046) and -7.90±5.39 to -7.41±4.84
(0.043), respectively.
Conclusions: Tomographic and refractive stability was shown in over
91% of eyes with progressive keratoconus who underwent TE-ACXL
Commercial Relationships: Alejandro Navas, None;
Andrew Olivo-Payne, None; Alexandra Abdala, None;
Erick Hernandez-Bogantes, None; Arturo J. Ramirez-Miranda,
None; Enrique O. Graue-Hernandez, None
Program Number: 2918 Poster Board Number: A0178
Presentation Time: 8:30 AM–10:15 AM
Health-Related Quality of Life Improvement in Keratoconic
Patients Subjected to the Athens Protocol Treatment
Ioannis Datseris1, George Asimellis2, 3, A. J. Kanellopoulos3, 4.
1
OMMA Surgical, Athens, Greece; 2Kentucky College of Optometry,
Pikeville, KY; 3LaserVision.gr Clinical & Research Eye Institute,
Athens, Greece; 4Ophthalmology, NY University, NY, NY.
Purpose: Considering both the importance of Health-Related
Quality of Life (HR-QoL) and the contribution of modern medicine
therapeutic methods concerning surgical visual rehabilitation, the
purpose of this research is to assess the HR-QoL before and after the
management of keratectasia with the Athens Protocol.
Methods: 34 patients (age 15 to 51 years, 25 male, 09 female) treated
for progressive keratoconus were randomly selected for retrospective
telephone interview and individual questionnaire submission. A
disease-specific health-related quality of life (HRQoL) questionnaire
was administered before and after the Athens Protocol intervention.
The administrative questionnaires NEI VFQ 25/39 and IVI-28 were
applied. Reliability of collected data was evaluated with Cronbach’s
Alpha test. Amsler-Krumeich Classification (keratoconus severity)
and Visual acuity (pre-operative) were used as criterion to form two
groups, Group-A, better visual acuity and Group-B, worse visual
acuity.
Results: Patient age was 15 to 51 years at the time of the operation.
Mean time past the operation during which the questionnaires were
administered was 15 months (range 3 to 36). General visual acuity,
psychological well - being and driving facility showed significant
improvement. Younger keratoconic patients tend to have more
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ARVO 2016 Annual Meeting Abstracts
enhanced psychology and to cope better with difficulties in everyday
activities (pre op) than older patients.
Conclusions: The Athens Protocol treatment has been proven
beneficial to patients in a large number of aspects.
Commercial Relationships: Ioannis Datseris, None;
George Asimellis, None; A. J. Kanellopoulos, i-Optics (C),
Keramed (C), Avedro (C), ISP Surgical (C), Allergan (C), Alcon (C)
Program Number: 2919 Poster Board Number: A0179
Presentation Time: 8:30 AM–10:15 AM
The persistence of pain relief after corneal crosslinking in mild
bullous keratopathy eyes
Takashi Ono1, Yukiko Terada2, Yosai Mori1, Ryohei Nejima1,
Miyuki Ogata1, Keiichiro Minami1, Kazunori Miyata1. 1Miyata
Eye Hospital, Miyakonojo, Japan; 2Tokyo Metropolitan Geriatric
Hospital, Itabashi-ku, Japan.
Purpose: Crosslinking (CXL) corneal collagen to edematous corneal
stroma effectively reduces central corneal thickness and relieves
pain. The prospective observational case study was to examine the
persistence of pain relief of bullous keratopathy (BK) up to 1 year
after CXL treatment and to observe the stroma using in vivo confocal
microscopy.
Methods: Eleven eyes from 11 patients who underwent consecutive
CXL treatments for BK between September 2011 and December
2013 were followed up over the course of one year. The mean patient
age was 78.6 ±12.0 (SD) years. The best-corrected visual acuity
(BCVA), intraocular pressure (IOP), and corneal thickness were
examined before treatment, as well as 1 week and 1, 3, 6, and 12
months after treatment. The intensity and frequency of pain were
scaled from 0 (minimum) to 10 (maximum). At 12 months after
CXL treatment, the corneal stroma at depths of 100 and 200 μm was
observed via confocal microscopy, and the densities of keratocytes
(cell/mm2) and nerve fibers (mm/mm2) were calculated.
Results: The BCVA after treatment did not significantly improve
from that before treatment (P=0.996, Kruskal-Wallis test). In the
CCT, there was no significant change at any examination point
(P=0.52). The mean pain intensity score was 6.27 (range: 0-9) before
treatment and significantly decreased after treatment (P<0.01):
the score at 12 months was 1.80 (range: 0-6; P<0.01). The mean
pain frequency score was 5.45 (range: 0-10) before treatment
and significantly decreased after treatment (P<0.05): the score at
12 months was 1.27 (range: 0-5; P<0.01). Confocal microscopy
observations showed keratocytes and nerve fibers were rarely
observed at 12 months after CXL. At a depth of 100 μm, the gross
keratocyte and nerve fiber densities for all images were 5.1 cells/mm2
and zero, respectively. At a depth of 200 μm, the gross densities were
2.9 cells/mm2 and 0.21 mm/mm2, respectively.
Conclusions: CXL effectively relieved the intensity and frequency
of BK pain for at least 1 year after treatment. In vivo confocal
microscopic observation and a lack of change in CCT demonstrated
that the persistence of pain relief was attributable to the inadequate
regeneration of nerve fibers in the corneal stroma.
Commercial Relationships: Takashi Ono; Yukiko Terada, None;
Yosai Mori, None; Ryohei Nejima, None; Miyuki Ogata, None;
Keiichiro Minami, None; Kazunori Miyata, None
Program Number: 2920 Poster Board Number: A0180
Presentation Time: 8:30 AM–10:15 AM
Correlation between central stromal demarcation line depth and
flattening of the cornea after corneal cross-linking comparing two
different treatment protocols
Niklas Pircher, Andreas Gschliesser, Ruth Donner, Jan Lammer,
Gerald Schmidinger. Ophthalmology, Medical University of Vienna,
Wien, Austria.
Purpose: A corneal stromal demarcation line (DL) induced by
corneal cross-linking (CXL) has lately been suggested as a possible
surrogate parameter for the flattening effect and success of the
CXL-procedure. Aim of this study was to investigate the correlation
between depth of the DL in the center of the cornea 1 month (mo) and
reduction in maximal keratometry values (Kmax) 12mo after CXL
treatment as well as comparing the effect in two different treatment
protocols.
Methods: Treatment-naive subjects with keratoconus were treated
either following the Standard Dresden Protocol (SDP, 30 minutes
(min) Riboflavin + 20% Dextran [Peschke D] soaking, 30min
irradiation UVX-1000, 3mW/cm2) or an Accelerated CXL Protocol
(ACP, 10min HPMC [Vibex Rapid] soaking, 10min irradiation
UVX-2000, 9mW/cm2). Depth of the DL was measured using Visante
anterior segment OCT (Carl Zeiss Meditec Inc.) imaging 1mo postoperatively (OP). Kmax (preOP) and change in Kmax (preOP - 12mo
postOP) were assessed using corneal topoghrapy (Pentacam HR
tomography, Oculus GmBH).
Results: 91 eyes were included in this retrospective study. 60 eyes
were treated according to the SDP and 31 eyes following the ACP.
PreOP mean±SD Kmax was 57.26±6.97 D in the SDP group, and
56.82±6.36 D in the ACP group (p=0.10). A DL at 1mo postOP was
observed in all eyes of both groups. Stromal depth was 326.57±76.64
µm in the SDP group, and 168.74±73.15 µm in the ACP group
(p<0.001). Mean change in Kmax was -1.17±0.79 D after 12mo in
the SDP group and -0.85±0.44 D in the ACP group. Change in Kmax
was significant in the SDP group (p<0.001), but not in the ACP group
(p=0.75). No statistically significant correlation between stromal
depth of the DL after 1mo and change in Kmax after 12mo was found
in either of the groups (Pearson r: -0.09 and -0.02 respectively).
Conclusions: Different CXL treatment protocols seem to induce
different depths of the stromal demarcation line. Even though
eyes that were treated following the Standard Dresden Protocol
showed a deeper DL and a significant change in Kmax at 12mo, the
interpretation of the stromal depth of the DL as a surrogate parameter
for the effect of the procedure may be doubted, since a statistically
significant association between DL depth and Kmax reduction after
12 months was not found in either of the groups.
Commercial Relationships: Niklas Pircher, None;
Andreas Gschliesser; Ruth Donner, None; Jan Lammer, None;
Gerald Schmidinger, None
Program Number: 2921 Poster Board Number: A0181
Presentation Time: 8:30 AM–10:15 AM
Progression after corneal cross-linking in keratoconus eyes with
KMax≥58.0 D
Samuel J. Küchler1, Christoph Tappeiner1, Dan Epstein2,
Beatrice E. Frueh1. 1Ophthalmology, University Hospital Berne,
Berne, Switzerland; 2Private Practice, Berne, Switzerland.
Purpose: To assess the effectiveness of corneal cross-linking (CXL)
in keratoconus eyes with KMax values ≥58.0D
Methods: Retrospective analysis of CXL (standard Dresden epi-off)
in progressive keratoconus. Inclusion criteria were KMax≥58.0D and
a minimum follow-up of 1 year. Corneal topography and tomography
were performed preoperatively and at 1 and 2 years. Those values
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ARVO 2016 Annual Meeting Abstracts
were compared by paired T-Test. Sixty-one eyes of 56 patients with a
mean age of 31.1 years (range 12 to 57 years) were included. Fortytwo of these eyes had a 2-year follow-up. Progression was defined as
in increase in KMax of ≥1.0D over 1 year.
Results: Preoperative KMax was 63.88 ± 6.05D (mean±SD). At 1
year it was 62.85 ± 5.90D. This represented a significant decrease
in steepness (p=0.0029). Fifteen of the 61 eyes (i.e. 24.6%) showed
progression at 1 year. Five of the 61 steepened >2.0D (8.2%).
Mean pachymetry at the thinnnest point was 433.72±44.81μm
preoperatively, and 422.79±41.70μm at 1 year.
For the eyes with a 2-year follow-up, KMax was 63.21 ± 5.25D
pre-CXL and 61.81 ± 5.05D at 2 years. This represented a significant
decrease in steepness (p=0.0089). Progression occurred in 9 out of 42
eyes (21.4%). Mean pachymetry was 437.29±43.14μm preoperatively
and 420.67±39.17μm at 2 years.
Two eyes underwent a second CXL and one a lamellar keratoplasty.
Conclusions: In progressive keratoconus with preoperative KMax
≥58.0D, progression was seen in 24.6% of eyes at 1 year and 21.4%
at 2 years after CXL. This is a considerably higher incidence of
progression than previously reported. Earlier CXL studies of very
steep keratoconus corneas included only a small number of eyes. To
the best of our knowledge, this study represents the largest number
of such corneas analyzed with respect to long-term post-CXL
progression.
Commercial Relationships: Samuel J. Küchler, None;
Christoph Tappeiner, None; Dan Epstein, None;
Beatrice E. Frueh, None
were found in CDVA (p=0.01) and Central corneal thickness
(p=0.001).
Conclusions: Results of pulsed-light accelerated CXL at 6 months
were encouraging, although a total of 8 eyes (13.33%) of the treated
eyes showed progression (3 eyes (5.0%) stromal pa-CXL, 5 eyes
(8.33%) transepithelial pa-CXL). Of the 8 eyes, 6 eyes (75.0 %)
had severe KC, 2 eyes (25.0 %) had moderate KC and no eyes (0%)
with mild KC progressed; 86.67% of treated eyes remained stable or
showed early signs of regression; mild (100%), moderate (91.3%)
and severe (62.5%) KC. Transepithelial and stromal pulsed-light
accelerated CXL techniques were both safe and effective although
CDVA was significantly better (p=0.01) in stromal vs transepithelial
pa-CXL.
Commercial Relationships: Andrew Olivo-Payne, None;
Alexandra Abdala; Erick Hernandez-Bogantes, None;
Arturo J. Ramirez-Miranda, None; Alejandro Navas, None;
Denise Loya, None; Enrique O. Graue-Hernandez, None
Program Number: 2922 Poster Board Number: A0182
Presentation Time: 8:30 AM–10:15 AM
Trans-epithelial and Stromal Pulsed-Light Accelerated Corneal
Cross-linking for Patients with Progressive Keratoconus
Andrew Olivo-Payne, Alexandra Abdala, Erick Hernandez-Bogantes,
Arturo J. Ramirez-Miranda, Alejandro Navas, Denise Loya,
Enrique O. Graue-Hernandez. Department of Ophthalmology,
Instituto de Oftalmologia Conde de Valenciana, Mexico City,
Mexico.
Purpose: Pulsed-light accelerated corneal cross-linking (pa-CXL)
theoretically achieves an additional oxygen concentration which
allows more singlet oxygen release for crosslinking of collagen
molecules rendering it more effective than continuous-light CXL.
To evaluate the effectiveness and safety of pa-CXL in patients with
progressive keratoconus (KC). Tomographic and refractive changes
were analyzed at baseline, 1, 3 and 6 months after treatment.
Methods:
Prospective, comparative, non-randomized, interventional study.
Refraction, UDVA, CDVA, and corneal tomography (Pentacam,
Occulus, Germany) at baseline, 1, 3, 6 and 12 months were measured.
CXL technique: Corneal soaking with riboflavin solution. UV-A
radiation: 1 second on, 1 second off (30 mW/cm2) x 8 minutes=7.2J/
cm2 total energy dose for both techniques.
Results: A total 60 eyes of which 16 (26.6%) had severe KC (>54D),
23 (38.3%) moderate KC (48-54 D) and 21 (35%) mild KC (<48 D)
The preoperative mean UDVA was 0.87±0.49 logMAR, after pa-CXL
the mean UDVA was 0.85±0.39 at 6.94±2.28 months follow up (2.610.67 months). Preoperative CDVA was 0.36±0.35 logMAR, after
pa-CXL the mean CDVA was 0.35±0.28 logMAR. Before treatment
the maximum keratometry (Kmax) was 54.19±5.77 D (44.6-69.2 D),
after pa-CXL the Kmax was 54.43±6.80 D (45.3-68.8 D). Paquimetry
at baseline was 440.86 ±46.90 microns to 435.80±43.46 microns at
last follow-up. When comparing transepithelial vs stromal pa-CXL,
no statiscally significant differences were found in UDVA (p=0.67),
KMax (P=0.39), Km (p=0.27). Statistically significant differences
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