You are on page 1of 6

CLINICAL SCIENCE

Comparative Analysis of Refractive and Topographic


Changes in Early and Advanced Keratoconic Eyes
Undergoing Corneal Collagen Crosslinking
Ritu Arora, MD, Parul Jain, MS, J. L. Goyal, MD, and Deepa Gupta, MS

Purpose: To compare the refractive and topographic changes at 1


year in eyes with early and advanced keratoconus undergoing
corneal collagen crosslinking (CXL). A prospective, nonrandomized
comparative clinical intervention study.

Methods: Thirty eyes of patients with keratoconus underwent


CXL. They were divided into 2 groups based on their mean central
keratometry: group A [mean central K # 53 diopters (D)] and group
B (mean central K . 53 D). Uncorrected visual acuity (UCVA),
best-corrected visual acuity (BCVA), refraction, topography, pachymetry, and endothelial cell counts were evaluated at baseline and at
1, 3, 6, and 12 months of follow-up.

Results: The mean baseline logarithm of the minimum angle of


resolution (logMAR) UCVA and logMAR BCVA in group A was
1.007 6 0.30 and 0.566 6 0.21, respectively. The values
improved to 0.727 6 0.29 (P = 0.001) and 0.306 6 0.15 (P =
0.001) at 1-year post CXL. The mean baseline logMAR UCVA
and logMAR BCVA in group B were 1.040 6 0.24 and 0.641 6
0.25, respectively. It changed to 0.953 6 0.26 (P = 0.054) and
0.633 6 0.27 (P = 0.891) at 1 year. The improvement in the
UCVA and BCVA was statistically signicant in group A as compared with that in group B. The mean baseline attest, steepest,
central, and apical keratometry in group A were 48.7 6 2.5 D,
54.9 6 3.3 D, 49.5 6 1.4 D, and 57.3 6 2.3 D, respectively. At 12
months, the values changed to 47.8 6 2.4 D, 54.1 6 3.0 D, 48.8 6
1.8 D, and 56.2 6 2.7 D, the change being statistically signicant
for mean at and apical K only (P , 0.05). All the 4 indices did
not show any statistically signicant difference at 12 months in
group B (P . 0.05).

Conclusions: Corneal CXL is more effective in improving the


refractive and topographical parameters at 1 year when it is performed
early in the course of the disease.

Received for publication October 13, 2012; revision received June 11, 2013;
accepted June 11, 2013.
From the Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi,
India.
The authors have no funding or conicts of interest to disclose.
All authors have (1) substantial contributions to conception and design,
acquisition of data, analysis and, interpretation of data; (2) drafting the
article and revising it critically for important intellectual content; and (3)
nal approval of the version to be published.
Reprints: Parul Jain, Guru Nanak Eye Centre, Maulana Azad Medical
College, New Delhi 110002, India (e-mail: pjain811@gmail.com).
Copyright 2013 by Lippincott Williams & Wilkins

Cornea  Volume 32, Number 10, October 2013

Key Words: corneal collagen crosslinking, stage of keratoconus


(Cornea 2013;32:13591364)

eratoconus is a degenerative, noninammatory, progressive


bilateral thinning of the cornea. It is characterized by stromal thinning leading to secondary conical ectasia. The manifestations of the disease vary from slight irregular astigmatism
to visual impairment secondary to stromal scarring. Progressive
distortion and bowing of the cornea result in optical aberrations
and in some cases an inability to achieve good functional
vision. Often, this has a negative impact on the quality of life.1,2
Treatment options for early keratoconus include correction of the refractive error by spectacles or contact lenses. In
contact lensintolerant patients with mild to moderate keratoconus, the implantation of intracorneal ring segments can be
considered. These treatment options do not arrest the progression of the disease and are useful only in less advanced cases. In
advanced cases of keratoconus, penetrating or lamellar keratoplasty procedures are the only treatment options. Surgical intervention is necessary in 10% to 25% of the cases.37
The advent of corneal collagen crosslinking (CXL) is
one of the promising developments of this decade in the
management of keratoconus. It has been reported to halt
progression and stabilize the disease.2,8 With variable criteria
used to dene success with CXL9 and reports of less effectivity of the procedure with maximum K reading .58 D,8 we
aimed to compare the efcacy of CXL between patients with
keratoconus with a mean central K # 53 and .53 diopters
(D) in a prospective manner by analyzing the refractive and
topographic outcomes post CXL at 12 months.

MATERIALS AND METHODS


Following Institutional Review Board approval, the
study was conducted at the Guru Nanak Eye Centre, Maulana
Azad Medical College, New Delhi. Thirty eyes of patients with
keratoconus were enrolled in the study. The diagnosis of
keratoconus was made based on corneal thinning and ectasia
on slit-lamp biomicroscopy in advanced cases and on topographic ndings of irregular astigmatism, central K . 48 D
and posterior oat . 40 mm. The criteria for irregular astigmatism on topography were inferior-superior asymmetry .1.4 D,
symmetric/asymmetric bow tie, and skewing of radial axes.
They were divided into 2 groups: group A comprised 15 eyes
of patients with a preoperative mean central keratometry
www.corneajrnl.com |

1359

Cornea  Volume 32, Number 10, October 2013

Arora et al

value #53 D, and group B comprised 15 eyes of patients with


a preoperative mean central keratometry value .53 D. A written
informed consent was obtained from the patient/guardian.
The inclusion criteria for patients were that they should
have keratoconus, age .12 years, corneal thickness $400 mm
at the thinnest point (epithelium on), and a mean central 3-mm
keratometry $48 D on Orbscan. The exclusion criteria
were corneal opacities, dry eyes, severe vernal keratoconjunctivtis, cornea guttata, endothelial irregularities, a history of
recurrent corneal erosions, and actual or intended pregnancy.
All the patients underwent uncorrected [uncorrected
visual acuity (UCVA)] and corrected [best-corrected visual
acuity (BCVA)] distance visual acuity assessment, slit-lamp
microscopy, basal Schirmer testing, tonometry by Tonopen
(Reichert, Depew, NY), dilated fundus examination, endothelial biomicroscopy (Topcon Specular Microscope SP-3000P;
Topcon Corp, Itabashi, Tokyo), ultrasonic pachymetry
(PACSCAN 300A; Sonomed Escalon, Lake Success, NY),
and optical tomography with the Orbscan II (Bausch &Lomb,
Rochester, NY). The patients were followed up in the early
postoperative period at 1, 3, and 7 days and 1, 3, 6, and
12 months after surgery. Parameters evaluated on corneal
topography on Orbscan were keratometry in central 3 mm,
sim K (at and steep K), apical K, and pachymetry at the
thinnest point. In addition, postoperatively, the patients were
evaluated for the presence of corneal stromal haze.

SURGICAL TECHNIQUE
All the patients underwent CXL as per the standard
Dresden protocol.9 The central 8.0 mm of the corneal epithelium was subjected to mechanical debridement under local or
general anesthesia. Riboavin 0.1% in dextran 20% (Ricrolin
Sooft, Italia Inc) was used for the procedure and was applied
topically every 2 to 3 minutes for 30 minutes. After conrming
that the stromal thickness at the thinnest point was at least
400 mm by ultrasonic pachymetry, ultraviolet-A irradiation
(CSO-Vega X-linker; Scandicci, Florence, Italy) was commenced using a wavelength of 370 nm, at a surface irradiance
of 3.0 mW/cm2 for 30 minutes (surface dose 5.4 J/cm2).
Throughout the irradiation phase, riboavin solution was
applied every 2 to 3 minutes, ensuring that the stromal surface
was kept moist. After surgery, the patients received 2% homatropine (Homatropine hydrobromide; Java Pharmaceuticals,
Delhi, India) and gatioxacin drops (Zymar; Allergan, Bangalore, India). A soft bandage contact lens was applied until
reepithelialization was complete. Topical 0.3% gatioxacin
was given 4 times daily for 7 days. Loteprednol acetate 0.5%
drops (L-pred; Allergan Inc, Irvine, CA) were administered 3
times daily for 20 days (after complete reepithelialization
occurred). Hypromellose 0.3% drops (Genteal; Novartis Pharmaceuticals, Basel, Switzerland) were applied 6 times daily
for 45 days.

DATA ANALYSIS
SPSS software for Windows (version 14) was used for
statistical analysis. Preoperative and postoperative parameters
within each group were compared using the paired t test (for

1360

| www.corneajrnl.com

normally distributed data), or nonparametric Wilcoxon signed


rank test (data not normally distributed).
Preoperative and postoperative parameters between the
2 groups were compared using the unpaired t test (data normally distributed), or nonparametric MannWhitney test (data
not normally distributed). A P value ,0.05 was considered
statistically signicant.

RESULTS
The follow-up ranged from 14 to 18 months post CXL,
the mean follow-up being 16 months and the median being 15
months. There was a minimum follow-up of 12 months for all
the patients included in the study. The mean epithelial healing
time was 4 6 2 days.
In group A, the mean age of the patients was 19.13 6 4.83
years. Most patients were in the age group of 15 to 24 years. In
group B, the mean age of the patient was 21.73 6 9.52 years.
The age range for patients in this group was 12 to 30 years.
All the patients enrolled in the study had bilateral disease.
The eye with more severe disease and/or fullling the inclusion
criteria underwent CXL. In both groups, there were 2 patients
who had undergone deep anterior lamellar keratoplasty for
advanced keratoconus in the fellow eye.
Visual acuity was measured using Snellen charts in
both groups. For the purpose of statistical analysis, the
Snellen visual acuity was converted to the corresponding
logarithm of the minimum angle of resolution (logMAR)
value using standard conversion tables.
The mean baseline logMAR UCVA in group A was
1.007 6 0.30. It ranged from 0.5 to 1.4 at presentation. It
improved to 0.727 6 0.29 [95% condence interval (CI)
0.5650.888, P = 0.001] at 12 months follow-up, which
was statistically signicant. In group B, the mean logMAR
UCVA at presentation was 1.040 6 0.24, and it ranged from
0.6 to 1.3. At 12 months, the mean logMAR UCVA was
0.953 6 0.26, and the change was not statistically signicant
(95% CI 0.8041.103, P = 0.054; Fig. 1).
In group A, the BCVA was obtained with spectacles in
11 patients and with contact lenses in 4 patients pre CXL and
post CXL. In group B, the BCVA was obtained with spectacles
in 10 patients and with contact lenses in 5 patients pre CXL
and with spectacles in 8 patients and with contact lenses in 7
patients post CXL at 12 months. The mean preoperative
logMAR BCVA in group A was 0.566 6 21, and it ranged
from 0.3 to 1.0. It improved to 0.306 6 15 (95% CI 0.2192
0.3941, P = 0.001). In group B, the mean preoperative logMAR BCVA was 0.641 6 0.25. It ranged from 0.20 to 1.0. At
12 months; the mean logMAR BCVA in group B was 0.633 6
0.27 (95% CI 0.48140.7852, P = 0.891). The change in the
BCVA at 12 months was found to be statistically signicant in
group A and not in group B (Fig. 1).
The mean preoperative subjective spherical correction in
group A was 24.4 6 4.6 D, and it ranged from 0 to 215.5 D.
The mean preoperative subjective cylindrical correction in
group A was 2.9 6 1.6 D, and it ranged from 0 to 26 D.
The mean spherical correction of the patients in group A
changed signicantly from 24.4 D pre CXL to 23.8 D at
1-year post CXL (P = 0.034), and there was no signicant
2013 Lippincott Williams & Wilkins

Cornea  Volume 32, Number 10, October 2013

A Comparative Analysis

FIGURE 1. Ninety-five percent CI plots of the UCVA and the BCVA at the 1-year follow-up post CXL in patients with central K # 53
D (group A) and .53 D (group B) (n = 15 eyes in each group). UCVA: group A: 95% CI 0.565 to 0.888, P value 0.001, group B:
95% CI 0.804 to 1.103, P value 0.054 BCVA: group A: 95% CI 0.2192 to 0.3941, P value 0.001, Group B: 95% CI 0.4814 to
0.7852, P value 0.891.

change in the mean subjective cylindrical power in group A


(P = 0.591).
The mean subjective sphere in group B was 26.4 6
5.6 D, and it ranged from 0 to 222 D. The mean subjective
cylinder was 22.3 6 2.1 D, and it ranged from 0 to 26 D.
The mean spherical correction of the patients in group B
changed signicantly from 26.4 to 25.8 D (P = 0.016);
however, the change in the cylindrical value was not significant (P = 1.000; Fig. 2).
A thorough topographical analysis was done for all
patients, and the parameters evaluated were mean central
K, mean steep K, mean at K, and mean apical K. In group
A, the mean central K, the mean steep K, mean at K, and
mean apical K were 49.5 6 1.4 D, 54.9 6 3.3 D, 48.7 6
2.5 D, and 57.3 6 2.3 D, respectively. Of the topographical parameters, the change was found to be statistically
signicant for at and apical keratometry only in group A.

There was no statistically signicant change in any of the


topographical parameters in group B at 1 year post CXL
(Table 1).
The mean preoperative anterior oat in group A was
0.060 6 0.013 mm (range, 0.0300.078), and in group B, it
was 0.078 6 0.020 mm (range, 0.0450.123). There was
a decrease in the anterior elevation in both groups at all
follow-up visits and at the nal follow-up at 12 months, the
corresponding values at the nal follow-up being 0.056 6
0.014- and 0.077 6 0.018-mm groups A and B. This decrease
was statistically signicant in group A when compared with
that in group B (P = 0.003). The posterior oat pre CXL in
group A ranged from 0.063 to 0.135 mm, and post CXL, the
values varied from 0.087 to 0.171 mm. In group B, the values
ranged from 0.075 to 0.156 mm preoperatively and 0.160 to
0.214 mm postoperatively. The posterior oat values post CXL
were variable and less reproducible.

FIGURE 2. Timeline charts of refractive changes pre and post CXL in patients with central K # 53 D (group A) and .53 D (group B).
2013 Lippincott Williams & Wilkins

www.corneajrnl.com |

1361

Cornea  Volume 32, Number 10, October 2013

Arora et al

TABLE 1. Table Showing Topographic Findings Pre and Post CXL in Patients With Central K # 53 D (Group A) and .53 D
(Group B)
Group A

Parameter
Central K
Flat K
Steep K
Apical K

Mean Value
Pre
CXL + SD

Range

6
6
6
6

4851.5
44.153.3
49.161.4
50.863.1

49.5
48.7
54.9
57.3

1.4
2.5
3.3
2.3

Group B

Mean Value
Post
CXL + SD

Range

6
6
6
6

46.151.3
42.550.6
48.459.2
49.461.7

0.057
0.021
0.170
0.006

48.8
47.8
54.1
56.2

1.8
2.4
3.0
2.7

The mean central pachymetry (ultrasonic) decreased


from 447.53 6 33.35 to 383.07 6 58.53 mm at 12 months
of follow-up in group A. A decrease of 70 mm was seen in the
mean thinnest (orbscan) pachymetry, which changed from
430.13 6 30.28 mm preoperatively to 360.87 6 57.03 mm at
the end of 12 months. The mean central ultrasonic pachymetry
in group B decreased from 414.5 6 16.89 to 346.05 6 23.89
mm at 12 months of follow-up. A decrease of 54 mm was seen
in the mean thinnest (orbscan) pachymetry, which changed
from 404.8 6 9.22 mm preoperatively to 350.14 6 32.12 mm
at the end of 12 months. The change in the pachymetry values
was found to be statistically signicant at all follow-up visits in
both groups with a P value of 0.001 (Fig. 3).
The mean preoperative specular count in group A was
2883.67 6 172 cells per square millimeter, and in group B, it
was 2878 6 162 cells per square millimeter. The specular
count at 1 year in group A was 2888.60 6 168 cells per
square millimeter, and in group B, it was 2880 6 162 cells
per square millimeter. The change in the specular count
within each group and between the groups at 12-month post
CXL was not statistically signicant.
In groups A and B, 33.3% and 20% of the patients,
respectively, had mild haze, and 20% of the patients in each
group had moderate stromal haze at 1 week. One patient in
group B developed sterile keratitis postoperatively. However,
at the end of 12 months, no patient in group A had any haze,
and 1 in group B had mild stromal haze because he developed
sterile inltrates post CXL.

Mean Value
Pre
CXL + SD
57.5
55.6
63.5
64.8

6
6
6
6

4.1
3.7
5.2
5.8

Range
53.370
51.163.8
55.677
5878

Mean Value
Post
CXL + SD

Range

6
6
6
6

53.670.2
51.263.5
55.777.2
5878.1

0.686
0.389
0.104
0.968

57.8
56.4
63.8
65.1

4.4
4.1
5.0
5.3

Post CXL, the patients were either given spectacle


correction or tted with contact lens at 3 months. In group
A, 11 patients were prescribed glasses, and 4 were successfully
tted with contact lenses. In group B, 8 patients were
prescribed glasses, and 7 were successfully tted with contact
lenses. Rigid gas permeable lenses were the most common type
of contact lenses prescribed. However, 2 patients in group B
were tted with customized Rose-K lenses. No patient lost any
lines on the Snellen chart during the 1-year follow-up.

DISCUSSION
Since the advent of CXL in 1996, there has been
a marked increase in the prominence of corneal CXL as
a treatment strategy for progressive keratoconus. Crosslinking
is thought to biomechanically strengthen the corneal stroma
by enhancing the covalent bonds between collagen brils,
thus slowing down the progression of keratoconus. There
have been many reports suggesting a consistent stabilizing
effect of CXL and a variable improvement in corneal shape
and visual functions in some patients.10,11
The reported results have been less than uniform. This
is because of the variability in the rate of progression of
keratoconus and variable study plans.2,8,1216 A study conducted by Vinciguerra et al12 reports an improvement in the
UCVA and the best spectacle-corrected visual acuity at 2
years post CXL in progressive advanced keratoconus. However, the pre CXL parameters of keratoconic eyes in the study

FIGURE 3. Timeline charts showing the trends of the mean central (ultrasonic pachymetry) and thinnest pachymetry (Orbscan)
pre and post CXL in patients with central K # 53 D (group A) and .53 D (group B).

1362

| www.corneajrnl.com

2013 Lippincott Williams & Wilkins

Cornea  Volume 32, Number 10, October 2013

do not qualify the patients to be in advanced stage III keratoconus as per the AmslerKrumeich classication. In a later
study, they have further reported the benecial effects of
CXL with improvement in the UCVA and the best spectaclecorrected visual acuity in patients with progressive keratoconus
and age ranging up to 18 years.13
A preoperative maximum K reading of ,58.0 D8 has
been proposed to reduce the failure rate (Failure being dened
as an increase in the maximum K reading of .1 D over the
preoperative value) to ,3%. However, there were only 3
cases with a maximum K reading of .58 D in this study.
To the best of our knowledge, there are no efcacy results
reported for CXL with respect to the stage of keratectasia. A
study was therefore designed to compare the efcacy of CXL
between early and advanced keratoconus.
The mean age of patients with keratoconus undergoing
CXL in this study was 20 6 8 years. This implies early onset
and a more severe form of keratoconus in the second decade
of life in this part of the subcontinent.
The UCVA and BCVA have been reported to improve
with or without a change in topographic parameters
post CXL.2,1618 In our study, the mean UCVA and BCVA
improved signicantly postoperatively at 1 year in patients
with early keratoconus, whereas in advanced keratoconus,
they did not change signicantly. There was an improvement
in the UCVA by 2 Snellen lines and by 1 Snellen line in the
BCVA in patients with early keratoconus only. The improvement in the visual acuity in Group A could be attributed to the
attening of the corneal curvature. The patients in both
groups could be visually rehabilitated with spectacles and
contact lenses. Although the BCVA pre and post CXL in
patients with advanced keratoconus remained less changed,
there was an improvement in the contact lens tting and
tolerance to contact lenses.
The reported changes in manifest refraction have been
0.40,14 1.43,2 and 2.2 D.15 In this study, the mean improvement
in the manifest sphere at 12 months post CXL was 0.61 D in
patients with early keratoconus and 0.68 D in patients with
advanced disease. The change was found to be statistically
signicant in both groups and could be caused by the attening
of the anterior corneal curvature in group A. In group B, the
reduction in the manifest sphere could be because of some
complex changes in the corneal optical contour and possibly
because of a better homogenization of the corneal surface as
a result of increased rigidity. However, the change in the spherical correction may not necessarily accompany the changes in
topographical parameters.9,16,19,20
There was maximum improvement in the mean apical
K and mean at K in patients with early keratoconus at 1-year
follow-up. Neither of these topographic parameters improved
or worsened signicantly in patients with advanced keratoconus post CXL at 1 year. The changes in the corneal
curvature measured on topography were more signicant in
early and moderate stages of the disease when compared with
that in an advanced stage of keratoconus. This implies that
advanced keratoconus might be less responsive to CXL.
There was a attening of the anterior oat in patients
with early keratoconus by a mean value of 0.004 mm, which
was statistically signicant, whereas the same value
2013 Lippincott Williams & Wilkins

A Comparative Analysis

changed by only 0.001 mm in advanced keratoconus, which


was not statistically signicant. Flattening of the anterior
oat in less advanced cases post CXL could be because of
less preoperative irregularity responding more to CXL than
in the advanced cases of keratoconus. There was however
no further increase in the anterior oat in advanced cases
indicating stabilization 1-year post CXL. To the best of our
knowledge, the effect of CXL on the anterior oat has not
been reported previously. The posterior oat changes in our
study were highly variable with a wide standard deviation
and were considered highly unreliable for commenting. The
posterior oat in the present series was .0.060 mm at the
time of enrollment and studies reporting a signicant
change in the posterior oat had pre CXL posterior oat
of ,0.060 mm.16,20 Hashemi et al16 have reported a significant reduction in the posterior oat only at 5 years of post
CXL follow-up.
The mean central and thinnest pachymetry however
followed a similar trend in both groups decreasing at
1-month post CXL. Greater compactness of collagen
lamellae immediately post CXL leads to a decrease in the
corneal thickness, which tends to improve with further time,
probably because of the production of new proteoglycans
by keratocytes.
This study highlights the benecial effect of CXL in
keratoconus in stablilzing the disease in early and advanced
keratoconus. However, the efcacy in the attening of the cornea
was signicantly more with an average central K # 53 D compared with that in patients with an average central K . 53 D.
CXL may be recommended in early keratoconus for the stabilization of disease and additional benecial improvement in the
BCVA and attening of corneal topographic parameters. However, the effect of CXL on the stabilization of keratoconus in this
study has been studied over a follow-up period of 1 year only,
and it would be more benecial to study the long-term effect of
CXL in keratoconus.
REFERENCES
1. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42:297319.
2. Caporossi A, Biaocchi S, Mazzota C, et al. Parasurgical therapy for
keratoconus by riboavin-ultraviolet type A rays induced cross-linking
of corneal collagen: preliminary refractive results in an Italian Study.
J Cataract Refract Surg. 2006;32:837845.
3. Betta AM, Mitchell GL, Zadnik K. Visual performance and comfort with
Rose K lens for keratoconus. Optom Vis Sci. 2002;79:493501.
4. Brierly SC, Izquierdo L, Mannis MJ. Penetrating keratoplasty for keratoconus. Cornea. 2000;19:329332.
5. Doyle SJ, Harper C, Marcyniuk B, et al. Prediction of refractive outcome
in penetrating keratoplasty for keratoconus. Cornea. 1996;15:441445.
6. Kirkness CM, Ficker LA, Steele AD, et al. The success of penetrating
keratoplasty for keratoconus. Eye (Lond). 1990;4(pt 4):673688.
7. Yousef N, Marvrikakis I, Mavrikakis E, et al. Penetrating keratoplasty:
indications over a 10-year period. Br J Ophthalmol. 2004;88:9981001.
8. Koller T, Mrochen M, Seiler T. Complication and failure rates after
corneal crosslinking. J Cataract Refract Surg. 2009;35:13581362.
9. Snibson GR. Collagen cross-linking: a new treatment paradigm in corneal diseasea review. Clin Exp Ophthalmol. 2010;38:141153.
10. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue.
Exp Eye Res. 1998;66:97103.
11. Wollensak G, Spoerl E, Seiler T. Riboavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol.
2003;135:620627.

www.corneajrnl.com |

1363

Cornea  Volume 32, Number 10, October 2013

Arora et al

12. Vinciguerra P, Albe E, Trazza S, et al. Intraoperative and postoperative


effects of corneal collagen cross-linking on progressive keratoconus.
Arch Ophthalmol. 2009;127:12581265.
13. Vinciguerra P, Albe E, Frueh BE, et al. Two-year corneal crosslinking
results in patients younger than 18 years with documented progressive
keratoconus. Am J Ophthalmol. 2012;154:520526.
14. Grewal DS, Brar GS, Jain R, et al. Corneal collagen crosslinking using
riboavin and ultraviolet-A light for keratoconus: one-year analysis using
Scheimpug imaging. J Cataract Refract Surg. 2009;35:425432.
15. Raiskup-Wolf F, Hoyer A, Spoerl E, et al. Collagen crosslinking with
riboavin and ultraviolet-A light in keratoconus: long term results.
J Cataract Refract Surg. 2008;34:796801.
16. Hashemi H, Seyedian MA, Miraftab M, et al. Corneal collagen crosslinking with riboavin and ultraviolet A irradiation for keratoconus:

1364

| www.corneajrnl.com

17.
18.
19.
20.

long-term results. Ophthalmology. 2013. pii: S0161-6420(13)00014-6.


doi: 10.1016/j.ophtha.2013.01.012. [epub ahead of print].
Agrawal VB. Corneal collagen cross-linking with riboavin and ultraviolet
a light for keratoconus: results in Indian eyes. Indian J Ophthalmol. 2009;57:
111114.
Vinciguerra P, Alb E, Trazza S, et al. Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal crosslinking. Ophthalmology. 2009;116:369378.
Hersh PS, Greenstein SA, Fry KL. Corneal collagen crosslinking for
keratoconus and corneal ectasia: one-year results. J Cataract Refract
Surg. 2011;37:149160.
Henriquez MA, Izquierdo L Jr, Bernilla C, et al. Riboavin/ultraviolet A
corneal collagen cross-linking for the treatment of keratoconus: visual
outcomes and Scheimpug analysis. Cornea. 2011;30:281286.

2013 Lippincott Williams & Wilkins

You might also like