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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
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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
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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
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.
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).
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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
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
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).
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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
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17.
18.
19.
20.