RESEARCH ARTICLE

Corneal Transplantation in Disease Affecting

Only One Eye: Does It Make a Difference to
Habitual Binocular Viewing?
1,2 1,2 1,3
Praveen K. Bandela , PremNandhini Satgunam , Prashant Garg , Shrikant
1,2
R. Bharadwaj *
1 Prof. Brien Holden Eye Research Centre, Hyderabad Eye Research Foundation, L V Prasad Eye
Institute, Hyderabad 500034 Telangana, India, 2 Bausch and Lomb School of Optometry, L V Prasad Eye
Institute, Hyderabad 500034 Telangana, India, 3 Cornea and Anterior Segment Services, L V Prasad Eye
Institute, Hyderabad 500034 Telangana, India

* bharadwaj@[Link]

Abstract
OPEN ACCESS

Citation: Bandela PK, Satgunam P, Garg P, Background

Bharadwaj SR (2016) Corneal Transplantation in
Disease Affecting Only One Eye: Does It Make a Clarity of the transplanted tissue and restoration of visual acuity are the two primary metrics
Difference to Habitual Binocular Viewing? PLoS ONE for evaluating the success of corneal transplantation. Participation of the transplanted eye
11(3): e0150118. doi:10.1371/[Link].0150118
in habitual binocular viewing is seldom evaluated post-operatively. In unilateral corneal dis-
Editor: Deepak Shukla, University of Illinois at ease, the transplanted eye may remain functionally inactive during binocular viewing due to
Chicago, UNITED STATES
its suboptimal visual acuity and poor image quality, vis--vis the healthy fellow eye.
Received: November 2, 2015

Accepted: February 9, 2016

Published: March 3, 2016

Methods and Findings
This study prospectively quantified the contribution of the transplanted eye towards habitual
Copyright: 2016 Bandela et al. This is an open
access article distributed under the terms of the binocular viewing in 25 cases with unilateral transplants [40yrs (IQR: 3242yrs) and 25 age-
Creative Commons Attribution License, which permits matched controls [30yrs (2537yrs)]. Binocular functions including visual field extent, high-
unrestricted use, distribution, and reproduction in any contrast logMAR acuity, suppression threshold and stereoacuity were assessed using stan-
medium, provided the original author and source are
credited.
dard psychophysical paradigms. Optical quality of all eyes was determined from wavefront
aberrometry measurements.
Data Availability Statement: Data may compromise
the privacy of study participants and may not be
Binocular visual field expanded by a median 21% (IQR: 1829%) compared to the mon-
shared publicly. Data are available upon request to ocular field of cases and controls (p = 0.63). Binocular logMAR acuity [0.0 (0.00.0)] almost
the authors. always followed the fellow eyes acuity [0.00 (0.00 -0.02)] (r = 0.82), independent of the
Funding: This study was supported by a grant transplanted eyes acuity [0.34 (0.20.5)] (r = 0.04). Suppression threshold and stereoacuity
from the Cognitive Science Research Initiative were poorer in cases [30.1% (13.544.3%); 620.8arc sec (370.3988.2arc sec)] than in
(CSRI), Department of Science and Technology,
controls [79% (63.5100%); 16.3arc sec (10.625.5arc sec)] (p<0.001). Higher-order wave-
Govt. of India to SRB [SR/CSRI/189/2013 (G)] and
a core grant from the Champalimaud Foundation, front aberrations of the transplanted eye [0.34 (0.210.51)] were higher than the fellow
Portugal to the Prof. Brien Holden Eye Research eye [0.07 (0.050.11)] (p<0.001) and their reduction with RGP contact lenses [0.09
Centre, Hyderabad Eye Research Foundation. The (0.080.12)] significantly improved the suppression threshold [65% (5072%)] and
authors have no proprietary or commercial interest
stereoacuity [56.6arc sec (47.7181.6arc sec)] (p<0.001).
in any materials discussed in this article. The
funders had

PLOS ONE | DOI:10.1371/[Link].0150118 March 3, 2016 1 / 12

 Corneal Transplantation and Its Benefit to Binocular Functional Vision

no role in study design, data collection and

Conclusions
analysis, decision to publish, or preparation of the
manuscript. In unilateral corneal disease, the transplanted eye does participate in gross binocular view-
Competing Interests: The authors have declared ing but offers limited support to fine levels of binocularity. Improvement in the transplanted
that no competing interests exist. eyes optics enhances its participation in binocular viewing. Current metrics of this treatment
success can expand to include measures of binocularity to assess the functional benefit of
the transplantation process in unilateral corneal disease.

Introduction
Corneal opacity is a leading cause of blindness and vision impairment worldwide[1,2]. Infec-
tions or trauma to one eye are the most common causes of corneal opacity in developing
nations and they are responsible for about 1.5 to 2 million new cases every year [3]. Vision
res- toration following corneal blindness involves surgically replacing the diseased tissue with
a healthy and clear cornea from a donor [3]. This procedurepenetrating keratoplasty
remains the gold-standard treatment even as newer surgical procedures are evolving to
transplant only parts of diseased cornea for vision restoration (e.g. Descemets Stripping
Endothelial Kerato- plasty [DSEK] for corneal endothelial disease[4]).
The success of penetrating keratoplasty is to-date evaluated on the post-operative clarity of
the transplanted tissue and the restoration of monocular high-contrast visual acuity in the
transplanted eye [5,6]. Successful transplantation also improves the quality of life of these
indi- viduals, with the improvement being understandably greater in bilateral than unilateral
trans- plants [7,8]. While these are perfectly acceptable metrics for evaluating the outcomes of
transplantation, they do not measure the transplanted eyes participation in habitual viewing.
Habitual viewing is a binocular process and many visual functions (e.g. fine depth perception)
are crucially dependent on the matching of corresponding features in the two eyes [9]. Such
binocular functions that require active participation of the transplanted eye are seldom evalu-
ated post-operatively.
Despite anatomical clarity, the transplanted eye may be optically severely degraded due to
irregular astigmatism (~3.2D after 1-yearof surgery [10,11]) and higher-order wavefront aber-
rations (HOAs; about six times greater in the transplanted eye than in age-matched controls
[12,13,14]) that arise post-operatively. Individuals undergoing transplantation for unilateral
corneal disease may therefore experience a large interocular difference in image quality, with
the transplanted eyes image quality being significantly inferior to that of the healthy fellow
eye. Previous studies examining the impact of induced interocular differences in image
quality all report that binocular visual functions such as stereoacuity [15] and binocular
summation [16] may be significantly deteriorated while other spatial visual functions may be
biased towards the eye providing better image quality (e.g. binocular logMAR acuity
[17,18,19]).
Overall, the eye experiencing the poor image quality may not actively participate in the
binocu- lar viewing process. While some of the interocular differences in image quality
following uni- lateral corneal transplantation may be corrected with sphero-cylindrical
spectacles, those arising from HOAs remain uncorrected with conventional spectacles. Given
this, to what extent does the transplanted eye participate in habitual binocular viewing of those
undergoing unilateral corneal transplantation? Also, how does the optical quality of the
transplanted eye influence its participation in functional binocular vision and does an
improvement in the eyes optical quality produce a commensurate improvement in binocular
vision? Overall, what is the functional utility of transplantation in unilateral corneal disease?
Answers to these questions
are unknown even while they have important implications for utilization of donor corneas
Table 1. Demographic details of the cases and controls who participated in this study.
Variable Cases Median (IQR) Controls Median (IQR) p value
Total Number 25 25
Age (years) 40 (3242) 30 (2537) 0.06
Duration between trauma and surgery (months) 4.06 (0.9312.25) NA
Duration between surgery and present investigation (months) 16.9 (9.233.3) NA
M (D) -0.75 (-3.210.06) 0.00D (-0.370.00) 0.22
J0 (D) 0.00 (-0.750.79) 0.00 (0.000.00) 0.91
J45 (D) -0.18 (-1.550.36) 0.00 (0.000.00) 0.13
doi:10.1371/[Link].0150118.t001

available for transplantation and for managing patients expectations about functional vision
restoration post-operatively. To the best of our knowledge, questions of similar nature have
been addressed by only one study in the past for individuals undergoing bilateral corneal
trans- plantation [20].

Materials and Methods

Two experiments were conducted in this study. The first experiment evaluated the participa-
tion of transplanted eye in a range of binocular visual functions in 25 patients (cases) [median
age: 40yrs (Inter Quartile Range (IQR): 3242yrs)] and compared these with 25 age-matched
controls with normal binocular vision [30yrs (2537yrs)] (Table 1). Cases underwent corneal
transplantation for the following reasons: microbial keratitis (n = 17), corneal scar from
trauma (n = 7) and pseudophakic bullous keratopathy (n = 1). All the transplanted donor
corneas were obtained from L V Prasad Eye Institutes Ramayamma International Eye bank,
Hyderabad. Eye bank procedures including consent from the relatives of the deceased donors
retrieval and stor- age of the donor corneas were done as per the standard operating
procedures of the eye bank.
A second experiment determined the impact of manipulating the transplanted eyes optics
using rigid gas permeable (RGP) contact lenses on binocular visual functions in a subset of 10
cases [38yrs (32.340.8yrs)] that participated in the first experiment. RGP contact lenses have
been used in the past for managing the post-operative refractive error in patients who undergo
corneal transplantation [10,21,22,23]. While these lenses have been shown to effectively
reduce irregular astigmatism, interocular difference in refractive power (anisometropia) and
improve logMAR acuity, very little is known about how they impact HOAs and sensory
binocular
visual performance in these patients [10,21,22,23].
The study adhered to the tenets of the Declaration of Helsinki and was approved by the
Institutional Review Board of L V Prasad Eye Institute (LVPEI), Hyderabad, India. All subjects
participated after signing a written informed consent form. The inclusion criteria for enrolling
cases in the study were: a) Cornea transplantation procedure in one eye only and the fellow
eye being free of any ocular pathology; 2) postoperative follow-up of at least 3 monthsthe
th th
median (25 75 IQR) follow-up duration was 16.9 (9.233.3) months between surgery and
the pres- ent investigation (Table 1); 3) Clear transplanted cornea and 4) absence of co-
morbidity that would affect the visual functions of the operated eye (e.g. glaucoma, iris
synechiae, etc). Cases with unstable refraction in previous follow-ups or with any manifest eye
deviation that affected binocularity were excluded. Standard clinical management was
followed in all cases, with no influence of the study on their care. Controls were students and
staff of LVPEI with normal binocular vision.
Wavefront aberrations were measured using the Imagine Eyes irx3 wavefront aberrometer
([Link]
[Link])
three times in each eye for 3mm pupil diameter and averaged [24]. All measurements were
made with the subjects natural pupil size and accommodative state in order to mimic habitual
viewing conditions. Subjects were fixated at optical infinity using the aberrometers target
presentation channel during these measurements. The wavefront aberrations were then scaled
to the 3mm pupil diameter for all subjects using algorithms previously developed and
described for this pur- pose [25]. The eyes optical quality was described in terms of the overall
rd th
root mean squared devia- tion of the 3 to 8 order wavefront aberration terms (HORMS).
Wavefront aberrations could not be obtained on one case and one control due to small pupils
(~2mm) and on 2 cases for unknown reasons.
Monocular and binocular visual fields, high contrast logMAR acuity, suppression threshold
and stereoacuity were measured on each subject with their best-corrected sphero-cylindrical
correction. For cases, performance of the fellow healthy eye was always evaluated first
followed by that of the transplanted eye and then binocular performance in order to maximize
task learning. The order of testing was randomized for controls. Kinetic perimetry (Humphrey
Visual Field Analyzer II, Carl Zeiss, Dublin) was performed to determine the subjects monocu-
lar and binocular visual fields [26]. Maximum of 150 of horizontal and 110 of vertical visual
fields were measured in 12 discrete meridians, interpolated using a spline algorithm, and the
area under this curve calculated using custom MATLAB1 software. The ratio of binocular to
monocular visual field area was calculated for all subjects, with a value >1 indicating an expan-
sion of the binocular visual field relative to its monocular counterparts [27]. For cases, the ratio
of binocular to healthy fellow eyes visual field area was calculated and a value of unity indi-
cated that the transplanted eye did not contribute to the expansion of binocular visual field.
Monocular visual field area of one eye was chosen randomly in controls for this ratio calcula-
tion. Four cases could not perform the kinetic perimetry test while all controls performed this
task successfully.
Monocular and binocular high-contrast (98%) logMAR acuity of all subjects was deter-
mined at 3m using COMPlog1 ([Link] [28]. A series of 5 Sloan
optotypes were randomly displayed and their angular subtense decreased using a staircase
thresholding algorithm until 3 out of 5 optotypes were incorrectly identified. LogMAR acuity
was recorded as the number of optotypes correctly identified at termination, with 0.02
logMAR units allotted per optotype [28]. All cases and controls performed this task
successfully.
Suppression threshold was determined at 40cm with the subjects best-corrected distance
and near refractive correction using a dichoptic motion coherence threshold task designed
pre- viously for subjects with amblyopia [29,30]. The task involves detecting the direction of
coher- ent motion of a field of signal dots from a field of randomly moving noise dots. A
binocular threshold is first estimated as the minimum number of signal dots required in the
two eyes to detect binocular coherent motion. This value is then used to determine the
magnitude of sup- pression by dichoptically presenting the coherently moving signal dots to
the affected eye (i.e. amblyopic eye in the previous studies [29,30] and transplanted eye in this
study) and randomly moving noise dots to the fellow eye. The contrast of signal dots is
maintained at ~100% while the contrast of noise dots is varied in a staircase manner until
coherent motion perception is abolished. This contrast threshold provides a quantitative
estimate of suppression of the affected eyelower the contrast of the noise dots, greater is the
magnitude of suppression of
the affected eye [29,30]. In controls, the noise dots were presented randomly to either eye as
there was no expectation of one eye being weaker than the other (ocular dominance status
of controls was not determined here). Five cases could not complete this task while all
controls performed this task successfully.
Stereoacuity was measured thrice using a custom-designed Howard Dolman apparatus
where subjects aligned two thin rods presented in depth against a monocular-depth-cue-
free
background [9,31]. One rod was moved back and forth in a motorized fashion, relative the
other, until the subjects perceived both rods to be at the same depth plane. Axial separation
between the two rods provided a measure of the subjects stereoacuity [9,31].
Measurements were usually made at 3m but they were shifted to 1m if subjects were unable
to perform the task at 3m. Between 1 and 3m, this set up produced disparities from 1.5 to
2263arcsec for
60mm IPD (variations in IPD of a few millimeters producing an inconsequential 56arc
sec change in disparity values [9]). All cases and controls performed this task successfully.
All aforementioned outcome variables (except visual fields whose outcomes on cases were
at par with controlssee results) were re-measured in a subset of 10 cases after 30min of
adap- tation to a customized RGP contact lens fitted to the transplanted eye. Subjects wore
CLAS- SIC1 or Purecon1 RGP lenses, both of which are commonly available for clinical
use in India. Residual refractive error obtained over the contact lenses was corrected with
spectacles during data collection.

Results
Table 1 shows the demographic details and the power vector representation of sphero-
cylindri- cal refractive error of all controls and cases [32]. Since most outcomes variables
obtained here did not follow a normal distribution (Shapiro-Wilk normality test), non-
parametric statistics were used for data analyses.
HORMS of the transplanted eye [0.34 (0.210.51)] was significantly greater than that of
the fellow healthy eye [0.07 (0.050.11)] of cases (Mann-Whitney U = 56; n = 46; p<0.001)
while they were similar to each other in the right and left eyes of controls [both eyes: 0.05
(0.050.08)] (p = 0.4) (Fig 1A). Interocular difference in HORMS was also greater in cases
[0.25 (0.140.48)] than in controls [0.00 (-0.020.01)] (U = 37.5; n = 46; p<0.001)
(Fig 1C).
The area occupied by the binocular visual field of both cases and controls was larger than
the area occupied by the individual eyes visual field (Fig 2A and 2B). Temporal crescents in
the visual field were evident in the data of every subject that participated in the study (Fig 2A
and 2B). The median ratio of binocular to monocular visual field area was 1.21 (1.181.29) in
cases and 1.20 (1.141.25) in controls, indicating that there was a median increase in the binoc-
ular visual field area of 21% and 20% in cases and controls, respectively, vis--vis, their respec-
tive monocular visual field area (U = 127; n = 36; p = 0.3) (Fig 2C). The transplanted eye of
cases indeed therefore contributed to an expansion of the binocular visual field, with the mag-
nitude of expansion being very similar to those of healthy controls [33].
Median best-spectacle corrected monocular logMAR acuity of the transplanted eye
[0.34 (0.20.5)] was significantly poorer than that of the fellow eye [0.00 (0.00 -0.02)] (U
= 20.5;
n = 50; p<0.001) and to that of controls [monocular: -0.12 (-0.180.00); binocular: -0.08 (-0.2
0.00)] (U = 14; n = 50; p<0.001) (Fig 3). Interocular difference in logMAR acuity of cases and
controls was -0.3 (-0.6 -0.2) and -0.04 (-0.120.00), respectively (U = 166; n = 50; p = 0.004).
Binocular logMAR acuity of cases [0.00 (0.000.00)] was similar to the logMAR acuity of
fellow eye (U = 282; n = 50; p = 0.5), with a Spearmans rank correlation of 0.82 (p<0.001)
(Fig 3A
and 3C). Binocular logMAR acuity was poorly correlated with the transplanted eyes acuity
(r = 0.04; p = 0.83) (Fig 3C). Binocular spatial resolution of cases was therefore largely
defined by the healthy eyes resolution, with little influence of the transplanted eye. A
multiple regres- sion analysis indicated that, other than the best-corrected logMAR acuity of
healthy fellow eye (p<0.001), other variables including the subjects age, duration of the
trauma, best corrected logMAR acuity and HORMS of transplanted eye, fellow eye and
interocular difference in HORMS did not have any impact on the binocular acuity of cases
(p>0.37).
Fig 1. Box and Whisker plot of the RMS deviation of higher-order wavefront aberrations (HORMS) measured for 3mm pupil diameter for cases (panel A)
and controls (panel B) that participated in this study. Panel C: The interocular difference in HORMS for cases and controls that participated in this study. The
solid horizontal line within the box indicates median value, lower and upper edges of the box indicate the 25th and 75thinterquartile range (IQR), lower and
st th
upper whiskers show the 1 and 99 quartiles and plus symbols indicate outliers.
doi:10.1371/[Link].0150118.g001

The median binocular threshold was similar in both cases [26.7% (21.635.75%)] and con-
trols [24.8% (17.227.2%)] (U = 189; n = 46; p = 0.16) (Fig 4A). This result is somewhat
expected, for the signal and noise dots were both presented binocularly in this paradigm and,
much like logMAR acuity, the binocular threshold may also be determined largely by the
fellow eye of cases (Fig 4A). The median contrast threshold was significantly lower in cases
[28.6% (14.545.2%)] than in controls [77% (62100%)] (U = 42; n = 45; p<0.001) (Fig 4B),
indicating that coherent motion perception could be abolished in cases with only 28.6% of
median con- trast in the healthy eye while it required up to 77% of median contrast in one eye
to abolish coherent motion perception in controls. These results may be interpreted to indicate
that the magnitude of suppression of the transplanted eye of cases was significantly greater
than the magnitude of suppression of one random eye of controls.
The results of stereoacuity largely followed the expectations of the contrast threshold
results, with the median stereoacuity of cases [620arc sec (370988arc sec)] being
significantly poorer
than that of controls [16.3arc sec (11.322.4arc sec)] (U = 45.5; n = 50; p<0.001) (Fig 4C).
Dispar- ity-based depth detection was therefore significantly impaired following unilateral
corneal trans- plantation, vis--vis, age-matched healthy controls. A second multiple regression
analysis
indicated that the patients age, duration of the trauma, best corrected HCVA, HORMS and the
contrast and binocular thresholds did not significant impact on the stereoacuity of cases
(p>0.31).
The median HORMS decreased significantly from 0.27 (0.190.49) without contact lens
to 0.09 (0.080.12) with RGP contact lens wear (Wilcoxon Sign rank test Z = -2.52; n =
17; p = 0.01) (Fig 5A). The median interocular difference in HORMS also decreased from
0.22
Fig 2. Binocular and monocular visual field of a representative case (panel A) and control (panel B) who participated in this study. Ratio of binocular
to monocular visual field area in cases and controls (panel C). Details of Box and Whisker plot same as Fig 1.
doi:10.1371/[Link].0150118.g002

(0.130.42) without contact lens to 0.05 (0.020.07) with contact lens wear (Z = -2.52;
n = 17; p = 0.01) (Fig 5A). The median best-corrected logMAR acuity of the transplanted eye
also improved from 0.25 (0.110.35) with spectacles to 0.11 (0.030.17) with contact lens wear
(Z = -2.4; n = 20; p = 0.01). Median binocular logMAR acuity did not show any significant
improvement [spectacles: -0.01(-0.140.04); contact lens: -0.05 (-0.09 -0.02); p = 0.4], as
binocular acuity appeared to be largely defined by the healthy eyes acuity that was not
manipu- lated during this experiment (Fig 5B). The contrast threshold of cases in the motion
coherence task increased from 33.5% (1353%) with spectacle wear to 65% (7250%) with
contact lens

Fig 3. Monocular and binocular high-contrast logMAR acuity of cases (panel A) and controls (panel B) that participated in this study. Details of Box and
Whisker plot same as Fig 1. Scatter diagram of monocular logMAR acuity of cases from the transplanted eye and the healthy fellow eye plotted against
their corresponding binocular logMAR acuity (panel C). Correlation coefficient between binocular and the respective monocular logMAR acuities are shown
in parenthesis in this panel.
doi:10.1371/[Link].0150118.g003
Fig 4. Binocular threshold (panel A), contrast threshold (panel B) and stereoacuity (panel C) of cases and controls that participated in this study. Details of
Box and Whisker plot same as Fig 1.
doi:10.1371/[Link].0150118.g004

Fig 5. HORMS (panel A), high-contrast logMAR acuity (panel B), binocular thresholds (BT) and contrast thresholds (CT) (panel C) and stereoacuity (panel
D) obtained with and without RGP contact lens in the second experiment of this study. Details of Box and Whisker plot same as Fig 1.
doi:10.1371/[Link].0150118.g005
wear (Z = -2.1; n = 17; p = 0.02), even while there was no change in the binocular threshold
val- ues in these subjects [both: ~25.2% (21.726.35%)] (Fig 5C). The higher contrast required
in
the fellow eye to abolish coherent motion perception of the transplanted eye suggested that the
magnitude of suppression in the latter decreased following contact lens wear. Median stereoa-
cuity improved from 662.3arcsec (417.5944.6arc sec) with spectacles to 56.6arc sec (47.68
181.6arc sec) with contact lenses (Z = -2.8; n = 20; p = 0.005) (Fig 5D).

Discussion
The results of this study indicate that the transplanted eye of individuals undergoing penetrat-
ing keratoplasty for unilateral corneal disease participates in gross binocular visual functions
(visual field expansion) but offers limited support to fine levels of binocularity (stereoacuity)
(Figs 24). These individuals may therefore experience greater levels of peripheral visual
aware- ness following surgery due to the expanded visual field but they may not benefit a great
deal for binocular visual resolution or stereoacuity. These individuals may remain functionally
monoc- ular even after transplantation and may continue to use only their healthy fellow eye
for all functional vision tasks like reading, watching television, etc. They may also rely more
on mon- ocular cues provided by their healthy fellow eye to obtain depth information as
disparity pro- cessing is significantly impaired and the transplanted eye appears to be on the
th th
verge of suppression (Fig 4B and 4C). The median (25 75 IQR) follow-up duration between
the cor- neal transplantation and the present investigation was 16.9 (9.233.3) months in all
cases
(Table 1), suggesting that the results reported here represent fairly well-established measures
of visual performance and not a transient behavior when the eye was in a state of flux after
surgery (e.g. during the corneal wound healing process).
The optical quality of the transplanted eye appears to play a crucial role in determining
the extent of its participation in the habitual binocular viewing process. As observed in
previous studies[12,13,14], the transplanted eye remained optically inferior to the healthy
fellow eye because of greater magnitudes of uncorrected HOAs (Fig 1). An improvement in
the trans- planted eyes optical quality and a reduction in the difference in optical quality
between the transplanted and healthy fellow eye produces a commensurate improvement in
the fine levels of binocularity (Fig 5). The intersubject variability of HOAs and stereoacuity
also reduced
with RGP contact lens wear, suggesting that the optical quality and visual performance became
more homogenous when the aberrated donor cornea was replaced with a more uniform RGP
contact lens surface (Fig 5A & 5D). As expected, gross tasks such a visual field expansion that
were already up to mark with spectacles and monocular spatial vision tasks like logMAR
acuity that were biased towards the healthy fellow eye remained unchanged with an
improvement in the optics of the transplanted eyes (Fig 5B). The metrics of evaluating the
corneal transplanta- tion procedure that are currently centered around the anatomical health
and acuity of the transplanted eye can now be expanded to include measures of the
transplanted eyes optical quality and the level of binocularity restored in order to assess the
functional benefit of trans- plantation in patients with unilateral corneal disease. Overall,
physicians will have to pay atten- tion to assessing and improving image quality in post
transplant eyes in order to provide full benefit of binocular vision to the patient. The steps in
this could include improved surgical technique to ensure superior corneal topography,
postoperative modifications or use of corneal topography correcting contact lenses [4].
The results of logMAR visual acuity, suppression thresholds and stereoacuity obtained in
this study are all somewhat expected from previous knowledge of how the visual system
han- dles inter-ocular differences in image quality. Binocular logMAR visual acuity tends to
follow the acuity of the least ametropic eye in the presence of induced spherical and
astigmatic
anisometropia [17,18,19]. The retinal image that is relatively more blurred is temporarily sup-
pressed and visual resolution is biased towards the fellow eye [18,19,34]. This, in fact, forms
the basis of monovision contact lens correction in presbyopia wherein anisometropia is inten-
tionally induced by wearing a myopic soft contact lens over the non-dominant eye for
focusing at near while the dominant eye is corrected for distance vision [35]. Despite the
persistence of interocular difference in image quality due to HOAs (Fig 1C), binocular
logMAR acuity of cases remained more or less equal to the acuity of their healthy fellow eye
(Fig 2). The input provided by the transplanted eye may be suppressed much like the
monovision scenario and binocular spatial resolution may be optimized by increasing
weightage to the healthy fellow eyes input. The lower contrast thresholds of cases, vis--vis,
controls reflect the increased mag- nitude of suppression of the transplanted eye in the current
study (Fig 4B).
Tasks requiring the matching of corresponding features in the two eyes (e.g. stereoacuity)
tend to deteriorate in the presence of interocular difference in image quality [15,17,36]. Poor
stereoacuity of cases with their best-corrected spectacles and its improvement with RGP con-
tact lens are very much in line with the existing literature (Figs 4C and 5D). Interestingly,
HORMS did not have a significant influence on the stereoacuity of cases in this study. This
may be because of a ceiling effect on stereoacuity caused by the high magnitude of HORMS
in the transplanted eye (median: 0.35; median interocular difference in HORMS: 0.25) (Fig
1). Indeed, the deterioration of other binocular functions like contrast summation and
disparity detectability saturate for interocular difference in HORMS >0.25 [16,37].
Alternatively, the HORMS per se may not have a direct bearing on stereoacuity but its
manifestation in terms of contrast loss or phase shifts in the retinal image may have a greater
influence on stereoacuity [38]. It is also possible that any aniseikonia (interocular difference
in retinal image size) that may be induced by spectacle wear in the transplanted eye may have
caused the stereoacuity loss [15,30,36]. HORMS of the transplanted eye, interocular
difference in HORMS, the associ-
ated contrast loss and phase shifts in the retinal image, interocular difference in logMAR acuity
and aniseikonia all would have reduced with RGP contact lens wear leading to a
commensurate improvement in stereoacuity of these individuals (Fig 5D). A systematic
analysis of the impact of these parameters on stereoacuity is however beyond the scope of the
current study.
This study has three limitations. First, functional participation of the transplanted eye was
assessed only post-operatively and, therefore, the status of binocularity prior to surgery
remains unknown. Given the poor pre-operative visual acuity of these subjects, it is likely
that the pre-operative contribution of the affected eye to binocular visual functions was, at
best, gross. The exact change in binocular visual performance after transplantation may only
be obtained when the pre- and post-operative data of the same subject are compared relative
to each other. Second, the sample size of cases and controls in this study was relatively small
(n = 25) and the cases were selectively chosen to have corneal transplantation as the only
ocular intervention and not associated co-morbidities. This combined with the relatively large
inter-sub- ject variability in the results (see error bars in Figs 14) preclude us from
generalizing the results to the entire pool of patients undergoing transplantation for unilateral
corneal disease. The
results shown here are however still very valid and informative for the controlled cohort of
cases selected for this study. Third, this study was only concerned with the visual functions of
individu- als undergoing corneal transplantation. Other important outcome measures of
treatment such as the post-operative quality of life [7,8], cost-utility ratio of treatment [39],
supply-demand ratio of donor tissue [3] and the risk of morbidity with unilateral vision [40]
were all not evaluated. A comprehensive analysis of all these variables is necessary to make a
final judgment on the utility
of the transplantation procedure in individuals with unilateral corneal disease.
Acknowledgments
The authors thank all the participants of this study. The authors also thank Dr Ben Thompson
for providing us with the software for measuring suppression and Prof Jill Keeffe for
reviewing an earlier version of this manuscript.

Author Contributions
Conceived and designed the experiments: PB PS PG SRB. Performed the experiments: PB.
Analyzed the data: PB SRB. Contributed reagents/materials/analysis tools: PB PG SRB. Wrote
the paper: PB PS PG SRB.

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