|Consensual ophthalmotonic reaction; Intraocular
pressure elevation; Selective laser trabeculoplasty
|Selective laser trabeculoplasty (SLT) has been used as a non-invasive
mean to lower intraocular pressure (IOP). The mechanisms by which
SLT works are thought to be multifaceted. SLT induces minimal
structural changes in the trabecular meshwork  in contrast to argon
laser trabeculoplasty. Therefore, the liberation of humoral factors is
thought to play a significant role in IOP reduction, which was also
observed in animal models involving rabbits [2,3]. There were a few
animal studies to suggest that the chemical components of the aqueous
was modified after SLT [4,5]. There were suggestions that the liberation
of cytokines could trigger the change of IOP in the contralateral
untreated eye through central response, and this is termed consensual
ophthalmotonic reaction (COR). In previous human studies, it was
shown that monocular SLT  and argon laser trabeculoplasty 
resulted in fellow eye IOP reduction. However, COR after
trabeculectomy has a more diverse outcome, with an increase, decrease
or no change in the fellow eye IOP all having been reported [8-10]. In
our study, IOP elevation was demonstrated in the fellow untreated eye
following SLT in rabbits, which, to the best of our knowledge, has not
been reported in the literature.
|Materials and Methods
|A total of 12 blue-purple rabbits of mixed gender, aged 12 months,
weighing 2-3.5 kg with normal ocular examination were included. The
baseline IOP were measured over both eyes by tonoVET tonometer
(iCare, Finland) under local anesthesia (0.4% Benoxil, Santen
Pharmaceutical Co., Ltd, Osaka, Japan). Five IOP readings were taken
each time and the average was used for analysis. The right eye of each
rabbit was subjected to 360° SLT with 532 nm frequency-doubled
green Nd:YAG laser (Laserex Tango, Ellex Medical Pty. Ltd.) via a
gonioscopy laser lens (Ocular Latina SLT Gonio Laser). The settings
were spot size of 400 um, duration of 3 ns, power of 0.5-1.1 mJ, and
100 laser spots over 360°. The IOP over both eyes was measured at 3
hours, 24 hours, 3 days and 7 days after SLT using the same technique
as baseline measurement. All IOP measurements were performed by
the same experienced personnel (CK) at the same time of the day to
reduce the possible effect of circadian rhythm (except at 3 hours). The
study protocol was approved by the Animal Ethics Committee of the
Tianjin Medical University and was conducted conforming to
|Data is presented as mean ± standard deviation. Paired t-test was
used to compare the baseline and post-SLT IOP; and unpaired t-test
was used to compare the difference of IOP between the 2 eyes at
different time points. A p value<0.05 was considered to reflect
|One out of the 12 rabbits demonstrated inflammatory exudation
over the right eye after SLT and was excluded from the study. The IOP
of the remaining 11 rabbits were analyzed. The mean IOP of both eyes
at baseline, 3 hours, 24 hours, 3 days and 7 days are presented in Figure
1. There was no statistical difference in the baseline IOP between the 2
eyes (p=0.78). Following a single session of SLT, right eye IOP was
lower than that of left eye from 3 hours to 7 days, and the difference
was statistically significant from 3 hours to 3 days. The mean IOP of
the treatment eyes were consistently lower than the baseline from 3
hours through 3 days after SLT, although the differences were not
statistically significant. On the contrary, the mean IOP of the untreated
eyes were consistently higher than baseline throughout the study
period (Figure 1). The IOP of the untreated eyes was significantly
higher than baseline at 3 days (p<0.01) and 7 days (p<0.01) (Figure 1),
|Regarding the change in IOP, a reduction in the mean IOP in the
range of 0.85-1.37mmHg compared to the baseline was demonstrated
in the treatment eye from 3 hours to 3 days after SLT (Figure 2).
However, over the untreated left eyes, there was an increase in IOP
demonstrated from 3 hours to 7 days after right eye SLT in the range of
0.71-1.91 mmHg. The effect was more pronounced in the later course
when there was a 23% and 22% increase in mean IOP from the baseline on the 3rd and 7th day respectively, compared to early post-
SLT period (3 hours and 24 hours) (Figure 2).
|IOP is determined by the balance between the amount and rate of
aqueous production and drainage. Both the aqueous production and
the outflow facilities are affected by the humoral and vascular
response, which is in turn governed by the central nervous system.
Therefore, a unilateral change in IOP could lead to a change in IOP of
the contralateral eye. This phenomenon is termed consensual
ophthalmotonic response (COR). COR has been observed in various
animal studies. Intracameral injection of prostaglandin A, E2 and F2a
into one eye was shown to result in delayed IOP rise in both the
treatment eye and the untreated fellow eye, while the miotic effect was
observed in only the treated eye . In another study, a significant rise in aqueous flow was observed in the fellow eye after unilateral
trabeculectomy, suggesting the central influence on aqueous
production in both eyes following unilateral IOP reduction .
|From our results, IOP reduction was observed in the treatment eye
as soon as 3 hours after SLT, and the effect was maintained to 3 days. In
response to the IOP reduction to the treatment eye, an IOP increase in
the fellow eye was seen starting from 3 hours, and the effect lasted till 7
days. This suggested that either IOP reduction in the treated eyes or
SLT itself might trigger an almost immediate IOP elevation effect on
the fellow eyes. Such immediate effect could possibly be regulated by
humoral, vascular and neuronal response, mediated by central system.
The IOP elevation over the untreated eyes was the most pronounced on the 3rd day, which might suggest the IOP regulatory system took
time to reach a maximal response.
|Despite the IOP reduction effect was lost after the 3rd day over the
treatment eyes, the IOP elevation of the untreated eyes was maintained
through the 7th days. We hypothesize that there was modification in
the microscopic structure of the untreated eyes which might involve
the ciliary body for aqueous production or the trabecular meshwork
for aqueous outflow, to maintain the IOP elevation effect of the
untreated eye. However, this hypothesis would need further analysis of
the anatomical structure of the IOP-controlling facilities to confirm. In
fact, we could see that the IOP elevation in the untreated eyes was even
more prominent than the IOP reduction in the treatment eyes from 24
hours to 7 days. Further analysis on this phenomenon would be
essential because this might propose a deleterious effect if this happens
in human eyes, where the fellow eye IOP might be dangerously
elevated in patients receiving unilateral SLT. After 7 days, the IOP
lowering effect of SLT was lost in the treated eyes, and the IOP
elevation of the fellow eyes was less pronounced than on the 3rd day.
One of our hypothesis was that the significantly elevated IOP in the
untreated eyes could lead to an auto-regulatory response such that the
IOP of both eyes returned to the baseline. However, we could only
confirm this observation with more IOP measurements between the
3rd and 7th days, as well as beyond the 7th day.
|Rhodes et al. had previously demonstrated in human subjects 
that the fellow untreated eye showed an IOP reduction following
unilateral SLT, which differs from our findings. However, their results
could have been confounded by improved glaucoma medication
following laser treatment, or even systemic absorption of glaucoma
medications. These confounding factors are eliminated in our study.
|Limitations of our study include a small sample size. Also, the
degree of IOP elevation in the fellow eye was rather small (1.91 mmHg and 1.86 mmHg). This could be due to the low baseline IOP (8.27
mmHg) in our rabbits. In future studies, animals with higher baseline
IOP could be used to evaluate the IOP response. Furthermore, as our
animal sampling represent healthy eyes, whether the same effect and
degree of IOP change will be observed in glaucomatous eyes would
need to be evaluated in future studies.
|In conclusion, we observed an IOP reduction after SLT in rabbit
eyes from 3 hours after the procedure. The untreated fellow eyes also
demonstrated an elevation of IOP which persisted till 7 days post laser.
This suggests there is a regulatory system governing the IOP of both
eyes despite treatment on unilateral eye. This possibility of significant
IOP elevation in the fellow untreated eye after unilateral SLT has
significant clinical implications, especially if SLT is performed
unilaterally, and the fellow eye has underlying glaucoma. Further
studies on the exact mechanisms and the risk factors (such as the
power of SLT, number of repeats of SLT and the type of glaucoma) of
the fellow eye IOP elevation would be warranted. To our best
knowledge, this is the first animal study looking into the effects of
unilateral SLT on the IOP profile over both eyes. This is also the first
study which demonstrated an elevation of IOP in the untreated fellow
eye following unilateral SLT.
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