Hindawi Publishing Corporation
Journal of Ophthalmology
Volume 2012, Article ID 642869, 5 pages
BaselineFactors Predictiveof SLT Response:
Robin Bruen,1Mark R.Lesk,1,2andPaul Harasymowycz1
1Department of Ophthalmology, University of Montreal, Montreal, QC, Canada
2Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, Canada
Correspondence should be addressed to Paul Harasymowycz, firstname.lastname@example.org
Received 25 February 2012; Accepted 13 May 2012
Academic Editor: Andrew G. Lee
Copyright © 2012 Robin Bruen et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Purpose. To study the response to Selective Laser Trabeculoplasty (SLT) according to baseline medical treatment, angle
pigmentation, age, diagnosis (open-angle glaucoma or ocular hypertension), and baseline intraocular pressure (IOP). Methods.
74 eyes of 74 patients were enrolled in this study. Baseline characteristics were recorded for each patient. IOP in the treated and
fellow eyes was measured at baseline, and 1 month, 6 months, and 12 months following SLT. IOP changes in the different groups
were compared using two-way ANOVA and Pearson’s correlation. Results.Themean age ofour cohortwas 71±10 years. The mean
Higher baseline IOP was highly correlated with greater absolute IOP decrease. Prostaglandin analogue use at baseline was shown
to be associated with a statistically decreased IOP-lowering response following SLT when corrected for baseline IOP. No significant
differences in IOP response were found when comparing groups stratified for age, angle pigmentation, phakic status, gender, or
diagnosis. Discussion. The results of this study confirm the finding that higher baseline IOP is a predictor of greater IOP response
following SLT, and that pretreatment with prostaglandin analogue therapy is associated with a decreased IOP-lowering response
following SLT. The study is limited by the small number of eyes with data available for complete case analysis.
The introduction of selective laser trabeculoplasty (SLT) by
Latina and colleagues in 1995  has provided ophthal-
mologists with an additional modality for the treatment
of open-angle glaucoma (OAG) and ocular hypertension
(OHT). The results of the recent SLT/Med study  support
earlier evidence [3–6] that primary therapy with SLT can
lower intraocular pressure (IOP) as much as certain medical
therapies. In clinical practice, however, SLT is often used as
adjunctive therapy with topical medications.
Latina first examined the interaction between SLT and
different classes of glaucoma medications in 2004  and
found an increased rate of nonresponders among patients
ical glaucoma treatments. Subsequently, three retrospective
case series have addressed the question directly with incon-
sistent findings. Scherer  reported a greater IOP decrease
following SLT in patients on concomitant prostaglandin
analogue therapy, while Singh et al.  did not find any
relationship, and most recently Kara et al.  showed
a decreased response to SLT in patients on prostaglandin
analogue versus timolol and dorzolamide therapy.
Several distinct mechanisms of action have been theo-
rized to cause the decrease in IOP following laser trabeculo-
plasty. The cellular theory holds that the phagocytic activity
of macrophages in response to trabecular meshwork (TM)
damage and cellular necrosis results in a clearing of debris
and improved outflow . The mechanical theory, which
was especially thought to play a role in argon laser trabeculo-
the laser allow better drainage of aqueous humour . A
third theorized mechanism of action for SLT-induced IOP
of proteolytic enzymes, known as matrix metalloproteinases
(MMPs), and their inhibitors, known as tissue inhibitors of
metalloproteinases (TIMPs) [13, 14].
The IOP-lowering mechanisms of prostaglandin ana-
logues have also been extensively studied. They have been
2Journal of Ophthalmology
the trabecular outflow pathways , and their mechanism
of action has also implicated the equilibrium of MMPs
and TIMPs . Commonalities between the IOP-lowering
mechanisms of prostaglandin analogues and SLT have been
demonstrated by in vitro studies by Alvarado and colleagues
, which have shown that both SLT and prostaglandin
analogues induce increased permeability of cultured trabec-
ular meshwork cells via intercellular junction disassembly.
SLT has been shown to decrease IOP not only in the
treated eye, but also in the fellow eye , suggesting that
at least some of the IOP-lowering effect of SLT is based on
cellular or MMP-mediated mechanisms.
This paper presents the results of a prospective non-
randomized interventional cohort study undertaken at our
institution to assess the response to SLT according to
baseline medical treatment, angle pigmentation, age, type of
open-angle glaucoma or ocular hypertension, and baseline
The Research Ethics Board at the University of Mon-
treal approved this prospective, interventional cohort study,
which adhered to the tenets of the declaration of Helsinki.
All patients were recruited from the clinics of two glaucoma
specialists, PH and ML, at the Montreal Glaucoma Institute
and Maisonneuve-Rosemont Hospital. Inclusion criteria
included patients with a diagnosis of either OAG or OHT.
Informed consent was obtained from all participants. In
total, 74 eyes (30 OD 44 OS) of 74 patients were enrolled.
In cases where both eyes were treated with SLT during the
study period, only the left eye was counted. In one case, the
left eye had been previously treated with SLT, so the results
from the right eye were included.
Baseline characteristics of all patients were recorded,
including age, gender, diagnosis (OAG or OHT), baseline
IOP, history of prior ALT treatment, and the number and
the type of medications being taken. In addition, angle
pigmentation was evaluated using standardized photographs
taken at the time of the procedure.
A Coherent Selecta 7000 laser (Coherent, Inc., Palo
Alto, CA) was used to perform SLT over 360 degrees, with
approximately 60 nonoverlapping applications in each eye.
The initial intensity used was 0.8mJ, but the energy was
occasional “champagne bubbles” during the treatment.
IOP was measured in both eyes at baseline, and 1 month,
6 months, and 12 months after SLT treatment. The outcome
measures were change in IOP compared to baseline, and
change in IOP compared to the fellow eye at each time point.
However, if SLT was performed on the fellow eye during
the study period, or if the medical therapy of the fellow eye
changed during the study period, then the data comparing
IOP in the SLT-treated eye to that of the fellow eye was not
included in the analysis.
The data was analyzed using SPSS statistical software
(version 15) using ANOVA for repeated measures, and
Pearson’s correlation. Time was used as a within-factors
effect, and several baseline characteristics were used, one
at a time, as between-factors effects: baseline IOP, age, sex,
degree of angle pigmentation, phakic status, diagnosis (OAG
or OHT), prior argon laser trabeculoplasty (ALT) treatment
status, and type and number of medications.
Given the known diurnal variation in IOP, and assuming
this diurnal variation is similar in both eyes, the analysis
of the effect of the different baseline factors was performed
using both the baseline IOP in the treated eye and the IOP in
the fellow eye at each time point as a control. For the analysis
using baseline IOP in the treated eye as a control, only eyes
with IOP measurements at each time point, or complete case
data, were included. For the analysis using the fellow eye IOP
It was assumed that there was random attrition of the data
The mean age of our subjects subjects was 71 ± 10 years.
Sixty-two patients (83.8%) had a verticalcup-to-disk ratio of
at least 0.7. Mean IOP was 21.5±5mmHg, and patients were
at the onset of the study. Subgroup analysis was performed
on the 42 patients for whom there was complete case data.
In our sample, the mean change in IOP from baseline
in the treated eye at one year was −4.67 ± 3.40 as shown in
Table 1. At every time point, there was a greater mean change
in IOP in the SLT-treated eye from baseline than when this
change was controlled for IOP changes in the fellow eye,
Baseline IOP in the SLT-treated eye was found to be
markedly predictive of IOP change across time in the same
eye, such that eyes with higher baseline IOPs tended to
have greater IOP reduction. Stratifying the eyes according to
baseline IOP percentiles, there was a statistically significant
difference in IOP decrease at the different time points
between groups above and below the 50th percentile of
20mmHg (P < 0.0001) (−6.37±2.94mmHg versus −2.10±
3.10mmHg at one year, for baseline IOP above and below
the 50th percentile, resp.), the 66th percentile of 23mmHg
(P < 0.003) (−7.25 ±3.00 versus −3.37 ±3.16mmHg at one
year for baseline IOP above and below the 66th percentile,
resp.), and the 80th percentile of 25mmHg (P < 0.001)
(−5.44 ± 2.61 versus −1.63 ± 2.57mmHg at one year, for
baseline IOP above and below the 80th percentile, resp.).
This difference in IOP decrease over time of eyes above
or below the given IOP percentiles was also noted when
IOP in the SLT-treated eye was compared to the fellow eye
at the different time points, although the relationship was
less strong and not statistically significant for the 50th and
66th percentile comparisons. For the 50th percentile, the
significance was P < 0.093 (−3.38 ± 2.94 versus −1.29 ±
2.88mmHg at one year for eyes above and below the 50th
P < 0.06(−4.86±2.73versus −1.57±2.65mmHgatoneyear
for eyes above and below the 66th percentile, resp.). For the
80th percentile, the significance was P < 0.03 (−5.44 ± 2.62
Journal of Ophthalmology3
Treated eye versus baseline
at 1 month
Treated eye versus fellow
eye at 1 month
Treated eye versus baseline
at 6 months
Treated eye versus fellow
eye at 6 months
Treated eye versus baseline
at 12 months
Treated eye versus fellow
eye at 12 months
Change compared to contralateral eye 1 month after SLT
Change compared to contralateral eye 6 months after SLT
Change compared to contralateral eye 12 months after SLT
versus −1.74 ± 2.81mmHg at one year for eyes above and
below the 80th percentile, resp.).
A total of 59 eyes (79.7%) from our sample of 74 eyes
received medical treatment with prostaglandin analogues
over the course of the study. Of the 42 patients for
whom complete case data was available, 32 had been on
prostaglandin analogue therapy at the beginning of our
study. Using baseline IOP as a control, there was not a
significant difference in IOP decrease over time between
patients who had been taking prostaglandin analogues
eye IOP as a control, there was a statistically significant
difference in IOP decrease over time between patients who
had been treated with prostaglandin analogues at baseline,
and those who had not been treated with prostaglandin
analogues at baseline.
For this latter analysis, complete case data including IOP
of the fellow eye at each time point was available for 35
patients, 26 of whom had been treated with prostaglandin
analogues prior to SLT. During the study period, medical
therapy was unchanged in 22 out of the 35 patients in
both eyes. Of the 13 patients with some modification of
their medical therapy during the study period, 10 were in
the prostaglandin group, 4 had additional drops added at
1 or 6 months due to inadequate IOP control (all in the
prostaglandin group), 4 had drops temporarily removed
following SLT then restarted at 1 or 6 months, and 5 had
changes to their drops but not to the number of drops,
including 2 who began taking prostaglandin analogues
instead of aqueous suppressants and beta blockers.
No interaction between time and prostaglandin use was
found (P = 0.606). Independently of time, a statistically
significant difference in IOP decrease was found between
eyes pretreated or not with prostaglandin analogues (P =
0.008), as shown in Table 2. This difference in IOP response
to SLT between prostaglandin users and those not using
prostaglandins remained significant even when the IOP
changeovertimewascorrectedforbaselineIOP(P = 0.006),
as displayed in Figure 1.
There were 36 eyes with OAG and 6 eyes with OHT with
complete case data to compare IOP response in the SLT-
There was a trend toward better IOP response in the OHT
group, but this was not significant (P < 0.225). In a similar
analysis, IOP in the SLT-treated eye was compared to IOP in
the fellow eye at each time point. There were 30 eyes with
OAG and 5 eyes with OHT for this analysis, and the results
also showed a trend toward better IOP response at each time
point for the OHT group, but the result was not significant
(P < 0.182).
4Journal of Ophthalmology
No prostaglandin used
IOP change over time
1 month6 months 12 months
Mean ± 1 SEM
Figure 1: Graph comparing IOP change over time of patients
treated with prostaglandin analogues to those treated with other
medical treatments prior to SLT. The IOP change shown in the
graph is the mean of the differences between the IOP of the treated
and fellow eyes in both groups at each time point, and the IOP
change has been controlled for baseline IOP.
There were a total of 38 phakic and 4 pseudophakic eyes
available for complete case analysis of the change in the SLT-
treated eye compared to baseline. Overall, there was not a
significant difference in IOP reduction over time between
phakic and pseudophakic eyes (P < 0.225). However, there
was a trend towards better response in phakic eyes compared
to pseudophakic eyes at 1 and 6 months.
There were 5 eyes with prior ALT and 35 eyes without
prior ALT available for the complete case analysis of the
change of IOP in the SLT-treated eye compared to baseline
IOP in the same eye. There was not a statistically significant
difference between the groups (P < 0.629). Similarly, IOP
in 29 eyes without prior ALT and 4 eyes with prior ALT was
compared to IOP in the contralateral eye at each time point,
and no statistically significant difference was found between
groups (P < 0.785).
for complete case analysis of the SLT-treated eye IOP
compared to baseline IOP in the same eye. The degree of
pigmentation was 0+ in 3 eyes; 1+ in 11 eyes; 2+ in 12 eyes;
3+ in 12 eyes; and 4+ in 4 eyes. There was not a statistically
significant difference in IOP change over time according
to pigmentation. However, there was a trend towards less
IOP response in the 0+ pigment eyes. A similar analysis
eye at each time point was conducted. The pigmentation
levels were 0+ in 2 eyes, 1+ in 11 eyes, 2+ in 8 eyes,
3+ in 10 eyes, and 4+ in 4 eyes. There was also not a
significant difference in IOP response over time according
to pigmentation levels (P < 0.127), but 0+ pigmentation
eyes showed a trend to worse IOP response. Furthermore,
no statistically significant difference in IOP response over
time according to pigmentation level was found even when
pigmentation levels were grouped combining 0+ and 1+, as
well as 3+ and 4+ pigmentation levels into larger groups.
There were 6 eyes enrolled in the study with pseudoexfo-
liative glaucoma (PXFG), but there were only two for which
IOP measurements in treated and fellow eyes were available
at each time point. There was not a statistically significant
difference (P = 0.231) in response to SLT between eyes with
PXFG and those with other forms of OAG or OHT.
The results of our study confirm the findings of some other
authors that high baseline IOP is a predictor of IOP-lowering
response after SLT [19–21]. In addition, our study found
that gender, age, and degree of angle pigmentation did not
predict response to SLT, which is consistent with much of
the other literature on the subject. Although pigmentation
did not influence IOP change over time in the present
study sample, IOP spikes following SLT in some heavily
pigmented eyes have previously been reported . The
trend to decreased IOP-lowering response over time in eyes
with 0+ pigmentation levels might be due to decreased
laser energy absorption or perhaps to increased difficulty in
delivering the laser energy to the appropriate location on the
Our study is limited by the small number of patients
enrolled and by missing IOP data in the treated and fellow
eyes, which limited the statistical power from our complete
case analysis. In addition, the majority of patients in our
sample were being treated with other glaucoma medications
concurrently, making it difficult to eliminate confounding
factors and drug interactions. The effect of premedication
with other drops on SLT remains to be seen.
In this study, we observed a statistically significant
weakening of the IOP-lowering response to SLT in eyes
treated with prostaglandin analogue therapy, compared to
prostaglandin na¨ ıve eyes. This diminished effect of SLT on
these patients persisted even when we controlled for baseline
IOP and was present at all time points. These findings are
consistent with the findings of Latina and De leon , and
Kara et al. .
Both prostaglandin analogues and selective laser tra-
beculoplasty result in intercellular junction disassembly,
paracellular pathway widening, and increased conductivity
in cultured Schlemm canal endothelial cells . This obser-
vation provides a possible explanation for the empirically
observed phenomenon of reduced marginal benefit of SLT
for patients receiving prostaglandin analogues, which has
been confirmed by the present study. Thus, the expected
benefit of SLT appears to be greatest in prostaglandin na¨ ıve
eyes with higher baseline IOP, and lower in prostaglandin-
treated eyes with lower baseline IOP.
It remains to be seen whether patients initially
treated with SLT would also benefit less from subsequent
prostaglandin analogue therapy. If this is not the case, then it
might be more beneficialto considerperformingSLT asfirst-
line therapy in some eyes, before instituting prostaglandin
Journal of Ophthalmology5
 M. A. Latina, S. A. Sibayan, D. H. Shin, R. J. Noecker, and
G. Marcellino, “Q-switched 532-nm Nd:YAG laser trabecu-
loplasty (selective laser trabeculoplasty): a multicenter, pilot,
clinical study,” Ophthalmology, vol. 105, no. 11, pp. 2082–
 L. J. Katz, W. C. Steinmann, A. Kabir, J. Molineaux, S. S.
Wizov, and G. Marcellino, “Selective laser trabeculoplasty
versus medical therapy as initial treatment of glaucoma: a
prospective, randomized trial,” Journal of Glaucoma. In press.
 I. McIlraith, M. Strasfeld, G. Colev, and C. M. L. Hutnik,
“Selective laser trabeculoplasty as initial and adjunctive treat-
ment for open-angle glaucoma,” Journal of Glaucoma, vol. 15,
no. 2, pp. 124–130, 2006.
 J. S. M. Lai, J. K. H. Chua, C. C. Y. Tham, and D. S. C.
Lam, “Five-year follow up of selective laser trabeculoplasty in
Chinese eyes,” Clinical and Experimental Ophthalmology, vol.
32, no. 4, pp. 368–372, 2004.
 M. Nagar, A. Ogunyomade, D. P. S. O’Brart, F. Howes, and
J. Marshall, “A randomised, prospective study comparing
selective laser trabeculoplasty with latanoprost for the control
of intraocular pressure in ocular hypertension and open angle
glaucoma,” British Journal of Ophthalmology, vol. 89, no. 11,
pp. 1413–1417, 2005.
 M. Mahdy, “Efficacy and safety of selective laser trabeculo-
plasty as a primary procedure for controlling intraocular pres-
sure in primary open angle glaucoma and ocular hypertensive
patients,” Sultan Qaboos University Medical Sciences Journal,
vol. 8, no. 1, pp. 53–58, 2008.
 M. A. Latina and J. M. S. De Leon, “The effect of topical
pp. 31–33, 2004.
 W. J. Scherer, “Effect of topical prostaglandin analog use on
outcome following selective laser trabeculoplasty,” Journal of
Ocular Pharmacology and Therapeutics, vol. 23, no. 5, pp. 503–
 D. Singh, M. A. Coote, F. O’Hare et al., “Topical prostaglandin
analogues do not affect selective laser trabeculoplasty out-
comes,” Eye, vol. 23, no. 12, pp. 2194–2199, 2009.
 N. Kara, C. Altan, B. Satana et al., “Comparison of selective
laser trabeculoplasty success in patients treated with either
prostaglandin or timolol/dorzolamide fixed combination,”
Journal of Ocular Pharmacology and Therapeutics, vol. 27, no.
4, pp. 339–342, 2011.
 S. S. Bylsma, J. R. Samples, T. S. Ascott, and M. Van Buskirk,
“Trabecular cell division after argon laser trabeculoplasty,”
Archives of Ophthalmology, vol. 106, no. 4, pp. 544–547, 1988.
 J. B. Wise, “Glaucoma treatment by trabecular tightening with
the argon laser,” International Ophthalmology Clinics, vol. 21,
no. 1, pp. 69–78, 1981.
 J. M. Bradley, A. M. Anderssohn, C. M. Colvis et al., “Medi-
ation of laser trabeculoplasty-induced matrix metallopro-
teinase expression by IL-1beta and TNFalpha,” Investigative
Ophthalmology and Visual Science, vol. 41, no. 2, pp. 422–430,
 M. Cellini, P. Leonetti, E. Strobbe, and E. C. Campos,
“Matrix metalloproteinases and their tissue inhibitors after
selective laser trabeculoplasty in pseudoexfoliative secondary
glaucoma,” BMC Ophthalmology, vol. 21, no. 8, article 20,
 C. B. Toris, C. B. Camras, M. E. Yablonski, and R. F.
Brubaker, “Effects of exogenous prostaglandins on aqueous
of Ophthalmology, vol. 41, supplement 2, pp. S69–S75, 1997.
 C. K. Bahler, K. G. Howell, C. R. Hann, M. P. Fautsch, and
D. H. Johnson, “Prostaglandins increase trabecular meshwork
outflow facility in cultured human anterior segments,” Amer-
ican Journal of Ophthalmology, vol. 145, no. 1, pp. 114–119,
 J. A. Alvarado, R. Iguchi, J. Martinez, S. Trivedi, and A.
S. Shifera, “Similar effects of selective laser trabeculoplasty
and prostaglandin analogs on the permeability of cultured
schlemm canal cells,” American Journal of Ophthalmology, vol.
150, no. 2, pp. 254–264, 2010.
laser trabeculoplasty,” Current Medical Research and Opinion,
vol. 25, no. 3, pp. 787–796, 2009.
 W. G. Hodge, K. F. Damji, W. Rock, R. Buhrmann, A. M.
Bovell, and Y. Pan, “Baseline IOP predicts selective laser
trabeculoplasty success at 1 year post-treatment: results from
a randomised clinical trial,” British Journal of Ophthalmology,
vol. 89, no. 9, pp. 1157–1160, 2005.
 E. Martow, C. M. L. Hutnik, and A. Mao, “SLT and adjunctive
medical therapy: a prediction rule analysis,” Journal of Glau-
coma, vol. 20, no. 4, pp. 266–270, 2011.
 M. Shibata, T. Sugiyama, O. Ishida et al., “Clinical results
of selective laser trabeculoplasty in open-angle glaucoma in
Japanese eyes: comparison of 180 degree with 360 degree SLT,”
Journal of Glaucoma, vol. 21, no. 1, pp. 17–21, 2012.
 P. J. Harasymowycz, D. G. Papamatheakis, M. Latina, M. De
Leon, M. R. Lesk, and K. F. Damji, “Selective Laser Trabeculo-
plasty (SLT) complicated by intraocular pressure elevation in
eyes withheavily pigmentedtrabecular meshworks,”American
“From the bedside to the bench and back again: predicting
and improving the outcomes of SLT glaucoma therapy,”
Transactions of the American Ophthalmological Society, vol.
107, pp. 167–181, 2009.