ORIGINAL ARTICLE
Prostaglandin Release During Femtosecond
Laser-Assisted Cataract Surgery: Main Inducer
Tim Schultz, MD; Stephanie C. Joachim, MD; Mathias Stellbogen; H. Burkhard Dick, MD, PhD
ABSTRACT
PURPOSE: To investigate a possible correlation between
intraocular prostaglandin concentrations and partial
steps of laser-assisted cataract surgery.
METHODS: Aqueous humor was collected from 67 pa-
tients after laser-assisted cataract surgery pretreatment
(only capsulotomy, only fragmentation, or both) and at
the beginning of routine cataract surgery. Total prosta-
glandin levels were measured in all four groups using an
enzyme-linked immunoassay.
RESULTS: Significantly higher levels of aqueous humor
prostaglandins were detected right after the full treat-
ment (capsulotomy and fragmentation [330.6 ± 110.6
pg/mL; P = .01] or only laser capsulotomy [362.4 ±
117.5 pg/mL; P = .01]), whereas the control group
showed lower values (52.5 ± 8.1 pg/mL). By itself, la-
ser-assisted cataract surgery fragmentation did not lead
to a prostaglandin increase (186.8 ± 114.0 pg/mL;
P = .14).
CONCLUSIONS: This study identified the anterior cap-
sulotomy as the main trigger for an increase of prosta-
glandins in the aqueous humor immediately after laser-
assisted cataract surgery. Optimized energy settings in
combination with nonsteroidal anti-inflammatory drugs
might help reduce the phenomenon of laser-induced
miosis.
[J Refract Surg. 2015;31(2):78-81.]
78
I n 2008, image-guided femtosecond lasers became avail-
able for cataract surgery.1 These systems led to several
benefits, including a reduction in used ultrasound energy
and more precise capsulotomies as a basis for capsule-fixated
intraocular lenses (IOLs).2-5 For the first time, these devices
also treated intraocular tissue. Therefore, triggered intraocular
effects are largely unknown and have not been sufficiently in-
vestigated. Several studies reported laser-induced miosis oc-
curred shortly after laser treatment, with varying frequencies.6-8
Narrowing of the pupil is potentially associated with a higher
complication rate.9 In a previous study, intraocular prostaglan-
din concentration increased immediately after laser treatment.
This was confirmed in two independent study arms.10
Prostaglandins (especially increased prostaglandin E2) are
known to play a role in inflammation-induced miosis. How-
ever, it is unclear which partial step of laser-assisted cataract
surgery leads to the observed prostaglandin release. To reduce
the occurrence, a further understanding of the mechanism is
needed. The aim of the current study was to investigate if the
fragmentation of the lens or capsulotomy induced inflamma-
tion after laser-assisted cataract surgery.11-14 Therefore, aque-
ous humor prostaglandin levels were analyzed right after
laser-assisted cataract surgery and laser-assisted capsulotomy
or fragmentation only.
PATIENTS AND METHODS
Aqueous humor samples were obtained from patients un-
dergoing routine microincision cataract surgery and three
From Institute for Vision Science (TS, HBD) and Experimental Eye Research
Institute (SCJ, MS, HBD), Ruhr University Eye Hospital, Bochum, Germany.
Submitted: November 10, 2014; Accepted: December 1, 2014
Supported by the FoRUM Program (Ruhr University, Bochum, Germany).
Dr. Dick is a paid consultant for Abbott Medical Optics (Santa Ana, CA). The
remaining authors have no financial or proprietary interest in the materials
presented herein.
Drs. Schultz and Joachim contributed equally to this work and should be con-
sidered as equal first authors.
Correspondence: Tim Schultz, MD, Institute of Vision Science, Ruhr University
Eye Hospital, In der Schornau 23-25, 44892 Bochum, Germany. E-mail: tim.
schultz@kk-bochum.de
doi:10.3928/1081597X-20150122-01
Copyright © SLACK Incorporated

laser-assisted cataract surgery groups. The samples
were collected at the beginning of the surgery and
stored at -80°C until used. All tenets of the Declaration
of Helsinki were observed. The Lens Opacities Classifi-
cation System III (LOCS III) was used and preoperative
nuclear opalescence was estimated by one indepen-
dent physician using a Haag Streit BQ 900 slit lamp
(Bern, Switzerland) at maximum illumination.
Inclusion Criteria
Patients who were scheduled for cataract surgery on
one eye and were willing to volunteer for the trial after
giving informed consent were randomly allocated to
one of four study groups based on the following inclu-
sion criteria.
In the control group, patients with a significant
cataract (LOCS III nuclear opalescence grading score,
grades II to IV) and without any other ocular diseases
were scheduled for traditional microincision phaco-
emulsification. Similarly, patients with significant
cataract and no ocular diseases were included in the
laser-assisted cataract surgery groups.
Exclusion Criteria
Patients with serious coexisting ocular disease, his-
tory of inflammatory eye disease, previous ocular sur-
gery or trauma, relevant corneal opacities, age-related
macular degeneration, diabetic and hypertensive reti-
nopathy, any kind of glaucoma, pseudoexfoliation,
dilated pupil size smaller than 6 mm, and rheumatic
and metabolic diseases were excluded. Age younger
than 22 years, pregnancy, the use of nonsteroidal anti-
inflammatory drugs or steroids in the past 6 months,
and participation in another clinical study were also
considered exclusion criteria.
Based on these criteria, 67 patients were included in
this prospective study.
Laser-Assisted Cataract and Control Surgery
All surgeries were performed at the Institute for
Vision Science, Ruhr University Eye Clinic, Bochum,
Germany. Manual and femtosecond laser surgeries
were performed by one experienced surgeon (HBD) in
all cases. Preoperatively, all groups received the same
topical medication. Medical mydriasis was induced
using topical 0.5% tropicamide eye drops (Mydriati-
cum; Stulln Pharma, Stulln, Germany) and 5.0% phen-
ylepherine eye drops (Neo-Synephrine; Ursapharm,
Saarbrücken, Germany) instilled three times within 1
hour prior to surgery. Oxybuprocaine eye drops (Con-
juncain EDO 0.4%; Dr. Mann Pharma and Bausch &
Lomb, Berlin, Germany) were applied three times for
topical anesthesia 30 minutes prior to surgery.
Journal of Refractive Surgery • Vol. 31, No. 2, 2015
Prostaglandin Release/Schultz et al
In the three laser-assisted cataract surgery groups
(capsulotomy, fragmentation, and combination), dif-
ferent steps of the procedure were performed with the
Catalys Precision Laser System (Abbott Medical Optics,
Santa Ana, CA). In the capsulotomy group, only the
capsulotomy was performed with the laser system. In
the fragmentation group, only lens fragmentation was
performed with the laser system. In the combination
group, both capsulotomy and lens fragmentation were
performed with the laser system (capsulotomy prior to
fragmentation). No corneal incisions were performed
with the laser system. In all capsulotomy cases, the set
capsulotomy size was 5.0 mm and the programmed
pulse energy was 4 µJ, with an incision depth of 600
µm (treatment time 1.6 sec). The iris safety distance
zone was set at 500 µm.
In the two lens treatment groups, an extensive seg-
mentation and softening pattern was used (waffle pat-
tern, grid spacing 350 µm, central cross repetition rate
of 3, anterior and posterior safety zone 500 µm, and
10-µJ pulse energy). Four to 5 minutes after laser treat-
ment, a paracentesis was made at the 11-o’clock posi-
tion and approximately 100 µL of aqueous humor was
collected. The samples were directly stored at -80°C in
a freezer located in the operating room. In the fragmen-
tation group, a manual capsulotomy was performed. In
all groups, subsequent nuclear disassembly was con-
ducted and an IOL was implanted.
In the control group, a 1.2-mm paracentesis was
created in the same manner as described for the laser-
assisted cataract surgery groups. Similar to the other
groups, approximately 100 µL of aqueous humor was
collected and immediately stored at -80°C. Routine
manual cataract surgery with implantation of an IOL
was then performed.
Measurements of Prostaglandin in Aqueous Humor
All samples from the four groups were measured at
the same time by the same investigator with the same
standard preparation to avoid inter-user or plate vari-
ability. Prostaglandin concentrations were determined
using a commercially available enzyme immunoassay
kit (Cayman Chemicals, Ann Arbor, MI) as previously
described.10 The enzyme immunoassay kits were used
according to the provided manufacturer instructions.
Briefly, assays were performed on 96 well plates by
adding 50 µL of standards, controls, and samples
(aqueous humor) into the wells, followed by a pros-
taglandin–acetylcholinesterase conjugated tracer and
an anti-prostaglandin antibody. After incubation,
the plates were rinsed, Ellmans reagent was added,
and measurements were performed at a wavelength
of 405 µm using a microplate reader (AESKU Reader
79
Prostaglandin Release/Schultz et al
TABLE 1
Clinical Patient Data for the Four Groups
Parameter Control
No. of patients (n = 67) 18
Mean age ± standard deviation, y 74.3 ± 7.4
Sex (male/female) 9/9
Eye (right/left) 8/10
Mean cataract grade ± standard deviation 3.1 ± 0.8
Figure 1. Mean prostaglandin levels in aqueous humor of all four groups:
control, fragmentation, capsulotomy, and combination (fragmentation and
capsulotomy). Measured prostaglandin levels were significantly higher in
the capsulotomy (P = .01) and combination (P = .01) groups compared
with the control group, whereas no significant increase was observed in the
fragmentation group (P = .14). Values are median ±25% to ±75% range.
with Gen5 ELISA Software; AESKU.Diagnostics, Wen-
delsheim, Germany).
Statistical Analysis
All statistical analyses were performed using Sta-
tistica software version 10 (Statsoft, Tulsa, OK). Sig-
nificant differences in prostaglandin concentration
between the groups were calculated using Student’s t
test. P values of less than .05 were considered statisti-
cally significant.
RESULTS
Patients were randomly placed in one of the four
study groups. After positioning the patient on the op-
erating bed, the surgeon opened the corresponding
envelope indicating which of the four procedures to
choose. In total, 67 aqueous humor samples were ana-
lyzed (49 samples of patients undergoing laser-assisted
cataract surgery and 18 samples of patients before con-
ventional cataract surgery) (Table 1). There was no
difference between the laser-assisted cataract surgery
80
Capsulotomy Fragmentation Combination
19 11 19
74.0 ± 4.9 81.0 ± 11.1 67.6 ± 10.7
10/8 5/6 13/6
11/8 6/5 11/8
3.1 ± 0.6 3.9 ± 1.0 3.1 ± 0.9
groups and the control group with regard to sex or cat-
aract density.
Prostaglandin Concentrations in Aqueous Humor
The prostaglandin level in the human aqueous
humor was detected in three different laser-assisted
cataract surgery groups and in the control group (con-
ventional cataract surgery). In the control group, total
prostaglandin concentration (mean ± standard error of
mean; 52.5 ± 8.1 pg/mL) was lower than in all of the
laser-assisted cataract surgery groups. Prostaglandin
concentration in the capsulotomy group (362.4 ± 117.5
pg/mL) was significantly higher than that in the con-
trol group (P = .01). Levels in the combination group
(330.6 ± 110.6 pg/mL) were also significantly higher
than those in the control group (P = .01) (Figure 1). No
difference was found between the fragmentation (186.8
± 114.0 pg/mL) and control (P = .14) groups (Figure 1).
Mean prostaglandin levels in the capsulotomy and
combination groups were approximately 80% to 98%
higher than those in the fragmentation group.
DISCUSSION
The number of laser-assisted cataract surgeries is
increasing worldwide. A laser-induced miosis was de-
scribed in multiple studies and prostaglandins have
been identified as potential inflammatory mediators.6
However, until now, it was unknown which step of the
treatment induces miosis.
In the current study, intraocular prostaglandin re-
lease after different partial steps of laser-assisted cat-
aract surgery was investigated. In comparison to the
control group, significantly higher prostaglandin lev-
els were observed after laser-assisted cataract surgery
capsulotomy alone and after capsulotomy in combina-
tion with lens fragmentation. The measured prosta-
glandin levels were comparable to concentrations in
the precursor trial.10 Lens fragmentation alone did not
result in an increased intraocular prostaglandin con-
centration.
Surprisingly, the results of this study indicate that
the anterior laser capsulotomy stimulates prostaglandin
Copyright © SLACK Incorporated

release. It was postulated that prostaglandins are re-
leased by the ciliary body due to an increase in tem-
perature, vibrations, or shockwaves.15 Because signifi-
cantly more energy was used for the fragmentation of
the lens than for the capsulotomy (fragmentation: 10
µJ, capsulotomy: 4 µJ) and treatment time for fragmen-
tation was up to 20 times longer, an increase in tem-
perature is not likely responsible for the inflammation.
Most likely, laser spots passing the aqueous humor in-
duced vibrations or shockwaves and may represent the
main trigger for miosis. Therefore, optimized capsulot-
omy laser settings have great potential to reduce the
described phenomenon and a complete fragmentation
of the lens (eg, a waffle pattern) seems to be uncriti-
cal. A reduced incision depth in the anterior chamber
during capsulotomy in combination with lower pulse
energy is especially necessary. Furthermore, we as-
sume that the safety distance of the capsulotomy to
the iris needs to be sufficient. A further decrease in
the incidence of laser-induced miosis seems possible
in combination with nonsteroidal anti-inflammatory
drug pretreatment.
The influence of penetrating corneal laser incisions
was not investigated in the current study. Similar to
the anterior capsulotomy, the laser fires into the anteri-
or chamber during this treatment. Potential vibrations
or shockwaves are created and could lead to a higher
prostaglandin release. However, in the precursor tri-
al, prostaglandin concentration was not significantly
higher with corneal incisions.10 Maybe the greater dis-
tance between laser treatment zone and ciliary body
reduces this effect. Interestingly, a capsular block syn-
drome occurred in none of the laser-assisted cataract
surgery cases with fragmentation alone. This observa-
tion allows the assumption that this complication does
not occur or only rarely occurs with current laser sys-
tem settings. One possible explanation is the fact that
the smaller numerical aperture of the Catalys Precision
Laser System results in less gas release.
Unfortunately, patients in the lens fragmentation
group were significantly older when compared to the
combination group (analysis of variance). An influence
on the measured values cannot be excluded. However,
in vivo prostaglandin measurements always show
inter-individual variations. Nonetheless, higher pros-
taglandin concentrations were measured in the com-
bination and capsulotomy groups and compared with
the control group, and the ages in these three groups
were comparable.
This study is the first to identify anterior capsulotomy
as the main trigger for an increase of prostaglandins
Journal of Refractive Surgery • Vol. 31, No. 2, 2015
Prostaglandin Release/Schultz et al
in the aqueous humor immediately after laser-assisted
cataract surgery. Consequently, an anterior capsu-
lotomy with optimized settings in combination with
nonsteroidal anti-inflammatory drug pretreatment may
reduce the incidence of laser-induced miosis.
AUTHOR CONTRIBUTIONS
Study concept and design (HBD, SCJ, TS); data collection (HBD,
MS, SCJ, TS); analysis and interpretation of data (SCJ, TS); drafting
of the manuscript (HBD, SCJ, TS); critical revision of the manuscript
(HBD, MS); statistical expertise (SCJ); supervision (HBD)
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