Anterior chamber flare after femtosecond laser-assisted cataract surgery
Robin G. Abell, MB BS, Penelope L. Allen, PhD, Brendan J. Vote, FRANZCO
PURPOSE: To determine whether postoperative ocular inflammation is less after femtosecondlaser–assisted cataract surgery than after conventional phacoemulsification (manual) cataractsurgery.
SETTING: Private clinic, Launceston, Tasmania, Australia.
DESIGN: Prospective consecutive investigator-masked nonrandomized parallel cohort study.
METHODS: Consecutive cataract patients who had femtosecond laser–assisted cataract surgery ormanual cataract surgery by the same surgeon at a single center were assessed. The primaryendpoint was postoperative aqueous flare measured by laser flare photometry at 1 day and 4 weeks. Secondary endpoints included retinal thickness measured by optical coherence tomography andslitlamp examination findings at 4 weeks.
RESULTS: The per-protocol population comprised 176 patients (100 in laser group; 76 in manualgroup). Postoperative aqueous flare was significantly greater in the manual cataract surgery groupat 1 day (PZ.0089) and at 4 weeks (PZ.003). There was a significant correlation between effectivephacoemulsification time and 1-day postoperative aqueous flare (r Z 0.35, P<.0001). The increasein outer zone thickness measured by optical coherence tomography was less in the laser group(PZ.007).
CONCLUSION: Anterior segment inflammation was less after femtosecond laser–assisted cataractsurgery than after manual cataract surgery, and this appeared to be due to a reduction in phaco-emulsification energy.
Financial Disclosure: No author has a financial or proprietary interest in any material or methodmentioned.
J Cataract Refract Surg 2013; 39:1321–1326 Q 2013 ASCRS and ESCRS
Advances in surgical equipment, ophthalmic viscosur-
surgical trauma and the resulting inflammation. At
gical devices, and phacoemulsification have led to a
present, there is early evidence of a reduction in post-
reduction in surgical trauma.The introduction of
operative swelling at the macula with femtosecond
femtosecond laser–assisted cataract surgery has led
laser–assisted cataract surgery over manual cataract
to further reductions in phacoemulsification energy re-
quirements.Combined with automated corneal in-
Postoperative inflammation is associated with a
cisions and anterior capsulotomy, femtosecond
breakdown of the blood–aqueous barrier as a result of
laser–assisted cataract surgery may further reduce
surgical trauma–induced prostaglandin production.The inflammation generally manifests as mild iritis,corneal edema, increased cells and protein (flare) inthe anterior chamber, and hyperalgesia or painEven
in its mildest form, postoperative inflammation remains
Final revision submitted: May 29, 2013.
a challenge, and patients have high expectations for
rapid visual recovery and minimal associated pain.
From the Tasmanian Eye Institute (Abell, Allen, Vote) and the Laun-
It is not known whether femtosecond laser–assisted
ceston Eye Institute (Vote), Launceston, Tasmania, Australia.
cataract surgery lens fragmentation leads to an increase
Corresponding author: Brendan J. Vote, FRANZCO, Launceston Eye
in particulate matter in the anterior chamber, which
Institute, 36 Thistle Street West, Launceston 7250, Australia.
may exacerbate inflammatioThis study was per-
formed to compare postoperative inflammation using
ANTERIOR CHAMBER FLARE AFTER LASER-ASSISTED CATARACT SURGERY
anterior chamber flare between femtosecond laser–as-
concentric regions were split into 4 zones each as follows:
sisted cataract surgery and manual cataract surgery.
superior, temporal, inferior, and nasal. The mean of the4 values in each ring comprised the inner OCT measurementand outer OCT measurement, respectively. The inner ring
and outer ring had a radius of 1.5 mm and 3.0 mm,
Anterior chamber aqueous flare was measured objectively
This was a prospective consecutive investigator-masked
using laser flare photometry (Kowa FM-600). This instru-
nonrandomized parallel cohort study performed at a single
ment and its operation have been described in detail.
center. The study was approved by the Tasmanian Human
Anterior chamber flare was measured by a masked investi-
Research Ethics Committee and was performed in accor-
gator who was unaware of the patient’s treatment group.
dance with the Declaration of Helsinki and its subsequent re-
Measurements were taken within 1 week preoperatively as
well as 1 day and 4 weeks postoperatively. Seven measure-
Consecutive patients who were older than 18 years and
ments were taken under scotopic conditions without phar-
planned to have femtosecond laser–assisted cataract surgery
macologic pupil dilation. The 2 extreme values were
or manual cataract surgery with insertion of a posterior
excluded from the mean value, according to the manufac-
chamber intraocular lens (IOL) were enrolled in the study.
turer’s guidelines. Measurement conditions were kept
All patients were given the option to have femtosecond
consistent for all patients. The 5 measurements were aver-
laser–assisted cataract surgery. Patients who elected to
aged to a single score in photons per millisecond.
have femtosecond laser–assisted cataract surgery were
Postoperatively, patients were seen at 1 day and 4 weeks.
placed in the laser group, and the remaining patients were
Study assessment at the postoperative visits included slit-
lamp examination, fluorescein staining for corneal epithelial
Patients were excluded from the study if they had a preop-
erosions, and intraocular pressure (IOP) measurement using
erative flare of more than 15 photons per millisecond (ph/
Goldmann applanation tonometry. Dilated fundoscopy was
ms) measured with a laser flare photometer without phar-
performed at 4 weeks. Concomitant medications used to
macologic pupil dilation, inflammatory or infectious pathol-
treat inflammation related to cataract surgery were recorded
ogy of the eye, history of postoperative intraocular infection
at the preoperative and at the postoperative visits.
in the fellow eye, glaucoma, posttraumatic cataract, exfolia-tion syndrome, diabetic retinopathy, history of uveitis, and
pathology requiring the use of topical or systemic antiinflam-matory or antiinfectious agents. Patients taking medications
All patients instilled topical ketorolac and chloramphen-
known to cause fluctuations or alterations in anterior cham-
icol for 2 days before the procedure. On the day of surgery,
ber protein composition or effect photometry flare values
patients received topical anesthesia and pupil dilation with
were excluded.Patients were also excluded from analysis
a gel formulation consisting of phenylephrine 2.5%, cyclo-
if they had an intraoperative complication of vitreous loss
pentolate 1.0%, tropicamide 1.0%, lidocaine hydrochloride
or complicated capsule rupture or had implantation of an
jelly 2.0% (Xylocaine), and diclofenac 0.1%. The femtosecond
laser procedure has been After the laser proce-dure, the patient was transferred to the operating room for
regional anesthesia via sub-Tenon injection. Patients in themanual group also had regional anesthesia. The interval be-
Eligible patients were included in the study after going
tween the completion of the laser treatment and the initiation
through an extensive preoperative assessment. Patients
of operative cataract surgery was recorded for all patients in
also had clinical and fundoscopic examinations using slit-
lamp biomicroscopy. Evaluations included optical coherence
Intraoperatively, corneal incisions were made manually
tomography (OCT) (Zeiss Cirrus HD-OCT 4.0, Carl Zeiss
using a 2.75 mm keratome and a 1.20 mm side-port blade.
Meditec AG), axial length (AL) and biometry (IOLMaster
Patients having the laser procedure had the cut anterior
4, Carl Zeiss Meditec AG), and laser flare photometry
capsule removed using a capsulorhexis forceps, after which
(Kowa FM-600, Kowa Co., Ltd.). The cataract grade was as-
hydrodissection was performed. Lens segmentation was
sessed objectively using Scheimpflug imaging (Pentacam
completed with the standard phacoemulsification procedure
Nuclear Staging System, Oculus Optikger€ate
(Megatron S4, Geuder AG). The effective phacoemulsifica-
Optical coherence tomography measurements were per-
tion time (EPT) was recorded for all patients. Patients who
formed preoperatively within 2 weeks of the surgery and
had manual cataract surgery had a continuous curvilinear
postoperatively at 4 weeks. The same trained individual ob-
capsulorhexis, hydrodissection, and phacoemulsification.
tained each scan and was masked to the patient’s treatment
After successful removal of lens cortex, both cohorts had
group. The repeatability and reproducibility of time-domain
IOL placement in the capsular bag. All surgical characteris-
tics except those related to the laser procedure were kept
Macular measurements were taken after pupil dilation.
Scans were performed using a default AL (24.46 mm) and
Postoperatively, all patients were prescribed topical chlor-
refractive error to allow consistency with usual practice.
amphenicol, dexamethasone, and ketorolac 4 times a day for
Scans were accepted if they were free of artifact. The instru-
ment software automatically determined retinal thickness asthe distance between the internal limiting membrane and
retinal pigment epithelium (RPE). Measurements were pro-vided for a central area as well as for 2 concentric regions.
The primary endpoint was aqueous flare measured with
The central area (foveal region) had a radius of 0.5 mm (cen-
laser flare photometry 1 day and 4 weeks after cataract sur-
tral macular thickness [CMT]). The inner and outer
gery. Secondary endpoints included EPT, fortified balanced
J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013
ANTERIOR CHAMBER FLARE AFTER LASER-ASSISTED CATARACT SURGERY
salt solution (BSS Plus) fluid volume used during surgery, in-terval between the laser procedure and initiation of manualsurgery steps, postoperative IOP, and the change in retinalthickness from baseline measured by OCT. Retinal thicknessmeasured by OCT included central thickness and the meanof the 4 inner pericentral and 4 outer quadrants separately,as described above, at 4 weeks. An ophthalmologist assessedpatients at 1 day and 4 weeks using slitlamp biomicroscopy(anterior segment and fundus).
All data were imported into Stata 12 (Stata Corp LP) for
analysis and examined with descriptive and frequency ana-lyses. Categorical data were analyzed using the chi-squaretest. Nonparametric continuous data were transformed to
Figure 1. Mean aqueous flare in the laser group and manual group
approximate a normal distribution, and t tests were used
1 day and 4 weeks after cataract surgery (ph/ms Z photons per
to detect differences in means. Correlations between EPT
and 1-day postoperative aqueous flare and between 1-dayaqueous flare and 4-week aqueous flare were assessed usingthe Pearson correlation coefficient (r). Regression models
mean aqueous flare was 11.1 G 8.1 ph/ms and 14.6
with post-estimation diagnostics were run to evaluate the
G 10.7 ph/ms, respectively (PZ.003) ). There
relationship between EPT, balanced salt solution used, andaqueous flare at 1 day and 4 weeks. All tests were 2 sided,
was no difference in IOP between groups at 1 day.
and a P value less than 0.05 was considered significant.
There was a significant correlation between the 1-day
A post hoc power analysis found that the study had statis-
and 4-week aqueous flare score (r Z 0.51, P!.0001).
tical power greater than the 0.80 level at a 0.05 to detect
There was also a significant correlation between EPT
a difference in mean aqueous flare between the laser group
and 1-day postoperative aqueous flare (r Z 0.35,
and manual group given the sample size in each group.
The multiple regression of EPT and balanced salt so-
lution use as predictors of aqueous flare at 1 day was
The study analyzed 100 eyes in the laser group and 76
significant (F3,101 Z 8.6, P!.05). For each 1-unit
eyes in the manual group. All eyes completed the
(1-second) increase in EPT, a 0.63 increase in aqueous
study. There were 53 (53%) men in the laser group
flare at 1 day would be expected. For each 1-unit
and 33 (56%) in the manual group. The mean age
(1 mL) increase in balanced salt solution, a 0.05 in-
was 72.5 years G 10.5 (SD) (range 41 to 94 years).
crease in aqueous flare at 1 day would be expected.
There was no significant difference in age, refractive
The regression of EPT and balanced salt solution as
error, AL, anterior chamber depth, smoking status,
predictors of aqueous flare at 1 month was also signif-
preoperative IOP, nonocular medical history, or ocular
The mean interval from completion of laser lens
The mean preoperative aqueous flare was 5.3 G
fragmentation to initiation of manual cataract surgery
3.1 ph/ms in the laser group and 5.3 G 3.4 ph/ms in
in the laser group was 35 G 16 minutes. There was a
the manual group; the difference was not statistically
trend toward increased aqueous flare at 1 day with
significant (PZ.96). The mean cataract grade was
greater intervals between laser treatment and cataract
2.8 G 0.8 and 2.9 G 0.8, respectively; the difference
surgery; however, it was not significant.
was not statistically significant (PZ.77).
At 4 weeks, the mean increase in OCT measure-
There was a significant difference in mean EPT be-
ments (CMT, inner zone, and outer zone) from base-
tween groups (P!.0001). The laser group had a lower
line were greater in the manual group ().
mean EPT (0.94 G 3.47 seconds) than the manual
There was a significantly larger increase in the outer
group (6.5 G 4.3 seconds). Similarly, the laser group
zone internal limiting membrane and RPE thickness
required less balanced salt solution volume during
the manual steps of surgery than the manual group
No statistically significant differences were found in
(175.2 G 71.8 mL versus 195.1 G 76.5 mL), although
the slitlamp examination and fundoscopy results be-
tween the treatment groups at 1 day and 4 weeks.
(PZ.08). There were no intraoperative complications
Furthermore, none of the study participants in either
group had raised IOP postoperatively or required
At 1 day, the mean aqueous flare was 16.6 G 8.9 ph/
concomitant medication to treat postsurgical inflam-
ms in the laser group and 21.8 G 12.0 ph/ms in the
mation. There were no adverse effects related to the
use of topical medications in either group.
J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013
ANTERIOR CHAMBER FLARE AFTER LASER-ASSISTED CATARACT SURGERY
Our original assumption was that residual lens ma-
Table 1. Between-group comparison of the increase in OCT
terial and particulate matter may be a consequence of
measurements from baseline to 4 weeks.
femtosecond laser lens fragmentation, resulting in a
higher incidence of postoperative inflammation as
measured by aqueous flare. The interval between the
completion of laser lens fragmentation and the initia-
tion of manual cataract surgery may also have an effect
on postoperative inflammation. Residual lens material
after cataract surgery or traumatic rupture of the lens
capsule is known to provoke intraocular inflamma-
tionhowever, this does not appear to be the case
in our study. The difference in aqueous flare readings
between groups was most likely due to the reduction
in EPT in the laser group. We also found no significant
association between the interval and aqueous flare
values, although generally the delay was less than45 minutes. Therefore, we believe lens particulatematter produced by the femtosecond laser during
lens fragmentation has a minimal impact with short
Several studieshave established the safety and
intervals. The maximum permitted interval between
efficacy of femtosecond laser–assisted cataract sur-
laser lens fragmentation and manual surgery to
gery; however, little is known about the postopera-
limit postoperative inflammation must still be
tive inflammation caused by surgical trauma and
fragmented lens matter. The objective of our study
In terms of secondary endpoints, there was no sig-
was to compare postoperative inflammation after un-
nificant between-group difference in CMT and inner
eventful femtosecond laser–assisted cataract surgery
zone change in retinal thickness from baseline
with that after uneventful manual cataract surgery
measured by OCT. The laser group had a significantly
to assess the degree of surgical trauma. Laser flare
lower increase in the outer zone retinal thickness on
meter measurements showed that femtosecond
OCT than the manual group. This is in agreement
laser–assisted cataract surgery resulted in less
with previous stAn association has been re-
aqueous flare than manual cataract surgery at 1 day
ported between phacoemulsification and the forma-
and 4 weeks. The laser flare meter was used as an
tion of significant clinical cystoid macular edema
objective assessment of flare; its use for this purpose
(CME).Most subclinical postoperative increases
has been validated in terms of quantification, sensi-
in retinal thickness are asymptomatic. Although this
tivity, reproducibility, and reliabilitSlitlamp
may represent the process that in its most advanced
examination or other scoring methods may be less
stages leads to the formation of it is unlikely
sensitive, more prone to observer bias or error, and
to be of clinical relevance unless symptomatic. Based
on our results, femtosecond laser–assisted cataract
Multiple factors can affect laser flare photometry
surgery may offer advantages in controlling the phys-
values.These include mydriatic agents, pupil size,
iologic changes contributing to CME. However, the
age, cataract, time of day, protein composition, and pa-
clinical relevance of this is unknown. Randomized
tient medicationTo reduce the probability of
controlled trials have shown that clinical CME and
laser photometric measurements being influenced by
perifoveal thickening on OCT are largely prevented
these factors, the factors were kept constant between
by nonsteroidal antiinflammatory drugs (NSAIDs)
patients and were taken into account when comparing
thus, the additional benefit of the femtosecond laser
values between patients and between serial measure-
is unlikely to be of clinical significance. It is difficult
ments over time. There was no difference in mean
to know whether, independently, the femtosecond
age between the groups. Multiple readings were taken
laser would offer sufficient protection against CME
to prevent sampling error. Medications that alter flare
were assessed preoperatively, and patients were
Limitations of this study include the use of topical
excluded if they were taking any of these medications.
corticosteroids and NSAIDs during the perioperative
All patients were assessed at roughly the same time of
period. Many cataract surgeons treat inflammation
day (early morning) and did not have dilating drops
prophylactically using topical corticosteroid and
before the test, and lighting conditions remained the
nonsteroidal antiinflammatory medications.Both
medications have been shown to be effective in the
J CATARACT REFRACT SURG - VOL 39, SEPTEMBER 2013
ANTERIOR CHAMBER FLARE AFTER LASER-ASSISTED CATARACT SURGERY
painhowever, corticosteroids carry the risk for
adverse effects, such as increased IOP and delayed
corneal healingThere were no unwanted effects
related to the use of these topical medications in either
group, and there was no difference in the 1-day IOP
between groups. Although both groups were treated
with the same drugs with the same frequency and
duration, we cannot rule out differences in compliance
between groups, which may have produced con-
In conclusion, femtosecond laser pretreatment in
cataract surgery significantly reduced the EPT. This
appears to result in reduced postoperative ocular
inflammation measured by aqueous flare and subse-
quently a lower risk for macular edema. It is unknown
whether this is solely due to the reduction in EPT
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