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Comparison of
postoperative
intraocular pressure
in patients with
Densiron-68 vs
conventional
silicone oil: a
case–control study
D Wong, I Kumar, SA Quah, H Ali, X Valdeperas
and MR Romano
Abstract
A solution of perfluorohexyloctane and
silicone oil with a specific gravity of 1.06 g/cm
3
(Densiron-68) has similar properties as
conventional silicone oil (SO) in terms of the
shape of the bubble and its ability to act as an
internal tamponade agent. We conducted a
case–control study to compare the
postoperative intraocular pressure (IOP) in
patients treated with Densiron-68 with those
treated with SO.
Methods Seventy-one eyes of 71 patients and
57 eyes of 57 patients who had received
Densiron-68 and SO, respectively, were
included in our study. Both groups were found
to have matched for their preoperative
comorbidities (diabetes, glaucoma, phakic
status, and refractive errors). IOP at first day,
between seventh and fourteenth day, and at
4 week postoperatively was recorded.
Results The mean IOP was higher in patients
treated with Densiron-68 at day 1 and between
seventh and fourteenth day postoperatively
(P¼0.05 and 0.01, respectively). By the 4th
week, the IOP difference between the two
groups was insignificant (P¼0.17). The
difference in the two groups could still be
clinically significant and the raised IOP in
Densiron-68 group was more difficult to treat
in some cases.
On day 1, nine eyes (12.7%) in the Densiron-68
group and two eyes (3.5%) in the SO group
had IOP greater than 30 mmHg. At 4 weeks,
IOP of more than 30 mmHg was seen in nine
eyes (12.7%) in the Densiron-68-treated group
and in one eye (1.8%) in the SO group.
Conclusion The use of Densiron-68 was
associated with a higher IOP in the early
postoperative period when compared with SO.
Eye (2009) 23, 190–194; doi:10.1038/sj.eye.6703055;
published online 7 December 2007
Keywords: Densiron-68; silicone oil;
postoperative; intraocular pressure
Introduction
Internal tamponade agents such as silicone oil
(SO) and long-acting gases used for retinal
detachment (RD) are lighter than water and
provide good support for the superior retina.
Proliferative vitreoretinopathy (PVR), however,
has the propensity for the inferior retina.
1
Conventional SO does not provide very
effective inferior support unless it completely
fills the vitreous cavity. Therefore, various
heavy tamponade agents with a specific gravity
higher than water have been tried in cases of
retinal breaks situated in the inferior retina,
especially in the presence of PVR.
Perfluorohexyloctane (F6H8) is a clear,
homogenous semifluorinated alkane initially
introduced as an SO solvent to remove SO
droplets adherent to intraocular lenses.
2,3
It is
heavier than water and has a low viscosity of
2.5 mPa. It was found to be well tolerated for up
to 3 months in a rabbit model.
4
In human
beings, however, the use of this agent as a long-
term tamponade was found to be associated
with dispersion, inflammation, and epiretinal
membrane formation. These complications were
Received: 10 June 2007
Accepted in revised form:
5 November 2007
Published online: 7
December 2007
St Paul’s Eye Unit, Royal
Liverpool University
Hospital, Liverpool, UK
Correspondence: D Wong,
Eye Institute,
The University of
Hong Kong,
23 Sassoon Road,
Hong Kong.
Tel: þ44 0 151 7063969;
Fax: þ44 0 151 7065905.
E-mail: saihungdavid@
mac.com
Eye (2009) 23, 190–194
&2009 Macmillan Publishers Limited All rights reserved 0950-222X/09 $32.00
www.nature.com/eye
CLINICAL STUDY
in turn thought to be related to the low viscosity of the
agent.
5
Densiron-68 is a solution of SO and F6H8. By Adding
F6H8 to silicone, the mixture has a specific gravity
greater than 1.06 g/cm
3
and a viscosity of 1387 cs. It is,
therefore, heavier than water and sufficiently viscous to
have a much lower propensity for dispersion (compared
with F6H8 on its own). We conducted an in vitro study
that demonstrated that in a polymethylmethacrylate
model eye chamber, a solution with a specific gravity of
1.06 g/cm
3
has similar physical properties to SO in terms
of the shape of the bubble and its ability to act as an
internal tamponade agent.
5
This is commercially
available as Densiron-68 and occasionally referred to as
heavy oil.
6
We used this agent and conducted a pilot clinical study
on its efficacy and monitored the complications. This
pilot study involved 42 cases recruited between
Rotterdam and Liverpool.
7
In this study, Densiron-68
was used in patients with RD arising from inferior retinal
breaks, in patients incapable of sustaining a head-down
posture, and in cases complicated by PVR. At 1 week and
1 month after heavy silicone oil (HSO) operation, six
patients (14%) had raised intraocular pressure (IOP) and
at 3 months after oil removal, three patients (7%) had IOP
higher than 30 mmHg. Similarly, Wolf et al found that
postoperatively IOP was raised higher than 30 mmHg in
four (12%) of 33 eyes treated with Oxane Hd (Baush and
Lomb), which is a mixture of silicone and
semifluorinated alkenes with a specific gravity of 1.03 g/
cm
3
.
8
In a pilot study by Tognetto and co-workers, the
authors found an early postoperative ocular
hypertension in eight patients (30.7%) treated with HSO,
which was easily controlled using topical antiglaucoma
medications or systemic carbonic anhydrase inhibitors.
9
There is an initial clinical impression that the use of
Densiron-68 may be associated with an early
postoperative IOP rise. It was not possible to know
whether the IOP rise after surgery was due to the surgery
or whether it was related to the Densiron-68. We
therefore conducted this case–control study to compare
patients treated with Densiron-68 with those treated with
conventional SO.
Materials and methods
A case–control study was carried out comparing 71 eyes
of 71 patients with RD who received Densiron-68 with 57
eyes of 57 patients with RD who received conventional
SO. All the surgeries in the Densiron-68 group were
performed between January 2003 and March 2005,
whereas those in the conventional SO group were before
November 2004. The inclusion criteria consisted of
rhegmatogenous or tractional retinal detachment with or
without PVR. The exclusion criteria were severe systemic
disease, pregnancy, and ocular disease other than retinal
detachment.
Thirty patients with RD in conventional SO group
were complicated by PVR: seven eyes PVR A, 10 eyes
PVR B, and 13 eyes PVR CP. Thirty-two patients with RD
in Densiron-68 group were complicated by PVR: three
eyes PVR A, nine eyes PVR B, and 20 eyes PVR CP.
All the operations were performed by consultants or
vitreoretinal fellows using Alcon Accurus
s
. Densiron-68
(Fluoron Company, Neu-Ulm, Germany) with an
interfacial tension against water of 40.82 mN/m at 251C, a
specific gravity of 1.06 g/cm
3
and a viscosity of 1387 cs
was used. Conventional SO used was of 1000, 5000, or
5700 cs viscosity at 251C with a specific gravity of
0.965 g/cm
3
and an interfacial tension against water of
35.5 mN/m at 251C.
In the Densiron-68 group, pars plana vitrectomy (PPV)
was performed in 56 eyes; 15 of the 71 eyes had
conventional SO already in situ and the surgery involved
first removing this oil, performing the surgery on the
retina, and injecting the Densiron-68. The
surgery-involved epiretinal membrane peeling was
carried out in seven eyes and PPV was combined with
phacoemulsification with intraocular lens implant in five
eyes and lensectomy in two eyes. Two eyes underwent
removal of subretinal bands.
In the conventional SO group, PPV was performed
in 52 eyes. In the other five eyes, there was oil in situ,
which was first removed. PPV was combined with
phacoemulsification and intraocular lens implantation
in five eyes and lensectomy in one eye. Two eyes had
epiretinal membrane peeling.
IOP was recorded using the Goldmann applanation
tonometer on day 1, between seventh and fourteenth day,
and at 4 weeks postoperatively in all patients. Surgical
success was defined as complete retinal attachment after
oil removal. Statistical analysis was performed using
w
2
-test, student’s t-test and analysis of variance (SPSS
ver12.0.01). As this work was performed as an audit, our
hospital did not require the study to have a specific
ethical approval.
Results
Matching
The mean age of patients who received Densiron-68 was
58.1±17.9 years (range 13–87 years) and those who
received conventional SO was 54.8±18.4 years (range
15–81 years). Both groups of patients were well matched
preoperatively for age, gender, and other features
including diabetes, preexisting glaucoma, rubeosis,
peripheral iridectomy, lens status (phakic, pseudophakic,
Comparison of postoperative intraocular pressure
D Wong et al
191
Eye
and aphakic), and refractive error (hypermetropia and
myopia). There was, however, a significant difference in
the extent of RD preoperatively in each treatment group
as shown in Table 1. The surgery performed on both
groups was similar, except that there was a higher
percentage of patients (42.3%, 30 patients) treated with
retinectomy in the Densiron-68 group as compared with
the conventional SO group (22.8%, 13 patients).
Additionally, three patients had encirclement in
the conventional SO group and none in the
Densiron-68-treated group.
Intraocular pressure
The mean, range, and standard deviations of the IOP in
the Densiron-68 group and the conventional SO group
are summarized in Table 2. IOP was significantly higher
in the group treated with Densiron-68 compared with the
group treated with conventional SO at day 1 and
between the seventh and fourteenth postoperative days.
The difference was not significant at 4 weeks.
On day 1, nine eyes (12.7%) in the Densiron-68 group
and two eyes (3.5%) in the conventional SO group had
IOP greater than 30 mmHg (Table 3). Between 7 and 14
days, 14 eyes (19.7%) in the Densiron-68 group and three
eyes (5.3%) in the conventional SO group had IOP greater
than 30 mmHg. At 4 weeks, IOP of more than 30 mmHg
was seen in nine eyes (12.7%) in the Densiron-68-treated
group and one eye (1.8%) in the conventional SO group.
On day 1, the median IOP in the Densiron-68 group was
20 mmHg (range 8–58 mmHg) as compared with
19 mmHg (range 8–32 mmHg) in the conventional SO
group. At 4 weeks, the median in Densiron-68 group was
18 mmHg (range 5–48 mmHg) while that in conventional
SO group was 16 mmHg (range 7–37 mmHg). In both
groups, some patients improved while others worsened
over the period of 4 weeks.
The patients in the Densiron-68 group did not require
more frequency and duration of steroid use as compared
with the conventional SO group, although there were a
higher percentage of patients with severe inflammation
in the Densiron-68 group.
Postoperatively, 30 patients (42.3%) in the Densiron-68
group required topical antiglaucoma medication to
control IOP. The patients were started on treatment when
their IOP was greater than 26 mmHg. Of these, six
patients required one medication, 12 patients required
two medications, eight patients required three
medications, three patients required four medications,
and one patient required five medications. In addition,
two patients were treated with cyclodiode therapy on
day 4 and day 24, and one patient required partial
removal of oil to control IOP on day 1. Of the 30 patients
who were started on treatment, nine patients (30%) did
not respond well to the treatment. More medications and
treatments were added after the first 4 weeks and IOP
was then controlled. Of these nine patients, one patient
had a history of glaucoma.
In the conventional SO group, 13 patients (22.8%)
required topical antiglaucoma drops to control IOP. None
of the patients required any surgical intervention and all
responded well to the treatment.
Only one of the three patients in the Densiron-68 group
with rubeosis had high IOP postoperatively and it was
well controlled on medication. None of the patients in the
conventional SO group had rubeosis.
Table 1 Matching of the clinical features in the two groups
Densiron-68 Conventional SO P-value
Age 58.1±17.9 54.8±18.4 0.30
Sex (M/F) 42/29 37/20 0.50
Diabetes 5 (7.04%) 7 (12.3%) 0.31
Glaucoma 5 (7.04%) 3 (5.3) 0.68
Rubeosis 3 (4.2%) 0 0.12
Peripheral iridectomy 10 (14.1%) 10 (17.5%) 0.59
Phakic 29 (40.8%) 25 (43.9%) 0.73
Pseudophakic 37 (52.1%) 25 (43.9%) 0.35
Aphakic 5 (7.04%) 7 (12.3%) 0.31
Hypermetropia 8 (11.3%) 2 (3.5%) 0.1
Myopia 16 (22.5%) 6(10.5%) 0.07
RD in 42 quadrants 13 (18.3%) 33 (57.9%) 0.000
Table 2 Postoperative intraocular pressures in patients who
received Densiron-68 and conventional silicone oil
Densiron-68 Conventional oil
Mean IOP±SD
(range)
Mean IOP±SD
(range)
P-value
Day 1 21.9±9.0 (8–58) 19.4±5.4 (8–32) 0.05
Days 7–14 21.1±10.1 (5–50) 17.1±6.2 (6–37) 0.01
Week 4 18.8±9.4 (5–48) 17.0±5.6 (7–37) 0.17
Table 3 Number of patients with IOP430 mmHg in Densiron-68
and conventional silicone oil group in the postoperative period
Densiron -68 Conventional oil P-value
Number of patients
with IOP 430 mmHg
(%)
Number of patients
with IOP430 mmHg
(%)
Day 1 9 (12.7) 2 (3.5) 0.11
Days 7–14 14(19.7) 3 (5.3) 0.019
Week 4 9 (12.7) 1 (1.8) 0.042
Comparison of postoperative intraocular pressure
D Wong et al
192
Eye
Postoperative inflammation
On the first postoperative day, the majority of patients
had mild inflammation: 43 eyes (60.6%) in the Densiron-
68 group and 34 eyes (59.6%) in the conventional SO
group (P¼0.916) (Table 4). There were six eyes (8.5%) in
the Densiron-68 group and one eye (1.8%) in the
conventional SO group with þþþ to þþþþ
postoperative inflammation (P¼0.098).
Postoperative anterior chamber shallowing, iris bombe,
and oil in the AC
Postoperatively, the anterior chamber (AC) was shallow
in three eyes (4.2%) in the Densiron-68-treated group and
three (5.3%) eyes in the conventional
SO-treated group (Table 4). All of these eyes were
pseudophakic. Iris bombe was seen postoperatively in
two eyes (2.8%) treated with Densiron-68 and in two eyes
(3.5 %) treated with the conventional SO. Eleven eyes
(15.5%) in the Densiron-68 group and none in the
conventional SO group had oil in AC as small bubbles,
within the first week after the surgery. Of these 11 eyes in
the Densiron-68 group, two were aphakic and nine were
pseudophakic. No attempt was made to make the oil
return to the posterior segment as it was present only in
form of small bubbles.
Anatomical results
At surgery, complete re-attachment of retina was
achieved in all cases in both the groups. The retina was
attached in 58 (81.7%) eyes in the Densiron-68 group and
39 (68.4%) eyes in the conventional SO group at the last
follow-up. There was no statistically significant
difference (P¼0.098).
Discussion
Postoperative IOP rise, however, is not uncommon after
vitrectomy and SO injection. In the literature, the
reported incidence varied from 3 to 40%.
10–13
Silicone
study report 4 observed a prevalence of chronically
elevated IOP of 8% in patients treated with conventional
SO.
14
We were not sure whether there was an increased
incidence with Densiron-68, thus we were prompted to
carry out this case–control study.
The matching of preoperative clinical features was
good, although the Densiron-68 group of patients had
less extensive retinal detachment (less than two
quadrants).
The results suggested that IOP was indeed higher in
eyes treated with Densiron-68 as compared with those
treated with conventional SO on day 1 and between day
7 and day 14. The difference between the mean IOP was
small and although it was statistically different at these
time points, was the difference clinically significant? Let
us assume that an IOP greater than 30 mmHg was
clinically significant. Then this pressure occurred more
frequently in Densiron-68 patients than conventional SO
patients. The proportion of patients with IOP of
30 mmHg or more on day 1 was 12.7% for Densiron-68
and 3.5% for conventional SO. The raised IOP also
seemed to be difficult to treat. Thirty Densiron-68
patients were treated for the raised IOP, nine (30%) did
not respond; a number of patients had increasing number
of medication; cyclodiode was necessary in two patients
and at 4 weeks, there were still 12.7% of patients with
IOP greater than 30 mmHg.
What could account for the differences in IOP
observed? More Densiron-68 patients were treated by
retinectomy during the surgery. Retinectomy is generally
associated with postoperative hypotony in the long term.
In the immediate postoperative period, however, there
may be increased inflammation due to the breakdown of
blood-ocular barrier or bleeding associated with cutting
the retina. We did observe a higher incidence of severe
inflammation in patients treated with Densiron-68. This
might be related to the retinectomy or it might be related
intrinsically to the Densiron-68. Theelan and Tilanus
observed an inflammatory response associated with the
use of high-density SO.
15
The oil was seen in AC in 11 (15.5%) eyes in the
Densiron-68 group and none of the eyes in the
Table 4 Postoperative inflammation, shallowing of the anterior chamber, iris bombe, and oil in the AC in the two groups
Densiron-68 (%) Conventional oil (%) P-value
Little or no inflammation 22 (31) 22 (38.6) 0.368
Mild inflammation ( þor þþ) 43 (60.6) 34 (59.6) 0.916
Moderate to severe inflammation ( þþþ or þþþþ) 6 (8.5) 1 (1.8) 0.098
AC shallowing 3 (4.2) 3 (5.3) 0.823
Iris bombe 2 (2.8) 2 (3.5) 0.823
Oil in the AC 11 (15.5) 0 0.002
Comparison of postoperative intraocular pressure
D Wong et al
193
Eye
conventional SO group. The incidence of this
complication was much higher than previously reported
in earlier studies by Wong et al
7
(7%) and Wolf et al
8
(0%).
Theoretically, Densiron-68 should have less of a tendency
to come into AC because it has a higher interfacial
tension against aqueous compared with SO. In the past,
we have reported on pupil block glaucoma associated
with conventional SO in the AC in phakic and
pseudophakic eyes and speculated that this was caused
by overfilling of the globe at the end of surgery.
16
Oil in
AC usually occurs in aphakic eyes and is often associated
with hypotony.
16
The fact that nine of the 11 eyes were
pseudophakic also suggested that the eyes were
overfilled.
16
When oil was present in AC, high IOP
usually ensued and the raised pressure could be difficult
to treat.
16
In summary, there did seem to be a difference in the
IOP response to Densiron-68 as compared with
conventional SO. The difference could be clinically
significant and the raised IOP could be difficult to treat.
This warrants caution for the use of Densiron in the
glaucomatous eyes. The cause of raised IOP may be
multifactorial including, inflammation and overfilling;
the latter at least should be avoided.
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