Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02376725 |
| Other study ID # |
R796/80/2010 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
February 12, 2015 |
| Last updated |
February 25, 2015 |
| Start date |
June 2011 |
| Est. completion date |
February 2015 |
Study information
| Verified date |
February 2015 |
| Source |
Singapore National Eye Centre |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Singapore: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to determine if phacoemulsification with intraocular lens
implant (phaco/IOL) alone or combined with goniosynechialysis is better at controlling
intraocular pressure in subjects with primary angle closure.
Description:
Study Background
Glaucoma is the worlds' leading cause of irreversible blindness with nearly 7 million
bilaterally blind due to the disease, by some estimates, and as such, represents a disease
with significant associated morbidity. Furthermore, as glaucoma is primarily a disease of
old age, as the number of elderly people in the world continues to rise, the number of
people with glaucoma blindness is likely to have increasing economic burden and public
health costs.
Primary glaucoma is classified into 2 types, Primary Open Angle Glaucoma (POAG) and Primary
Angle Closure Glaucoma (PACG). Classification depends on configuration of the anterior
chamber drainage angle, specifically if it is open or if it shows evidence of closure. The
proportions of people with POAG and PACG are approximately equal, with the latter disease
more common in Asians and women. Although the result of both diseases is progressive cupping
of the optic disc with corresponding visual fields loss, the mechanism by which this occurs
is thought to be quite different in the two diseases. In POAG the mechanism is still to be
established but in PACG it is thought that apposition of the peripheral iris to the drainage
angle results in damage to the trabecular meshwork (TM) and the formation of peripheral
anterior synaechiae (PAS) which act as a mechanical obstruction of aqueous outflow via the
trabecular meshwork. This in turn results in raised intraocular pressure (IOP) and
subsequent optic nerve damage. Apposition can occur in anatomically predisposed eyes,
although a physiological dynamic element is likely to be involved also. Areas of the TM not
obstructed by PAS are likely to retain some function, although it is not clear if this is at
the same level as in normal subjects. The functioning of the TM posterior to the areas of
PAS has also yet to be established and it is hope that this study will help to elucidate
this matter.
Conventional initial management of PACG is to perform laser peripheral iridotomy (LPI) to
allow flow of aqueous from the posterior chamber to the anterior chamber through the
iatrogenically created iridotomy. This has two benefits - in those subjects where
pupillary-block is thought to be the mechanism for angle closure, it can reduce the risks of
an acute rise in IOP occurring (acute angle closure). In other subjects with PAC, LPI has
been shown to increase the drainage angle and this has led to lowering of the IOP in some
subjects. However, in a retrospective review of 65 subjects with PACG who had had LPI, after
5 years follow-up the vast majority required further interventions (medications and/or
surgery) to lower the IOP. Furthermore, PAS formation has been show to still occur in the
presence of a patent PI. Clearly, the current conventional management strategy for PAC/PACG
is inadequate and likely to lead to further ocular morbidity.
The poor results of LPI in the long-term for subjects with PACG in terms of IOP control has
led many clinicians to study the effect of cataract surgery on IOP control in these
patients. It was thought that removing the lens would increase anterior chamber depth and
increase the drainage angle and hence increase outflow. Cataract surgery does indeed seem to
open the drainage angle and its effects on IOP control have been promising. However, opening
of the drainage angle may be limited in subjects with significant PAS. This could compromise
the IOP lowering effect of cataract surgery in this group of patients. In such cases,
cataract surgery with mechanical breaking of PAS (i.e. goniosynechialysis) might lower IOP
to a greater extent than cataract surgery alone. Phacoemulsification + intraocular lens +
Goniosynechialysis (PEI-GSL) has been carried out in several published studies, with all
studies reporting a reduction in post-operative IOP compared to pre-operative. The main
complications associated with PEI-GSL are excessive post-operative anterior chamber
fibrinous reaction and anterior chamber bleeding. Theoretically, excessive pressure to break
PAS could also cause iridodialysis or cyclodialysis, with resultant ocular hypotony. In an
effort to reduce these complication risks, Varma and Fraser described phacoemulsification +
intraocular lens + viscogonioplasty (PEI-VGP) in which a viscoelastic is used to break PAS
in a non-iris contact method, rather than using an instrument to push the iris back. The
authors proposed that this procedure would reduce the complications of PEI-GSL but still
open the angle sufficiently. It is not clear however, if PEI-VGP would provide sufficient
force to open areas of PAS and therefore be as efficacious as PEI-GSL in lowering IOP.
Furthermore, there is no evidence that either PEI-GSL or PEI-VGP are superior to
phacoemulsification + intraocular lens (PEI) alone in reducing IOP. Most surgeons will
perform cataract surgery in patients with PAC/PACG and uncontrolled IOP. By adding the
relatively simple step of goniosynechialysis during the surgical procedure, it has been
proposed that this will result in further IOP lowering and hence less risk of glaucoma
development/progression. This has yet to be proven.
An alternative treatment modality in subjects with PAC/PACG, visually significant cataract
and high IOP, would be to perform phaco-trabeculectomy. Two recent randomized controlled
trials published by Tham and co-workers, compared PEI versus phaco-IOL-trabeculectomy in
subjects with medically controlled and medically uncontrolled angle-closure glaucoma. For
the medically controlled group, there was no clinically significant difference in IOP
lowering effect between the two surgical modalities. For the medically uncontrolled group,
both modalities reduced IOP but the phaco-IOL-trabeculectomy group had a significantly lower
IOP. However, the phaco-IOL-trabeculectomy group in both studies had a significantly higher
complication rate than did the PEI group. Furthermore, only 4/27 (14.8%) of eyes in the PEI
group (in the medically uncontrolled IOP study) required subsequent trabeculectomy to
control IOP over the 2 years follow up period. In all these 4 cases, trabeculectomy was
carried out successfully. Extrapolating from these data it would appear that although
phaco-trabeculectomy does lower IOP more than PEI in patients with medically uncontrolled
angle-closure glaucoma, many of these patients would not require 2 combined simultaneous
procedures. Furthermore, trabeculectomy surgery has significant complication rates, even
many years after the surgery is performed. Performing either PEI, or PEI-GSL (with or
without viscoelastic assistance) would likely result in a significant reduction in IOP and
still leave open the option of trabeculectomy (or glaucoma drainage device surgery) later on
as the conjunctiva and sclera would be untouched. This multicentre study is designed to
determine which of these 2 surgical options would superior in terms of efficacy and
complications.
There have been no randomized controlled trials comparing PEI versus PEI-GSL (or PEI-VGP).
There have been several case series and these will be summarized below.
Effect of phacoemulsification + intraocular lens on intraocular pressure in subjects with
primary angle closure In patients with PAC or PACG, there is considerable evidence that PEI
lowers IOP. Hayashi and coworkers, in a prospective study of 77 eyes of 77 consecutive
patient with PACG found that IOP decreased significantly from baseline by an average of 6.1
± 3.9 mmHg at 1 year follow up.5 Tham and co-workers showed an even more considerable
decrease in IOP from a pre-operative mean of 24.4 mmHg to a mean of 15.4 mmHg at 15 months
in a cohort of 27 patients with medically uncontrolled PACG.13 The same group examined the
effect of PEI in a cohort of 35 eyes with medically controlled PACG.14 Pooling the results
from both studies, PEI significantly reduced IOP from a pre-operative mean of 20.4 ± 5.8
mmHg to a mean of 14.6 ± 2.9 mmHg at 1 year, irrespective of pre-operative IOP control.
Effect of phacoemulsification + intraocular lens + goniosynechialysis on intraocular
pressure in subjects with primary angle closure The largest case series on this topic, and
the only prospective study performed on PEI-GSL was that performed by Teekhasaenee and
coworkers. Fifty-two eyes of 48 patients (from Thailand) with PACG all underwent laser
peripheral iridotomy but continued to have raised IOP defined as IOP >21 mmHg. Subjects
underwent PEI-GSL and IOP decreased from a pre-operative mean of 29.7 ± 7.9 mmHg to 13.2 ±
2.9 mmHg at final examination (mean follow up 20.8 ± 15.5 months, range 5-76 months). This
is a mean decrease of 16.5 mmHg.
There are 2 studies on the effect of PEI-VGP on IOP control, both retrospective case series.
In the first, a consecutive series of 15 eyes of patients with refractory PACG, PEI-VGP
reduced IOP significantly from 27.4 mmHg (on medication) to 14.1 mmHg (off all medication in
14/15 eyes), at 6 months.13 This represents a decrease of 13.3 mmHg. A subsequent study of
11 patients (11 eyes) on subjects with PACG (all of whom had refractory control despite
patent peripheral iridotomy) showed a decrease in IOP from 39.4 mmHg pre-operatively to a
mean of 13.4 mmHg after PEI-VGP at 7.8 months follow up.
Effect of phacoemulsification + intraocular lens alone or phacoemulsification + intraocular
lens + goniosynechialysis on angle opening in subjects with primary angle closure
There are several studies which have shown that the drainage angle opens significantly after
PEI in subjects with PAC/G.17;18 Only one paper described the effects of PEI on extent of
peripheral anterior synaechiae. This showed that in subjects with PACG and PAS, there was a
significant reduction in the extent of PAS after PEI, by approximately 25%.8 Most studies of
PEI-GSL also describe opening of the drainage angle in subjects with PAC/G. Several studies
also describe reduction in extent of PAS, including complete elimination of PAS.
The population to be studied will be all patients attending Singapore national Eye Centre
(SNEC), Tan Tock Sen Hospital (TTSH), National University Hospital Singapore (NUHS), Vietnam
National Institute of Ophthalmology, Thailand Faculty of Medicine Siriraj Hospital, Mahidol
University and Hongkong, Queen Mary Hospital
This study will be conducted in compliance with the protocol, Singapore Good Clinical
Practice (SGCP) and the applicable regulatory requirement(s).
Study Objectives and Purpose
To evaluate and compare the effect of two different surgical interventions in patients with
primary angle-closure (with or without glaucoma), high intraocular pressure, and cataract.
These interventions are:
1. phacoemulsification + intraocular lens (PEI)
2. phacoemulsification + intraocular lens + goniosynechialysis (PEI-GSL).
Study Design
Experimental design This is prospective, longitudinal multicentre randomized control trial.
The study sites will be SNEC, TTSH, NUHS, Vietnam National Institute of Ophthalmology,
Thailand Faculty of Medicine Siriraj Hospital, Mahidol University and Hongkong, Queen Mary
Hospital All subjects will undergo baseline and subsequent follow-up and evaluation in a
standardized manner. Those who complete the informed consent process will be randomized to
undergo either treatment with PEI or PEI-GSL. Subjects will then be followed-up for 12
months.
Study hypothesis We hypothesize that, compared to PEI, PEI-GSL will result in significantly
lower IOP reduction both in the short and long term, with a reduction in amount of PAS, a
wider drainage angle and a similar complication rate as PEI.
Patient Selection All subjects attending the glaucoma clinic at SNEC, TTSH, NUHS, Vietnam
National Institute of Ophthalmology,Thailand Faculty of Medicine Siriraj Hospital, Mahidol
University and Hongkong, Queen Mary Hospital will be eligible to be included in the study if
they fulfill the inclusion/exclusion criteria (see below).
Once these criteria are fulfilled, subjects will be enrolled and divided into 2 groups using
a random number generator. Group 1 will undergo PEI alone and Group 2 will undergo PEI-GSL.
Randomization and masking Block randomization method is used for randomization in this
study. A pre-randomized list is generated according to Singapore Eye Research Institute's
(SERI) standard operating procedure for randomization process by the clinic director and
delegated stand-in. Following consent the study coordinator will contact the study centre
(SERI) to obtain the randomization for each enrolled patient. Enrolled patient will be
randomized to undergo either treatment with PEI or PEI-GSL. Randomization will be of
patients and not eyes i.e. if two eyes of the same patient are eligible they will undergo
the same intervention as allocated.
The investigator will be masked to the IOP measurement. Two individuals (an operator and a
reader) will perform the IOP measurement. The operator operating the slit lamp and
instrument dial will not be aware of the readings while the reader will read and record the
results.
Surgical technique Anaesthetic will be general or peribulbar (approximately 3ml volume of
50/50 mix of 2% lignocaine and Marcaine with hyaluronidase). A superior or temporal clear
corneal incision will be performed followed by creation of a paracentesis, injection of 3%
sodium hyaluronate, 4% chondroitin sulfate (Viscoat, Alcon laboratories) and capsulorhexis.
Hydrodissection is then performed using balanced salt solution and the lens is removed using
phacoemulsification of the lens nucleus and aspiration (automated or manual) of cortical
lens matter. After further injection of Viscoat, an acrylic injectable intraocular lens will
be inserted into the capsular bag, its power having been determined pre-operatively based on
biometric measurements. The Viscoat will then be removed (automated or manual), in the case
of subjects undergoing PEI.
For those subjects PEI-GSL, the goniosynechialysis will be performed after partially filling
the anterior segment with Sodium Hyaluronate 14mg/ml ("Healon GV", Advanced Medical Optics
(AMO), California, USA). Using a goniolens (with coupling agent) to visualize those areas of
PAS (defined pre-operatively), the viscoelastic will be used to break areas of PAS wherever
possible, without touching the TM or iris. In cases where the viscoelastic is unable to
break PAS, an iris repositor will be used to gently break the PAS in the areas where it
exists. After this is performed, the surgery will continue as above, with removal of any
remaining viscoelastic by automated or manual irrigation and aspiration.
Surgeries will be performed by senior ophthalmic surgeons. Any intraoperative complications
(such as posterior capsular rupture, hyphaema, iris damage) will be recorded.
