Citation: Zhang
J, Wang NL. Progression on canaloplasty for primary open angle glaucoma. Int
J Ophthalmol 2019;12(10):1629-1633. DOI:10.18240/ijo.2019.10.16
·Review Article·
Progression
on canaloplasty for primary open angle glaucoma
Jun Zhang1,2, Ning-Li Wang1
1Beijing Tongren Eye Center, Beijing
Tongren Hospital, Capital Medical University, Beijing 100005, China
2Dalian Aier Eye Hospital, Dalian
116031, Liaoning Province, China
Correspondence to: Ning-Li Wang. Beijing Tongren Eye
Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100005,
China. wningli@vip.163.com
Received:
Abstract
As a non-penetrating glaucoma
surgery (NPGS), canaloplasty aims to reconstruct the physiological outflow of
aqueous humor by dilating the Schlemm’s canal. Ab interno canaloplasty (ABiC),
which can reconstruct the natural outflow pathways of aqueous humor in
mild-to-moderate primary open angle glaucoma (POAG) patients, is a new
minimally invasive glaucoma surgery (MIGS) procedure improving from traditional
canaloplasty. Canaloplasty can reduce intraocular pressure (IOP) with high
efficiency and security. There are no complications such as scar formation and
encapsulation for this no-bleb canaloplasty.
KEYWORDS: glaucoma; canaloplasty; ab-interno
canaloplasty
DOI:10.18240/ijo.2019.10.16
Citation: Zhang
J, Wang NL. Progression on canaloplasty for primary open angle glaucoma. Int
J Ophthalmol 2019;12(10):1629-1633
INTRODUCTION
Glaucoma is
the leading cause of irreversible blindness worldwide[1].
It is estimated to be 3.54% of the the global prevalance of glaucoma.The number
of people with glaucoma worldwide (aged 40-80y) will increase to 111.8 million
in 2040[2]. Currently intraocular pressure (IOP) reduction is the only therapeutic
measure for glaucoma management. The effective treatment for glaucoma not only
is reduction of IOP but also is modulation of IOP[3].
In medically uncontrolled primary open angle glaucoma (POAG), the gold standard
for reduction of IOP is trabeculectomy[4]. However,
serious complications, such as bleb encapsulation, bleb scarring, wound
leakage, shallow anterior chamber, hypotension and choroidal detachment are
associated with trabeculectomy. Canaloplasty is a newly developed surgery by
circumferential viscodilation and tensioning of Schlemm’s canal with a
flexible microcatheter[5]. It reconstructs and
increases the natural outflow of aqueous humor. This minimally invasive
glaucoma surgery (MIGS) which has better clinical application prospects[6] can avoid the complications of the traditional
incisional glaucoma surgery.
ORIGIN OF CANALOPLASTY
As a non-penetrating glaucoma
surgery (NPGS), canaloplasty aims to reconstruct the physiological outflow of
aqueous humor by dilating the Schlemm’s canal[7].
The flexible microcatheter (Menlo Park, California, USA) guided by He-Ne
laser was inserted and leaded in the Schlemm’s canal to a circle. A single or
double 10-0 prolene suture was tied to the distal tip. The microcatheter was
withdrawn and leaded back through the canal in the opposite direction. A
THE MECHANISM OF CANALOPLASTY IN PRIMARY OPEN ANGLE GLAUCOMA SURGERY
Xin et al[9]
reported that the mechanisms of IOP reduction in reconstruction of aqueous
outflow drainage (RAOD) in POAG of canaloplasty were as follows: 1) Circumferential
dilation of the Schlemm’s canal (SC) and surrounding collector channels. Swain et
al[10] reported that Schlemm’s canal
collapsed in most POAG patients. The Schlemm’s canal was expanded and the
aqueous humor outflow was increased during the reconstruction of the
physiological aqueous humor outflow system. At the same time, the partitions,
bridge and valve-like structures in the Schlemm’s canal were cut off. 2)
Instant formation of microcracks through RAOD procedures. Irshad et al[11] reported that the average diameter of Schlemm’s canal
in vivo was 121 micron, while the microcatheter was 250 micron. This
would make the Schlemm’s canal expand sufficiently during the process of
microcatheter insertion and viscodilation. The endothelial cells and TM of the
Schlemm’s canal were broken slightly simultaneously. The micropore of the
Schlemm’s canal can be directly connected with the surrounding tissue. 3)
Formation of more pores, and local detachment between the Schlemm’s canal
endothelium (SCE) and basement membrane. The resistance of the inner wall of
Schlemm’s canal restricts aqueous humor outflow. Braakman et al[12] reported that the number of pores on Schlemm’s
canal wall was reduced in glaucoma patients. More pores of the Schlemm’s canal
were made by biomechanical tension. The outflow of aqueous humor was increased
with the tight junction among endothelial cells, basement membrane and
surrounding tissues. 4) Activation of stem cells by constant mechanical stress
caused by the tensional suture placed at the anterior part of the Schlemm’s
canal. Braunger et al[13] reported that
there were a group of typical cells near the Schwalbe line confirmed by
immunohistochemical staining. TM stem cells could differentiate into TM cells
with phagocytic function by constant mechanical stress in glaucoma patients.
Roubeix et al[14] reported that IOP
decreased rapidly and persistently when bone marrow mesenchymal stem cells were
injected into the eyes of mice with ocular hypertension. The expression of COT4
and Sox2 markers were up-regulated with the persistence of TM tension. Then TM
stem cells differentiate and migrate to repaire the glaucomatous damaged TM and
the aqueous humor outflow was increased[15]. 5)
Reversal of TM herniation. TM was attached to the outer wall of Schlemm’s canal
under the physiological IOP. However, the TM entered Schlemm’s canal to form TM
hernia under high IOP. Canaloplasty could relieve TM hernia and dilate
Schlemm’s canal[16]. 6) Mobilization of the
reserve of the aqueous drainage. Chang et al[17]
reported the segmental outflow of aqueous humor was determined by the uneven
distribution of pores and collecting channels in Schlemm’s canals. The
collecting channels modulated the IOP when it fluctuates. This imbalanced
segmental outflow was more prominent in glaucoma patients. 7) Change of SCE
phenotype. The endothelium of Schlemm’s canal possess the characteristic of
lymphocytes and vascular endothelium. The integrity of Schlemm’s canal were
determined by lymphocyte regulatory factors PROX1 and vascular endothelial
growth factor-C/-3. Lymphocytes possess the characteristic of drainage. The IOP
of some incisional filtration surgery with failed bleb was well controlled,
which may be related to the stimulated lymphocyte configuration cells. These
cells could restore and reconstruct the physiological drainage function of
Schlemm’s canal. 8) Strengthened mechanical induction and conduction of TM:
Fuchshofer and Tamm[18] reported that the
degenerated TM would cause the increase of resistance of aqueous humor outflow.
The hardness of the aqueous humor outflow system was depended on TM and
extracellular matrix. Changes in tissue hardness could also lead to changes in
TM[19]. Continuous biomechanical tension
by suture in canaloplasty could stimulate the cellular regulation of TM and
extracellular matrix. It could also activate stem cells to secrete cytokines.
These molecules and cytokines could adjust and repair the dysfunctional
microenvironment of TM.
COMPARISONS BETWEEN CANALOPLASTY AND OTHER TYPES OF GLAUCOMA SURGERY FOR POAG
Compared with trabeculectomy,
canaloplasty has the following advantages: 1) no filtering bleb formation; 2)
without antimetabolites; 3) rapid visual recovery; 4) fewer complications; 5)
simple postoperative nursing; 6) stable postoperative IOP. Khaimi[20] reported that canaloplasty was as effective as
trabeculectomy. Compared to trabeculectomy complications, many of these
problems were easily resolved and some should perhaps not be classified as
complications at all. As noted earlier, a study by Grieshaber[21] showed that the absence of microhyphaema on the first
postoperative day actually seems to be a negative prognostic indicator in
uneventful canaloplasty procedures in patients with POAG. It is reported that
the success rates of trabeculectomy were 80%, 66.2% and 42% in 2, 3 and 4y
respectively, while canaloplasty was 76%, 52.9% and 21% respectively[22]. Harvey and Khaimi[23]
reported that canaloplasty had repeatedly been shown to be safe and effective
at significantly lowering IOP and medication dependence in different patient
populations with POAG. Whites, blacks and selected Asian patients responded
similarly to canaloplasty making this procedure favorable for many races
despite the more robust scar tissue formation seen in blacks or the narrower
angle anatomy seen in Asians. Interventions of failed filtering blebs include
needling, subconjunctival injection of 5-FU and other complicated
post-operative nursing. Most postoperative patients of trabeculectomy have the
ocular surface problem. Heidelberg corneal scan revealed conjunctival
microcysts formation and dilatation of aqueous veins which suggested that
canaloplasty could increase aqueous humor passing through sclera and
conjunctiva. It was also the mechanism of IOP reduction in canaloplasty[24].
The integrity and function of Schlemm’s canal could be
assessed by blood reflux which could be observed by gonioscopy examination or
Schlemm’s canal fluorescence angiography. Congestion and emptying of Schlemm’s
canal were slower in mild-to-moderate glaucoma and there was almost no blood
filling in advanced glaucoma. When IOP was below
ADVERSE EVENTS AND COMPLICATIONS ASSOCIATED WITH CANALOPLASTY
When compared with trabeculectomy,
canaloplasty offers a more favorable side effects profile[23].
Inability to cannulate Schlemm’s canal, Descemet’s membrane detachment and
improper microcatheter passage are the main side effects of canaloplasty.
Postoperative microhyphaema is a positive prognostic indicator in canaloplasty[27]. The outflow of blood from the collector channels
indicated that the channels of aqueous humor outflow was opened and effective.
There were 1.9% patients with TM damaged by suture and 26% patients unfinished
with tension suture placed in the canaloplasty. There were 11% postoperative
choroidal detachment, 9.8% hypotension and 9.1% Descemet’s membrane detachment.
There were 1.6% IOP higher than
CANALOPLASTY COMBINED WITH OTHER OPERATIONS AND DRAINAGE IMPLANTATION IN POAG
In POAG, canaloplasty combined with
phacoemulsification can reduce IOP more significantly than single operation[28]. Stegmann Schlemm canal dilator was a new implantable
device that would make canaloplasty a simple, controllable and reproducible
procedure. The material of the expander was polyimide resin, biocompatible, and
non-metallic. The device has a diameter of 240 microns that was used to expand
TM and Schlemm’s canal permanently. Grieshaber et al[29]
reported that 45 patients with POAG of white race who were treated with
medication for uncontrolled IOP (IOP was still >
EVOLUTION, ADVANTAGES AND DISADVANTAGES OF INTERNAL CANALOPLASTY FOR POAG
Ab interno canaloplasty (ABiC) is a
new type of minimally invasive surgery for glaucoma[30].
The incision is about 1.5
FUTURE APPLICATION OF CANALOPLASTY IN GENE THERAPY FOR POAG
The method of reducing permanent
outflow resistance through gene therapy has attracted extensive attention of
researchers. But the safety and effectiveness of TM-targeted gene therapy
needed to be further developed. Canaloplasty can be used for direct delivery of
gene vectors in Schlemm’s canal and TM for gene therapy of POAG. Tian and
Kaufman[31] reported that Schlemm’s canal and the
cells of the inner wall of the juxtacanalicular tissue were the target of gene
therapy. Gene therapy by canaloplasty could transfer nucleic acid vector to the
target tissue and improve its expression which can reduce the resistance of
aqueous humor outflow. Gene therapy can permanently reduce the outflow
resistance of aqueous humor with the development of molecular biology and gene
technology. At present, TM targeting gene therapy includes dominant inhibition
of Rho gene, Rho kinase, exoenzyme C3 transferase, calmodulin binding protein
and so on[32]. Gene therapy for POAG can
induce immune inflammation in anterior chamber by injecting gene carrier
material through corneal incision. Thus, gene vector is loaded into Schlemm’s
canal by canaloplasty. Virus vectors from Schlemm’s canal to TM increases
substantially for Schlemm’s canal to break slightly when injected the
viscoelastic agent. Additionally, the transgene expression at the TM/Schlemm’s
canal is further enhanced by expression of the whole Schlemm’s canal. No immune
inflammation was induced in anterior chamber by canaloplasty gene therapy for
POAG.
PROSPECT
POAG is a major public health
problem with its increasing prevalence and substantial impact on quality of
life for patients, their families, and caregivers. MIGS procedures could reduce
IOP with lower risk than traditional filtration surgery. Canaloplasty is an
option for mild-to-moderate POAG and antimetabolites are not needed. There is
no filtering bleb formation and less surgical induced astigmatism (SIA) in this
minimally invasive operation[33]. For its safety
and effectiveness, canaloplasty will change the current concept of POAG.
Canaloplasty focus on reconstruct of the aqueous humor physiological drainage
directly. Continuous stretching of sutures in Schlemm’s canal promotes and
strengthens the drainage of aqueous humor. Future research should focus on how
to simplify the operation procedure. ABiC is the most minimally invasive
canaloplasty at present. It can reduce the economic burden of glaucoma
medications, avoid the complications of traditional glaucoma filtration surgery
and lessen the complex postoperative care. Canaloplasty will play an important
role in POAG treatment.
ACKNOWLEDGEMENTS
Conflicts of Interest: Zhang J, None; Wang NL,
None.
REFERENCES