This LCD addresses use of a group of new surgical procedures for glaucoma
referred to as micro-invasive glaucoma surgery (MIGS). NGS considers one
iStent, iStent inject, or Hydrus device per eye medically reasonable and
necessary for the treatment of adults with mild or moderate open-angle
glaucoma and a cataract when the individual is currently being treated with an
ocular hypotensive medication and the procedure is being performed in
conjunction with cataract surgery. One XEN45 device per eye is covered for the
management of refractory glaucoma, defined as prior failure of
filtering/cilioablative procedure and/or uncontrolled IOP (progressive damage
and mean diurnal medicated IOP 20 mm Hg) on maximally tolerated medical
therapy (i.e., 4 classes of topical IOP-lowering medications, or fewer in the
case of tolerability or efficacy issues). XEN45 insertion must be performed by
an ophthalmologist with experience with trabeculectomy and bleb management.



Primary open-angle glaucoma (POAG) has a prevalence in the US of 2% of adults
over 40 years old, or about 2.2 million people, and is expected to increase to
3.3 million in 2020 as the population ages (1). POAG is a chronic, progressive
optic neuropathy in adults in which there is a characteristic acquired atrophy
of the optic nerve and loss of retinal ganglion cells and their axons. It is
associated with an increased intraocular pressure (IOP), due to a buildup of
aqueous fluid within the eye which can lead to visual field loss and optic
nerve damage, usually without any associated pain or discomfort. The increased
IOP is secondary to an imbalance between aqueous fluid secretion and fluid
outflow despite an open angle. Nearly 40% of those with otherwise
characteristic POAG may not have elevated IOP measurements (1).  
  
In the primary (conventional) outflow pathway from the eye, aqueous humor
passes through the trabecular meshwork, enters a space lined with endothelial
cells (Schlemm canal), drains into collector channels, and then into the
aqueous veins. Increases in resistance in the trabecular meshwork or the inner
wall of the Schlemm canal can disrupt the balance of aqueous humor inflow and
outflow, resulting in an increase in IOP and glaucoma risk.  
  
The goal in POAG is to reduce the IOP to slow the development of optic nerve
damage. The IOP can be reduced by medical treatment or surgery, alone or in
combination. IOP above 21 mmHg has been shown to increase rates of visual
field loss. However, because of the differences in susceptibility to pressure-
related disc damage among POAG patients, pressure-lowering treatments are
aimed at achieving a lower "target" pressure individualized to each patient's
baseline IOP in which glaucomatous damage occurred.  
  
When the maximum tolerated medical therapy fails to control progression of
glaucomatous optic neuropathy, surgical care is considered the next treatment
option. Traditional filtration surgery includes trabeculectomy (including
ExPress shunt) and aqueous drainage implants (Ahmed, Baerveldt, Molteno).
Trabeculectomy uses the patient's own sclera to create a fistula to the
subconjunctival space over the sclera superiorly. Aqueous drainage implants
use silicone/plastic tubing and large plates to shunt aqueous to the
subconjunctival space in the equatorial region of the eyeball.  
  
While IOP outcomes are generally worse with aqueous drainage implants compared
with trabeculectomy, complications such as hypotony (low pressure), and
postoperative infection are reduced. However, failure rates are similar
(approximately 10% of devices fail annually), and shunts still have
complications, including corneal endothelial failure and erosion of the
overlying conjunctiva.  
  
The term micro-invasive or minimally invasive glaucoma surgery (MIGS) refers
to a group of newer surgical procedures that are performed by using an ab
interno (from inside the eye) approach via gonioscopic guidance and involve
minimal trauma to ocular tissues. In contrast to external filtration surgeries
such as trabeculectomy and aqueous tube shunt, these procedures are
categorized as internal filtration surgeries. Compared with traditional
filtration surgery, MIGS holds the promise of faster recovery time and less
severe complications.  
  
It is this potentially improved safety profile that opened up the indications
for MIGS to include patients with early-stage glaucoma to reduce the burden of
medications and problems with compliance (due to eye drop application
difficulty, cost, cosmetic effects, and frequency). Another area of
investigation is patients with glaucoma who require cataract surgery. An
advantage of ab interno shunts is that they may be inserted into the same
incision and at the same time as cataract surgery. In addition, most devices
do not preclude subsequent trabeculectomy if needed. Therefore, health
outcomes of interest are the IOP achieved, reduction in medication use,
ability to convert to trabeculectomy, complications, and device durability.

There are five FDA approved/cleared micro-invasive surgical stents, the iStent
Trabecular Micro-Bypass Stent (2011), the CyPass Micro-Stent System (July,
2016), the XEN Glaucoma Treatment System (Nov., 2016), the Hydrus Microstent
(Aug., 2018), and the iStent inject (Jun, 2018). The iStent is a small (1 mm x
0.5 mm) L-shaped titanium device that is inserted into Schlemm's canal to
augment the natural outflow system. The iStent inject system comprises 2
heparin-coated titanium stents (each having 0.23 mm diameter x 0.36 mm height,
0.08 mm central lumen diameter, and four 0.05 mm side outlets to allow for
multidirectional outflow), both inserted into Schlemm's canal using a pre-
loaded auto-injection trocar. Hydrus is a 8 mm nitinol, crescent-shaped
microstent with alternating spines for support and windows to provide outflow,
also placed into Schlemm's canal. CyPass is a 6.35 mm long fenestrated
microstent made of biocompatible polyimide inserted into the supraciliary
space, thus using an alternative outflow system. The XEN45 is a 6 mm long
porcine-derived gelatin stent inserted into the subconjunctival space,
bypassing the natural outflow system.

iStent, iStent inject, Hydrus and CyPass were FDA approved (Cypass recalled by
FDA for safety concerns Sept., 2018) for use in combination with cataract
surgery to reduce IOP in adults with mild or moderate OAG and a cataract that
are currently being treated with medication to reduce IOP. XEN45 was granted
FDA clearance for the management of refractory glaucoma, including cases where
previous surgical treatment has failed, cases of primary open angle glaucoma,
and pseudoexfoliative or pigmentary glaucoma with open angles that are
unresponsive to maximum tolerated medical therapy. The published pivotal trial
data for each, constituting the main evidentiary support, is summarized in the
attached table. MIGS Pivotal Trials





According to the 2015 AAO POAG Preferred Practice Pattern (PPP), the
"potential benefits of a combined procedure (cataract extraction with IOL
implantation and glaucoma surgery) are protection against the IOP rise that
may complicate cataract surgery alone, the possibility of achieving long-term
glaucoma control with a single operation, and elimination of the risk of bleb
failure with subsequent cataract surgery when glaucoma surgery is performed
first. Therefore, an ophthalmologist may reasonably choose to perform a
combined surgery because of these perceived advantages to an individual
patient (1)." ~~  
  
~~In summary, NGS considers one iStent, iStent inject*, or  Hydrus device per
eye medically reasonable and necessary for the treatment of adults with mild
or moderate open-angle glaucoma and a cataract when the individual is
currently being treated with an ocular hypotensive medication and the
procedure is being performed in conjunction with cataract surgery. In that
setting these procedures offer a reduction in IOP, decreased dependence on
glaucoma medications, and an excellent safety profile. However, their role
within the glaucoma treatment algorithm continues to be clarified and differs
from the role of more invasive, external filtration glaucoma surgeries such as
trabeculectomy or external aqueous drainage implants. Therefore, all other
indications are considered not reasonable and necessary at this time. There is
no additional payment for multiple devices (so-called "dosing"), regardless of
method, since a statistical benefit has not been demonstrated (27), especially
in conjunction with cataract surgery.  

The XEN45 device received 510K clearance based on having a similar mechanism
(subconjunctival pathway) as "gold standard" filtration procedures
(trabeculectomy and tube shunts), demonstrating "substantial equivalence" in
the pivotal prospective study of patients with refractory glaucoma (17).
Equivalency was further established by a relatively large retrospective cohort
study comparing XEN45 with trabeculectomy, finding "no detectable difference
in risk of failure and safety profiles" (11). In addition, the American
Glaucoma Society (AGS), the New York State Ophthalmological Society (NYSOS),
and numerous glaucoma experts wrote NGS to support XEN45 as a minimally
invasive method that, "would improve the access of older patients with
refractory glaucoma to surgical care with reduction in post-operative
discomfort, shorter post-operative disability, equivalent efficacy and
safety."

NGS considers one XEN45 device per eye medically reasonable and necessary for
the management of refractory glaucoma, defined (based on the pivotal trial
criteria) as prior failure of filtering/cilioablative procedure and/or
uncontrolled IOP (progressive damage and mean diurnal medicated IOP 20 mm Hg)
on maximally tolerated medical therapy (i.e., 4 classes of topical IOP-
lowering medications, or fewer in the case of tolerability or efficacy
issues). XEN45 insertion must be performed by an ophthalmologist with
experience with trabeculectomy and bleb management.

*The iStent inject device consists of the 2-stent system. There is no coverage for placement of part of the device (i.e., only one of the two stents).