This LCD addresses use of a group of surgical procedures for glaucoma referred
to as Micro-Invasive Glaucoma surgery (MIGS). Noridian considers up to two
iStent aqueous drainage devices, or one 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. According to CPT, in this
setting a 'device' is a 'stent'. Therefore, 'two iStent aqueous drainage
devices' means two (initial generation) iStents or one pair of stents that are
contained in iStent inject.

One XEN45 device per eye is covered for the management of refractory glaucoma,
defined as prior failure of a filtering/cilioablative procedure and/or
uncontrolled Intraocular Pressure (IOP) on maximally tolerated medical
therapy. 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 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 mm Hg 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. More 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 frequently performed using an
ab interno (from inside the eye) approach via gonioscopic guidance and involve
minimal trauma to ocular tissues. In contrast, traditional filtration
surgeries such as trabeculectomy and aqueous tube shunt, are typically
performed from an external approach.

Compared with traditional filtration surgery, MIGS holds the promise of faster
recovery time and less severe complications and 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
MIGS devices do not preclude subsequent trabeculectomy if needed. Therefore,
health outcomes of interest are the IOP lowering achieved, reduction in
medication use, ability to convert to trabeculectomy, complications, and
device durability.

There are five Food and Drug Administration (FDA) approved/cleared micro-
invasive surgical stents:

(Initial Generation) iStent Trabecular Micro-Bypass Stent (2011) a small (1 mm
x 0.5 mm) L-shaped titanium device that is inserted into the Schlemm canal to
augment the natural outflow system

CyPass Micro-Stent System (July, 2016) a 6.35 mm long fenestrated microstent
made of bio compatible polypeptide inserted into the supraciliary space, thus
using an alternative outflow system

XEN45 Glaucoma Treatment System (November 2016) a 6 mm long porcine-derived
gelatin stent inserted into the subconjunctival space, bypassing the natural
outflow system

Hydrus Microstent (August 2018) an 8 mm nitinol, crescent-shaped microstent
with alternating spines of support and windows to provide outflow, also place
into the Schlemm canal

iStent inject (June, 2018), two 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 instered
into the Schlemm canal using a pre-loaded auto-injection trocar.

The (initial generation) iStent, iStent inject, Hydrus and CyPass were FDA
approved (CyPass was recalled by FDA for safety concerns in September 2018 and
remains so) 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.

According to the 2020 AAO POAG Preferred Practice Pattern (PPP), the
"potential benefits of a combined procedure (cataract extraction with
Intraocular Lens (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, Noridian considers up to two stents (either two initial generation
iStents, or the pair of two stents included in iStent inject*, or one 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 the potential for 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 aqueous drainage implants. Therefore, all
other indications are considered not reasonable and necessary at this time,
including insertion of additional devices beyond what is stated, regardless of
method, since a statistical benefit has not been demonstrated,27 especially in
conjunction with cataract surgery.

The XEN45 device received FDA 510(k) 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 Noridian 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."

Noridian considers one XEN45 device per eye medically reasonable and necessary
for the management of refractory glaucoma, defined as prior failure of
filtering/cilioablative procedure and/or uncontrolled IOP on maximally
tolerated medical therapy. XEN45 insertion must be performed by an
ophthalmologist with experience with trabeculectomy and bleb management.