**Background** :

[Dextenza](https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208742s001lbl.pdf)
(Ocular Therapeutix, Inc., Bedford, MA, USA) is a resorbable hydrogel
corticosteroid implant indicated for treating ocular inflammation and pain
after ophthalmic surgery. After surgery, the insert is placed in the lower
lacrimal punctum and into the canaliculus. The insert releases 0.4 mg of
dexamethasone over 30 days onto the eye surface. It is made from a
polyethylene glycol-based hydrogel conjugated with fluorescein, which is
resorbable and does not require removal. Anterior chamber inflammation (10%)
and elevated intraocular pressure (IOP) (6%) were the most common adverse
reactions. IOP should be monitored during treatment. Dextenza should not be
used in patients with active corneal, conjunctival, or canalicular infections,
including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia,
varicella, mycobacterial infections, fungal eye diseases, and dacryocystitis.

Dextenza is an alternative to topical corticosteroid preparations (e.g., eye
drops) used to reduce pain and inflammation after cataract surgery. Persistent
inflammation may lead to complications, such as increased IOP, cystoid macular
edema, secondary glaucoma, delayed recovery, ocular pain, and reduced vision.
However, patients may have difficulty delivering the correct dose when using
topical eye drop preparations; eye drops may need to be tapered over time and
are associated with poor patient adherence.1 The elderly population, in
particular, typically has more difficulty using eye drops to deliver topical
corticosteroids after eye surgery.

**Coverage Indications and limitations** :

Palmetto GBA considers the use of the Dextenza dexamethasone insert
reasonable and necessary for the treatment of ocular inflammation and pain
following ophthalmic surgery.

Dextenza is contraindicated in patients with the following conditions:

  * active corneal, conjunctival or canalicular infections, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella
  * mycobacterial infections of the eye
  * fungal diseases of the eye
  * dacryocystitis.

An integrated assessment of Dextenza's efficacy in ophthalmic surgery was
demonstrated across 3 Phase 3 trials that included a total of 926 subjects
(n=541, Dextenza, n=385, placebo insert).1-3 An ad hoc pooled analysis of the
3 Phase 3 studies demonstrated patients receiving Dextenza achieved
statistically, significantly superior outcomes compared to patients receiving
placebo vehicle in both primary efficacy endpoints, with 42.7% of
Dextenza-treated patients observed to have absence of anterior chamber cells
(score of 0) at Day 14 (placebo: 27.5%; P < 0.0001), and 79.2% of
Dextenza-treated patients observed to have absence of ocular pain (score of
0) at Day 8 (placebo: 56.9%; P < 0.0001) with a favorable safety profile.
Across all 3 studies, a greater proportion of subjects in the placebo group
experienced at least 1 ocular adverse event in the study eye, as compared to
patients receiving the Dextenza insert. The most common Dextenza ocular
adverse events (>1%) were increased (IOP), anterior chamber inflammation
including iritis and iridocyclitis, eye inflammation, reduced visual acuity,
corneal edema, and cystoid macular edema. There were no treatment-related
serious adverse events.1-3

Physician-administered Dextenza delivers a 30-day tapered dose of
dexamethasone to the eye (consistent with current standard of care tapered
dosing regimen of patient-administered topical steroid drops).1,2 Physician
administration of Dextenza avoids risk of improper patient installation
techniques with post-op topical eye drop therapy, complicated steroid tapering
dosing regimens for patient administration, manual dexterity challenges
associated with older age,5 and may reduce the potential for ophthalmic
sequelae typically associated with poor patient adherence during the critical
post-operative care period. Persistent ocular inflammation can potentially
increase the risk for secondary ocular complications, such as increased IOP,
cystoid macular edema (CME), posterior synechiae formation, posterior capsule
opacification, secondary glaucoma, delayed recovery, ocular pain, and reduced
visual outcomes, whereas untreated pain can affect overall patient surgical
satisfaction.6-8

Dexamethasone is a potent corticosteroid, and the Dextenza Phase 3 data
support the utility of a sustained-release intracanalicular insert delivery
approach of dexamethasone to the ocular surface following ocular surgery.1,2
Relevant to IOP increases associated with ophthalmic surgery, the overall
safety outcomes of an ad hoc pooled analysis of the Phase 3 Dextenza studies
showed IOP elevation with Dextenza (6.3%) compared to placebo (3.4%);3 of all
events, only 1 IOP increase in the dexamethasone insert arm (0.2%) out of 538
patients across 3 studies was considered by the investigator to be related to
treatment.1-3 It is hypothesized the observed rates of IOP increase
demonstrated with Dextenza compared to placebo in the Phase 3 studies may
potentially be associated with the reduced Cmax of sustained release
preparations (e.g., Dextenza), as compared to topical steroid therapy.1

Additionally, the benefits of consistent tapered dosing with a dexamethasone-
eluting intracanalicular insert is potentially clinically meaningful in the
context of the demonstrated poor bioavailability of topical steroid eye drop
preparations.9 The pharmacokinetic properties of the drug-eluting
intracanalicular insert, in preclinical animal models, suggests sustained and
tapered drug release into the tear film may minimize the potential of ocular
rebound inflammation and demonstrate dexamethasone is eluted directionally and
unilaterally towards the ocular surface, indicating limited systemic exposure
and reduced wasted drug product.10

By being physician-administered, Dextenza eliminates the potential for
improper drop installation techniques, including missing the eye, instilling
an incorrect number of drops, bottle tip contamination with ocular surface
contact, and failure to wash hands prior to patient-administered topical
therapy;11 these challenges may be common amongst Medicare-aged patients.
Researchers observed in an elderly ( _>_ 80 years) population with chronic
ophthalmic pathologies, 61% scratched the eyedrop container along the
conjunctiva or cornea upon administration, and 11% of patients in this cohort
failed to successfully apply a drop to the ocular surface.2,13

Finally, placement of Dextenza into the intracanalicular space may afford the
additional benefit of punctal occlusion. Available data indicate punctal
occlusion following ophthalmic surgery is associated with improvement in
postoperative healing and may prevent post-operative dry eye complications. In
a study of refractive ocular surgery patients who received unilateral punctal
occlusion following LASIK surgery, statistically significant ocular surface
index score improvement was demonstrated, suggesting a decrease in dry eye
disease severity.14

Overall, results of the Phase 3 Dextenza pooled studies support a greater
proportion of patients treated with Dextenza demonstrated an absence of
ocular pain as early as the day after surgery (Day 2), and absence of
inflammation as early as 3 days after surgery (Day 4). Additionally, there
were consistently similar results with Dextenza across all the evaluated time
points compared to placebo.3 Treatment with Dextenza in the Phase 3 Clinical
Trials demonstrated tolerability and efficacy during the post-operative
period.1-3

There have been 4 high quality, multicenter, double-blind random control
trials (RCTs) all conducted within the United States. The trials were industry
supported and lacked a comparison with the standard of care, dexamethasone eye
drops. A limitation in the available studies is the lack of a comparison study
between dexamethasone eye drops and Dextenza. Studies reported outcomes up to
120 days after implant use with an excellent safety profile; however, no long-
term data exists for potential adverse events.

Despite these limitations, given the availability of sufficient safety and
efficacy data and the studies referenced above, the use of the dexamethasone
insert to treat ocular inflammation and pain following ophthalmic surgery is
reasonable and necessary. Off-label use of the dexamethasone insert for
treatment of non-surgical conditions lacks evidentiary support and is
considered investigational and will not be covered by Medicare outside of
otherwise covered clinical trials.