Rates of Middle Meatus Synechiae Formation Post Endoscopic Sinus Surgery

Endoscopic sinus surgery (ESS) is the gold standard surgical intervention for chronic
rhinosinusitis that is not adequately controlled with medical therapy. Synechiae formation in
the middle meatus is the most common complication of endoscopic sinus surgery. Synechiae
describes the adhesion of two opposing mucosal surfaces in the nasal cavity that can cause
scarring and obstruction of the nasal passage. Incidence of synechiae formation varies in
literature and ranges between 4-35 %. Presence of middle meatal synechiae can impair sinus
drainage, promote sinusitis, and limit endoscopic visualization of the sinus cavities
postoperatively. This may result in difficulty in performing postoperative routine endoscopic
debridement and examination, which is paramount to a successful outcome from ESS.

To prevent synechiae formation, numerous studies have been published evaluating the
effectiveness of absorbable and non-absorbable spacers placed in the middle meatus for 1-2
weeks postoperatively. The spacer is meant to prevent contact between the denuded surfaces of
the middle turbinate and the lateral nasal wall during re-epithelialization. In general,
non-resorbable spacers that have been used include sponges, cotton gauze and plastic sheets.
Of these, Silastic Silicone sheets have been used in a number of hospitals across the US and
Canada. Lee and Baguley have demonstrated the effectiveness of Silastic spacers in reducing
the risk of synechiae formation to between 0-6 %. There are also a number of resorbable
spacers that are in use, which are preferred by some physicians because there is minimal need
to remove the packing materials as they naturally are removed or resorbed during the healing
period.

In a recent meta-analysis, Lee et al has revealed that usage of middle meatal spacers
(absorbable and non-absorbable) did not decrease the rate of synechiae formation to a
statistically significant degree compared to not using any spacer. However, when subgroup
analysis was performed, non-absorbable spacer usage demonstrated a statistically significant
lower incidence of synechiae compared to no spacers. This can be explained in part by an
inherent capability of the absorbable spacer material to degrade to smaller size particulates
that, if caught in the healing tissue, could illicit local inflammatory response to slow down
the healing and cause further synechiae formation. This mechanism was demonstrated by
Maccabee et al in a rabbit model, where fibers of the absorbable spacer became incorporated
into healing mucosa and increased the extent of the inflammatory response and formation of
fibrosis.

To improve outcomes, physicians have attempted to load steroids such as Triamcinolone and
antibiotics such as Neosporin into nasal packing and/or stents. However, residence of the
drug in the intended treatment space is minimized as the drug, which is not bound to the
spacer, quickly releases and may not remain long enough to impact inflammatory response. A
Mometasone Furoate coated stent (Propel™), manufactured by Intersect ENT, is currently the
only drug coated nasal stent that has a claim of longer sustained release. In a randomized,
controlled, double-blind trial, Marple et al found that this Mometasone Furoate
steroid-eluting bio-absorbable stent could significantly improve postoperative outcomes
compared to a non-steroid eluting placebo arm with the same stent. Zhao et al conducted a
systematic review of the efficacy of this steroid-eluting stent (Propel) vs inert (both
resorbable and non-resorbable) spacers and again confirmed that there are lower rates of
synechiae formation in the steroid-eluting treatment groups. However, anecdotal evidence,
based on discussion with a number of surgeons in the field, suggests that a drug-loaded
resorbable spacer may be subject to the same issues as non-drug-loaded resorbable spacers,
namely late stage degradation of the material that can cause a secondary spike of the
inflammatory cascade, requiring additional surgical intervention to remove the remaining
debris.

Therefore, it has been hypothesized that a steroid eluting non-absorbable spacer may provide
optimal benefit for the patient's outcome. The Restora™ spacer is made of a biocompatible
non-resorbable material that is expected to deliver up to 370 µg of Mometasone Furoate. The
steroid elutes out of the spacer and onto the surrounding mucosal tissue during the 6-8 day
period during which it is retained.

This study is designed to evaluate basic device usability and confirm safety and
effectiveness of the Restora™ Steroid eluting spacer as compared to the standard of care
Silastic Silicone spacer.

Inclusion Criteria:

1. Age between 18 and 75 years

2. Diagnosis of chronic rhinosinusitis (CRS), per current guidelines

3. Patients who need to undergo primary bilateral complete endoscopic sinus surgery

4. Subject has the ability to follow the study instructions, is willing to be available
on the specific required study visit days, and is willing to complete all study visit
procedures and assessments

5. Subject must understand the research nature of this study and sign an informed consent
prior to the performance of any study-specific procedure or assessment

Exclusion Criteria:

1. Subject is pregnant or breast feeding

2. Patients with sino-nasal tumors

3. Patients solely undergoing nasal septal reconstruction

4. Patients with previous history of endoscopic sinus surgery

5. Cystic fibrosis or syndromic patients

6. Patients with autoimmune diseases

7. Patients who have taken oral steroids less than 30 days prior to surgery

8. Patients with a history or diagnosis of glaucoma or ocular hypertension

9. Any other circumstance or condition that in the Investigator's opinion causes the
subject to be an inappropriate candidate for participating in this study