Chronic rhinosinusitis (CRS) is an inflammatory syndrome affecting more than 10% of Western populations and is characterized by persistent nasal obstruction, drainage, facial pressure, and loss of smell. CRS is often divided into two phenotypes based on nasal endoscopy—CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP)—but there is notable clinical overlap. CRSwNP is most commonly characterized by type 2 eosinophilic inflammation in Western countries. The etiology and pathogenesis continue to be investigated, but severe mucosal inflammation in the ethmoid sinuses can result in polyp formation that can project into the nasal cavity, obstructing the nasal airway. ^,

First-line management for both phenotypes consists of saline nasal rinses and topical intranasal corticosteroid sprays (INCSs). In severe or resistant cases, extended courses of systemic corticosteroids are used to reduce symptom burden and potentially aid in avoiding surgery. ^, Corticosteroids diminish eosinophil infiltrates, reverse type 2 inflammation, and remain the standard medical treatment for CRSwNP. ^, Systemic corticosteroids can decrease polyp size. However, the effect may be transient, and the duration of therapy may need to be limited to avoid side effects. INCSs have a high margin of safety, but efficacy is blunted by patient noncompliance and the limited access of these drugs to the ethmoid sinus mucosa. The exhalation delivery system with fluticasone is a more recent device that uses a novel closed-palate mechanism to deliver the topical steroid more effectively to the superior and posterior portions of the nasal passage.

Despite the use of topical and systemic corticosteroids, more than 250,000 endoscopic sinus surgeries (ESSs) are performed in the United States annually, with an average of 20% requiring revision surgery within 5 years. The estimated direct and indirect costs of CRS in the United States exceed $30 billion, and CRS accounts for 7% of all antibiotic prescriptions in the United States. ^, Alternative treatment options are particularly needed for CRSwNP, which is associated with higher symptom burden, increased medication use, greater revision rate, and higher costs compared to CRSsNP. ^,

Bioabsorbable sinus implants, which elute corticosteroids in a targeted and localized manner, were designed to address the limitations of topical INCSs and rinses, reduce the need for intermittent systemic corticosteroids, and improve surgical outcomes. Notably, frontal sinus ostium stenosis has represented a particular challenge in ESS, with loss of 28% to 33% of the neo-ostium diameter seen in modified Lothrop procedures. Local sinus stenting and subsequently developed steroid-eluting stents were first introduced to address frontal sinus stenosis and other healing issues within the sinuses. These stents were subsequently developed into the various steroid-eluting stents in use today.

Stenosis of the frontal neo-ostium has presented a challenge in ESS. Local stenting was first considered to help mitigate postoperative stenosis with varying results. Steroid-eluting sinus stents were subsequently introduced in the early 2000s by Hosemann et al. to increase the efficacy of previously used frontal sinus stents. Sinus stents were first developed for the frontal sinus to address wound-healing issues in the frontal sinus outflow tract, such as reactive scar formation, since topical steroid sprays and ointments have difficulty reaching and treating these critical areas. The early studied steroid-eluting stents released approximately 60 µg of dexamethasone per day and were removed 3 to 4 weeks postoperatively, with promising results. Beule et al. further assessed dexamethasone-releasing stents in animal models by comparing them to standard silicone stents and demonstrated lesser granulation formation and significantly thinner stromal thickness.

Early trials assessing the efficacy and safety of first-generation steroid-eluding sinus implants in patients with CRS demonstrated significantly improved postoperative healing characterized by a reduction in inflammation, minimization of adhesion formation and middle turbinate (MT) lateralization, and preservation of postoperative sinus patency. The safety profile was also favorable, with no notable systemic side effects from long-term steroid implantation and no clinically significant ocular complications. Subsequent research has further demonstrated that the use of steroid-eluting sinus implants may decrease or eliminate the need for immediate postoperative systemic steroids for patients with CRSwNP.

Second-generation steroid implants were developed for in-office treatment of recurrent nasal polyposis as an alternative to revision surgery, some of which contain nearly 4-fold higher corticosteroid content than prior implants (1350 µg vs. 370 µg), and are released over a longer period of time (90 days vs. 30 days). These implants are inserted in the ethmoid sinuses under local anesthesia. Early trials with this implant have shown positive trends for treatment of recurrent nasal polyps (NPs) with an excellent safety profile.

Patients with a history of ESS with significant polyp recurrence that fails to resolve despite medical management can consider placement of long-acting steroid-eluting sinus implants which may help avoid revision surgery. These implants have demonstrated reduction in nasal obstruction, reduction in polyp burden, improved sense of smell, and a reduced need for revision sinus surgery. ^, There is no current indication for steroid-eluting sinus stents in patients who are surgically naïve; however, investigational trials are currently being undertaken to assess steroid-eluting stent efficacy in patients who are refractory to medical management and have not undergone surgery. ^,

PROPEL: Three PROPEL sinus implant (Intersect ENT, California) devices exist—PROPEL, PROPEL Mini, and PROPEL Contour ( Fig. 17.1A )—all of which contain 370 µg of mometasone furoate (MF) and are indicated for patients 18 years or older after EES. Each of the three PROPEL implants can be used for different applications, and each is designed with a different size and shape to best accommodate the sinus for which they are indicated. They function to maintain sinus patency by helping separate mucosal tissue, providing stabilization of the MT, preventing obstruction by adhesions, and reducing edema with a goal of reducing the need for postoperative lysis of adhesion and/or the need for postoperative oral corticosteroids.

(A) PROPEL Contour in expanded state before loading into the delivery system. (B) SINUVA Implant in expanded state before loading into the delivery system.

The PROPEL is approved by the US Food and Drug Administration (FDA) for application within the ethmoid sinuses after undergoing ethmoid sinus surgery. The PROPEL Mini sinus implant is indicated by the FDA for application within the ethmoid sinus cavity and frontal sinus opening, and the PROPEL Contour sinus implant is indicated for maintaining patency of the frontal sinus opening and maxillary sinus ostia.

SINUVA: The SINUVA Sinus Implant (Intersect ENT, California) is a corticosteroid-eluting (mometasone furoate) implant that contains 1350 µg of mometasone furoate and is indicated for the treatment of NPs in patients 18 years and older who have had prior ethmoid sinus surgery ( Fig. 17.1B ). These can be maintained in the sinuses for 90 days prior to removal of the residual implant. SINUVA sinus implants contain mometasone furoate, and inactive copolymer compounds poly-(DL-lactide-co-glycolide) which is biodegradable, and polyethylene glycol which is nontoxic and nonimmunogenic.

Lyra: LYR-210 and LYR-220 (Lyra Therapeutics, Massachusetts) are possible upcoming biodegradable mometasone furoate drug delivery systems with higher steroid concentrations than the current FDA-approved implants. These implants are currently undergoing investigational trials with encouraging early results and require FDA approval. The LYR-210 and LYR-220 each contain 7500 µg of mometasone furoate, with a goal of maintaining both within the sinus cavity for up to 6 months. The LYR-210 is currently being studied in patients who have not undergone prior ESS, and the LYR-220 is being evaluated in patients who have undergone prior sinus surgery. ^,

Intraoperative drug-eluting sinus implantation: A drug-eluting sinus stent may be prepared and placed near the conclusion of an endoscopic sinus surgery once the appropriate patency of the sinuses has been established and hemostasis has been achieved. The implant and delivery system ( Fig. 17.2 ) should be prepared in a sterile fashion no more than 3 minutes before their use, as earlier preparation may affect the extensibility and deployment of the implant. Once the device is prepared, the tip is inserted with appropriate orientation into the intended sinus cavity ( Fig. 17.3 ) or sinusotomy ( Fig. 17.4 ) and deployed in accordance with the manufacturer’s instructions. Applicators may be modified if recommended by the manufacturer, such as the PROPEL Contour applicator, which has a tip that can be bent between 70 and 110 degrees as needed. Final placement and position should be confirmed under endoscopic visualization with particular importance placed on ensuring the implant is well apposed to the tissues to maximize drug delivery. The implant may be adjusted as needed using standard endoscopic instruments. Implants are designed in a fashion to have radial strength to help dilate the tissue, as well as be self-retaining as the edema or polypoid tissue recedes. Postoperatively, the implants can be removed with standard endoscopic sinus instrumentation. ^,

SINUVA delivery system loaded with implant ( top device ) and PROPEL Contour delivery system loaded with implant ( bottom device ).

PROPEL Mini deployed within the right ethmoid sinus cavity, which provides stabilization of the middle turbinate, and is well approximated to the mucosal tissues

PROPEL Contour deployed within the left frontal sinusotomy with appropriate approximation to the surrounding edematous mucosal tissues.

In-office drug-eluting sinus implantation: Patients may be positioned and prepared in routine fashion for an in-office rigid sinonasal endoscopic procedure. Topical anesthetics and decongestants are applied to the sinonasal mucosa, such as 4% tetracaine and 0.25% neosynephrine. An approved sinus implant is loaded into a provided delivery system in accordance with the manufacturer’s recommendation and then placed in the ethmoid sinus under endoscopic visualization. The implant is deployed within the intended sinus cavity, and the delivery system is withdrawn. Care should be taken to avoid bending, twisting, or damaging the implant, and implants are not designed to be modified by the physician. The implant, such as SINUVA, may be left in the sinus to gradually release the corticosteroid over 90 days and can be removed at day 90 or earlier per the physician’s discretion ( Fig. 17.5 ). The implant is left in the sinus to gradually release the corticosteroid over 90 days and can be removed at day 90 or earlier per the physician’s discretion.

(A) Nasal polyps medial and lateral to the right middle turbinate before the placement of SINUVA implant. (B) Right middle meatus of the same nasal cavity after placement of a SINUVA implant. Note the medialization of the right middle turbinate.

Steroid-eluting stents for surgically naïve patients are not currently approved but are undergoing investigational trials with encouraging early results (LYR-210, a 7500 µg mometasone furoate-containing implant; Lyra Pharmaceuticals) and may see application in the future for in-office medical management of recalcitrant CRS. ^,

The use of steroid-eluting sinus stents has demonstrated favorable outcomes during the post-operative course for CRS and in patients who have had in-office placement of steroid-eluting stents for recurrent nasal polyposis. Mometasone furoate stents placed in patients undergoing ESS aid in the reduction of adhesions, MT lateralization, inflammation, polyp formation, and improvement in patient-reported symptoms. Additionally, in-office mometasone implants have demonstrated a reduction in polyp grade, ethmoid cavity obstruction, and the need for sinus surgery, suggesting that these second-generation implants play an important role in management of recurrent NP.

PROPEL sinus implants have demonstrated efficacy in multiple trials, which has been supported by notable symptomatic improvement and statistically significant reduction in ethmoid obstruction and polyp grade. Mur et al. performed a prospective, randomized, double-blind trail comparing drug-eluting sinus stents (370 µg mometasone furoate) to non–drug-eluting stents in 38 patients who underwent ESS. Their trial demonstrated a statistically significant reduction in polypoid mucosal changes, inflammation, and adhesion formation over a 3- to 6-week period of time.

Forwith et al. performed a prospective multisite trial entitled ADVANCE that assessed the safety and efficacy of PROPEL (370 µg mometasone furoate) bioabsorbable steroid eluting implants in 50 patients after ESS. They found steroid-eluting implants correlated with a statistically significant reduction in the Sino-Nasal Outcome Test-22 (SNOT-22) score and Rhinosinusitis Disability Index (RDI) at 30 days, 60 days, and 6 months postoperatively. They also estimated an average of 14.9% of the stent material remained at day 30, and 0.2% remained at day 60, confirming the bioabsorbable nature of the stents. Middle turbinate (MT) lateralization was noted in 4.4% of patients who had a steroid-eluting stent and significant adhesion formation in 1.1% of patients. These findings can be compared to the findings by Mur et al., who demonstrated MT lateralization in 5.3% of the treatment group and 15.8% of the control group and significant adhesion formation rate of 5.3% in their treatment group and 21.1% in the control group.

Second-generation implants (i.e., SINUVA) containing a higher concentration of steroid (1350 µg vs. 370 µg) and released over 90 days rather than 30 days were subsequently developed for in-office treatment of recurrent NP as an alternative to revision ESS. Trials have demonstrated favorable results supporting the efficacy and safety of in-office placement of 1350 µg of mometasone furoate implants for treatment of recurrent polyposis after ESS and a reduction in the need for revision ESS. Han et al. demonstrated symptomatic improvement and statistically significant reduction in polyp grade and ethmoid sinus obstruction over a 3-month period in their RESOLVE trial, a randomized, controlled, blinded study that included 100 patients. A follow-up study further assessed outcomes in the same patients over 6 months and noted a persistent reduction in patient-reported symptoms and statistically significant greater reduction in bilateral polyp grade and percent ethmoid obstruction through the entire 6 months compared to the control group. Lavigne et al. demonstrated similar results in a prospective study of 11 patients, with statistically significant reduction in mean bilateral polyp grade (4.5 at baseline, 2.3 at 1 month, P = 0.008; 2.33 at 6 months, P = 0.008) and SNOT-22 score at 1 month and sustained through 6 months. A further phase 3 trial by Kern et al. was designed as a randomized, sham-controlled, double-blind trial that included 300 adults with refractory CRSwNP who were candidates for repeat surgery. At 90 days after implant, subjects demonstrated a statistically significant reduction in the need for sinus surgery (39.0% treatment vs. 63.3% sham-control, P = 0.0004), percent ethmoid sinus obstruction, nasal obstruction/congestion, and decreased sense of smell. There was no statistically significant reduction in facial pain/pressure.

Investigational trials for longer-lasting (6 month vs. 30-90 days) implants containing higher concentration (2500-7500 µg mometasone furoate) for surgically naïve patients with medically recalcitrant CRS are under way. A phase 1 trial assessing LYR-210 (2500 µg mometasone; Lyra Therapeutics, Massachusetts) efficacy and safety has demonstrated statistically significant reduction in SNOT-22 score by week 1 lasting to week 24. A subsequent phase 2 trial assessed 2500 µg and 7500 µg mometasone sinus implants against a saline irrigation control. The LYR-210 (2500 µg and 7500 µg) demonstrated significant improvement in nasal blockage, facial pain/pressure, and nasal discharge in a dose-dependent fashion at weeks 16, 20, and 24 compared with the control. They also demonstrated a dose-dependent reduction in SNOT-22 score and a significantly reduced ethmoid sinus opacification and the need for rescue treatment in Lyr-210 (7500µg mometasone) compared with the control. The implant is currently undergoing a multicenter, phase 3, randomized, blinded, controlled trial (ENLIGHTEN 2) for patients who have failed current standard medical treatment for CRS, demonstrate confirmed ethmoid sinus disease on CT sinus imaging, and require further intervention. ^{, ,}