The results of this study demonstrate that the dexamethasone 0.4 mg intracanalicular insert effectively controlled postoperative inflammation and pain following phacoemulsification, with no clinically relevant differences in outcomes when the insert was placed either in the operating room at the completion of surgery or in the office the next day. The insert exhibited excellent safety, with stable mean IOP, no clinically significant IOP elevations, and no insert-related adverse events.
In this study, anterior chamber cells were ubiquitous on the first postoperative day and resolved in all but 1 eye by day 7. Flare was not seen in any eye at any time, and only a single eye reported pain at a single time point. No insert-related adverse events occurred, no eyes required rescue corticosteroid therapy, and no eyes required insert removal. These results are at least as favorable as those reported in prior studies. In three phase 3 trials of the dexamethasone insert versus vehicle (a similar intracanalicular insert not containing dexamethasone) placed immediately postoperatively on the day of surgery in a total of 926 eyes undergoing phacoemulsification,14,16 postoperative pain was absent at day 8 in ~ 80% of insert eyes versus ~ 45–60% of vehicle eyes (with the differences being significant in all 3 studies), and anterior chamber cells were absent at day 14 in ~ 35–50% of insert eyes and ~ 15–30% of vehicle eyes (with the differences being significant in 2 of the 3 studies). Rescue therapy with topical steroids in the first 2 postoperative weeks was required in ~ 5–15% of insert eyes and ~ 10–45% of vehicle eyes. Given the similar or better outcomes seen in both groups in the current study, it is reasonable to consider that the timing of insert administration—same-day versus next day—is safely flexible based on individual surgeon and patient characteristics.
Existing approaches to ocular drug delivery are limited by numerous issues that compromise clinical outcomes in a number of disease states, and there remains unmet need for improvement in ocular drug delivery for a variety of ocular conditions, particularly those that require chronic therapy. Topical medical therapy for glaucoma remains the mainstay of treatment, yet its most important limitation—poor adherence17—is a key cause of disease progression.18 Inhibitors of vascular endothelial growth factor (VEGF) have revolutionized therapy for many retinal vascular disorders, yet the burden of treatment—monthly or every few months for life—results in significant undertreatment and suboptimal outcomes.19,20 Sustained drug delivery platforms that remove the responsibility for daily self-dosing would significantly improve the management of glaucoma, and longer-acting formulations of anti-VEGF agents would similarly be of great benefit in treating retinal vascular diseases such as age-related macular degeneration and diabetic retinopathy.
The perioperative anti-inflammatory and antimicrobial regimen for cataract surgery can also benefit from advances in therapy. Almost 90% of American Medicare beneficiaries undergoing cataract surgery in 2016 were prescribed perioperative topical medications, including antibiotics (89%), steroids (86%), and nonsteroidal anti-inflammatory drugs (66%), with 55% receiving all three drugs.9 Therapy with these three drugs poses a complex regimen that may require different drugs to be dosed once, twice, three, or even four times daily, with the added complexity of a tapering steroid dosing frequency over time. This would be challenging under the best of circumstances and is likely even more so among the elderly population typically undergoing cataract surgery, many of whom may have temporary blurred vision in the acute postoperative period. Such a regimen is even more problematic in the COVID-19 pandemic era, in which elderly patients may have less access to postoperative caregivers and in whom repeated contact between hands and face are discouraged to minimize infection risk. Perhaps not surprisingly, half of patients are poorly adherent to their perioperative medication regimen following cataract surgery,21 and most demonstrate improper and potentially unsafe self-instillation techniques.22
Sustained release corticosteroid formulations—as with the dexamethasone intracanalicular insert or the dexamethasone intraocular suspension (Dexycu, EyePoint Pharmaceuticals, Watertown, MA)—are an important step in the paradigm shift to dropless cataract surgery. This approach—utilizing intracameral antibiotics and sustained release steroid products—has been advocated by multiple surgeons as an important step forward in optimizing therapeutic efficacy and postoperative quality of life in patients undergoing the most commonly performed outpatient surgery in adults in the United States.10–13 Replacing self-administered topical therapy with surgeon-administered therapy reduces risks associated with improper instillation technique and eliminates nonadherence, resulting in better efficacy, safety, and quality of life outcomes.
These attributes of sustained dexamethasone delivery with the intracanalicular insert are valued by both physician and patients. In the phase 3 insert trials, 98% of surgeons rated the insert as easy or moderately easy to insert, and 99.5% of inserts were easily visualized at day 14.23 A patient experience study was conducted in a subset of phase 3 participants.24 Among 25 subjects undergoing a semi-structured survey, 100% reported that the insert was comfortable, and the majority (84%) were unaware of its presence in the canaliculus. Overall, 92% reported being very satisfied with the insert, and 96% rated it convenient or very convenient compared to their prior experience with topical eye drop use. Also, a recent study evaluating the effectiveness of the insert placed in the office the day after femtosecond-assisted phacoemulsification demonstrated complete resolution of anterior chamber cells and flare within the first 2 postoperative weeks in all eyes.25
This study was intended to complement the phase 3 investigations by characterizing outcomes in the real-world setting, in a less artificially homogenous patient sample and with less rigorous protocol requirements. Particular to this study was the flexibility in administering the insert either immediately postoperatively or the next day (no outcome differences were observed), which expands treatment timing options for surgeons and patients. The study is limited by a small sample size, but as no specific hypotheses were proposed or tested, the sample size was deemed adequate to characterize the outcomes of interest, namely resolution of postoperative pain and inflammation.