Hawaiian Eye 2019 – Novel Methods of Intraocular Steroid Delivery Following Cataract Surgery
Cataract surgery is one of the most widely performed surgeries and has had a huge impact on reducing visual disability worldwide.1 Despite usually achieving successful outcomes, cataract surgery may result in significant postoperative inflammation as a result of mechanical damage due to tissue manipulation and a mild reaction to intraocular lenses.2 If untreated, inflammation can result in a variety of complications including cystoid macular oedema, increased intraocular pressure, posterior capsular opacification, chronic uveitis, fibrin formation, and protein leakage from the breakdown of the blood–aqueous barrier.3,4 In addition, moderate or severe pain and ocular discomfort such as itchiness, burning, foreign-body sensation, and tearing are relatively common.5 As a result, the use of corticosteroids to reduce postoperative inflammation has become a mainstay of cataract surgery medication regimens.2
Corticosteroids are usually administered as drops. However, topical application of corticosteroids fails to provide a therapeutic level lasting more than several hours. Within two minutes after instillation over 80% of the topical product is eliminated via the nasolacrimal drainage system, limiting ocular penetration of the drug to less than 1% of the administered dose.6 Treatment, therefore, involves repeated applications of eye drops, which can result in poor compliance, considerable expense, and potential toxicity at a time when the eye is most vulnerable.7,8 Patients may be sensitive to the preservatives, particularly if they have been on medication a long time. In addition, patients often have a poor instillation technique: failing to wash hands, contaminating bottle tips, missing the eye, and using an incorrect amount of drops.9 Some patients, particularly those with arthritis, cannot generate enough force to squeeze a bottle, and have difficulty with the other movements required to administer drops.7 As a result, researchers have been exploring new ways to treat postoperative inflammation. One of the key talking points at Hawaiian Eye 2019, which was held in Waikoloa, Hawaii, was new products that can deliver postoperative medication without eye drops. The US Food and Drug Administration has approved two such products in the past year: DexycuTM (ICON Bioscience Inc., now EyePoint Pharmaceuticals, Watertown, MA, US) and Dextenza® (Ocular Therapeutix, Bedford, MA, US).
Dexycu is a liquid suspension that is injected into the anterior chamber using a standard 30-gauge needle to deliver an extended release, biodegradable formulation of dexamethasone. It is generally given as a slow release over 21 days although, depending on surgeon preference, it can be customized to dispense from one week to over nine months with a single injection.10 In a phase III clinical study (NCT02006888), 394 patients undergoing unilateral cataract surgery by phacoemulsification were randomly assigned to receive a 5 μL injection of Dexycu (342 or 517 μg) in the anterior eye chamber or placebo. At eight days after the operation, 25.0% of eyes in the placebo group and in 63.1% and 66.0% of eyes in the 342 μg and 517 μg treatment groups, respectively (p=<0.001), had clearing of the anterior chamber cell. Anterior chamber flare clearing occurred in 63.8% of eyes in the placebo group and in 92.4% and 89.1% of eyes in the 342 μg and 517 μg Dexycu groups, respectively (p=<0.001). The injection also demonstrated a high level of safety: adverse events among the three groups were similar, and no serious ocular adverse events were reported at 90-day follow-up.10 In another study, 201 patients were randomised 2:1 to receive 517 μg Dexycu or topical prednisolone 1.0% drops (one drop, four times daily for three weeks). The most common adverse events were increased intraocular pressure (11.1%), iritis (6.3%), and systemic effects (7.9% Dexycu group; 10.9% prednisolone group). Among the patients receiving Dexycu, 68.7% strongly agreed that not having to use eyedrops was very convenient. 39.2% of those using topical prednisolone strongly agreed that they would have preferred dropless therapy.11
Dextenza is a sustained release, hydrogel, 3 mm, cylindrical-shaped, preservative-free insert containing 0.4 mg of dexamethasone, and is implanted in the lacrimal canaliculus immediately after surgery. It swells on contact with moisture from the tear fluid and continues to expand inside the eye, where it stays in place and delivers dexamethasone over a month. The insert eventually softens, liquefies, and is cleared through the nasolacrimal duct. In a phase III clinical study (NCT02736175), 438 patients with planned clear corneal cataract surgery were randomly assigned to receive Dextenza or placebo. Fourteen days after implantation, significantly more patients had an absence of anterior chamber cells in the Dextenza arm compared with placebo (52.3% versus 31.1%; p<0.0001). In addition, patients receiving Dextenza had decreased inflammation after surgery as early as day four and a decrease in pain as early as one day after surgery, both of which were maintained to day 45. The Dextenza insert was well tolerated, with adverse events similar to placebo. Twice as many placebo patients required rescue therapy, compared with Dextenza patients at day 14.12 A small, qualitative survey found that treatment satisfaction with Dextenza is high.13
Possible disadvantages of intraocular delivery devices include the potential for angle or corneal endothelium damage from physical migration of the device, localised damage at the implantation site, and difficult extraction, if removal is required. In addition, if intraocular pressures remain high, it may be more difficult to control and monitor dosage compared with topical formulations, which may be easily discontinued.14 However, to date, no such problems have been reported with the Dextenza implant.
These new products should help patients, many of whom are elderly, avoid noncompliance and dosing errors, and their approval has been received with great enthusiasm. In an interview filmed at Hawaiian Eye, John A. Hovanesian, MD, of Harvard Eye Associates in Laguna Hills, CA, said, “In the future, a substantial number of our patients will receive anti-inflammatory medication not in the form of an eye drop, which is great news for clinicians and our patients.”15
Published: 6 February 2019
References
1. Davis G. The evolution of cataract surgery. Mo Med. 2016;113:58–62.
2. Duan P, Liu Y, Li J. The comparative efficacy and safety of topical non-steroidal anti-inflammatory drugs for the treatment of anterior chamber inflammation after cataract surgery: A systematic review and network meta-analysis. Graefes Arch Clin Exp Ophthalmol. 2017;255:639–49.
3. Dick HB, Schwenn O, Krummenauer F, et al. Inflammation after sclerocorneal versus clear corneal tunnel phacoemulsification. Ophthalmology. 2000;107:241–7.
4. da Rocha Lima B, Pichi F, Nucci P, et al. Fibrin reaction after uveitic cataract surgery: Treatment and prevention. Eur J Ophthalmol. 2014;24:626–8.
5. Porela-Tiihonen S, Kokki H, Kaarniranta K, et al. Recovery after cataract surgery. Acta Ophthalmol. 2016;94 Suppl. 2:1–34.
6. Shell JW. Ophthalmic drug delivery systems. Surv Ophthalmol. 1984;29:117–28.
7. Winfield AJ, Jessiman D, Williams A, et al. A study of the causes of non-compliance by patients prescribed eyedrops. Br J Ophthalmol. 1990;74:477–80.
8. Hermann MM, Ustundag C, Diestelhorst M. Electronic compliance monitoring of topical treatment after ophthalmic surgery. Int Ophthalmol. 2010;30:385–90.
9. An JA, Kasner O, Samek DA, et al. Evaluation of eyedrop administration by inexperienced patients after cataract surgery. J Cataract Refract Surg. 2014;40:1857–61.
10. Donnenfeld E, Holland E. Dexamethasone intracameral drug-delivery suspension for inflammation associated with cataract surgery: A randomized, placebo-controlled, phase III trial. Ophthalmology. 2018;125:799–806.
11. Donnenfeld ED, Solomon KD, Matossian C. Safety of IBI-10090 for inflammation associated with cataract surgery: Phase 3 multicenter study. J Cataract Refract Surg. 2018;44:1236–46.
12. Tyson SL, Bafna S, Gira JP, et al. Multicenter randomized phase 3 study of a sustained-release intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. 2019;45:204–212.
13. Gira JP, Sampson R, Silverstein SM, et al. Evaluating the patient experience after implantation of a 0.4 mg sustained release dexamethasone intracanalicular insert (Dextenza): Results of a qualitative survey. Patient Prefer Adherence. 2017;11:487–94.
14. Tan DT, Chee SP, Lim L, et al. Randomized clinical trial of a new dexamethasone delivery system (Surodex) for treatment of post-cataract surgery inflammation. Ophthalmology. 1999;106:223–31.
15. Hovanesian JA. New steroid delivery methods augment anti-inflammatory armamentarium. 2019. Available at: www.healio.com/ophthalmology/cataract-surgery/news/online/%7B9cdb44c2-63c8-49b5-9722-c815a288a839%7D/video-new-steroid-delivery-methods-augment-anti-inflammatory-armamentarium (January 31, 2019).