Simplified Regimens, Extended Delivery Options Among Recent Advances in Steroid Delivery for Cataract Surgery
By Damien F. Goldberg, MD; Featured in Cataract & Refractive Surgery Today
Steroid medications are an integral part of how we care for patients after cataract surgery. I still recall the drop packs my attendings used to give our cataract surgical patients when I started residency. Every patient left with a postoperative pack containing an eye shield, sunglasses, an antibiotic drop, a steroid drop, and an NSAID drop.
Prednisolone acetate ophthalmic suspension 1% (Pred Forte, Allergan) was a popular choice for the steroid, and ketorolac tromethamine ophthalmic solution 0.5% (Acular, Allergan) was popular for the NSAID. Strong empirical data supported the use of both steroid and NSAID as a significant way to reduce the potential side effect of cystoid macular edema after cataract surgery.1 However, prescribing triple eye drop therapy had its issues. Not every patient was willing or would remember to use all three medications q.i.d. Not to mention, 268 drops per eye (assuming the antibiotic was taken for 1 week and the steroid and NSAID each for 4 weeks) from three bottles with three different preservatives was rough on the corneal surface and complicated the healing process.
ADVANCES IN DOSING, DELIVERY
Since that time, through advances in drug delivery and posology, the dosing schedules for both antibiotic and antiinflammatory drops have been significantly simplified. Difluprednate ophthalmic emulsion 0.05% (Durezol, Alcon) was the first steroid that allowed us to reduce dosing. It was shown to have double the potency of prednisolone acetate, and it remains the most potent topical steroid in our arsenal. It can be dosed t.i.d. rather than q.i.d.2
More recently, two formulations of loteprednol etabonate, a softer steroid, have become available, and each helps to improve bioavailability in different ways. A gel formulation, loteprednol etabonate ophthalmic gel 0.38% (Lotemax SM, Bausch + Lomb), increases residence time for the drug.3 And a formulation using nanoparticles, or mucus-penetrating particle technology, helps the drug penetrate to target tissues. Both of these loteprednol formulations can be dosed b.i.d.
Another familiar formulation, fluorometholone acetate ophthalmic suspension 0.1% (Flarex, now Eyevance Pharmaceuticals), has had a resurgence and gained popularity.
SIMPLIFY: MULTIPLE MEDICATIONS, ONE DROP
These medications decrease the frequency of steroid treatment, but navigating three different postoperative medications remains a compliance and cost barrier for patients. Many physicians who may have previously preferred to prescribe brand name drugs have noted the burden of prices in the current complex health care landscape. In the search for alternative solutions, many practices have begun routine use of compounded combination topical steroid, antibiotic, and NSAID medications. One option is prednisolone phosphate 1%/gatifloxacin 0.5%/bromfenac 0.075% (Omni, OSRX Pharmaceuticals), prescribed t.i.d. for 1 month.
Advantages of the compounded approach include improving patient compliance, preventing health plans or pharmacies from changing or denying prescribed medications, and eliminating staff time spent dealing with callbacks from health insurance plans. Additionally, compounded drops can considerably lower patients’ out-of-pocket costs. Moreover, one study found that inflammation was reduced in patients treated with a compounded combination. In a randomized, double-masked prospective US multicenter study,4 an earlier version of the compounded prednisolone/gatifloxacin/bromfenac demonstrated a 50% reduction in summed ocular inflammation score, compared with a 23% reduction in control patients using separate brand name medications: Pred Forte, moxifloxacin ophthalmic solution (Vigamox, Novartis), and nepafenac ophthalmic suspension 0.3% (Ilevro, Novartis). The success of the compounded drops has been attributed to the innovative simplicity of freeing patients to administer fewer drops postoperatively.
Some cataract surgeons have also begun to use compounded intracameral injections of a corticosteroid and fluoroquinolone antibiotic combination, dexamethasone phosphate 0.1%/moxifloxacin HCl 0.5% sterile ophthalmic injection (Omni Intracameral Injection, OSRX Pharmaceuticals).
SUSTAINED RELEASE DELIVERY IS HERE
In the past year, we have also seen the introduction of two extended release options for steroid drug delivery that look promising to treat postoperative inflammation. The dexamethasone ophthalmic insert 0.4 mg (Dextenza, Ocular Therapeutix) is an intracanalicular corticosteroid insert placed in the punctum.5 The dexamethasone intraocular suspension 9% (Dexycu, EyePoint Pharmaceuticals) is an intracameral option.6
There is a great deal of enthusiasm to see the development of new steroid drug delivery options such as these, but working through the details of the cost barrier with these new drug delivery options can be challenging. (Editor’s note: For more on this topic, see “The Economics of Transitional Pass-Through Status.”) Once drug coverage for these agents is widely established, it will no doubt lead to greater adoption.
The traditional regimen of prescribing steroid eye drops remains the main method of postoperative cataract surgery care, but new technologies and compounded formulations such as those described here offer great promise.
When used appropriately, there is potential for improving compliance, comfort, and reliability. Innovation in pharmacotherapy is continual, and these new options have allowed us to greatly improve the method of delivering steroid medications for our patients’ care.
Damien F. Goldberg, MD:
- Partner, Wolstan & Goldberg Eye Associates, Torrance, California
- Member, CRST Editorial Advisory Board
- Financial disclosure: Consultant (Allergan/Abbvie, Alcon, Bausch + Lomb, Kala Pharmaceuticals, Ocular Science, Ocular Therapeutix
1. Wittpenn J, Silverstein S, Hunkler J, et al. A masked comparison of Acular LS plus steriod versus steroid alone for the prevention of macular leakage in cataract patients. Am J Ophthalmol. 2008;146(4):554-560.
2. Smith S, Lorenz D, Peace J, McLeod K, Crockett RS, Vogel R. Difluprednate ophthalmic emulsion 0.05% (Durezol) administered two times daily for managing ocular inflammation and pain following cataract surgery. Clin Ophthalmol. 2010;4:983-991.
3. Phillips E, Coffey MJ, Shawer M. Viscoelastic and dissolution characterization of submicron loteprednol etabonate ophthalmic gel, 0.38%. Invest Ophthalmol Vis Sci. 2015;56(7):1525.
4. Fram N, Masket S, Shamie N, et al. Prospective US multicenter study of safety and efficacy of combination drop prednisolone phosphate, moxifloxacin, and ketorolac in treating post-op inflammation and pain after cataract surgery. Paper presented at: the ASCRS Annual Meeting; May 5-9, 2017; Los Angeles.
5. Tyson SL, Bafna S, Gira JP, et al; Dextenza Study Group. Multicenter randomized phase 3 study of a sustained-release intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery [published correction appears in J Cataract Refract Surg. 2019;45(6):895]. J Cataract Refract Surg. 2019;45(2):204-212.
6. 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(10):1236-1246.
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Dr. Goldberg is the Chief Medical Officer at Ocular Science® (an affiliate of OSRX™) and holds a financial stake in the company.