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Feature | Nov/Dec '16

NSAID Selection in the Perioperative Cataract Surgery Period

What exactly should we be thinking about?

The phrase innovations in cataract surgery usually refers to technological improvements that give surgeons a better chance of performing the required steps less invasively and more precisely, or to new techniques that might make the surgeon more efficient, the surgery safer, or the procedure applicable in complex cases. An often-overlooked aspect of cataract surgery innovations are the topical medications used in the perioperative period.

Patients are typically prescribed a topical antibiotic to be used a few days before and after surgery to lower the risk of infection. In addition, a corticosteroid and a nonsteroidal antiinflammatory drug (NSAID) are frequently used in the perioperative period to inhibit postoperative inflammation, thus lessening the risk of cystoid macular edema and other complications.

Although dual antiinflammatory agents appear at first redundant, it is important to note that corticosteroids and NSAIDs act on different mechanisms in the inflammatory cascade, thus providing complementary and synergistic benefit.1,2 In addition, because NSAIDs specifically target prostaglandin formation via inhibition of cyclooxygenase (COX-1 and COX-2),3 they are also relevant for reducing postoperative pain and discomfort, assuming that the appropriate agents are selected. NSAIDs have also been found to reduce miosis intraoperatively when they are used preoperatively.4


Safety, efficacy, and tolerability are the most important factors for any topical ocular agent. In light of innovations in NSAID offerings, it seems prudent to consider additional factors, such as the convenience of the dosing schedule and the propensity to induce discomfort.

Newer-generation NSAIDs and those approaching the market certainly have a more favorable safety profile than older agents. They may also feature additional ingredients or vehicles that make them mechanistically more favorable in certain situations. For example, studies suggest that several factors can lower the effective dose delivered, including volume loss due to dose spillage5,6; tearing and blinking5-9; tear film turnover5-8; conjunctival and scleral absorption5,6; and corneal absorbption.6,7 Drug design and development have, therefore, focused on solutions that increase the effective dose5; improve the molecular design to enhance lipophilicity and solubility10; and alter the formulation to increase viscosity, residence time, and corneal penetration.11

Dosing convenience is a multifactorial consideration. Studies indicate that the more agents a patient uses, the greater the chance for noncompliance.12 However, that is an incomplete viewpoint. If a patient were to use a corticosteroid alone, he or she may have to use that three to six times a day (depending on the agent) to avoid inflammation and reduce pain as effectively as combination topical steroid and NSAID. Add in the potential for pressure elevations associated with frequent and cumulative corticosteroid dosing, and the use of a nonsteroidal in the perioperative regimen becomes much more palatable. Using an NSAID, then, may mean more total agents for the patient to manage but fewer total instillations throughout the day—and, with that, fewer chances to cause discomfort, pain, or other complications.

Another variable to consider in agent selection is the potential to irritate the ocular surface. Prolensa (bromfenac, 0.07%; Bausch + Lomb) and Ilevro (nepafenac ophthalmic suspension 0.3%; Alcon) are available for once-daily dosing, thereby minimizing the potential to harm the ocular surface. Each of these agents is indicated to treat postoperative pain. Another NSAID, BromSite (bromfenac 0.075%; Sun Pharmaceuticals) formulated in DuraSite, a vehicle designed to increase ocular surface residence time, has received FDA approval for twice-daily dosing; this agent is expected to be released to the market Q4 2016. Unlike other NSAID formulations, the forthcoming offering has an indication to prevent, rather than solely treat, postoperative pain—a consideration that could have important implications. Patients tend to associate any postoperative pain with the effectiveness of their surgery; fair or not, the surgeon will be judged based on those pain reports, and that may include how reimbursement is factored when patient satisfaction is considered. This does not even consider the fact that patient expectations are on the rise and at the forefront of every surgeon’s efforts.


The availability of generic NSAIDs adds another element to agent selection. Third-party payers in some cases dictate the use of nonbranded drugs, while pharmacy swaps may take the choice out of the physician’s hands. In other cases, cost-conscious patients ask for cheaper options.

As physicians, we cannot be immune to these cost realities, but I also think it may be a disservice to simply capitulate to using generics. For one thing, the fact that branded medications have gone through rigorous clinical trials (and generics have not) is immediately reassuring. However, what is often missed is that there has been a regression in generic NSAIDs offerings. A few years ago, patients had the option of a topical ketorolac 0.045% concentration solution; whereas, now, there are only two options: diclofenac or ketorolac, both at a 0.05% concentration that are indicated for use four times daily. As each instillation is an opportunity to induce discomfort, and because the cumulative dose heightens the risk of keratopathy, I am frankly uncomfortable with that level of dosing frequency.


When I have a discussion with patients who are expressing concerns about cost, I tend to be very honest with them. Taking oral ibuprofen as opposed to oral Advil may not make much of a difference, but, in eye care, there is no comparison between topical and branded NSAIDs. The frequency of dosing, the efficacy, and the level of discomfort associated with generics are all varied. It makes sense for patients to consider investing in the branded formulations.

If we are asking patients to commit a financial investment to increase the chance of a great outcome, then we should be thoughtful about agent selection for the topical regimen used in the perioperative period. We need to look beyond safety, efficacy, and tolerability and also consider the dosing frequency and the potential to induce discomfort in order to make decisions that align with the goal of minimizing inflammatory potential and attendant complications.

1. Heier JS, Topping TM, Baumann W, Dirks MS, Chern S. Ketorolac versus prednisolone versus combination therapy in treatment of acute pseudophakic cystoid macular edema. Ophthalmology. 2000;107(11):2034-2039.

2. Flach AJ. Discussion: ketorolac vs prednisolone vs combination therapy in the treatment of acute pseudophakic CMD. Ophthalmology. 2000;107:2039.

3. Jampol LM. Pharmacologic therapy of aphakic cystoid macular edema. A review. Ophthalmology. 1982;89:891-897.

4. Stewart R, Grosserode R, Cheetham JK, Rosenthal A. Efficacy and safety profile of ketorolac 0.5% ophthalmic solution in the prevention of surgically induced miosis during cataract surgery. Clin Ther. 1999,21:723-732.

5. Ghate D, Edelhauser HF. Ocular drug delivery. Expert Opin Drug Deliv. 2006;3(2):275-287.

6. Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12(3):348-360.

7. Coffey MJ, Decory HH, Lane SS. Development of a non-settling gel of 0.5% loteprednol etabonate for anti-inflammatory use as an ophthalmic drop. Clin Ophthalmol. 2013;7:299-312.

8. McGhee CN. An overview of topical ophthalmic drugs and the therapeutics of ocular infection. https://www.fmhs.auckland.ac.nz/som/ophthalmology/teaching/_docs/optometry-355-05-pharmacokinetics.pdf. Accessed October 25, 2016.

9. Kaur IP, Kanwar M. Ocular preparations: the formulation approach. Drug Dev Ind Pharm. 2002;28(5):473-493.

10. Shirasaki Y. Molecular design for enhancement of ocular penetration. J Pharm Sci. 2008;97(7):2462-2496

11. Barar J, Javadzadeh AR, Omidi Y. Ocular novel drug delivery: impacts of membranes and barriers. Expert Opin Drug Deliv. 2008;5(5):567-581

12. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296-1310.

Elizabeth Yeu, MD
Elizabeth Yeu, MD
  • Private practice at Virginia Eye Consultants
  • Assistant Professor of Ophthalmology at Eastern Virginia Medical School, Norfolk, Virginia
  • Chief Medical Edtior, MillennialEYE
  • eyeu@vec2020.com
  • Financial interest: Consultant (Alcon, Abbott Medical Optics, Bausch + Lomb), Speaker (Sun Pharmaceuticals)