Necessity of Steroids to Achieve Optimal Results and Patient Satisfaction after Cataract Surgery

Necessity of Steroids to Achieve Optimal Results and Patient Satisfaction after Cataract Surgery

Corticosteroids have been utilized in ophthalmology since the 1950s for the control of ocular inflammation. Through their interference with phospholipase A2, they are able to inhibit the arachidonic acid cascade and reduce the inflammatory response. Corticosteroids can be delivered systemically and/or topically, and currently there are approximately ten ophthalmic corticosteroid preparations available. When used following cataract surgery, corticosteroids have been demonstrated to prevent inflammation, hasten recovery of visual acuity, and decrease postoperative pain.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are also useful following cataract surgery, and several studies have shown them to also be effective in reducing inflammation and pain after cataract surgery. That said, should they be used alone? I believe that a combination of steroid and NSAID therapy is critical to achieving successful outcomes.

In today’s climate, we must do all that we can to meet patient expectations, which often include good to excellent vision and as little pain as possible a few days after surgery. While NSAIDs have been shown to reduce inflammation and improve postoperative comfort, they are not 100% successful. The author states that several studies have been performed using an NSAID exclusively to control pain and inflammation. What he fails to mention are the results of these trials. In all of these, when using an NSAID alone, even when dosed prior to surgery, outcomes are not as impressive as one would hope (Table 1). In fact, in most of these trials, patients are still not inflammation free at two weeks, and some of the inflammation scores are somewhat forgiving (where a 0 equals 5 or less anterior chamber [AC] cells). To me, this is unacceptable, and one of the main reasons why I feel that both a steroid and an NSAID should be part of a perioperative regimen.

Table 1 Trials using an NSAID alone to prevent postoperative inflammation

Drug / TrialDesignEndpointsResultsReference
(ISTA Pharmaceuticals)

Safety and Efficacy of Bromfenac Ophthalmic Solution (Bromday) Dosed Once Daily for Postoperative Ocular Inflammation and Pain
  • 872 subjects
    (584 Bromday; 288 placebo)
Summed Ocular Inflammation Score (SOIS) = 0 (AC cells = 0 + AC flare = 0)
Proportion of subjects at each visit with SOIS of 0:

Day 15
- 51.1% (Bromday)
vs 27.4% (placebo)
Henderson BA, Gayton JL, Chandler SP, Gow JA, Klier SM, McNamara TR. Bromfenac Ophthalmic Solution (Bromday) Once Daily Study Group. Ophthalmology 2011 Jul 16
(ISTA Pharmaceuticals)

Bromfenac ophthalmic solution 0.09% (Xibrom) for postoperative ocular pain and inflammation
  • 527 subjects
    (356 Xibrom; 171 placebo)
  • Dosed BID day after surgery and continued for 14 days for total of 28 doses
SOIS = 0 (AC cells ? 5 + AC flare = 0)
Proportion of subjects at each visit with SOIS of 0:
  • Day 3
    - 8.4% (Xibrom) vs 1.2% (placebo)
  • Day 8
    - 34.8% (Xibrom) vs 13.5% (placebo)
  • Day 15
    - 59.3% (Xibrom)
    vs 26.9% (placebo)
Donnenfeld ED, Holland EJ, Stewart RH, Gow JA, Grillone LR. Bromfenac Ophthalmic Solution 0.09% (Xibrom) Study Group. Ophthalmology 2007 Sep;114(9):1653-62
(Alcon Laboratories, Inc.)

Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery
  • 476 subjects
    (243 Nevanac; 233 placebo)
  • Dosed TID one day before surgery and then for 14 days
  • No steroid
Clinical cure: AC cells ≤ 5 + AC flare = 0 (same as Xibrom study)
Clinical cure:
Day 1
- 11.5% (Nevanac) vs 1.3% (placebo)
    • Day 3
      - 36.6% (Nevanac) vs 5.6% (Placebo)
    • Day 7
      - 63% (Nevanac) vs 11.6% (placebo)
Day 14
- 81.9% (Nevanac)
vs 25.3% (placebo)

Primary endpoint:
Day 1
- 0.4% (Nevanac) vs 0.0% (placebo)
  • Day 3
    - 6.6% (Nevanac) vs 3.0% (placebo)
  • Day 7
    - 29.6% (Nevanac) vs 3.0% (placebo)
  • Day 14
    - 62.6% (Nevanac)
    vs 17.2% (placebo)
Lane SS, Modi SS, Lehmann RP, Holland EJ. J Cataract Refract Surg 2007 Jan;33(1):53-8
Acular (Allergan)
Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial
  • 102 subjects
    (51 Acular; 51 placebo)
  • Dosed QID one day after surgery
  • No steroid
AC cell grade = 0 (no cells) + AC flare score = 0
Day 14
-29% (Acular)
vs 8% (placebo)
Heier J, Cheetham JK, Degryse R, Dirks MS, Caldwell DR, Silverstone DE, Rosenthal A. Am J Ophthalmol 1999 Mar;127(3):253-9

Based upon the results shown in the table, if an NSAID is used alone, it seems inevitable that some patients will require steroids as rescue therapy. Those patients may feel that something has gone wrong with their surgery because they now have to purchase another medication they did not think was necessary. Furthermore, steroids and NSAIDs work at different levels of the arachidonic acid cascade, and as such will provide a synergistic effect allowing even more postoperative comfort than either drop alone could provide.

Cystoid macular edema, or CME, is a serious and potentially sight-threatening consequence of uncontrolled inflammation. Depending on how you define this (angiographic CME or clinical CME), and what study you reference, the rates of CME post surgery are anywhere between 3 and 30%. This is at least 10–100 times more common than endophthalmitis rates. I would propose that no one would take a chance with endopthalmitis, and CME risk should be no different.

There have been many other trials showing that the combination of a steroid and NSAID are better than a steroid or NSAID alone in preventing cystoid macular edema. These studies, conducted by John Wittpenn, Jeff Heier, and other respected surgeons, all corroborate the synergistic mechanisms of steroids and NSAIDs.

Regarding risks of steroids, the most concerning adverse event is elevated intraocular pressure (IOP). This has been shown to occur in approximately 8% of patients. However, ophthalmologists are very comfortable treating elevated IOP, and steroid regimens are becoming shorter and shorter, further decreasing the possibility of steroid responsive elevated pressure. NSAIDs are not without risks, and by combining NSAIDs and steroids I find I am able to lessen the dose of each and still maintain excellent efficacy.

Cost is another factor that must be weighed. Do the benefits of adding a steroid justify the added cost? My response is a resounding yes. Prednisolone acetate is available as a generic that costs between $10 and $25. Difluprednate ophthalmic emulsion (Durezol®, Alcon Laboratories, Inc.), a more potent benzylalkonium chloride (BAK)-free steroid emulsion, is $35 on average with the support of a manufacturer’s rebate, and also has improving Tier 2 coverage on many Medicare Part D plans. The NSAID I am using most now is nepafenac ophthalmic suspension 0.1% (Nevanac,), which has predominantly Tier 2 coverage costing about $40 per co-pay. I dose both of these medications in an off-label schedule (BID for two weeks, then decreasing the steroid to QD for two weeks while maintaining the NSAID at BID for an additional two weeks) and have had no adverse events and excellent inflammatory and pain control. One bottle of each will last the entire course of therapy and cost less than $100. In contrast, to prescribe a four-week course of Bromday would require two bottles, each of which are often more than $100. My patients are extremely pleased with the ease of BID dosing, and their postoperative outcomes have been outstanding.

Ultimately, when considering patient expectations, frequency of adverse events, and cost, the decision to use a steroid with NSAID following cataract surgery is well worth the investment. Proper use of both medications can ensure excellent postoperative outcomes with continued practice growth.

  1. Heier JS, Topping TM, Baumann W, Dirks MS, Chern S. Ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema. Ophthalmology 2000;107(11):2034–2028;discussion:2039.
  2. Wittpenn JR, Silverstein S, Heier J, Kenyon KR, Hunkeler JD, Earl M. Acular LS for Cystoid Macular Edema (ACME) Study Group. A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients. Am J Ophthalmol 2008 Oct;146(4):554–60. Epub 2008 Jul 2.
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