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Healio
ByEdward J. Holland, MD
July 15, 2007
5 min read
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Inflammation prophylaxis optimizes visual outcomes in cataract surgery

ByEdward J. Holland, MD

Cystoid macular edema is the most frequent cause of visual decline following uncomplicated cataract surgery. Prophylactic treatment with anti-inflammatory agents can help reduce the incidence of this complication, but a disappointingly low percentage of surgeons take advantage of the protection with these agents in all of their cataract procedures. This article discusses the adjunctive use of perioperative pharmaceutical agents for inflammation prophylaxis and how it can maximize visual outcomes and avoid cystoid macular edema.

Characteristics of CME

Cystoid macular edema (CME) can occur late — up to 4 to 6 weeks postoperatively1 — and it is estimated to occur in approximately 12% of low-risk cataract surgeries.2 At first glance, it seems that, if a surgeon can restore 20/20 visual acuity in an eye that develops CME, then this complication is not particularly devastating. This is not the case, however. Although acuity may reach this level, contrast sensitivity and other aspects of vision are often never optimal after the occurrence of CME. Thus, preventing it is of the utmost importance.

Topical NSAIDs can reduce the incidence of CME and can have a beneficial effect on visual function.

— Edward J. Holland, MD

When considering the risk factors patients might have for CME, it is important to remember that simply undergoing intraocular surgery is the most significant risk factor. All patients are at risk. Other predisposing conditions include pre-existing ocular inflammation, epiretinal or vitreoretinal membranes, diabetic retinopathy, ocular vascular or cardiovascular disease, and retinitis pigmentosa. Prophylaxis for CME should be initiated even earlier in patients deemed to be at higher risk.3

NSAIDs

A number of studies have demonstrated the efficacy of NSAIDs in preventing CME. These agents work synergistically with steroids to minimize inflammation following ocular surgery.4,5 NSAIDs minimize prostaglandin formation through action on the cyclooxygenase-1 and cyclooxygenase-2 pathways. Steroids, meanwhile, act primarily on phospholipase A2 to inhibit the release of arachidonic acid. Together, these mechanisms are effective at preventing inflammation.

Topical NSAIDs can reduce the incidence of CME and can have a beneficial effect on visual function. It is critical, however, to achieve therapeutic concentrations of the drug in the posterior chamber in order to maximize the effect on the retina.6

Steroids alone, on the other hand, do not treat or prevent CME as effectively as NSAIDs. One study of 60 patients undergoing cataract surgery compared one group receiving both an NSAID and a corticosteroid from the day of surgery through 4 weeks postoperatively with a group receiving only a corticosteroid over that period. Both groups were given NSAIDs for 2 days prior to surgery. At an evaluation at week 6, zero patients who received both agents had CME vs. 12% of those who received only the corticosteroid.2

NSAIDs such as nepafenac, ketorolac and bromfenac can be used for treatment of CME and inflammation.

Penetration and efficacy

A pharmacokinetic study of three NSAIDs examined the agents’ penetration into human aqueous humor.7 Seventy-five patients were randomly assigned to receive commercially available ketorolac, bromfenac or the combination nepafenac + amfenac at five preoperative time points on the day of surgery, as well as postoperatively. An aqueous humor sample was collected at the time of paracentesis.

Mean Aqueous Humor Concentrations
Figure 1: Comparison of bromfenac, ketorolac and the combination nepafenac + amfenac applied topically prior to cataract surgery Figure 1. In a comparison of the mean aqueous humor concentrations of the commercially available NSAIDs bromfenac, ketorolac and the combination nepafenac + amfenac applied topically prior to cataract surgery, the nepafenac + amfenac combination demonstrated higher concentration levels.7

Source: Holland EJ

Although all three of the NSAIDs showed some penetration into the eye, the nepafenac + amfenac combination had the highest penetration (Figure 1). The better the intraocular penetration, the greater is the likelihood for efficacy of the NSAID in preventing inflammation.

Another recent study evaluated the efficacy of nepafenac in decreasing pain and inflammation following cataract surgery in 476 eyes at multiple centers.8 With regard to clinical cures as defined by 0-5 cell/0 flare, at each study point — days 1, 3, 7 and 14 after surgery — nepafenac was significantly better (P<.0001 for each time point) (Figure 2). A similar result was found when considering clinical cures as 0 cell/0 flare.

Percentage Clinical Cures by Visit
(defined by 0-5 cell/0 flare)
Figure 2: Nepafenac demonstrated better efficacy than placebo in reduction of pain and inflammation Figure 2. Nepafenac demonstrated better efficacy than placebo in reduction of pain and inflammation following cataract surgery.8

Source: Holland EJ

In a comparison study of the anesthetic effects and ocular tolerability of nepafenac and bromfenac, Maris and colleagues found nepafenac and bromfenac to be comparable in terms of anesthetic effects and both drugs resulted in minimal ocular discomfort.9

Several studies have compared nepafenac with ketorolac. One European study of more than 200 eyes found that, although both NSAIDs reduced inflammation in comparison to placebo, nepafenac achieved greater reduction than ketorolac. A pain questionnaire in this study also found that patients who received nepafenac had less postoperative pain and discomfort.10

One other comparison of these two agents was conducted in 80 eyes undergoing PRK and looked at epithelial healing and analgesic effects.11 Again, both drugs performed well with regard to average postoperative pain scores, but nepafenac slightly outperformed ketorolac (pain score of 1.7 out of 5 vs. 2.29, P=.009). Both drugs also did well in terms of epithelial healing, with no patients developing any persistent epithelial defects.

Recommendations and summary

Given all this information, what is the recommended therapeutic regimen? NSAID therapy should be initiated 1 to 3 days preoperatively in routine patients and 7 days preoperatively in high-risk patients. The preoperative therapy will blunt the onset of the inflammatory cascade and deplete preformed prostaglandin. Administration of the agent should be maintained intraoperatively to prevent surgically induced miosis.

NSAID therapy should be initiated 1 to 3 days preoperatively in routine patients and 7 days preoperatively in high-risk patients.

— Edward J. Holland, MD

Postoperatively, NSAID treatment should continue for 3 to 4 weeks in routine patients and 6 to 12 weeks in high-risk patients. This extended period is necessary because of the generally late onset of CME.

It is important to remember that all patients undergoing intraocular surgery are at risk for CME, and every patient should therefore receive NSAID therapy pre- and postoperatively. Patient expectations have grown in recent years, and any loss of vision will be considered a poor result. With our currently available arsenal of topical prophylaxis, the most common cause of visual loss after cataract surgery can be significantly reduced.

References

  1. Samiy N, Foster CS. The role of nonsteroidal anti-inflammatory drugs in ocular inflammation. Int Ophthalmol Clin. 1996;36:195-206.
  2. McColgin AZ, Raizman MB. Efficacy of topical diclofenac in reducing the incidence of postoperative cystoid macular edema. Invest Ophthalmol Vis Sci. 1999;40:S289.
  3. Heier JS. Preventing Post-cataract extraction CME: Early identification of patients at risk and prophylactic treatment may avert vision loss. Ophthalmology Management. 2004;63-72.
  4. Heier JS, Topping TM, Baumann W, et al. Ketorolac versus prednisolone versus combination therapy in treatment of acute pseudophakic cystoid macular edema. Ophthalmology. 2000;107:2034-2038.
  5. Flach AJ. Discussion: Ketorolac vs. prednisolone vs combination therapy in the treatment of acute pseudophakic CME. Ophthalmology. 2000;107:2039.
  6. Gaynes BI, Fiscella R. Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: A safety review. Drug Saf. 2002;25:233-250.
  7. Walters TR, Raizman M, Ernest P, et al. A double-masked, randomized, single-dose, pharmacokinetic study of nepafenac, amfenac, ketorolac, and bromfenac in human aqueous humor following topical administration of Nevanac, Acular LS, or Xibrom. J Cataract Refract Surg (in press).
  8. Lane SS, Modi SS, Lehmann RP, et al. Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery. J Cataract Refract Surg. 2007;33:53-58.
  9. Maris PJ Jr, Perry HD, Donnenfeld ED, Chou T. Anesthesia and ocular tolerability of topical non-steroidal anti-inflammatory drugs: a direct comparison between bromfenac and nepafenac. Invest Ophthalmol Vis Sci. 2006;47:E-Abstract 4993.
  10. Nardi M, Cunliffe I, Cano J, Cochener B, et al. Nepafenac 0.1% compared to ketorolac 0.5% and placebo in cataract surgery. Invest Ophthalmol Vis Sci. 2007;48: E-Abstract B684.
  11. Donnenfeld ED, Durrie DS, Holland EJ, et al. A double-masked study of nepafenac 0.1% and ketorolac 0.4% for pain and epithelial healing following PRK. Presented at the American Academy of Ophthalmology, November 2006; Las Vegas, Nev.