The role of NSAIDs in refractive cataract surgery

ByEric D. Donnenfeld, MD

Among the most important adjunctive pharmaceutical tools available in the realm of refractive cataract surgery are ophthalmic NSAIDs. This article discusses how these agents can optimize surgery in a variety of ways, as well as prevent postoperative inflammatory complications.

As ophthalmic surgery has improved, patient expectations have increased, as well. Patients now want excellent vision without significant rehabilitation time, with no reduction in contrast sensitivity and with freedom from even minor transient complications. NSAIDs can facilitate some of these demands to a large extent.

How do NSAIDs work?

How do NSAIDs affect inflammation? Prostaglandins, lipid compounds derived from fatty acids, are responsible for most cases of postoperative inflammation; these compounds along with leukotrienes (an eicosanoid lipid mediator) are synthesized as a part of the arachidonic acid cascade. NSAIDs — as well as steroids — block various parts of this cascade, thereby inhibiting the synthesis of prostaglandins and leukotrienes and reducing inflammation.¹

Cystoid macular edema

Among the most common complications following cataract surgery is cystoid macular edema (CME). Although the incidence has decreased as surgical methods have improved, angiographic evidence of CME can be found in 3% to 70% of patients, with clinical CME occurring in 0.1% to 12%.^2-4 The large variations in incidence are most likely due to changes in disease definition and diagnostic procedures. With optical coherence tomography, one study found that 41% of eyes have increased retinal thickness (at least 10 µm was used to define CME) 6 weeks postoperatively, and 88% of eyes had some leakage at 12 weeks.

Whatever the precise incidence may be, CME is a common cause of decreased vision following cataract surgery, and it can occur in both simple and complicated surgeries. The etiology of CME remains elusive, but intraocular inflammation appears to play a role.

The definition of CME has evolved somewhat. Previously, cystic yellow appearance of the fovea, petaloid leakage in the macula and a visual acuity of 20/40 or worse were required to diagnose CME. Now, however, VA reduction is not necessarily a characteristic of this complication. In fact, any visual deficit at all, even if a patient has 20/20 acuity, can indicate the presence of CME; complaints of a lack of clarity in vision or decreased contrast sensitivity also fit into the new definition.

One study designed to assess overall VA following cataract surgery compared patients who did and did not receive prophylactic NSAID therapy. Among the group that did not receive NSAIDs, 12% of patients had decreased vision, whereas the group that received NSAID therapy had no cases of decreased vision. This loss of VA can sometimes be permanent.⁵

CME with multifocal IOLs

Another area of evolving interest regarding CME in ophthalmic surgery is refractive lens exchange in normal patients with the use of multifocal and accommodating IOLs. CME is a more important issue with these procedures than with monofocal lens procedures. One study examining the use of the topical NSAID ketorolac in the implantation of multifocal IOLs found a significant difference in foveal thickness (202.5 µm with ketorolac vs. 220.39 µm without, P<.001)⁶ (Figure 1). The study also found better VA results when the NSAID was used.

Foveal Thickness

Figure 1. The use of the topical NSAID ketorolac resulted in a significantly decreased foveal thickness.⁶

Source: Donnenfeld ED

Furthermore, the intrinsic optics of multifocal IOLs are associated with a loss of contrast sensitivity. When this loss is combined with the decline in contrast sensitivity caused by CME, there is a combined effect on quality of vision. Patient satisfaction will suffer significantly and the decrease in vision quality may be permanent. To avoid this complication, patients should initiate NSAID therapy at least 3 days prior to surgery and continue topical NSAIDs for 1 month postoperatively.⁷

NSAIDs and cataract surgery

Various studies have found that NSAIDs can improve outcomes of cataract surgery by increasing pupil size, reducing intraoperative miosis, decreasing postoperative pain and anterior chamber inflammation.^8-10

NSAIDs can improve outcomes of cataract surgery by increasing pupil size, reducing intraoperative miosis, decreasing postoperative pain and anterior chamber inflammation.

— Eric D. Donnenfeld, MD

The timing of prophylactic NSAID therapy is important, as one study assessing the agents’ pharmacokinetic response curve found.⁵ One hundred patients undergoing phacoemulsification were randomly assigned into four groups with ketorolac 0.4% treatment initiated 3 days, 1 day and 1 hour prior to surgery, with one control group receiving placebo. All patients in the three NSAID groups received ketorolac for 3 weeks postoperatively, while the placebo patients did not.

Control patients had a mean pupil constriction of 1.5 mm, compared to 1.1 mm in the 1-hour group, 0.42 mm in the 1-day group and 0.12 mm in the 3-day group (P<.002 for all three vs. control). As a result of the larger pupils, the mean surgery time was also reduced in the NSAID treatment groups. The control patients’ procedures lasted an average of 8.4 minutes, compared to 6.7 minutes in the 1-hour group, 5.9 minutes in the 1-day group and 5.5 minutes in the 3-day group (P<.001 for the latter two groups vs. control). The mean ultrasound time also was reduced in the NSAID groups (2 minutes for control group and 1 minute for 3-day group).

NSAID treatment also improved VA outcomes in this study. At 1 day and 2 weeks postoperatively, there was a significant difference in best-corrected visual acuity between the 1-day and 3-day pretreatment groups vs. the control group (P<.007) (Figure 2). Although it did not remain significant, there was still a trend toward better VA in the NSAID groups at 3 months postoperatively.

Visual Outcomes

Figure 2. Patients treated with a topical NSAID preoperatively achieved better postoperative BCVA vs. the control group that received placebo.⁵

Source: Donnenfeld ED

Other outcomes were better as well, including corneal clarity and reduced postoperative inflammation inside the anterior segment. Patients in the 1-day and 3-day treatment groups experienced significantly less discomfort during and after the procedure vs. those in the control group. Also, there was a reduced need for additional anesthesia in the 1-day and 3-day groups; only 8% of patients in those groups required additional anesthesia vs. 40% in the control group and 20% in the 1-hour group (P<.008).

Perhaps most importantly, the use of NSAIDs for 1 day or 3 days affected the incidence of CME in these patients. Among those in the control group, 12% had CME at 2 weeks postoperatively; 4% of those in the 1-hour group had CME, and no patients in either of the longer treatment groups experienced this complication. There was also less loss of endothelial cells with the longer duration of NSAID treatment.

Overall, the research that has been performed on NSAID use in cataract and refractive surgery affirms the utility of these agents. They facilitate surgery, improve VA outcomes and reduce the incidence of CME. NSAIDs are an inexpensive and easy way to improve patients’ intraoperative experience and postoperative satisfaction with refractive cataract surgery.

References

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