Usage of Nonsteroidal Anti-inflammatory Drugs (NSAIDs) with Corticosteroids After Cataract Surgery:
A Clinical Update
Cataracts remain the leading cause of blindness worldwide. While cataract surgery is one of the most common surgeries in medicine today, the operation is not entirely void of risks. Pseudophakic macular edema (PME) is the most prevalent complication to result in impaired vision (although this finding is almost always transient and self-resolving, and rarely associated with visual morbidity). Recent research suggests that PME is found in 0.2% to 2.35% of post-operative cases, with this risk increasing in men, older patients, the presence of epiretinal membranes prior to surgery, and a four-fold increase in diabetics. A near linear increase of developing PME was found as diabetic retinopathy severity increased (ETDRS-graded)1.
The current accepted standard-of-care following cataract surgery includes three different classes of topical drops: an antibiotic, a corticosteroid, and a nonsteroidal anti-inflammatory (NSAID). However, an understanding of the arachidonic acid pathway suggests two of the drugs listed above are redundant in preventing PME.
Figure 1. The Arachidonic Acid Pathway
In a recent survey by the American Society of Cataract and Refractive Surgery, 90% of physicians concomitantly prescribed an NSAID with a corticosteroid during cataract surgery2. Despite this accepted practice, there is zero clinical evidence suggesting that the benefits of NSAID therapy cannot be achieved with corticosteroids alone2. Additionally, at approximately $200 per brand prescription by adding an NSAID, the global cost per year is estimated at $540 million.
When different drugs are prescribed to achieve a common therapeutic goal, these drugs are termed synergistic. That is, one of the drugs provides a mechanism of action that the other cannot, but together produce an effect greater than the sum of each drug in isolation. A classic example of synergy in medicine involves the use of aminoglycosides with the penicillin class: aminoglycosides bind to the 30s ribosomal sub-unit to disrupt protein synthesis, while penicillins inhibit cross-linking activity and prevent new bacterial cell wall formation. Taken together, bacterial replication is minimized, rendering the drugs synergistic.
This is hardly the case when NSAIDs are used with corticosteroids to prevent PME as they act on the same pathway. The difference between corticosteroids and NSAIDs is where they exert their clinical benefit. While NSAIDs decrease inflammation by acting upon the cyclooxygenase enzyme (decreasing all downstream proinflammatory prostaglandins thereafter), corticosteroids inhibit prostaglandins more upstream in the arachidonic acid pathway. Thus, corticosteroids possess anti-inflammatory profiles that are far superior to NSAIDS. This can be seen by the propensity to use steroids over NSAIDs in autoimmune diseases and systemic inflammation in various medical disciplines. There is no compelling evidence or even rational benefit for using NSAIDs with corticosteroids to reduce inflammation in the macula following cataract surgery. Doing so would effectively be similar to treating a bacterial corneal ulcer with a third-generation and a fourth-generation fluoroquinolone, which is clearly superfluous. So how did prescribing NSAIDs for routine cataract surgery become so popular despite convincing proof for a visual benefit to patients?
Companies who have strong financial interests in NSAIDs aggressively promote their application into routine care for post-operative cataract patients. Like many reports that show promise of clinical drugs, the benefit of NSAIDs to reduce PME is strongly industry-sponsored and ubiquitous, continuing to raise concerns over conflicts of interest. In a recent study by the American Academy of Ophthalmology, the data concluded that there was no level 1 evidence that supported long-term visual benefit with NSAID therapy to prevent vision loss from PME3.
Truly, even zealous supporters of NSAIDs will not abandon corticosteroid altogether due to the inability to act higher up on the inflammatory cascade. Many advocates of NSAIDs will point to its ability to decrease pain and reduce surgical miosis as an explanation for its continued use following cataract surgery, yet corticosteroids also possess these same benefits4. NSAIDs used to decrease PME are perhaps inflated, as trials that suggest such have compared them with less efficient corticosteroids (i.e.- fluorometholone alcohol 0.1%).
In conclusion, it is imperative to remember that nearly any drug can be published as beneficial, especially when strong financial interest in invested. Therefore, an affinity to peer-reviewed articles with no financial disclosures is crucial, and will best serve to shine a light upon what is best for our patients and streamline care in the future.