Cataract surgery patients report better postop outcomes with branded NSAID treatment

Asim V. Farooq, MD

Hovanesian and Holland have presented the results of a study comparing branded nepafenac 0.3% and generic ketorolac 0.5% in patients undergoing cataract surgery. Specifically, the study analyzed patient-reported tolerability, impact on quality of life, interference with activities of daily living and ocular surface toxicity. In this randomized, controlled, open-label prospective study, patients were randomized to receive either nepafenac (dosed once daily) or ketorolac (dosed four times daily) beginning 3 days before cataract surgery and continuing 28 days postoperatively.

Topical NSAIDs are prescribed routinely by cataract surgeons, and yet the comparative effects and tolerance of various topical NSAIDs have not been well studied. The authors found that while nepafenac was more commonly associated with temporary blurry/hazy/foggy vision, it was tolerated significantly better than ketorolac overall, based on both subjective measures and the objective measures of corneal fluorescein staining and conjunctival injection.

The study has several strengths. Patients were randomized, with roughly 90 patients in each group, which had similar demographic characteristics. The authors carefully considered the choice of generic ketorolac among three options, by conducting a small tolerability study and choosing the option with neither the most nor least adverse symptoms. Patients also took two subjective surveys to help assess the effects of each medication the Impact of Dry Eye on Everyday Life (IDEEL) questionnaire and the Eye Drop Comfort Scale (EDCS).

Limitations of this study include the use of only one specific formulation of ketorolac. The authors also included patients undergoing both femtosecond laser-assisted cataract surgery and manual cataract surgery, as well as some patients who underwent limbal relaxing incisions; an analysis of potential differences among these groups was not provided.

In summary, this is an important study demonstrating that once-daily nepafenac 0.3% was better tolerated overall compared with four-times-daily ketorolac 0.5% in patients undergoing cataract surgery. It should prompt further investigations to assess the effect and tolerability of various topical NSAIDs. Such studies will have the potential to help us improve patient satisfaction and compliance.

Rishi P. Singh, MD

The authors should be congratulated on investigating the differences between nepafenac 0.3% and ketorolac 0.5%. Indeed, there are significant differences with regards to the drug structure, which might have led to the outcomes seen within the study. Within the eye, prostaglandins promote miosis, vasodilation, disruption of the blood-ocular barrier and leukocyte migration.

In addition, nonsteroidal drugs, in particular nepafenac, have been shown to reduce the risk for postoperative macular edema associated with cataract surgery. In both in vitro and ex vivo animal studies, nepafenac rapidly permeates into the cornea and sclera and is converted into its active metabolite, amfenac, primarily in the retina/choroid and iris-ciliary body. Amfenac is a potent inhibitor of constitutive (cyclooxygenase-1) and inducible (cyclooxygenase-2) cyclooxygenases that catalyze the formation of pro-inflammatory prostaglandins. Both nepafenac and amfenac block the inflammation-mediated breakdown of the blood-retinal barrier that contributes to plasma extravasation and edema.

In contrast, ketorolac is not a prodrug and thus can exert nonsteroidal effects on the cornea instead of the intended target tissues. The side effects of NSAIDS are well known, including corneal epithelial cell loss and even corneal melt.

This study is supportive of the safety of the NSAID prodrug rather than the active metabolite to target issues. From the clinical perspective, we as physicians struggle with drug approvals for patients due to the tiered drug systems present. Hopefully this study will become known to the patients and insurers such that formularies can be adjusted when there is an intolerance to the ketorolac drug.

Reference: Singh RP, et al. Ophthalmology. 2017;doi:10.1016/j.ophtha.2017.01.036.