NSAIDs: suitable prophylaxis after cataract surgery?

The addition of corticosteroids (ie, prednisolone) to NSAID eyedrops (ie, ketorolac) did not provide additional benefit relative to ketorolac alone or dropless surgery using a sub-Tenon capsule depot as an anti-inflammatory prophylactic regimen to prevent postoperative central macular thickening following uncomplicated cataract surgery, a Danish study suggests.

“To control inflammatory response and reduce the risk of pseudophakic cystoid macular oedema, prophylactic anti-inflammatory eyedrops are prescribed parallel to cataract surgery,” said the researchers. However, the choice of prophylaxis remains unclear. [Cochrane Database Syst Rev 2016;11:CD006683; Cochrane Database Syst Rev 2017;7:CD010516]

A total of 470 individuals (mean age 72 years, 62 percent female) scheduled to undergo phacoemulsification for age-related cataract were randomized equally to one of five anti-inflammatory prophylactic regimens: prednisolone acetate 1% (PRDL) and ketorolac tromethamine 0.5% with (preop PRDL-NSAID [control]) or without preoperative* initiation (postop PRDL-NSAID), ketorolac monotherapy with (preop NSAID) or without preoperative initiation (postop NSAID), or sub-Tenon depot of dexamethasone phosphate 0.5 mL (4 mg/mL). Eyedrops were administered TID until 3 weeks postop. [JAMA Ophthalmol 2021;doi:10.1001/jamaophthalmol.2021.2976]

PRDL-NSAID vs NSAID monotherapy

At 3 months, mean central subfield thickness (CST) was similar across the NSAID-containing arms (250.7, 250.7, 251.3, and 249.2 μm for control, postop PRDL-NSAID, preop NSAID, and postop NSAID, respectively). When the NSAID-containing arms were compared against control, these generated differences of 0.1 μm (p=0.97), 0.6 μm (p=0.79), and −1.5 μm (p=0.51), respectively.

PRDL-NSAID vs sub-Tenon

Dropless approaches have emerged due to reports of difficulty with eyedrops, with evidence showing similar effects to corticosteroid monotherapy. [J Cataract Refract Surg 2011;37:1589-1597; J Ocul Pharmacol Ther 2013;29:516-522]

In the current study however, sub-Tenon was inferior to control in terms of mean CST (255.2 vs 250.7 μm; difference, 4.5 μm; p=0.04), with more than half of recipients requiring additional topical anti-inflammatory treatment. These imply that sub-Tenon was not on par with NSAID-containing regimens for preventing macular thickening following cataract surgery.

“[Nonetheless, for] patients with suspected poor adherence with topical treatment, placing a depot of corticosteroid during surgery could serve as adjuvant therapy,” noted the researchers.

IOP, timing of treatment

Mean intraocular pressure (IOP) was higher among those who received PRDL (−3.3 and 0.2 mm Hg for control and postop PRDL-NSAID, respectively) vs those on NSAID monotherapy (−0.3 mm Hg for both pre- and postop) or sub-Tenon (−0.2 mm Hg) in the first 3 weeks. “However, mean IOP in all arms was low in the reference range, [with] no elevations of >25 mm Hg at any postop visit,” said the researchers.

There were also no differences between pooled preop and postop initiations of treatment for CST (p=0.91 [3 weeks] and p=0.53 [3 months]), IOP (p=0.97 and p=0.74), and corrected distance visual acuity (p=0.78 and p=0.98). “[These suggest that initiating preoperative] prophylactic treatment was not superior to initiating treatment on the day of surgery in preventing thickening of the central subfield [following] surgery,” added the researchers.

The drawbacks

However, controversies surround NSAID monotherapy for post-cataract surgery prophylaxis especially in the US, as NSAIDs are not recommended by the AAO**. [Ophthalmology 2020;127:573-581; Ophthalmology 2015;122:2159-2168]

Also, the findings may not be extrapolated to individuals with risk factors (eg, diabetes) as the cohort included patients at low risk of complications. The results may have also been limited by the lack of evaluations on corticosteroid monotherapy, on other commonly used corticosteroid drops, or other dropless approaches. The effects beyond 3 months were also not studied. “[As such,] later presentations of PCME may not have been identified,” the researchers pointed out.

“[Nonetheless, the collective findings imply that] NSAID plus corticosteroid drops were not superior to NSAID monotherapy or sub-Tenon dexamethasone depot … NSAID monotherapy initiated on the day of surgery may be preferred as an anti-inflammatory prophylactic regimen in [this setting],” said the researchers.