Twice-daily clobetasol 0.05% cleared cells in 26.5% vs 8.6% of patients and pain in 75.1% vs 32.4% after cataract surgery, with no added endothelial cell loss.
Twice-daily clobetasol propionate ophthalmic suspension 0.05% (Byqlovi; Formosa Pharmaceuticals/AimMax Therapeutics) produced sustained clearance of anterior chamber cells and ocular pain after
The FDA approved the nanosuspension in 2024 for postoperative inflammation and pain after ocular surgery, bringing to ophthalmology a corticosteroid long kept out of eye drops by poor aqueous solubility.1 CPN-302 is the second pivotal trial behind the approval. Unlike its companion study, it included a prespecified corneal endothelial cell substudy, which addresses a safety question raised by the drug's high glucocorticoid-receptor binding affinity.1
Investigators at 29 US sites randomly assigned 370 patients with at least 10 anterior chamber cells on postoperative day 1 after uncomplicated phacoemulsification to clobetasol 0.05% or matching vehicle. Both groups dosed twice daily for 14 days with no taper, and the double-masked trial enrolled patients from March 2021 through July 2022.1 Mean patient age was 67.6 years, and baseline inflammation and pain grades were similar between arms.1
Both co-primary end points favored clobetasol. Sustained anterior chamber cell clearance from day 8 through day 15 occurred in 26.5% of the clobetasol group vs 8.6% of the vehicle group, and sustained absence of pain from day 4 through day 15 occurred in 75.1% vs 32.4% (both P <.001).1 All 4 prespecified sensitivity analyses confirmed both results, and the benefit held across subgroups defined by age, sex, race, and iris color.
Pain and inflammation resolved on different timelines. By day 4, 85.4% of clobetasol-treated patients were pain-free vs 51.4% with vehicle, while cell clearance did not separate until day 8 (29.7% vs 13.0%) and widened by day 15 (57.8% vs 18.9%; both P <.001).1 The least-squares mean difference in cell grade reduction grew steadily, from −0.5 at day 4 to −1.2 at day 15 (all P <.001).1
Rescue therapy during the 14-day course was needed in 7.0% of clobetasol patients vs 38.4% of vehicle patients (P <.001), a roughly fivefold reduction.1 Sustained flare clearance from day 8 to day 15 occurred in 78.9% vs 37.3%. Across visits, a loss of 2 or more lines of acuity occurred in 2.9% to 4.1% of clobetasol eyes vs 8.0% to 13.3% of vehicle eyes.1
Treatment-emergent adverse events occurred at similar rates (25.5% vs 25.9%), with no deaths and no discontinuations for adverse events in the clobetasol arm.1 Seven clobetasol patients (3.8%) and no vehicle patients met a protocol-defined IOP criterion; all elevations were mild, resolved, and did not interrupt dosing.1 Peak IOP occurred at day 4 in 4 of the 7 patients, and the investigators recommended IOP checks at day 4 and day 8.1
In the endothelial substudy, mean endothelial cell density fell 11.1% with clobetasol and 14.1% with vehicle from screening to day 85, both within the range expected after phacoemulsification.1 Losses of 30% or more occurred in 12.1% (8/66) vs 15.7% (11/70) of eyes. Eighteen of 19 outlier eyes carried a recognized risk factor for impaired endothelial repair, most often age older than 70 years or diabetes.1
"An effective, well-tolerated, taper-free short-course corticosteroid, with corneal endothelial safety demonstrated prospectively through three months," the CPN-302 investigators concluded in the poster.1
Results from both pivotal trials, CPN-301 and CPN-302, were published together in Ophthalmology in 2026, and the AAO poster adds study-level CPN-302 detail to the combined report.1,2 Bacharach disclosed research support from AimMax among relationships with numerous ophthalmic companies.1
