Search

Purpose To demonstrate the efficacy and safety of once-daily nepafenac 0.3% ophthalmic suspension versus vehicle, based on clinical outcomes, after cataract surgery in patients with diabetes. Design Two prospective, randomized, multicenter, double-masked, vehicle-controlled phase 3 studies. Participants Total, 615 patients in study 1 and 605 patients in study 2. Methods Patients were randomized (1:1) to topical nepafenac 0.3% or vehicle once-daily starting the day before surgery and continuing for 90 days thereafter. Main Outcome Measures Key efficacy variables were: patients (%) in whom macular edema (ME) developed (≥30% increase from preoperative baseline central subfield macular thickness) within 90 days after cataract surgery and the patients (%) with a best-corrected visual acuity (BCVA) improvement of ≥15 letters from preoperative baseline through day 14 maintained through day 90. Secondary end points included: patients (%) with a BCVA improvement of ≥15 letters from preoperative baseline through days 90 and 60 and safety over 3 months. Results A significantly lower percentage of patients demonstrated ME within 90 days after surgery with nepafenac 0.3% versus vehicle (study 1: 2.3% vs. 17.3%; P P = 0.001; pooled: 4.1% vs. 15.9%; P P P = 0.671) in study 2, and 55.4% versus 46.7% ( P = 0.003) in the pooled analysis. A greater percentage of patients treated with nepafenac 0.3% versus vehicle in study 1 and similar percentage in study 2 had a BCVA improvement of ≥15 letters from preoperative baseline through day 90 (77.2% vs. 67.7% [ P = 0.009] and 65.4% vs. 65.9% [ P = 0.888]) and through day 60 (76.2% vs. 64.7% [ P = 0.002] and 68.9% vs. 62.1% [ P = 0.092]). No unanticipated adverse events were observed. Conclusions These studies demonstrated the clinical benefits of nepafenac 0.3% over vehicle in reducing the risk of postoperative ME, with the integrated analysis showing improved BCVA after cataract surgery in patients with diabetic retinopathy, with no unanticipated safety events.

Purpose Lifitegrast is an integrin antagonist that decreases T-cell–mediated inflammation associated with dry eye disease (DED). We report the results of OPUS-2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED. Design A 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial. Participants Adults aged ≥18 years with use of artificial tears within 30 days, inferior corneal staining score ≥0.5 (0–4 scale), Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, and eye dryness score ≥40 (0–100 visual analogue scale [VAS]). Methods Subjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days. Main Outcome Measures Co-primary efficacy end points were change, from baseline to day 84, in eye dryness score (VAS, both eyes) and inferior corneal fluorescein staining score in the designated study eye. Secondary end points were change, from baseline to day 84, in ocular discomfort score (0–4 scale) in study eye, eye discomfort score (VAS), total corneal staining score in the study eye, and nasal conjunctival lissamine green staining score (0–4 scale) in the study eye. Treatment-emergent adverse events (TEAEs) were recorded. Results A total of 718 subjects were randomized: placebo, n=360; lifitegrast, n=358 (intent-to-treat population). Lifitegrast-treated subjects experienced greater improvement in eye dryness than placebo-treated subjects (treatment effect, 12.61; 95% confidence interval [CI], 8.51–16.70; P P = 0.6186). There was nominally significant improvement of secondary symptom end points among lifitegrast-treated subjects: ocular discomfort (nominal P = 0.0005) and eye discomfort (nominal, P Conclusions Lifitegrast met the co-primary symptom end point (eye dryness) but not the co-primary sign end point (inferior corneal staining). Secondary end point findings were consistent with this pattern. Most ocular TEAEs were mild to moderate; there were no unexpected TEAEs. Lifitegrast warrants further consideration as a treatment for DED.