Phase 3, Randomized Study Comparing Intracameral Bimatoprost Implant 15 µg and Selective Laser Trabeculectomy in Patients with Open-Angle Glaucoma or Ocular Hypertension.

Purpose: We evaluate the safety and intraocular pressure (IOP)-lowering effect of 15-µg bimatoprost implant (higher dose than the currently approved product) compared with selective laser trabeculoplasty (SLT) in patients with open-angle glaucoma or ocular hypertension. Methods: Randomized, phase 3, 12-month, multicenter, paired-eye, patient- and efficacy evaluator-masked noninferiority study. Patients with inadequate IOP control were randomized to receive 360° SLT (day 1) or up to 3 administrations of 15-µg bimatoprost implant (day 4, weeks 16 and 32) in the primary eye and the alternative treatment in the contralateral eye. The primary endpoint was IOP change from baseline at weeks 4, 12, and 24. Results: At weeks 4, 12, and 24, mean IOP change from baseline ranged from -7.01 to -6.65 mm Hg in implant-treated eyes (N=138) and -6.45 to -6.26 mm Hg in SLT-treated eyes (N=138). Differences in IOP change from baseline ranged from -0.70 to -0.25 mm Hg favoring implant; the upper limit of the 95% confidence interval of the difference (implant minus SLT) was <1.0 mm Hg at all 3 visits. The probability of requiring no additional (rescue) IOP-lowering treatment in implant-treated versus SLT-treated eyes was 93.6% versus 86.5% at day 180 and 74.6% versus 77.1% at day 360. Corneal endothelial cell loss was more common in implant-treated eyes and typically occurred after repeated implant administration. Conclusion: Bimatoprost implant 15 µg met prespecified criteria for statistical and clinical noninferiority to SLT in lowering IOP, and after 1, 2, or 3 administrations, demonstrated a duration of IOP lowering similar to SLT. Bimatoprost implant 15 µg was associated with corneal adverse events in some patients, especially after repeated administrations at a fixed interval, and has been discontinued from development. A lower dose strength of implant (bimatoprost implant 10 µg, Durysta) is US Food and Drug Administration-approved for single administration.

Single Administration of Bimatoprost Implant: Effects on 24-Hour Intraocular Pressure and 1-Year Outcomes.

PURPOSE: To evaluate the effects of a single bimatoprost implant administration on 24-hour intraocular pressure (IOP) lowering at 8 weeks, and 1-year IOP-lowering efficacy and safety outcomes. DESIGN: Multicenter, open-label, 12-month, phase 3b study (NCT04285580). PARTICIPANTS: Adults with open-angle glaucoma or ocular hypertension. METHODS: Participants (n = 31) received 10-µg bimatoprost implant in the study eye on day 1; IOP (sitting and/or supine) was measured with pneumatonometry every 2 hours throughout a 24-hour period at baseline and week 8. IOP was measured by Goldmann applanation tonometry (GAT) at hour 0 (8 am ± 1 hour) at baseline, weeks 8 and 16, and months 6, 9, and 12. MAIN OUTCOME MEASURES: The primary endpoint was the week-8 hour-matched change from baseline in habitual position IOP over 24 hours assessed with pneumatonometry. Hour 0 IOP change from baseline measured with GAT in study eyes that received no additional (rescue) IOP-lowering treatment, treatment-emergent adverse events (TEAEs), and central corneal endothelial cell density (CECD) were evaluated through 12 months. RESULTS: The mean (standard deviation [SD]) baseline IOP at hour 0 was 24.2 (2.70) mmHg and 25.3 (7.15) mmHg by GAT and pneumatonometry, respectively. Pneumatonometer measurements of IOP taken over 24 hours at week 8 with the participant in habitual position (sitting from 8 am to 10 pm, supine from 12 am to 6 am) showed consistent IOP lowering through the day and night and reduced fluctuation in IOP. The range in IOP measurements over 24 hours was reduced from baseline by a mean (SD) of -1.6 (2.98) mmHg. All 31 bimatoprost implant-treated participants completed the 12-month study; 23 (74%) required no rescue IOP-lowering treatment. The mean (SD) IOP reduction from baseline at month 12 in nonrescued eyes was -4.3 (3.35) mmHg. The most common TEAE was conjunctival hyperemia (incidence 35.5%, 11/31). No implant-treated eye had a ≥ 15% loss in CECD from baseline. CONCLUSIONS: A single intracameral administration of the bimatoprost implant lowered IOP in the habitual position consistently throughout the day and night at week 8. The majority of participants continued to have reduced IOP for 1 year without additional therapy. The 1-year safety profile was favorable. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical Evaluation of a Modified Light Transmission Short-Wavelength Filtering Intraocular Lens Compared to a Colorless Control.

INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of a violet-light filtering intraocular lens (IOL) compared to a colorless IOL control. METHODS: This was a prospective, bilateral, randomized, comparative, patient/evaluator-masked multi-center clinical trial at 12 sites in the USA. Patients underwent standard small-incision phacoemulsification cataract extraction. Visual acuity, contrast sensitivity, and color vision were tested 12 months postoperatively. Patient satisfaction and vision-related quality of life were evaluated based on directed patient responses obtained from a binocular subjective questionnaire. RESULTS: A total of 250 subjects were bilaterally implanted with the violet-light filtering TECNIS monofocal ZV9003 (n = 126) and colorless TECNIS monofocal ZA9003 (n = 124). Mean uncorrected distance visual acuity (UDVA) was 0.123 LogMAR for ZV9003 and 0.116 LogMAR for the ZA9003 group. Mean corrected distance visual acuity (CDVA) was 0.00 LogMAR for both groups. No significant difference was found between the groups for 22/25 questionnaire categories, including color perception. A significant difference was found in favor of the ZV9003 group for day driving, night driving, and frustration with vision. Contrast sensitivity mean difference was < 0.05 log units across all lighting conditions and spatial frequencies. CONCLUSION: No difference was found between groups for visual acuity, contrast sensitivity, color testing, and adverse events as well as with the majority of optical/visual symptoms. A statistical difference was noted in driving and frustration with eyesight that may be related to benefits of using a violet-light filtering chromophore. Overall, the violet-light filtering ZV9003 showed excellent visual acuity and contrast sensitivity results with a low incidence of optical/visual symptoms.

Visual outcomes and safety of an extended depth-of-focus intraocular lens: results of a pivotal clinical trial.

PURPOSE: To compare the effectiveness and safety of the TECNIS Symfony intraocular lens (IOL; ZXR00) with the TECNIS 1-piece monofocal IOL (ZCB00). SETTING: 15 sites in the United States. DESIGN: Prospective, randomized, patient-masked/evaluator-masked clinical trial. METHODS: Randomized participants received either the ZXR00 or ZCB00 IOL bilaterally. The 6-month postoperative outcomes included monocular and binocular distance, intermediate, and near visual acuity (VA), spherical equivalent refraction and refractive cylinder, spectacle wear, and visual symptoms. RESULTS: Overall, 299 patients were implanted with a study IOL (ZXR00 IOL, n = 148; ZCB00 IOL control, n = 151). At the 6-month follow-up, mean binocular uncorrected distance VA was comparable between ZXR00 and ZCB00 IOL recipients (P = .1011). The ZXR00 IOL group had significantly better mean binocular uncorrected intermediate VA and uncorrected near VA (both P < .0001) than the ZCB00 IOL group. The mean binocular distance-corrected intermediate VA and distance-corrected near VA were also better in the ZXR00 IOL group (both P < .0001). More ZXR00 IOL recipients reported wearing spectacles none of the time or a little of the time for overall vision at 6 months compared with the ZCB00 IOL group (85.0% vs 59.9%, P < .0001). In the ZXR00 IOL-implanted patients, low incidence rates of night glare (mild to moderate, 2.7%), halo (mild to moderate, 13.6%; severe, 2.7%), and starbursts (mild to moderate, 7.5%; severe, 1.4%) were reported. CONCLUSIONS: The TECNIS Symfony IOL provided comparable distance vision and improved uncorrected and distance-corrected intermediate and near vision, along with decreased spectacle wear and low incidence rates of dysphotopsia, compared with the TECNIS 1-piece monofocal IOL.

24-Month Phase I/II Clinical Trial of Bimatoprost Sustained-Release Implant (Bimatoprost SR) in Glaucoma Patients.

OBJECTIVE: The objective of this study was to evaluate the safety and intraocular pressure (IOP)-lowering effects over 24 months of biodegradable bimatoprost sustained-release implant (Bimatoprost SR) administration versus topical bimatoprost 0.03% in patients with open-angle glaucoma (OAG). METHODS: This was a phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial. At baseline following washout, adult patients with OAG (N = 75) received Bimatoprost SR (6, 10, 15, or 20 µg) intracamerally in the study eye; the fellow eye received topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or single repeat administration with implant was permitted. The primary endpoint was IOP change from baseline. Safety measures included adverse events (AEs). RESULTS: At month 24, mean IOP reduction from baseline was 7.5, 7.3, 7.3, and 8.9 mmHg in eyes treated with Bimatoprost SR 6, 10, 15, and 20 µg, respectively, versus 8.2 mmHg in pooled fellow eyes; 68, 40, and 28% of pooled study eyes had not been rescued/retreated at months 6, 12, and 24, respectively. AEs in study eyes that occurred ≤ 2 days post-procedure typically were transient. After 2 days post-procedure, overall AE incidence was similar between study and fellow eyes, with some events typically associated with topical prostaglandin analogs having lower incidence in study eyes. CONCLUSIONS: Bimatoprost SR showed favorable efficacy and safety profiles up to 24 months, with all evaluated dose strengths demonstrating overall IOP-reducing effects comparable to those of topical bimatoprost. Targeted and sustained delivery of bimatoprost resulted in protracted IOP lowering, suggesting that Bimatoprost SR may represent a transformational new approach to glaucoma therapy. Clinicaltrials.gov identifier: NCT01157364.

Clinical evaluation of a bacterially derived sodium hyaluronate 2.3% ophthalmic viscosurgical device.

PURPOSE: To compare the safety and effectiveness of bacterially derived and animal-derived sodium hyaluronate 2.3% ophthalmic viscosurgical devices (OVD) (Healon5 PRO and Healon5, respectively) in cataract surgery. SETTING: United States multicenter study. DESIGN: Prospective, randomized, masked, controlled study. METHODS: Adult patients having bilateral cataract extraction and posterior chamber intraocular lens implantation were randomly assigned to receive Healon5 PRO OVD in 1 eye (study group) and Healon5 OVD in the fellow eye (control group). The endothelial cell count (ECC) was measured preoperatively and 3 months postoperatively. Tonometry was performed preoperatively and at the 6-hour, 1-day, 1-week, 1-month, and 3-month timepoints. The cumulative rate of postoperative intraocular pressure (IOP) spikes (≥30 mm Hg) was calculated. Changes from baseline in IOP, edema, inflammation, serious adverse events, and visual acuity were also assessed. RESULTS: The study comprised 213 and 208 treated and paired-eye patients, respectively. At 3 months, there was no statistically significant difference in the mean percentage ECC change from baseline between study group and the control group (-5.55% versus -6.66%; mean difference 1.11% ± 11.89% [SD]; 95% confidence interval (CI), -0.52 to 2.74) or the cumulative IOP spike rate (8.2% versus 6.3%; mean percentage difference -1.9%; 95% CI, -5.46% to 1.61%). At 3 months, both OVD groups had significant reductions in IOP from baseline (-1.37 mm Hg and -1.32 mm Hg, respectively; both P < .0001). The distribution of edema, inflammation, serious adverse events, and visual acuity outcomes was also similar between the groups. CONCLUSION: The 2 OVDs were clinically similar in terms of safety and effectiveness for cataract surgery.

Bimatoprost Sustained-Release Implants for Glaucoma Therapy: 6-Month Results From a Phase I/II Clinical Trial.

PURPOSE: To evaluate the safety and intraocular pressure (IOP)-lowering effect of a biodegradable bimatoprost sustained-release implant (Bimatoprost SR). DESIGN: Phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial. METHODS: At baseline following washout, open-angle glaucoma patients (n = 75) were administered Bimatoprost SR (6 µg, 10 µg, 15 µg, or 20 µg) intracamerally in the study eye; the fellow eye began topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or a single repeat treatment with implant was allowed. The primary endpoint was IOP change from baseline. The main safety measure was adverse events. Results through month 6 are reported. RESULTS: Bimatoprost SR provided rapid, sustained IOP lowering. Overall mean IOP reduction from baseline through week 16 in study eyes was 7.2, 7.4, 8.1, and 9.5 mm Hg with the 6-µg, 10-µg, 15-µg, and 20-µg dose strengths of implant, respectively, vs 8.4 mm Hg in topical bimatoprost-treated pooled fellow eyes (data censored at rescue/retreatment). Rescue/retreatment was not required in 91% and 71% of study eyes up to week 16 and month 6, respectively. Adverse events in study eyes usually occurred within 2 days after the injection procedure and were transient. Conjunctival hyperemia with onset later than 2 days after the injection procedure was more common with topical bimatoprost than Bimatoprost SR (17.3% vs 6.7% of eyes). CONCLUSIONS: Bimatoprost SR demonstrated favorable efficacy and safety through 6 months. All dose strengths were comparable to topical bimatoprost in overall IOP reduction through week 16. A single administration controlled IOP in the majority of patients for up to 6 months.

Once-daily nepafenac ophthalmic suspension 0.3% to prevent and treat ocular inflammation and pain after cataract surgery: phase 3 study.

PURPOSE: To evaluate once-daily nepafenac 0.3% to prevent and treat ocular pain and inflammation after cataract surgery. SETTING: Sixty-five centers in the United States and Europe. DESIGN: Randomized double-masked vehicle- and active-controlled phase 3 study. METHODS: Patients received nepafenac 0.3% once daily, nepafenac 0.1% 3 times daily, or their respective vehicles from day -1 to day 14 after cataract extraction. An additional drop of study drug was administered 30 to 120 minutes preoperatively. The primary endpoint was the percentage of patients with a cure for inflammation (score of 0 for both aqueous cells and flare) at day 14. RESULTS: Of randomized patients, 817 received nepafenac 0.3%, 819 received nepafenac 0.1%, and 200 and 206 received the respective vehicles. Significantly more nepafenac 0.3% patients had no inflammation (68.4% versus 34.0%) and were pain free (91.0% versus 49.7%) at day 14 than vehicle patients (both P<.0001). Nepafenac 0.3% was noninferior to nepafenac 0.1% for inflammation (95% confidence interval [CI], -5.73% to 3.17%) and pain-free rates (95% CI, -3.08% to 2.70%). At all postoperative visits, fewer treatment failures (P≤.0012) and more clinical successes (P ≤ .0264) were observed with nepafenac 0.3% versus vehicle. Nepafenac 0.3% was well tolerated and had a safety profile comparable to that of nepafenac 0.1%. CONCLUSIONS: Once-daily nepafenac 0.3% was noninferior to nepafenac 0.1% 3 times daily for prevention and treatment of ocular inflammation and pain following cataract surgery. The safety of nepafenac 0.3% was comparable to that of nepafenac 0.1%, with the added convenience of once-daily dosing. FINANCIAL DISCLOSURE: Drs. Modi, Lehmann, Walters, Fong, Christie, Roel, Nethery, and Reiser have been paid consultants to Alcon Research, Ltd. Ms. Sager is an employee of Alcon Research, Ltd. Drs. Tsorbatzoglou, Philipson, and Traverso have no financial or proprietary interest in any material or method mentioned.