The purpose of this study was to evaluate nepafenac ophthalmic suspension 0.1% (Nevanac(®); Alcon Research Ltd) in the prevention of macular edema following cataract surgery in diabetic retinopathy ...patients.
This was a multicenter, randomized, double-masked, vehicle-controlled study of 263 adult diabetic patients with nonproliferative diabetic retinopathy requiring cataract surgery. Patients were randomized (1:1) to instill nepafenac or vehicle three times daily beginning 1 day prior to surgery through day 90. Efficacy included the percentage of patients who developed macular edema (≥30% increase in central subfield macular thickness from baseline) and the percentage of patients with decreases of more than five letters in best-corrected visual acuity from day 7 to 90.
A significantly lower percentage of patients in the nepafenac group developed macular edema relative to patients in the vehicle group (3.2% versus 16.7%; P < 0.001). A significantly lower percentage of patients in the nepafenac group had best-corrected visual acuity decreases of more than five letters relative to patients in the vehicle group on day 30 (P < 0.001), day 60 (P = 0.002), and day 90 (P = 0.006). The mean central subfield macular thickness and mean percent change from baseline in macular volume were also significantly lower in the nepafenac group versus the vehicle group at days 14 through 90 (P ≤ 0.005). No safety issues or trends were identified when dosing was increased to 90 days that negatively impacted the favorable benefit/risk profile of nepafenac.
Nepafenac demonstrated statistically significant and clinically relevant advantages compared with vehicle in preventing macular edema and maintaining visual acuity in diabetic patients following cataract surgery. These advantages were seen at multiple time points over the course of the 90-day therapy period. There was no clinically relevant increase in risk from 90 days dosing compared with 14 days. Therefore, with a similar safety profile and benefit in preventing macular edema and maintaining vision, the risk/benefit to the diabetic patient undergoing cataract surgery appears to be positive.
To evaluate once-daily nepafenac 0.3% to prevent and treat ocular pain and inflammation after cataract surgery.
Sixty-five centers in the United States and Europe.
Randomized double-masked vehicle- ...and active-controlled phase 3 study.
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.
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%.
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.
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.
To evaluate the effectiveness and safety of the DFT015 intraocular lens (IOL) (AcrySof IQ Vivity Extended Vision) compared with an aspheric monofocal control IOL (AcrySof IQ model SN60WF).
11 ...investigation sites in the U.S.
Prospective randomized controlled clinical study.
Patients aged 22 years or older with bilateral cataracts were randomized to receive bilateral implantation of DFT015 or SN60WF. The 4 coprimary effectiveness outcomes (6 months postoperatively) were monocular photopic distance-corrected intermediate visual acuity (DCIVA), monocular photopic corrected distance visual acuity (CDVA), monocular depth of focus (DoF), and the percentage of patients achieving a DCIVA of 0.2 logMAR or better. The mean monocular photopic distance-corrected near visual acuity (DCNVA) was a secondary effectiveness outcome. Safety and patient-reported visual disturbances were evaluated through questionnaires.
218 patients (435 eyes) completed the study. Compared with SN60WF, DFT015 demonstrated superior mean monocular photopic DCIVA ( P < .001), noninferior mean monocular photopic CDVA, and superior mean monocular photopic DCNVA ( P < .001) and provided an extended monocular DoF (increase of 0.54 diopters at 0.2 logMAR). With DFT015, 78 first eyes (72.9%) achieved a DCIVA of 0.2 logMAR or better at 6 months. Incidences of ocular serious adverse events and patient-reported most bothersome visual disturbances were low and consistent between groups.
DFT015 is safe and effective for the visual correction of aphakia, exceeding American National Standards Institute criteria for an extended depth-of-focus IOL by providing superior DCIVA and DCNVA, with comparable CDVA and visual disturbances to the SN60WF monofocal IOL.
This study evaluated nepafenac ophthalmic suspension 0.1% for prevention of macular oedema (MO) when used 90 days following cataract surgery in patients with diabetic retinopathy (DR).
Randomised, ...double-masked, vehicle-controlled, parallel group study conducted at 32 centres across the world. Participants were patients with diabetes with non-proliferative diabetic retinopathy scheduled for cataract surgery with (posterior chamber) intraocular lens implantation. Patients were randomised to nepafenac ophthalmic suspension 0.1% or vehicle three times daily, beginning on the day before surgery and continuing through the last study visit (day 90 or early exit). All patients were instilled one drop of tobramycin 0.3% and dexamethasone 0.1% four times daily for 2 weeks after surgery. Primary efficacy end point was the percentage of patients who developed MO (defined as ≥30% increase in central subfield macular thickness from baseline) within 90 days following surgery. The secondary end point was mean change in best-corrected visual acuity (BCVA) from baseline to day 90.
A total of 175 patients were randomised, with 87 and 88 patients in the nepafenac and vehicle groups, respectively. A significantly greater percentage of eyes in the vehicle group (17.5%; 95% CI 9.9% to 27.6%) developed MO within 90 days following surgery compared with the nepafenac group (5.0%; 95% CI 1.4% to 12.3%, p=0.01). Mean change in BCVA from baseline to day 90 following surgery was greater in the nepafenac group (17.7±14.6 letters) relative to the vehicle group (14.3±13.9 letters), though the difference was not statistically significant (p=0.14). No new safety issues or trends were identified.
A 90-day nepafenac treatment regimen prevented MO after cataract surgery in patients with DR and demonstrated no safety issues within this study group.
NTC00782717 and NCT00939276.
To compare the preservative-free corticosteroid 0.2% betamethasone sodium phosphate BID (SURF-201) to vehicle BID in patients undergoing routine cataract surgery.
Phase 2, multicenter, randomized ...(1:1 ratio), double-masked, vehicle-controlled, parallel-group study in patients scheduled for uncomplicated cataract surgery without the aid of a femtosecond laser. Subjects instilled topical medications for 16 days beginning the day before cataract surgery (Day -1), 1 dose administered at least 1 hour prior to cataract surgery (on Day 0) and 1 dose on the evening after cataract surgery, and then 2 doses administered each day through Day 15; patients were re-evaluated on Days 22 and 32 to ensure no rebound inflammation. Primary outcome was the difference in the proportion of subjects with anterior chamber cell (ACC) grade 0 between the two groups at Day 15. Secondary outcomes included pain scores and overall safety.
There was a statistically significant difference (P=0.004) in the proportion of subjects in the SURF-201 treatment group with an ACC grade of 0 at Day 15 (n=22/39 56.4%) compared to subjects in the vehicle treatment group (n=9/43 20.9%). There was no statistically significant difference (P=0.528) in the proportion of subjects in the SURF-201 treatment group who had a visual analog scale pain score of 0 at Day 15 (n=35/38 89.7%) compared to subjects in the vehicle group (n=33/40 82.5%). A slightly higher incidence of adverse events occurred in subjects in the SURF-201 treatment group (n=27/40 67.5%) compared to the vehicle treatment group (n=23/43 53.5%).
SURF-201 is an effective topical, preservative-free corticosteroid when dosed BID for the treatment of postoperative inflammation and prevention of pain in a post-cataract population.
Nepafenac ophthalmic suspension 0.1% was dosed topically once (QD), twice (BID), or three-times (TID) daily to assess the resolution of ocular pain and anterior-segment inflammation following ...cataract surgery.
This was a prospective, multicenter, double-masked, randomized, placebo-controlled study of 212 adults. Patients received nepafenac 0.1% or placebo, 1 drop QD, BID, or TID beginning 1 day before cataract surgery, continuing on the day of surgery, and for 14 days thereafter. One (1) additional drop was administered 30-120 min prior to surgery. The primary efficacy endpoint was percent of treatment failures (>or=16 aqueous cells, aqueous flare = severe, or ocular pain score = moderately severe or severe) through postoperative day 14.
On days 7 and 14, the QD, BID, and TID all nepafenac posologies significantly reduced the percent of treatment failures, compared to placebo ( p <or= 0.0029). Compared with placebo, the TID posology achieved statistical significance beginning on day 3 ( p <or= 0.0080). Nepafenac treatment significantly increased the proportion of patients with resolved ocular inflammation, compared to placebo, beginning on day 1 for TID dosing ( p <or= 0.0208) and beginning on day 3 for QD dosing ( p <or= 0.0483). A significantly greater percentage of nepafenac-treated patients were pain free, compared to placebo, beginning on postoperative day 1 with BID and TID dosing ( p <or= 0.0150) and beginning on day 3 for QD dosing (p <or= 0.0220). No serious ocular adverse events were reported, and fewer patients experienced adverse events in the nepafenac groups than in the placebo group.
Nepafenac ophthalmic suspension 0.1% was well tolerated and effectively resolved ocular inflammation and increased the incidence of ocular pain-free patients following cataract surgery when dosed QD, BID, or TID. By postoperative day 14, all nepafenac posologies significantly reduced the incidence of treatment failures and the incidence of patients presenting with ocular inflammation, and significantly increased the incidence of ocular pain-free patients relative to placebo.
Purpose: To evaluate the long-term (>1 yr) outcomes a non-diffractive extended vision intraocular lens (AcrySof IQ Vivity) compared to monofocal control. Setting: This was a multicenter trial that ...took place in 4 separate private ophthalmology practices throughout the United States. Design: This was a prospective, non-interventional, controlled, multicenter trial. All subjects were enrolled from participants in the Food and Drug Administration (FDA) clinical trial that led to the approval of the AcrySof IQ Vivity. Methods: Binocular uncorrected distance visual acuity (UCDVA), distance corrected visual acuity (DCVA), uncorrected intermediate visual acuity (UIVA) at 66cm, distance corrected intermediate visual acuity (DCIVA) at 66cm, uncorrected near visual acuity (UNVA) at 40cm, and distance corrected near visual acuity (DCNVA) at 40cm were measured. The binocular defocus curve was measured. A 23-question survey on visual performance including questions on spectacle independence, satisfaction, dysphotopsias, and like-lihood of recommending their lens to another person was used administered. Results: A total of 64 eyes of 32 subjects were enrolled. Seventeen subjects had bilateral implantation of the AcrySof IQ Vivity lens, and 15 subjects had bilateral implantation of the AcrySof IQ Monofocal (SN60WF). Mean follow up time was 1078 days for the study group compared to 1067 days for the control group (p = 0.92). There were no differences in UCVA or DCVA between the two groups. Compared to control, the AcrySof IQ Vivity group had better mean binocular UIVA (logMAR 0.29 vs 0.18; p = 0.09), DCIVA (logMAR 0.33 vs 0.11; p = 0.003), UNVA (logMAR 0.49 vs 0.30, p = 0.01), and DCNVA (logMAR 0.54 vs 0.29; p = 0.001). Conclusion: The AcrySof IQ Vivity is a novel, non-diffractive extended range of vision intraocular lens that provides long-term, enhanced visual acuity at intermediate and near ranges with high levels of patient satisfaction and minimal dysphotopsias. Keywords: Vivity, extended depth of focus, defocus curve, cataract surgery
Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD), including potentially improved outcomes ...and decreased treatment burden.
To assess safety and efficacy of aflibercept, 8 mg, in patients with nAMD.
The CANDELA trial was a phase 2, randomized, single-masked, open-label, 44-week clinical trial conducted in the US. Treatment-naive patients with active subfoveal choroidal neovascularization secondary to nAMD and a best-corrected visual acuity score of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled between November 2019 and November 2021.
Eligible participants were randomized 1:1 to receive 3 monthly doses of 8 mg (70 μL) or 2 mg (50 μL) of aflibercept followed by doses at weeks 20 and 32.
Coprimary end points were the proportion of eyes without fluid (absence of intraretinal and subretinal fluid) in the central subfield at week 16 and safety.
All 106 eligible eyes were randomized to receive aflibercept, 8 mg (n = 53), or aflibercept, 2 mg (n = 53). Overall, 66 participants (62.3%) were female. The proportion of eyes without fluid in the central subfield with 8-mg vs 2-mg aflibercept was 50.9% (n = 27) vs 34.0% (n = 18) (difference, 17.0 95% CI, -1.6 to 35.5 percentage points; P = .08) at week 16 and 39.6% (n = 21) vs 28.3% (n = 15) (difference, 11.3 95% CI, -6.6 to 29.2 percentage points; nominal P = .22) at week 44. At week 44, mean (SE) change in central retinal thickness was -159.4 (16.4) vs -137.2 (22.8) μm with 8 mg vs 2 mg of aflibercept, respectively (least squares mean difference, -9.5 95% CI, -51.4 to 32.4; nominal P = .65) and mean (SE) change in best-corrected visual acuity score was +7.9 (1.5) vs +5.1 (1.5) letters (least squares mean difference, +2.8 95% CI, -1.4 to +7.0; nominal P = .20). No differences in safety profiles between the groups were observed.
Although aflibercept, 8 mg, did not achieve the primary efficacy end point at week 16 at the 2-sided significance level of 5%, the observed trends in anatomic and visual improvements over 44 weeks with aflibercept, 8 mg, indicate potential additional therapeutic benefit over aflibercept, 2 mg. No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of exudative retinal diseases including nAMD and diabetic macular edema.
ClinicalTrials.gov Identifier: NCT04126317.
PurposeTo compare the preservative-free corticosteroid 0.2% betamethasone sodium phosphate BID (SURF-201) to vehicle BID in patients undergoing routine cataract surgery. MethodsPhase 2, multicenter, ...randomized (1:1 ratio), double-masked, vehicle-controlled, parallel-group study in patients scheduled for uncomplicated cataract surgery without the aid of a femtosecond laser. Subjects instilled topical medications for 16 days beginning the day before cataract surgery (Day -1), 1 dose administered at least 1 hour prior to cataract surgery (on Day 0) and 1 dose on the evening after cataract surgery, and then 2 doses administered each day through Day 15; patients were re-evaluated on Days 22 and 32 to ensure no rebound inflammation. Primary outcome was the difference in the proportion of subjects with anterior chamber cell (ACC) grade 0 between the two groups at Day 15. Secondary outcomes included pain scores and overall safety. ResultsThere was a statistically significant difference (P=0.004) in the proportion of subjects in the SURF-201 treatment group with an ACC grade of 0 at Day 15 (n=22/39 56.4%) compared to subjects in the vehicle treatment group (n=9/43 20.9%). There was no statistically significant difference (P=0.528) in the proportion of subjects in the SURF-201 treatment group who had a visual analog scale pain score of 0 at Day 15 (n=35/38 89.7%) compared to subjects in the vehicle group (n=33/40 82.5%). A slightly higher incidence of adverse events occurred in subjects in the SURF-201 treatment group (n=27/40 67.5%) compared to the vehicle treatment group (n=23/43 53.5%). ConclusionSURF-201 is an effective topical, preservative-free corticosteroid when dosed BID for the treatment of postoperative inflammation and prevention of pain in a post-cataract population.
PurposeTo evaluate the long-term (>1 yr) outcomes a non-diffractive extended vision intraocular lens (AcrySof IQ Vivity) compared to monofocal control. SettingThis was a multicenter trial that took ...place in 4 separate private ophthalmology practices throughout the United States. DesignThis was a prospective, non-interventional, controlled, multicenter trial. All subjects were enrolled from participants in the Food and Drug Administration (FDA) clinical trial that led to the approval of the AcrySof IQ Vivity. MethodsBinocular uncorrected distance visual acuity (UCDVA), distance corrected visual acuity (DCVA), uncorrected intermediate visual acuity (UIVA) at 66cm, distance corrected intermediate visual acuity (DCIVA) at 66cm, uncorrected near visual acuity (UNVA) at 40cm, and distance corrected near visual acuity (DCNVA) at 40cm were measured. The binocular defocus curve was measured. A 23-question survey on visual performance including questions on spectacle independence, satisfaction, dysphotopsias, and likelihood of recommending their lens to another person was used administered. ResultsA total of 64 eyes of 32 subjects were enrolled. Seventeen subjects had bilateral implantation of the AcrySof IQ Vivity lens, and 15 subjects had bilateral implantation of the AcrySof IQ Monofocal (SN60WF). Mean follow up time was 1078 days for the study group compared to 1067 days for the control group (p = 0.92). There were no differences in UCVA or DCVA between the two groups. Compared to control, the AcrySof IQ Vivity group had better mean binocular UIVA (logMAR 0.29 vs 0.18; p = 0.09), DCIVA (logMAR 0.33 vs 0.11; p = 0.003), UNVA (logMAR 0.49 vs 0.30, p = 0.01), and DCNVA (logMAR 0.54 vs 0.29; p = 0.001). ConclusionThe AcrySof IQ Vivity is a novel, non-diffractive extended range of vision intraocular lens that provides long-term, enhanced visual acuity at intermediate and near ranges with high levels of patient satisfaction and minimal dysphotopsias.
PDF
