Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Intracameral sustained-release implants

24 evidence topics · 12 sources

Summary: approved intracameral prostaglandin implants as comparators

Two intracameral prostaglandin implants are FDA approved for IOP reduction in OAG or OHT. The bimatoprost 10 mcg biodegradable implant (Durysta) is labeled for a single administration per eye without retreatment because of corneal endothelial cell loss. In the ARTEMIS 1 (3 arms of 198 participants) and ARTEMIS 2 (528 participants) phase 3 trials, the implant was noninferior to twice-daily timolol through week 12; in ARTEMIS 1, with 3 administrations at fixed 16-week intervals, 10.2% of eyes (10 mcg) and 21.8% (15 mcg) had 20% or greater endothelial cell density loss. In the phase 3b TRITON study (441 participants), median time to retreatment or rescue after a single implant was 392 days. The travoprost 75 mcg titanium implant (iDose TR) is anchored in the sclera at the iridocorneal angle; in 2 phase 3 trials (1,150 participants pooled), it was noninferior to timolol over the first 3 months, and at month 12, 81.4% of slow-eluting implant eyes were free of topical IOP-lowering medication. Its current label notes that noninferiority was not demonstrated over the subsequent 9 months and permits readministration no more than once per year, with removal of the previous implant. Both implants are administered as separate intracameral procedures, whereas the investigational BIM-IOL System is placed in the capsular bag during cataract surgery.

AAO Preferred Practice Pattern: sustained drug delivery within medical therapy

“Multiple drug delivery systems have been developed to address the problems of patient adherence and side effects associated with glaucoma medical therapy.” (opens the source at this quote in a new tab)
“This implant is currently FDA approved only for a single administration because repeat intracameral implants were associated with a higher degree of corneal endothelial cell loss.” (opens the source at this quote in a new tab)
“In 2023, a travoprost-eluting implant (iDose TR, Glaukos, Aliso Viejo, CA) was FDA approved to be surgically implanted into the trabecular meshwork based on two prospective, randomized, multicenter, double-masked phase 3 trials that showed noninferiority to topical timolol.” (opens the source at this quote in a new tab)

European Glaucoma Society guidelines: availability in Europe

“For selected patients drug delivery by sustained release devices may be a future option to reduce burden of daily therapy thereby increasing compliance. Currently, a variety of these slow-release drug delivery systems are being developed but are not yet available in Europe.” (opens the source at this quote in a new tab)

Bimatoprost intracameral implant: labeled administration limit

“DURYSTA is an ophthalmic drug delivery system for a single intracameral administration of a biodegradable implant. DURYSTA should not be readministered to an eye that received a prior DURYSTA.” (opens the source at this quote in a new tab)
“The presence of DURYSTA implants has been associated with corneal adverse reactions and increased risk of corneal endothelial cell loss. Administration of DURYSTA should be limited to a single implant per eye without retreatment.” (opens the source at this quote in a new tab)
“DURYSTA demonstrated an IOP reduction of approximately 5-8 mmHg in patients with a mean baseline IOP of 24.5 mmHg” (opens the source at this quote in a new tab)

Bimatoprost implant pivotal trial ARTEMIS 1: efficacy and corneal safety

“Study eyes received bimatoprost implant 10 μg (n = 198) or 15 μg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198).” (opens the source at this quote in a new tab)
“Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration.” (opens the source at this quote in a new tab)
“Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant).” (opens the source at this quote in a new tab)

Bimatoprost implant pivotal trial ARTEMIS 2: efficacy and treatment-free probability

“This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye.” (opens the source at this quote in a new tab)
“Mean IOP reductions from baseline ranged from 6.2-7.4, 6.5-7.8, and 6.1-6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively.” (opens the source at this quote in a new tab)
“Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant).” (opens the source at this quote in a new tab)

Bimatoprost implant phase 3b TRITON: duration after a single administration

“In total, 441 patients received the 10-µg bimatoprost implant in the study eye on day 1 (cycle 1), 179 patients received a second administration (cycle 2), and 378 patients had at least 12 months of follow-up data available. The median time (95% confidence interval) from the first administration to a second administration or rescue was 392 (369, 485) days; the probability of not requiring retreatment or rescue by day 360 was 57.5%.” (opens the source at this quote in a new tab)

Bimatoprost implant versus SLT: ATHENA paired-eye trial

“The probability of not having required nonstudy (rescue) IOP-lowering treatment at days 360 and 720, respectively, was 67.5% and 50.2% for implant-treated eyes versus 68.7% and 60.6% for SLT-treated eyes.” (opens the source at this quote in a new tab)
“Mean (±SE) percentage change in corneal endothelial cell density from baseline at month 24 was -6.2 ± 1.13% in implant-treated eyes (-7.9 ± 2.04% with fixed readministration; -5.2 ± 1.35% with flexible readministration) versus -3.1 ± 0.43% in SLT-treated eyes.” (opens the source at this quote in a new tab)

Travoprost intracameral implant: label indication, efficacy, and readministration

“iDose® TR (travoprost intracameral implant) is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).” (opens the source at this quote in a new tab)
“iDose TR demonstrated non-inferiority to timolol ophthalmic solution in IOP reduction during the first 3 months. Subsequently, iDose TR did not demonstrate non-inferiority over the next 9 months.” (opens the source at this quote in a new tab)
“It is not recommended to readminister an iDose TR more than once per year.” (opens the source at this quote in a new tab)
“Note: When readministering an iDose TR implant, always remove the previous iDose TR implant AFTER implantation of the new implant.” (opens the source at this quote in a new tab)

Travoprost implant pivotal trial GC-010: 3-month primary endpoint

“Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193).” (opens the source at this quote in a new tab)
“Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group.” (opens the source at this quote in a new tab)
“Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively.” (opens the source at this quote in a new tab)

Travoprost implant: pooled 12-month analysis of two phase 3 trials

“A total of 1150 subjects were randomized (385 FE implant, 380 SE implant, and 385 sham/timolol) across the two trials.” (opens the source at this quote in a new tab)
“With regards to reduction in topical pharmacotherapy, at month 12, 77.6% of FE and 81.4% of SE implant eyes were completely free of all topical IOP-lowering medications” (opens the source at this quote in a new tab)
“The most common TEAEs related to study treatment were hyperemia (conjunctival or ocular), iritis, and IOP increased.” (opens the source at this quote in a new tab)

Travoprost implant pivotal trial GC-010: 12-month results

“A total of 590 patients were enrolled at 45 sites and randomized to one of three treatment groups: 197 SE-implant (the intended commercial product), 200 FE-implant, and 193 timolol.” (opens the source at this quote in a new tab)
“The SE-implant was non-inferior to timolol eye drops in IOP lowering over the first 3 months, and was also non-inferior to timolol at months 6, 9, and 12.” (opens the source at this quote in a new tab)

Bimatoprost implant pivotal trial: noninferiority margin and primary analysis population

“Analysis of IOP change from baseline used a similar MMRM approach with IOP hour-matched change from baseline as the response variable, and noninferiority was to be declared if the 95% CI of the between-group difference was within a 1.5-mmHg noninferiority margin at both hours 0 and 2 at week 12.” (opens the source at this quote in a new tab)
“The primary analyses of IOP used observed values in the intent-to-treat population of all randomized subjects.” (opens the source at this quote in a new tab)

Bimatoprost implant pivotal trial: corneal adverse events rose with each repeated administration

“Although most TEAEs showed generally similar incidence rates after the first, second, and third implant administration, corneal TEAEs of interest occurred more frequently after repeated treatment.” (opens the source at this quote in a new tab)
“Furthermore, the rate of corneal TEAEs of interest (but not other TEAEs) increased with each subsequent administration. These findings suggest that the events likely occurred secondary to a physical interaction between the implant(s) and the cornea.” (opens the source at this quote in a new tab)
“Because 3 implants were administered at fixed 4-month treatment intervals, the slow biodegradation allowed as many as 3 implants to be present at the same time in some eyes.” (opens the source at this quote in a new tab)

Bimatoprost implant pivotal trial: corneal events attributed to implant accumulation in the iridocorneal angle

“Comparison of findings from the phase 1/2 and phase 3 studies suggests that when more implants occupy the inferior angle in a short period of time, there is greater potential for endothelial cell contact and loss.” (opens the source at this quote in a new tab)
“Furthermore, the occurrence of corneal events in some subjects appeared to be related to accumulation of implant material in the iridocorneal angle, and these corneal events may have been abated with less frequent administration.” (opens the source at this quote in a new tab)

Bimatoprost implant pivotal trial: implant removal for corneal adverse events

“Implant removal should be avoided when possible because of the increased risk of adverse events associated with intraocular procedures, such as endophthalmitis, iritis, and lens and corneal damage.” (opens the source at this quote in a new tab)
“We observed that in general, corneal TEAEs resolved after implant removal, and CECD stabilized in subjects who had undergone corneal endothelial cell loss.” (opens the source at this quote in a new tab)

Bimatoprost implant versus laser trabeculoplasty: noninferiority margins applied

“the upper limit of the 95% CI for the between-group difference (bimatoprost implant minus SLT) was within the statistical and clinical noninferiority margins (1.5 mm Hg and 1.0 mm Hg, respectively) at all 3 timepoints, demonstrating statistical and clinical noninferiority of the bimatoprost implant to SLT” (opens the source at this quote in a new tab)

Bimatoprost implant versus laser trabeculoplasty: endothelial cell loss by administration schedule and angle width

“Among eyes treated with the bimatoprost implant, ≥20% ECL was observed in 9.0% of eyes on the fixed administration schedule and 7.1% of eyes on the flexible administration schedule” (opens the source at this quote in a new tab)
“The incidence of ≥20% ECL with the flexible administration schedule of bimatoprost implant versus SLT was 4.9% versus 4.0% in eyes with Shaffer grade 4 angles and 9.1% versus 2.6% in eyes with Shaffer grade 3 angles.” (opens the source at this quote in a new tab)
“Results of this study indicate that the risk of corneal events and ECL associated with bimatoprost implant treatment can be lessened by using the implant in eyes with wide open (Shaffer grade 4) angles.” (opens the source at this quote in a new tab)

Bimatoprost implant versus laser trabeculoplasty: proposed mechanism of endothelial loss and effect on visual acuity

“The most important safety concern with the bimatoprost implant is ECL, which has been proposed to result from physical interactions between the implant(s) and the cornea, and to be more frequent after multiple implants are administered because of slow biodegradation of the polymer and accumulation of residual implant.” (opens the source at this quote in a new tab)
“Within the subgroup of implant-treated eyes with a reported ≥20% loss in CECD, 7 eyes had a ≥ 3-line loss in BCVA.” (opens the source at this quote in a new tab)

Travoprost implant phase 3 trial: noninferiority margin, observed confidence intervals, and planned sample size

“The maximal mean difference in IOP change from baseline across all 6 time points was 0.10 mmHg (with an upper 95% CI of 0.83 mmHg) for the FE implant versus timolol groups and 0.10 mmHg (with an upper 95% CI of 0.82 mmHg) for the SE implant versus timolol groups. Therefore, the criteria for statistical and clinical noninferiority to timolol was met for both implant groups because the upper limit of the 95% CI of the difference between the implant groups and the timolol group was < 1.5 mmHg and also < 1 mmHg for all 6 time points” (opens the source at this quote in a new tab)
“With a true mean difference of 0, 85% power to declare noninferiority for at least 1 implant group over the timolol group would be achieved with 186 patients per treatment group or 558 patients overall.” (opens the source at this quote in a new tab)

Travoprost implant phase 3 trial: extent of corneal endothelial cell monitoring

“Another limitation of our analyses may be the small subset of patients (only 10% to 13% of patients in each of the treatment groups) in which endothelial cell counts were measured.” (opens the source at this quote in a new tab)

Travoprost implant 12-month report: status of the month 6, 9, and 12 noninferiority analyses

“After the phase 3 trial was initiated, but prior to the database lock and unmasking, a 12-month non-inferiority comparison to timolol was included as a secondary endpoint based on regulatory agency guidance; however, the trial was not prospectively powered for the noninferiority comparison at 12 months.” (opens the source at this quote in a new tab)
“A second limitation is that the non-inferiority analyses for the month 6 and 9 visits were not prospectively defined. However, the analyses used the same definition as for month 12. A third limitation of the study is that the trial was not prospectively powered for the 6, 9, and 12-month IOP efficacy evaluations.” (opens the source at this quote in a new tab)
“At months 6 and 9 (visits at which IOP was measured at 8 A.M., 10 A.M., or 4 P.M. and used time-matched baseline), non-inferiority to timolol was demonstrated for both implant groups using the same definition as used for month 12” (opens the source at this quote in a new tab)

Travoprost implant 12-month report: intraocular pressure reduction by visit and change in medication burden

“IOP reductions with the to-be-marketed SE-implant ranged from 6.6 to 8.5 mmHg at the primary efficacy endpoint (8 A.M. and 10 A.M. at day 10, week 6, and month 3) used for application of regulatory approval in the USA. At months 6 and 9, when IOP was measured at 8 A.M., 10 A.M., or 4 P.M., IOP reductions were 5.7 mmHg at both visits, while at month 12, when IOP was measured at 8 A.M. and 10 A.M., IOP reductions were 5.5 mmHg at both timepoints, with non-inferiority of the SE-implant to timolol being demonstrated over the entire 12 months.” (opens the source at this quote in a new tab)
“In addition, in the current trial, of those patients who were on glaucoma medication at screening, 83.5% of patients in the SE-implant group versus only 23.9% of patients in the timolol group were well controlled on fewer topical medications at month 12 compared to screening.” (opens the source at this quote in a new tab)

Travoprost implant 12-month report: completion and discontinuation through month 12

“A total of 565 of 590 randomized patients (95.8%) completed the month 12 visit, and 22 patients discontinued prior to month 12, primarily as a result of withdrawal of consent (seven patients, 1.2%).” (opens the source at this quote in a new tab)