Sustained release glaucoma drug delivery systems are a collective term for devices that continuously release glaucoma medications over an extended period, replacing traditional eye drop therapy2)3).
Eye drops are the first-line treatment for glaucoma, but poor adherence is a major challenge. Up to 80% of patients do not follow prescribed dosing regimens. In Japan, approximately 40% of patients newly prescribed glaucoma eye drops discontinue treatment within one year1). Poor adherence is a significant factor in glaucoma progression1).
The causes of non-adherence are diverse. Reported factors include medication cost, side effects, complex dosing regimens, ocular surface disease, lifestyle issues, lack of disease understanding, and poor communication with physicians1)2). Sustained release devices are positioned as a future option to address these issues2).
| Category | Representative Devices |
|---|---|
| Punctal Plug | L-PPDS, OTX-TP |
| Conjunctival Fornix Insert | Bimatoprost Ocular Insert |
| Intracameral implant | Durysta, iDose TR |
In glaucoma eye drop treatment, up to 80% of patients have poor adherence, and in Japan, about 40% discontinue treatment within one year 1). The main factors are forgetting to instill eye drops, difficulty in instillation due to physical limitations, complexity of multi-drug therapy, and ocular surface damage caused by preservatives 2). Sustained-release devices release medication over several weeks to months with a single administration, eliminating the daily burden of eye drops and fundamentally improving adherence. Additionally, compared to eye drops, they offer less intraocular pressure fluctuation and maintain stable drug concentrations.
Punctal plug type
L-PPDS (Evolute): A lacrimal canalicular plug filled with latanoprost. In a phase II trial, IOP decreased by 5.7 mmHg at 4 weeks, and 87% reported no discomfort.
OTX-TP: A punctal plug that releases travoprost over 3 months. In a phase III trial, no significant difference from placebo. Development discontinued.
Advantages: Non-invasive, easy to insert and remove.
Conjunctival fornix / contact lens type
Bimatoprost ocular insert: A ring-shaped silicone implant. Inserted into the superior and inferior conjunctival fornices. Retention rate 88.5% (6 months). IOP reduction equivalent to timolol.
TODDD: A polymer inserted into the superior conjunctival fornix. Drug diffusion over 3 months or more. In animal studies, IOP decreased by 37%.
Drug-filled contact lenses: Filled with latanoprost or bimatoprost. LL-BMT1 showed a 19% IOP reduction at 3 weeks in a phase II trial.
Durysta (bimatoprost)
Approval: FDA-approved in 2020. First sustained-release therapy approved for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension3)
Structure: Made of biodegradable polymer. Injected into the anterior chamber via a 28-gauge needle. Placed in the inferior anterior chamber angle
Release characteristics: Non-pulsatile steady-state release over 90 days. Active drug concentration in the iris and ciliary body is 4,400 times higher compared to topical administration
Outcomes: IOP from 24.6 to 17.7 mmHg (approximately 30% reduction). Non-inferior to timolol3)4)
iDose TR (travoprost)
Structure: Titanium reservoir (0.5 mm wide × 1.2 mm long). Sustained release of 75 μg preservative-free travoprost through a nanoporous EVA membrane
Placement: Positioned in the trabecular meshwork and fixed with a scleral anchor. Combined with cataract surgery or performed as a standalone procedure
Outcomes: IOP reduction of 5.5–8.5 mmHg. At 12 months, 81% were medication-free. Conjunctival hyperemia less frequent than with topical travoprost
Advantages: No iris pigmentation or periorbital fat atrophy observed
OTX-TIC: Implant incorporating travoprost-filled microparticles in a biodegradable hydrogel. Aims for sustained release over 4–6 months, but did not meet the primary endpoint in a Phase III trial.
ENV515/travoprost XR: PEA biodegradable implant manufactured using PRINT® technology. Preclinical studies showed 35% IOP reduction over 24 weeks. Phase IIa trial demonstrated 25% IOP reduction at 11 months.
PA5108/latanoprost FA SR: Rod-shaped biodegradable implant. Achieves zero-order release profile. Preclinical studies demonstrated IOP reduction for 10–34 weeks. Phase I trial ongoing.
SpyGlass system: A drug-release pad is attached to the junction of the optic and haptic of an intraocular lens during cataract surgery. Placed off the visual axis, it achieves drug release for up to 3 years. IOP reduced by 45% at 9 months (23 eyes).
| Device | Key Outcomes | Safety |
|---|---|---|
| Durysta | IOP reduction 30% | Conjunctival hyperemia 27% |
| iDose TR | 81% medication-free | Endophthalmitis 1 case |
| Bimatoprost ocular insert | Retention rate 88.5% | Safe and well tolerated |
Durysta: In a phase III trial (1,122 patients), it achieved non-inferiority to timolol3)4). In phase I/II trials, a single dose maintained intraocular pressure control for 12 months in 40% of patients and for 24 months in 28%. The most common side effect was conjunctival hyperemia (27%), with foreign body sensation, eye pain, photophobia, and corneal endothelial cell loss occurring in 5–10%. It is contraindicated in patients with corneal endothelial dystrophy, history of corneal transplantation, or posterior capsule rupture.
iDose TR: In a phase II trial (3 years), it showed similar intraocular pressure reduction to the timolol group, with 63–69% of the implant group achieving IOP control with the same or fewer medications. A phase III trial (590 patients) demonstrated non-inferiority to timolol over 12 months. Notably, iris pigmentation and periorbital fat atrophy associated with topical prostaglandin analogs were not observed.
OTX-TP / OTX-TIC: Neither achieved the primary efficacy endpoint. The punctal plug type OTX-TP has been discontinued.
Durysta (bimatoprost) is made of a biodegradable polymer that is naturally placed in the anterior chamber angle and releases the drug for 90 days. iDose TR (travoprost) is a titanium reservoir fixed to the trabecular meshwork, allowing longer drug release. Both achieved non-inferiority to timolol, but iDose TR showed a high rate of 81% being medication-free at 12 months. The most common side effect of Durysta is conjunctival hyperemia (27%), whereas iDose TR had a lower frequency of conjunctival hyperemia compared to topical prostaglandin analogs.
Glaucoma is a chronic progressive disease that requires patients to consistently follow treatment recommendations2). The concept of “adherence,” which includes the patient’s active participation, is more widely used than “compliance”2).
Factors contributing to poor adherence are classified as follows1)2):
To improve adherence, simplification of medication regimens, patient education, effective communication, and use of reminders are recommended1)2). However, currently only a limited number of facilities are adequately implementing these measures1).
Sustained-release devices offer the following pharmacokinetic advantages.
Maintenance of constant drug concentration: Eye drops show a fluctuating pattern with high concentration immediately after administration followed by a rapid decline. Sustained-release formulations maintain stable drug concentrations through zero-order release.
Achievement of high local concentration: Durysta achieves an active drug concentration 4,400 times higher than topical administration in the iris and ciliary body. This results in efficient intraocular pressure reduction.
Avoidance of systemic side effects: Intracameral administration avoids systemic absorption via the nasolacrimal duct, thereby reducing cardiopulmonary side effects of beta-blockers and periorbital fat atrophy associated with prostaglandin analogs.
The field of sustained-release glaucoma drug delivery systems is rapidly evolving.
Future challenges include the following.
For intracameral implants, PA5108 (latanoprost, zero-order release, Phase I ongoing) and ENV515 (travoprost, Phase IIa completed) are under development. The IOL-based SpyGlass system is an innovative platform that achieves drug release for up to 3 years when integrated with cataract surgery. Drug-eluting contact lenses (LL-BMT1) have shown efficacy in Phase II trials as a non-invasive option. In the future, simultaneous sustained release of multiple drugs and further improvements in biodegradable materials are expected.
- 日本緑内障学会. 緑内障診療ガイドライン（第5版）. 日眼会誌. 2022;126:85-177.
- European Glaucoma Society. Terminology and Guidelines for Glaucoma, 6th Edition. Br J Ophthalmol. 2025.
- American Academy of Ophthalmology. Primary Open-Angle Glaucoma Preferred Practice Pattern®. 2020.
- American Academy of Ophthalmology. Primary Open-Angle Glaucoma Suspect Preferred Practice Pattern®. 2020.
- Fellman RL, Mattox CG, Ross C, et al. Reporting Clinical Endpoints in Studies of Minimally Invasive Glaucoma Surgery. Ophthalmology. 2025;132(2):141-159.
