Summary: development status as of September 2026

The BIM-IOL System is investigational and not approved in any jurisdiction. Two identical registrational phase 3 trials (SGP-005, Rhine, NCT07218783; SGP-006, Rhone, NCT07218796) compare the 78 mcg system with a commercial monofocal IOL plus twice-daily timolol 0.5%; each plans to enroll approximately 400 participants at 45 sites. The sponsor expects enrollment to complete in 2027, 12-month data in 2028, 24-month data in 2029, and submission of a 505(b)(2) NDA in 2028. The sponsor expects regulation as a drug-led, drug-device combination product with CDER as lead center and states no current plans to seek device premarket approval. No FDA expedited-program designation was identified in the sponsor's SEC filings. SpyGlass Pharma completed its initial public offering on Nasdaq (ticker SGP) in February 2026 with gross proceeds of $172.5 million.

Investigational status and registrational phase 3 program

“In July 2025, we initiated two registrational Phase 3 trials, each expected to enroll approximately 400 patients across 45 sites. We expect to complete enrollment in 2027 and, pending successful Phase 3 results, we plan to submit a 505(b)(2) New Drug Application (NDA) to the FDA in 2028.” (opens the source at this quote in a new tab)
“We plan to complete Phase 3 enrollment by 2027 and report 12 month data in 2028 and 24 month data in 2029.” (opens the source at this quote in a new tab)

“Enrollment remains on track in the registrational Phase 3 trials of the Bimatoprost Drug Pad-IOL System (BIM-IOL System), with completion of enrollment expected in 2027.” (opens the source at this quote in a new tab)

Phase 3 registry records

Field	SGP-005
Brief title	“Evaluation of the Safety and Efficacy of the Bimatoprost Implant System Used in Combination With the SpyGlass IOL Compared to Timolol Ophthalmic Solution (Rhine)”
Start date	“2025-10-15”
Estimated primary completion date	“2029-03-31”
Estimated enrollment	“400”

Field	SGP-006
Brief title	“Evaluation of the Safety and Efficacy of the Bimatoprost Implant System Used in Combination With the SpyGlass IOL Compared to Timolol Ophthalmic Solution (Rhone)”
Estimated primary completion date	“2029-05-31”
Estimated enrollment	“400”

FDA regulatory pathway: 505(b)(2) NDA

“We believe this approach positions us to pursue a streamlined regulatory approval process under the FDA’s 505(b)(2) pathway because the active ingredient in our BIM-IOL System, bimatoprost, has been previously approved by the FDA.” (opens the source at this quote in a new tab)
“We believe our approach is consistent with regulatory guidance from the FDA and we have communicated our strategy to seek approval via the 505(b)(2) pathway to the FDA. The FDA will ultimately determine our regulatory pathway following the submission of our 505(b)(2) NDA.” (opens the source at this quote in a new tab)

“If the FDA does not allow us to pursue the Section 505(b)(2) regulatory pathway for a product candidate as anticipated, we may need to conduct additional clinical trials, provide additional data and information and meet additional standards for regulatory approval.” (opens the source at this quote in a new tab)

Drug-device combination product: lead center and device component

“We believe this product candidate will be regulated by the FDA as a drug-led, drug-device combination product.” (opens the source at this quote in a new tab)
“While we have no current plans to seek premarket approval for any device products, our lead combination product candidate is subject to regulation by CDER and by CDRH, although CDER has primarily jurisdiction over the drug-led combination product. The device component of our combination product candidate must comply with the applicable medical device quality controls.” (opens the source at this quote in a new tab)

Investigational new drug application

“Our investigational new drug application (IND) for the Phase 1/2 trial of the BIM-IOL System in patients with OAG or OHT undergoing cataract surgery was cleared by the FDA, and we completed enrollment in November 2024.” (opens the source at this quote in a new tab)

Initial public offering and SEC reporting status

“SpyGlass Pharma, Inc. (Nasdaq: SGP) (“SpyGlass Pharma”), a late-stage biopharmaceutical company, today announced the closing of its initial public offering of 10,781,250 shares of its common stock, which includes the exercise in full of the underwriters’ option to purchase 1,406,250 additional shares of its common stock, at a public offering price of $16.00 per share. The aggregate gross proceeds from the offering were $172.5 million, before deducting underwriting discounts and commissions and other offering expenses payable by SpyGlass Pharma.” (opens the source at this quote in a new tab)

“Cash, cash equivalents and short-term investments of $234.2 million on June 30, 2026, are expected to fund planned operations through 2028.” (opens the source at this quote in a new tab)

Patents and licensed intellectual property

“As of December 31, 2025, our co-owned and exclusively licensed patent estate contains eight (8) patent families comprising fifteen (15) issued U.S. patents” (opens the source at this quote in a new tab)
“The fifteen (15) issued U.S. patents are projected to expire between 2039 and 2043, before accounting for potentially available patent term adjustments or patent term extension, as appropriate, and assuming timely payment of appropriate maintenance, renewal, annuity and other governmental fees.” (opens the source at this quote in a new tab)
“All patents and patent applications in our intellectual property portfolio are co-owned with a single co-Applicant, the Regents of the University of Colorado, a body corporate (CU). We exclusively license the co-Applicant’s rights in these patents and patent applications that are co-owned.” (opens the source at this quote in a new tab)

Patent limitation: active ingredient in the public domain

“The selected API of our BIM-IOL System, bimatoprost, is an approved and known pharmaceutical that has been in the public domain and used for the treatment of eye disorders for many years and we are therefore not able to seek and obtain patent protection for the form of crystalline bimatoprost we use in our BIM-IOL System.” (opens the source at this quote in a new tab)

Regulatory exclusivity potentially applicable to a non-NCE product

“The FDCA also provides for a period of three years of non-patent exclusivity for non-NCE drugs if the NDA or NDA supplement includes reports of one or more new clinical investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to the approval of the application or supplement.” (opens the source at this quote in a new tab)

Related product in development: BIM-DRS for pseudophakic participants

“Bimatoprost-Drug Ring System (BIM-DRS) first-in-human trial is on track to start in the second half of 2026.” (opens the source at this quote in a new tab)

Field	Quoted record
Brief title	“Evaluation of the Safety, Efficacy, Dose Response of the Bimatoprost Drug Ring System (BIM-DRS) in Pseudophakic Patients Diagnosed With Open Angle Glaucoma or Ocular Hypertension”
Estimated enrollment	“24”

FDA fast track, breakthrough therapy, or other expedited-program designations

No evidence found.

Regulatory submission: NDA planned for 2028

“pending successful Phase 3 results, we plan to submit a 505(b)(2) New Drug Application (NDA) to the FDA in 2028 to seek approval of the BIM-IOL System” (opens the source at this quote in a new tab)

Launch

No evidence found.

Manufacturer: SpyGlass Pharma

“SpyGlass Pharma, Inc.” (opens the source at this quote in a new tab)

Product names

“SpyGlass Pharma’s lead product candidate, the Bimatoprost Drug Pad-IOL System (BIM-IOL System), comprising novel, proprietary non-bioerodible drug pads attached to its intraocular lens, was designed to be implanted during routine cataract surgery to reduce elevated intraocular pressure (IOP) in patients who have either open-angle glaucoma (OAG) or ocular hypertension (OHT).” (opens the source at this quote in a new tab)

Registry field	Quoted record
Intervention name	“Bimatoprost Implant System”
Intervention description	“Bimatoprost Implant System used in combination with the SpyGlass IOL”
Device intervention	“SpyGlass Intraocular Lens”

Therapeutic class of the active ingredient

“The BIM-IOL System is designed to consistently deliver three years of bimatoprost, a prostaglandin analog approved for topical use by the U.S. Food and Drug Administration (FDA) in 2001, for the reduction of elevated IOP in patients with OAG or OHT.” (opens the source at this quote in a new tab)

Proprietary (brand) name

No evidence found.

Components: drug pads, intraocular lens, and injector

“Our first system in development, the Drug Pad-IOL System, leverages the SpyGlass Platform and integrates approved medicines into two drug pads that are fixed to the haptic arms of our single-piece, hydrophobic acrylic IOL.” (opens the source at this quote in a new tab)
“Our first system in development comprises novel drug pads attached to our IOL (Drug Pad-IOL System), both of which are non-bioerodible, meaning that these components do not break down and they retain their structure and shape as the system elutes medicine.” (opens the source at this quote in a new tab)

Pad material, lens specifications, and dimensions

“The studied drug delivery system consists of two silicone molded pads attached to an IOL (defined as the bimatoprost implant system). Each pad sits at the optic–haptic junction, contains a multiyear bimatoprost load, and delivers slow, continuous elution of bimatoprost with a near-zero-order delivery profile.” (opens the source at this quote in a new tab)
“The SpyGlass IOL itself is a monofocal lens made of hydrophobic acrylic material with a UV inhibitor. Available powers range from 10.0 to 32.0 diopters (D). With pads equipped, the overall product measures 6 mm wide and 12.5 mm long (Fig. 1).” (opens the source at this quote in a new tab)

Strength selected for phase 3 (intended commercial dose)

“In July 2025, we initiated two identical, registrational, Phase 3 clinical trials to evaluate the BIM-IOL System with 78 mcg of bimatoprost, which is designed to consistently deliver three years of bimatoprost.” (opens the source at this quote in a new tab)

“The trial compared BIM-IOL System at the intended commercial dose of 78-mcg (N=51), and 39-mcg (N=23) compared to a physician's choice of commercially available monofocal IOLs from Alcon, Bausch + Lomb or Johnson & Johnson with twice-daily administration of timolol eyedrops as the control group (N=30).” (opens the source at this quote in a new tab)

Strengths studied in earlier trials and their correspondence

“Based on our preclinical results, we designed a FIH trial to evaluate the BIM-IOL System with 75 mcg, 150 mcg and 300 mcg of bimatoprost.” (opens the source at this quote in a new tab)
“Based on the results of our FIH trial, we designed a Phase 1/2 trial to evaluate the safety and efficacy of the BIM-IOL System with 39 mcg and 78 mcg of bimatoprost, which are designed to have similar daily release profiles to the 75 and 150 mcg doses in our FIH trial, respectively.” (opens the source at this quote in a new tab)

Total drug content relative to topical bimatoprost

“The BIM-IOL System is designed to consistently deliver three years of IOP-lowering therapy using less bimatoprost than is contained in a 5mL bottle of topical bimatoprost drops.” (opens the source at this quote in a new tab)

Lens optic configurations under development

“While we believe, based on management projections and internal estimates, that 90% of glaucoma patients receive standard monofocal (or single focus) IOLs during cataract surgery, we are designing for a range of optics, including toric IOLs.” (opens the source at this quote in a new tab)

Commercial packaging, storage conditions, and shelf life

No evidence found.

BIM-IOL System price

Not applicable.

Anticipated reimbursement basis for the drug component

“We believe that the IOP-lowering element of our lead product candidate will be classified as a physician-administered drug, which are typically reimbursed at the ASP plus 6%.” (opens the source at this quote in a new tab)

Pricing benchmark used in the sponsor's market estimate: iDose TR

“Based on the wholesale acquisition cost for iDose TR and the percentage of patients with glaucoma who have OAG” (opens the source at this quote in a new tab)
“we estimate that the total addressable market for OAG/OHT and cataract patients is approximately $13 billion.” (opens the source at this quote in a new tab)

“Glaukos has established a wholesale acquisition cost for iDose TR of $13,950, per dose (or implant).” (opens the source at this quote in a new tab)

Durysta wholesale acquisition cost

No evidence found.

Pharmacologic class of bimatoprost: Lumigan labeling

“LUMIGAN® 0.01% is a prostaglandin analog indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. (1)” (opens the source at this quote in a new tab)
“LUMIGAN® (bimatoprost ophthalmic solution) 0.01% is a synthetic prostamide analog with ocular hypotensive activity.” (opens the source at this quote in a new tab)

Product classification: drug-led combination product

“Combination products where the drug is intended to provide the primary mechanism of action, such as those we intend to develop, are often referred to as “drug-led combination” products.” (opens the source at this quote in a new tab)

AHFS classification

No evidence found.

Proposed use under investigation

“SpyGlass Pharma’s lead product candidate, the Bimatoprost Drug Pad-IOL System (BIM-IOL System), comprising novel, proprietary non-bioerodible drug pads attached to its intraocular lens, was designed to be implanted during routine cataract surgery to reduce elevated intraocular pressure (IOP) in patients who have either open-angle glaucoma (OAG) or ocular hypertension (OHT).” (opens the source at this quote in a new tab)

Population studied in the phase 3 trials

“Each prospective, multicenter, randomized, masked, controlled Phase 3 clinical trial evaluates the safety and efficacy of the BIM-IOL System (78 mcg) in patients with OAG or OHT and a concomitant cataract, who are taking up to two IOP-lowering medications.” (opens the source at this quote in a new tab)

“Diagnosis of mild to moderate open-angle glaucoma or ocular hypertension” (opens the source at this quote in a new tab)
“Planned removal of cataract” (opens the source at this quote in a new tab)

Approved indication

Not applicable.

Bimatoprost mechanism of action: Lumigan labeling

“Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes.” (opens the source at this quote in a new tab)

Delivery mechanism: diffusion from capsular-bag pads into the aqueous humor

“Once the Drug-Pad IOL System is positioned in the capsular bag, the drug pads remain outside the visual axis and deliver the integrated medicine by” (opens the source at this quote in a new tab)
“diffusion directly into the aqueous humor, which carries the drug to the targeted tissues.” (opens the source at this quote in a new tab)

Rationale for intraocular delivery: sponsor statement on topical penetration

“Even when patients describe taking their glaucoma drops as prescribed, studies have shown that less than 5% of the administered dose penetrates the eye and reaches the target tissue.” (opens the source at this quote in a new tab)

Onset and time to maximum IOP effect of topical bimatoprost: Lumigan labeling

“Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.” (opens the source at this quote in a new tab)

Onset and durability of IOP lowering: first-in-human study

“By week 1, all groups achieved mean IOP reductions exceeding 40% (p < 0.05 all). This extent of IOP control generally held stable across 2 years of follow-up, with a small uptick in IOP in the medium configuration (150 μg) cohort at year 3 (Fig. 3).” (opens the source at this quote in a new tab)
“For the aggregate sample, mean percentage IOP reduction from baseline was 36.7 ± 9.4% (p < 0.0001) by month 36.” (opens the source at this quote in a new tab)

Dose response: first-in-human study

“Outcomes were not significantly different between low, medium, and high concentrations of sustained release bimatoprost. One may hypothesize that higher doses would correlate with more substantive IOP-lowering. However, this did not necessarily hold true in the current sample; the greatest IOP reduction from baseline to month 36 was achieved in the 75 μg cohort.” (opens the source at this quote in a new tab)

Dose response: phase 1/2 trial at 3 and 12 months

“At three months, we observed mean IOP reductions of -9.29 mmHg (8 a.m.) and -9.19 mmHg (10 a.m.) for the 78 mcg dose group, -9.64 mmHg (8 a.m.) and -8.70 mmHg (10 a.m.) for the 39 mcg dose group, and -9.63 mmHg (8 a.m.) and -10.24 mmHg (10 a.m.) for the control group.” (opens the source at this quote in a new tab)
“Evaluable patients in the 78-mcg (N=47) and 39-mcg (N=21) dose groups achieved a 34% and 42% reduction in mean IOP from baseline, respectively, compared to a 35% reduction in the control (N=29) group at 8 a.m. Results were similar at the 10 a.m. timepoint.” (opens the source at this quote in a new tab)

Nonclinical toxicology: 39-week single-dose rabbit study

“Under the conditions of the pivotal, 39-week, single-dose toxicity study, the no observed adverse effect level (NOAEL) for bimatoprost was determined to be 300 mcg/eye/dose (1000 ng/eye/day in vitro), which was also the highest dose tested.” (opens the source at this quote in a new tab)
“The inflammatory response was comparable across the groups in each study, and for the 39-week study, was comparable to the standard commercial IOL control group. Importantly, no bimatoprost-related ophthalmic or microscopic observations were noted.” (opens the source at this quote in a new tab)

In vitro release: sponsor description of three-year release

“Additionally, long-term in vitro release studies have demonstrated that our BIM-IOL System delivered bimatoprost in a sustained and consistent manner over multiple years.” (opens the source at this quote in a new tab)
“Consistent Daily Release of Bimatoprost in vitro Maintained Over Three Years” (opens the source at this quote in a new tab)

Pad elution data: in vitro release rate and aqueous humor concentrations in dogs

“As illustrated in FIG. 8 , which is a graph 800 of daily release or elution (in micrograms) of Bimatoprost in vitro versus time (day), the release rate over a four-hundred-day study is essentially a zero-order and/or a steady state elution rate. The target release rate in this study on rabbits was 0.050 to 0.100 micrograms per day. As illustrated in FIG. 8 , the average release rate is slightly less than 0.100 micrograms per day with a range of about 0.075 micrograms to about 0.100 micrograms.” (opens the source at this quote in a new tab)
“As found with the low dose group (Grp 1), the mid-dose group (Grp 2), and the high dose group (Grp 3), the level of Bimatoprost in the aqueous humor exhibited a zero-order elution rate over the study period of about one hundred thirteen days.” (opens the source at this quote in a new tab)

Pad configurations and target daily release rates described in patent filings

“In certain embodiments, the drug delivery system 700 of FIG. 7A is sized and configured for about a three-year release of the therapeutic agent, with a release rate of about 80 to about 150 nanograms (ng) per day (e.g., about 120 ng/day bimatoprost). By decreasing the surface area of the drug delivery component 80, as illustrated in FIG. 7B, the drug delivery system 700 is sized and configured for about a three-year release of the at least one therapeutic agent with a release rate of about 60 ng per day, (e.g., bimatoprost).” (opens the source at this quote in a new tab)

Systemic exposure: nonclinical toxicokinetics

“Following bilateral administration, plasma levels of the bimatoprost and bimatoprost acid remained below the lower limit of quantitation for all samples collected at all time points, indicating no systemic exposure.” (opens the source at this quote in a new tab)

Bimatoprost absorption, distribution, metabolism, and excretion: Lumigan labeling

“Bimatoprost is moderately distributed into body tissues with a steady-state volume of distribution of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. Approximately 12% of bimatoprost remains unbound in human plasma.” (opens the source at this quote in a new tab)
“Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing. Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites.” (opens the source at this quote in a new tab)
“Following an intravenous dose of radiolabeled bimatoprost (3.12 mcg/kg) to six healthy subjects, the maximum blood concentration of unchanged drug was 12.2 ng/mL and decreased rapidly with an elimination half-life of approximately 45 minutes. The total blood clearance of bimatoprost was 1.5 L/hr/kg. Up to 67% of the administered dose was excreted in the urine while 25% of the dose was recovered in the feces.” (opens the source at this quote in a new tab)

Systemic exposure after intracameral bimatoprost: Durysta labeling

“After a single administration of DURYSTA, bimatoprost concentrations were below the lower limit of quantitation (0.001 ng/mL) in the majority (approximately 92%) of patients. The maximum bimatoprost concentration observed in any patient was 0.00224 ng/mL.” (opens the source at this quote in a new tab)

Human aqueous humor or plasma pharmacokinetics of the BIM-IOL System

No evidence found.

FDA-approved prescribing information for the BIM-IOL System

Not applicable.

Ocular adverse events: phase 1/2 trial at 3 and 12 months

“Only one patient receiving the BIM-IOL System reported allergic conjunctivitis (1/50, 2.0%) and there were no other reports of conjunctival hyperemia. Similar AE rates were observed in the 78 mcg (35.3%), 39 mcg (39.1%) and the control (33.3%) groups.” (opens the source at this quote in a new tab)
“AE rates were similar across the 78-mcg (41.2%), 39-mcg (43.5%), and control (36.7%) groups. No serious ocular AEs were observed.” (opens the source at this quote in a new tab)

Adverse event through three months	78 mcg (n = 51)	39 mcg (n = 23)	Control (n = 30)
Iritis	“4 (7.8)”	“1 (4.3)”	“1 (3.3)”
Corneal edema	“3 (5.9)”	“2 (8.7)”	“1 (3.3)”
Eye inflammation	“3 (5.9)”	“0”	“0”
Visual impairment (i.e., halos)	“2 (3.9)”	“0”	“0”
Dry eye	“0”	“4 (17.4)”	“1 (3.3)”
Visual acuity reduced (BCDVA loss ≥ 10 letters)	“2 (3.9)”	“2 (8.7)”	“2 (6.7)”
Meibomian gland dysfunction	“4 (7.8)”	“0”	“2 (6.7)”

Corneal endothelial cell loss: phase 1/2 trial

“Endothelial cell density loss was within the expected range for post-cataract surgery glaucoma patients, with patients receiving the BIM-IOL System demonstrating an average loss of 14.9% compared to 12.1% in the control group. Importantly, endothelial cell density levels remained stable between three and six months.” (opens the source at this quote in a new tab)

Adverse events and implant stability through 36 months: first-in-human study

“There were no serious implant-related adverse events. The most common events were dry eye (21.7%), transient vision decrease (13.0%), and subconjunctival hemorrhage (8.7%). All implants remained in the capsular bag.” (opens the source at this quote in a new tab)
“There were no cases of prostaglandin-associated periorbitopathy, no abnormal eyelash growth, and no cases of iris hyperpigmentation. There were no IOL dislocations, bimatoprost drug pad displacements, explantations, or reports of clinically significant posterior capsule opacification.” (opens the source at this quote in a new tab)
“There was a reduction from a baseline of 2308 ± 223 cells/mm2 to 2068 ± 374 cells/mm2 (− 10.4%) by month 6 and 2013 ± 407 cells/mm2 (− 12.8%) by month 12.” (opens the source at this quote in a new tab)

Warnings and precautions for topical bimatoprost: Lumigan labeling

“Pigmentation: Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation is likely to be permanent. (5.1)” (opens the source at this quote in a new tab)
“Prostaglandin analogs, including bimatoprost, have been reported to cause intraocular inflammation. In addition, because these products may exacerbate inflammation, caution should be used in patients with active intraocular inflammation (e.g., uveitis).” (opens the source at this quote in a new tab)
“Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution. LUMIGAN® 0.01% should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.” (opens the source at this quote in a new tab)

Contraindications and warnings for intracameral bimatoprost: Durysta labeling

“DURYSTA is contraindicated in patients whose posterior lens capsule is absent or ruptured, due to the risk of implant migration into the posterior segment.” (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)
“Intraocular surgical procedures and injections, including DURYSTA, have been associated with endophthalmitis.” (opens the source at this quote in a new tab)

Sponsor-disclosed risk: future identification of bimatoprost adverse effects

“In addition, although bimatoprost has been commercially available for several years, regulatory authorities may identify adverse side effects related to bimatoprost in the future.” (opens the source at this quote in a new tab)

Procedures for implant removal or exchange

No evidence found.

Age of participants: eligibility and baseline

Study	Quoted minimum age
SGP-005 phase 3	“22 Years”

“Mean age was 70.5 ± 9.6 years, with a near-equal gender ratio. All subjects were of Hispanic/Latino ethnicity and Caucasian race, and all were diagnosed with primary open-angle glaucoma (POAG) with a mean vertical cup-to-disc ratio of 0.6 ± 0.2.” (opens the source at this quote in a new tab)

“Patients with glaucoma and cataracts are primarily over the age of 65, making Medicare the primary payor.” (opens the source at this quote in a new tab)

Pregnancy and contraception: phase 3 eligibility

“Female participants of childbearing potential must have a negative urine pregnancy test at the baseline visit and agree to the use of contraception” (opens the source at this quote in a new tab)

Glaucoma subtypes excluded from phase 3

“Any glaucoma diagnosis other than OHT, open-angle, pseudoexfoliative, or pigmentary glaucoma” (opens the source at this quote in a new tab)
“History of incisional glaucoma surgery or intraocular injections” (opens the source at this quote in a new tab)

Ocular comorbidities excluded from the first-in-human study

“Central corneal endothelial cell count < 2000 cells/mm2 by specular microscopy” (opens the source at this quote in a new tab)
“Diabetic retinopathy or diabetic maculopathy” (opens the source at this quote in a new tab)
“Any pathology of the zonules including evidence of zonular weakness, zonular instability, zonular damage, or coloboma effecting zonules” (opens the source at this quote in a new tab)

Pregnancy, lactation, pediatric, and geriatric use of bimatoprost: Lumigan labeling

“Because animal reproductive studies are not always predictive of human response LUMIGAN® 0.01% should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.” (opens the source at this quote in a new tab)
“Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.” (opens the source at this quote in a new tab)
“No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.” (opens the source at this quote in a new tab)

Pregnancy, lactation, and pediatric use of intracameral bimatoprost: Durysta labeling

“There is no information regarding the presence of bimatoprost in human milk, the effects on the breastfed infants, or the effects on milk production.” (opens the source at this quote in a new tab)
“Safety and effectiveness of DURYSTA in pediatric patients have not been established.” (opens the source at this quote in a new tab)

Generalizability of first-in-human data to other populations

“The single-site design with a sample comprised entirely of white Latino patients with POAG further limits generalizability to wider populations.” (opens the source at this quote in a new tab)

Renal or hepatic impairment

No evidence found.

Additional prostaglandin analog dosing: Lumigan labeling

“LUMIGAN® (bimatoprost ophthalmic solution) 0.01% should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect.” (opens the source at this quote in a new tab)

Protocol medication exclusions: first-in-human study

“Any medication in the fellow eye that would impact IOP in the study eye” (opens the source at this quote in a new tab)
“Use of tamsulosin or silodosin (e.g., Flomax, Flomaxtra, Rapaflo) or similar medications” (opens the source at this quote in a new tab)

Clinical drug interaction studies

No evidence found.

Bimatoprost metabolism and systemic exposure: Lumigan labeling

“Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing. Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites.” (opens the source at this quote in a new tab)

Clinical drug interaction studies

No evidence found.

Intended commercial dose and duration

“For SpyGlass Pharma’s intended commercial dose of 78-mcg, patients receiving the BIM-IOL System achieved robust clinical improvement:” (opens the source at this quote in a new tab)

“In July 2025, we initiated two identical, registrational, Phase 3 clinical trials to evaluate the BIM-IOL System with 78 mcg of bimatoprost, which is designed to consistently deliver three years of bimatoprost.” (opens the source at this quote in a new tab)

Single eye treated per participant in clinical trials

“Enrolled patients who meet the surgical eligibility criteria will receive cataract surgery in one eye (the study eye) after receiving a baseline washout of all IOP-lowering medications.” (opens the source at this quote in a new tab)

Dose levels studied: first-in-human study

“Enrolled patients were sequentially assigned 1:1:1 into three groups, where patients received a BIM-IOL System containing 75, 150 or 300 mcg of bimatoprost that continuously released a low (1x), mid (2x) or high (4x) dose of bimatoprost per day, respectively.” (opens the source at this quote in a new tab)

Retreatment after drug depletion

“We believe the BIM-DRS could be implanted in a standalone procedure, enable retreatment of patients who had received the BIM-IOL System, and offer extended care for pseudophakic patients with OAG or OHT.” (opens the source at this quote in a new tab)

Proposed labeled dosing and retreatment interval

No evidence found.

Surgical implantation procedure

“In a typical procedure using this system (as depicted in the images below), the proprietary drug pads are securely attached at the haptic-optic junction of our IOL, which is then loaded into a standard IOL injector in the operating room (similar to current IOL preparatory procedures). Using routine cataract surgery techniques, the IOL is then injected through a standard cataract incision directly into the capsular bag of the eye.” (opens the source at this quote in a new tab)

“In use, the drug pads are attached to the SpyGlass IOL by either the sterile technician or the surgeon with the assistance of the primary packaging. Once attached, the system is loaded into a commercially available IOL inserter. Next, the tip of the inserter is placed into the primary incision. Lastly, the system is advanced through the inserter into the capsular bag and implanted in the same manner as other marketed C-loop haptic IOLs.” (opens the source at this quote in a new tab)

Surgical skills and workflow

“The implantation technique should be familiar to most cataract surgeons and does not require a change in the positioning of the microscope or the patient’s head. The IOL is folded and loaded into an off-the-shelf injector and then inserted into the capsular bag through a standard clear corneal incision, similar to standard cataract surgery.” (opens the source at this quote in a new tab)

Lens power range and single-surgeon experience: first-in-human study

“Procedures were performed by a single ophthalmologist; given that cataract surgery approaches vary, other operators may realize challenges with a new product.” (opens the source at this quote in a new tab)
“this study was not designed to explore the frequencies at which target vision was achieved without correction. The lens selection was limited to the + 19.0 to + 25.0 D range.” (opens the source at this quote in a new tab)

Injector compatibility

“Our BIM-IOL System is designed to be compatible with a number of off-the-shelf injectors from various manufacturers. We have a supply agreement with an injector manufacturer to distribute its injector globally for use with the BIM-IOL System.” (opens the source at this quote in a new tab)

Procedure coding: add-on Category III CPT code

“In May 2026, the American Medical Association’s CPT® (Current Procedural Terminology) Editorial Panel approved a new add-on Category III CPT code (+1090T released to AMA website on July 1, 2026) in combination with established Category I CPT codes, such as 66984 and 66991.” (opens the source at this quote in a new tab)

Current access: investigational use in clinical trials only

“We are not permitted to commercialize, market, promote or sell any product candidate in the United States without obtaining marketing approval from the FDA.” (opens the source at this quote in a new tab)

Anticipated buy-and-bill model, Medicare Part B coverage, and J-code

“If we obtain marketing authorization for the BIM-IOL System, we anticipate that providers and facilities, including ASCs, will be able to immediately bill the product under a temporary J-code (J3490 or J3590). In parallel, we expect to apply for a Healthcare Common Procedure Coding System (HCPCS) Permanent J-code, similar to Durysta (J7351) and iDose (J7355), which are currently reimbursed at ASP plus 6%, consistent with other physician-administered drugs.” (opens the source at this quote in a new tab)
“Because the BIM-IOL System is implanted during cataract surgery, we expect that our product candidate will be covered through Medicare Part B.” (opens the source at this quote in a new tab)

Coding risk: miscellaneous J-codes before a product-specific code

“To the extent separate coverage or reimbursement is available for any product candidate, if approved, and a specific J-Code is not available, physicians would need to use a non-specific miscellaneous J-Code to bill third-party payors for these” (opens the source at this quote in a new tab)

Site of care

“We believe this presents an opportunity for providers and facilities, including ASCs, where approximately 90% of cataract surgeries in the United States are performed” (opens the source at this quote in a new tab)

Manufacturing and supply chain

“We currently use contract manufacturing organizations (CMOs) to manufacture and supply the components of our drug delivery system, including the drug pads, IOL and injector system.” (opens the source at this quote in a new tab)
“Clinical and commercial supply agreements for our proprietary IOL have been secured with our IOL supplier to meet our planned clinical and commercial requirements through our first year of commercialization.” (opens the source at this quote in a new tab)
“We have granted a right of first negotiation to an affiliate of this CMO to become an exclusive distributor of our potential commercial product in Asia, Europe, the Middle East and Africa.” (opens the source at this quote in a new tab)

Planned commercial field force

“We estimate that a limited number of cataract surgeons and ASCs perform the majority of cataract surgery procedures in the United States each year, with the top 5% of surgeons performing over 25% of the procedures” (opens the source at this quote in a new tab)
“We believe this concentrated market will enable us to build an efficient field-based sales force that can quickly unlock a significant portion of the market opportunity.” (opens the source at this quote in a new tab)

Expanded access program, specialty distribution, and REMS

No evidence found.

Postoperative regimen: first-in-human study

“The postoperative regimen included a weekly taper of topical steroid/antibiotic combination from Q4H to Q6H to Q8H over a 3-week period. IOP-lowering drops were not reintroduced unless clinically necessary.” (opens the source at this quote in a new tab)

Masking drops: phase 1/2 trial

“A total of 104 patients were randomized 2:1:1 to receive the 78 mcg BIM-IOL System (N=51) and 39 mcg BIM-IOL System (N=23) with daily administration of artificial tear drops, or a commercially available monofocal IOL from Alcon, Bausch + Lomb or Johnson & Johnson with twice-daily administration of timolol eye drops as the control group (N=30).” (opens the source at this quote in a new tab)

Preoperative washout of IOP-lowering medications

“Informed by our Phase 1/2 data, we have implemented minor protocol modifications to the inclusion and exclusion criteria. Key changes include tightening the baseline IOP range, enrolling patients on up to two IOP-lowering medications, tailoring washout periods based on drug class pharmacokinetics, and standardizing IOP measurement timing.” (opens the source at this quote in a new tab)

Adjunctive topical IOP-lowering medication after implantation

“98% of evaluable patients (48 of 49) in the 78-mcg dose group and 96% of evaluable patients (22 of 23) in the 39-mcg dose group were free from all topical IOP-lowering medications.” (opens the source at this quote in a new tab)

“All 16 subjects in the 75 μg and 150 μg cohorts remained off glaucoma drops through month 36. A single subject in the 300 μg arm required reintroduction of a topical IOP-lowering medication at month 30.” (opens the source at this quote in a new tab)

Concomitant topical ocular therapy: Lumigan labeling

“LUMIGAN® 0.01% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.” (opens the source at this quote in a new tab)

Combination with MIGS, SLT, or later angle procedures

“The system can be used during routine cataract surgery, either with MIGS or as a standalone procedure, in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).” (opens the source at this quote in a new tab)

“Second, it leaves the angle untouched, allowing for concurrent or subsequent gonioscopic intervention, or subsequent selective laser trabeculoplasty.” (opens the source at this quote in a new tab)

Clinical data on use combined with MIGS or SLT

No evidence found.

MIPS Quality ID 141: POAG reduction of IOP by 20% or plan of care

“Percentage of patients aged 18 years and older with a diagnosis of primary open-angle glaucoma (POAG) whose glaucoma treatment has not failed (the most recent IOP was reduced by at least 20% from the pre-intervention level) OR if the most recent IOP was not reduced by at least 20% from the pre-intervention level, a plan of care was documented within the 12 month performance period.” (opens the source at this quote in a new tab)

Proportion of eyes with IOP reduction of more than 20%: first-in-human study

“All month 36 subjects maintained an IOP reduction > 20% and all but two subjects (90.5%, n = 19) achieved an IOP < 18 mmHg.” (opens the source at this quote in a new tab)

MIPS Quality ID 191: visual acuity after cataract surgery, with glaucoma exclusion

“Percentage of cataract surgeries for patients aged 18 years and older with a diagnosis of uncomplicated cataract and no significant ocular conditions impacting the visual outcome of surgery and had best-corrected visual acuity of 20/40 or better (distance or near) achieved in the operative eye within 90 days following the cataract surgery.” (opens the source at this quote in a new tab)

Table 1 - Significant Ocular Conditions	Quoted entry
Condition listed	“Glaucoma”

Visual acuity endpoint in the phase 3 trials

“The co-primary endpoints are (1) the time-matched mean IOP change from baseline at 8 and 10 a.m. at two and six weeks and three months and (2) BCDVA of 20/40 or better at 12 months.” (opens the source at this quote in a new tab)

MIPS Quality ID 389: refractive outcome after cataract surgery

“Percentage of patients aged 18 years and older who had cataract surgery performed and who achieved a final refraction within +/- 1.0 diopters of their planned (target) refraction.” (opens the source at this quote in a new tab)

HEDIS measures for glaucoma and BIM-IOL System-specific effect on quality measures

No evidence found.

Summary

No head-to-head clinical comparison of the BIM-IOL System with Durysta, iDose TR, topical bimatoprost, SLT, or MIGS has been reported. The phase 3 comparator is a commercial monofocal IOL plus twice-daily timolol 0.5%, the same active control used in the registrational trials of Durysta and iDose TR. Product characteristics differ by labeling and sponsor disclosures: Durysta is a biodegradable 10 mcg intracameral bimatoprost implant limited to a single implant per eye; iDose TR is a nonbiodegradable titanium implant containing 75 mcg travoprost, anchored in the sclera through the trabecular meshwork using gonioscopy, with readministration permitted no more than once per year subject to corneal endothelial cell density criteria; topical Lumigan 0.01% is dosed once daily. The BIM-IOL System places two nonbioerodible pads containing 78 mcg bimatoprost (phase 3 dose) on an IOL in the capsular bag during cataract surgery, with a sponsor-stated design duration of three years, and is therefore limited to eyes undergoing cataract surgery; retreatment would require the separate BIM-DRS in development. Reported conjunctival hyperemia rates were 31% with Lumigan 0.01% and 27% with Durysta in their labeling, compared with 1 of 23 participants (4.3%) in the nonrandomized BIM-IOL first-in-human study; these are cross-trial observations with different designs. The iDose TR wholesale acquisition cost announced by Glaukos is $13,950 per implant; no BIM-IOL System price has been announced.

Sustained-release glaucoma therapies: review comparison table

Product	Developer	Active agent	Route of administration	Duration of action	Development stage
Durysta	“Allergan, North Chicago, IL, USA”	“Bimatoprost”	“Biodegradable intracameral implant”	“4–6 months”	“FDA approved”
iDose TR	“Glaukos, Aliso Viejo, CA, USA”	“Travoprost”	“Non-degradable implant”	“Up to 36 months”	“FDA approved”
Paxtrava	“Ocular Therapeutix, Bedford, MA, USA”	“Travoprost”	“Biodegradable intracameral implant”	“6 months”	“Phase II NCT05335122”
Bimatoprost ocular ring	“Allergan, North Chicago, IL, USA”	“Bimatoprost”	“Nondegradable ring inserted into the conjunctival fornices”	“Up to 6 months”	“Phase II”
SpyGlass System	“SpyGlass Pharma, Aliso Viejo, CA, USA”	“Bimatoprost”	“IOL pads eluting bimatoprost”	“Up to 3 years”	“Phase I/II”

Single-use limitation of approved intracameral implants: review

“Currently, the two available intracameral implants are only approved by the FDA for single use due to safety issues. The travoprost implant is not degradable, and if the drug is depleted, the implant must be removed and re-administered.” (opens the source at this quote in a new tab)

Durysta: dosage form, administration limit, and efficacy versus timolol

“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)
“Intracameral implant containing 10 mcg of bimatoprost in a drug delivery system.” (opens the source at this quote in a new tab)
“Efficacy was evaluated in two multicenter, randomized, parallel-group, controlled 20-month (including 8-month extended follow-up) studies of DURYSTA compared to twice daily topical timolol 0.5% drops, in patients with OAG or OHT. DURYSTA demonstrated an IOP reduction of approximately 5-8 mmHg in patients with a mean baseline IOP of 24.5 mmHg (see Figures 3 and 4).” (opens the source at this quote in a new tab)
“The most common ocular adverse reaction observed in two randomized, active-controlled clinical trials with DURYSTA in patients with OAG or OHT was conjunctival hyperemia, which was reported in 27% of patients.” (opens the source at this quote in a new tab)

iDose TR: dosage form, implantation, readministration, and efficacy versus timolol

“Intracameral implant containing 75 mcg travoprost, pre-loaded in a single-dose inserter.” (opens the source at this quote in a new tab)
“iDose TR is administered intracamerally through a small, clear corneal incision and is anchored into the sclera at the iridocorneal angle.” (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)
“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)
“Dislocation of the iDose TR has been observed in clinical trials. Patients should be monitored routinely to confirm the location of the iDose TR at the site of administration.” (opens the source at this quote in a new tab)

Topical bimatoprost: dosing, efficacy, and conjunctival hyperemia

“The recommended dosage is one drop in the affected eye(s) once daily in the evening.” (opens the source at this quote in a new tab)
“In a 12-month clinical study of patients with open angle glaucoma or ocular hypertension with an average baseline IOP of 23.5 mmHg, the IOP-lowering effect of LUMIGAN® 0.01% once daily (in the evening) was up to 7.5 mmHg.” (opens the source at this quote in a new tab)
“In a 12-month clinical study with bimatoprost ophthalmic solutions 0.01%, the most common adverse reaction was conjunctival hyperemia (31%). Approximately 1.6% of patients discontinued therapy due to conjunctival hyperemia.” (opens the source at this quote in a new tab)

Sponsor-stated differentiation from intracameral implants and MIGS

“Similarly, novel procedural pharmaceuticals such as intracameral implants offer sustained drug delivery, but present their own limitations. These implants are placed near the cornea and iris, which can result in corneal endothelial cell loss, inflammation, or other complications. Similar to MIGS, non-bioerodible intracameral implants also require specialized training, use of nondominant hand, mid-surgery adjustments of the patient and microscope, and additional post-operative follow-up care. To date, adoption of these implants has been limited.” (opens the source at this quote in a new tab)

Cross-trial comparison with trabecular bypass MIGS: first-in-human study

“In medication-washout clinical trials of trabecular bypass devices combined with CEIOL, mean IOP reduction ranged from 31.1 to 36.9%, reduction > 20% was achieved by 75.8 to 80.0% of subjects, and medication-free rates at 1 year were 77.1 to 85% [18–22]. The currently studied drug delivery system appeared comparable in magnitude to published MIGS outcomes, although cross-trial comparisons are exploratory and hypothesis-generating only.” (opens the source at this quote in a new tab)
“As with any investigation that examines a technology paired with cataract extraction, one must consider the standalone 2–4 mmHg reduction achieved by the latter in glaucoma populations [26, 27]. We did not include a CEIOL-only group comparator, which should be considered in future trials.” (opens the source at this quote in a new tab)

Sponsor-identified competitors

“Our lead product candidate, the BIM-IOL System, is designed to treat OAG and OHT, placing us in direct competition with a range of therapies, devices, procedures and technologies, including topical eye drops, laser-based interventions, MIGS, and intracameral implants.” (opens the source at this quote in a new tab)

Head-to-head comparison of the BIM-IOL System with Durysta, iDose TR, SLT, or MIGS

No evidence found.

Definition: primary open-angle glaucoma

“Primary open-angle glaucoma (POAG) in adults is a chronic, progressive optic neuropathy in which there is a characteristic acquired atrophy of the optic nerve and irreversible loss of retinal ganglion cells and their axons. In POAG, the anterior chamber is open by gonioscopy and secondary causes of IOP elevation are absent. Primary open-angle glaucoma is a potentially blinding eye disease, but early diagnosis and treatment can generally prevent visual disability.” (opens the source at this quote in a new tab)
“Primary open-angle glaucoma is a chronic ocular disease process that is progressive, generally bilateral, but often asymmetric.” (opens the source at this quote in a new tab)

“The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease.” (opens the source at this quote in a new tab)

Definition: ocular hypertension and primary open-angle glaucoma suspect

“A primary open-angle glaucoma (POAG) suspect is an individual with clinical findings and/or a constellation of risk factors that indicate an increased likelihood of developing POAG.” (opens the source at this quote in a new tab)
“A diagnosis of POAG suspect is established by the presence of an open angle and at least one of the following conditions: a consistently elevated IOP, also known as ocular hypertension, or a suspicious optic nerve, circumpapillary RNFL/macular ganglion cell layer on optical coherence tomography, or visual field.” (opens the source at this quote in a new tab)

Classification: open-angle and angle-closure glaucoma

“Glaucomas can be classified into 2 broad categories: open-angle glaucoma and angle-closure glaucoma. In the United States, more than 80% of cases are open-angle glaucoma; however, angle-closure glaucoma is responsible for a disproportionate number of patients with severe vision loss.” (opens the source at this quote in a new tab)

Etiology and risk factors

“Glaucoma is a chronic progressive optic neuropathy, characterized by damage to the optic nerve and retinal nerve fiber layer, that can lead to permanent loss of peripheral or central vision. Intraocular pressure is the only known modifiable risk factor. Other important risk factors include older age, nonwhite race, and a family history of glaucoma. Several systemic medical conditions and medications including corticosteroids, anticholinergics, certain antidepressants, and topiramate may predispose patients to glaucoma.” (opens the source at this quote in a new tab)

“Risk factors for primary open-angle glaucoma-the most common form of glaucoma-include older age, elevated intraocular pressure, sub-Saharan African ethnic origin, positive family history, and high myopia.” (opens the source at this quote in a new tab)

Etiology: genetic contribution

“Despite promising results, susceptibility genes that have been identified to date for primary open-angle glaucoma only have a modest effect size in explaining glaucoma risk.” (opens the source at this quote in a new tab)

Baseline predictors of conversion from ocular hypertension to primary open-angle glaucoma

“In multivariate analyses, baseline factors that predicted the development of POAG included older age, larger vertical or horizontal cup-disc ratio, higher intraocular pressure, greater pattern standard deviation, and thinner central corneal measurement.” (opens the source at this quote in a new tab)
“Central corneal thickness was found to be a powerful predictor for the development of POAG.” (opens the source at this quote in a new tab)

Magnitude of risk by age, ancestry, and refractive error

“In a meta-analysis of population-based studies, the odds ratio for primary open-angle glaucoma was 1·73 (95% CI 1·63–1·82) for each decade increase in age beyond 40 years.” (opens the source at this quote in a new tab)
“Across all ethnic origins, individuals of African ancestry had the highest prevalence of glaucoma (6·11%, 95% CI 3·83–9·13) and primary open-angle glaucoma (5·40%, 3·17–8·27)” (opens the source at this quote in a new tab)
“High myopia with a myopic refractive error of roughly more than –8 diopters was another strong risk factor for glaucoma.” (opens the source at this quote in a new tab)

Heritability and the proportion of Mendelian disease

“Glaucoma, a highly heritable complex human disease, has an estimated heritability of 70%.” (opens the source at this quote in a new tab)
“Approximately 5% of primary OAG is Mendelian, with autosomal-dominant inheritance.” (opens the source at this quote in a new tab)

Familial risk among siblings of affected individuals

“Siblings of affected individuals have nearly an eight times increased risk of primary open-angle glaucoma and a five times increased risk of angle closure when compared with siblings of unaffected individuals.” (opens the source at this quote in a new tab)

Global incidence: systematic review and meta-analysis of prospective studies

“A total of 9050 articles were identified in literature search, and 50 articles provided incidence data of glaucoma subtypes. In 2022, the global incidence rate of POAG was 23.46 (95% confidence interval (CI) = 15.68-32.91) per 10 000 person-years among 40-79 years.” (opens the source at this quote in a new tab)
“The pooled ACI of POAG was 0.21% (95% CI = 0.13%-0.30%).” (opens the source at this quote in a new tab)

United States incidence: Medicare fee-for-service beneficiaries, 2017 to 2021

“From 2017 to 2021, 5.5-6.2% of Medicare FFS beneficiaries were identified with prevalent POAG, with ~1% categorized as incident.” (opens the source at this quote in a new tab)

United States incidence: Olmsted County, Minnesota

“The overall age- and gender-adjusted annual incidence rate of OAG in a predominantly Caucasian population is conservatively estimated to be 14.5 per 100,000 population. The rates increased with age from 1.6 in the fourth decade of life to 94.3 in the eighth decade.” (opens the source at this quote in a new tab)

United States incidence of open-angle glaucoma and ocular hypertension: Los Angeles Latino Eye Study

“Among the 3939 participants (mean age, 54.7 ± 10.5 years) with complete data for a diagnosis of glaucoma at both baseline and follow-up examination, incident OAG at the 4-year follow-up was identified in 87 persons (4-year incidence rate, 2.3%; 95% confidence interval, 1.8% to 2.8%). Incident OHT at the 4-year follow-up was identified in 124 persons (4-year incidence rate, 3.5%; 95% confidence interval, 2.9% to 4.1%).” (opens the source at this quote in a new tab)

Incidence of primary open-angle glaucoma among individuals with ocular hypertension: Ocular Hypertension Treatment Study, 20-year follow-up

“A total of 1636 individuals (mean [SD] age, 55.4 [9.6] years; 931 women [56.9%]; 1138 White participants [69.6%]; 407 Black/African American participants [24.9%]) were randomized in phase 1 of the clinical trial. Of those, 483 participants (29.5%) developed POAG in 1 or both eyes (unadjusted incidence). After adjusting for exposure time, the 20-year cumulative incidence of POAG in 1 or both eyes was 45.6% (95% CI, 42.3%-48.8%) among all participants, 49.3% (95% CI, 44.5%-53.8%) among participants in the observation group, and 41.9% (95% CI, 37.2%-46.3%) among participants in the medication group.” (opens the source at this quote in a new tab)

Global prevalence: systematic review and meta-analysis with projections to 2040

“The global prevalence of glaucoma for population aged 40-80 years is 3.54% (95% CrI, 2.09-5.82). The prevalence of POAG is highest in Africa (4.20%; 95% CrI, 2.08-7.35), and the prevalence of PACG is highest in Asia (1.09%; 95% CrI, 0.43-2.32). In 2013, the number of people (aged 40-80 years) with glaucoma worldwide was estimated to be 64.3 million, increasing to 76.0 million in 2020 and 111.8 million in 2040.” (opens the source at this quote in a new tab)

Global prevalence of open-angle glaucoma: updated meta-analysis with projections to 2060

“Global OAG prevalence (≥40 years) is expected to rise from 2.8% (95% CI, 2.6%-3.0%) in 2024 to 3.5% (95% CI, 3.2%-3.8%) by 2060, with the affected population increasing from 80.5 (95% CI, 75.4-85.6) million to 186.6 (95% CI, 174.3-199.0) million.” (opens the source at this quote in a new tab)

“It was estimated that 52.68 million people in the world had POAG in the year 2020.” (opens the source at this quote in a new tab)
“Prevalence studies suggest that POAG will increase by 50% worldwide from 52.7 million in 2020 to 79.8 million in 2040 as the population ages” (opens the source at this quote in a new tab)

United States prevalence in 2022: CDC Vision and Eye Health Surveillance System estimates

“For 2022, an estimated 4.22 million people (95% uncertainty interval [UI], 3.46 million to 5.23 million) in the US were living with glaucoma, with a prevalence of 1.62% (UI, 1.33%-2.00%) among people 18 years or older and 2.56% (UI, 2.10%-3.16%) among people 40 years or older. An estimated 1.49 million people (UI, 1.17 million to 1.90 million) were living with vision-affecting glaucoma, with a prevalence of 0.57% (UI, 0.45%-0.73%) among people 18 years or older and 0.91% (UI, 0.71%-1.16%) among people 40 years or older.” (opens the source at this quote in a new tab)
“Black adults had a prevalence of 3.15% (UI, 2.32%-4.09%) compared with 1.42% (UI, 1.10%-1.85%) among White adults; adults in the Hispanic and all other racial and ethnic categories combined had a prevalence of 1.56% (UI, 1.13%-2.06%).” (opens the source at this quote in a new tab)

United States prevalence: Medicare fee-for-service beneficiaries

“From 2017 to 2021, 5.5-6.2% of Medicare FFS beneficiaries were identified with prevalent POAG, with ~1% categorized as incident. A higher proportion of POAG beneficiaries were older and/or Black.” (opens the source at this quote in a new tab)

United States prevalence and undiagnosed disease: National Health and Nutrition Examination Survey, 2005 to 2008

“The estimated overall prevalence of glaucoma in the US civilian, noninstitutionalized population 40 years of age and older was 2.1% (95% confidence interval [CI], 1.7%-2.6%). Glaucoma affected 2.9 million individuals, including 1.4 million women; 1.5 million men; 2.3 million people 60 years of age and older; and 0.9 million blacks, Mexican Americans, and people of other races.” (opens the source at this quote in a new tab)
“Over half of participants with glaucoma were unaware that they had the disease.” (opens the source at this quote in a new tab)

“Prevalence of undiagnosed glaucoma was 2.9%, increasing with age to 6.6% of the population over 70 years old. Among those with glaucoma, 78% were previously undiagnosed and untreated.” (opens the source at this quote in a new tab)
“Approximately 2.4 million persons in the US have undetected and untreated glaucoma.” (opens the source at this quote in a new tab)

Racial and ethnic differences in prevalence

“Overall, there appears to be a threefold higher prevalence of open-angle glaucoma (OAG) in Black individuals relative to non-Hispanic White individuals in the United States.” (opens the source at this quote in a new tab)
“Recent evidence suggests that Latino individuals have high prevalence rates of OAG that are comparable to those of Black individuals.” (opens the source at this quote in a new tab)

Prevalence of ocular hypertension in the United States

“Using this definition, the prevalence of ocular hypertension in non-Hispanic White individuals who are 40 and older and live in the United States is 4.5% (ranging from 2.7% in persons 43 to 49 years old to 7.7% in those 75 to 79 years old).” (opens the source at this quote in a new tab)
“In Latino individuals 40 and older, the overall prevalence is 3.5% (ranging from 1.7% in persons 40 to 49 years old to 7.4% in those 80 and older).” (opens the source at this quote in a new tab)
“For example, the Los Angeles Latino Eye Study (LALES) showed that 75% of Latino individuals with IOP greater than 21 mmHg were previously undiagnosed.” (opens the source at this quote in a new tab)

“Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension.” (opens the source at this quote in a new tab)

Coexisting glaucoma and cataract: prevalence among Medicare cataract surgery patients

“133,896 records of 82,246 CMS FFS claims were included in the analysis. The average patient age was 73.8, and 58.2% were females. The cataract surgery setting was ASC (71.3%) followed by HOPD (27.6%).” (opens the source at this quote in a new tab)
“The most common comorbidities included diabetes (28.6%), glaucoma (22.1%), and macular degeneration (21.7%).” (opens the source at this quote in a new tab)

“Cataract and glaucoma are leading causes of blindness worldwide, and their co-existence is common in elderly people.” (opens the source at this quote in a new tab)

Coexisting glaucoma and cataract: manufacturer estimate of United States cataract surgeries in patients with glaucoma or ocular hypertension

“There are expected to be approximately five million cataract surgeries in the United States in 2025, which is expected to grow by 3% to 4% per year” (opens the source at this quote in a new tab)
“The same report estimates that approximately one million of these surgeries will be performed in patients with glaucoma or OHT.” (opens the source at this quote in a new tab)
“Patients with glaucoma and cataracts are primarily over the age of 65, making Medicare the primary payor.” (opens the source at this quote in a new tab)

Contribution of population aging and rising myopia to the projected increase

“Compared to 2024, the global OAG population in 2060 is projected to increase by 106.2 million (131.9%). Accounting only for the aging and demographic effect, the increase is estimated to be 77.3 million (72.8% of the total increase), with the remaining 28.9 million (27.2%) attributable to the rising prevalence of myopia.” (opens the source at this quote in a new tab)
“The global prevalence of OAG is projected to rise from 2.8% to 3.5% between 2024 and 2060, with an estimated 193 million cases anticipated by 2060.” (opens the source at this quote in a new tab)

Evidence base and stated limitations of the 2060 projection

“After exclusion, 57 studies published between 1991 and 2023 were included and the data were extracted.” (opens the source at this quote in a new tab)
“First, we did not stratify by the degree of myopia; instead, we used a single risk ratio for overall myopia, given the dose-response relationship between myopia severity and OAG.” (opens the source at this quote in a new tab)
“Fourth, the current estimation of OAG prevalence among the 20–39-year age group was highly approximate, as it relied on only 3 studies.” (opens the source at this quote in a new tab)

Relative frequency of open-angle and angle-closure glaucoma and differences by sex and ancestry

“Primary open-angle glaucoma, with a global prevalence of about 3·1%, was six times more common than primary angle-closure glaucoma, which had a global prevalence of about 0·5%.” (opens the source at this quote in a new tab)
“With respect to primary open-angle glaucoma, men were more likely than women to have this disorder (odds ratio [OR] 1·36), as were people of African ancestry compared with people of European ancestry (OR 2·80)” (opens the source at this quote in a new tab)

Conversion from ocular hypertension to primary open-angle glaucoma: Ocular Hypertension Treatment Study, 5-year results

“During the course of the study, the mean +/- SD reduction in IOP in the medication group was 22.5% +/- 9.9%. The IOP declined by 4.0% +/- 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001).” (opens the source at this quote in a new tab)

Conversion from ocular hypertension to primary open-angle glaucoma: Ocular Hypertension Treatment Study, 20-year results

“The 20-year cumulative incidence of POAG was 55.2% (95% CI, 47.9%-61.5%) among Black/African American participants and 42.7% (95% CI, 38.9%-46.3%) among participants of other races. The 20-year cumulative incidence for visual field loss was 25.2% (95% CI, 22.5%-27.8%). Using a 5-factor baseline model, the cumulative incidence of POAG among participants in the low-, medium-, and high-risk tertiles was 31.7% (95% CI, 26.4%-36.6%), 47.6% (95% CI, 41.6%-53.0%), and 59.8% (95% CI, 53.1%-65.5%), respectively.” (opens the source at this quote in a new tab)

Progression of untreated and treated early glaucoma: Early Manifest Glaucoma Trial

“After a median follow-up period of 6 years (range, 51-102 months), retention was excellent, with only 6 patients lost to follow-up for reasons other than death. On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) (P =.007) and occurred significantly later in treated patients.” (opens the source at this quote in a new tab)

“After 6 years, 53% of patients progressed. In multivariate analyses, progression risk was halved by treatment (HR = 0.50; 95% CI, 0.35-0.71).” (opens the source at this quote in a new tab)
“Progression risk decreased by about 10% with each millimeter of mercury of IOP reduction from baseline to the first follow-up visit (HR = 0.90 per millimeter of mercury decrease; 95% CI, 0.86-0.94).” (opens the source at this quote in a new tab)

Lifetime risk of blindness in treated open-angle glaucoma: Sweden

“Five hundred and ninety-two patients were included. At the time of the last visit 250 patients (42.2%) had at least 1 blind eye because of glaucoma, while 97 patients (16.4%) were bilaterally blind, and 12 patients (0.5%) had low vision. Median time with a glaucoma diagnosis was 12 years (<1-29), median age when developing bilateral blindness was 86 years, and median duration of bilateral blindness was 2 years (<1-13). The cumulative incidences of blindness in at least 1 eye and bilateral blindness from glaucoma were 26.5% and 5.5%, respectively, after 10 years, and 38.1% and 13.5% at 20 years.” (opens the source at this quote in a new tab)

Probability of blindness in treated open-angle glaucoma: Olmsted County, Minnesota

“Probability of glaucoma-related blindness in at least one eye at 20 years decreased from 25.8 % (95% Confidence interval [CI]: 18.5–32.5) for subjects diagnosed in 1965–1980, to 13.5% (95% CI: 8.8–17.9) for subjects diagnosed in 1981–2000 (P=0.01).” (opens the source at this quote in a new tab)
“However, a significant proportion of patients still progress to blindness despite recent diagnostic and therapeutic advancements.” (opens the source at this quote in a new tab)

“At 20-years' follow-up, the Kaplan-Meier cumulative probability of glaucoma-related blindness in at least one eye was estimated to be 27% (95% confidence interval, 20%-33%), and for both eyes, it was estimated to be 9% (95% confidence interval, 5%-14%).” (opens the source at this quote in a new tab)

Global blindness and vision impairment attributable to glaucoma

“Globally, in 2020, 3.61 million people were blind and nearly 4.14 million were visually impaired by glaucoma. Glaucoma accounted for 8.39% (95% uncertainty intervals [UIs]: 6.54, 10.29) of all blindness and 1.41% (95% UI: 1.10, 1.75) of all MSVI. Regionally, the highest proportion of blindness relating to glaucoma was found in high-income countries (26.12% [95% UI: 20.72, 32.09]), while the region with the highest age-standardized prevalence of glaucoma-related blindness and MSVI was Sub-Saharan Africa.” (opens the source at this quote in a new tab)

“The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases [9% IU 12·7-18·0]), followed by glaucoma (3·6 million cases [2·8-4·4]), undercorrected refractive error (2·3 million cases [1·8-2·8]), age-related macular degeneration (1·8 million cases [1·3-2·4]), and diabetic retinopathy (0·86 million cases [0·59-1·23]).” (opens the source at this quote in a new tab)

Disease severity at detection: population screening

“Among the screened subjects, who were 77.5% of all invited subjects, a total of 406 subjects (1.23%) were identified with previously undetected glaucoma.” (opens the source at this quote in a new tab)
“Most eyes had early (35%) or moderate (31%) glaucomatous visual field defects, but 134 subjects (33%) had advanced visual field loss in at least one eye. No subject was blind in both eyes, but 3.4% of the newly diagnosed patients were unilaterally blind due to glaucoma.” (opens the source at this quote in a new tab)

Mortality: systematic review and meta-analysis of prospective studies

“Seven articles were included. The pooled ACM of POAG was 3.42% (95% confidence interval [CI] 1.70%-5.58%). The mortality rate of POAG was reported in one study as 6.1 (95% CI 5.5-6.7) per 1000 person-years. A significant association between POAG and mortality was observed in the pooled unadjusted relative mortality risk estimates (HR 2.14, 95% CI 1.32-3.47). Fully adjusted relative mortality risk estimates did not show a significant association with mortality (HR 1.13, 95% CI 0.91-1.40).” (opens the source at this quote in a new tab)

Follow-up duration and form of the first glaucoma endpoint in the Ocular Hypertension Treatment Study

“The median duration of follow-up was 72 months for African American participants and 78 months for other participants. Of the expected follow-up visits, 90% were completed during the study, and the visit completion rate did not differ by randomization group.” (opens the source at this quote in a new tab)
“Approximately 55% (69 of 125) of the initial POAG endpoints involved optic disc deterioration in the absence of visual field abnormalities meeting study criteria for a visual field endpoint.” (opens the source at this quote in a new tab)

Probability of blindness over 20 years of follow-up

“The rate of blindness from glaucoma in one or both eyes over 20 years of follow-up is approximately 13%.” (opens the source at this quote in a new tab)

Vision impairment and blindness after 14 years in the Early Manifest Glaucoma Trial

“The number of analyzed subjects was 128 in the treatment group and 123 in the initially untreated control group.” (opens the source at this quote in a new tab)
“The mean age at baseline was nearly identical in both study arms, but the mean age at study end was 1 year higher and mean follow-up time was more than 1 year longer in the control group (14.8 years) than in the treatment group (13.7 years)” (opens the source at this quote in a new tab)
“This was true both for VI in at least one eye and bilateral impairment 19.5% vs 18.7% and 4.7% vs 3.3%, respectively, as well as for unilateral and bilateral blindness, 12.5% vs 7.3% and 3.1% vs 2.4%, respectively.” (opens the source at this quote in a new tab)
“More than half of the subjects died during the study period: 68 (53%) in the treated group and 65 (53%) in the control group.” (opens the source at this quote in a new tab)

Derivation and evidence base of the pooled annual cumulative mortality estimate

“Cumulative mortality was defined as the number of deaths during the follow-up period over the total glaucoma individuals at baseline.” (opens the source at this quote in a new tab)
“Random-effects meta-analysis was conducted on the remaining four articles with available follow-up period.” (opens the source at this quote in a new tab)
“The included articles did not cover the regions of Africa and the Eastern Mediterranean, with the majority concentrated in high-income countries or regions (71.4%).” (opens the source at this quote in a new tab)

Effect of comorbidity adjustment on the association between glaucoma and mortality

“Another article based on data from Finnish social insurance found a cumulative mortality of 17.2% for POAG in Finland from June 2004 to January 2013” (opens the source at this quote in a new tab)
“This difference may be partly explained by adjustment for comorbidities and differences in covariate selection across studies.” (opens the source at this quote in a new tab)
“Given the impact of these comorbidities on mortality, we speculate that the observed association may be influenced by underlying health status and comorbidity burden rather than glaucoma itself” (opens the source at this quote in a new tab)

Aqueous humor dynamics and intraocular pressure

“Although the pathogenesis of glaucoma is not fully understood, the level of intraocular pressure is related to retinal ganglion cell death.” (opens the source at this quote in a new tab)
“In patients with open-angle glaucoma, there is increased resistance to aqueous outflow through the trabecular meshwork.” (opens the source at this quote in a new tab)

Mechanical stress at the lamina cribrosa and axonal transport

“The sclera is perforated at the lamina where the optic nerve fibers (retinal ganglion cell axons) exit the eye. The lamina is the weakest point in the wall of the pressurized eye. Intraocular pressure–induced stress and strain may result in compression, deformation, and remodeling of the lamina cribrosa with consequent mechanical axonal damage and disruption of axonal transport” (opens the source at this quote in a new tab)

Pressure-independent mechanisms

“Glaucomatous optic neuropathy can occur in individuals with intraocular pressures within the normal range. In such patients, there may be an abnormally low cerebrospinal fluid pressure in the optic nerve subarachnoid space resulting in a large pressure gradient across the lamina.” (opens the source at this quote in a new tab)
“Impaired microcirculation, altered immunity, excitotoxicity, and oxidative stress may also cause glaucoma.” (opens the source at this quote in a new tab)

Pattern of retinal ganglion cell loss and visual field damage

“Retinal ganglion cell loss causes progressive deterioration of visual fields, which usually begins in the midperiphery and may progress in a centripetal manner until there remains only a central or peripheral island of vision.” (opens the source at this quote in a new tab)

Guideline: comprehensive initial glaucoma evaluation

“The comprehensive initial glaucoma evaluation (history and physical examination) includes all components of the comprehensive adult medical eye evaluation” (opens the source at this quote in a new tab)
“The evaluation may require more than one visit. For instance, an individual might be suspected of having glaucoma on one visit but may return for further evaluation to confirm the diagnosis, including additional IOP measurements; gonioscopy; CCT determination; visual field assessment; and ONH, circumpapillary RNFL, and macular ganglion cell layer imaging.” (opens the source at this quote in a new tab)

Guideline: diagnostic tests

Diagnostic test	Quoted record
Corneal thickness	“CCT measurement”
Corneal biomechanics	“Corneal hysteresis measurement”
Visual function	“Visual field evaluation”
Structural imaging	“ONH, circumpapillary RNFL, and macular ganglion cell layer imaging”

Structural and functional criteria and limits of early detection

“With retinal ganglion cell death and optic nerve fiber loss in glaucoma, characteristic changes in the appearance of the optic nerve head and retinal nerve fiber layer occur.” (opens the source at this quote in a new tab)
“Because there is no single perfect reference standard for establishing the diagnosis of glaucoma, early diagnosis can be challenging.” (opens the source at this quote in a new tab)
“Presence of characteristic visual field defects can confirm the diagnosis, but as many as 30% to 50% of retinal ganglion cells may be lost before defects are detectable by standard visual field testing.” (opens the source at this quote in a new tab)
“These techniques, including confocal scanning laser ophthalmoscopy, scanning laser polarimetry, and optical coherence tomography, have improved the identification of early disease and also enhanced the observation of progressive optic nerve fiber loss over time” (opens the source at this quote in a new tab)

Intraocular pressure alone does not establish the diagnosis

“Although elevated intraocular pressure is a very consistent risk factor for the presence of glaucoma, several population-based studies found intraocular pressure was lower than 22 mm Hg in 25% to 50% of individuals with glaucoma.” (opens the source at this quote in a new tab)

Diagnostic and monitoring tests in clinical practice

“Diagnostic testing to assess for glaucoma and to monitor for disease progression includes measurement of intraocular pressure, perimetry, and optical coherence tomography.” (opens the source at this quote in a new tab)

“Glaucoma is diagnosed using ophthalmoscopy, tonometry, and perimetry.” (opens the source at this quote in a new tab)

“Eye doctors can check for glaucoma as part of a comprehensive dilated eye exam.” (opens the source at this quote in a new tab)
“The exam includes a visual field test to check your side vision.” (opens the source at this quote in a new tab)
“If you’re at higher risk, you need to get a comprehensive dilated eye exam every 1 to 2 years.” (opens the source at this quote in a new tab)

Test variability and the number of examinations needed to detect deterioration

“Perimetry describes the subjective psychophysical defect as experienced by the patient, but it has fairly high intervisit variability, so at least three perimetric examinations could be necessary to detect visual-field deterioration reliably.” (opens the source at this quote in a new tab)
“One measurement of intraocular pressure has a low sensitivity to detect glaucoma under screening conditions.” (opens the source at this quote in a new tab)

Proportion of cases undiagnosed and the case against population-wide screening

“A large proportion (50–90%) of patients with glaucoma remain undiagnosed in developed, developing, and underdeveloped regions of the world.” (opens the source at this quote in a new tab)
“Because of the fairly low prevalence of glaucoma (about 3·5% in individuals aged 40 years or older), and since diagnostic measures with sufficient precision are not yet available, general screening for glaucoma would result in an unacceptably high number of false-positive diagnoses.” (opens the source at this quote in a new tab)

Early disease: absence of symptoms

“At first, glaucoma doesn’t usually have any symptoms. That’s why half of people with glaucoma don’t even know they have it.” (opens the source at this quote in a new tab)
“Over time, you may slowly lose vision, usually starting with your side (peripheral) vision” (opens the source at this quote in a new tab)

“Chronic forms of glaucoma are painless and symptomatic visual-field defects occur late.” (opens the source at this quote in a new tab)

Visual symptoms: peripheral vision loss and associated complaints

“Symptoms more common among glaucoma patients compared with glaucoma suspects included better vision in 1 eye, blurry vision, glare, sensitivity to light, cloudy vision, missing patches of vision, and little peripheral vision. Worse severity ratings for the symptom "little peripheral vision" explained the most variance in VF damage (43%).” (opens the source at this quote in a new tab)

Visual symptoms: distinguishing glaucoma from cataract

“Compared with cataract patients, glaucoma patients were more likely to report poor peripheral vision (OR 7.24, 95% CI: 2.53-20.72) and missing patches (OR 4.91, 95% CI: 1.52-15.84), but less likely to report worsening vision (OR 0.08, 95% CI 0.03-0.22), explaining 33% of the variance in diagnosis (ie, glaucoma vs. cataract).” (opens the source at this quote in a new tab)
“Asking about visual symptoms may serve as a useful diagnostic adjunct and inform decision-making, for example, in glaucoma patients considering cataract surgery.” (opens the source at this quote in a new tab)

Functional symptoms: late-stage vision loss and daily activities

“Glaucoma progresses without causing symptoms until the disease is advanced with substantial amounts of neural damage. When symptoms do occur, the disease results in vision loss with concomitant reduction in quality of life and the ability to perform daily activities, such as driving.” (opens the source at this quote in a new tab)

Signs: optic nerve and retinal nerve fiber layer findings

“Diffuse or focal narrowing, or notching, of the optic disc rim, especially at the inferior or superior poles” (opens the source at this quote in a new tab)
“Progressive narrowing of the neuroretinal rim with an associated increase in cupping of the optic disc” (opens the source at this quote in a new tab)
“Diffuse or localized thinning of the parapapillary RNFL, especially at the inferior or superior poles.” (opens the source at this quote in a new tab)

Psychological symptoms: depression

“Thirty-eight studies including 21,705 patients with glaucoma contributed to the single-group prevalence meta-analysis; pooled depression prevalence was 26.03% (95% CI, 21.10%-31.64%; prediction interval 5.98%-66.04%).” (opens the source at this quote in a new tab)
“GRADE certainty was very low for the comparative, prevalence, and longitudinal evidence domains.” (opens the source at this quote in a new tab)

Falls and fractures: population-based cohort in England

“Compared with comparators, there was an increased risk of falls in those with cataract (adjusted hazard ratio [HR], 1.36; 95% CI, 1.35-1.38), AMD (HR, 1.25; 95% CI, 1.23-1.27), and glaucoma (HR, 1.38; 95% CI, 1.35-1.41). Likewise for fractures, there were increased risks in all eye diseases, with an HR of 1.28 (95% CI, 1.27-1.30) in the cataract cohort, an HR of 1.18 (95% CI, 1.15-1.21) for AMD, and an HR of 1.31 (95% CI, 1.27-1.35) for glaucoma.” (opens the source at this quote in a new tab)

Falls by glaucoma severity: United States clinic cohort

“Of the glaucoma participants, 36% reported at least one fall in the prior 12 months compared to 20% of controls (adjusted odds ratio [OR], 2.7; 95% CI, 1.18–6.17; p=0.018). Compared to controls, the mild glaucoma group trended towards a higher fall risk (adjusted OR, 2.43; 95% CI, 0.97–6.08; p=0.059) and the advanced group had the highest fall risk (adjusted OR, 7.97; 95% CI, 2.44–26.07; p=0.001).” (opens the source at this quote in a new tab)

Falls or fractures by severity: United States claims analysis

“Severe OAG patients had significantly higher odds of fall or fracture compared with OHT patients (odds ratio, 1.34; 95% confidence interval, 1.13-1.59).” (opens the source at this quote in a new tab)

Driving: motor vehicle collisions

“over six times more likely to have been involved in one or more MVCs in the previous 5 years (OR(adjusted) = 6.62; 95% CI, 1.40-31.23), and more likely to have been at fault (OR(adjusted) = 12.44; 95% CI, 1.08-143.99).” (opens the source at this quote in a new tab)

Visual disability and activities of daily living

“Patients with glaucoma may struggle with daily activities such as reading, walking, and driving.” (opens the source at this quote in a new tab)
“Performance on these activities deteriorates with worsening of glaucoma severity or when both eyes are affected.” (opens the source at this quote in a new tab)
“Patients with glaucoma are more likely to experience falls and more likely to be involved in motor vehicle collisions compared with people without glaucoma.” (opens the source at this quote in a new tab)

Vision-affecting glaucoma in the United States

“An estimated 1.49 million people (UI, 1.17 million to 1.90 million) were living with vision-affecting glaucoma, with a prevalence of 0.57% (UI, 0.45%-0.73%) among people 18 years or older and 0.91% (UI, 0.71%-1.16%) among people 40 years or older.” (opens the source at this quote in a new tab)

Guideline statement: quality of life across disease stages

“Quality of life is affected for patients with all stages of glaucoma, even those with early disease.” (opens the source at this quote in a new tab)

Vision-related quality of life by visual field loss: Ocular Hypertension Treatment Study, 20-year follow-up

“Of 1636 participants originally enrolled in the OHTS, 679 (42%) completed the 20-year examination and VRQoL surveys.” (opens the source at this quote in a new tab)
“The mean (SD) Rasch-calibrated total VFQ scores were 72.5 (13.4) in the no POAG group (control) vs 72.7 (13.8) in the unilateral disc POAG group (difference, 0.17; 95% CI, -3.17 to 3.41; P = .92), 73.4 (14.0) in the bilateral disc POAG group (difference, 0.92; 95% CI, -2.93 to 4.77; P = .64), 69.2 (14.5) in the unilateral VF POAG group (difference, 3.33; 95% CI, -6.38 to -0.27; P = .03), and 58.5 (16.9) in the bilateral VF POAG group (difference, -13.96; 95% CI, -17.73 to -10.19; P<.001).” (opens the source at this quote in a new tab)

Vision-related quality of life and visual impairment: Early Manifest Glaucoma Trial, 20-year follow-up

“NEI VFQ-25 scores were significantly higher for patients with no visual impairment (mean 73 ± 22) than for visually impaired patients (mean 31 ± 15, p < 0.001). VFI worse than 50% or MD worse than -18 dB was significantly associated with low VRQOL scores (p < 0.001).” (opens the source at this quote in a new tab)

Health-related quality of life by visual field loss: Los Angeles Latino Eye Study

“A trend of worse NEI-VFQ-25 scores for most subscales was observed with worse VF loss (using both monocular and calculated binocular data). Open-angle glaucoma participants with VF loss had lower scores than participants with no VF loss. This association was also present in participants who were previously undiagnosed and untreated for OAG (N = 160). Participants with any central VF loss had lower NEI-VFQ-25 scores than those with unilateral or bilateral peripheral VF loss. There was no significant impact of severity or location of VF loss on SF-12 scores.” (opens the source at this quote in a new tab)

Psychological burden of diagnosis and treatment

“The disease itself as well as the medical or surgical treatment can have an enormous impact on a patient's QoL. Even the mere diagnosis of a chronic, irreversible, potentially blinding disorder can adversely affect the patient's sense of well-being and QoL by eliciting significant anxiety.” (opens the source at this quote in a new tab)

“Sixteen studies including 14,030 glaucoma participants and 4,472,723 controls contributed to the primary odds ratio meta-analysis. Glaucoma was associated with higher odds of depression (OR, 2.80; 95% CI, 1.66-4.74; I 2 = 95.95%; approximate prediction interval 0.32-24.47).” (opens the source at this quote in a new tab)

Falls, fear of falling, and activity avoidance

“A greater risk of a high fear of falling and high avoidance of at-risk activities occurred at the moderate stage of glaucoma compared to controls (adjusted OR, 4.66; 95% CI, 1.24–17.49; p=0.023 and adjusted OR, 4.49; 95% CI, 1.34–15.05; p=0.015, respectively).” (opens the source at this quote in a new tab)

United States incremental health care expenditures: Medical Expenditure Panel Survey, 2016 to 2018

“After 1:3 propensity matching for sociodemographics and the Charlson Comorbidity Index, this study analyzed 1521 glaucoma patients (mean expenditures: $13,585.68±1367.03) and 4563 patients without glaucoma (mean expenditures: $12,048.92±782.49).” (opens the source at this quote in a new tab)
“Controlling for comorbidities and socioeconomic factors, propensity-matched glaucoma patients incur an annual incremental health care burden of $1863.17 (95% confidence interval, 393.44-3117.23, P=0.013), translating into an additional $9.2 billion in population-level US health care expenditures. By health care service sector, the expenditure ratio for health care expenditures was higher for prescription medications (expenditure ratio=1.20, 95% confidence interval, 1.02-1.42, P=0.031).” (opens the source at this quote in a new tab)

United States costs by disease severity: commercial claims analysis

“One hundred seventy-seven thousand three hundred fifty-two OHT and OAG patients were identified (67.8% with OAG). Open-angle glaucoma patients showed higher eye-related outpatient costs than OHT patients (median, $516 [interquartile range (IQR), $323-$898] vs. $344 [IQR, $197-$617], respectively). Patients with severe OAG showed higher eye-related outpatient costs than moderate and mild OAG patients (median, $639 [IQR, $381-$1264] vs. $546 [IQR, $345-$950] vs. $476 [IQR, $304-$765], respectively; P < 0.0001), as well as higher glaucoma-related pharmacy costs (median, $493 [IQR, $122-$1457] vs. $244 [IQR, $84-$1113] vs. $139 [IQR, $66-$818], respectively; P < 0.0001). In adjusted analyses, disease worsening was associated with at least 2-fold higher annual eye-related outpatient costs (P < 0.0001).” (opens the source at this quote in a new tab)

United States direct costs by disease stage: multicenter medical record review

“Direct ophthalmology-related resource use, including ophthalmology visits, glaucoma surgeries, and medication use, increased as disease severity worsened. Average direct cost of treatment ranged from $623 per patient per year for glaucoma suspects or patients with early-stage disease to $2511 per patient per year for patients with end-stage disease. Medication costs composed the largest proportion of total direct cost for all stages of disease (range, 24%-61%).” (opens the source at this quote in a new tab)

Guideline summary of direct and indirect costs

“The costs of managing a chronic disease like glaucoma can be broken down into direct medical costs, direct nonmedical costs, and indirect costs.” (opens the source at this quote in a new tab)
“One study from 2005 estimated that nearly $3 billion per year was spent in the United States on direct medical costs from glaucoma.” (opens the source at this quote in a new tab)
“Using Medicare claims data and Markov modeling, one study from 2010 estimated that the average direct and indirect medical costs for patients with POAG are $1688 higher over a lifetime than other patients without this condition.” (opens the source at this quote in a new tab)
“For those with advanced disease, indirect costs such as costs for home health care and rehabilitation predominate.” (opens the source at this quote in a new tab)

Medicare Part D spending on prostaglandin analogs

“In 2013, Medicare spent $733 million on prostaglandin analogs; in 2017, this increased to $1.09 billion, with $943 million (86%) spent on branded prostaglandins and $148 million (14%) spent on generics.” (opens the source at this quote in a new tab)
“Median out-of-pocket cost of branded prostaglandins without generic equivalents was $35 (IQR = $29-$40) in 2009, $45 (IQR = $42-$101) in 2013, and $90 (IQR = $45-$159) in 2017.” (opens the source at this quote in a new tab)

Medicare Part D glaucoma medication spending per beneficiary, 2019 to 2023

“Median spending per beneficiary was $403.81 (interquartile range [IQR], $359.74-$444.73), and median spending per claim was $104.22 (IQR, $89.49-$118.41).” (opens the source at this quote in a new tab)
“Utilization intensity varied minimally across socioeconomic strata (claims per beneficiary, 3.8-4.0), and neither ADI nor income was consistently associated with brand spending or claims share.” (opens the source at this quote in a new tab)

Medicare reintervention and costs after incisional glaucoma surgery

“At 1 year, 15.1% of EX-PRESS shunt patients, 11.6% of tube shunt patients, and 8.8% of trabeculectomy patients had experienced failure based on postindex procedures. By 5 years follow-up, these rates were 31.5% of EX-PRESS shunt patients, 27.1% of tube shunt patients, and 23.5% of trabeculectomy patients. Five-year rates of glaucoma reoperations were 18.3%, 14.0%, and 15.1%, respectively.” (opens the source at this quote in a new tab)

Health care resource utilization: Medicare beneficiaries with glaucoma

“Among 78 526 participants with glaucoma, mean age was 79.1 years (standard deviation, 7.9 years), 60.9% were female, 78.4% were non-Hispanic White, and 13.8% met enrollment-based criteria for low-SES. Compared with White beneficiaries, Blacks had lower counts of outpatient visits (RR, 0.92; 95% confidence interval [CI], 0.90-0.93), visual field (VF) tests (RR, 0.92; 95% CI, 0.90-0.94), but more inpatient/ED encounters (RR, 2.42; 95% CI, 1.55-3.78) and surgeries (RR, 1.14; 95% CI, 1.03-1.27).” (opens the source at this quote in a new tab)

Burden increases with disease severity

“The economic burden of glaucoma is significant and increases as the disease worsens.” (opens the source at this quote in a new tab)

Direct and indirect costs: nationwide register study, Finland

“The annual additional total direct costs were EUR 2,660/glaucoma patient, EUR 1,769/glaucoma patient with medication, and EUR 3,979/operated glaucoma patient compared with persons without glaucoma. The respective additional total indirect costs were EUR 4,288, EUR 3,246, and EUR 12,902 per year.” (opens the source at this quote in a new tab)

Eye-related outpatient visits and procedure use by disease severity: United States commercial claims

“Patients with OAG appeared to have higher use of outpatient visits compared with patients with OHT only (mean, 4.2 visits [SD, 3.2 visits] vs. 3.0 visits [SD, 2.9 visits] per user, respectively). The mean number of eye-related outpatient visits increased with increasing baseline OAG severity (P < 0.0001).” (opens the source at this quote in a new tab)
“More patients in the OAG group had a physician office visit for a laser or surgical glaucoma procedure compared with patients in the OHT group (9.4% vs. 2.2%, respectively). The proportion of patients undergoing laser or surgical glaucoma procedures increased with increasing baseline OAG severity (P < 0.0001).” (opens the source at this quote in a new tab)

Adjusted drivers of annual eye-related outpatient costs: baseline severity and number of topical medication classes

“Costs increased with increasing baseline severity (from 30% to 129%) and number of TGM classes at baseline (from 8% to 68%; P < 0.0001 for both).” (opens the source at this quote in a new tab)

Documented disease worsening over 12 months and associated procedure rates

“Approximately 12% of the study population had a worsening in coded severity during the 12-month follow-up period” (opens the source at this quote in a new tab)
“Open-angle glaucoma surgery or procedure rates were substantial among patients with a worsening in coded severity, with the highest observed rates among OAG patients developing severe disease (52.1% and 47.0% of patients with a worsening in coded severity from moderate to severe and mild to severe, respectively).” (opens the source at this quote in a new tab)
“Treatment intensification also was observed in patients without a worsening in coded severity, ranging from 11.8% to 45.1% across baseline severity cohorts.” (opens the source at this quote in a new tab)

Aggregate United States direct medical costs and principal cost components

“Glaucoma is estimated to account for $US2.9 billion of direct medical costs among US adults annually.” (opens the source at this quote in a new tab)
“In general, they have shown that increased glaucoma severity correlates with increased costs, and medication and ophthalmologist examinations account for a majority of direct costs across studied North American and European regions.” (opens the source at this quote in a new tab)

Cost components in end-stage glaucoma with visual rehabilitation care

“In a retrospective evaluation of resource use and costs for patients with end-stage glaucoma who were receiving visual rehabilitation care, three US centres provided 81 patient records indicating patient level billing and reimbursement for eye care visits, medications, procedures and specialized low vision and glaucoma-related services.” (opens the source at this quote in a new tab)
“Visual rehabilitation services included low vision devices, assessment of daily functioning, orientation and mobility training and counselling.” (opens the source at this quote in a new tab)
“Total costs for 2 years were determined to comprise 15% for visual rehabilitation, 37% for ophthalmology care and 48% for pharmaceuticals.” (opens the source at this quote in a new tab)

Caregiver burden in glaucoma-related blindness

“A cross-sectional study enrolled 110 adult patients with glaucoma-related blindness and their caregivers.” (opens the source at this quote in a new tab)
“Similarly, caregivers demonstrated higher PHQ-9 and ZBI-22 scores with rising levels of patient VI (all P < 0.05).” (opens the source at this quote in a new tab)
“Glaucoma-related blindness imposes significant psychological and functional burdens on patients and caregivers, with evidence of emotional contagion.” (opens the source at this quote in a new tab)

Practical, financial, and emotional challenges for informal caregivers

“The study involved 11 informal caregivers, out of which 8 were females.” (opens the source at this quote in a new tab)
“These included caregiving roles (basic activities of daily living, instrumental activities of daily living and emotional support), caregiving challenges (practical challenges, emotional challenges and financial challenges), coping strategies (adaptive and maladaptive coping strategies) and recommendations to clinicians (quantity of medication, review appointments and health education).” (opens the source at this quote in a new tab)

Indirect costs including informal care: vision loss in the United States

“We estimated an economic burden of VL of $134.2 billion: $98.7 billion in direct costs and $35.5 billion in indirect costs.” (opens the source at this quote in a new tab)
“Those with VL incurred $16 838 per year in incremental burden.” (opens the source at this quote in a new tab)

Guideline statement: caregiver productivity losses

“Direct nonmedical costs (e.g., costs for transportation to appointments and nursing home care) and indirect costs (e.g., loss of productivity of the patient or caregivers) can be more difficult to quantify but are substantial.” (opens the source at this quote in a new tab)

Guideline statement: ancillary testing as a component of direct costs

“Direct costs include costs of visits to eye care clinicians, ancillary testing, and medical and surgical interventions.” (opens the source at this quote in a new tab)

Medicare Part B payments: optical coherence tomography of the optic nerve (CPT 92133), 2024

Field	Office and other non-facility settings	Facility settings
Service description	“Imaging of optic nerve”	“Imaging of optic nerve”
Place of service code	“O”	“F”
Total beneficiaries	“2353950”	“59478”
Total services	“2704197.1”	“67036”
Average submitted charge (USD)	“111.02944985”	“107.26792037”
Average Medicare allowed amount (USD)	“34.480219382”	“21.326738021”
Average Medicare payment amount (USD)	“24.047622387”	“14.822967212”

Medicare Part B payments: extended visual field examination (CPT 92083), 2024

Field	Office and other non-facility settings	Facility settings
Service description	“Exam of visual field with extended testing”	“Exam of visual field with extended testing”
Place of service code	“O”	“F”
Total beneficiaries	“2256481”	“57345”
Total services	“2654750”	“67503”
Average submitted charge (USD)	“150.1505657”	“121.66678933”
Average Medicare allowed amount (USD)	“62.079533207”	“26.88252611”
Average Medicare payment amount (USD)	“43.643536035”	“18.909151741”

Utilization trends: visual field testing and ocular imaging in open-angle glaucoma

“169,917 individuals with OAG and 395,721 with suspected glaucoma age ≥40 enrolled in a national United States managed care network between 2001–2009.” (opens the source at this quote in a new tab)
“For patients with OAG, the odds of undergoing VF testing decreased by 36% from 2001 to 2005, 12% from 2005 to 2009, and 44% from 2001 to 2009. By comparison, the odds of having OOI increased by 100% from 2001 to 2005, 24% from 2005 to 2009, and 147% from 2001 to 2009.” (opens the source at this quote in a new tab)
“The probability of undergoing OOI increased from 26% in 2001 to 47% in 2009 for patients of optometrists and from 30% in 2001 to 46% in 2009 for patients of ophthalmologists.” (opens the source at this quote in a new tab)

Visual field examination costs within direct costs of glaucoma management

“Direct costs by specific resource types, including ophthalmology visits, glaucoma surgeries, medications, visual field examinations, and other glaucoma services, were also assessed.” (opens the source at this quote in a new tab)

Geographic variation in diagnostic testing after open-angle glaucoma diagnosis

“Of the 56675 enrollees with newly-diagnosed OAG, the mean proportion of patients undergoing VF testing within two years of initial diagnosis was 74% ± 7%, ranging from as low as 51% in Rochester, MN to as high as 95% in Lancaster, PA. The mean proportion undergoing OOI was 63% ± 10% and varied from 34% in Palm Springs/Rancho Mira, CA to 85% in Charleston, SC.” (opens the source at this quote in a new tab)

AAO Primary Open-Angle Glaucoma Preferred Practice Pattern: prostaglandin analogs as initial medical therapy

“Topical medical therapy is currently the most common initial intervention to lower IOP (see Table 4 for an overview of options available). Prostaglandin analogs are the most frequently prescribed eye drops for lowering IOP in patients with glaucoma because they are most efficacious and well tolerated, and they need to be instilled only once daily.” (opens the source at this quote in a new tab)
“Therefore, prostaglandin analogs are often selected as initial medical therapy unless other considerations, such as contraindications, cost, side effects, intolerance, or patient refusal preclude this.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: prostaglandin analog class profile (bimatoprost, latanoprost, latanoprostene bunod, omidenepag, tafluprost, travoprost)

Field	Quoted record
Mechanism of action	“Increase uveoscleral outflow”
IOP reduction	“25%–33%”
Potential contraindications	“Macular edema”; “History of herpetic keratitis”; “Active uveitis”

European Glaucoma Society guidelines, 6th edition: first-choice medical treatment

“Recommendation: Prostaglandin analogs (PGAs) are the most effective medication, and they are usually recommended as first-choice medical treatment for open-angle glaucoma.” (opens the source at this quote in a new tab)
“Level of evidence: high” (opens the source at this quote in a new tab)
“PGAs have become the first-choice therapy largely on the basis of their efficacy, as well as the practicality of once-daily dosing and of their systemic safety profile. The United Kingdom Glaucoma Treatment Study (UKGTS) has provided high level evidence for the vision-preserving effect of topical latanoprost treatment.” (opens the source at this quote in a new tab)

NICE NG81: generic prostaglandin analog when SLT is declined, unsuitable, or insufficient

“Offer a generic PGA to people with COAG if:” (opens the source at this quote in a new tab)
“they choose not to have 360° SLT or” (opens the source at this quote in a new tab)
“360° SLT is not suitable (for example because they have pigment dispersion syndrome) or” (opens the source at this quote in a new tab)
“they are waiting for an 360° SLT and need an interim treatment or” (opens the source at this quote in a new tab)
“they have previously had 360° SLT but need additional treatment to reduce their IOP sufficiently to prevent the risk of visual impairment.” (opens the source at this quote in a new tab)

Network meta-analysis of first-line topical medications: mean IOP reduction at 3 months

“We included 114 randomized controlled trials with data from 20,275 participants.” (opens the source at this quote in a new tab)
“The mean reductions (95% credible intervals) in IOP in mmHg at 3 months, ordered from the most to least effective drugs were: bimatoprost 5·61 (4·94; 6·29), latanoprost 4·85 (4·24; 5·46), travoprost 4·83 (4·12; 5·54), levobunolol 4·51 (3·85; 5·24), tafluprost 4·37 (2·94; 5·83), timolol 3·7 (3·16; 4·24), brimonidine 3·59 (2·89; 4·29), carteolol 3·44 (2·42; 4·46), levobetaxolol 2·56 (1·52; 3·62), apraclonidine 2·52 (0·94; 4·11), dorzolamide 2·49 (1·85; 3·13), brinzolamide 2·42 (1·62; 3·23), betaxolol 2·24 (1·59; 2·88), and unoprostone 1·91 (1·15; 2·67).” (opens the source at this quote in a new tab)
“Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within-class differences were small and may not be clinically meaningful.” (opens the source at this quote in a new tab)

UKGTS: latanoprost versus placebo and visual field preservation

“We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010.” (opens the source at this quote in a new tab)
“At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003).” (opens the source at this quote in a new tab)

Network meta-analysis: bimatoprost concentrations analyzed and efficacy of bimatoprost 0.01%

“Of the 17 bimatoprost trials included in our network, 15 evaluated bimatoprost 0·03% and two evaluated bimatoprost 0·01%.” (opens the source at this quote in a new tab)
“Bimatoprost 0.01% is no more effective than latanoprost or travoprost in lowering IOP at 3 months.” (opens the source at this quote in a new tab)
“Bimatoprost, when the two concentrations (0·03% and 0·01%) are not differentiated, resulted in a statistically significant lower IOP than any other active drug except tafluprost, although the pair-wise differences in lowering IOP at 3 months among bimatoprost, latanoprost, travoprost, and tafluprost are small and may not be clinically meaningful.” (opens the source at this quote in a new tab)

Limitations of the first-line medication evidence base

“An evidence synthesis such as the network meta-analysis we have done does not overcome the underlying fact that some studies we included were at high or unclear risk of bias, had small sample size, short follow-up time and used IOP, a surrogate outcome to assess treatment effect.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: topical beta-blockers

“Topical beta adrenergic antagonists are commonly prescribed to treat glaucoma and have demonstrated good efficacy and tolerability.” (opens the source at this quote in a new tab)
“Topical beta-blockers may be dosed once or twice daily.” (opens the source at this quote in a new tab)
“Cardioselective beta-blockers (e.g., betaxolol) target beta-1 receptors and minimize, but do not completely eliminate, the risk of pulmonary adverse effects in patients with obstructive airway disease.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: beta-blocker class profile (carteolol, levobunolol, timolol, betaxolol)

Field	Quoted record
Mechanism of action	“Decrease aqueous production”
IOP reduction	“20%–25%”
Potential contraindications	“Chronic obstructive pulmonary disease”; “Asthma”; “CHF”; “Bradycardia”; “Hypotension”

European Glaucoma Society guidelines: relative efficacy and combination use

“The greatest reduction of IOP is obtained with PGAs, followed by non-selective β-blockers, Rh-kinase inhibitors, alpha-adrenergic agonists, selective β-blockers and topical carbonic anhydrase inhibitors.” (opens the source at this quote in a new tab)
“The most frequently used combination is a PGA with a β-blocker.” (opens the source at this quote in a new tab)

NICE NG81: beta-blocker as second choice when prostaglandin analogs are not tolerated

“Offer another pharmacological treatment to people with an IOP of 24 mmHg or more who cannot tolerate their current treatment. The first choice should be an alternative generic PGA, and if this is not tolerated, offer a beta‑blocker.” (opens the source at this quote in a new tab)

Timolol as the active comparator in sustained-release registrational trials

“Both trials are designed to demonstrate noninferiority of the BIM-IOL System to a standard of care commercial IOL plus twice-daily administration of timolol eye drops.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: other classes for long-term IOP reduction

“Other glaucoma medications used to provide long-term IOP reduction include alpha2 adrenergic agonists, parasympathomimetics, rho-kinase inhibitors, and topical and oral carbonic anhydrase inhibitors.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: expected IOP reduction by class

Drug classification (agents)	IOP reduction
Alpha-2 adrenergic agonists (apraclonidine, brimonidine)	“20%–25%”
Parasympathomimetic agents (pilocarpine, echothiophate)	“20%–25%”
Rho kinase inhibitors (netarsudil)	“10%–20%”
Topical carbonic anhydrase inhibitors (brinzolamide, dorzolamide)	“15%–20%”
Oral carbonic anhydrase inhibitors (acetazolamide, methazolamide)	“20%–30%”

Adding medications: incremental IOP reduction

“Addition of a second, third, or fourth glaucoma medication has been shown to result in an incremental reduction in IOP, but the effect is usually smaller than for the first medication.” (opens the source at this quote in a new tab)
“A study evaluating the IOP following a pre-randomization glaucoma medication washout in the HORIZON and COMPASS Trials noted a 24% reduction in IOP with the first medication, whereas each additional drop conferred only about 4% further reduction.” (opens the source at this quote in a new tab)

European Glaucoma Society guidelines: switching and fixed combinations

“If the initial therapy is not effective or the drug is not tolerated, one should switch to another monotherapy (in the same or another class) rather than adding a second drug.” (opens the source at this quote in a new tab)
“Multiple topical treatments may reduce adherence and increase exposure to preservatives. Therefore, fixed combination therapy, when available, is preferable to two separate instillations of agents.” (opens the source at this quote in a new tab)
“Combination therapy is not recommended as first choice treatment.” (opens the source at this quote in a new tab)

NICE NG81: escalation to another therapeutic class

“a medicine from another therapeutic class (a beta-blocker, carbonic anhydrase inhibitor or sympathomimetic); topical medicines from different therapeutic classes may be needed at the same time to control IOP or” (opens the source at this quote in a new tab)
“Latanoprost–netarsudil is recommended as an option in NICE technology appraisal guidance for reducing IOP in adults with primary open-angle glaucoma (COAG) when a PGA alone has not reduced IOP enough, only if they have then tried a fixed-dose combination treatment and it has not reduced IOP enough, or a fixed-dose combination treatment containing beta-blockers is unsuitable.” (opens the source at this quote in a new tab)

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)

AAO Preferred Practice Pattern: initial or adjunctive laser therapy

“Laser trabeculoplasty surgery may be used as initial or adjunctive therapy in patients with POAG.” (opens the source at this quote in a new tab)
“A 2022 Cochrane Systematic Review found that laser trabeculoplasty surgery may be more effective than topical drops in slowing the progression of visual field loss in OAG and may be similar to topical drops in controlling IOP at a lower cost.” (opens the source at this quote in a new tab)
“Several studies have demonstrated that repeat SLT is both safe and effective and that it achieves a similar reduction in IOP and duration of response as the initial treatment.” (opens the source at this quote in a new tab)

European Glaucoma Society guidelines: first-line option

“It is recommended to initiate the treatment for IOP lowering with monotherapy (see Ch II.3.4, Fc XVII, XVIII and XIX). Laser trabeculoplasty is also a good option for first-line treatment (see Ch II.3.12.2).” (opens the source at this quote in a new tab)
“There is no evidence regarding effectiveness of trabeculoplasty in patients with severe glaucoma and pigmentary glaucoma (PG). SLT and argon laser trabeculoplasty (ALT) have similar efficacy and are more effective in people with higher IOP.” (opens the source at this quote in a new tab)

NICE NG81: 360° SLT as initial treatment

“Offer 360° SLT to people with newly diagnosed COAG that is not advanced (excluding cases associated with pigment dispersion syndrome).” (opens the source at this quote in a new tab)
“that having 360° SLT can delay the need for eye drops and can reduce but does not remove the chance they will be needed at all” (opens the source at this quote in a new tab)
“Consider a second 360° SLT for people with COAG if the effect of an initial successful SLT has subsequently reduced over time. [2022]” (opens the source at this quote in a new tab)

LiGHT trial: 3-year results

“Of 718 patients enrolled, 356 were randomised to the selective laser trabeculoplasty and 362 to the eye drops group.” (opens the source at this quote in a new tab)
“At 36 months, 74·2% (95% CI 69·3-78·6) of patients in the selective laser trabeculoplasty group required no drops to maintain intraocular pressure at target.” (opens the source at this quote in a new tab)

LiGHT trial: 6-year results

“Of eyes in the SLT arm, 69.8% remained at or less than the target IOP without the need for medical or surgical treatment. More eyes in the drops arm exhibited disease progression (26.8% vs. 19.6%, respectively; P = 0.006). Trabeculectomy was required in 32 eyes in the drops arm compared with 13 eyes in the SLT arm (P < 0.001); more cataract surgeries occurred in the drops arm (95 compared with 57 eyes; P = 0.03). No serious laser-related adverse events occurred.” (opens the source at this quote in a new tab)

LiGHT: drop-free intraocular pressure control and medication use in both arms at 6 years

“Drop-free IOP control at 72 months, obtained without incisional surgery, was achieved in 69.8% of eyes initially treated with SLT compared with 18.0% of eyes initially treated with IOP-lowering eye drops.” (opens the source at this quote in a new tab)
“At 72 months, 61.2% of eyes initially treated with eye drops were using 1 or 2 medications compared with 18.5% of eyes initially treated with SLT.” (opens the source at this quote in a new tab)
“Of the eyes initially treated with eye drops and being drop free at 72 months, 79.5% of eyes (66 eyes) had switched to SLT, and 20.5% underwent either cataract surgery alone or cataract surgery and SLT.” (opens the source at this quote in a new tab)

LiGHT: eyes at target intraocular pressure and number of laser treatments required

“Overall, 94.2% of eyes initially treated with SLT were at target at 72 months, and target IOP was achieved at 92.8% of visits, compared with 94.7% of eyes and 93.2% of visits for eyes initially treated with medication.” (opens the source at this quote in a new tab)
“Of the eyes initially treated with SLT and being drop and surgery free at 6 years, 90% of eyes (295 eyes) needed up to 2 SLT treatments in total.” (opens the source at this quote in a new tab)

LiGHT: adverse events of selective laser trabeculoplasty over 6 years

“A total of 274 transient SLT-related adverse events were reported, including 10 incidents of a rise in IOP (1.0% of all SLT treatments, with only 1 eye requiring treatment).” (opens the source at this quote in a new tab)
“The safety profile of SLT remains very good, with no sight-threatening complications.” (opens the source at this quote in a new tab)
“Intraocular pressure rose > 5 mmHg from IOP before treatment in only 1% of treated eyes, and of these, only 1 eye needed treatment.” (opens the source at this quote in a new tab)

LiGHT: timing of trabeculectomy during the 6-year trial

“Of the 32 eyes that needed a trabeculectomy during trial’s 6-year duration, 11 eyes initially treated with drops underwent a trabeculectomy during the first 3 years of the trial; none of the eyes initially treated with SLT required a trabeculectomy during the initial 3 years of the trial.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: MIGS compared with traditional surgery

“Traditional glaucoma surgery generally produces greater IOP reduction than MIGS but also has a higher risk of complications.” (opens the source at this quote in a new tab)
“Modest IOP reduction has been reported following MIGS, and postoperative pressures are typically in the mid to upper teens.” (opens the source at this quote in a new tab)
“They are commonly combined with phacoemulsification; some are FDA approved only to be performed concurrently with phacoemulsification.” (opens the source at this quote in a new tab)
“These trials generally enrolled patients with mild to moderate OAG with elevated IOP.” (opens the source at this quote in a new tab)

European Glaucoma Society guidelines: MIGS indications and contraindications

“MIGS tend to have a modest IOP-lowering effect but can reduce the burden of medication, although the latter is not in line with the traditional aim of glaucoma surgery.” (opens the source at this quote in a new tab)
“These techniques mainly aim to reduce the IOP and/or the medication burden in patients with early to moderate open angle glaucoma or OHT.” (opens the source at this quote in a new tab)
“MIGS are not usually indicated for patients with advanced glaucoma, those needing lower target IOPs and those with angle closure.” (opens the source at this quote in a new tab)

Overview of Cochrane reviews of MIGS

“Moderate certainty evidence indicated that adding a Hydrus safely improved the likelihood of drop-free glaucoma control at medium-term (relative risk [RR], 1.6; 95% CI, 1.4 to 1.8) and long-term (RR, 1.6; 95% CI, 1.4 to 1.9) follow-up and conferred 2.0-mm Hg (95% CI, -2.7 to -1.3 mm Hg) greater IOP reduction at long-term follow-up, compared with cataract surgery alone. Adding an iStent also safely improved drop-free disease control compared with cataract surgery alone (RR, 1.4; 95% CI, 1.2 to 1.6), but the short-term IOP-lowering effect of the iStent was not sustained.” (opens the source at this quote in a new tab)

Trabeculectomy: AAO Preferred Practice Pattern

“Trabeculectomy remains the most effective surgical procedure to lower IOP; it is generally indicated when medications and appropriate laser surgery are insufficient to control disease and can be considered in selected cases as initial therapy.” (opens the source at this quote in a new tab)
“Estimates of success rates over time range from 31% to 88% in different populations and with varying definitions of success and failure.” (opens the source at this quote in a new tab)

TAGS: primary trabeculectomy versus medication in advanced glaucoma, 5 years

“The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was -2.56 (95% CI, -3.80 to -1.32; P < 0.001).” (opens the source at this quote in a new tab)
“At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile.” (opens the source at this quote in a new tab)

PTVT: tube shunt versus trabeculectomy, 5 years

“The cumulative probability of failure after 5 years of follow-up was 42% in the tube group and 35% in the trabeculectomy group (P = 0.21; hazard ratio = 1.31; 95% confidence interval = 0.86 to 2.01).” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: options for patients with POAG and visually significant cataract

“If IOP control is at target on one or two medications, cataract surgery alone may be adequate, with the additional benefit that it may lower IOP slightly.” (opens the source at this quote in a new tab)
“Cataract surgery alone consistently produces modest reductions in IOP and glaucoma medical therapy in patients with POAG.” (opens the source at this quote in a new tab)
“Patients with higher preoperative IOP generally experience greater IOP reduction with cataract extraction.” (opens the source at this quote in a new tab)
“Other types of glaucoma surgery can also be combined with cataract surgery, such as implantation of aqueous shunts, nonpenetrating glaucoma surgery, MIGS, and ECP.” (opens the source at this quote in a new tab)

European Glaucoma Society guidelines: mild to moderate glaucoma with cataract

“– IOP at or near target: Phacoemulsification alone or phacoemulsification with MIGS.” (opens the source at this quote in a new tab)
“– IOP significantly above target: Glaucoma intervention should be offered. Bleb-forming surgery with or without phacoemulsification is advisable.” (opens the source at this quote in a new tab)
“Cataract surgery alone is not recommended for controlling glaucoma, although it can modestly but consistently reduce IOP and medications in POAG, with a more pronounced effect in eyes with PXG and higher preoperative IOP values.” (opens the source at this quote in a new tab)

Cataract extraction in the OHTS observation group

“In the cataract group, postoperative IOP was significantly lower than the preoperative IOP (19.8 ± 3.2 mmHg vs. 23.9 ± 3.2 p<0.001). The postoperative IOP remained lower than preoperative IOP for at least 36 months. The average decrease in postoperative IOP from preoperative IOP was 16.5%, and 39.7% of eyes had postoperative IOP ≥ 20% below preoperative IOP.” (opens the source at this quote in a new tab)

HORIZON: Hydrus Microstent with cataract surgery, 5 years

“Three hundred sixty-nine eyes were randomized to HMS treatment, and 187 eyes were randomized to CS only.” (opens the source at this quote in a new tab)
“The number of glaucoma medications was 0.5 ± 0.9 in the HMS group and 0.9 ± 0.9 in the CS group (P < 0.001), and 66% of eyes in the HMS group were medication free compared with 46% in the CS group (P < 0.001).” (opens the source at this quote in a new tab)

iStent inject pivotal trial with cataract surgery, 2 years

“At 24 months, 75.8% of treatment eyes versus 61.9% of control eyes experienced ≥20% reduction from baseline in unmedicated DIOP (P = 0.005), and mean reduction in unmedicated DIOP from baseline was greater in treatment eyes (7.0±4.0 mmHg) than in control eyes (5.4±3.7 mmHg; P < 0.001).” (opens the source at this quote in a new tab)

HORIZON: secondary intraocular pressure-lowering procedures through 5 years

“Twenty-two events occurred in 18 eyes (4.9%) in the HMS group, and 30 events occurred in 14 eyes (7.5%) in the CS group.” (opens the source at this quote in a new tab)
“A finding of particular interest in this study is that, among a cohort of patients with predominantly mild glaucoma that was controlled with 1 or 2 topical medications, a significant proportion needed invasive glaucoma surgery over 5 years, particularly in the CS group.” (opens the source at this quote in a new tab)

HORIZON: medication count from 1 to 5 years after surgery

“From the 1-year to 5-year follow-up, the mean medication count increased by 0.2 in both groups, resulting in no change in the between-group margin over the course of the study.” (opens the source at this quote in a new tab)

HORIZON: visual acuity and visual field adverse findings through 5 years

“After 5 years, cumulative BCVA loss of 2 lines or more was 1.9% in the HMS group and 2.1% in the CS group.” (opens the source at this quote in a new tab)
“A loss of 2.5 dB or more in VF mean deviation was defined as an adverse finding in the protocol.” (opens the source at this quote in a new tab)
“This condition was met in 8.4% of HMS eyes and 9.6% of CS eyes.” (opens the source at this quote in a new tab)

HORIZON: corneal endothelial cell loss through 5 years

“The authors observed an ECL of 13% and 11% in the HMS and CS groups, respectively, at the first postoperative assessment performed at 3 months.” (opens the source at this quote in a new tab)
“Additionally, no shift toward increased ECL was found in years 4 or 5 compared with prior years.” (opens the source at this quote in a new tab)
“None of the eyes with 30% or more ECL in either group had associated corneal edema, decompensation, or other clinical sequelae.” (opens the source at this quote in a new tab)

HORIZON: medication washout schedule and its effect on later pressure comparisons

“The medication washout requirement enabled a direct assessment of the device alone on IOP not confounded by medication use but simultaneously limited the population to patients with mild and moderate severity of disease who could tolerate the washout procedure safely.” (opens the source at this quote in a new tab)
“Additionally, medication washout was not repeated after 2 years; thus, the possibility of medication introduction bias must be considered for later IOP assessments.” (opens the source at this quote in a new tab)

iStent inject pivotal trial: medication burden and drop-free proportion at 23 months

“In the treatment group, the mean number of ocular hypotensive medications was 1.6 (SD, 0.8) preoperatively and 0.4 (SD, 0.8) at 23 months, a mean reduction of 1.2 medications (SD, 1.0; P < 0.001).” (opens the source at this quote in a new tab)
“In this study, 84% of treatment eyes meeting the primary study end point were not taking ocular hypotensive medications at 23 months, compared with 67% of control eyes.” (opens the source at this quote in a new tab)

iStent inject pivotal trial: washout design and medication-free proportions at 6 and 12 months

“At the month 11 and 23 visits, subjects using ocular hypotensive medication(s) were instructed to undergo medication washout to permit unmedicated DIOP assessment at months 12 and 24, respectively.” (opens the source at this quote in a new tab)
“Eyes with secondary surgical interventions to lower IOP or other events (including loss of light perception or hypotony (IOP <6 mmHg) associated with clinically significant findings) were considered nonresponders.” (opens the source at this quote in a new tab)
“At 6 months, 81.4% of treatment subjects versus 64.1% required no additional medications or surgeries; in these subjects, mean IOP reduction was 9.2 mmHg in the treatment group and 8.2 mmHg in the control group.” (opens the source at this quote in a new tab)

iStent inject pivotal trial: intraocular pressure in medication-free eyes from 6 to 24 months

“Among medication-free eyes, the mean observed IOP from 6 to 24 months ranged from 15.4 to 17.1 mmHg for the treatment group and 15.8 to 17.8 mmHg for the control group.” (opens the source at this quote in a new tab)

iStent inject pivotal trial: visual field and cup-to-disc stability through 24 months

“Visual field MD was stable over time (mean change close to zero) from screening to 24 months in both groups.” (opens the source at this quote in a new tab)
“Mean C:D ratio also was stable over time from screening to month 24 in both groups.” (opens the source at this quote in a new tab)

iStent inject pivotal trial: endothelial cell loss through 24 months

“There was little difference in endothelial cell loss (ECL) between the treatment and control groups.” (opens the source at this quote in a new tab)
“The percentage of eyes with an ECL >30% at the 24-month visit was similar between the 2 groups (10.4% in the iStent inject group vs. 9.5% in the control group).” (opens the source at this quote in a new tab)
“In both study groups, the most substantial decline in ECD occurred within the first 3 months postoperatively (12.5% in the iStent inject group and 11.6% in the control group), and the rate of decline was minimal thereafter.” (opens the source at this quote in a new tab)

Visual field progression after cataract surgery with a microstent compared with cataract surgery alone

“In the HORIZON trial, the rate of VF progression was significantly slower in eyes that received cataract surgery in combination with the Hydrus microstent compared with the control group receiving only cataract surgery, despite similar medicated IOP in both arms.” (opens the source at this quote in a new tab)

Summary

Topical therapy depends on daily self-administration. A 2025 meta-analysis of 47 studies (961,000 patients) estimated that 44% of patients on prostaglandin analogs were adherent at year 1 and that persistence fell from 75% at month 6 to 31% at year 3; in a claims cohort of 3,623 patients with diagnosed glaucoma and 1,677 suspects, nearly one half discontinued all topical therapy within 6 months. The AAO guideline cites a study in which nearly 45% of patients took fewer than 75% of prescribed doses despite free medication, dosing aids, and electronic monitoring. In the CIGTS medication arm (307 participants), predicted 8-year mean deviation loss was 0.62 dB with no reported missed doses and 2.23 dB with missed doses at two thirds of visits. Drop instillation is frequently incorrect: 6 of 70 patients (8.57%) instilled drops correctly in one study, and 33.8% of 500 Canadian patients demonstrated improper technique. Ocular surface disease symptoms were reported by 305 of 630 patients (48.4%) using topical therapy, with higher scores as the number of medications increased. Among procedural alternatives, SLT effect may wane and require repetition, MIGS are indicated mainly for mild to moderate disease and are performed routinely by about one third of US cataract surgeons (company estimate), incisional surgery carries higher complication risk, and approved intracameral implants carry corneal endothelial cell loss warnings and administration limits.

Adherence and persistence with prostaglandin analogs: systematic review and meta-analysis

“The SLR included 50 publications reporting on 47 unique studies and involving 961,000 patients.” (opens the source at this quote in a new tab)
“The mean proportion of patients on any/unspecified PGA who were adherent at Year 1 was 44% (95% CI: 31%-58%).” (opens the source at this quote in a new tab)
“The mean proportion of patients on any/unspecified PGA who were persistent fell from 75% (95% CI: 66%-85%) at Month 6 to 31% (95% CI: 12%-55%) at Year 3” (opens the source at this quote in a new tab)

Persistence with topical therapy: US claims cohort

“Nearly one half of the individuals who had filled a glaucoma prescription discontinued all topical ocular hypotensive therapy within six months, and just 37% of these individuals recently had refilled their initial medication at three years after the first dispensing.” (opens the source at this quote in a new tab)

Adherence measured by pharmacy claims: GAPS

“The mean medication possession ratio (MPR) was 0.64 (median 0.57) for the 13,956 subjects. Although 59% potentially had an ocular hypotensive agent at 12 months, only 10% had such medication available continuously.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: adherence and instillation barriers

“Adequate treatment of glaucoma requires a high level of adherence to therapy. Frequently this is not achieved, and studies indicate relatively poor adherence to therapy.” (opens the source at this quote in a new tab)
“Even with instruction, free medication, once-daily administration, use of a dosing aid, and electronic monitoring of adherence, nearly 45% of patients in one study took fewer than 75% of their prescribed doses.” (opens the source at this quote in a new tab)
“Instilling eye drops correctly is difficult for many patients, and their ability to instill them may worsen with aging and comorbidities and as glaucoma progresses.” (opens the source at this quote in a new tab)

Nonadherence and visual field loss: CIGTS medication arm

“Worse medication adherence was associated with loss of MD over time (p=0.005). For subjects who reported never missing a dose of medication, the average predicted MD loss over 8 years was 0.62 dB, consistent with age-related loss (95% confidence interval, CI=0.17−1.06; p=0.007); subjects reporting missing medication doses at 1/3 of visits had a loss of 1.42 dB (CI, 0.86−1.98; p<0.0001); subjects reporting missing medication doses at 2/3 of visits had a loss of 2.23 dB (CI, 1.19−3.26; p<0.0001).” (opens the source at this quote in a new tab)

Pharmacy refill adherence, IOP, and structural and functional progression

“A total of 13 670 eyes from 8163 patients were included with a median (interquartile range) PDC of 60 (40.9-77.5). Below the 60% adherence threshold (median), each 10% decrease in PDC was associated with higher mean IOP (β = 0.82 mmHg, P < 0.001)” (opens the source at this quote in a new tab)

Barriers to adherence: cross-sectional survey

“27% of the sample reported poor adherence.” (opens the source at this quote in a new tab)
“Logistic regression analysis, adjusted for age, revealed that the following barriers were associated with higher odds of non-adherence: decreased self-efficacy, OR = 4.7 [95% CI 2.2–9.7, p= < 0.0001]; difficulty instilling drops, OR = 2.3 [95% CI 1.1–4.9, p= 0.03]; forgetfulness, OR = 5.6 [95% CI 2.6–12.1, p= < 0.0001]; and difficulties with the medication schedule, OR = 2.9 [1.4–6.0, p= 0.006].” (opens the source at this quote in a new tab)

Drop instillation errors

“Only 6 patients (8.57%) were able to correctly instill the eye drops (squeeze out 1 drop and instill it into the conjunctival sac without bottle tip contact).” (opens the source at this quote in a new tab)
“Nearly, 9 of 10 glaucoma patients were unable to instill eye drops correctly.” (opens the source at this quote in a new tab)

“500 patients from 10 centers across Canada participated in the study.” (opens the source at this quote in a new tab)
“With regard to drop administration, 6.8% missed their eye and 28.8% contaminated the bottle tip; overall, 33.8% demonstrated improper technique.” (opens the source at this quote in a new tab)

Ocular surface disease with topical therapy

“Overall, 630 patients from 10 sites participated. Of these, 305 patients (48.4%) had an OSDI score indicating either mild (n = 134, 21.3%), moderate (n = 84, 13.3%), or severe (n = 87, 13.8%) OSD symptoms.” (opens the source at this quote in a new tab)
“The severity of OSD symptoms is positively correlated to the number of IOP-lowering medications used.” (opens the source at this quote in a new tab)

“Using Ocular Surface Disease Index for measuring symptoms of dry eye, 60 (59%) patients reported symptoms in at least 1 eye.” (opens the source at this quote in a new tab)
“After adjustment for age and sex, each additional BAK-containing eyedrop was associated with an approximately 2 times higher odds of showing abnormal results on the lissamine green staining test (odds ratio=2.03; 95% confidence interval: 1.06 to 3.89; P=0.034).” (opens the source at this quote in a new tab)

European Glaucoma Society guidelines: preservatives and ocular surface disease

“Preserved topical glaucoma medications may cause and/or exacerbate pre-existing ocular surface disease (OSD), such as dry eye and meibomian gland dysfunction, which have a high prevalence in elderly adults.” (opens the source at this quote in a new tab)
“A possible unwanted effect of long-term BAC use is a reduction in the success rate of filtering surgery.” (opens the source at this quote in a new tab)

Procedural limitations: MIGS uptake and intracameral implants (manufacturer perspective)

“As a result, approximately two-thirds of cataract surgeons in the United States do not perform MIGS procedures routinely despite an estimated 20% of their cataract patients having glaucoma or OHT” (opens the source at this quote in a new tab)
“These implants are placed near the cornea and iris, which can result in corneal endothelial cell loss, inflammation, or other complications.” (opens the source at this quote in a new tab)

Laser trabeculoplasty: waning effect and IOP spikes

“For eyes that have failed to maintain a previously adequate response, repeat ALT has a low long-term rate of success, with failure occurring in nearly 90% of these eyes by 2 years.” (opens the source at this quote in a new tab)
“Intraocular pressure spikes have been noted after SLT in 4.5% to 27% of eyes in various studies” (opens the source at this quote in a new tab)

“that a second 360° SLT procedure may be needed at a later date. [2022]” (opens the source at this quote in a new tab)

Traditional incisional surgery: complication risk

“Traditional glaucoma surgery generally produces greater IOP reduction than MIGS but also has a higher risk of complications.” (opens the source at this quote in a new tab)

Medication possession ratio on prostaglandin analogs relative to the threshold for good adherence

“The mean MPR/PDC of 54% at Year 1 in this review was similar to that reported in Reardon et al (mean MPR/PDC: 56%).” (opens the source at this quote in a new tab)
“Both values (54% and 56%) were below the 80% threshold for good adherence” (opens the source at this quote in a new tab)

Definition of persistence and pattern of decline, including by individual prostaglandin analog

“In the measurement of persistence, persistent patients were defined as those who did not switch or discontinue their therapies, with an allowable refill gap of up to 90 days. Duration of therapy was defined as the period between initial therapy prescription and therapy discontinuation or switch.” (opens the source at this quote in a new tab)
“The estimated persistence rates over time for patients on PGAs in our MA suggest that in real-world settings, persistence among patients initiating PGA monotherapy is likely to substantially decline within three years, with the fastest rates of discontinuation occurring in the first 6 to 12 months.” (opens the source at this quote in a new tab)
“Patients on latanoprost were more likely to be persistent at each of the timepoints analyzed compared with patients on travoprost or bimatoprost.” (opens the source at this quote in a new tab)
“However, the CIs of the persistence rates of patients on travoprost, bimatoprost and latanoprost in this review overlapped substantially, suggesting that differences between the individual PGAs were not statistically or clinically significant.” (opens the source at this quote in a new tab)

Agreement between self-reported adherence and electronically monitored adherence

“Two studies evaluated differences between patient-reported adherence (using the MMAS) and adherence as measured using electronic dose monitoring devices, with both studies reporting low agreement between them. Patients tended to report themselves as more adherent than the objective measures recorded.” (opens the source at this quote in a new tab)

Adherence at three years by drug class in a United States claims cohort

“A total of 3623 patients with diagnosed glaucoma and 1677 patients with suspect glaucoma filled at least one prescription for topical ocular hypotensive agents.” (opens the source at this quote in a new tab)
“With a definition for adherence that allows individuals to intermittently refill prescriptions (which means medications are taken substantially less than prescribed), only 37% of patients had refilled their initially prescribed medication within 60 to 120 days at 3 years after their initial dispensing. Adherence estimates at 3 years ranged from 15% to 58%, depending on drug class.” (opens the source at this quote in a new tab)

Direction of bias in claims-based persistence estimates

“We have assumed a liberal duration for each dispensing on the basis of bottle sizes. It is likely therefore that even the very low estimates of persistence and adherence that we found were overestimations of the true levels.” (opens the source at this quote in a new tab)
“Successful glaucoma surgery or laser treatment may have obviated the need for further topical therapy in some patients, but the occurrence of such treatments was rare in this population (approximately 5% had surgery or laser treatment at any time during the follow-up period) and cannot account for the low persistence estimates that we have observed.” (opens the source at this quote in a new tab)

One-year refill patterns: gaps, restarts, switches, and discontinuation

“Among 10,260 subjects who were followed up for at least 1 year after the index prescription, to measure persistency as a function of gaps between refills, 10% used the originally prescribed prostaglandin without any gaps in refilling the prescription, 8% as monotherapy, and 2% with a second drug added to their regimen.” (opens the source at this quote in a new tab)
“Sixteen percent switched from the index drug to another drug, and 20% discontinued all glaucoma medications without adding, switching, or restarting.” (opens the source at this quote in a new tab)
“More than 55% of the patients who had at least 1 year of follow-up, failed to continuously refill their initial medications for a period and later restarted it.” (opens the source at this quote in a new tab)
“In this study, a survival analysis would have identified 90% as failing to refill medications continuously over the study period.” (opens the source at this quote in a new tab)

Effect of free samples on measured adherence

“One fifth of subjects (20%) reported receiving samples on a regular basis, 57% received samples one or two times, and 23% reported never receiving samples. The mean MPRs for these three groups were 0.62, 0.64, and 0.76, respectively” (opens the source at this quote in a new tab)

Prevalence of noncompliance and of combined noncompliance or improper technique

“Of these, 25.6% reported missing at least 1 drop of medication per week, and 4.2% were unable to accurately describe their medication regimen. The overall proportion of noncompliance was 27.9%.” (opens the source at this quote in a new tab)
“Over 50% of the patients surveyed were either noncompliant or demonstrated improper administration technique.” (opens the source at this quote in a new tab)

Observed instillation technique and waiting interval between medications

“Four hundred and seventy-three patients demonstrated their eye drop administration technique. Of those, 365 (77.2%) were judged to be “on target,” 76 (16.1%) were “awkward,” and 32 (6.8%) “missed the eye,” while 136 (28.8%) patients contaminated the bottle tip.” (opens the source at this quote in a new tab)
“In addition, of the 296 patients who required more than 1 type of medication in the same eye, 26 (8.8%; 95% CI 5.8%–12.6%) reported waiting less than 3 minutes between administrations.” (opens the source at this quote in a new tab)

Reasons for missed doses and receipt of instillation instruction

““Forgetfulness” (35.4%) and “being away from drops” (31.1%) were the most common reasons indicated.” (opens the source at this quote in a new tab)
“In our current study only 19.1% of patients had received instructions on ophthalmic medication administration from their pharmacist” (opens the source at this quote in a new tab)

Summary

The BIM-IOL System is investigational and has no guideline-defined place in therapy. Its studied use is a single implantation during routine cataract surgery, placed in the capsular bag, in adults with mild to moderate OAG or OHT and a concomitant cataract. The phase 3 trials SGP-005 (Rhine) and SGP-006 (Rhone), each planned for about 400 participants, enroll patients taking up to two IOP-lowering medications and compare the 78 mcg system with a commercial monofocal IOL plus twice-daily timolol. Guidelines currently offer patients with glaucoma and cataract whose IOP is at or near target on one or two medications cataract surgery alone or cataract surgery with MIGS; the BIM-IOL System would be an additional option in this setting, and the manufacturer positions it for surgeons who do not perform angle-based MIGS. The AAO guideline states that sustained medication delivery methods may be better options for patients who find drop administration very difficult. The manufacturer designs the pads to deliver bimatoprost for about 3 years; retreatment would require the separate investigational BIM-DRS. Cataract surgery in the United States is performed mainly in ambulatory surgery centers (manufacturer estimate about 90%), and a Category III add-on CPT code was approved in May 2026 for use with cataract surgery codes. The manufacturer estimates about one million US cataract surgeries per year in patients with glaucoma or OHT. Cataract surgery alone lowered IOP by 16.5% in the OHTS observation group, and no comparison of the BIM-IOL System with cataract surgery alone or with MIGS combined with cataract surgery is available.

Anticipated use: implantation during routine cataract surgery

“Our lead product candidate, the BIM-IOL System, is being developed for the reduction of IOP in patients with OAG or OHT who are undergoing cataract surgery.” (opens the source at this quote in a new tab)
“The BIM-IOL System is designed to address key limitations of current glaucoma care by enabling all cataract surgeons, not just those trained in MIGS, to treat elevated IOP when performing their routine cataract procedures, thereby reducing the reliance on patient adherence to topical medications in managing IOP.” (opens the source at this quote in a new tab)
“We believe the BIM-IOL System could redefine the current standard of care for OAG and OHT patients undergoing cataract surgery.” (opens the source at this quote in a new tab)

Studied population: phase 3 registrational trials

“Each prospective, multicenter, randomized, masked, controlled Phase 3 clinical trial evaluates the safety and efficacy of the BIM-IOL System (78 mcg) in patients with OAG or OHT and a concomitant cataract, who are taking up to two IOP-lowering medications.” (opens the source at this quote in a new tab)
“Each trial is expected to enroll approximately 400 patients across 45 clinical sites.” (opens the source at this quote in a new tab)

Studied population: registry eligibility for the Rhine trial

Field	Quoted record
Inclusion	“Diagnosis of mild to moderate open-angle glaucoma or ocular hypertension”; “Planned removal of cataract”
Exclusion	“Any glaucoma diagnosis other than OHT, open-angle, pseudoexfoliative, or pigmentary glaucoma”; “History of incisional glaucoma surgery or intraocular injections”; “History of incisional/refractive corneal surgery”
Planned enrollment	“400”

Duration of therapy and retreatment pathway

“The BIM-IOL System is designed for long-acting, sustained delivery of bimatoprost over three years, which we believe can reduce or eliminate the need for daily topical medications.” (opens the source at this quote in a new tab)
“The BIM-DRS is designed to consistently deliver at least three years of bimatoprost and is intended to provide IOP-lowering therapy beyond the initial three-year duration that we are targeting with the BIM-IOL System.” (opens the source at this quote in a new tab)

Guideline setting for combined treatment at cataract surgery

“Q7. What is the recommended approach for patients with early or moderate open-angle glaucoma and visually significant cataracts?” (opens the source at this quote in a new tab)
“– IOP at or near target: Phacoemulsification alone or phacoemulsification with MIGS.” (opens the source at this quote in a new tab)

Patients with difficulty administering drops

“Drop administration may be exceedingly difficult for some patients, and laser trabeculoplasty surgery, sustained medication delivery methods, or other surgery may be better options for these patients.” (opens the source at this quote in a new tab)

Angle-sparing placement and compatibility with later procedures

“First, the implantation of the system is highly accessible to all surgeons who routinely perform CEIOL procedures. Second, it leaves the angle untouched, allowing for concurrent or subsequent gonioscopic intervention, or subsequent selective laser trabeculoplasty. Third, the positioning of the system within the capsular bag may limit mechanical injury to the corneal endothelium.” (opens the source at this quote in a new tab)

Care setting and reimbursement pathway

“We believe this presents an opportunity for providers and facilities, including ASCs, where approximately 90% of cataract surgeries in the United States are performed” (opens the source at this quote in a new tab)
“We believe that the IOP-lowering element of our lead product candidate will be classified as a physician-administered drug, which are typically reimbursed at the ASP plus 6%.” (opens the source at this quote in a new tab)

“In May 2026, the American Medical Association’s CPT® (Current Procedural Terminology) Editorial Panel approved a new add-on Category III CPT code (+1090T released to AMA website on July 1, 2026) in combination with established Category I CPT codes, such as 66984 and 66991.” (opens the source at this quote in a new tab)

Anticipated population size (manufacturer estimate)

“We remain deeply focused on delivering long-term, eye drop-free therapy for the approximately one million glaucoma and ocular hypertension patients who undergo cataract surgery in the United States each year.” (opens the source at this quote in a new tab)

BIM-IOL System first-in-human study: no difference across 3 dose arms

“Each treatment arm realized mean IOP reductions from 32.3% to 49.3% over 3 years of follow-up visits. There were no significant intergroup differences.” (opens the source at this quote in a new tab)
“Outcomes were not significantly different between low, medium, and high concentrations of sustained release bimatoprost. One may hypothesize that higher doses would correlate with more substantive IOP-lowering. However, this did not necessarily hold true in the current sample; the greatest IOP reduction from baseline to month 36 was achieved in the 75 μg cohort.” (opens the source at this quote in a new tab)

BIM-IOL System first-in-human study: limits on generalizability to nonresponders and other populations

“All subjects were required to have previously responded to topical prostaglandin analogues. This criterion selected for eyes that would be more likely to benefit from the bimatoprost implant, possibly inflating efficacy metrics. Generalizability to nonresponders is thus limited.” (opens the source at this quote in a new tab)
“The single-site design with a sample comprised entirely of white Latino patients with POAG further limits generalizability to wider populations.” (opens the source at this quote in a new tab)
“Most subjects required only a single glaucoma medication prior to washout; as such, it is less clear how this product would perform for more recalcitrant glaucomas.” (opens the source at this quote in a new tab)

BIM-IOL System phase 1/2 trial: results by dose group at 12 months

“Evaluable patients achieved a 34% and 42% reduction in mean IOP from baseline in the 78-mcg and 39-mcg dose groups, respectively, compared to a 35% reduction in the control group at 8 a.m. Results were similar at the 10 a.m. timepoint.” (opens the source at this quote in a new tab)
“98% of evaluable patients (48 of 49) in the 78-mcg dose group and 96% of evaluable patients (22 of 23) in the 39-mcg dose group were free from all topical IOP-lowering medications.” (opens the source at this quote in a new tab)

Effect of baseline IOP on response to IOP-lowering treatment

“IOP-lowering treatment efficacy depends on untreated IOP, with larger reductions in patients with higher untreated IOP levels.” (opens the source at this quote in a new tab)

“A greater reduction in postoperative IOP occurred in the eyes with the highest preoperative IOP.” (opens the source at this quote in a new tab)

Variation in optic nerve susceptibility and target IOP

“Individuals differ in the susceptibility of their optic nerves to IOP-related damage. A reasonable initial treatment goal in a patient with POAG is to reduce IOP 20% to 30% below baseline and to adjust up or down as indicated by disease course and severity.” (opens the source at this quote in a new tab)

EMGT: treatment effect across subgroups and baseline predictors of progression

“Treatment effects were also evident when stratifying patients by median IOP, mean deviation, and age as well as exfoliation status.” (opens the source at this quote in a new tab)

“Predictive baseline factors were higher intraocular pressure (IOP) (ie, the higher the baseline IOP, the higher the risk), exfoliation, and having both eyes eligible (each of the latter 2 factors doubled the risk), as well as worse mean deviation and older age.” (opens the source at this quote in a new tab)

AGIS: outcome of surgical sequence differed by race

“Surgical outcome varied by race. Black patients did better with laser trabeculoplasty surgery first (30% IOP reduction), whereas White patients did better with trabeculectomy first (48% IOP reduction).” (opens the source at this quote in a new tab)

LiGHT: visual field benefit of first-line SLT by severity

“When stratified by severity, this difference was significant only in mild OAG (P = 0.035, the largest sub-group).” (opens the source at this quote in a new tab)

SLT responsiveness: features of nonresponsive eyes

“A subset of 27 eyes (15.0%) was identified as potentially nonresponsive and found distinctive with older age (mean [SD], 54.1 [12.5] years vs 44.2 [14.2] years; difference, 10.5 years; 95% CI, 2.9 to 18.1; P = .009), higher proportion of female participants (difference, 27.5%; 95% CI, 3.6 to 51.5; P = .03), and lower baseline IOP (difference, -3.2 mm Hg; 95% CI, -5.2 to -1.3; P = .001).” (opens the source at this quote in a new tab)

Subgroup efficacy results for the BIM-IOL System by race, disease severity, glaucoma subtype, or baseline IOP

No evidence found.

Medication-free rate after combined surgery varies with preoperative medication count

“Eyes requiring only a single medication for pressure control before surgery reached a higher rate of drop-free IOP control than eyes receiving multiple drops.” (opens the source at this quote in a new tab)
“Even among eyes receiving maximum preoperative medical therapy (3 or 4 classes of medications), 59% were receiving fewer medications at 5 years, and 48% were completely medication free in the HMS group.” (opens the source at this quote in a new tab)

LiGHT: proportional visual field benefit across baseline severity groups

“This difference was also proportionally similar across the different severity subgroups (∼30% slower in the SLT-first arm) but was only statistically significant for mild OAGs.” (opens the source at this quote in a new tab)

LiGHT: severity mix of the trial population

“The LiGHT Trial population consisted of a large proportion of eyes with OHT and mild OAG for which IOP reduction targets are less stringent than those for more advanced disease.” (opens the source at this quote in a new tab)

UKGTS: severity range and representativeness of the study population

“Furthermore, individuals with advanced open-angle glaucoma were excluded so that the results of the trial only apply to patients with mild to moderate glaucoma.” (opens the source at this quote in a new tab)
“Because consecutive new patients were assessed and recruited for the UKGTS trial, the population studied was representative of the target population considered for treatment and on which the trial results will be applied.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: consensus follow-up intervals

Target IOP achieved	Progression of damage	Duration of control (months)	Follow-up interval, mild-moderate (months)	Follow-up interval, severe (months)
“Yes”	“No”	“≤6”	“3–6”	“3–4”
“Yes”	“No”	“>6”	“6–12”	“3–6”
“Yes”	“Yes”	“NA”	“1–3”	“1–2”
“No”	“Yes”	“NA”	“1–2”	“1–2”
“No”	“No”	“NA”	“1–6”	“1–3”

AAO Preferred Practice Pattern: adherence assessment and education at each visit

“Adherence to medical therapy should be assessed and addressed at each visit (see Medical Management section for more details).” (opens the source at this quote in a new tab)
“Ophthalmologists or trained staff should consider providing instructions to patients, and companions if applicable, on drop administration techniques and having patients demonstrate their preferred technique in the office.” (opens the source at this quote in a new tab)
“Thus, adherence interventions are left to the judgment of the treating ophthalmologist. (I-, Moderate Quality, Discretionary Recommendation)” (opens the source at this quote in a new tab)

European Glaucoma Society guidelines: identifying and improving nonadherence

“Clinicians are unable to detect non-adherence unless such information is volunteered by patients.” (opens the source at this quote in a new tab)
“Adherence may be improved by simplifying the drop regimen, with patient education, by improving communication and setting alarms/messages.” (opens the source at this quote in a new tab)
“– Always evaluate adherence to treatment and monitoring schedule.” (opens the source at this quote in a new tab)

NICE NG81: instillation technique and adherence checks

“Demonstrate correct eye drop installation technique and observe the patient using the technique when eye drops are first prescribed. [2022]” (opens the source at this quote in a new tab)
“Ask about adherence to treatment and check the eye drop instillation technique in people with COAG whose IOP has not been reduced sufficiently to prevent the risk of progression to sight loss, despite pharmacological treatment with a generic PGA. [2009, amended 2022]” (opens the source at this quote in a new tab)

SEE program: personalized glaucoma coaching randomized trial

“Of 236 participants enrolled (108 in UM and 128 in HFHS), 235 (mean [SD] age, 67.3 [10.9] years; 124 [53%] female) were randomized to the SEE intervention (n = 117) or control (n = 118).” (opens the source at this quote in a new tab)
“Medication adherence was significantly better in the SEE intervention group compared with that among control participants (mean [SD], 77.6% [19.7%]; n = 113 vs 58.0% [25.2%]; n = 114; difference, 19.7%; 95% CI, 13.7 to 25.6; P < .001), and more achieved 80% or greater adherence (62 of 113 [54.9%] vs 27 of 114 [23.7%]; P < .001).” (opens the source at this quote in a new tab)

Cochrane review of multifaceted behavioral adherence interventions

“We included 17 RCTs that enrolled 4536 participants, ranging from 64 to 1800 per study.” (opens the source at this quote in a new tab)

Corneal endothelial monitoring for intracameral implants

“Perform specular microscopy to evaluate the corneal endothelium and establish pre-implantation baseline corneal endothelial cell density prior to the initial administration of iDose TR and prior to each readministration” (opens the source at this quote in a new tab)

Perioperative responsibilities after glaucoma surgery

“Perform follow-up evaluations as indicated based on the procedure and specific clinical scenario to evaluate visual acuity, IOP, the status of the anterior segment and posterior segments” (opens the source at this quote in a new tab)

Referral and multidisciplinary support

“If the diagnosis or management of POAG is in question, or if the condition is refractory to treatment, consultation with or referral to an ophthalmologist with special training or experience in managing glaucoma should be considered. Patients with glaucoma can be referred for and encouraged to use appropriate vision rehabilitation, social services, and counseling.” (opens the source at this quote in a new tab)

Care management programs specific to the BIM-IOL System

No evidence found.

Absence of a specular microscopy monitoring requirement for the bimatoprost implant

“Because of the large safety margin with a single implant, there is no regulatory requirement of specular microscopy monitoring in the bimatoprost implant prescribing information. Use of bimatoprost implant with multiple administrations would be off-label at the time of publication, and this is currently not recommended.” (opens the source at this quote in a new tab)

Summary

The goal of IOP-lowering therapy is to keep IOP within a target range that preserves optic nerve and visual field status and vision-related quality of life. The AAO guideline sets a reasonable initial goal of a 20% to 30% IOP reduction from baseline; the EGS guideline suggests at least 20% reduction (IOP 18 to 20 mmHg) in early glaucoma and at least 30% (15 to 17 mmHg) in moderate glaucoma. Randomized trials link IOP lowering to slower disease progression: in OHTS (1,636 participants), a 22.5% IOP reduction lowered 5-year conversion to POAG from 9.5% to 4.4% (hazard ratio 0.40); in EMGT (255 participants), a 25% reduction lowered progression from 62% to 45%, with about 10% lower progression risk per mmHg of initial reduction; in UKGTS (516 participants), latanoprost prolonged visual field preservation versus placebo (hazard ratio 0.44); and in AGIS, eyes with IOP below 18 mmHg at all visits had mean visual field change close to zero. For the BIM-IOL System, the phase 3 co-primary endpoints are time-matched mean IOP change from baseline through month 3 and best-corrected distance visual acuity of 20/40 or better. Reported company outcomes are a 34% mean IOP reduction with 98% of evaluable participants free of topical medication at 12 months (78 mcg, phase 1/2) and a 37% mean reduction with 95% drop-free at 36 months (first-in-human, 21 evaluable participants). Visual field preservation has not been reported for the BIM-IOL System.

AAO Preferred Practice Pattern: management goals and target IOP

“The goals of managing patients with POAG are as follows:” (opens the source at this quote in a new tab)
“Control of IOP in the target range” (opens the source at this quote in a new tab)
“Stable optic nerve/circumpapillary RNFL status” (opens the source at this quote in a new tab)
“Stable visual fields” (opens the source at this quote in a new tab)
“Lowering the pretreatment IOP by 25% or more has been shown to slow the progression of POAG.” (opens the source at this quote in a new tab)

European Glaucoma Society guidelines: setting the target IOP

“In early glaucoma, an IOP of 18 to 20 mmHg with a reduction from baseline of at least 20% may be sufficient. In moderate glaucoma, an IOP of 15 to 17 mmHg with a reduction of at least 30% may be required. Lower Target IOP, e.g., 8 to 12 mmHg may be needed in more advanced disease.” (opens the source at this quote in a new tab)
“The goal of glaucoma management is to promote the best possible well-being and quality of life with minimal visual disability caused by glaucoma, within a sustainable health care system. The only approach proven to be effective in preserving visual function is lowering IOP.” (opens the source at this quote in a new tab)

OHTS: prevention of conversion from ocular hypertension to POAG

“During the course of the study, the mean +/- SD reduction in IOP in the medication group was 22.5% +/- 9.9%. The IOP declined by 4.0% +/- 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001).” (opens the source at this quote in a new tab)

EMGT: IOP reduction and glaucoma progression

“On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) (P =.007) and occurred significantly later in treated patients.” (opens the source at this quote in a new tab)

“In multivariate analyses, progression risk was halved by treatment (HR = 0.50; 95% CI, 0.35-0.71).” (opens the source at this quote in a new tab)
“Progression risk decreased by about 10% with each millimeter of mercury of IOP reduction from baseline to the first follow-up visit (HR = 0.90 per millimeter of mercury decrease; 95% CI, 0.86-0.94).” (opens the source at this quote in a new tab)

EMGT long-term follow-up: immediate versus delayed treatment

“At study end, percentages of eyes with VI or blindness were slightly higher in the treated group than in the untreated control group, 12.1% vs 11.0%, and 9.4.% vs 6.1% respectively, as were subjects with VI in at least one eye, 19.5% vs 18.7%. The differences were not statistically significant, nor were cumulative incidences of VI in at least one eye.” (opens the source at this quote in a new tab)

UKGTS: visual field preservation over 24 months

“Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003).” (opens the source at this quote in a new tab)

AGIS: sustained low IOP and visual field stability

“In the Associative Analysis, eyes with 100% of visits with intraocular pressure less than 18 mm Hg over 6 years had mean changes from baseline in visual field defect score close to zero during follow-up, whereas eyes with less than 50% of visits with intraocular pressure less than 18 mm Hg had an estimated worsening over follow-up of 0.63 units of visual field defect score (P =.083).” (opens the source at this quote in a new tab)

LiGHT: 6-year rate of visual field progression with first-line SLT versus drops

“The mean [95% credible interval] MD rate was -0.37 [-0.43 to -0.31] decibels (dB)/year in the drops-first arm and -0.26 [-0.31 to -0.21] dB/year in the SLT-first arm (P = 0.007).” (opens the source at this quote in a new tab)

BIM-IOL System phase 3 endpoints

“The co-primary endpoints are (1) the time-matched mean IOP change from baseline at 8 and 10 a.m. at two and six weeks and three months and (2) BCDVA of 20/40 or better at 12 months. Secondary outcome measures will also be evaluated, including mean IOP, time to postoperative introduction of IOP-lowering medications, and number of IOP-lowering medications introduced postoperatively. Participants will be followed through 36 months, allowing us to compare long-term safety, efficacy, and durability.” (opens the source at this quote in a new tab)

BIM-IOL System reported outcomes to date

“In our FIH trial, evaluable patients who received the BIM-IOL System achieved a mean IOP reduction of 37% compared to baseline, 95% of evaluable patients were off all topical IOP-lowering eye drops, and 100% of evaluable patients achieved 20/30 or better corrected visual acuity, in each case at 36 months.” (opens the source at this quote in a new tab)
“100% of evaluable patients achieved an IOP reduction of more than 20% from baseline and 90.5% (19/21) of evaluable patients maintained an IOP ≤18 mmHg through 36 months.” (opens the source at this quote in a new tab)

“For SpyGlass Pharma’s intended commercial dose of 78-mcg, patients receiving the BIM-IOL System achieved robust clinical improvement:” (opens the source at this quote in a new tab)
“A mean, time-matched IOP reduction from baseline of 34%.” (opens the source at this quote in a new tab)
“98% of evaluable BIM-IOL patients were free from all topical IOP-lowering medications.” (opens the source at this quote in a new tab)

Visual field outcomes with the BIM-IOL System

No evidence found.

Target intraocular pressure and the proportion of visits at which it was met in the Ocular Hypertension Treatment Study

“Participants randomized to medication began treatment to achieve a target IOP of 24 mm Hg or less and a minimum 20% reduction in IOP from the average of the qualifying IOP and IOP at the baseline randomization visit, except that an IOP of less than 18 mm Hg was not required.” (opens the source at this quote in a new tab)
“The IOP goal was met in both eyes at 87% (7515 of 8621) and in one eye at 7% (613 of 8621) of the scheduled follow-up visits completed by medication participants.” (opens the source at this quote in a new tab)

Visual field change per millimeter of mercury of intraocular pressure during early follow-up

“In the adjusted model 2 for all visits there is a predicted worsening in visual field defect score of 0.10 from baseline for each 1 mm Hg increase in average intraocular pressure, a finding that is statistically significant” (opens the source at this quote in a new tab)
“For example, an eye with intraocular pressure greater than 18 mm Hg at seven or more of twelve 6-month visits can expect, on average, a worsening of visual field defect score at 84 months that is approximately two units greater than an eye with intraocular pressure less than 18 mm Hg at each of these twelve 6-month visits” (opens the source at this quote in a new tab)
“A limitation of the present study and of previous studies of the association between intraocular pressure reduction and visual field damage is that the comparison between groups of eyes achieving low and high levels of intraocular pressure is not based on a random allocation.” (opens the source at this quote in a new tab)

Mean intraocular pressure by proportion of visits below 18 mmHg and visual field change through 96 months

“The mean intraocular pressure over the first 6 years of follow-up is 12.3 mm Hg for group A, 14.7 mm Hg for group B, 16.9 mm Hg for group C, and 20.2 mm Hg for group D.” (opens the source at this quote in a new tab)
“For group A (eyes presenting with intraocular pressure less than 18 mm Hg at each visit over 6 years), the mean changes in visual field defect score remain close to zero, whereas in each of the other three groups (B, C, and D), the mean change progressively increases over time to an average worsening in visual field defect score of about two to three points by 96 months” (opens the source at this quote in a new tab)
“Starting at 54 months, mean changes for the four groups diverge and remain consistently ranked according to the percent of visits with intraocular pressure less than 18 mm Hg.” (opens the source at this quote in a new tab)

Visual field loss in eyes maintained below 18 mmHg at every visit

“Although the average change in visual field is close to zero, a proportion of eyes in this group experienced visual field loss despite having intraocular pressure at what is believed to be a safe level.” (opens the source at this quote in a new tab)
“To illustrate, a worsening of four or more units of visual field defect score from baseline was experienced by 13.1% of eyes at 2 years, 13.9% at 5 years, and 14.4% at 7 years.” (opens the source at this quote in a new tab)

Basis for setting an individual target intraocular pressure and the usual size of reduction

“From a pathophysiological and therapeutic point of view, intraocular pressure is the primary modifiable risk factor, since progression of glaucoma usually stops if this pressure is lowered by 30–50% from baseline.” (opens the source at this quote in a new tab)
“The target intraocular pressure for a particular eye is estimated based on the pretreatment intraocular pressure, the severity of damage, presence of risk factors for progression, life expectancy, and potential for adverse effects from treatment.” (opens the source at this quote in a new tab)
“The aim is usually for a reduction in intraocular pressure of 20–50%.” (opens the source at this quote in a new tab)

Rate of visual field progression with immediate versus delayed treatment

“The median rate of progression was –0.14 dB/y slower in the treatment group in the eye with the worse rate (not statistically significant) and –0.10 dB/y slower in the eye with the better rate” (opens the source at this quote in a new tab)
“As opposed to the results in terms of VI, these differences were consistently in favor of the group that received immediate treatment. The treatment group started out with worse MD values than the control group but ended up better.” (opens the source at this quote in a new tab)

UKGTS: proportion of participants with visual field deterioration at 24 months

“59 (25·6%; 95% CI 20·1–31·8) patients in the placebo group reached the deterioration endpoint at 24 months compared with 35 (15·2%; 10·8–20·4) in the latanoprost group (p=0·006).” (opens the source at this quote in a new tab)

Mechanisms proposed for slower visual field progression with drop-independent treatment

“The exact mechanisms for this effect are still unclear and might be related to a more consistent control of IOP, a shorter time to achieve target pressure, and less reliance on patients’ compliance with treatment.” (opens the source at this quote in a new tab)

Visual field outcome reporting in trials of first-line topical medications

“Not a single trial reported a difference or ratio between treatment groups with respect to visual field outcomes, although some trials provided group level data and treatment effect could be calculated based on the group level data.” (opens the source at this quote in a new tab)