Prospective Pilot Study of Sustained Release Bimatoprost Implant with SpyGlass Intraocular Lens: 3-Year Results

Abstract

Introduction

This study aimed to explore the safety and efficacy of sustained release bimatoprost implant with SpyGlass intraocular lens (SpyGlass Pharma, Inc., Aliso Viejo, CA, USA).

Methods

Twenty-four subjects diagnosed with cataracts and mild-to-moderate primary open-angle glaucoma were consented at a single site in Honduras. Those with pathologies that could confound outcomes were excluded. All subjects were required to have responded to topical prostaglandin analogues. Medication washout was performed prior to intervention. One eye of each subject was sequentially assigned to one of three arms (75 μg, 150 μg, or 300 μg of bimatoprost pads). The product was delivered in-the-bag via a commercially available intraocular lens (IOL) inserter and did not modify the steps of standard phacoemulsification cataract surgery other than attachment of bimatoprost implants to the IOL. We report interim results through 36 months.

Results

Twenty-one of 24 enrollees (87.5%) were retained through 36 months. Through 24 months, all subjects achieved the primary endpoint of intraocular pressure (IOP) reduction > 20% from baseline without any additional glaucoma medications. By month 36, all but a single subject (95.2%, n = 20) remained drop-free with continued IOP reductions > 20% across all remaining subjects. 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. All eyes had a final best-corrected distance visual acuity of 20/30 or better. 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.

Conclusions

The first human study of a novel system that mounts bimatoprost-infused pads to a single-piece IOL suggests favorable safety and efficacy and does not require additional surgical skills beyond routine cataract surgery. A larger sample with comparative data is necessary to further assess effects.

Trial Registration

ClinicalTrials.gov identifiers, NCT07154797 and NCT07154810. Retrospectively registered on September 3, 2025.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40123-026-01313-4.

Key Summary Points

Why carry out this study?

There is increasing interest in surgical solutions for reducing intraocular pressure that offer less operative and postoperative complexity.

Most current market options, including microinvasive glaucoma surgery and sustained released prostaglandins, impact the iridocorneal angle and can add surgical steps.

We hypothesized that bimatoprost pads attached to an intraocular lens would deliver sustained intraocular pressure control with few complications in patients who previously required glaucoma drops.

What was learned from the study?

In this nonrandomized, proof-of-concept study of sustained release bimatoprost with SpyGlass intraocular lens, we found robust pressure reductions, a high degree of topical medication independence, and good tolerance through 36 months of follow-up.

Novel intraocular lens-mounted bimatoprost pads may enable durable intraocular pressure control without complicating standard phacoemulsification cataract surgery; further, randomized studies are indicated.

Introduction

Adherence challenges to topical glaucoma therapies are well documented [1–3]. Accordingly, there has been increasing interest in utilizing interventional techniques for intraocular pressure (IOP) control [4]. Selective laser trabeculoplasty, microinvasive glaucoma surgery (MIGS), and injectable prostaglandin analogues are three such modalities currently available to ophthalmologists [5–8]. Each approach achieves mild to moderate IOP reduction without the complication profile of filtering surgeries [9]. However, difficulties exist even with newer technologies. Whether ab interno or ab externo, every MIGS device has a learning curve that may deter ophthalmologists who lack fellowship training [10, 11]. Accelerated corneal endothelial cell loss is a specific concern among implantable devices [5, 12]. And though all procedures undergo waning efficacy over time, trabecular bypass stents and trabecular meshwork excision physically limit additional angle-based interventions, whereas current sustained release prostaglandin analogues are only US Food and Drug Administration (FDA)-approved for one-time use [13].

We therefore sought to design an IOP-lowering technology that would be highly accessible to all ophthalmologists who perform standard cataract extraction and intraocular lens placement (CEIOL), pose minimal anatomic risk, and maximize options for future procedures. This novel product is the sustained release bimatoprost implant with SpyGlass intraocular lens (SpyGlass Pharma, Inc., Aliso Viejo, CA, USA). The SpyGlass system utilizes silicone pads infused with bimatoprost to provide continuous release of the hypotensive agent. Bimatoprost has already shown effectiveness as an intracameral implant (DURYSTA, Allergan, an AbbVie company, Chicago, IL, USA), and the location of the medicated pads on the intraocular lens (IOL) may facilitate tissue-friendly distribution [5]. The goal of the current study was to assess early safety and efficacy of different doses of the product in a human sample.

Methods

This nonrandomized, prospective, proof-of-concept interventional study was approved by the National Health Research Ethics Committee in El Salvador (CNEIS/2022/01H). The study was conducted in accordance with the tenets of the Declaration of Helsinki and subsequent amendments. Written informed consent was obtained from all subjects. The initial 6-month pilot study was registered on ClinicalTrials.gov under NCT07154797, and extended monitoring through 7 years of follow-up was registered under NCT07154810.

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. Studied drug content selections include 75 μg, 150 μg, and 300 μg of bimatoprost. 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). 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.

Fig. 1.

Bimatoprost drug pads attached to SpyGlass IOL

All subjects were enrolled in a non-randomized fashion at a single clinic, Centro Oftalmologico Robles, located in Santa Rosa de Copan, Honduras. Participants were sequentially assigned by the local investigator (author MR) to receive either the low configuration (75 μg bimatoprost), medium configuration (150 μg), or high configuration (300 μg) of the product in a 1:1:1 allocation ratio. Neither subjects nor investigators were masked to assignments. Only one eye per subject was designated for treatment in the study. A placebo arm was not included because the current study was designed as a pilot to help guide dose selection for future research. Full inclusion and exclusion criteria are included in Table 1. Key inclusion criteria were visually significant cataract, ocular hypertension or mild-to-moderate primary open-angle glaucoma, controlled IOP while already on at least a topical prostaglandin analogue, and post-washout IOP ≥ 22 mmHg and ≤ 36 mmHg. Exclusion highlights were secondary glaucomas, prior glaucoma surgery, diabetic retinopathy, other pathologies that could increase surgical complexity or compromise postoperative metrics, and inability to receive an IOL ranging from 19.0 to 25.0 D.

Table 1.

Inclusion and exclusion criteria

Inclusion criteria

1. Ability to understand a written informed consent and willingness to participate as demonstrated by signature

2. Male or female subjects at least 22 years of age

3. Diagnosis of OHT or mild to moderate POAG as defined by: glaucomatous visual field defects (with mean deviation less severe than − 12 dB) or nerve abnormality characteristic of glaucoma (including one or more of the following: segmental loss of neuroretinal rim, disc hemorrhage, pseudo-pit of the disc, nerve fiber layer loss, or visible laminar dots)

4. Age-related cataract eligible for phacoemulsification, with BCDVA 20/30 or worse

5. Screening IOP ≤ 24 mmHg while on at least a prostaglandin analogue, with a stable medication regimen for ≥ 4 weeks

6. Baseline unmedicated (post-washout) IOP ≥ 22 mmHg and ≤ 36 mmHg, and at least 3 mmHg higher than medicated screening IOP

7. Screening cup-to-disc ratio of 0.8 or less

8. Normal open-angle anatomy (Shaffer grade ≥ 2) by gonioscopy

9. Ability to provide an adequate, interpretable visual field

Exclusion criteria

1. Pregnancy as confirmed via urine pregnancy test for women of childbearing age at screening

2. BCDVA worse than 20/200 in the non-study eye

3. Pseudoexfoliation, pigmentary, traumatic, uveitic, neovascular, or angle-closure glaucoma, or glaucoma associated with vascular disorders

4. Central corneal endothelial cell count < 2000 cells/mm2 by specular microscopy

5. Central corneal thickness < 470 mm or > 630 mm (or a difference between eyes > 70 mm) by pachymetry

6. History of incisional glaucoma surgery, argon laser trabeculoplasty, iridectomy, or iridotomy, or completion of selective laser trabeculoplasty within 90 days before screening

7. Visual field mean deviation equal to or worse than − 12 dB

8. Ocular disease affecting safety or eligibility for washout

9. Any corneal, lenticular, choroidal, retinal, or other ocular or systemic condition that would preclude safe surgery, surgical success, or follow-up examinations

10. Any medication in the fellow eye that would impact IOP in the study eye

11. Visual field status that would be placed at risk by the washout period

12. Any medication that would be contraindicated for a glaucoma surgical procedure

13. History of uveitis/iritis

14. History of macular edema

15. Inability to receive an IOL ranging from 19 to 25 D

16. History of ocular trauma in study eye

17. Use of tamsulosin or silodosin (e.g., Flomax, Flomaxtra, Rapaflo) or similar medications

18. Any pathology of the zonules including evidence of zonular weakness, zonular instability, zonular damage, or coloboma effecting zonules

19. Corneal abnormalities or conditions other than regular topographic corneal astigmatism

20. Diabetic retinopathy or diabetic maculopathy

21. Subjects with known hypersensitivity or allergy to bimatoprost ophthalmic eye drops

22. Participation in another clinical trial within 30 days of screening

Intraoperative exclusion criteria

1. Significant zonular damage/rupture during cataract extraction procedure

2. Significant capsular tear or rupture during cataract extraction procedure

3. Uncontrollable intraocular pressure

4. Vitreous loss

5. Capsulotomy diameter greater than 6.0 mm or less than 4.0 mm

6. Posterior pressure from aqueous misdirection, suprachoroidal hemorrhage (partial or total), or other cause preventing the inflation of the capsular bag with viscoelastic

7. Complicated cataract surgery that prevents implantation of the SpyGlass IOL

8. Concerns by the surgeon that safe implantation of the IOL is not feasible or that postoperative follow-up would be compromised for any reason

OHT ocular hypertension, POAG primary open-angle glaucoma, BCDVA best-corrected distance visual acuity, IOP intraocular pressure, IOL intraocular lens

At the screening visit, several items were addressed: informed consent, demographics, best-corrected distance visual acuity (BCDVA), medications, IOP by Goldmann applanation tonometry, pachymetry, gonioscopy, slit lamp and dilated fundus exams, and 24–2 Humphrey visual fields (only if no reliable fields were available within 6 months). Crystalline lens opacity was evaluated on the basis of the 1–4 grading scale described in the Lens Opacity Classification System [14]. After passing initial inclusion and exclusion criteria, consented subjects proceeded to medication washout. Washout of ocular hypotensive agents followed the medication-specific durations recommended by prior pharmacologic studies [15–17]. Next, at the post-washout baseline visit, Goldmann IOPs were remeasured to ensure eligibility. Konan specular microscopy and IOL calculations with biometry targeting emmetropia were obtained, and the investigator sequentially assigned the study eye to one of the three treatment arms. At the subsequent visit, small-incision CEIOL with phacoemulsification, using the SpyGlass implant, was performed. A single ophthalmologist (author MR) completed all surgeries. 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.

The initial exploratory study design targeted 6 months of follow-up. The first patient was consented in April 2022, and the completion date of this initial pilot was December 2022. The internal clinical study report was generated in June 2023. At that time, findings were reviewed, and the decision was made to extend study monitoring through 7 years. This was done to better guide future study design and to provide surgeons with further information on a device that had already generated anecdotal interest. The protocol was amended to include future follow-up visits and the corresponding assessments. Eligible enrollees were reconsented accordingly. Trial registration was performed retrospectively, on September 3, 2025, to enable publication of the findings for interested ophthalmologists to critique. For this interim report, postoperative follow-up visits occurred at day 1, week 1, and months 1, 3, 6, 9, 12, 18, 24, 30, and 36. At each of these timepoints, Goldmann applanation IOP, glaucoma medications, BCDVA, slit lamp findings, and adverse events were recorded. All scheduled IOP measurements were performed at approximately 8 AM. To minimize bias, IOP was assessed by two observers—one masked observer who performed the measurements and a second observer who recorded the measurements. Two measurements were taken, with a third measurement required if the difference between the two was more than 2 mmHg. The mean of the IOP measurements was used for data analysis. Dilated fundus exams were repeated on months 6, 12, 24, and 36. Specular microscopy was performed at months 6 and 12, with no further specular microscopy testing done thereafter. Endothelial cell analyses were fully automated; no formal reading center was used to confirm cell counts.

The primary endpoint was the proportion of unmedicated eyes with IOP reduction > 20% from baseline at month 6 and onward. Secondary outcomes included adverse events, mean changes in IOP, and mean changes in glaucoma medications. The enrollment target was set at up to 30 subjects. Sample size was not calculated to attain pre-determined power for specified assumptions and type I error. Instead, the sample size was determined on the basis of ethical considerations, to adequately characterize safety across the three doses, and to obtain initial estimates of mean change-from-baseline IOPs with corresponding standard deviations. Paired IOP outcomes were analyzed using the Wilcoxon signed-rank test. Comparisons between mean IOPs across the three treatment arms were conducted via the Kruskal–Wallis test and with mixed model repeated measure analysis. If an ocular antihypertensive medication was reintroduced in a subject during follow-up, the IOP values used for analyses at subsequent visits were carried forward from the last unmedicated IOP. The statistical significance threshold was set at p < 0.05. Data were analyzed both on a per-protocol basis and with intention-to-treat analysis, by a trained statistician.

Results

A total of 29 subjects were consented for the study from April through June 2022 (Fig. 2). Of those, four subjects failed either inclusion or exclusion criteria prior to surgery, and one withdrew consent prior to any study procedures being performed. The remaining 24 enrollees all received surgical interventions corresponding to their sequential assignments. Eight subjects per group received the low, medium, and high dose implants. All procedures were uncomplicated except for a single subject in the low dose cohort who experienced mild iris prolapse into the main incision after anterior chamber overinflation; the iris appearance had normalized without sequelae on scheduled follow-up. No enrollees dropped out during the first 6 months of follow-up. At month 3 it was discovered that a single subject in the high dose implant cohort had preexisting diabetic retinopathy. This subject should have failed eligibility criteria prior to surgery (Table 1) but was followed for safety until referral to the retina clinic. Data was collected for this patient with diabetic retinopathy up to and including month 6, the end of the initial pilot, but they did not partake in extended study follow-up. To focus on the effect of the technology on a consistent cohort inclusive of the other 23 enrollees who completed subsequent visits, we primarily implemented a per-protocol approach. An intention-to-treat analysis, including the subject with preexisting diabetic retinopathy, is included in the Supplementary Material. All 23 subjects were retained through the month 30 follow-up visit. Between months 30 and 36, two subjects in the high-dose cohort withdrew. The first subject moved to another country, and the second exited to undergo palliative care in the setting of newly diagnosed pancreatic cancer.

Fig. 2.

CONSORT enrollment flowchart

Baseline characteristics are compiled in Table 2. 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. Median BCDVA prior to cataract surgery was 20/50. The mean preoperative refractive spherical equivalent was 0.2 ± 1.6 D. The majority of cataracts were nuclear sclerotic and graded as 1+ or 2+ (Supplemental Table 1). Target pressures for most subjects were achieved preoperatively on a single ocular hypotensive agent (n = 20, 87.0%), while the remainder required two or three. Prior to medication washout, mean IOP was 16.5 ± 3.5 mmHg. Post-washout mean IOP was 25.1 ± 2.5 mmHg. Mean visual field mean deviation was − 11.8 ± 10.1 dB, and mean pattern standard deviation was 5.3 ± 3.6 dB.

Table 2.

Baseline information of enrolled subjects

Demographics and ocular characteristics	Data (n = 23)
Age, mean years ± SD	70.5 ± 9.6
Gender, n (%)
Male	11 (47.8%)
Female	12 (52.2%)
Race, n (%)
American Indian or Alaska Native	0 (0%)
Asian	0 (0%)
Black or African American	0 (0%)
Native Hawaiian or other Pacific Islander	0 (0%)
Caucasian	23 (100%)
Other	0 (0%)
Ethnicity, n (%)
Hispanic or Latino	23 (100%)
Not Hispanic or Latino	0 (0%)
Diagnosis, n (%)
Primary open-angle glaucoma	23 (100%)
Ocular hypertension	0 (0%)
Best-corrected distance visual acuity, median (range)	20/50 (20/30, 20/100)
Refractive error spherical equivalent, mean D ± SD	0.2 ± 1.6 D
Pre-washout screening IOP, mean mmHg ± SD	16.5 ± 3.5
Post-washout baseline IOP, mean mmHg ± SD	25.1 ± 2.5
Ocular hypotensive medications, n (%)
0	0 (0%)
1	20 (87.0%)
2	1 (4.3%)
3	2 (8.7%)
Vertical cup-to-disc ratio, mean ratio ± SD	0.6 ± 0.2
Central corneal thickness, mean μm ± SD	547 ± 32
Endothelial cell density, mean cells/mm2 ± SD	2308 ± 223
Enrolled eye, n (%)
Right	11 (47.8%)
Left	12 (52.2%)
Visual field mean deviation, mean dB ± SD	− 11.8 ± 10.1
Visual field pattern standard deviation, mean dB ± SD	5.3 ± 3.6

SD standard deviation, D diopters, IOP intraocular pressure, dB decibels

Changes in mean IOP via per-protocol analysis are shown in Table 3. 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). At month 6, every individual study eye achieved an unmedicated IOP reduction ≥ 20% versus baseline. When compared to the intention-to-treat IOP analysis through 6 months, outcomes were similar (Supplemental Table 2). Through month 24, all study eyes continued to maintain an IOP reduction > 20%, and all but one study eye measured at an IOP of 18 mmHg or less. 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. Thus, at last follow-up, 95.2% of study eyes (n = 20) remained topical medication-free. All month 36 subjects maintained an IOP reduction > 20% and all but two subjects (90.5%, n = 19) achieved an IOP < 18 mmHg. Mean final IOPs were 14.9 ± 2.0 mmHg for the 75 μg implant cohort, 17.2 ± 2.4 mmHg for the 150 μg cohort, and 15.3 ± 3.8 mmHg for the 300 μg cohort (p = 0.50 for intergroup comparison). Mean final IOPs in the 75 μg and 150 μg arms were statistically significant reductions from the post-washout baseline (p < 0.01 each). The 300 μg group, retaining five subjects at month 36, did not achieve a statistically significant final IOP reduction (p = 0.06). Regarding the two 300 μg subjects who dropped out for aforementioned reasons after month 30, one subject had a measured IOP of 11.0 mmHg, while the other’s was 16.5 mmHg at their final study visits. Neither subject required reintroduction of a topical agent prior to dropout. Hence, their dropout may have contributed to statistical underestimation of the 300 μg dose effect. For the aggregate sample, mean percentage IOP reduction from baseline was 36.7 ± 9.4% (p < 0.0001) by month 36. A mixed model repeated measure analysis was performed with change from baseline IOP at each visit (week 1 and months 1, 3, 6, 9, 12, 18, 24, 30, and 36) as the response variable. Baseline IOP, time in months, treatment, and the interactions of baseline IOP by time in months and time in months by treatment were imputed as fixed effects; the subject was imputed as a random effect. This model resulted in a two-sided p value of 0.36 for the time in months by treatment interaction, showing no overall difference between groups in IOP change over time.

Table 3.

Changes in mean IOP over time for bimatoprost implant dosing cohorts

	Screening	Baseline	Month 3	Month 6	Month 9	Month 12	Month 18	Month 24	Month 30	Month 36
Treatment arm: 75 μg strength implant
Study eyes in cohort, n	8	8	8	8	8	8	8	8	8	8
IOP, mean mmHg ± SD	14.5 ± 2.3	24.6 ± 2.1	12.4 ± 1.9	12.7 ± 2.5	13.1 ± 1.8	13.8 ± 2.8	13.9 ± 2.2	14.4 ± 2.4	16.1 ± 3.9	14.9 ± 2.0
CFB IOP, mean mmHg ± SD	N/A	N/A	− 12.1 ± 2.3	− 11.9 ± 2.6	− 11.5 ± 2.7	− 10.8 ± 3.7	− 10.7 ± 1.8	− 10.2 ± 2.4	− 8.5 ± 2.7	− 9.7 ± 1.7
p value (CFB = 0)a	N/A	N/A	0.0078	0.0078	0.0078	0.0078	0.0078	0.0078	0.0078	0.0078
% IOP reduction from baseline	N/A	N/A	49.3 ± 7.2	48.4 ± 9.3	46.5 ± 8.0	43.7 ± 12.1	43.6 ± 6.9	41.5 ± 8.8	35.1 ± 12.3	39.5 ± 6.3
% eyes with ≥ 20% reduction (95% CI)	N/A	N/A	100% (63%, 100%)	100% (63%, 100%)	100% (63%, 100%)	100% (63%, 100%)	100% (63%, 100%)	100% (63%, 100%)	87.5% (47%, 100%)	100% (63%, 100%)
Treatment arm: 150 μg strength implant
Study eyes in cohort, n	8	8	8	8	8	8	8	8	8	8
IOP, mean mmHg ± SD	17.6 ± 2.5	25.6 ± 3.3	13.9 ± 2.7	14.4 ± 3.2	14.6 ± 2.7	14.1 ± 1.4	14.9 ± 2.0	14.8 ± 1.9	14.4 ± 2.3	17.2 ± 2.5
CFB IOP, mean mmHg ± SD	N/A	N/A	− 11.7 ± 3.6	− 11.2 ± 3.9	− 11.1 ± 3.3	− 11.5 ± 3.8	− 10.7 ± 3.4	− 10.8 ± 3.7	− 11.2 ± 4.7	− 8.4 ± 3.1
p value (CFB = 0)a	N/A	N/A	0.0078	0.0078	0.0078	0.0078	0.0078	0.0078	0.0078	0.0078
% IOP reduction from baseline	N/A	N/A	45.5 ± 9.8	43.2 ± 12.3	42.8 ± 10.3	44.0 ± 9.9	41.1 ± 9.5	41.4 ± 9.9	42.7 ± 13.5	32.3 ± 9.4
% eyes with ≥ 20% reduction (95% exact CI)	N/A	N/A	100% (63%, 100%)	100% (63%, 100%)	100% (63%, 100%)	100% (63%, 100%)	100% (63%, 100%)	100% (63%, 100%)	87.5% (47%, 100%)	100% (63%, 100%)
Treatment arm: 300 μg strength implant
Study eyes in cohort, n	7	7	7	7	7	7	7	7	7	5
IOP, mean mmHg ± SD	17.6 ± 4.8	25.0 ± 1.8	14.3 ± 2.4	14.3 ± 3.0	13.9 ± 2.8	13.8 ± 2.9	12.7 ± 2.2	14.4 ± 4.7	15.1 ± 3.3	15.3 ± 3.8
CFB IOP, mean mmHg ± SD	N/A	N/A	− 10.7 ± 2.4	− 10.7 ± 2.9	− 11.1 ± 2.1	− 11.2 ± 3.7	− 12.3 ± 2.6	− 10.6 ± 3.8	− 9.9 ± 2.2	− 9.8 ± 2.9
p value (CFB = 0)a	N/A	N/A	0.016	0.016	0.016	0.016	0.016	0.016	0.016	0.06
% IOP reduction from baseline	N/A	N/A	42.8 ± 9.2	42.8 ± 11.9	44.5 ± 9.2	44.5 ± 12.8	49.0 ± 9.2	43.1 ± 16.7	40.1 ± 10.1	39.3 ± 12.4
% eyes with ≥ 20% reduction (95% exact CI)	N/A	N/A	100% (59%, 100%)	100% (59%, 100%)	100% (59%, 100%)	100% (59%, 100%)	100% (59%, 100%)	100% (59%, 100%)	100% (59%, 100%)	100% (48%, 100%)
Overall sample
Study eyes, n	23	23	23	23	23	23	23	23	23	21
IOP, mean mmHg ± SD	16.5 ± 3.5	25.1 ± 2.5	13.5 ± 2.4	13.8 ± 2.9	13.8 ± 2.4	13.9 ± 2.3	13.9 ± 2.2	14.5 ± 3.0	15.2 ± 3.2	15.9 ± 2.8
CFB IOP, mean mmHg ± SD	N/A	N/A	− 11.6 ± 2.8	− 11.3 ± 3.1	− 11.2 ± 2.7	− 11.2 ± 3.6	− 11.2 ± 2.7	− 10.5 ± 3.2	− 9.9 ± 3.4	− 9.2 ± 2.6
p value (CFB = 0)a	N/A	N/A	< 0.0001	< 0.0001	< 0.0001	< 0.0001	< 0.0001	< 0.0001	< 0.0001	< 0.0001
p value (CFB among Tx)b	N/A	N/A	0.65	0.72	1.00	0.84	0.42	0.99	0.28	0.50
% IOP reduction from baseline	N/A	N/A	46.0 ± 8.8	44.9 ± 11.0	44.6 ± 8.9	44.0 ± 11.1	44.4 ± 8.8	41.9 ± 11.5	39.3 ± 12.0	36.7 ± 9.4
% eyes with ≥ 20% reduction (95% exact CI)	N/A	N/A	100% (85%, 100%)	100% (85%, 100%)	100% (85%, 100%)	100% (85%, 100%)	100% (85%, 100%)	100% (85%, 100%)	91.3% (72%, 99%)	100% (84%, 100%)

IOP intraocular pressure, SD standard deviation, CFB change from baseline, CI confidence interval, Tx treatment arms, N/A not applicable

^aCalculated with Wilcoxon signed rank test

^bCalculated with Kruskal–Wallis test

Fig. 3.

Change in IOP over time after differing doses of bimatoprost implant with spyglass IOL. Error bars indicate standard deviation

From month 18 through month 36, 100% of study eyes maintained a BCDVA of 20/30 or better. Temporary loss of ≥ 2 Snellen lines occurred in the study eyes of three subjects, each at the month 1 visit. Two were attributed to ocular surface disease and responded to topical drops by subsequent visits. Ocular surface disease is commonly observed following cataract surgery, and it was unclear whether the investigational product had any contribution to the ocular surface disease. The third instance had no associated ocular findings and self-resolved by the next visit. Regarding postoperative changes, mild corneal edema was noted in 13 study eyes at day 1 (56.5%). This decreased to a single eye (4.3%) by week 1. At all subsequent visits, no corneal edema was reported. Although endothelial cell density measurements did not employ a validated reading center methodology, outcomes from automated measurements are reported. 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. At postoperative month 1, only two subjects (8.7%) had faint anterior chamber cells in their study eyes; all other study eyes were clear. There was no anterior chamber inflammation observed in any subject’s study eye for the remainder of follow-up. A single subject experienced idiopathic anterior uveitis in the non-study eye at an unscheduled visit that resolved with topical prednisolone and NSAIDs.

Adverse events (AE) in study eyes are included in Table 4. Descriptive analyses of individual AEs, including if they had occurred only in the study eye or in both eyes, are compiled in Table 5. The most common AE was dry eye. It occurred in five subjects (21.7%), four of whom received the lowest dosing of bimatoprost. However, the dry eye was bilateral in two of those five subjects (Table 5). Bilateral conjunctival hyperemia in context of bilateral meibomian gland dysfunction was recorded in a single subject (4.3%) at a non-study visit after postoperative month 1, which resolved with warm compresses, lid scrubs, and anti-inflammatory drops. Spontaneous subconjunctival hemorrhages were observed in two subjects (8.7%); the causes were unclear and not considered product-related, treatment was not required, and there was resolution without clinical sequalae. Individual episodes of bacterial conjunctivitis, photokeratitis from welding, a corneal laceration from a metallic object, and a scar from a foreign body were all unrelated to the surgery or implant. 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. One subject was hospitalized and diagnosed with pancreatic carcinoma approximately 3 months after completing the month 30 visit. There was no apparent link between the cancer and the product. No deaths or serious adverse events related to the implant occurred.

Table 4.

Cumulative adverse events

Adverse event	75 μg strength implant n = 8 (%)	150 μg strength implant n = 8 (%)	300 μg strength implant n = 7 (%)	Overall sample n = 23 (%)
Blepharitis	1 (12.5%)	0 (0.0%)	0 (0.0%)	1 (4.3%)
Bacterial conjunctivitis	1 (12.5%)	0 (0.0%)	0 (0.0%)	1 (4.3%)
Conjunctival chemosis	0 (0.0%)	1 (12.5%)	0 (0.0%)	1 (4.3%)
Conjunctival hyperemia	0 (0.0%)	1 (12.5%)	0 (0.0%)	1 (4.3%)
Corneal laceration	0 (0.0%)	1 (12.5%)	0 (0.0%)	1 (4.3%)
Corneal scar	0 (0.0%)	0 (0.0%)	1 (14.3%)	1 (4.3%)
Dry eye	4 (50.0%)	0 (0.0%)	1 (14.3%)	5 (21.7%)
Intraoperative iris prolapse	1 (12.5%)	0 (0.0%)	0 (0.0%)	1 (4.3%)
Meibomian gland dysfunction	0 (0.0%)	0 (0.0%)	1 (14.3%)	1 (4.3%)
Photokeratitis	0 (0.0%)	1 (12.5%)	0 (0.0%)	1 (4.3%)
Subconjunctival hemorrhage	0 (0.0%)	2 (25.0%)	0 (0.0%)	2 (8.7%)
Transient BCDVA loss of ≥ 2 lines	2 (25.0%)	0 (0.0%)	1 (14.3%)	3 (13.0%)

BCDVA best-corrected distance visual acuity

Table 5.

Adverse events in study eyes

Adverse event	Cohort (μg)	Onset date	Resolution datea	Severity	Relationship to device	Relationship to surgery	Treatment	Outcome
Bacterial conjunctivitis (bilateral)	75	25 Aug 2025	Ongoing	Moderate	Not related	Not related	Medication	Ongoing
BCDVA loss of ≥ 2 lines (unilateral)	75	06 Jul 2022	01 Sep 2022	Mild	Not related	Not related	None	RWS
BCDVA loss of ≥ 2 lines (unilateral)	75	06 Jul 2022	02 Sep 2022	Mild	Not related	Not related	None	RWS
BCDVA loss of ≥ 2 lines (unilateral)	300	27 Jul 2022	12 Aug 2022	Mild	Not related	Not related	None	RWS
Blepharitis (bilateral)	75	25 May 2023	03 Nov 2023	Mild	Not related	Not related	None	RWS
Conjunctival chemosis (unilateral)	150	27 Dec 2023	08 Jan 2024	Mild	Not related	Not related	Medication	RWS
Conjunctival hyperemia (unilateral)	150	08 Jan 2024	15 Jan 2024	Mild	Not related	Not related	None	RWS
Corneal laceration (unilateral)	150	24 Nov 2023	27 Dec 2023	Mild	Not related	Not related	Medication	RWS
Corneal scar (unilateral)	300	12 Jan 2024	Ongoing	Mild	Not related	Not related	None	Ongoing
Dry eye (bilateral)	75	16 Mar 2023	22 May 2023	Mild	Not related	Not related	Medication	RWS
Dry eye (bilateral)	75	10 May 2024	Ongoing	Moderate	Not related	Not related	Medication	Ongoing
Dry eye (unilateral)	75	16 Jun 2022	02 Sep 2022	Mild	Possibly related	Possibly related	Medication	RWS
Dry eye (unilateral)	75	02 Aug 2022	Ongoing	Mild	Possibly related	Possibly related	Medication	Ongoing
Dry eye (unilateral)	300	21 Jul 2022	13 Sep 2022	Mild	Possibly related	Possibly related	Medication	RWS
Iris prolapse (unilateral)	75	08 Jun 2022	08 Jun 2022	Mild	Not related	Definitely related	Iris reposition	RWS
Meibomian gland dysfunction (bilateral)	300	05 Aug 2022	12 Sep 2022	Mild	Not related	Not related	Medication	RWS
Pancreatic carcinoma	300	27 Apr 2025	Ongoing	Severe	Not related	Not related	Palliative care	Ongoing
Photokeratitis (unilateral)	150	07 Aug 2023	24 Nov 2023	Mild	Not related	Not related	None	RWS
Subconjunctival hemorrhage (unilateral)b	150	14 Jul 2023	04 Aug 2023	Moderate	Not related	Not related	None	RWS
Subconjunctival hemorrhage (unilateral)b	150	05 Jan 2024	08 Jan 2024	Mild	Not related	Not related	None	RWS
Subconjunctival hemorrhage (unilateral)	150	08 Jan 2024	15 Jan 2024	Mild	Not related	Not related	None	RWS

BCDVA best-corrected distance visual acuity, RWS resolved without sequelae

^aEvents noted as “ongoing” are per the most recent study report (September 2025)

^bThese events of subconjunctival hemorrhage occurred at two different times in the study eye of the same patient

Discussion

This prospective study describes the first in-human data of a combination product that reduces IOP via novel, bimatoprost-eluting pads attached to a single-piece acrylic IOL. Efficacy outcomes were robust. Across 3 years of follow-up in a sample comprising previously medicated POAG subjects, all but a single eye remained free of topical ocular hypotensive drops. By week 1, mean IOP reduction in the sample was > 40% versus baseline, and remained at similar levels throughout the course of the study. However, there was a slight uptick in IOP at year 3 in the medium configuration (150 μg) cohort. Though exact reasons are unclear, this may be more attributable to the greater variability of a small sample and less likely due to waning efficacy. If the latter were the case, the low-dose (75 mcg) cohort would most likely show a similar trend, which did not appear to occur. All study eyes met the primary endpoint of an IOP reduction > 20% at month 36, and 90.5% of eyes reached a final IOP of 18 mmHg or lower.

These findings may inform surgeons in the context of commercially available MIGS. 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. Comparisons are further limited by the current study’s sequential, unmasked assignment that risks selection bias and the lack of a control group.

The sustained release bimatoprost implant with SpyGlass IOL was well tolerated. There were no serious adverse events related to the product or postoperative dislocations of the pads or IOL. Postoperative inflammation was unremarkable. Anterior chamber cell clearance at 1 month was 91.7%, a value within the range of cataract surgery with standard IOLs [23]. Best-corrected visual acuity was 20/30 or better for all subjects. No posterior capsular opacification was recorded thus far through 36 months of follow-up. Though dry eye was noted in five subjects (21.7%), the effect did not seem to be dose dependent. In a prospective study of CEIOL combined with iStent inject (Glaukos Corporation, San Clemente, CA) versus CEIOL alone, the latter group experienced postoperative ocular surface disease at a rate of 16.8% [18]. Cosmetic side effects of topical prostaglandin analogues such as periorbitopathy, iris heterochromia, and lash growth were not observed in any patients. Studies of intracameral bimatoprost and travoprost intraocular implant have similarly reported a lower incidence of the adverse outcomes seen with topical equivalents [5, 8]. Though no formal reading center was used, the month 6 and month 12 declines in automated endothelial cell count of 10.4% and 12.8%, respectively, versus screening are in line with known changes from standalone cataract surgery and age-related changes [24]. Other distinct MIGS side effects, such as transient hyphema, Descemet’s detachment, and iridodialysis, did not occur in our sample. Further, no eye had an early postoperative IOP spike that required the addition of medication.

An additional goal of the current study was to examine the performance of different dosing levels. 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. There were also no distinct trends in adverse effects relating to dosing. Thus, for future trials, it appears that each dosing scheme may be worth exploring further.

This first-in-human study has important limitations, including small sample size, nonrandomized design, and selection of prior prostaglandin analogue responders. A small, nonrandomized sample with no control group greatly limits validity and may have contributed to underestimation of adverse effects. Subject withdrawals disproportionately affected the 300 μg cohort, likely contributing to insufficient power for IOP analysis to demonstrate a statistically significant IOP reduction at month 36 in that group. Notwithstanding, there was still a clinically significant IOP reduction of 39.3% in that cohort. 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. For sustained release technologies, clinicians are often most interested in duration of effect [25]. Our study only reports interim data to 36 months, though further follow-up in this cohort is planned through 84 months. The single-site design with a sample comprised entirely of white Latino patients with POAG further limits generalizability to wider populations. Procedures were performed by a single ophthalmologist; given that cataract surgery approaches vary, other operators may realize challenges with a new product. Though the SpyGlass system utilizes a single-piece acrylic IOL similar in design to current market options, 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. Further, corneal endothelial cell count data were not sufficiently reliable as they were derived directly from automated machine output and not verified by a reading center.

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. 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. IOPs were measured only at the time of each in-clinic visit. There is known variation in IOP over 24-h cycles, and it may be interesting to explore how the implant’s sustained secretion of bimatoprost affects such circadian changes [28]. Retrospective registration of the current study increases risk for bias; outcomes should thus be interpreted cautiously. Larger phase 2 and phase 3 pivotal studies that are prospective, randomized, multicenter, masked, and utilize control arms including standard CEIOL and timolol are currently underway.

Several potential advantages to the SpyGlass system exist. 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. Fourth, its immediate IOP effect could be useful in combination with nonvalved tube shunts, which are typically occluded or ligated in the early postoperative period.

Conclusions

The positive findings of this exploratory, nonrandomized study of sustained release bimatoprost with SpyGlass IOL suggest a potential new option for the surgical management of glaucoma. IOP reductions were moderately strong and reasonably sustained through 3 years of follow-up. All but one subject remained free of glaucoma drops, and adverse effects were generally mild and infrequent. The technology itself offers unique advantages in sparing the iridocorneal angle and minimally modifying standard cataract surgery. However, large-scale comparisons against existing treatment modalities over longer follow-up are necessary to determine the extent of clinical utility.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Gregory Katz, Marco Robles, Preeya K Gupta, Malik Kahook, Glenn Sussman, and Nathan Radcliffe contributed to the conceptualization and design of this study. Marco Robles contributed to the data acquisition. Nicholas Tan and an independent statistician contributed to the data analysis. Nicholas Tan, Glenn Sussman, and Paul Yoo contributed to the manuscript writing. All authors contributed to the interpretation of the results and critical review of the manuscript. All authors read and approved the final manuscript.

Funding

This study was sponsored by SpyGlass Pharma, Inc., Aliso Viejo, CA, USA. The sponsor participated in the design of the study, conducting the study, data collection, data management, data analysis, interpretation of the data, preparation, and review and approval of the manuscript. The study sponsor is also funding the journal’s Rapid Service fee.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of Interest

Nicholas E Tan: SpyGlass Pharma—consultant. Gregory Katz: SpyGlass Pharma—medical monitor, investigator; Alcon—consultant, speaker; Bausch + Lomb—consultant, speaker; Eyenovia—consultant; New World Medical—consultant; Sun Pharma—consultant. Marco Robles: SpyGlass Pharma—consultant, investigator; Aquea Health—consultant, investigator, shareholder; Bausch + Lomb—consultant, investigator; Glaukos—consultant, investigator; iSTAR Medical—consultant, investigator; New World Medical—consultant, investigator; ViaLase—consultant, investigator, shareholder. Preeya K Gupta: SpyGlass Pharma—consultant, medical advisory board member, shareholder; Abbvie—consultant; Alcon—consultant; Aldeyra—consultant; Azura—consultant, shareholder; Bausch + Lomb—consultant; Dompe—consultant; Expert Opinion—consultant, shareholder; HanAll Biopharma—consultant; J&J Vision—consultant; Kala—consultant; Mazado—consultant; Nordic Pharma—consultant; Ocular Science—consultant; Oculis—consultant; Orasis—consultant, shareholder; Sight Sciences—consultant; Science Based Health—consultant; Surface Ophthalmics—consultant, shareholder; Tarsus—consultant, shareholder; Tear Clear—consultant, shareholder; Thea—consultant; Tissue Tech, Inc—consultant; Trukera—consultant; Viatris—consultant; Visionology—consultant, shareholder; Vital Tears—consultant; Zeiss—consultant. Malik Kahook: SpyGlass Pharma—president, patent royalties; Alcon—patent royalties; FCI Ophthalmics—consultant, patent royalties; New World Medical—consultant, patent royalties. Glenn Sussman: SpyGlass Pharma—employee. Paul Yoo: SpyGlass Pharma—employee. Nathan M Radcliffe: SpyGlass Pharma—consultant, medical advisory board member, shareholder; Alcon Laboratories—consultant, speaker; Aldeyra Therapeutics—consultant; Alimera Sciences—consultant, speaker; Allergan—consultant, speaker, grant support; Avellino Labs—consultant; Bausch + Lomb—consultant, speaker; Beaver-Visitec International—consultant; Belkin Laser—consultant; Carl Zeiss Meditec—consultant; Dompe—consultant; Elios Vision—consultant; Ellex—consultant, speaker; EyePoint Pharmaceuticals—consultant; Glaukos Corporation—consultant, speaker; ImprimisRx—consultant; Iridex—consultant, speaker; IrisVision—consultant; Iveric Bio—consultant; Kala Pharmaceuticals—consultant, speaker; Lumenis Vision—consultant, speaker; New World Medical—consultant, speaker; Novartis Pharma AG—consultant, speaker; Ocular Therapeutix—consultant, grant support; Omeros Corporation—consultant; Orasis Pharmaceuticals—consultant; Quantel Medical—consultant; Rayner—consultant, speaker; Reichert—consultant, speaker; Santen—consultant; Shire—consultant; Tarsus Pharmaceuticals—consultant; TearClear—consultant, shareholder; Thea—consultant; ViaLase Inc—consultant.

Ethical Approval

The study was approved by the National Health Research Ethics Committee in El Salvador (CNEIS/2022/01H). The study was conducted in accordance with the tenets of the Declaration of Helsinki and subsequent amendments. Written informed consent was obtained from all subjects.