Registered study purpose

“The goal of this clinical trial is to further observe and learn if the SpyGlass Pharma Bimatoprost Implant System / IOL Combination works to treat cataracts and either ocular hypertension or glaucoma. It will also further observe and learn about the safety of the Bimatoprost Implant System / IOL Combination.” (opens the source at this quote in a new tab)

Rationale for extended follow-up

“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.” (opens the source at this quote in a new tab)

Study dates and site

Field	Registry record
Study start (actual)	“2023-03-16”
Primary completion (estimated)	“2031-04-14”
Study completion (estimated)	“2031-04-14”
First submitted	“2025-08-22”
Facility	“Centro Oftalmológico Robles”
City	“Santa Rosa de Copán”
Country	“Honduras”

Retrospective registration

“Trial registration was performed retrospectively, on September 3, 2025, to enable publication of the findings for interested ophthalmologists to critique.” (opens the source at this quote in a new tab)

Registered observational design

Design element	Registry record
Study type	“Observational”
Observational model	“Cohort”
Time perspective	“Prospective”
Sampling method	“Non-Probability Sample”

“Observational Study to Evaluate Long-term Follow-up of Subjects Implanted With Sustained-release Bimatoprost With the SpyGlass IOL in Subjects With Ocular Hypertension or Mild-to-moderate Open-angle Glaucoma” (opens the source at this quote in a new tab)
“This is an observational extension to a proof of concept trial (first in human).” (opens the source at this quote in a new tab)

Protocol amendment, visit schedule, and IOP measurement

“The protocol was amended to include future follow-up visits and the corresponding assessments. Eligible enrollees were reconsented accordingly.” (opens the source at this quote in a new tab)
“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.” (opens the source at this quote in a new tab)
“All scheduled IOP measurements were performed at approximately 8 AM. To minimize bias, IOP was assessed by two observers” (opens the source at this quote in a new tab)

Registered eligibility criteria and study population

“Be able to understand a written informed consent and be willing to participate by evidence of signing an informed consent form” (opens the source at this quote in a new tab)
“Met all inclusion criteria, participated in and completed the SGP-SPEC-001 study” (opens the source at this quote in a new tab)
“Planned participation in another clinical trial within 30 days of the initial study visit that, in the investigator's opinion, could confound the study results” (opens the source at this quote in a new tab)
“Ocular hypertension or open-angle glaucoma participants in Honduras who completed the SpyGlass Pharma Inc. SGP-SPEC-001 study.” (opens the source at this quote in a new tab)

Exclusion of the participant with preexisting diabetic retinopathy

“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.” (opens the source at this quote in a new tab)

Dose cohorts followed (no new intervention)

Cohort	Registry arm label
Low dose	“Bimatoprost Implant System / IOL Combination Low Dose”
Medium dose	“Bimatoprost Implant System / IOL Combination Medium Dose”
High dose	“Bimatoprost Implant System / IOL Combination High Dose”

Bimatoprost content by cohort

“One eye of each subject was sequentially assigned to one of three arms (75 μg, 150 μg, or 300 μg of bimatoprost pads).” (opens the source at this quote in a new tab)

Registered primary and other outcomes

Outcome type	Measure	Time frame
Primary	“Unmedicated eyes with an IOP Reduction from SGP-SPEC-001 Baseline”	“From Month 9 post-operative through the end of post-operative follow-up at Month 84”
Other	“Mean change in unmedicated IOP from SGP-SPEC-001 baseline visit for each follow-up time up to the month 84 exam.”	“From Month 9 post-operative through the end of post-operative follow-up at Month 84”
Other	“Assessment of Postoperative Adverse Events”	“From Month 9 post-operative through the end of post-operative follow-up at Month 84”
Other	“Supplementary Safety Parameter - Specular Microscopy”	“Month 12 post-operative”

Primary outcome definition

“The proportion of eyes that remain unmedicated and with an IOP reduction ≥ 20% from the SGP-SPEC-001 baseline visit for each follow-up time through the month 84 exam.” (opens the source at this quote in a new tab)

Rationale for the 20% IOP reduction threshold

No evidence found.

Registered enrollment

Enrollment type	Participants
Actual	“23”

Participants analyzed at 36 months

“Twenty-one of 24 enrollees (87.5%) were retained through 36 months.” (opens the source at this quote in a new tab)

Per-protocol and intention-to-treat analyses, statistical tests, and handling of rescue medication

“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.” (opens the source at this quote in a new tab)
“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.” (opens the source at this quote in a new tab)

Retention through 36 months

“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.” (opens the source at this quote in a new tab)

Baseline characteristics of the extension cohort

Characteristic	Data (n = 23)
Age, mean years ± SD	“70.5 ± 9.6”
Female, n (%)	“12 (52.2%)”
Hispanic or Latino, n (%)	“23 (100%)”
Primary open-angle glaucoma, n (%)	“23 (100%)”
Ocular hypertension, n (%)	“0 (0%)”
Pre-washout screening IOP, mean mmHg ± SD	“16.5 ± 3.5”
Post-washout baseline IOP, mean mmHg ± SD	“25.1 ± 2.5”
One ocular hypotensive medication, n (%)	“20 (87.0%)”
Two ocular hypotensive medications, n (%)	“1 (4.3%)”
Three ocular hypotensive medications, n (%)	“2 (8.7%)”
Endothelial cell density, mean cells/mm2 ± SD	“2308 ± 223”

Summary: IOP and medication outcomes from month 9 through month 36

In the per-protocol cohort, mean IOP decreased from 25.1 ± 2.5 mmHg at post-washout baseline to 13.8 ± 2.4 mmHg at month 9, 13.9 ± 2.3 mmHg at month 12, 14.5 ± 3.0 mmHg at month 24, and 15.9 ± 2.8 mmHg at month 36 (n=21), corresponding to mean reductions of 44.6%, 44.0%, 41.9%, and 36.7% (p < 0.0001 at each visit). All 21 eyes followed to month 36 maintained an IOP reduction greater than 20%, and 19 of 21 (90.5%) had IOP below 18 mmHg. All 16 participants in the 75 μg and 150 μg cohorts remained drop-free through month 36; one participant in the 300 μg cohort restarted topical medication at month 30, giving 20 of 21 (95.2%) drop-free at 36 months. Month-36 IOP did not differ significantly among dose cohorts (p = 0.50), and the 300 μg cohort (n=5) did not reach statistical significance for IOP reduction from baseline (p = 0.06). The sponsor reported that 4-year follow-up data are expected in the fourth quarter of 2026.

IOP over time, overall per-protocol sample

Measure	Month 9	Month 12	Month 18	Month 24	Month 30	Month 36
Study eyes, n	“23”	“23”	“23”	“23”	“23”	“21”
IOP, mean mmHg ± SD	“13.8 ± 2.4”	“13.9 ± 2.3”	“13.9 ± 2.2”	“14.5 ± 3.0”	“15.2 ± 3.2”	“15.9 ± 2.8”
% IOP reduction from baseline	“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)	“100% (85%, 100%)”	“100% (85%, 100%)”	“100% (85%, 100%)”	“100% (85%, 100%)”	“91.3% (72%, 99%)”	“100% (84%, 100%)”
p value (CFB among Tx)	“1.00”	“0.84”	“0.42”	“0.99”	“0.28”	“0.50”

IOP at month 36 by dose cohort

Measure	75 μg	150 μg	300 μg
Study eyes, n	“8”	“8”	“5”
IOP, mean mmHg ± SD	“14.9 ± 2.0”	“17.2 ± 2.5”	“15.3 ± 3.8”
% IOP reduction from baseline	“39.5 ± 6.3”	“32.3 ± 9.4”	“39.3 ± 12.4”
p value (CFB = 0)	“0.0078”	“0.0078”	“0.06”

Medication-free status and IOP targets through month 36

“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.” (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)
“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.” (opens the source at this quote in a new tab)

36-month results as reported by the sponsor

“At 36 months, 95% of evaluable patients (n=21) were off all topical IOP-lowering drops. In addition, we observed a statistically significant reduction in mean IOP from 25.1 ± 2.5 mmHg at baseline post-washout to 15.9 ± 2.8 mmHg at 36 months (p<0.0001), with a mean IOP reduction of 37% across all doses compared to baseline.” (opens the source at this quote in a new tab)

Visual acuity at 36 months

“From month 18 through month 36, 100% of study eyes maintained a BCDVA of 20/30 or better.” (opens the source at this quote in a new tab)

BCDVA	Screening	36 Months
n	“23”	“21”
20/20 or better	“0%”	“62%”
20/30 or better	“35%”	“100%”
20/40 or better	“48%”	“100%”

36-month results as presented at the Interventional Glaucoma Consortium 2025

“37% reduction in mean IOP in evaluable patients across all dose groups from 25.1 ± 2.5 mmHg at baseline post-washout to 15.9 ± 2.7 mmHg.” (opens the source at this quote in a new tab)
“95% of evaluable patients were off all topical IOP-lowering medications.” (opens the source at this quote in a new tab)
“100% of evaluable patients achieved 20/30 or better BCDVA.” (opens the source at this quote in a new tab)
“No product-related AEs were reported.” (opens the source at this quote in a new tab)

Earlier data cut: 18 months presented at ASCRS 2025

“To start, patients’ baseline post-washout IOP was 25.1 ± 2.5 mmHg.” (opens the source at this quote in a new tab)
“By 18-months postop, IOP was reduced to 14.1 ± 2.6 mmHg (p < 0.0001).” (opens the source at this quote in a new tab)
“By the 18-month follow-up visit, investigators reported that all 23 patients remained off IOP-lowering topical medications” (opens the source at this quote in a new tab)

Earlier data cut: 18 months presented at Glaucoma 360 2025

“After 18 months, mean IOP reduction was 43.7%, with 96% of patients maintaining pressure at or below 18 mm Hg.” (opens the source at this quote in a new tab)

Earlier data cut: 24 months

“At 24 months, 100% of patients had discontinued topical IOP-lowering therapy, a 42% mean reduction in IOP was achieved across all three bimatoprost doses, and 100% of patients had a distance BCVA of 20/30 or better.” (opens the source at this quote in a new tab)

Four-year follow-up

“BIM-IOL System: Four-year efficacy and safety follow-up expected in fourth quarter of 2026.” (opens the source at this quote in a new tab)

Effect of the two withdrawals in the 300 microgram cohort on the month 36 analysis

“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.” (opens the source at this quote in a new tab)

Cumulative adverse events through 36 months

Adverse event	75 μg, n = 8 (%)	150 μg, n = 8 (%)	300 μg, n = 7 (%)	Overall, 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%)”

Prostaglandin-class effects, implant stability, and serious events

“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)
“No deaths or serious adverse events related to the implant occurred.” (opens the source at this quote in a new tab)

Corneal endothelial cell density and anterior chamber inflammation

“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)
“There was no anterior chamber inflammation observed in any subject’s study eye for the remainder of follow-up.” (opens the source at this quote in a new tab)

Sponsor summary of product-related adverse events

“All AEs that were observed were considered to be related to the cataract procedure and none were deemed to be associated with our product candidate.” (opens the source at this quote in a new tab)

Anterior chamber cell clearance at month 1

“Anterior chamber cell clearance at 1 month was 91.7%, a value within the range of cataract surgery with standard IOLs” (opens the source at this quote in a new tab)

Method used for the endothelial cell density measurements

“Although endothelial cell density measurements did not employ a validated reading center methodology, outcomes from automated measurements are reported.” (opens the source at this quote in a new tab)
“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.” (opens the source at this quote in a new tab)

Summary

The long-term evidence comes from one sponsor-funded, single-surgeon, single-site cohort of 23 eyes in Honduras, with sequential unmasked dose assignment, no control group, and registration completed retrospectively in September 2025, after the 6-month pilot ended and 36-month follow-up was in progress. All participants were Hispanic or Latino with primary open-angle glaucoma, 87.0% were controlled on one medication before washout, and prior response to topical prostaglandin analogs was required. The study did not include a cataract-surgery-only comparator, although cataract extraction alone lowers IOP by 2 to 4 mmHg in glaucoma populations. Endothelial cell counts were automated without reading-center verification, and specular microscopy stopped after month 12. The authors state that the sponsor participated in design, analysis, and manuscript preparation, and that several authors are SpyGlass employees, consultants, or shareholders. The studied doses (75, 150, and 300 μg) differ from the Phase 3 dose (78 mcg).

Limitations stated by the authors

“This first-in-human study has important limitations, including small sample size, nonrandomized design, and selection of prior prostaglandin analogue responders.” (opens the source at this quote in a new tab)
“This criterion selected for eyes that would be more likely to benefit from the bimatoprost implant, possibly inflating efficacy metrics.” (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” (opens the source at this quote in a new tab)
“Retrospective registration of the current study increases risk for bias; outcomes should thus be interpreted cautiously.” (opens the source at this quote in a new tab)

Sponsor role in the publication

“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.” (opens the source at this quote in a new tab)