High-Volume Intravitreal Injections Show No Increased Glaucoma Risk, with Deepak Sambhara, MD

According to recent research, there is no increased risk in the development of glaucoma or ocular hypertension with the use of new, high-volume intravitreal agents avacincaptad pegol (ACP), pegctacoplan (PEG), and aflibercept 8mg (AFL8), despite higher injection volumes compared to other intravitreal therapies.

Presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, this retrospective, multicenter, database analysis exclusively included treatment-naïve eyes starting intravitreal therapy for neovascular age-related macular degeneration (nAMD).1

HCPLive sat down with lead investigator Deepak Sambhara, MD, Eye Clinic of Wisconsin, to discuss his presentation and the rationale behind the study.

“We have all these new medicines that have hit the market, and in 2023, between aflibercept 8mg, pegcetacoplan, and avacincaptad pegol, we had three new medicines hit the market in one calendar year, all requiring higher volumes of administration relative to what we’ve been used to with intravitreal treatments,” Sambhara told HCPLive. “So, the natural question becomes, do these newer, higher volume medicines pose an additional risk for developing glaucoma or ocular hypertension?”

Investigators collected data from 2015-2024; they gathered the baseline characteristics, change in intraocular pressure (IOP) from baseline, treatment intervals, and formal diagnoses of ocular hypertension or glaucoma for each patient. Eligible patients were required to have ≥6 months of follow-up and ≥3 injections. Patients were excluded if they had any history of significantly elevated IOP, ocular trauma, ocular hypertension or glaucoma, evidence of IOP-lowering therapies, baseline phakic lens status, or prior use of ocular or systemic steroids.1

Investigators also notably censored eyes from the study on the first evidence of ocular trauma, steroid use, switching intravitreal agents, receiving multiple concurrent treatments, or treatment discontinuation in follow-up.1

Patients receiving ACP, PEG, and AFL8 were matched in a 1:1 or 1:2 ratio with a control cohort, the members of which received 50 µL intravitreal injections, across several baseline characteristics such as age, IOP, total injections, and duration of follow-up. Investigators used mixed-effects Cox regression models to assess risk of adverse events; P <.05 was considered statistically significant.1

A total of 2405 eyes were included in the study; of these, 565 received ACP, 1526 received PEG, and 314 received AFL8. Another 3751 eyes were included in the control cohort; 861 for ACP, 574 for AFL8, and 2316 for PEG. Mean (standard deviation [SD]) age of patients was 82.7 (5.7) years in the ACP group and 82.6 (5) in the ACP control group, 83.1 (5.1) in the PEG group and 83.1 (5) in the PEG control group, and 81.9 (6.9) in the AFL8 group and 81.6 (6.7) in the AFL8 control group.1

Investigators noted high myopia at baseline in <1% of patients across all groups. Mean (SD) IOP in mmHg at baseline for the overall study and control cohorts were 14 (3) and 14(3), respectively. Mean (SD) visual acuity in ETDRS letters at baseline for the overall study and control cohorts were 56.3 (22) and 57.6 (22.3), respectively.1

Investigators noted an insignificant mean IOP change at 6 months and 1 year. Per injections, mean IOP change at 3 injections was -.1 (0) for ACP and -.2 (0) for ACP control, 0 (0) for PEG and -.1 (0) for PEG control, and -.5 (-1) for AFL8 and -.3 (0) for AFL8 control. At 7 injections, it was .3 (0) for ACP and 0 (0) for ACP control, -.2 (0) for PEG and 0 (0) for PEG control, and -.5 (0) for AFL8 and .5 (1) for AFL8 control.1

Additionally, investigators found nothing to support an increased risk of ocular hypertension or glaucoma, an IOP elevation of >5, or a significant IOP of 25 among the study cohort compared to control during the 18-month follow-up period.1

Sambhara also commented on the possible explanation for the lower IOP during the trial, citing alternative techniques applied during the medications’ approval processes.

“We know that, in the clinical trials, in order to obviate the necessity of more interventions during the procedure or immediately after, there were techniques that were administered: Q-tip decompression, preoperative drops, or immediately post-operative anti-ocular hypertensive drops,” Sambhara said. “The problem with large real-world data is sometimes we are beholden to what’s actually being documented, so there’s not a standardized way to capture that.”

Editor's Note: Sambhara reports disclosures with Evolve Medical, Genentech, Regeneron, Apellis Pharmaceuticals, Advernum, 4DMT, and others.

References

1. Sambhara D. Real-World Intraocular Pressure (IOP) and Glaucoma Outcomes from Intravitreal Treatments Based on Injection Volume. Presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, July 30-August 2, 2025.