A comprehensive real-world analysis of over 6,000 eyes has demonstrated that newer high-volume intravitreal therapies do not increase the risk of developing glaucoma or ocular hypertension, addressing a key safety concern following the 2023 approval of three agents requiring larger injection volumes.
The retrospective, multicenter database analysis, presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists, examined outcomes for avacincaptad pegol (ACP), pegcetacoplan (PEG), and aflibercept 8mg (AFL8) compared to standard 50 µL intravitreal injections in treatment-naïve patients with neovascular age-related macular degeneration.
Study Design and Patient Population
Lead investigator Deepak Sambhara, MD, from the Eye Clinic of Wisconsin, explained 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."
The study utilized data from the Vestrum Health database spanning 2015-2024, applying strict inclusion and exclusion criteria. A total of 2,405 eyes received the high-volume agents: 565 received ACP (100 µL), 1,526 received PEG (100 µL), and 314 received AFL8 (70 µL). These were matched in a 1:1 or 1:2 ratio with 3,751 control eyes receiving standard 50 µL injections.
Patients were required to have at least 6 months of follow-up and three or more injections. The study excluded eyes with any history of significantly elevated intraocular pressure (IOP), ocular trauma, glaucoma, or prior use of IOP-lowering therapies.
Baseline Characteristics and Demographics
Mean patient age was consistent across groups, ranging from 81.6 to 83.1 years. Baseline IOP was 14 mmHg (standard deviation 3) for both study and control cohorts. Mean visual acuity at baseline was 56.3 ETDRS letters for the study cohort and 57.6 letters for controls. High myopia was present in less than 1% of patients across all groups.
Intraocular Pressure Outcomes
The analysis revealed stable IOP measurements throughout the follow-up period. Mean IOP changes were minimal and not statistically significant at both 6 months and 1 year. At 3 injections, mean IOP changes were -0.1 mmHg for ACP versus -0.2 mmHg for controls, 0 mmHg for PEG versus -0.1 mmHg for controls, and -0.5 mmHg for AFL8 versus -0.3 mmHg for controls.
At 7 injections, the changes remained within 1 mmHg across all groups, with no clinically meaningful differences between high-volume agents and their matched controls.
Glaucoma Risk Assessment
Cox proportional hazards analysis found no statistically significant increase in the risk of IOP elevation greater than 5 mmHg for aflibercept 8mg and ACP groups. While PEG showed a statistically significant risk compared to controls (P=0.038), Sambhara cautioned against drawing broad conclusions from this isolated finding.
Importantly, there was no statistically significant risk of IOP rising above 25 mmHg in any treatment group during the 18-month follow-up period. The incidence of newly diagnosed glaucoma did not differ significantly between patients receiving higher-volume agents and their control counterparts.
Clinical Implications and Future Monitoring
The findings provide reassurance for clinicians using these newer therapies. "The real-world data that exist corroborate what we've seen in the clinical trials, which is that there is not a higher risk, at least at this point, in developing glaucoma," Sambhara noted.
However, he emphasized the need for continued vigilance: "As newer agents come to the market that have higher than normal volumes that are injected, we need to have longitudinal follow up to better contextualize data and monitor these patients over time."
The study's results are particularly significant given the volume differences between these agents and traditional intravitreal therapies, with the new medications requiring 40-100% more volume per injection. The data support the continued use of these therapies without additional IOP monitoring beyond standard clinical practice.
