Intraocular Pressure Events Rare After Lampalizumab for Geographic Atrophy


These data pointed to a low risk of persistent IOP increases of intravitreous 0.1-mL injection volumes administered for 1 year in eyes with GA.

| Image Credit: V2osk/Unsplash

Credit: V2osk/Unsplash

A post hoc analysis of two randomized clinical trials (RCTs) identified low rates of intraocular pressure (IOP)-related events after 1 year of 0.1 mL intravitreous injections of lampalizumab for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).1

The research, published in JAMA Ophthalmology, showed that IOP increases remained rare, with no observed changes in mean pre-injection IOP rates in participants treated with either lampalizumab or sham at Week 48.

“This information could help inform future clinical trial design as well as support safety evaluations of more recently approved intravitreous injections that use volumes of 0.07 to 0.01 mL,” wrote the investigative team, led by Jillian Martin, MD, MPH, Genentech.

Anti-vascular endothelial growth factor (anti-VEGF) therapies are the standard-of-care for retinal diseases, including AMD, and are typically associated with low incidence of serious adverse events.2 Acute IOP increases have been observed in those receiving 0.05-mL intravitreous anti-VEGF injections, but typically return to baseline levels at ≤30 minutes post-injection.3

Recent approvals of intravitreous agents have involved greater volumes of monthly or every other-month 0.07 to 0.1 mL intravitreal injections.4 However, there are a lack of data on whether repeat injections at these volumes may result in IOP-associated adverse outcomes.1

This post hoc analysis sought to describe IOP-associated outcomes at 1 year, including glaucoma and ocular hypertension, after 1 year of repeated injections of 0.1 mL volume of lampalizumab. The drug was evaluated in patients with GA secondary to AMD in 2 identical global Phase 3 clinical trials: CHROMA and SPECTRI.

These randomized, double-masked trials were conducted between 2014 and 2018 and recruited individuals who were ≥50 years old and had bilateral GA. Participants were randomized to receive intravitreous lampalizumab, 0.1 mL every 4 weeks (Q4W) or every 6 weeks (Q6W) or sham injection Q4W or Q6W for 48 weeks.

Posthoc analyses focused on the data for the Q4W arms, assuming monthly treatments could carry greater risk for IOP-related adverse events. IOP was measured at screening, baseline, and before treatment administration at every study visit in the study and fellow eyes.

Among the study population, the mean number of injections per participant in the lampalizumab (n = 627) and sham procedures (n = 311) were 11.6 and 11.7 injections, respectively. Upon analysis, investigators found no change in mean pre-injection IOP values through Week 48 in either lampalizumab- or sham-treated participants.

Safety data showed adverse events requiring IOP-lowering medication were reported more frequently in the lampalizumab arm than the sham arm (65 participants [10.4%] vs. 5 participants [1.6%]). In particular, glaucoma and ocular hypertension were reported for 1.8% of those treated with lampalizumab and 1.6% of those treated with sham.

However, Martin and colleagues indicated most participants who required IOP-lowering medications or procedures to treat these events required the interventions for only a single day (lampalizumab: 41 of 65 [63.1%]; sham procedure: 3 of 5 [60.0%]).

Although these data provide hypotheses for future investigations, limitations, as a result of the posthoc design, could not determine a definitive causal relationship between lampalizumab 0.1 mL injections and changes in IOP. However, Martin and colleagues noted the 48-week follow-up period revealed no persistent increase in mean pre-injection IOP.

“These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL,” investigators wrote.


  1. Bressler NM, Freund KB, Bakri SJ, et al. Intraocular Pressure Outcomes After Lampalizumab Injections in Patients With Geographic Atrophy. JAMA Ophthalmol. Published online June 20, 2024. doi:10.1001/jamaophthalmol.2024.2061
  2. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419-1431. doi:10.1056/NEJMoa054481
  3. Kim JE, Mantravadi AV, Hur EY, Covert DJ. Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial growth factor agents. Am J Ophthalmol. 2008;146(6):930-4.e1. doi:10.1016/j.ajo.2008.07.007
  4. Meyer CH, Melo GB, Khanani AM. Can intravitreal injections with higher volume cause higher intraocular eye pressure? Considerations for anti-complement injections in normal and glaucomatous eyes. Int J Retina Vitreous. 2023;9(1):80. Published 2023 Dec 14. doi:10.1186/s40942-023-00517-1
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