High-Dose Eylea Not Associated With Elevated IOP Risk | ASRS 2024

At 70 microliters, the volume of the intravitreal injection of the high-dose, 8-milligram (mg) version of Eylea (aflibercept) is larger than the 50 microliter volume of the original 2-mg version of the anti-vascular endothelial growth factor (VEGF) drug used to treat several common retinal diseases, including wet age-related macular degeneration, diabetic macular edema (DME) and diabetic retinopathy (DR). That higher volume has caused some concern that high-dose version of the injections, although given less frequently, might cause harmful increases in pressure within the eye, known as intraocular pressure (IOP) and possibly glaucoma-related treatment.

Results of a post-hoc analysis of the PHOTON trial presented at the America Society of Retina Specialists(ASRS) this week may allay those worries. Positive results from the PHOTON study led to FDA approval of high-dose Eylea for diabetic macular edema and diabetic retinopathy.

Jordana Fein, M.D., M.S.

Jordana Fein, M.D., M.S., a retinal specialist at the Retina Group of Washington in Washington, D.C., and the nearby areas of Maryland and Virginia, shared data showing that in patients with diabetic macular edema there was little difference in IOP in all the treatment groups from the start of the 48-week PHOTON trial to its end. The PHOTON trial had three treatment groups: patients who received the standard 2-mg version, the high-dose, 8-mg every 12 weeks or that higher dose every 16 weeks. Fein noted patients could receive the 2-mg in the “fellow eye,” according to the discretion of investigators. At the start of the study, the mean I0P in the in 2-mg, 8-mg every 12 weeks and 8-mg every 16 weeks groups were 15.9 mm Hg, 15.3 mmHg and 14.9 mmHg, respectively. At Week 48, the IOP for those three groups 15.7 mmHg, 15.1 mmHg and 14.8 mmHg, respectively. The abstract of her presentation noted that across all the three group, the mean changes from baseline to the end of trial, a 48 week span, did not exceed ± 1 mmHg. She noted that changes in IOP were similar in the treated and the untreated fellow eyes “suggesting that there was no drift in IOP over time.”

Three eyes were treated with a glaucoma procedure, anterior chamber paracentesis, which involves removing aqueous humor from the eye. Two of the eyes were in the 8-mg study arms and was in the 2-mg fellow study arm, Fein said.

A small percentage — 8% — of the patients in the PHOTON study were classified as having a glaucoma-related history, which meant having glaucoma or “glaucoma suspect,” a term that ophthalmologists use for patients with signs that suggest that are at high risk for developing the disease. Of those patients, 7.7% of those receiving 8-mg injections of Eylea were treated with IOP-lowering drops compared with 16.7% of those receiving 2-mg injections.

Two other analyses of the large amounts of data generated PHOTON study were presented in the Wednesday morning session devoted to findings about high-dose Eylea and Vabysmo (faricimab), an anti-VEGF agent that is FDA-approved treating retinal diseases.

One compared patients with poor vision (best-corrected visual acuity [BCVA] 20/50 or worse] to those with better vision (BVCA 20/40 or better). The results shared by Diana V. Do, M.D., vice chair of clinical affairs and a professor of Ophthalmology at the Byers Eye Institute at the Stanford University School of Medicine, showed that vision improved among both those with poor and better vision but larger gains among those who started with worse vision. A measure of the anatomical effects of Eylea, the changes in central retinal thickness, were also more favorable in those with poor vision.

The other study compared patients whose diabetic macular edema had been treated before they enrolled in the PHOTON trial to those whose hadn’t been treated. While generally comparable, the results shown by Dennis Marcus, M.D., of Southeast Retina in Augusta, Georgia, showed that those who hadn’t been treated experienced the greater gains in BCVA and in central retinal thickness than those that had,. “This might be expected,” Marcus told the ASRS audience. “”At baseline these eyes [without treatment] had slightly greater severity of retinopathy, leaving more room for improvement” Marcus noted that the group of patients who had been previously treated who were treated with 8-mg Eylea at 16 week intervals experienced lower gains in vision than others in the study.