Aflibercept yields visual acuity gains, anatomic benefits in polypoidal choroidal vasculopathy
Intravitreal aflibercept injection (IAI) appears to be safe and effective in the treatment of polypoidal choroidal vasculopathy (PCV), producing improvements in visual and/or functional outcomes without any signs of leakage lesions in most patients, according to the results of the PLANET study.
The one-year data from the PLANET study “show that IAI monotherapy is a suitable treatment option to safeguard most people with PCV from deteriorating to a level at which rescue treatment would be required,” the investigators said. “However, it is not known how adjunctive combination treatment with PDT [photodynamic therapy] at the initiation of IAI treatment would compare with IAI given alone.”
“Considering the potential risks of PDT, including cumulative damage to normal choroidal vasculature and retinal pigment epithelium following repeated administration, deferring PDT in patients in whom fluid is detected on OCT [optical coherence tomography] but with good visual acuity, as in the PLANET protocol, appears to be a reasonable approach,” they added.
Conducted at multiple centres in Asia and Europe, the 96-week PLANET trial included 333 patients with symptomatic macular PCV and a best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/40–20/320 Snellen equivalent). All patients received 2 mg of IAI at weeks 0, 4 and 8.
Patients who showed a suboptimal response at week 12 (n=318; mean age 70.6 years; 30.2 percent women; 47.8 percent Japanese) were randomized to treatment with either IAI plus sham PDT (IAI monotherapy; n=157) or IAI plus rescue PDT (IAI/PDT; n=161). Those who did not qualify for rescue received IAI every 8 weeks. Those who did qualify received IAI every 4 weeks, with the interval gradually extended to 8 weeks when the rescue criteria were no longer met.
The main outcome measure of noninferiority of IAI monotherapy to IAI/PDT was achieved. Specifically, the mean BCVA from baseline to week 52 increased by 10.7 vs 10.8, respectively (p=0.55), with few patients requiring rescue treatment (12.1 percent vs 14.3 percent, respectively). Moreover, reductions in central subfield thickness were comparable between the two treatment groups (–137.7 μm with IAI monotherapy vs –143.5 μm with IAI/PDT). [JAMA Ophthalmol 2018;doi:10.1001/jamaophthalmol.2018.1804]
There were no polypoidal lesions observed on indocyanine green (ICG) angiography in 38.9 percent of patients in the IAI monotherapy arm and in 44.8 percent in the IAI/PDT arm. Furthermore, the majority showed no polypoidal lesions with leakage (81.7 percent and 88.9 percent, respectively).
Safety did not significantly differ between IAI monotherapy and IAI/PDT, with ocular treatment-emergent adverse events (AEs) at week 52 occurring in 31.2 percent and 29.2 percent, respectively. The most commonly reported AEs were conjunctival haemorrhage and dry eye.
The present data show that IAI is associated with reduced ICG angiographic leakage or presence of polypoidal lesions in most patients and is well tolerated, the investigators said.
“The addition of PDT to IAI did not demonstrate additional benefits in visual outcomes. However, as only a few participants required and received PDT, the benefit of adding PDT to IAI for PCV cannot be elucidated from this trial,” they added.
There are several limitations to the study. As the investigators acknowledged, the number of participants who qualified and received rescue PDT therapy (<15 percent qualified for rescue up to week 52) was small. Also, the rescue criteria for PLANET may not be reflective of all clinical practice (BCVA ≤73 ETDRS letters; BVCA gain of <5 ETDRS letters or gain of ≥5 but <10 ETDRS letters; new or persistent fluid on OCT; and evidence of active polypoidal lesions).