Adding reduced-fluence photodynamic therapy to intravitreal aflibercept injections may not improve 52-week visual acuity outcomes compared with aflibercept alone in patients with polypoidal choroidal vasculopathy, according to a randomized clinical trial. However, the combination therapy could help achieve higher early polypoidal lesion closure rates.
Researchers conducted the double-masked, sham-controlled randomized clinical trial at two centers in Singapore between 2021 and 2024. The study enrolled 60 treatment-naive patients aged 50 years or older with symptomatic macular polypoidal choroidal vasculopathy confirmed on indocyanine green angiography. The researchers randomly assigned the patients to receive reduced-fluence photodynamic therapy plus 2 mg intravitreal aflibercept injections or sham photodynamic therapy plus 2 mg intravenous aflibercept injection. Following baseline treatment, the patients were evaluated every 4 weeks through week 52 and received additional aflibercept injections according to a protocol-defined pro re nata regimen.
The primary outcome of the study was the change in best-corrected visual acuity at week 52. Nonetheless, the researchers reported that the mean visual acuity gains were similar between the groups, with patients gaining 12.7 letters in the combination therapy arm compared with 11.9 letters in the monotherapy arm. One-third of the patients in both groups gained at least 15 Early Treatment Diabetic Retinopathy Study letters, and no patients lost five or more letters. Approximately 80% of the patients receiving combination therapy and 73% receiving monotherapy achieved visual acuity of 20/40 or better by week 52.
Secondary anatomic outcomes favored combination therapy for polypoidal lesion closure. At week 12, lesion closure occurred in 67% of the patients receiving reduced-fluence photodynamic therapy plus intravitreal aflibercept injection compared with 33% of those receiving intravitreal aflibercept injection alone. By week 52, the closure rates increased to about 73% and 47%, respectively. Reductions in central subfield thickness were similar between the two patient groups.
The researchers noted that the patients in the combination group received a mean of four aflibercept injections during follow-up compared with nearly five injections in the monotherapy group. They reported no cases of endophthalmitis, retinal detachment, or treatment-emergent vitreous or submacular hemorrhage in either group.
The researchers noted several limitations, including enrollment of only 60 of the planned 160 patients because of delays associated with the COVID-19 pandemic and a global verteporfin shortage. The reduced sample size limited the researchers' ability to establish superiority or non-inferiority for visual acuity outcomes. They also stated that secondary outcomes weren't adjusted for multiple analyses and should be considered hypothesis generating.
“In summary, with less than half of the planned sample size enrolled, no superiority in [best-corrected visual acuity] outcomes for either arm was detected,” wrote lead study author Yu Jeat Chong, MD, of the Singapore Eye Research Institute and the Department of Medical Retina at the Singapore National Eye Centre, and colleagues. The researchers added that greater polypoidal lesion closure with combination therapy was "not associated with a clinically relevant functional outcome in this trial.”
The study was funded by the Singapore Ministry of Health's National Medical Research Council. Full disclosures of the study authors can be found in the study.
Source: JAMA Ophthalmology
