Researchers led by Tock H. Lim, MBBS, of Singapore, set out to determine the 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV). This 24-month, phase 4, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among 322 Asian participants with symptomatic macular PCV confirmed using indocyanine green angiography. Participants were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group). All participants received 3 consecutive monthly ranibizumab injections, followed by a PRN regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a PRN regimen based on the presence of active polypoidal lesions.

Key outcome measures were evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions. Among 322 participants, the adjusted mean BCVA gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24. Participants in the combination group received fewer ranibizumab injections than the monotherapy group. The combination group required a median of 2.0 vPDT treatments for 24 months, with 44.6% requiring only 1 vPDT treatment. The 24-month findings, published in JAMA Ophthalmology, confirm that ranibizumab therapy, given as monotherapy or in combination with vPDT, is efficacious and safe for treatment of PCV. Combination therapy with vPDT added to ranibizumab achieved superior BCVA gain, increased odds of complete polypoidal lesion regression, and fewer treatment episodes compared with ranibizumab monotherapy.