Photodynamic Therapy, Aflibercept Combination Regresses Most Polyps in PCV

Combined photodynamic therapy and aflibercept, injected according to a treat and extend (TAE) protocol, can facilitate complete regression of polyps with higher odds than aflibercept monotherapy for treatment-naïve polypoidal choroidal vasculopathy (PCV), according to a study published in Clinical Ophthalmology. Researchers report that anatomical and visual improvements for patients who received the combination therapy were not significantly different from those seen after intravitreal aflibercept monotherapy.

This retrospective study included 51 eyes of 51 patients (80.4% men; average age, 74.1±1.0 years) who were diagnosed with untreated PCV and had been treated with photodynamic therapy and aflibercept injections in a TAE regimen for 2 years at Gunma University Hospital, Japan, between September 2015 and May 2018.

Diagnosis of PCV was based on the presence of elevated orange-red lesions observed on fundus examination, and characteristic polypoidal with a branching vascular network on indocyanine green angiography (ICGA). 

The team assessed best corrected visual acuity (BCVA), central macular thickness (CMT), and central choroidal thickness (CCT) on each visit. Both CMT and CCT were measured manually on B-scan optical coherence tomography (OCT) images. Macular atrophy was determined by assessing hypoautofluorescence regions in the macula. The greatest linear dimension and area of these regions were measured at baseline, 12 months, and 24 months after the initial treatment.

A total of 32 eyes (62.7%) that underwent both photodynamic therapy and aflibercept did not experience recurrence of exudation after receiving the first 3 aflibercept injections (loading dose). At baseline, the researchers recognized a mean number of 2.24±0.16 polypoidal lesions on ICGA.

Mean BCVA (logMAR units) improved significantly from baseline to 3 months (0.32±0.03 vs 0.21±0.03, P <.01), and remained significantly better after 12 and 24 months (0.15±0.03 [P <.01] and 0.18±0.04 [P <.05], respectively). Mean CMT was 295±15 µm at baseline, and reduced significantly to 157±6 µm at 3 months (P <.001), 156±5 µm at 12 months (P <.001), and 162±7µm after 24 months (P <.001). Initial CCT of 237±15 µm was reduced significantly to 189±14 µm after 3 months (P <0.05), 194±14 µm after 12 months (P <.05), and 183±13 µm (P <.01) after 24 months.

The total mean number of injections in the first year was 7.61±0.16, and 5.12±0.16 in the second year. A total of 17 eyes that were treated with photodynamic therapy and aflibercept had development or progression of macular atrophy (33.4%). The mean area of atrophy was 0.083±0.06 mm² at baseline. It increased significantly after 1 and 2 years (0.49±0.23 mm², 0.70±0.31 mm², respectively, P <.001 for both). 

The study shows complete regression of polypoidal lesions on ICGA in 48 (94.1%) eyes.

The researchers previously conducted a similar trial testing the efficiency of intravitreal aflibercept without photodynamic therapy  for the treatment of patients with PCV, using the same methods. In comparing the 2-year results of the 2 studies, the researchers reportno statistically significant difference between the 2-year CCT and CMT of the 2 groups (P =.2708). The mean number of injections received by patients in each group was comparable (13.2±3.3 and 12.7±1.8 injections, for aflibercept monotherapy and combined photodynamic therapy and aflibercept injection, respectively, P =.06). 

The researchers note no significant difference between the incidence of macular atrophy expansion detected in the groups (25.9 vs 33.4%, odds ratio: 1.40, P =.4253). 

A significantly higher number of eyes had complete resolution of polypoidal lesions after the loading phase in the combined group than in the monotherapy group (94.1 vs 55.2%, P <.0001). 

In earlier research, the EVEREST II (ClinicalTrials.gov Identifier: NCT00209274) trial, combination therapy using ranibizumab and photodynamic therapy had better visual outcomes, thinner central macular thickness, and more regression of polypoidal lesions than ranibizumab monotherapy. “The EVEREST study reported the rates of complete regression of polyps of 77.8% for [photodynamic therapy] with ranibizumab, 71.4% for [photodynamic] monotherapy, and 28.6% for ranibizumab monotherapy at 6 months. In the current study, polypoidal lesions regressed completely in 48 eyes (94.1%) at 3 months,” the researchers explain.

The limitations of the study include its retrospective nature.