Combined half-dose verteporfin photodynamic therapy and anti-vascular endothelial growth factor injection in the treatment of polypoidal choroidal vasculopathy

Abstract

Polypoidal choroidal vasculopathy (PCV) is a disorder of the macula affecting central vision. The hallmark of the disease is presence of choroidal polypoidal lesions. Typical presenting features include reduction in vision, metamorphopsia, subretinal exudation, hemorrhage, with eventual subretinal scar formation and loss of central vision. It belongs to the spectrum of diseases called pachychoroid. Conventionally, recommended treatment consist of performing photodynamic therapy (PDT) with the drug verteporfin, combined with intravitreal injection so anti-vascular endothelial growth factors. This regimen has been proven to be effective in bringing about improved vision and regression of choroidal polyps. The use of PDT is justified in PCV as it brings about polyp regression through choroidal vascular remodelling. However, it is also known to cause potential side effects, including reduction in retinal sensitivity, choroidal hypoperfusion, subretinal hemorrhage, choroidal neovascularization formation. There is a need to modify the settings of PDT to minimize the risks of side effects yet maximizing treatment outcome. The initial pilot study reported outcomes in treating 19 treatment-naive PCV subjects with half-dose PDT combined with intravitreal injections of ranibizumab. With half-dose PDT, 100% polyp regression rate at 12 months was achieved with no reported treatmentrelated complications. Best-corrected logMAR visual acuity increased from 0.64 } 0.37 at baseline to 0.41 } 0.25 at 12 months. The mean central foveal thickness reduced from 459.6 } 167.3μm at baseline to 384.2 } 194.9μm at 12 months. The differences were statistically significant (P = 0.03, P = <0.01 respectively). Next, a Sprague Dawley rat model experiment was carried out to investigate how modification of the PDT settings could bring about the least damaging effects in the retina and choroid. A total of 64 SD rats were used, and results showed that in-vitro findings suggested that half-dose PDT produced less damaging effects than half-fluence or standarddose PDT. This was shown through histological examination of the choroidal vasculature, and also electroretinogram testing of live SD rats that have received the treatments. This confirmed that half-dose PDT was safer than half-fluence or standard-dose PDT Lastly a randomized controlled trial with 58 PCV subjects was conducted, where they were assigned to received either half-dose PDT or standard-dose PDT, combined with intravitreal injections of ranibizumab. Best-corrected visual acuity in the half-dose PDT arm improved significantly from baseline to Month-12 (P = 0.004), while that in the standarddose PDT arm did not reach statistical significance (P = 0.256). Polyp regression was achieved in all subjects at Month-12. Polyp regression rate after one single PDT session was 73.1% (19 out of 26) in the half-dose PDT arm and 87.5% (28 out of 32) in the standard-dose PDT arm. Treatment outcome showed that visual performance were grossly similar amongst the two groups of subjects, showing non-inferiority in treatment efficacy. Evidences from these studies proved half-dose PDT modification could be a viable option for patients with PCV. Based on presenting features, some patients with less severe disease may benefit from this modified protocol to maximize treatment outcome.