Polypoidal Choroidal Vasculopathy Landmark Studies

Medical Treatment of PCV

Current treatment plans can be formulated based on three pieces of information: the location of the PCV complex, the baseline vision, and the response to previous therapy. Options available are photodynamic therapy (PDT), anti-VEGF therapy, combination of PDT and anti-VEGF, and laser photocoagulation.


The results of the EVEREST clinical trial highlighted a higher rate of polyp closure with PDT alone or when combined with ranibizumab.   They found a greater polyp regression with PDT combined with ranibizumab (77.8%), followed by PDT alone (71.4%) and less closure with ranibizumab alone (28.6%).   

The EVEREST-II and PLANET evaluated anti-VEGF and combination therapy. EVEREST II compared ranibizumab with combination of ranibizumab and PDT at baseline and PLANET, aflibercept with or without rescue PDT available after 3 months. Both studies showed a significant gain in visual acuity in the anti-VEGF monotherapy arm at 1 year. Polyp closure rates were 34.7% (EVEREST-II) and 38.9% (PLANET). The mean of injections was 7.3 for (EVEREST-II) and 8.1 (PLANET). 

A recently published analysis of the Japanese cohort of EVEREST II study over 12 months confirmed the same conclusion as in the 24–month study. The best available evidence suggests that combination therapy resulted in improved vision and achieved a higher rate of complete polyp regression with a lower number of anti-VEGF injections when compared with monotherapy

Our recommendations based on available study data to include PDT as art of treatment are based on the following:

  1. If subfoveal or juxtafoveal PCV and
    1. a.
      Baseline vision worse than 20/40 PDT monotherapy or PDT plus anti-VEGF better than no PDT;
    2. b.
      If vision 20/40 or better an intense and consistent treatment with anti-VEGF alone may be preferable because of the rare PDT complication of choroidal ischemia or subretinal hemorrhage.

2.Anti-VEGF alone can reduce serosanguinous complications in PCV.

Anti-VEGF Therapy

PCV has a less reliable response to anti-VEGF therapy than exudative AMD. Aqueous humor of eyes with PCV contains high levels of VEGF when compared to controls but less than in eyes with exudative AMD. In Asia, PDT has been the first-line therapy for PCV while in the USA, anti-VEGF is often first-line treatment for serosanguinous maculopathy. 

Few retrospective studies with bevacizumab showed a low rate of polyp closure (21%). 

Characteristics associated with better vision outcome such as smaller lesion, absence of PED at baseline, and no CNV recurrences. 

The PEARL 1 study, a prospective, open-label clinical trial of monthly intravitreal ranibizumab injections (IRI) in 13 eyes showed statistically significant improvement in visual acuity and decrease in central foveal thickness (CFT) at 1 year. This study found a decreased volume of the PCV complexes in 38%, but an increase in 31% after 1 year. When a higher dose of IRI was used (2.0 mg) in 19 eyes in the PEARL 2 study , there was a better response in polyp regression at 6 months (78.9% decreased polyps vs 21.1% stable), similar to EVEREST study results in the PDT subgroups. 

EVEREST II showed that combination therapy resulted in superior visual and angiographic outcomes at the same time reducing the need for repeat injections during the first year of treatment.

In the LAPTOP study, a prospective, multicenter randomized clinical trial comparing PDT with IRI showed a superior visual acuity in the IRI arm. Recently, long-term visual acuity results in 29 eyes with PCV based on the first-choice treatment, either PDT or IVR concluding that the better VA in the initial IRI group compared with the PDT group at 2 years was retained at the 5-year follow-up. 

The EPIC study was a 6-month prospective open-label investigator-sponsored trial in 21 eyes that evaluated the treatment results of intravitreal aflibercept injections (IAI) for PCV with hemorrhage and exudation in eyes previously treated with ranibizumab and bevacizumab. At 6 months, vision was stable or improved in 19/21 eyes (91%). Subretinal fluid resolved in 72% of the eyes, and subretinal hemorrhage resolved in 75%. The polyps regressed in 67% of the eyes and the BNV decreased in one eye only but was stable in all other eyes. The retinal pigment epithelial detachment (PED) improved in 87% of the eyes. 

The 96-week multicenter randomized clinical trial PLANET study compared IAI monotherapy with IAI with rescue PDT. They all received initially monthly IAI for 3 months. Vision and/or functional outcomes were achieved in more than 85% of participants who were treated with IAI only, and no signs of leakage from polypoidal lesions in more than 80%. The potential benefit of adding PDT could not be determined unfortunately since only fewer than 15% met the criteria of a suboptimal response to receive PDT. 

Currently, there is no evidence that adding PDT to aflibercept can give any additional benefit to the patient. If aflibercept is used, fixed dosing should be planned and patient prepared.

Reference : 

  1. Goldhardt R, Rosen BS. Polypoidal Choroidal Vasculopathy. Curr Ophthalmol Rep. 2019;7: 66–72. doi:10.1007/s40135-019-00201-4

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