PCV treatment options

Polypoidal choroidal vasculopathy is a complex disease demanding 
a customised approach

Dermot McGrath

Posted: Thursday, March 1, 2018

There is pronounced inter-individual variability in subfoveal choroidal thickness and values were distributed over a wide range. Image courtesty of Won Ki Lee MD, PhD

Polypoidal choroidal vasculopathy (PCV) is a complex disease and may require a customised approach that draws on different treatment strategies to ensure the best patient outcomes in the long term, according to Won Ki Lee MD, PhD.

“There are lots of unanswered questions in relation to PCV management. Is anti-VEGF monotherapy or combination therapy with anti-VEGF and photodynamic therapy (PDT) better? Are there any prognostic factors in indocyanine green angiography (ICGA), optical coherence tomography (OCT) or choroidal morphology to guide our treatment choices? Is there an optimal anti-VEGF drug, what is the ideal dosing and how can we determine a non-responder or poor responder to a given drug?” Dr Lee said at the 17th EURETINA Congress in Barcelona.

Other relevant questions include at what point the clinician should consider switching to other drugs or PDT, and how many PDT sessions can be applied safely without significant complications, he added.

Dr Lee said that anti-VEGF therapy is usually the first-line treatment of choice. He noted that the recent EVEREST II clinical trial found that ranibizumab and PDT was superior to ranibizumab monotherapy in improving visual acuity and achieving complete polyp regression at 12 months.
However, bearing in mind that many clinicians remain concerned about PDT-related complications, Dr Lee and co-workers decided to perform a retrospective study looking at the long-term outcomes of 47 treatment-naïve PCV eyes over nine years of treatment. Patients were treated initially using PDT alone or combination therapy between December 2004 to June 2008 followed by additional PDT and/or anti-VEGF monotherapy on an as-needed basis.

The study showed that initial PDT/anti-VEGF combination therapy could reduce the injection frequency. However, patients treated with multiple PDTs initially received more anti-VEGF injections later and had poorer final visual acuity outcomes, implying either that multiple-session PDTs had a negative impact on the outcomes, or that poor responders to PDT also responded poorly to anti-VEGF treatment.

“I believe that PDT is still a viable treatment option in PCV. However, multiple PDTs result in cumulative damage to the surrounding choroid, with choroidal ischaemia and VEGF upregulation, which induces more malignant or bizarre patterns of polyps and neovascularisation, fibrous scarring and RPE atrophy,” he said.
For this reason, Dr Lee said that he endeavours to keep PDT sessions to the strict minimum.

“If a repeat session can’t be avoided I try to use either selective PDT, which was also used in the EVEREST II study, or some reduced fluence or half-dose PDT. My own personal preference, however, is for deferred PDT, where it is reserved as a rescue therapy in patients with active polyps and a limited response to anti-VEGF injections,” he said.

This strategy was tested in the PLANET study, in which 318 patients initially received three monthly aflibercept injections and were randomised into two arms at week 12, stratified by qualification for rescue treatments: one with aflibercept plus sham PDT or the other with aflibercept plus active PDT.
The results showed that aflibercept monotherapy was effective in the treatment of PCV over 52 weeks, with mean improvement in best-corrected visual acuity (BCVA) of 10.7 letters. More than 85% of patients did not require any rescue therapy and more than 80% of patients had no active polyps. The authors concluded that the combination of intravitreal aflibercept with PDT did not appear to provide any additional functional benefits, and PDT therapy does not seem to be required for the vast majority of patients with PCV when treated with aflibercept.

Nevertheless, Dr Lee said there was no “one size fits all” approach to treating PCV.
“It is actually very heterogeneous in terms of polyp size, number, internal structure, branching pattern, total lesion size and lesion location. There is also a lot of diversity in the choroidal features between patients,” he said.
In general, PCV with small polyps and small lesion sizes respond well to anti-VEGF treatments as well as combination therapy. By contrast, PCV lesions associated with choroidal hyperpermeability and/or increased choroidal thickness do not respond favourably to anti-VEGF therapy. One recent study, however, reported that aflibercept induced significant reduction of choroidal thickness and was effective in eyes with choroidal vascular hyperpermeability.
Summing up, Dr Lee said that his preference to treat PCV is anti-VEGF therapy and deferred PDT, starting with three loading doses of anti-VEGF and using aflibercept in cases with increased choroidal thickness.

“I try to determine responsiveness to a drug, including switched drugs, at six-to-12 months. I maintain anti-VEGF treatment in good responders with an acceptable injection frequency and consider PDT in non-responders or cases requiring too frequent injections. For recurrent lesions after PDT, I recommend restricting the number of PDT sessions with anti-VEGF as first-line treatment. In refractory cases, I try selective PDT or laser, or half or reduced-fluence PDT covering the whole lesion before considering standard PDT covering the whole lesion,” he said.