The future is looking a bit brighter for patients with polypoidal choroidal vasculopathy (PCV). Not only is imaging technology making it easier for clinicians to diagnose PCV, but recent studies are laying the groundwork to establish treatment guidelines.
To discuss these revelations in PCV diagnosis, imaging, treatment and management, world-renown ophthalmologists recently convened at a Bayer-sponsored symposium at the Asia-Pacific Vitreo-retina Society’s annual congress in Seoul, Korea (APVRS 2018).
On clinical features and diagnosis
While there is no universally accepted definition of PCV – its epidemiological aspects, clinical features and imaging characteristics can help with diagnosis. And according to Dr. Glenn Jaffe, from Duke University, North Carolina, USA, PCV has a variety of features.
“It’s thought to be a subtype of age-related macular degeneration (AMD), characterized by a branching or polypoidal vascular network that lies between Bruch’s membrane and the retinal pigment epithelium (RPE),” he explained. In addition, Dr. Jaffe says that there is typically a choroidal thickening in PCV, and serous retinal detachments are more likely to happen in eyes with PCV than with neovascular AMD (nAMD).
Its differential diagnoses include a variety of conditions: typical nAMD, central serous retinopathy (CSR), pathological myopia with choroidal neovascularization (CNV), choroidal hemangioma (with potential serious detachments), metastasis with serious detachments and lesions in the choroid, and posterior scleritis.
To diagnose PCV, physicians must be aware of its characteristics on the various imaging platforms – and Dr. Jaffe says using a multi-modal approach with different systems can help physicians make the most accurate diagnosis.
Many ophthalmologists consider indocyanine green angiography (ICGA) to be the gold standard in PCV diagnosis. “With ICG angiogram you can have branching vascular networks, along with polyps . . . you can have polyps alone, and you can see these. I like to use dynamic ICGA because you can see different features in different phases of the angiogram that can give diagnostic, and even therapeutic, information,” shared Dr. Jaffe, adding that the late phases provide diagnostic information, too. “You can see a washout phase where the leaking goes away in a lesion that is not active. But in an active lesion, the hypercyanescence persists, so you know that the lesion is still active.”
Of course, not every clinic has access to ICGA. And according to Dr. Jaffe, PCV can be diagnosed on other platforms quite effectively – if physicians know what they’re looking for.
Using optical coherence tomography (OCT), PCV is seen as multiple, peaked pigment epithelial detachments (PED), (which may or may not be related to hemorrhages, exudation, pachychoroid or pachydrusen). It can also appear as a “string of pearls,” with multiple PCV structures under the surface of a detached RPE.
He explained that on fundus photography (FP), orange-yellowish polyp lesions are an indicator of PCV, and OCT angiogram (OCTA) provides additional three-dimensional information about the lesion’s structure. Dr. Jaffe says that fundus autofluorescence (FAF) is an interesting way to look at the lesions, and the polyps can have a variety of appearances: “Most commonly, in about half of the cases, you see a hypo auto-florescent lesion with a surrounding ring of hyper auto-florescence . . . you can also see a reverse pattern, but this is the most common,” he shared.
He also said that fluorescein angiography (FA) is not as helpful for diagnosis. “It tends to be more non-specific, but it can show leakage,” he explained. “I think it’s more useful in follow-up where you can see leakage that either goes away or comes back depending on the treatment. So, it can demonstrate disease activity.”
In addition to the diagnostic variances seen in imaging platforms, there are ethnic differences as well. The prevalence of PCV in Asians is higher than in Caucasians and African Americans (although Dr. Jaffe mentions this could be underdiagnosed in the West due to lack of ICGA systems). In Asians, PCV is more common in males, it appears in a macular location and it’s primarily unilateral.
In other ethnicities, it’s more common in females, with a papillary location and is primarily bilateral. In any case, once a diagnosis is made, Dr. Jaffe notes that treatment is key: “More than 50 percent of untreated patients will lose two lines of visual acuity (VA) over 12 months.”
Determining treatment regimens
Just as the definition of PCV is still in flux, so are the management and treatment regimens. Various clinical trials have reported that treatment with anti-VEGF alone or in combination with photodynamic therapy (PDT) is showing promise in managing PCV. During the symposium, Dr. Min Kim, assistant professor at Gangnam Severance Hospital and Yonsei University College of Medicine in Korea, discussed some of these study results and their implications.
Regarding anti-VEGF monotherapy, several studies (like VIEW 1, VIEW 2 and APOLLO) show that patients treated with aflibercept monotherapy either maintained or improved visual gains. In addition, the APOLLO study showed that 54.8 percent of patients had complete regression of polypoidal lesions at month 6; and by month 12 the number increased to 72.5 percent.
The VAULT study is another example of aflibercept monotherapy, where patients with PCV gained an average of 9 letters at month 12 and showed an improvement in their central macular thickness. In the same study, 67 percent of patients had polyp regression after 12 months.
Dr. Kim also highlighted results from first year of the PLANET study which looked at the safety and efficacy of intravitreal aflibercept (IVT-AFL) monotherapy for treatment of PCV. In this study, all patients received a three-loading dose of IVT-AFL. At three months, participants were randomized into two groups: one with an active rescue PDT arm, the other with a sham arm. At 52 weeks, there was an option for treat-and-extend (T&E).
In the first year, investigators found that patients gained an average of 10 letters and only 15 percent of participants required rescue PDT. At the end of year one, they concluded that IVT-AFL monotherapy was noninferior to IVT-AFL plus PDT.
In addition, real world studies are corroborating this clinical trial data. In two different post-marketing studies (PMS) in Japan and Korea, patients with PCV treated with IVT-AFL achieved vision gains similar to the PLANET study.
Exploring PLANET’s year two results
Adding to the conversation on aflibercept monotherapy was Dr. Tien Yin Wong from Singapore National Eye Centre (SNEC), who discussed year two results from the PLANET study.
“The idea behind the PLANET study was to show the non-inferior qualities of monotherapy,” explained Dr. Wong. “So, if indeed it [PCV] is what we’re now thinking, that it’s a type 1 CNV AMD, what would you expect PLANET to show over two years?”
Dr. Wong says that from 52 to 96 weeks, patients maintained a nine to 10 letter gain – and this is a good outcome for patients. In addition, 94 percent of study participants avoided a loss of vision and more than 80 percent had a dry retina at 52 weeks and up to 96 weeks.
“Basically, this fits with our clinical experience of treating PCV like nAMD,” said continued Dr. Wong.
Polyp activity versus regression
Another outcome of PLANET assessed polyp regression. At 96 weeks, about 30 percent of patients had complete polyp regression – suggesting that two-thirds of patient had some sort of polyp. But are they active polyps? Not necessarily, in fact more than 80 percent did not have active polyps. This is where Dr. Wong makes an important distinction between polyp activity and regression.
“Sometimes, polyps are seen (on ICGA) without any activity – meaning there’s no fluid or impact on function. You may not need to treat if those polyps have not regressed, and if there is no activity” he said. “An active polyp is not the same of having one that’s just still there.”
Dr. Wong says that longer term data is needed to determine if aflibercept monotherapy is sufficient for complete polyp regression, noting that patients who received rescue PDT did not have any additional polyp regression.
So, what about PDT?
Studies, like those mentioned above, have shown that IVT-AFL monotherapy has several benefits over PDT combination therapy. It provides meaningful outcomes in diverse disease subtypes; it’s a simple regimen with no need to purchase specialized equipment; and it avoids the potential long-term side effects associated with PDT.
So, with that said, what role should PDT play in the future?
Dr. Kim warns against mandating PDT at baseline – this could result in overtreatment for many patients, noting that at week 12 of the PLANET study, only 6 percent of patients qualified for rescue PDT treatment.
“Anti-VEGF monotherapy is a simple regimen, and there is no need to access special equipment,” said Dr. Kim, explaining that PDT requires more preparation, is more time-consuming to perform, is costlier to acquire and maintain, and requires specific training.
There are also side-effects associated with long-term use of PDT. “Treating these patients repeatedly with PDT could result in the occlusion of the choriocapillaris which may lead to RPE atrophy,” said Dr. Kim. He also mentioned other studies concerning long-term PDT use – one of which found a 64 percent recurrence of polypoidal lesions and an abnormal branching vascular network (BVN) in all patients.
Thus, the PLANET study is setting the stage to enable PDT to be reserved as a rescue treatment. Dr. Kim notes that this combination therapy (IVT-AFL plus rescue PDT) could be considered in the following cases: if there’s a loss, no change or insufficient VA gains; if persistent fluid is showing on OCT; or if active polyps are observed on ICGA.
Dr. Wong also mentions that PDT does not help non-responders: “We know that in all AMD cases, there is a group that will not respond . . . the fluid will be there and it will be difficult to improve their vision.”
And he says that patients who don’t respond to monotherapy likely won’t respond to PDT either: “The small group that’s not responsive – even if you want to do PDT, it doesn’t help that much anyway. This group just doesn’t respond.”
Overall, results from PLANET (and other studies) have shown that IVT-AFL is non-inferior to combination PDT therapy. In addition, the average number of injections was reduced in the second year of PLANET (where there was a treat-and-extend option), from about 8 injections to 4.6 – which can help ease the treatment burden on both patients and doctors. And, indeed, these results certainly pave the way for improvement in diagnosis and treatment for patients with PCV.
Editor’s Note: The APVRS 2018 Congress was held in Seoul Korea, on December 14-16, 2018. Media MICE Pte Ltd, PIE Magazine’s parent company, was the official media partner of APVRS 2018. Reporting for this story also took place at APVRS 2018.
