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Clinical implications of unique RAP/PCV prevalence patterns in Asian patients


Clinical Implications of Unique RAP and PCV Prevalence Patterns in Asian Patients



Neovascular exudative age-related macular degeneration is a leading cause of blindness in patients over 50 years of age in developed countries. It is classified into three types: polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP) and typical AMD represented by classic and/or occult choroidal neovascularization as documented by indocyanine green angiography1,2

Nowadays, anti-vascular endothelial growth factor therapy (eg, ranibizumab or bevacizumab) is the most common intervention used to maintain and improve visual acuity in AMD.3,4 However, more than a few AMD patients are nonresponders to anti-VEGF therapy Cho and associates5 reported that these cases possibly included PCV, and could be improved by the combination of anti-VEGF therapy and verteporfin photodynamic therapy (PDT). This may indicate there are quite a few “hidden” PCV patients who have not undergone ICG angiography.

The number of patients in Japan with neovascular AMD was thought to be fewer than that in western countries.6-11 However, Miyazaki and associates12 reported that the five-year incidence for AMD in the Hisayama study of the Japanese population was 0.8%; this result was the similar to 0.9% found in the Beaver Dam Eye study and 1.1% in the Blue Mountains Eye study.13,14 These data may indicate the prevalence of AMD in Japan is increasing and catching up with that in western countries.

In a recent study, Maruko and associates15 reported that among 289 patients, 158 (54.7%) were diagnosed with PCV, 102 (35.3%) with typical AMD and 13 (4.5%) with RAP. All patients successfully underwent ICG angiography.

Indocyanine green angiogram demonstrates typical polypoidal lesions with branching vascular network at the macular area. IMAGE COURTESY OF TOMOHIRO IIDA, MD

The proportion of PCV in neovascular AMD was more than 50% in Japanese patients. Yannuzzi and associates16 reported that the proportion of PCV was approximately 5% to 10% in the United States. Sho and associates17 stated that the proportion of PCV was 24% of AMD in Japanese patients, Wen and associates18 reported 22.3% in Chinese patients, and Byeon and associates19 reported 24.6% in Korean patients. These are thought to be due to ethnic differences. At the same time, the proportion of RAP in neovascular AMD was 10% to 15% in the United States; this number was much higher than the 4.5% reported in Japan.2 Therefore, neovascular AMD in Japanese and Asian patients has demographic features that differ much from that in Caucasian patients.

The higher proportion of PCV in Japanese patients helps to develop the new concept of a clinical type of neovascular AMD. Maruko and associates20 reported 20 combined cases of PCV and typical AMD among 349 patients with neovascular AMD; these patients had a combination type of neovascular AMD, ie, one eye had PCV and the other eye had typical AMD. Although some cases could include the early stages of development in PCV or PCV unproved by ICG angiography, the combined cases might imply that both PCV and typical AMD are not independent and possibly overlap. Thus, it is sometimes difficult, even for retinal specialists, to distinguish PCV from typical AMD without ICG angiography.

Photodynamic therapy has already been established as an effective treatment for AMD,21-26 especially PCV in recent years.25,27-33 It is common knowledge in Japan that PDT is effective for PCV, because the JAT study — the first clinical trial in Japan of PDT for AMD — was significantly effective compared to other studies in western countries. This might seem to include PCV patients.22-24 In addition, the efficacy of anti-VEGF therapy for PCV has not been determined yet.5,32-34 Even today, PDT is still a useful and common therapy in Japan.

However, PDT has complications, such as sub- or intraretinal fluid accumulation after PDT as a temporary reaction and sudden severe vision loss because of subretinal bleeding.35-38 ICG angiography-guided PDT is sometimes performed to reduce the laser-exposed area and associated adverse events. In Japan, a prospective multicenter study comparing the efficacy and safety of fluorescein and ICG angiography-guided PDT is now being conducted by the Ophthalmic PDT Study Group.

Recently, combination therapy with PDT and anti-VEGF therapy was reported by several groups.33,39-43 The FOCUS study showed ranibizumab+PDT was more effective than PDT alone.39 Combination therapy for PCV is expected to continue to reduce the frequency of treatments and the recurrence rates.

The natural course of RAP has poorer visual outcomes and a higher risk of bilateral neovascularization than typical AMD, and the treatment results of laser photocoagulation, surgical abrasion and monotherapy of PDT have not been adequate.44-48 Because PDT is still a common therapy for AMD in Japan, as previously mentioned, many retinal specialists in Japan consider performing combination therapy to manage cases of RAP. Saito and associates40,43 reported that combination therapy of bevacizumab and PDT for RAP maintained and improved visual acuity after six and 12 months follow-up. Although further large and long-term prospective randomized studies are needed, this result may indicate that combination therapy should be considered for RAP.

Neovascular AMD in Japanese and other Asian patients has different demographic features from those in white patients, such as the predominance of PCV, low frequency of RAP, and the combined cases of PCV and typical AMD. Although we understand the interethnic differences between east and west, we may consider PDT as one of the treatment options for patients with PCV or RAP in case of the poor response to anti-VEGF therapy. RP

Ichiro Maruko, MD and Tomohiro lida, MD are affiliated with the Department of Ophthalmology, Fukushima Medical University School of Medicine in Fukushima, Japan. The authors have no financial interest in any products mentioned in this article. Dr. Maruko can be contacted at


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