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[Age-related Macular Degeneration in the Japanese].

Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in agreement. We also found more cases of PCV among the Japanese than among the French. II. PCV. About 50% of exudative AMD cases in the Japanese population are PCV. Because of its peculiar angiographic findings, PCV has long been considered to be a distinct clinical entity different from the usual exudative AMD. Also, there have been serious discussions on the nature of PCV. In our analyses, about 20% of PCV cases show rather large lesion sizes that exceed the vascular arcade. Scar formation in the macula and compromised vision are frequent findings in such cases. The occurrence of PCV in the inferior staphyloma or in angioid streaks shows heterogeneity in PCV. These findings suggest that PCV may be a finding on indocyanine green angiography rather than a distinct clinical entity. Spectral domain OCT examination shows that the branching vascular network of PCV is located between the retinal pigment epithelium and Bruch's membrane. In cases with retinal pigment epithelial detachment, CNV from the branching vascular network was found to extend along the roof of the detached retinal pigment epithelium. Such findings show that the branching vascular network of PCV is type 1 CNV. Complement factor H (CFH) and age-related maculopathy 2 (ARMS2)/High temperature requirement 1 (HTRA1) located on chromosome 10 (10q26) are well-established disease susceptible genes of AMD. In the Japanese, the prevalence of CFH Y402H gene polymorphism is low and ARMS2/HITRA1 plays a more important role in the development of AMD. In ARMS2 A69S polymorphism, a large deletion/insertion (443de1/54ins) that is reported in Caucasians was also found in Japanese. Thus, the genetic background of Caucasian and Japanese AMD is quite similar, as is also the case with exudative AMD and PCV. Our findings show that PCV is not a distinct clinical entity but is a subtype of exudative AMD. III. Exudative AMD with choroidal vascular hyperpermeability. Choroidal vascular hyperpermeability observed in central serous chorioretinopathy can be found in about 20% to 30% of exudative AMD cases in Japanese. Such cases often show a thick choroid, lack of drusen, and rather good visual prognosis with slow progression of the disease. Recently, "pachychoroid neovasculopathy" has been described by a group from New York. Such cases of AMD with choroidal vascular hyperpermeability, a thick choroid, and lack of drusen appears to belong to pachychoroid neovasculopathy. We studied the risk allele frequencies of CFH I62V and ARMS2 A69S gene polymorphisms in three groups : usual exudative AMD, pachychoroid neovasculopathy, and normal controls. Interestingly, cases of pachychoroid neovasculopathy show different gene polymorphisms of CFH I62V and ARMS2 A69S from the usual cases of exudative AMD and a more similar pattern to normal controls. Therefore, the possible mechanisms of the CNV development in such cases may differ from the classic well-documented drusen-dependent pathways. IV. Atrophic AMD in Japanese. Data from the Nagahama Cohort study show an increasing prevalence of drusen in Japanese. Recently, more extensive information on drusen has become available and the redefinition of drusen is currently in progress. In particular, the importance of reticular pseudodrusen (RPD) is more widely appreciated. This type of drusen is often found in Japanese AMD. Although the nature and location of RPD are still debatable, many investigators believe that this type of drusen is located under the sensory retina rather than under Bruch's membrane. In our analyses, RPD was found in 18.4% of late AMD cases in Japanese. It was more common in eyes with RAP or atrophic AMD and was seldom found in PCV. ARMS2 A69S gene polymorphism was found more frequently in cases of exudative AMD with RPD, than in cases of exudative AMD without RPD. Eyes with RPD show a thin choroid and diminished vascular densities of choroidal vessels.

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