This study is the first and the largest study to report the incidence and risk of advanced AMD in eyes with drusenoid PED in Asians. In this study, the 5-year cumulative incidence of advanced AMD was approximately 30%. (MNV:12.2%, GA:17.9%) In eyes developing MNV, the incidence of RAP (type 3 NV) was the highest followed by neovascular AMD in subtypes of MNV. The baseline PED width was associated only with advanced AMD.
The presence of large drusen and confluent drusen is a well-known risk factor for advanced AMD, including MNV and GA.6,7 Considering the formation process in drusenoid PED including large drusen aggregation and coalescence, the prevalence of drusenoid PED is considered lower compared with conventional (hard/soft) drusen. A total of 387(8.1%) out of 4757 participants had drusenoid PED in at least one eye.4 However, there have been no reports regarding the prevalence of drusenoid PED in epidemiological studies except AREDS, and there are a few studies investigating the natural history of drusenoid PED using SD-OCT in clinic-based studies.5,8,9
Balaratnasigam et al. conducted a longitudinal study investigating 21 eyes with large drusenoid PED (mean PED width:2427µm) using SD-OCT and demonstrated that baseline PED volume was associated with PED collapse leading to GA.5 On the other hand, Fragiotta et al. studied the risk factors for neovascular AMD using 73 eyes with intermediate AMD and revealed that the presence of drusenoid PED increased the risk for neovascular AMD and the PED width, but not height, which was associated with the development of neovascular AMD.8 The results are consistent with the results of the present study. Assuming that the drusenoid PED is a hemisphere with a radius “R,” PED width and PED height can represent “2R” and “R,” respectively, although PED height is actually less than “R” because the top of the drusenoid PED is usually flattened. This indicates that the PED width is more closely associated with the PED volume than the PED height, and the results between the studies might be almost the same. However, the PED width was associated with MNV (P = 0.004), but not with GA (P = 0.12) in the present study. This might be because the number of participants was small or the follow-up period was short. Regarding subfoveal choroidal thickness, a recent study reported that subfoveal choroidal thickness decreased in eyes with drusenoid PED just before the PED collapse. However, we could not find any association between baseline subfoveal choroidal thickness and GA development.9
Several studies in Asia have studied the 5-year incidence of second eye involvement in contralateral eyes with MNV.10–15 In eyes with unilateral PCV and unilateral neovascular AMD, the 5-year incidence of second eye MNV involvement was 9.3% and 11.3%, respectively.10 In pseudodrusen eyes with contralateral eyes involving MNV, the 5-year incidence of advanced AMD was 45%.13 Considering the previous results, eyes with drusenoid PED in the contralateral eyes with MNV are considered to have a similar risk for MNV to the fellow eye with unilateral neovascular AMD and they have a lower risk for advanced AMD compared with pseudodrusen eyes with contralateral eyes involving MNV. It has been reported that the presence of reticular pseudodrusen increases the risk for GA and MNV in the fellow eye of patients with unilateral MNV compared to patients without this condition.16,17 However, the presence of reticular pseudodrusen did not increase the risk of advanced AMD in eyes with drusenoid PED in the present study. Although further studies are needed, it can be concluded that reticular pseudodrusen might not be associated with an increased risk of advanced AMD in eyes with drusenoid PED.
Of the eight eyes developing MNV, retinal angiomatous proliferation was the most common and it was seen in six eyes. In MNV subtypes, retinal angiomatous proliferation is associated with greater large drusen and thinner choroidal thickness.18 Given that drusenoid PED is the merge of large drusen, it is reasonable that drusenoid PED is likely to develop retinal angiomatous proliferation.
The baseline characteristics did not differ between patients who developed MNV and GA in the study. This might be because the number of patients in both groups was small. Therefore, a large-scale study is needed accordingly.
The limitations of this study should be mentioned. The major limitation was the retrospective design of the study. The follow-up interval and SD-OCT scan protocol differed between the participants and institutes. Second, our SD-OCT analyses did not include the retinal microstructure analyses. It might be possible to predict the risk of advanced AMD more accurately if detailed retinal microstructure analyses were performed. A prospective cohort study is needed to confirm the results of this study.
In summary, the 5-year incidence of advanced AMD was approximately 30% in eyes with drusenoid PED among elderly Japanese patients. Baseline PED width was associated with advanced AMD.