Reticular Pseudodrusen May Be An Early Signal of AMD

Macular degeneration
Optical coherence tomography (OCT) showing signs of macular degeneration. (Photo by: BSIP/Universal Images Group via Getty Images)
The finding occurs more commonly with age, and is sometimes present without other disease indications.

The currently approved imaging to discern reticular pseudodrusen (RPD) is multimodal optical coherence tomography (OCT) plus infrared reflectance (IR) — color fundus photography is not as sensitive to visualize RPD — and so it may become more important to consider which imaging technologies are routine in clinics now that these subretinal drusenoid deposits are suspected to potentially indicate an earlier state of age-related macular degeneration (AMD).

Most prior studies have employed fundus photography to distinguish RPD, finding incidence in populations older than 65 years ranging from <1.0% to 4.9%. A new investigation based on the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS 2) has found occurrence of RPD in 16% (74) of 466 participants; women, mean age 81 years, enrolled in CAREDS 2 from 2016 to 2019, according to data published in Ophthalmology Retina.

The analysis examines morphological features of RPD and associations of RPD with AMD status. RPD were detected with SD-OCT plus IR imaging in 130 eyes (14% of eyes), but with color fundus photography, the subretinal drusenoid deposits only appeared in 38 eyes (4% of eyes). It also found RPD in eyes that did not show other structural signs of AMD.

RPD incidence increased with age (P <.0001). Of eyes with RPD, 7% of participants younger than 78 years exhibited the deposits, as well as 14% of patients from 78 to 83 years of age, and 30% of individuals older than 83 years. Further, incidence of RPD increased with AMD severity. Employing clinical AMD classification with color fundus photography, RPD were found in eyes of 11.5% with early AMD, 25.1% with intermediate AMD, and 51.1% with late AMD. In AMD graded using OCT, RPD were associated with a 2- to 6-times greater frequency of structural features such as hyperreflective foci (P <.0001), large drusen (P <.0001), and “incomplete RPE and outer retinal atrophy (P <.02),” or these features combined.

RPD occurred within the ETDRS grid 6 mm outer circle for 34%, and both inside and outside of ETDRS grid in 65%. One eye displayed RPD only outside the circle. Overall, RPD were found in patients’ superior retinal quadrants more than the other quadrants. Two morphologic forms were assessed; ribbons appeared in 53%, dots in 36%, and both ribbons and dots in 10%. The peripapillary region was involved for 35% of those with RPD.

This research was conducted at University of Iowa, Oregon Health & Science University, and University of Wisconsin, Madison. The sample was limited by the inclusion of primarily educated individuals with higher family incomes. SD-OCT and IR imaging was not available from baseline visits in 2001 to 2004, so investigators were not able to examine evolving relationships of RPD with AMD. Conversely, a strength was inclusion of data from OCT and IR, and 97.1% intergrader agreement.

“The lack of relationships to comorbidities and strong relationships with late AMD suggest that RPD are an independent risk factor for the progression of AMD and are particularly predictive of the later stages of AMD,” the investigation explains.


Cleland SC, Domalpally A, Liu Z et al, for the CAREDS 2 Research Group. Reticular pseudodrusen characteristics and associations in the carotenoids in age-related eye disease study 2 (CAREDS2), an ancillary study of the women’s health initiative. Ophthal Retina. 2021;5(8):721-729. doi:10.1016/j.oret.2020.12.019