Reticular Pseudodrusen a Risk for More Rapid AMD Progression

By Marilynn Larkin

August 23, 2019

NEW YORK (Reuters Health) - Patients with reticular pseudodrusen (RPD)-associated age-related macular degeneration (AMD) are at increased risk of progression to geographic atrophy, researchers say

"Ophthalmologists have known about RPD and their relationship to AMD for over 30 years, but the diagnosis was rarely made," Dr. Amitha Domalpally of the University of Wisconsin-Madison School of Medicine and Public Health said by email. "Fortunately, recent advances in retinal imaging have brought pseudodrusen in the spotlight because we can see them so much better."

"We now know that patients with RPD-associated AMD need frequent follow-up, as they are at risk for faster progression to end-stage geographic atrophy," she told Reuters Health. "Following up patients over five years, the AREDS2 study showed that almost 60% of eyes with RPD developed geographic atrophy compared to about 15% without."

"There is currently no treatment to reverse or slow the progression of dry AMD, but it is important to identify and counsel patients with RPD, as they are at higher risk of progression and retina specialists can provide lifestyle education for impending vision related issues," she noted. "One such issue is that patients with RPD tend to have night vision problems."

Dr. Domalpally and colleagues analyzed fundus autofluorescence (FAF) images from a subset of participants with intermediate AMD in one or both eyes enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a five-year multicenter study of nutritional supplement.

FAF images were evaluated annually for RPD. Six single nucleotide polymorphisms (SNPS) were assessed - rs10490924 (ARMS2), rs1061170 (CFH), rs2230199 (C3), rs116503776 and rs114254831 (C2/CFB), and rs943080 (VEGF-A) - as was the genetic risk score (GRS).

As reported online July 29 in Ophthalmology, FAF images were evaluated for 5,021 eyes of 2,516 participants. For those with RPD, the mean age was 79 (65% women); the mean age of those without RPD was 75, and 53% were women.

RPD was seen in 1,186 eyes (24%). Prevalence varied with baseline AREDS AMD severity for the eye: 6% in early AMD, 26% in intermediate AMD, 36% in geographic atrophy, and 19% in neovascular AMD.

After adjustment for baseline age, gender, race, educational status, smoking and AMD severity, the odds ratio for 1,710 eyes at risk of developing late AMD at the next annual visit was 2.42 for geographic atrophy and 1.21 for neovascular AMD.

Further, RPD was significantly associated with higher GRS and ARMS2 risk alleles (rs10490924), and, at a nominal level, with C3 (rs2231099) and CFH risk alleles (rs1061170).

Summing up, the author state, "Participants with RPD have an increased risk of progression to geographic AMD but not neovascular AMD. ARMS2 risk alleles and higher GRS were associated with the presence of RPD. This study suggests that RPD are an important risk marker and should be included in classification systems used for patient prognosis."

Dr. Domalpally added, "Pseudodrusen are difficult to detect and (we) need an array of retinal imaging to make the call. Future directions would be to develop artificial intelligence algorithms that can accurately detect their presence and identify patients at higher risk."

Dr. Milam Brantley Jr., Associate Professor, Ophthalmology and Visual Sciences and Molecular Physiology and Biophysics at Vanderbilt Eye Institute in Nashville, commented by email, "Previous cross -sectional studies had shown a link between RPD and late AMD, and prospective studies looking at the fellow eye of patients with late AMD in one eye had also found RPD to be associated with progression to late AMD."

"This study provides new information because it prospectively evaluates RPD as an independent risk factor for progression to late AMD in patients with early AMD," he told Reuters Health.

"Practically, I think it means two things for the ophthalmologist," said Dr. Brantley, who was not involved in the study. "First, we need to make sure we are looking specifically for RPD in our patients with AMD and noting RPD presence or absence in the medical record."

"Second," he said, "because correctly identifying RPD is so important, we should likely be imaging our patients, even those with early AMD, with FAF and OCT to help identify RPD."

"I believe that predictive scales for late AMD development will be updated to include RPD as a risk marker," he noted. "This will happen as future studies include RPD in their predictive models and the specific associations with progression to late AMD are confirmed."

"The current study categorized RPD only by presence or absence," he added. "It would be informative to know how RPD area and location relate to progression to late AMD in patients with early AMD."

"One of the more important findings was that RPD have a larger effect on risk of progression to late AMD in patients in the very early stages of AMD, (who) had almost a 10-fold higher risk of AMD than those without RPD," he said. "This stresses the importance of looking closely for RPD even in patients with what appears to be very early AMD."


Ophthalmol 2019.