The findings support the hypothesis that AMD is a panretinal disease but emphasize that progression risk is primarily linked to macular drusen, these researchers argue. Standard and UWF imaging show significant agreement in assessing AMD severity, highlighting the need for standardized imaging approaches. These images show macular and peripheral drusen, as well as multifocal atrophy, in and AMD patient. Photo: Pivovar A, et al. J. Clin. Med. 2021, 10, 3993. Click image to enlarge.

With the widespread availability of ultra-widefield (UWF) imaging, the presence and role of peripheral retinal abnormalities in age-related macular degeneration (AMD) have garnered recent attention. In a recent follow-up to the Optos PEripheral RetinA (OPERA) study, an ancillary work of the seminal Age-related Eye Disease Study, researchers characterized and quantified peripheral retinal features longitudinally with the aim of providing new insights into the role of peripheral abnormalities in progression of AMD. They found that AMD features often extend beyond the macula, suggesting that AMD is a panretinal disease, although peripheral findings were not associated with increased risk of progression to late AMD. The team’s paper on the work was recently published in Ophthalmology.

A total of 137 OPERA participants (265 eyes) with gradable UWF color and autofluorescence imaging at year five and year ten were included.

A high prevalence of peripheral retinal abnormalities were observed, with almost all eyes showing peripheral drusen and observed an increase in drusen area over the five-year period. Pigmentary changes were less common in the periphery but also increased over time. Isolated geographic atrophy (GA) or neovascular AMD in peripheral zones was uncommon. Substantial peripheral findings defined as greater than one disc area of drusen or hypo/hyperpigmentation in zones 2 or 3, were associated with higher macular AMD severity scale but not with progression to late AMD.

Peripheral drusen are associated with AMD and increase with AMD severity, supporting the hypothesis that AMD is possibly a panretinal disease. However, peripheral drusen do not contribute to disease progression. These panretinal findings align with the understanding of AMD as a systemic complement dysregulation with primarily known ocular manifestations and previous studies where peripheral drusen increase with AMD severity however are not critical markers for predicting progression to more severe forms of the disease.

“While peripheral changes do not confer increased risk for progression to late AMD, these peripheral findings may still contribute significantly to the constellation of symptoms seen with AMD including dark adaptation and poor low-contrast vision,” the authors wrote. “A comparison of AMD severity scales between standard and UWF imaging showed significant agreement, with 95% of cases agreeing within two steps. This is relevant because a two-step change is considered a critical outcome measure for AMD progression.”

Additionally, progression rates of AMD were found to have substantial agreement between the two imaging types for macular assessments, the authors added.

Fundus autofluorescence (FAF) showed most eyes with abnormal FAF at both timepoints with an increasing proportion of both GA and reticular pseudodrusen over five years. FAF detection of GA was higher when compared to UWF color photography with 20% vs. 15% at year five and 34% vs. 27% at year 10 for FAF and UWF color, respectfully, which is consistent with prior research that FAF may detect GA earlier than standard color photographs. Higher rates of reticular pseudodrusen were observed with 8% vs. 4% at year five and 15% vs. 5% at year 10 for FAF and UWF color, respectfully, which is increasingly recognized as an important risk factor in AMD progression, the authors noted.

“These insights are crucial for improving the staging and monitoring of AMD,” the authors concluded. “Further research is needed to explore the impact of peripheral changes on functional and patient-reported outcomes and to investigate potential genetic associations.”