Age-related macular degeneration (AMD) is a leading cause of vision loss, primarily affecting the macula. However, new findings from research published in Ophthalmology suggest that AMD-related changes might extend beyond the macula.
Give me some background first.
While traditional imaging techniques for AMD have largely focused on the macula, advancements and widespread availability in ultrawide field (UWF) imaging have allowed researchers to examine the peripheral retina more comprehensively.
Now, talk about the study.
The Optos PEripheral RetinA (OPERA) study, an adjunct longitudinal study of the Age-Related Eye Disease Study 2 (AREDS2), utilized three retinal imaging modalities:
- Standard color fundus photography
- UWF color imaging
- Fundus autofluorescence (FAF)
These were then used to characterize and quantify peripheral retinal abnormalities in AMD patients over five years; the images were then graded using the AMD Severity Scale (AMDSS).
Who was included in the study?
The study included 137 participants (265 eyes) from the original AREDS2 cohort with gradable UWF images at five-year and 10-year follow-up points.
These participants were slightly younger (74 years old vs. 69.9 years old), and had lower rates of diabetes compared to the initial AREDS2 population (13% vs. 5.8%), possibly due to survivorship bias, the investigators noted.
Findings?
The study found peripheral drusen in 99% of participants.
Over the five-year period: Substantial drusen (drusen > 1 optic disc area) increased from 69% to 77%.
The investigators also discovered that large peripheral drusen were linked to higher AMD severity, with 48% of AMDSS 3-5 participants and 75% of AMDSS 6-8 participants showing substantial findings (including large drusens and areas of hypo/hyperpigmentation).
Despite this: Peripheral changes did not increase the risk of late AMD progression, as 41% of AMDSS 6-8 participants progressed regardless of these changes.
- To note: This was unlike macular drusen findings.
Tell me more.
Comparisons made between standard color photographs and UWF images on AMD feature detection showed significant agreement, with 95% agreement within two steps on the AMDSS, but exact agreement only 60.5% of the time.
Comparisons between UWF and FAF images also revealed that UWF had lower detection rates of geographic atrophy (GA) and reticular pseudodrusen (RPD) over the five-year study, aligning with previous studies indicating FAF detects GA earlier than UWF:
- GA detection at Year 5 vs. Year 10: FAF = 20% → 34% | UWF = 15% → 27%
- RPD detection at Year 5 vs. Year 10: FAF = 8% → 15% | UWF = 4% → 5%
Any limitations?
A few … among them:
The inclusion of participants with advanced age and high disease may have severely limited the generalizability of the study’s findings.
Additionally, the lack of other imaging modalities such as optical coherence tomography (OCT) may have limited the study's insights into retinal changes and AMD grading.
Expert opinion?
Although the OPERA study findings supported the hypothesis that AMD is a panretinal disease, the study authors noted that more research is still needed to fully understand the implications of peripheral retinal changes, their role in AMD progression, clinical outcomes, and potential genetic attributions to said changes.
Take home.
In all, the OPERA study provided valuable insights on peripheral retinal changes associated with AMD, suggesting its classification as a panretinal disease.
While these changes are common, they do not increase the risk of progression to late AMD.
As such: Providers should use UWF imaging as a complementary imaging modality to comprehensively assess the retina while maintaining a primary focus on the macula for progression risk assessment.