Macular Thickness in Intermediate Age-Related Macular Degeneration Is Influenced by Disease Severity and Subretinal Drusenoid Deposit Presence

Abstract

To investigate how macular thickness varies with intermediate age-related macular degeneration (iAMD) severity and the presence of subretinal drusenoid deposits (SDDs). METHODS. A longitudinal prospective study of 143 participants >50 years of age with no to intermediate AMD who were followed with multimodal imaging and functional testing. Participants were stratified by iAMD severity according to imaging features. Macular thicknesses measurements over the central circles with 1-mm, 3-mm, and 6-mm diameters obtained from ocular coherence tomography imaging were compared across severity categories using cross-sectional (143 eyes) and longitudinal (subset of 77 eyes followed for 4 years) multivariate analyses. RESULTS. Compared with control eyes without large drusen or SDDs (Group 0), central maculas of lower risk eyes with unilateral large drusen (Group 1) were thicker (P = 0.014), whereas higher risk eyes with SDDs (Group SDD) were thinner (P = 0.02) in cross-sectional multivariate analyses. In longitudinal analyses, maculas with SDDs thinned more rapidly over 4 years relative to control eyes (P = 0.0058), which did not show significant thinning. More rapid central macular thinning was associated with worse baseline best-corrected visual acuity (BCVA) (P = 0.016) and more rapid BCVA decline (P = 0.0059). CONCLUSIONS. Macular thickness in iAMD varies with disease severity, showing small increases in eyes with large drusen and decreases in eyes with SDDs. Active processes possibly related to neuroinflammation and neurodegeneration may be contributory. Longitudinal central macular thickness evaluation is an accessible outcome measure relevant to functional measures and is potentially useful for iAMD interventional studies.

Inner Retinal Layer Thickness Alterations in Early Age Related Macular Degeneration in Eyes with Subretinal Drusenoid Deposits or Conventional Drusen

“…Recently Chiang et al carried out a study of the retinal macular thickness (including the central 1 mm area) in patients with SDD, patients with various degrees of AMD, and a control group. Their study of the inner retina showed a trend of retinal thickness reduction in the central 1 mm area in patients with SDD compared to controls [ 32 ]. Our study showed a reduction of the inner retina thickness in the central 1 mm area in patients with CD and in patients with SDD compared to controls.…”

Exploring the pathogenesis of age-related macular degeneration: A review of the interplay between retinal pigment epithelium dysfunction and the innate immune system

“…Histologically, the subretinal presence of RPD is associated with RPE and photoreceptor disruption ( Greferath et al, 2016 ). Clinical data from intermediate AMD patients indicate that RPD are associated with decreased photoreceptor function ( Flamendorf et al, 2015 ), choroidal changes ( Keenan et al, 2020 ), and over time with increased retinal thinning and degeneration ( Chiang et al, 2020 ). The histological studies that have been undertaken show RPD to contain similar components to drusen such as photoreceptor outer segment debris including opsins; lipid in the form of unesterified cholesterol; RPE fragments (melanolipofuscin granules); ApoE, a protein important for lipid trafficking; vitronectin; and the immunogenic protein, CFH ( Rudolf et al, 2008 ; Greferath et al, 2016 ; Wu et al, 2022 ).…”

Early Stages of Age-Related Macular Degeneration: Racial/Ethnic Differences and Proposal of a New Classification Incorporating Emerging Concept of Choroidal Pathology

“…Interestingly, compared with control eyes without large drusen or SDDs, the central maculas of eyes at lower risk with unilateral large drusen were thicker, whereas higher-risk eyes with SDDs were thinner in cross-sectional multivariate analyses, suggesting that macular thickness in intermediate AMD varies with disease severity and that there were small increases in eyes with large drusen and decreases in eyes with SDDs. The investigators assumed that active processes possibly related to neuroinflammation and neurodegeneration may be contributory to such biphasic changes [ 33 ]. Regarding the choroidal changes, early AMD seems to undergo biphasic alterations similarly; initially, choroidal volume and choroidal vascular index increased during early drusen formation but decreased thereafter.…”