Outer Macular Distribution of Cuticular Drusen Linked to Higher AMD Progression Risk

Using en face OCT, researchers identified distinct spatial patterns of cuticular drusen in patients with intermediate AMD and found that lesions concentrated in the outer macula were associated with a greater likelihood of progression to late-stage disease. The findings, published in Eye, suggest that lesion distribution may provide prognostic information beyond traditional structural biomarkers and could help explain the variable risk previously reported in patients with cuticular drusen. The above images from the study show cluster plots (A-C), en face images (D-F) and B-scans (G-I) of the central-dominant, outer-macular-dominant and diffuse phenotypes. Photo: Suzanne Sherman, OD. Click image to enlarge. The presence of cuticular drusen is believed to confer a unique added risk for development of geographic atrophy and neovascularization; however, its impact on age-related macular degeneration (AMD) progression remains uncertain, as studies are contradictory. The discrepancies may be due to the types of imaging used to categorize cuticular drusen: OCT vs. fundus photography. On funduscopy, they appear as small, round, yellowish sub-RPE deposits, while fluorescein angiography demonstrates the characteristic “stars-in-the-sky” pattern. On OCT, cuticular drusen typically present as small RPE elevations, often with a “sawtooth” configuration, although this feature is not universally present. A new study used en face OCT for the first time to investigate the spatial distribution of cuticular drusen and if its patterns confer a risk for progression to late AMD over a two-year period. The results were published in the journal Eye.  This study included 87 eyes from 57 participants with intermediate AMD and cuticular drusen enrolled in the Amish Eye Study who completed two years of follow-up. The mean age of this cohort was 70.3 and 34 patients (59.6%) were women. Multimodal imaging, including volumetric spectral-domain OCT, was performed. Density of cuticular drusen was quantified on en face OCT across three ETDRS grid zones. A research team from China, Taiwan, Japan and the US evaluated potential association between cuticular drusen distribution categories and progression to late AMD at two years. According to the results, three spatial phenotypes of cuticular drusen were identified: central-dominant (57.5%), outer-macular-dominant (32.2%) and diffuse (10.3%). Over two years, five eyes progressed to late AMD, four of which belonged to the outer-macular-dominant group. The outer-macular-dominant phenotype was associated with higher odds of progression than the other phenotypes (odd ratio [OR]: 7.16). After adjustment for subretinal drusenoid deposits (SDDs) and large drusen, the association between spatial phenotype and progression remained (OR: 11.53), while SDDs were also associated with progression (OR: 9.26). The authors noted that their study’s strength may be limited by the short follow-up. Also, they wrote, “It should be noted that large drusen were defined using a threshold of >125μm in our study, compared with >200μm,” the biomarker typically used. “A more peripheral distribution reflects a shift in lesion location rather than greater areal involvement; thus, the increased risk observed in the outer macular-dominant phenotype may not be explained by lesion extent alone.”  They suggest that it’s possible that peripheral localization reflects region-specific vulnerability of the RPE or choroidal circulation. “Spatial variation in metabolic demand or perfusion across the macula may contribute to differential susceptibility to progression, suggesting that lesion distribution may serve as a marker of underlying biological heterogeneity rather than disease burden alone,” they wrote in their paper. Some limitations, in addition to the retrospective design and relatively small sample size, include the presence of only five progression events in the cohort—the corresponding confidence intervals were wide. “Therefore, the observed association between the outer-macular-dominant phenotype and progression to late AMD should be considered exploratory,” wrote the researchers. “To validate our conclusions regarding the risk of late AMD, future investigations will necessitate a longer follow-up period with larger cohorts. Furthermore, the manual labelling of cuticular drusen introduces the potential for subjective bias.” Despite these limitations, the authors say this study demonstrates the feasibility of quantitatively characterizing spatial phenotypes of cuticular drusen using en face OCT. “Identification of distinct spatial patterns may help explain heterogeneity in reported progression risk among patients with cuticular drusen and may contribute to improved phenotypic stratification in future AMD studies,” they concluded.Click here for the journal source. Huang J, Nittala MG, Corradetti G, et al. Spatial distribution of cuticular drusen and its association with category-specific progression risk in intermediate AMD. Eye. June 19, 2026. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.