Optical Coherence Tomography Predictors of Risk for Progression to Non-Neovascular Atrophic Age-Related Macular Degeneration

Abstract

Purpose The appearance of geographic atrophy (GA) on color photography (CP) is preceded by specific features on spectral domain optical coherence tomography (SDOCT). We aimed to build SDOCT-based risk assessment models for 5-year new onset of GA and central GA on CP. Design Prospective longitudinal study. Participants Age-related macular degeneration (AMD) patients with bilateral large drusen and/or non-central GA, and at least one eye without advanced disease (n=317) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SDOCT study. Methods For one eye per participant, qualitative and quantitative SDOCT variables were derived, respectively, from standardized grading and semi-automated segmentation at baseline. Up to 7 years later, annual outcomes were extracted and analyzed to fit multivariate logistic regression models and build a risk calculator. Main Outcome Measures New onset of CP-visible GA and central GA. Results Over a follow-up median of 4.0 years and among 292 AMD eyes (without advanced disease at baseline) with complete outcome data, 46 (15.8%) developed central GA. Among a subset of 265 eyes without any GA on baseline CP, 70 (26.4%) developed CP-visible GA. Final multivariate models were adjusted for age. In the model for GA, the independent predicting SDOCT factors (p <0.001 to 0.03) were (1) hyperreflective foci (HF) and (2) retinal pigment epithelium layer atrophy or absence (RPEA), followed by (3) choroidal thickness in absence of subretinal drusenoid deposits, (4) photoreceptor outer segment loss, (5) RPE drusen complex (RPEDC) volume and (6) RPEDC abnormal thinning (RAT) volume. For central GA, the independent predicting SDOCT factors (p<0.001) were (1) RAT volume, (2) intraretinal fluid or cystoid spaces, (3) HF, and (4) RPEA. The models yielded a calculator that computes the probabilities of CP-visible new-onset GA and central GA after 1 through 5 years. Conclusions For AMD eyes with large drusen and no advanced disease, we built a novel risk assessment model – based on age and SDOCT segmentation, drusen characteristics, and retinal pathology – for progression to CP-visible GA over up to 5 years. This calculator may simplify SDOCT grading and, with future validation, have a promising role as a clinical prognostic tool.

Measuring the Contributions of Basal Laminar Deposit and Bruch's Membrane in Age-Related Macular Degeneration

“…Persistent BLamD has been erroneously considered the outer plexiform layer by some authors, possibly contributing to a false impression of viable photoreceptors in atrophic areas. 89,90 Thus, we encourage developers of automated OCT segmentation strategies 91 and nomenclatures 92,93 to incorporate the presence of BLamD, especially in atrophy. Further, because the fourth hyper-reflective outer retinal band of the consensus lexicon correlates to the RPE-BL-BrM complex 94 (see Fig.…”

Quantitative Fundus Autofluorescence in Rhesus Macaques in Aging and Age-Related Drusen

“…Our findings are also consistent with studies using SD-OCT imaging, in which soft drusen in macaques demonstrate homogenous internal reflectivity, whereas those in humans exhibit greater heterogeneity in reflectivity with variable internal substructures. 8,58,59 Thus our data suggests both localized and global impact on lipofuscin distribution in eyes with drusen and AMD in primate species. As the pathogenesis of AMD is complex and multifactorial, including oxidative stress, 60 lipid accumulation, 61,62 immune dysregulation, 63,64 and vascular changes, 65,66 the role of lipofuscin accumulation among these factors remains unclear.…”

Association between Drusen Burden Determined by OCT and Genetic Risk in Early and Intermediate Age-Related Macular Degeneration

“…SD-OCT can quantify variation in morphology in a way that is accurate and reproducible. Other AMD phenotypes detectable on OCT including subfoveal fluid, retinal and choroidal thickness, retinal hyperreflective foci, other drusen characteristics such as hyper-reflectivity and homogeneity, are opportunities for exploration in the context of subtyping AMD and assessing risk of progression, 15,16,23,48 as well as defining the associations with genetic variants.…”

“…14 Sleiman et al demonstrated that OCT based drusen measurements were associated with appearance of geographic atrophy on color photographs over 4 years. 48 Schmidt-Erfurth et al found that drusen area was an important quatitative feature for progression. 16 Higher drusen volume was related to advanced AMD in a retrospective review by Lei et al, but other OCT parameters were more strongly related in their cases.…”