Purpose: Detect changes in the neurosensory retina using spectral-domain optical coherence tomography (SD OCT) imaging over drusen in age-related macular degeneration (AMD). Quantitative imaging biomarkers may aid in defining risk of disease progression.Design: Cross-sectional, case-control study evaluating SD OCT testing in AMD. Participants and Controls: Seventeen eyes of 12 subjects with nonneovascular AMD and drusen and 17 eyes of 10 age-matched control subjects.Methods: Spectral-domain OCT imaging across the fovea in the study eye with multiple 10-to 12-mm scans of 1000 A scans each.Main Outcome Measures: In summed SD OCT scans, the height of individual retinal layers either over drusen or at corresponding locations in the control eye and qualitative changes in retinal layers over drusen. Secondary measures included photoreceptor layer (PRL) area, inner retinal area, and retinal pigment epithelium (RPE)/drusen area.Results: The PRL was thinned over 97% of drusen, average PRL thickness was reduced by 27.5% over drusen compared with over a similar location in controls, and the finding of a difference was valid and significant (P ϭ 0.004). Photoreceptor outer segments were absent over at least 1 druse in 47% of eyes. Despite thinning of the PRL, inner retinal thickness remained unchanged. We observed 2 types of hyperreflective abnormalities in the neurosensory retina over drusen. Distinct hyperreflective speckled patterns occurred over drusen in 41% of AMD eyes and never in control eyes. A prominent hyperreflective haze was present in the photoreceptor nuclear layer over drusen in 67% of AMD eyes and more subtly in the photoreceptor nuclear layer in 18% of control eyes (no drusen).Conclusions: With SD OCT as used in this study, we can easily detect and measure changes in PRL over drusen. Decreased PRL thickness over drusen suggests a degenerative process, with cell loss leading to decreased visual function. The hyperreflective foci overlying drusen are likely to represent progression of disease RPE cell migration into the retina and possible photoreceptor degeneration or glial scar formation. A longitudinal study using SD OCT to examine and measure the neurosensory retina over drusen will resolve the timeline of degenerative changes relative to druse formation. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2009;116:488 -496 © 2009 by the American Academy of Ophthalmology.Herein are reported the results from a search for imaging biomarkers of neurosensory retinal injury resulting from age-related macular degeneration (AMD), which is the leading cause of visual impairment in patients older than 65 years in the developed world. 1,2 An estimated 8 million persons older than 55 years in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. If neurosensory retinal injury is detected and measured promptly, then the recent advances in genetics, cell and molecular biology, and pharmacologic therapeutic approaches can b...

Purpose Describe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading. Design Prospective cross-sectional study. Participants We included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD. Methods Both eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with ≥1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility. Main Outcome Measures We assessed SD-OCT characteristics at baseline. Results In 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy. Conclusions Macular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression.

Purpose To evaluate and quantify visual function metrics to be used as predictors of AMD progression and visual acuity (VA) loss in patients with early and intermediate AMD. Design Baseline data of observational, cross-sectional, prospective study. Methods 101 patients were enrolled at Duke Eye Center: 80 patients with AMD age-related eye disease study (AREDS) stage 2 (N=33) and stage 3 (N=47) and 21 age-matched, normal controls. A dilated retinal examination, macular pigment optical density measurements, and several functional assessments: best-corrected VA, mesopic microperimety with eye tracking (MAIA), dark adaptometry (AdaptDx), low luminance VA (LLVA) (standard using log 2.0 neutral density filter and computerized method) and cone contrast test (CCT) (Innova Systems Inc) were performed. Low luminance deficit (LLD) was defined as the difference in numbers of letters read at standard vs. low luminance. Group comparisons were performed to evaluate differences between the control and the AREDS 2 and AREDS 3 groups using two-sided significance tests. Results Functional measures that significantly distinguished between normal and AREDS3 were standard and computerized (0.5 cd/m2) LLVA, percent reduced threshold and average threshold on microperimetry, CCTs, and rod intercept on dark adaptation (p < 0.05). The AREDS 3 group demonstrated deficits in microperimetry reduced threshhold, computerized LLD2 and dark adaptation rod intercept (p < 0.05) relative to AREDS 2. Conclusions and Relevance Our study suggests that LLVA, MAIA microperimetry, CCT and dark adaptation may serve as functional measures of AMD progression.

Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.