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PurposeTo assess the influence of lesion morphology and location on geographic atrophy (GA) growth rate.MethodsWe manually delineated GA on color fundus photographs of 237 eyes in the Age-Related Eye Disease Study. We calculated local border expansion rate (BER) as the linear distance that a point on the GA border traveled over 1 year based on a Euclidean distance map. Eye-specific BER was defined as the mean local BER of all points on the GA border in an eye. The percentage area affected by GA was defined as the GA area divided by the total retinal area in the region.ResultsGA enlarged 1.51 ± 1.96 mm2 in area and 0.13 ± 0.11 mm in distance over 1 year. The GA area growth rate (mm2/y) was associated with the baseline GA area (P < 0.001), perimeter (P < 0.001), lesion number (P < 0.001), and circularity index (P < 0.001); in contrast, eye-specific BER (mm/y) was not significantly associated with any of these factors. As the retinal eccentricity increased from 0 to 3.5 mm, the local BER increased from 0.10 to 0.24 mm/y (P < 0.001); in contrast, the percentage of area affected by GA decreased from 49.3% to 2.3%.ConclusionsUsing distance-based measurements allows GA progression evaluation without significant confounding effects from baseline GA morphology. Local GA progression rates increased as a function of retinal eccentricity within the macula which is opposite of the trend for GA distribution, suggesting that GA initiation and enlargement may be mediated by different biological processes.

PurposeTo establish a continuous topography of retinal vessel density in normal eyes using optical coherence tomography angiography (OCTA).MethodsA retrospective chart review was performed, and 8-mm × 8-mm OCTA images from 22 normal eyes were analyzed. Vessel density was plotted as a continuous function of distance from the foveal center (radial vessel density) and directional meridians (directional vessel density) for the superficial capillary plexus and deep capillary plexus.ResultsContinuous radial and directional vessel density plots for the superficial and deep capillary plexus were generated. Radial vessel density analysis revealed transition points at 657 microns (95% confidence interval [CI], 619-696) and 950 microns (95% CI, 903-997) from the foveal center for the superficial plexus and deep plexus, respectively. Directional vessel density analysis demonstrated significant vessel density variations in these vascular layers and provided greater detail compared to traditional quadrant analysis.ConclusionsThere are significant topographic variations of retinal vessel density in normal eyes. Continuous vessel density analysis offers greater sensitivity in detecting topographic vessel density changes compared to traditional methods of analysis.Translational relevanceThis study establishes a normative continuous vessel density topography that may help elucidate the role of the vascular bed in different chorioretinal diseases.

Background The associations of geographic atrophy (GA) progression with systemic health status and medication use are unclear. Methods We manually delineated GA in 318 eyes in the Age-Related Eye Disease Study. We calculated GA perimeter-adjusted growth rate as the ratio between GA area growth rate and mean GA perimeter between the first and last visit for each eye (mean follow-up= 5.3 years). Patients' history of systemic health and medications was collected through questionnaires administered at study enrolment. We evaluated the associations between GA perimeter-adjusted growth rate and 27 systemic health factors using univariable and multivariable linear mixed-effects regression models. Results In the univariable model, GA perimeter-adjusted growth rate was associated with GA in the fellow eye at any visit (p=0.002), hypertension history (p=0.03), cholesterol-lowering medication use (p<0.001), beta-blocker use (p=0.02), diuretic use (p<0.001) and thyroid hormone use (p=0.03). Among the six factors, GA in the fellow eye at any visit (p=0.008), cholesterol-lowering medication use (p=0.002), and diuretic use (p<0.001) were independently associated with higher GA perimeter-adjusted growth rate in the multivariable model. GA perimeter-adjusted growth rate was 51.1% higher in patients with versus without cholesterol-lowering medication use history and was 37.8% higher in patients with versus without diuretic use history. Conclusions GA growth rate may be associated with the fellow eye status, cholesterol-lowering medication use, and diuretic use. These possible associations do not infer causal relationships, and future prospective studies are required to investigate the relationships further. [ABSTRACT FROM AUTHOR]

Background The macular central 1 mm diameter zone is crucial to patients' visual acuity, but the long-term natural history of central sparing in eyes with geographic atrophy (GA) is unknown. Methods We manually segmented GA in 210 eyes with GA involving central 1 mm diameter zone (mean follow-up= 3.8 years) in the Age-Related Eye Disease Study. We measured the residual area in central 1 mm diameter zone and calculated central residual effective radius (CRER) as square root of (residual area/p). A linear mixed-effects model was used to model residual size over time. We added a horizontal translation factor to each data set to account for different durations of GA involving the central zone. Results The decline rate of central residual area was associated with baseline residual area (p=0.008), but a transformation from central residual area to CRER eliminated this relationship (p=0.51). After the introduction of horizontal translation factors to each data set, CRER declined linearly over approximately 13 years (r2=0.80). The growth rate of total GA effective radius was 0.14 mm/year (95% CI 0.12 to 0.15), 3.7-fold higher than the decline rate of CRER (0.038 mm/year, 95% CI 0.034 to 0.042). The decline rate of CRER was 53.3% higher in eyes with than without advanced age-related macular degeneration in the fellow eyes at any visit (p=0.007). Conclusions CRER in eyes with GA declined linearly over approximately 13 years and may serve as an anatomic endpoint in future clinical trials aiming to preserve the central zone. [ABSTRACT FROM AUTHOR]