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Purpose: The symmetry of major macular fundus features in both eyes of the same patient with age-related macular degeneration (AMD) was investigated using swept-source(SS)-OCT., Design: Retrospective review of a prospective study., Participants: Patients with AMD., Methods: Grading was performed on the first SS-OCT images obtained on the patients. Two graders diagnosed the presence of drusen, geographic atrophy (GA), and exudative AMD (eAMD) in each eye. Medical records were reviewed to assess prior exudation. To assess symmetry, 1 eye of each patient was randomly selected as the index eye and compared with the fellow eye. The kappa statistic (κ) was used to assess the symmetry of diagnosis. The intraclass correlation coefficient (ICC) was used to assess the symmetry of drusen area and volume., Main Outcome Measures: Interocular symmetry of the AMD stages: drusen, GA, and eAMD., Results: A total of 1310 patients with AMD were included. The average age was 78 years (range, 50-102; 60% women). Of the 1310 subjects, 54% (701) presented with symmetric disease: 20% with bilateral drusen, 11% with bilateral GA, and 22% with bilateral eAMD. Only 0.5% of the subjects had both GA and eAMD in both eyes. Of the randomly selected index eyes, 825 (47%) were right eyes. Overall, limited interocular agreement was observed between the index and fellow eyes (54%; κ = 0.29). Kappa coefficients were poor (< 0.4) for index eyes diagnosed with drusen (κ = 0.27), eAMD (κ = 0.17), and mixed disease (κ = 0.03). There was moderate agreement between the index and fellow eyes for GA (κ = 0.50). Of the 265 patients with bilateral drusen, the symmetry of drusen area measurements had moderate ICC values of 0.70, 0.71, and 0.70 in the 3- and 5-mm diameter foveal-centered circles and in the total scan area, respectively. The ICC values for the drusen volumes were 0.65, 0.66, and 0.64, respectively., Conclusions: Interocular symmetry was poor for eyes with drusen, eAMD, and mixed disease, but moderate for GA. Although the diagnosis of drusen was not very symmetric between eyes, when present in both eyes, the drusen area and volume measurements were moderately symmetric., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether the outer retinal layer (ORL) thickness around geographic atrophy (GA) could serve as a clinical biomarker to predict the annual enlargement rate (ER) of GA., Design: Retrospective analysis of a prospective, observational case series., Methods: Eyes with GA were imaged with a swept-source OCT 6 × 6 mm scan pattern. GA lesions were measured from customized en face OCT images and the annual ERs were calculated. The ORL was defined and segmented from the inner boundary of outer plexiform layer (OPL) to the inner boundary of retinal pigment epithelium (RPE) layer. The ORL thickness was measured at different subregions around GA., Results: A total of 38 eyes from 27 participants were included. The same eyes were used for the choriocapillaris (CC) flow deficit (FD) analysis and the RPE to the Bruch membrane (RPE-BM) distance measurements. A negative correlation was observed between the ORL thickness and the GA growth. The ORL thickness in a 300-μm rim around GA showed the strongest correlation with the GA growth (r = -0.457, P = .004). No correlations were found between the ORL thickness and the CC FDs; however, a significant correlation was found between the ORL thickness and the RPE-BM distances around GA (r = -0.398, P = .013)., Conclusions: ORL thickness showed a significant negative correlation with annual GA growth, but also showed a significant correlation with the RPE-BM distances, suggesting that they were dependently correlated with GA growth. This finding suggests that the loss of photoreceptors was associated with the formation of basal laminar deposits around GA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: A training exercise was performed to study the ability of graders to reliably identify precursor lesions to geographic atrophy (GA), known as persistent choroidal hypertransmission defects (hyperTDs), using en face OCT images from eyes with nonexudative age-related macular degeneration (AMD)., Design: Intergrader agreement study., Participants: Eleven graders participated in this exercise., Methods: Formal training on how to identify persistent hyperTDs on en face OCT images was provided to the graders. A persistent hyperTD was defined as a bright lesion having a greatest linear dimension (GLD) of at least 250 μm. Training consisted of a tutorial session followed by the grading of 3 pretest exercises, each consisting of 3 cases. After all graders scored 100% on the pretest exercises, they performed a final exercise consisting of 30 en face OCT images from 29 eyes with nonexudative AMD containing 107 hyperTDs that each grader needed to evaluate. The cases contained a variety of AMD-related atrophic lesions., Main Outcome Measures: The sensitivity, positive predictive value (PPV), and modified accuracy were assessed for each grader., Results: A total of 1177 hyperTDs from 30 en face OCT images were reviewed by the graders. The mean sensitivity, PPV, and modified accuracy for all the graders were calculated to be 99.0%, 99.2%, and 98.2%, respectively. There was a 97% agreement observed between all the graders (first-order agreement coefficient [AC 1 ] = 0.97). Internal graders from the Bascom Palmer Eye Institute had a slightly higher agreement compared with the external graders (AC 1  = 0.98 vs. AC 1  = 0.96). The hyperTDs most often incorrectly identified included the following features: (1) hyperTDs containing hypotransmission defect cores, (2) single hyperTDs that were incorrectly graded as 2 separate lesions, and (3) hyperTDs with borderline GLDs that were close to 250 μm., Conclusions: The accurate detection of persistent hyperTDs on en face OCT images by graders demonstrates the feasibility of using this OCT biomarker to identify disease progression in eyes with nonexudative AMD, especially when used as a clinical trial end point in studies designed to test new therapies that may slow disease progression from intermediate AMD to GA., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether persistent hypertransmission defects (hyperTDs), previously shown to have a greatest linear dimension (GLD) ≥250 µm on en face swept source OCT (SS-OCT) images, serve as a stand-alone early biomarker for the future formation geographic atrophy (GA)., Design: Post hoc cohort study using a subgroup of a prospective study., Methods: Patients with intermediate age-related macular degeneration (iAMD) underwent 6- × 6-mm SS-OCT raster scans at baseline and during their follow-up period. En face images were generated using a slab with segmentation boundaries positioned 64 µm to 400 µm beneath the Bruch's membrane. Two graders independently evaluated all en face structural images for the presence of hyperTDs with a GLD ≥250 µm and GA., Results: A total of 190 eyes were included with a mean ± SD follow-up of 31 ± 13.2 months. At baseline, 31 eyes (16%) had at least 1 hyperTD ≥250 µm, and 13 eyes (42%) progressed to GA. In those eyes without a hyperTD ≥250 µm at baseline, 42 (26%) developed hyperTDs ≥250 µm during their follow-up, and 11 eyes (7%) progressed to GA. At the last available follow-up visit, 25 eyes (13%) progressed to GA and of these 25 eyes, a prior hyperTD ≥250 µm was detected in 24 eyes before GA formed. A time-dependent Cox-survival regression analysis estimated an 80-fold (95% CI, 10.7-614, P < .001) increased risk of developing GA once a hyperTD ≥250 µm appeared., Conclusions: Persistent hyperTDs detected on en face OCT images were shown to serve as an early stand-alone OCT biomarker for the future formation of GA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The retinal pigment epithelium (RPE) to Bruch membrane (BM) distance around geographic atrophy (GA) was measured using an optical attenuation coefficient (OAC) algorithm to determine whether this measurement could serve as a clinical biomarker to predict the annual square root enlargement rate (ER) of GA., Design: A retrospective analysis of a prospective, observational case series., Methods: Eyes with GA secondary to age-related macular degeneration (AMD) were imaged with swept-source OCT (SS-OCT) using a 6 × 6-mm scan pattern. GA lesions were identified and measured using customized en face OCT images, and GA annual square root ERs were calculated. At baseline, the OACs were calculated from OCT datasets to generate customized en face OAC images for GA visualization. RPE-BM distances were measured using OAC data from different subregions around the GA., Results: A total of 38 eyes from 27 patients were included in this study. Measured RPE-BM distances were the highest in the region closest to GA. The RPE-BM distances immediately around the GA were significantly correlated with GA annual square root ERs (r = 0.595, P < .001 for a 0- to 300-µm rim around the GA). No correlations were found between RPE-BM distances and previously published choriocapillaris (CC) flow deficits in any subregions., Conclusions: RPE-BM distances from regions around the GA significantly correlate with the annual ERs of GA. These results suggest that an abnormally thickened RPE/BM complex contributes to GA growth and that this effect is independent of CC perfusion deficits., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The local growth rates of geographic atrophy (GA) adjacent to non-exudative type 1 macular neovascularization (MNV) were investigated to determine if MNV influenced GA growth., Methods: Eyes with GA and non-exudative type 1 MNV were followed for at least 1 year. Both GA and the MNV were imaged and measured using swept-source optical coherence tomography angiography (SS-OCTA) scans. Pearson correlations were computed between local growth rates of GA, which were estimated using a biophysical GA growth model, and local distances-to-MNV. Corresponding P values for the null hypothesis of no Pearson correlation were computed using a Monte Carlo approach that adjusts for spatial autocorrelations., Results: Nine eyes were included in this study. There were positive correlations (Pearson's r > 0) between distance-to-MNV and local GA growth in eight (89%) of the eyes; however, in all but one eye (11%), correlations were relatively weak and statistically nonsignificant after Bonferroni correction (corrected P > 0.05)., Conclusions: SS-OCTA imaging combined with GA growth modeling and spatial statistical analysis enabled quantitative assessment of correlations between local GA growth rates and local distances-to-MNV. Our results are not consistent with non-exudative type 1 MNV having a strong inhibitory effect on local GA growth rates.

Purpose: To evaluate the prognostic significance of persistent choroidal hypertransmission defects (HyperTDs) detected on en face OCT imaging for predicting the progression of drusen to geographic atrophy (GA) by analyzing their association with the presence of nascent GA (nGA)., Design: Retrospective, post hoc subgroup analysis of a prospective study., Participants: Patients with bilateral soft drusen from a natural history study., Methods: Participants underwent both Spectralis SD-OCT (Heidelberg Engineering, Heidelberg, Germany) and Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA) imaging over 36 months at 6-month intervals. The Spectralis SD-OCT B-scans were used to grade nGA. En face imaging of Cirrus SD-OCT scans was used to detect HyperTDs, masked to nGA gradings. Hypertransmission defects with greatest linear dimension (GLD) of 125 μm or more were tracked throughout visits., Main Outcome Measures: The GLD at baseline for best discrimination between persistent and transient HyperTDs over 36 months and the association between these HyperTDs with nGA assessed with odds ratio., Results: A total of 157 eyes from 81 patients were enrolled. Cirrus SD-OCT scans were available for 133 eyes at baseline, and 39 HyperTDs lesions from 27 eyes of 22 participants were classified as either persistent (26 lesions) or transient (13 lesions) over 36 months. Receiver operating characteristic curve analysis suggested that HyperTDs with baseline GLD of 250 μm or more or 300 μm fit the definition of persistent. After grading the entire population of 157 eyes, a significant association (P < 0.001) was found between nGA gradings and masked HyperTD gradings with GLD of 250 μm or more (odds ratio, 14.5; 95% confidence interval, 4.8-54.0) or 300 μm (odds ratio, 15.2; 95% confidence interval, 5.0-56.7). Identification of HyperTDs was associated with more nGA false-positive results than false-negative results (P < 0.001). Hypertransmission defects with GLD of 250 μm or more or 300 μm showed excellent negative predictive value of 94% or more, but poor positive predictive value of 40% or less, for detecting nGA., Conclusions: Choroidal HyperTDs on en face OCT imaging were associated strongly with nGA. The potential of using HyperTDs with GLD of 250 μm or more or 300 μm as a risk factor for the progression of drusen to GA is promising and requires further study., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To demonstrate the applicability of a growth modeling framework for quantifying spatial variations in geographic atrophy (GA) lesion kinetics., Methods: Thirty-eight eyes from 27 patients with GA secondary to age-related macular degeneration were imaged with a commercial swept source optical coherence tomography instrument at two visits separated by 1 year. Local GA growth rates were computed at 6-µm intervals along each lesion margin using a previously described growth model. Corresponding margin eccentricities, margin angles, and growth angles were also computed. The average GA growth rates conditioned on margin eccentricity, margin angle, growth angle, and fundus position were estimated via kernel regression., Results: A total of 88,356 GA margin points were analyzed. The average GA growth rates exhibited a hill-shaped dependency on eccentricity, being highest in the 0.5 mm to 1.6 mm range and lower on either side of that range. Average growth rates were also found to be higher for growth trajectories oriented away from (smaller growth angle), rather than toward (larger growth angle), the foveal center. The dependency of average growth rate on margin angle was less pronounced, although lesion segments in the superior and nasal aspects tended to grow faster., Conclusions: Our proposed growth modeling framework seems to be well-suited for generating accurate, spatially resolved GA growth rate atlases and should be confirmed on larger datasets., Translational Relevance: Our proposed growth modeling framework may enable more accurate measurements of spatial variations in GA growth rates.

Purpose: To investigate the characteristics of treatment-naïve nonexudative macular neovascularization (MNV) in age-related macular degeneration before the onset of exudation using swept-source optical coherence tomography angiography., Methods: MNV area, choriocapillaris (CC) flow deficits (FDs), vessel area density (VAD), vessel skeleton density (VSD), retinal pigment epithelial detachment (PED) volume, mean choroidal thickness (MCT), and choroid vascularity index (CVI) measurements were assessed at two visits prior to exudation. We compared measurements made at the second visit and the rate of change between visits in eyes with and without exudation. The differences in these parameters between eyes with and without subsequent exudation were summarized with 95% confidence intervals (CIs)., Results: Twenty-one eyes with nonexudative MNV were identified and followed. Nine eyes developed exudation, and 12 eyes did not develop exudation. Differences between these groups of eyes for all parameters tended to be small, and the 95% CIs largely ruled out any substantial differences. Overall, eyes with exudation had 24% smaller VAD, 20% smaller VSD, and 33% smaller PED volume measurements. No noteworthy differences were observed for MNV area, CC FDs, MCT, or CVI measurements., Conclusions: The onset of exudation was correlated with lesions having less vascularity and smaller PED volume measurements, but measurements of MNV area, CC FDs, MCT, and CVI were not correlated with near-term exudation. Investigations are ongoing to further explore these and other anatomic changes as harbingers of near-term exudation.

Purpose: Correlations among enlargement rates (ERs) of geographic atrophy (GA) and choriocapillaris (CC) flow deficits (FDs), mean choroidal thickness (MCT), and choroidal vascularity index (CVI) were investigated using swept source-optical coherence tomography (SS-OCT) in age-related macular degeneration (AMD)., Design: A retrospective review of prospective, observational case series., Methods: Eyes with GA from AMD were imaged with SS-OCT using 6 × 6-mm scan pattern. GA lesions were identified and measured using customized en face structural images, and annual square root ERs of GA were calculated. At baseline, choriocapillaris FDs from different regions outside the GA were measured, and MCT and CVI from the entire scan area were measured. All measurements were performed using previously published and validated algorithms., Results: A total of 38 eyes from 27 patients were included. The CC FDs within each region around GA lesions were highly correlated with ERs of GA (all P < .005). CVI inside the GA region was correlated with the ERs (P = .03), whereas other choroidal measurements had no significant correlation with the ERs of GA (P > .06)., Conclusions: Statistically significant correlations were found between the ERs of GA and CC percentage of FD (FD%) from the entire scan region outside the GA and not just the region immediately adjacent to the GA. These results suggest that abnormal CC perfusion throughout the macula contributes to disease progression in eyes with GA. CVI inside the GA region could also be a potential indicator for the growth of GA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Swept source optical coherence tomography angiography (SS-OCTA) was used to study the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with unilateral nonexudative age-related macular degeneration., Design: Prospective cohort study., Methods: Patients were imaged using 3- × 3-mm and 6- × 6-mm SS-OCTA scan patterns. MNV was detected using the outer retina to choriocapillaris en face slab. Prevalence and incidence of subclinical MNV, Kaplan-Meier cumulative estimates for the overall risk of exudation, and the association between neovascular lesion size and the risk of exudation were assessed through 2 years., Results: From August 2014 through March 2018, 227 patients (154 intermediate and 73 late age-related macular degeneration eyes) underwent SS-OCTA imaging. Thirty eyes (13.2%) had subclinical MNV at first imaging and 12 eyes (8.9%) developed subclinical MNV during follow-up. Of the 191 eyes with >1 visit, 19 developed exudation. Fourteen of these eyes had pre-existing subclinical MNV. The incidence of exudation from the time of first detection of any subclinical MNV was 34.5%. The relative risk of exudation after detection of subclinical MNV was 13.6 times greater (95% confidence interval 4.9-37.7) than in the absence of subclinical MNV (P < .001). There was no significant risk of exudation based on lesion size alone (P = .91)., Conclusions: By 24 months, the risk of exudation was 13.6 times greater for eyes with subclinical MNV detected by SS-OCTA compared with eyes without subclinical MNV. For eyes with subclinical MNV in the absence of symptomatic exudation, we recommend close follow-up without treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To determine the possible correlation between the annual enlargement rates (ERs) of geographic atrophy (GA) with the percentage and size of the choriocapillaris (CC) flow deficits (FDs) surrounding GA, measured with swept-source OCT angiography (SS-OCTA) images., Design: Prospective, observational case series., Participants: Patients with GA secondary to nonexudative AMD., Methods: Patients were imaged with a 100-kHz SS-OCTA instrument (PLEX Elite 9000, Carl Zeiss Meditec, Dublin, CA) using a 6×6-mm field of view scan pattern. The GA area measurements were obtained from en face SS-OCT sub-retinal pigment epithelium (RPE) slab images. Visualization of the CC and quantification of FDs were performed using a previously published validated algorithm based on a 20-μm thickness slab with the inner boundary located beneath Bruch's membrane. The percentage of CC FDs (FD%) and the average FD area measurements were calculated in different regions around the GA., Main Outcome Measures: The correlation between the CC FDs and the ERs of GA., Results: Twenty-two eyes from 15 patients were eligible for the analysis. The annual square root ERs for GA ranged from 0.07 to 0.75 mm/year. The CC FD% and average FD area measurements were highly correlated with each other (P < 0.001), with the highest FD values found in the region closest to the margin of GA. The ERs correlated best with the average CC FD area measurements in the total scan area minus the area of GA (Pearson r = 0.747; P < 0.001) than those in the regions immediately surrounding the GA (r = 0.544; P = 0.009)., Conclusions: Contrary to expectations, the global CC FD measurements had a better correlation with the ERs of GA than those in the regions immediately around the GA. The most likely explanation for this outcome is that normal age-related increases in FDs within the central macula confound the correlations between the ERs of GA and FDs, whereas the regions furthest away from the margins of GA are less affected by normal age-related changes and reflect FD alterations related to AMD severity., (Copyright © 2019. Published by Elsevier Inc.)