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This review covers advancements in geographic atrophy (GA) research. It discusses genetic contributions to AMD, explores treatment strategies, including complement inhibition, and highlights recent FDA approvals, safety concerns and promising future directions., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

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 investigate the association of nascent geographic atrophy (GA) preceding the development of exudative type 3 macular neovascularization (MNV) in patients with age-related macular degeneration (AMD)., Design: Retrospective longitudinal study., Participants: Patients with AMD diagnosed with treatment-naive exudative type 3 MNV in 1 or both eyes were evaluated. Inclusion criteria included serial tracked structural OCT examinations for ≥ 2 years before the detection of exudative type 3 MNV., Methods: Clinical characteristics and retinal imaging, including structural OCT at baseline and at each follow-up examination, were analyzed. Eyes showing the presence of nascent GA during the follow-up were selected for analysis of prevalence, and clinical characteristics at the site of subsequent type 3 MNV development., Main Outcome Measures: Description of the prevalence and clinical characteristics of nascent GA at the site of subsequent type 3 MNV development., Results: Overall, 97 eyes affected by type 3 MNV meeting inclusion criteria were analyzed. Of 97 eyes (71 patients), 22 eyes of 21 patients (mean age 82 ± 9 years) showed nascent GA preceding exudative type 3 MNV. The observed prevalence of nascent GA preceding exudative type 3 MNV was 22.7% (95% confidence interval, 14.4%-31.0%). Exudative type 3 MNV developed a mean of 9 ± 6 months after detection of nascent GA. The presence of reticular pseudodrusen in the study eye did not significantly influence the timing of exudative type 3 MNV development after the observation of nascent GA (P > 0.1 in all analyses). Reduced best-corrected visual acuity was recorded at the exudative type 3 stage in comparison with the nascent GA stage (P = 0.003)., Conclusions: As nascent GA may precede the development of exudative type 3 MNV, the detection of nascent GA in eyes with AMD may warrant closer surveillance to identify early exudative type 3 MNV warranting treatment., 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: Geographic atrophy (GA) is a late-stage form of age-related macular degeneration (AMD) characterized by the expansion of atrophic lesions in the outer retina. There are currently no approved pharmacological treatments to prevent or slow the progression of GA. This review describes the progression and assessment of GA, predictive imaging features, and complement-targeting investigational drugs for GA., Methods: A literature search on GA was conducted., Results: Expansion of atrophic lesions in patients with GA is associated with a decline in several measures of visual function. GA lesion size has been moderately associated with measures obtained through microperimetry, whereas GA lesion size in the 1-mm diameter area centered on the fovea has been associated with visual acuity. Optical coherence tomography (OCT) can provide 3-dimensional quantitative assessment of atrophy and is useful for identifying early atrophy in GA. Features that have been found to predict the development of GA include certain drusen characteristics and pigmentary abnormalities. Specific OCT features, including hyper-reflective foci and OCT-reflective drusen substructures, have been associated with AMD disease progression. Lesion characteristics, including focality, regularity of shape, location, and perilesional fundus autofluorescence patterns, have been identified as predictors of faster GA lesion growth. Certain investigational complement-targeting drugs have shown efficacy in slowing the progression of GA., Conclusion: GA is a progressive disease associated with irreversible vision loss. Therefore, the lack of treatment options presents a significant unmet need. OCT and drugs under investigation for GA are promising future tools for disease management., (© 2022. The Author(s).)

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: 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.