OCT Signs of Early Atrophy in Age-Related Macular Degeneration: Interreader Agreement

Wu, Zhichao; Pfau, Maximilian; Blodi, Bárbara A.; Holz, Frank G.; Jaffe, Glenn J.; Liakopoulos, Sandra; Sadda, Srinivas R; Staurenghi, Giovanni; Bjelopera, Elvira; Brown, Tyler; Chang, Petrus; Choong, John; Corradetti, Giulia; Corvi, Federico; Domalpally, Amitha; Hurtenbach, Cynthia; Nittala, Muneeswar Gupta; Olson, Anthony W.; Pak, Jeong W.; Pappe, Judith; Saßmannshausen, Marlene; Skalak, Cindy; Thiele, Sarah; Guymer, Robyn H.; Schmitz-Valckenberg, Steffen

doi:10.1016/j.oret.2021.03.008

Cited by 52 publications

(40 citation statements)

References 31 publications

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“…The Age-Related Eye Disease Study (AREDS) research group found that the reproducibility of the type of the drusen ranges from 59.0 to 77.5% (exact agreement) ( 31 ). In this study, there were only two readers and they were from the same center and the reading standards were unified before reading; thus, our interobserver agreement was different from that reported by the Classification of Atrophy Meetings (CAM) group ( 32 ) (by 12 readers from 6 reading centers). In this study, the level of interobserver and intraobserver agreement for each morphological parameter was generally more than 90% for the drusen reflectivity, shape, and RPE damage, while the drusen homogeneity and the EZ damage showed the lowest agreement at 82.7%.…”

Section: Discussioncontrasting

confidence: 65%

Low-Reflectivity Drusen With Overlying RPE Damage Revealed by Spectral-Domain OCT: Hint for the Development of Age-Related Macular Degeneration

et al. 2021

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Purpose: To observe the relationship between the characteristic changes in the drusen morphology revealed by the spectral-domain optical coherence tomography (SD-OCT) and the progression of age-related macular degeneration (AMD).Methods: A total of 380 drusen in 45 eyes in 35 patients with the intermediate drusen were longitudinally followed up every 6 months by SD-OCT for a period of 24 months. The drusen were divided into the dynamic group and stable group according to the following parameters: number, volume, concurrent retinal pigment epithelium (RPE)/ellipsoid zone (EZ) damage, and the development of advanced AMD. The morphological characteristics of the progressive or stable drusen were further analyzed. Odds ratios (ORs) and the risk for the drusen progression were calculated.Results: The level of interobserver and intraobserver agreement for each drusen tomographic morphological parameters ranged from 82.7 to 90%. At the end of an average follow-up of 15.92 ± 6.99 months, six patients developed choroidal neovascularization and no patients developed geographic atrophy. Finally, 139 drusen changed and 241 drusen remained stable. The drusen with low reflectivity (p < 0.001; OR: 5.26; 95% CI: 2.24–12.36), non-homogeneity without a core (p < 0.001; OR: 4.31; 95% CI: 2.08–8.92), RPE damage (p < 0.001; OR: 28.12; 95% CI: 9.43–83.85), and the EZ damage (p < 0.001; OR: 14.01; 95% CI: 5.28–37.18) were significantly associated with active change; the drusen with low reflectivity (p = 0.01; OR: 2.95; 95% CI: 1.29–6.75) and decreased overlying RPE reflectivity (p < 0.001; OR: 21.67; 95% CI: 9.20–51.02) were the independent predictors for progression. The drusen with high reflectivity were significantly associated with stabilization (p = 0.03; OR: 0.17; 95% CI: 0.04–0.84).Conclusion: Spectral-domain optical coherence tomography is an optimized, accurate, and efficient method to follow-up the drusen. The intermediate non-exudative AMD prognosis of the patient was most strongly correlated with the drusen reflectivity and disruption of the overlying RPE layer. The drusen with low reflectivity and overlying RPE damage were more likely to progress and required frequent follow-up.

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Section: Discussioncontrasting

confidence: 65%

Low-Reflectivity Drusen With Overlying RPE Damage Revealed by Spectral-Domain OCT: Hint for the Development of Age-Related Macular Degeneration

et al. 2021

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“…The main OCT biomarkers related to progression to advanced AMD include drusen volume, hyperreflective foci (HRF), reticular pseudodrusen or subretinal drusenoid deposits (SDD), incomplete retinal pigment epithelial and outer retinal atrophy (iRORA), hyper-transmission defects, and OCT-reflective drusen substructures (ODS) [9][10][11][12][13][26][27][28].…”

Section: Optical Coherence Tomography (Oct) Findingsmentioning

confidence: 99%

“…The term iRORA refers to the localized loss of tissue in the outer layers of retina without definite RPE loss. iRORA represent the new nomenclature obtained by the Consensus International Group (CAM-Classification of Atrophy Meeting) and has, more or less, replaced the so called "Nascent GA" [9][10][11][12][13]. Nascent GA and iRORA have not exactly the same meaning, because nascent GA should be only used in the absence of current or prior macular neovascularization.…”

Section: Incomplete Retinal Pigment Epithelial and Outer Retinal Atrophymentioning

confidence: 99%

“…A variety of terms were proposed including sub-RPE illumination, choroidal hyperreflectivity, narrow columns of hyper-reflectivity, and hyper-transmission defects. CAM participants agreed that the term hyper-transmission defects was the preferred term because it reports to the cause for the observed phenomenon and includes all cases even those with tall PEDs, where the hyper-transmission may not always penetrate to the underlying choroid [9][10][11][12][13].…”

Section: Hyper-transmission Defectsmentioning

confidence: 99%

“…This wide variation in AMD risk progression reflects the population heterogeneity and explains the particular interest in exploring different phenotypes and in searching predictive biomarkers. Since 2017, the Consensus International Group (CAM-Classification of Atrophy Meeting) has been discussing and publishing on this subject, whose main objective is to provide standardized biomarkers for future interventional clinical trials [9][10][11][12][13]. Predictive knowledge is also an important goal in clinical practice, supporting the identification of patients at increased risk of late AMD changes.…”

Section: Introductionmentioning

confidence: 99%

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Retinal Progression Biomarkers of Early and Intermediate Age-Related Macular Degeneration

Flores

Carneiro

Tenreiro

et al. 2021

Life

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Early and intermediate AMD patients represent a heterogeneous population with an important but variable risk of progression to more advanced stages of the disease. The five-year progression from early and intermediate AMD to late disease is known to range from 0.4% to 53%. This wide variation explains the particular interest in searching predictive AMD biomarkers. Clinical parameters such as drusen size, presence of pigmentary abnormalities, and fellow eye status were, traditionally, the more important predictive elements. Multimodal retinal assessment (Color Fundus Photography, Optical Coherence Tomography, Optical Coherence Angiography and Fundus Autofluorescence) is providing new and accurate image biomarkers, useful in research and in daily practice. If individual progression risk could be anticipated, then management plans should be adapted accordingly, considering follow-up intervals and therapeutic interventions. Here, we reviewed the most important image progression biomarkers of early and intermediate AMD with relevant interest in clinical practice.

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Association of Pegcetacoplan With Progression of Incomplete Retinal Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular Degeneration

Nittala

Metlapally

et al. 2022

JAMA Ophthalmol

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IMPORTANCE Change in areas of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) within eyes with geographic atrophy (GA) might reflect similar changes among eyes with drusen but no GA.OBJECTIVE To evaluate the potential association of pegcetacoplan with progression of iRORA in eyes with GA secondary to AMD. DESIGN, SETTING, AND PARTICIPANTSThis post hoc analysis of the phase 2 multicenter, randomized, single-masked, sham-controlled FILLY trial of intravitreal pegcetacoplan for 12 months took place from February 2 to July 7, 2020. Participants comprised 167 patients with GA secondary to AMD who received pegcetacoplan monthly (n = 41) or every other month (n = 56) or a sham injection (n = 70) in the FILLY trial, completed the month 12 study visit, and did not develop exudative AMD.INTERVENTIONS Intravitreal pegcetacoplan, 15 mg, or sham injection, monthly or every other month for 12 months.MAIN OUTCOMES AND MEASURES Masked readers analyzed spectral-domain optical coherence tomography scans in regions beyond a perimeter of 500 μm from the GA border according to the Classification of Atrophy Meetings criteria. Primary outcome measures were progression from iRORA to complete RPE and outer retina atrophy (cRORA) from baseline to 6 and 12 months. RESULTS Among the 167 patients in the study, at baseline, iRORA was present in 45.0% of study eyes (18 of 40) in the pegcetacoplan monthly group, 61.8% of study eyes (34 of 55) in the pegcetacoplan every other month group, and 50.7% of study eyes (34 of 67) in the sham group. At 12 months, progression from iRORA to cRORA occurred in 50.0% of study eyes (9 of 18) in the pegcetacoplan monthly group (P = .02 vs sham), 60.6% of study eyes (20 of 33) in the pegcetacoplan every other month group (P = .06 vs sham), and 81.8% of study eyes (27 of 33) in the sham group. Compared with sham treatment, the relative risk of progression at 12 months from iRORA to cRORA was 0.61 (95% CI, 0.37-1.00) for eyes in the pegcetacoplan monthly group and 0.74 (95% CI, 0.54-1.02) for eyes in the pegcetacoplan every other month group.CONCLUSIONS AND RELEVANCE Eyes receiving intravitreal pegcetacoplan had lower rates of progression from iRORA to cRORA compared with controls, suggesting a potential role for pegcetacoplan therapy earlier in the progression of AMD prior to the development of GA.

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OCT Signs of Early Atrophy in Age-Related Macular Degeneration: Interreader Agreement

Cited by 52 publications

References 31 publications

Low-Reflectivity Drusen With Overlying RPE Damage Revealed by Spectral-Domain OCT: Hint for the Development of Age-Related Macular Degeneration

Low-Reflectivity Drusen With Overlying RPE Damage Revealed by Spectral-Domain OCT: Hint for the Development of Age-Related Macular Degeneration

Retinal Progression Biomarkers of Early and Intermediate Age-Related Macular Degeneration

Association of Pegcetacoplan With Progression of Incomplete Retinal Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular Degeneration

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