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Updated: Aug 13, 2026
A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration
Published on: March 10, 2023
The Double Layer Sign Is Highly Predictive of Progression to Exudation in Age-Related Macular Degeneration
Lajos Csincsik1, Katherine A Muldrew1, Alessandra Bettiol2
1Centre for Public Health, Faculty of Medicine and Health Sciences, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
Purpose:
The presences of a double layer sign (DLS) and a shallow irregular retinal pigment epithelium (RPE) elevation (SIRE) were investigated using spectral domain-OCT (SD-OCT) imaging to determine their ability to predict progression to exudative macular neovascularization (eMNV) in the unaffected fellow eyes (study eye) of participants with age-related macular degeneration (AMD) with newly diagnosed unilateral eMNV.
Design:
Retrospective, reanalysis of SD-OCT scans of study eyes from the Early Detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU).
Participants:
The EDNA study repository of SD-OCT scans was assessed for inclusion. Cases with incomplete data sets, low quality scans, or exhibiting other pathology were excluded, which resulted in 459 eligible cases.
Methods:
Spectral domain-OCT volume scans of study eyes were graded for irregular elevation of the RPE (IE), with length, and height measurements made on the most affected B-scan. Eyes with heterogeneous reflectivity within the IE were classified as exhibiting the DLS. Eyes with DLS where the length of separation between RPE and Bruch's membrane was ≥ 1000 μm in length and < 100 μm in height were subclassified as SIRE.
Main Outcome Measures:
Hazard of progression to eMNV for DLS and SIRE.
Results:
Of the 459 eyes, 268 had IE, of which 101 were DLS-like and 51 also fulfilled criteria for SIRE. Over the 3 years FU period, 104 (23%) eyes progressed to eMNV. After an FU of 18 months, a significantly higher proportion of study eyes (P < 0.001) with IE, DLS, and SIRE developed eMNV compared with those without these features (IE: 17% vs. no IE 6.3%; DLS: 23% vs. no DLS 9.9%; SIRE: 22% vs. no SIRE 11%). In the adjusted Cox regression models, a significantly greater hazard of progression (P < 0.001) was associated with the presence of IE (adjusted hazard ratio [HR], 3.01; 95% confidence interval [CI], 1.88-4.82), DLS (adjusted HR, 3.41; 95% CI, 2.26-5.14), or SIRE (adjusted HR, 2.83; 95% CI, 1.68-4.75).
Conclusion:
The DLS is a highly sensitive predictor of progression to eMNV, and the use of SIRE does not improve predictability.
Financial Disclosure(S):
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
