The double layer sign is highly predictive of progression to exudation in age-related macular degeneration

Lajos Csincsik; Katherine A. Muldrew; Alessandra Bettiol; David M. Wright; Philip J. Rosenfeld; Nadia K. Waheed; Theo Empeslidis; Eduard De Cock; Taffeta Ching Ning Yamaguchi; Ruth E. Hogg; Tunde Peto; Usha Chakravarthy

doi:10.1016/j.oret.2023.10.006

The double layer sign is highly predictive of progression to exudation in age-related macular degeneration

Lajos Csincsik, Katherine A. Muldrew, Alessandra Bettiol, David M. Wright, Philip J. Rosenfeld, Nadia K. Waheed, Theo Empeslidis, Eduard De Cock, Taffeta Ching Ning Yamaguchi, Ruth E. Hogg, Tunde Peto, Usha Chakravarthy^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	234-245
Number of pages	12
Journal	Opthalmology Retina
Volume	8
Issue number	3
DOIs	https://doi.org/10.1016/j.oret.2023.10.006
Publication status	Published - Mar 2024

Keywords

AMD
Age-related macular degeneration
DLS
OCT
Optical coherence tomography
SIRE
double layer sign
eMNV
exudative macular neovascularization
shallow irregular RPE elevation

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10.1016/j.oret.2023.10.006Licence: CC BY

The double layer sign is highly predictive of progression to exudation in age-related macular degeneration
Copyright 2023 The American Academy of Ophthalmology. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.15 MBLicence: CC BY

Cite this

Csincsik, L., Muldrew, K. A., Bettiol, A., Wright, D. M., Rosenfeld, P. J., Waheed, N. K., Empeslidis, T., De Cock, E., Yamaguchi, T. C. N., Hogg, R. E., Peto, T., & Chakravarthy, U. (2024). The double layer sign is highly predictive of progression to exudation in age-related macular degeneration. Opthalmology Retina, 8(3), 234-245. https://doi.org/10.1016/j.oret.2023.10.006

@article{7b2aba3ef7f94a55ab19f4320a0fbdf7,

title = "The double layer sign is highly predictive of progression to exudation in age-related macular degeneration",

abstract = "PurposeThe 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.DesignRetrospective, reanalysis of SD-OCT scans of study eyes from the Early Detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU).ParticipantsThe 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.MethodsSpectral 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{\textquoteright}s membrane was ≥ 1000 μm in length and < 100 μm in height were subclassified as SIRE.Main Outcome MeasuresHazard of progression to eMNV for DLS and SIRE.ResultsOf 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).ConclusionThe 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.",

keywords = "AMD, Age-related macular degeneration, DLS, OCT, Optical coherence tomography, SIRE, double layer sign, eMNV, exudative macular neovascularization, shallow irregular RPE elevation",

author = "Lajos Csincsik and Muldrew, {Katherine A.} and Alessandra Bettiol and Wright, {David M.} and Rosenfeld, {Philip J.} and Waheed, {Nadia K.} and Theo Empeslidis and {De Cock}, Eduard and Yamaguchi, {Taffeta Ching Ning} and Hogg, {Ruth E.} and Tunde Peto and Usha Chakravarthy",

year = "2024",

month = mar,

doi = "10.1016/j.oret.2023.10.006",

language = "English",

volume = "8",

pages = "234--245",

journal = "Opthalmology Retina",

issn = "2468-6530",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - The double layer sign is highly predictive of progression to exudation in age-related macular degeneration

AU - Csincsik, Lajos

AU - Muldrew, Katherine A.

AU - Bettiol, Alessandra

AU - Wright, David M.

AU - Rosenfeld, Philip J.

AU - Waheed, Nadia K.

AU - Empeslidis, Theo

AU - De Cock, Eduard

AU - Yamaguchi, Taffeta Ching Ning

AU - Hogg, Ruth E.

AU - Peto, Tunde

AU - Chakravarthy, Usha

PY - 2024/3

Y1 - 2024/3

N2 - PurposeThe 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.DesignRetrospective, reanalysis of SD-OCT scans of study eyes from the Early Detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU).ParticipantsThe 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.MethodsSpectral 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 MeasuresHazard of progression to eMNV for DLS and SIRE.ResultsOf 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).ConclusionThe 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.

AB - PurposeThe 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.DesignRetrospective, reanalysis of SD-OCT scans of study eyes from the Early Detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU).ParticipantsThe 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.MethodsSpectral 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 MeasuresHazard of progression to eMNV for DLS and SIRE.ResultsOf 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).ConclusionThe 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.

KW - AMD

KW - Age-related macular degeneration

KW - DLS

KW - OCT

KW - Optical coherence tomography

KW - SIRE

KW - double layer sign

KW - eMNV

KW - exudative macular neovascularization

KW - shallow irregular RPE elevation

U2 - 10.1016/j.oret.2023.10.006

DO - 10.1016/j.oret.2023.10.006

M3 - Article

C2 - 37839548

SN - 2468-6530

VL - 8

SP - 234

EP - 245

JO - Opthalmology Retina

JF - Opthalmology Retina

IS - 3

ER -

The double layer sign is highly predictive of progression to exudation in age-related macular degeneration

Abstract

Keywords

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