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Original Investigation |

Correlation of 3-Dimensionally Quantified Intraretinal and Subretinal Fluid With Visual Acuity in Neovascular Age-Related Macular Degeneration

Sebastian M. Waldstein, MD1; Ana-Maria Philip, MD1; Roland Leitner, PhD1; Christian Simader, MD1; Georg Langs, PhD2; Bianca S. Gerendas, MD1; Ursula Schmidt-Erfurth, MD1
[+] Author Affiliations
1Vienna Reading Center, Department of Ophthalmology and Optometry, Christian Doppler Laboratory for Ophthalmic Image Analysis, Medical University of Vienna, Vienna, Austria
2Computational Imaging Research Laboratory, Department of Biomedical Imaging and Image-Guided Therapy, Christian Doppler Laboratory for Ophthalmic Image Analysis, Medical University of Vienna, Vienna, Austria
JAMA Ophthalmol. 2016;134(2):182-190. doi:10.1001/jamaophthalmol.2015.4948.
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Importance  Robust and sensitive imaging biomarkers for visual function are an unmet medical need in the management of neovascular age-related macular degeneration.

Objective  To determine the correlation of 3-dimensionally quantified intraretinal cystoid fluid (IRC) and subretinal fluid (SRF) with best-corrected visual acuity (BCVA) in treatment-naive neovascular age-related macular degeneration and during antiangiogenic therapy.

Design, Setting, and Participants  Retrospective cohort study between November 2009 and November 2011 at an institutional referral center and reading center of patients with treatment-naive subfoveal choroidal neovascularization receiving intravitreal ranibizumab or aflibercept over 12 months. All individual IRC and SRF lesions were manually delineated on each of the 128 B-scan sections of spectral-domain optical coherence tomographic volume scans at baseline and months 1, 6, and 12. Correlations were computed between the IRC and SRF parameters and the baseline BCVA, final BCVA, and BCVA change. A systematic parameter search was conducted to detect annotation-derived variables with best predictive value. An exponential model for BCVA change balancing for the ceiling effect was constructed.

Main Outcomes and Measures  Goodness of fit of correlations between the IRC and SRF parameters and the baseline BCVA, final BCVA, and BCVA change.

Results  Thirty-eight patients were included (25 female, 13 male; mean [SD] age at enrollment, 78.49 [8.23] years; mean [SD] BCVA score at baseline, 54 [16] Early Treatment Diabetic Retinopathy Study letters [Snellen equivalent approximately 20/160], with a gain to 63 [19] letters [Snellen equivalent approximately 20/100] at month 12). A total of 19 456 scans underwent complete quantification of IRC and SRF. The best correlation with BCVA at baseline was achieved using a coverage-based, foveal area–weighted IRC parameter (R2 = 0.59; P < .001). The same baseline parameter also predicted BCVA at 12 months (R2 = 0.21; P = .003). The BCVA gain correlated with IRC decrease in the exponential model (R2 = 0.40; P < .001) and linear model (R2 = 0.25; P = .002). No robust associations were found between SRF and baseline BCVA (R2 = 0.06; P = .14) or BCVA change (R2 = 0.14; P = .02).

Conclusions and Relevance  In this proof-of-principle study, IRC-derived morphometric variables correlated well with treatment-naive BCVA and BCVA outcomes in antiangiogenic therapy. While IRC reduction was associated with BCVA gains, some IRC-mediated neurosensory damage remained permanent.

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Figure 1.
Example of 3-Dimensional Volumetric Annotation of Intraretinal Cystoid Fluid and Subretinal Fluid in Treatment-Naive Neovascular Age-Related Macular Degeneration

Turquoise indicates intraretinal cystoid fluid; orange, subretinal fluid. A, Foveal optical coherence tomographic B-scan (fast scanning direction), where the tracings were performed. B, Reconstruction along the slow scanning direction (A-scan). C, Reconstructed en face plane (C-scan). D, A 3-dimensional rendering of the annotations.

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Figure 2.
Illustration of the Annotation Weighting Function A(x,y) and Spatial Weighting Function S(x,y)

The annotation weighting function computes various variables out of given fluid annotations. A, Two exemplary spheres with different diameters are shown. B, The annotation weighting function total volume includes the lesions in their entire dimensions, while the maximum and minimum height functions and the area function include only certain aspects of the fluid. C, The spatial weighting function assigns weights to fluid regions depending on their location in relation to the foveal center. In this case, the central 1-mm area is assigned 3 times the weight of the 2- to 3-mm ring. Fluid regions outside the 3-mm area are not considered. An exemplary en face projection of intraretinal cystoid fluid annotations is shown in green.

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Figure 3.
Correlations Between Intraretinal Cystoid Fluid (IRC)–Derived Variables and Best-Corrected Visual Acuity (BCVA) in Treatment-Naive Neovascular Age-Related Macular Degeneration

Correlations of IRC volume (A), IRC area (B), and optimized IRC area indicator (C) with BCVA. In general, increasing amounts of IRC are associated with worse BCVA. The IRC area (B) shows a better correlation with vision than the IRC volume (A), and the best correlation is achieved with an optimized IRC area indicator accentuating central areas and considering IRC height only up to 20 µm (C). The clusters of points on the y-axis represent patients without IRC at baseline (34% of the cohort). AU indicates artificial units; solid line, the regression line; and dashed lines, 95% confidence interval of the regression line.

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Figure 4.
Correlations Between Subretinal Fluid (SRF)–Derived Variables and Best-Corrected Visual Acuity (BCVA) in Treatment-Naive Neovascular Age-Related Macular Degeneration

No robust correlations were detected for SRF volume (A) and area (B) with BCVA. However, eyes with greater amounts of SRF tended to show better BCVA values, indicating a possible protective effect of SRF. Solid line indicates the regression line; dashed lines, 95% confidence interval of the regression line.

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Figure 5.
Prediction of Best-Corrected Visual Acuity (BCVA) After 1 Year of Antiangiogenic Therapy

A, Roughly 20% of final BCVA could be predicted by assessment of intraretinal cystoid fluid (IRC) at baseline, signifying that IRC-mediated damage may partially remain permanent. B, Up to 40% of BCVA change from baseline to month 12 could be explained by the resolution of IRC using a relative BCVA change model. C, When using BCVA as a linear variable, the correlation was weaker. AU indicates artificial units; solid line, the regression line; and dashed lines, 95% confidence interval of the regression line.

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