Quantitative assessment of retinal fluid in neovascular age-related macular degeneration under anti-VEGF therapy

Abstract

The retinal world has been revolutionized by optical coherence tomography (OCT) and anti-vascular endothelial growth factor (VEGF) therapy. The numbers of intravitreal injections are on a constant rise and management in neovascular age-related macular degeneration (nAMD) is mainly driven by the qualitative assessment of macular fluid as detected on OCT scans. The presence of macular fluid, particularly subretinal fluid (SRF) and intraretinal fluid (IRF), has been used to trigger re-treatments in clinical trials and the real world. However, large discrepancies can be found between the evaluations of different readers or experts and especially small amounts of macular fluid might be missed during this process. Pixel-wise detection of macular fluid uses an entire OCT volume to calculate exact volumes of retinal fluid. While manual annotations of such pixel-wise fluid detection are unfeasible in a clinical setting, artificial intelligence (AI) is able to overcome this hurdle by providing real-time results of macular fluid in different retinal compartments. Quantitative fluid assessments have been used for various post hoc analyses of randomized controlled trials, providing novel insights into anti-VEGF treatment regimens. Nonetheless, the application of AI-algorithms in a prospective patient care setting is still limited. In this review, we discuss the use of quantitative fluid assessment in nAMD during anti-VEGF therapy and provide an outlook to novel forms of patient care with the support of AI quantifications.

Keywords: age-related macular degeneration; artificial intelligence; deep learning; intraretinal fluid; macular neovascularization; subretinal fluid.

Figure 1.

Example of real-time quantification of macular fluid volumes (SRF = blue; IRF = yellow) for a patient with neovascular age-related macular degeneration following a treat-and-extend regimen using the Vienna Fluid Monitor. The green lines mark the border of the central millimeter. (a) Baseline; (b) Month 1; (c) Month 2; (d) after the loading dose of 3 consecutive injections, the patient presents with a dry macula; (e and f) IRF remained on low level with some residual IRF; (g) after a missed visit, IRF volumes greatly increased; (h and i) after interval reduction, the macular remained without fluid. The quantitative measurements are shown in Figure 2.

Figure 2.

Course of SRF (blue), IRF (yellow) within the central millimeter and best-corrected visual acuity (orange) of the patient presented in Figure 1 using the Vienna Fluid Monitor. The patient was managed using a treat-and-extend regimen and anti-VEGF was administered at each visit. The increase of IRF after the sixth visit was caused by a missed visit and was accompanied by a decline of visual acuity. After full resolution of macular fluid, visual acuity was partly regained.

Figure 3.

Degenerative cystoid fluid (red arrow) mimicking resistant intraretinal fluid (IRF) before (a) and after (b) anti-VEGF treatment.

Figure 4.

Outer retinal tubulations (ORT – exemplary ORTs: green arrows) imitating intraretinal fluid (IRF). A qualified reader is needed to distinguish ORT from IRF based on the characteristic appearance of ORT.