A Quantitative Approach to Predict Differential Effects of Anti-VEGF Treatment on Diffuse and Focal Leakage in Patients with Diabetic Macular Edema: A Pilot Study

Abstract

PurposeWe use semiautomated segmentation of fluorescein angiography (FA) to determine whether anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME) differentially affects microaneurysm (MA)–associated leakage, termed focal leakage, versus non-MA–associated leakage, termed diffuse leakage.MethodsWe performed a retrospective study of 29 subjects treated with at least three consecutive injections of anti-VEGF agents for DME (mean 4.6 injections; range, 3–10) who underwent Heidelberg FA before and after anti-VEGF therapy. Inclusion criteria were macula center involving DME and at least 3 consecutive anti-VEGF injections. Exclusion criteria were macular edema due to cause besides DME, anti-VEGF within 3 months of initial FA, concurrent treatment for DME besides anti-VEGF, and macular photocoagulation within 1 year. At each time point, total leakage was semiautomatically segmented using a modified version of our previously published software. Microaneurysms were identified by an expert grader and leakage within a 117 μm radius of each MA was classified as focal leakage. Remaining leakage was classified as diffuse leakage. The absolute and percent changes in total, diffuse, and focal leakage were calculated for each subject.ResultsMean pretreatment total leakage was 8.2 mm2 and decreased by a mean of 40.1% (P < 0.0001; 95% confidence interval [CI], [−28.6, −52.5]) following treatment. Diffuse leakage decreased by a mean of 45.5% (P < 0.0001; 95% CI, [−31.3, −59.6]) while focal leakage decreased by 17.9% (P = 0.02; 95% CI, [−1.0, −34.8]). The difference in treatment response between focal and diffuse leakage was statistically significant (P = 0.01).ConclusionsAnti-VEGF treatment for DME results in decreased diffuse leakage but had relatively little effect on focal leakage as assessed by FA. This suggests that diffuse leakage may be a marker of VEGF-mediated pathobiology. Patients with predominantly focal leakage may be less responsive to anti-VEGF therapy.Translational RelevanceFluorescein angiography can define focal and diffuse subtypes of diabetic macular edema and these may respond differently to anti-VEGF treatment.

Evaluation of Navigated Laser Photocoagulation (Navilas 577+) for the Treatment of Refractory Diabetic Macular Edema

“…Predominantly, focal leakage from MAs showed less responsive to anti-VEGF therapy [ 19 ]. In our study, especially in cases where leaking MAs are mainly localized outside of the perifoveal capillary network, navigated laser therapy was effective.…”

Deep learning-based single-shot prediction of differential effects of anti-VEGF treatment in patients with diabetic macular edema

“…Section (2) describes material and methods in detail, including the clinical dataset, pre-processing, and CNN-based classification methods. Experimental results on OCT dataset are reported in Section (3). Sections (4) and (5) discuss and conclude this study and suggest our prospective research lines and future works.…”

“…Current options for DME treatment include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents such as bevacizumab, ranibizumab, and aflibercept, injections of corticosteroid drugs, or use of a macular thermal laser [2]. Intravitreal anti-VEGF agents are the most common first line of therapy for DME, but not every patient responds to them [3] and other forms of treatment are often required [4,5].…”

“…In a previous study, we developed a semi-automatic method to predict treatment outcomes in DME patients based on invasive fluorescein angiography imaging. [3] Here we use a fully automatic and non-invasive method to predict treatment outcomes in DME patients after three consecutive monthly anti-VEGF injections based solely on analysis of pretreatment optical coherence tomography (OCT) images. The single-shot term in our study emphasizes that the proposed method predicts the response to therapy by analyzing a single timepoint pre-treatment OCT volume, without the need for longitudinal treatment information such as time-series OCT images, patient records, or other metadata.…”

Intravitreal Bevacizumab In Diabetic Macular Edema At RSUP Cipto Mangunkusumo in 2017

“…Intravitreal anti-VEGF injection is the main therapy for current DME. 12 The use of Intravitreal Bevacizumab (IVB) injection proved effective on DME. 13 Diabetic Retinopathy Clinical Research (DRCR) network stated improved visual acuity in the third week after anti-VEGF injection.…”