Correlation of vascular and fluid-related parameters in neovascular age-related macular degeneration using deep learning.

PURPOSE: To identify correlations between the vascular characteristics of macular neovascularization (MNV) obtained by optical coherence tomography angiography (OCTA) and distinct retinal fluid volumes in neovascular age-related macular degeneration (nAMD). METHODS: In this prospective interventional study, 54 patients with treatment-naïve type 1 or 2 nAMD were included and treated with intravitreal aflibercept. At baseline and month 1, each patient underwent a SD-OCT volume scan and volumetric flow scan using a swept-source OCTA. A deep learning algorithm was used to automatically detect and quantify fluid in OCT scans. Angio Tool, a National Cancer Institute algorithm, was used to skeletonize MNV properties and quantify lesion size (LS), vessel area (VA), vessel density (VD), total number of endpoints (TNE), total number of junctions (TNJ), junction density (JD), total vessel length (TVL), average vessel length (AVL) and mean-e-lacunarity (MEL). Subsequently, linear regression models were used to investigate a correlation between OCTA parameters and fluid quantifications. RESULTS: The median amount of fluid within the central 6-mm EDTRS ring was 173.7 nl at baseline, consisting of 156.6 nl of subretinal fluid (SRF) and 2.3 nl of intraretinal fluid (IRF). Fluid decreased significantly in all compartments to 1.76 nl (SRF) and 0.64 nl (IRF). The investigated MNV parameters did not change significantly after the first treatment. There was no significant correlation between MNV parameters and relative fluid decrease after anti-VEGF treatment. Baseline fluid correlated statistically significant but weakly with TNE (p = 0.002, R2  = 0.17), SRF with TVL (p = 0.04, R2  = 0.08), VD (p = 0.046, R2  = 0.08), TNE (p = 0.001, R2  = 0.20) and LS (p = 0.033, R2  = 0.09). IRF correlated with VA (p = 0.042, R2  = 0.08).The amount of IRF at month 1 correlated significantly but weakly with VD (p = 0.036, R2  = 0.08), JD (p = 0.019, R2  = 0.10) and MEL (p = 0.005, R2  = 0.14). CONCLUSION: Macular neovascularization parameters at baseline and month 1 played only a minor role in the exudation process in nAMD. None of the MNV parameters were correlated with the treatment response.

Baseline predictors for subretinal fibrosis in neovascular age-related macular degeneration.

To find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.

Morphologic and Microvascular Differences Between Macular Neovascularization With and Without Subretinal Fibrosis.

Purpose: To evaluate morphologic and microvascular differences between eyes with and without subretinal fibrosis (SF) caused by neovascular age-related macular degeneration (nAMD). Methods: Patients with nAMD with a minimum history of 12 months of anti-VEGF treatment were prospectively included in this cross-sectional study. Patients were imaged using standard imaging, swept-source optical coherence tomography angiography for quantitative microvascular analysis and polarization-sensitive OCT as an ancillary method for automated SF segmentation. The presence of reticular pseudodrusen, hyperreflective foci (HRF), and outer retinal tubulation (ORT) were also evaluated. Results: Sixty eyes of 60 participants (37 female) with nAMD and a mean 3.1 (±2.7)-year history of anti-VEGF treatment were included, 20 (33%) of which were diagnosed with SF. Eyes with SF had a higher prevalence of ORT (P < 0.001) and a lower prevalence of HRF (P = 0.004) than eyes without SF. Fifty eyes were analyzed quantitatively for microvascular biomarkers. Eyes with SF had a larger greatest vascular caliber (P = 0.001) and greatest linear diameter (P = 0.042), a larger microvascular neovascularization (MNV) area (P = 0.026), larger vessel area (P = 0.037), higher number of vessel junctions (P = 0.025), longer total vessel length (P = 0.027), higher number of vessel endpoints (P = 0.007), and higher endpoint density (P = 0.047). Conclusions: This multimodal imaging approach demonstrated in vivo microvascular and morphological differences in eyes with and without SF. Eyes with SF tend to have larger MNV lesions with thicker vessels and are often associated with the presence of ORT. Translational Relevance: This study points out imaging biomarkers in patients with SF, which may help identifying high-risk patients.

Impact of large choroidal vessels on choriocapillaris flow deficit analyses in optical coherence tomography angiography.

PURPOSE: To investigate the impact of large choroidal vessels (LCV) on Choriocapillaris (CC) flow deficit (FD) analyses with swept-source optical coherence tomography angiography (SS-OCTA). DESIGN: Prospective, cross-sectional study. METHODS: Macular 6x6mm SS-OCTA scans were obtained from intermediate age-related macular degeneration (iAMD) and healthy eyes. Images were captured and processed according to most common standards and analyzed for percentage of flow-deficits (FD%) within four 1x1mm squares at the corners of each image. Choroidal thickness (CT), iris color and refraction error were considered as potential influential factors for LCV visibility. A linear mixed model and logistic regression models were calculated for statistical evaluation. RESULTS: Sixty-nine iAMD and 49 age-matched healthy eyes were enrolled. LCV were visible in at least one sector in 52% of iAMD and 47% of healthy eyes. Within the iAMD group FD% were significantly lower in areas containing LCV (p = 0.0029). Increasing CT resulted in an odds ratio decrease of LCV (OR: 0.94, p<0.0001). Below a CT value of ≤118µm LCV could be expected with a sensitivity of 86% and a specificity of 85%. CONCLUSIONS: LCV can significantly affect CC FD analyses of SS-OCTA images. Their visibility is negatively associated with CT. The impact of LCV should be taken into account when performing CC FD assessments, especially in patients where reduced CT is to be expected and inclusion of affected areas should be considered carefully.

Three-dimensional composition of the photoreceptor cone layers in healthy eyes using adaptive-optics optical coherence tomography (AO-OCT).

PURPOSE: To assess the signal composition of cone photoreceptors three-dimensionally in healthy retinas using adaptive optics optical coherence tomography (AO-OCT). METHODS: Study population. Twenty healthy eyes of ten subjects (age 23 to 67). Procedures. After routine ophthalmological assessments, eyes were examined using AO-OCT. Three-dimensional volumes were acquired at 2.5° and 6.5° foveal eccentricity in four main meridians (superior, nasal, inferior, temporal). Cone densities and signal compositions were investigated in four different planes: the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST) and full en-face plane (FEF) combining signals from all mentioned cone layers. Additionally, reliability of a simple semi-automated approach for assessment of cone density was tested. Main outcome measures. Cone density of IS/OS, IS/OS+, COST and FEF. Qualitative depiction and composition of each cone layer. Inter-rater agreement of cone density measurements. RESULTS: Mean overall cone density at all eccentricities was highest at the FEF plane (21.160/mm2), followed by COST (20.450/mm2), IS/OS+ (19.920/mm2) and IS/OS (19.530/mm2). The different meridians and eccentricities had a significant impact on cone density, with lower eccentricity resulting in higher cone densities (p≤.001), which were highest at the nasal, then temporal, then inferior and then superior meridian. Depiction of the cone mosaic differed between all 4 layers regarding signal size and packing density. Therefore, different cone layers showed evident but not complete signal overlap. Using the semi-automated technique for counting of cone signals achieved high inter-rater reliability (ICC > .99). CONCLUSIONS: In healthy individuals qualitative and quantitative changes in cone signals are found not only in different eccentricities and meridians, but also within different photoreceptor layers. The variation between cone planes has to be considered when assessing the integrity of cone photoreceptors in healthy and diseased eyes using adaptive optics technology.

LONGITUDINAL CHANGES IN QUANTITATIVE AUTOFLUORESCENCE DURING PROGRESSION FROM INTERMEDIATE TO LATE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To prospectively investigate the development of quantitative autofluorescence (qAF) during progression from intermediate to late age-related macular degeneration (AMD). METHODS: Quantitative autofluorescence images from patients with intermediate AMD were acquired every three months with a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) using a built-in autofluorescence reference. The association between changes in longitudinal qAF and progression toward late AMD was assessed using Cox regression models with time-dependent covariates. RESULTS: One hundred and twenty-one eyes of 71 patients were included, and 653 qAF images were acquired. Twenty-one eyes of 17 patients converted to late AMD (median follow-up: 21 months; 12 eyes: atrophic AMD; nine eyes: neovascular AMD). The converting patients' mean age was 74.6 ± 4.4 years. Eleven eyes in the converting group (52.4%) were pseudophakic. The presence of an intraocular lens did not affect the qAF regression slopes (P > 0.05). The median change for atrophic AMD was -2.34 qAF units/3 months and 0.78 qAF units/3 months for neovascular AMD. A stronger decline in qAF was significantly associated with an increased risk of developing atrophic AMD (hazard ratio = 1.022, P < 0.001). This association, however, was not present in the group progressing toward neovascular AMD (hazard ratio = 1.001, P = 0.875). CONCLUSION: The qAF signal declines with progression to atrophy, contrary to developing neovascularization. Quantitative autofluorescence may allow identification of patients at risk of progressing to late AMD and benefits individualized patient care in intermediate AMD.