Validation of Deep Learning-based Automatic Retinal Layer Segmentation Algorithms for AMD with Two SD-OCT Devices

Local Anatomic Precursors to New-Onset Geographic Atrophy in Age-Related Macular Degeneration as Defined on OCT

PurposeTo evaluate the outcome of macular surgery with ILM- and epiretinal membrane peel associated with significant dry age-related macular degeneration (AMD) as defined by the Age-Related Eye Disease Study (AREDS).Patients and MethodsInstitutional. Retrospective case-control study. A total of 42 pseudophacic eyes of 39 patients (7 with full thickness macular hole and 35 with epiretinal membrane) with coexisting dry AMD underwent pars plana vitrectomy (PPV) with internal limiting membrane (ILM) and epiretinal membrane peel. Preoperative and postoperative data including best corrected visual acuity (BCVA), AMD grade according to AREDS, central retinal thickness (CRT), development of choroidal neovascularization (CNV), and central retinal atrophy have been evaluated. Twenty-eight fellow eyes with dry AMD of the included 39 patients served as a control group.ResultsA significant improvement in the visual acuity could be observed after surgery (initial BCVA 0.47±0.31 logarithm of the minimal angle of resolution (logMAR) vs 0.33±0.29logMAR 9 months postoperatively; p=0.006). CRT decreased significantly after surgery (p<0.001). In the surgery group, there were 4 eyes (9.5%) with CNV and 1 eye (2.5%) with new central retinal atrophy development after surgery. All these eyes had preoperative AREDS 3 (4 eyes) or AREDS 4 (1 eye) AMD category. In the control group, there was 1 eye (4%) with CNV and 4 eyes (14%) with new central retinal atrophy development during the follow-up of 9 months. These eyes had initially AREDS 2 (1 eye), AREDS 3 (3 eyes) or AREDS 4 (1 eye) AMD category.ConclusionEyes with dry AMD of AREDS 3 and AREDS 4 with coexisting VMI abnormalities improve significantly after PPV with membrane peel. While there is a higher risk of CNV development after surgery (9.5%) in these eyes, the vitrectomy does not seem to accelerate central retinal atrophy progression compared to the fellow eyes course.

Assessment of Artifacts and Reproducibility across Spectral- and Time-Domain Optical Coherence Tomography Devices

Nonhuman primates are the only mammals to possess a true macula similar to humans, and spontaneously develop drusenoid lesions which are hallmarks of age-related macular degeneration (AMD). Prior studies demonstrated similarities between human and nonhuman primate drusen based on clinical appearance and histopathology. Here, we employed fundus photography, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR) to characterize drusenoid lesions in aged rhesus macaques. Of 65 animals evaluated, we identified lesions in 20 animals (30.7%). Using the Age-Related Eye Disease Study 2 (AREDS2) grading system and multimodal imaging, we identified two distinct drusen phenotypes – 1) soft drusen that are larger and appear as hyperreflective deposits between the retinal pigment epithelium (RPE) and Bruch’s membrane on SD-OCT, and 2) hard, punctate lesions that are smaller and undetectable on SD-OCT. Both exhibit variable FAF intensities and are poorly visualized on IR. Eyes with drusen exhibited a slightly thicker RPE compared with control eyes (+3.4 μm, P=0.012). Genetic polymorphisms associated with drusenoid lesions in rhesus monkeys in ARMS2 and HTRA1 were similar in frequency between the two phenotypes. These results refine our understanding of drusen development, and provide insight into the absence of advanced AMD in nonhuman primates.

To identify features correlating with drusenoid pigment epithelial detachment (DPED) progression in the Age-Related Eye Disease Study 2 Ancillary spectral-domain optical coherence tomography study cohort. In this retrospective analysis of a prospective longitudinal study, eyes with intermediate age-related macular degeneration and DPEDs were followed longitudinally with annual multimodal imaging. Thirty-one eyes of 25 participants (mean age 72.6 years) in the Age-Related Eye Disease Study 2 Ancillary spectral-domain OCT substudy (A2A study) had DPED identified in color fundus images. Spectral-domain optical coherence tomography inspection confirmed a subretinal pigment epithelium drusenoid elevation of ≥433 µm diameter in 25 eyes (80.6%). Twenty-four of these eyes were followed longitudinally (median 4.0 years), during which 7 eyes (29.2%) underwent DPED collapse (with 3/7 further progressing to geographic atrophy), 6 (25.0%) developing neovascular age-related macular degeneration, and 11 (45.8%) maintaining DPED persistence without late age-related macular degeneration. On Kaplan-Meier analysis, mean time to DPED collapse was 3.9 years. Both DPED collapse and progression to neovascular age-related macular degeneration were preceded by the presence of hyperreflective foci over the DPED. The natural history of DPED comprises collapse (sometimes followed by the development of atrophy), vascularization followed by exudation, or DPED persistence. Spectral-domain optical coherence tomography can confirm retinal pigment epithelial elevation caused by drusenoid accumulation and facilitate the identification of high-risk features that correlate with progression.

Comparison between Spectral-domain and Swept-source OCT Angiography Scans for the Measurement of Hyperreflective Foci in Age-related Macular Degeneration

Objective To observe the morphologic characteristics of drusen in atrophic age-related macular degeneration (AMD) by spectral domain optical coherence tomography (SD-OCT).Methods Fifty-four patients (84 eyes) with macular drusen and atrophic AMD,and 56 age-matched control patients (56 eyes) with cataract were included in this study.Atrophic AMD patients were divided into two groups:D1 group with drusen involving the fovea (42 eyes) and D2 group with drusen not involving the fovea (42 eyes).The SD-OCT images in macular (6 mm× 6 mm scans) were acquired,and the foveal retinal thickness (FRT) was measured.The size,morphology,inner reflection,homogeneity of drusen and its relationship with surrounding tissues were analyzed.Results The FRT of D1 group,D2 group and control group were (160.90±38.47),(194.21±26.11),(222.42± 19.29) μm respectively.The FRT of D1 group and D2 group were thinner than that of control group (F=57.08,P=0.00).Totally 1124 drusen were found by SD-OCT images in 84 eyes,with an average of 10.84 drusen in each eye.3.0％,12.5％ and 84.5％ of all 1124 drusen were small,medium and large sized respectively.56.6％,14.2％,20.4％ and 8.8％ of all drusen were dome,pointed,saw-toothed and basal-shaped respectively.17.1 ％,57.5％ and 25.4％ of all drusen had low,medium and high internal reflectivity respectively.The internal reflectivity of 65.6％,2.8％ and 31.7％ of all drusen were homogeneous,nonhomogeneous with core,and nonhomogeneous without core respectively.Overlying retinal pigment epithelium (RPE) damage and photoreceptor inner segment/outer segment (IS/OS) junction damage were presented in 34.5 ％ and 24.8 ％ drusen respectively.The most common type of drusen was dome-shape,homogeneous,with medium internal reflectivity,and without overlying RPE or IS/OS junction damage (81.0％).Conclusions The FRT becomes thinner in patients with drusen.The most common drusen types are dome-shaped,homogeneous,with medium internal reflectivity,and without overlying RPE or IS/OS junction damage. Key words: Retinal drusen/diagnosis; Tomography, optical coherence; Macular degeneration/ diagnosis; Diagnostic imaging

Spectral-Domain Optical Coherence Tomography Characteristics of Intermediate Age-related Macular Degeneration

The traditional method for documenting and quantifying geographic atrophy (GA) is color photography. This method has been shown to be reproducible in several clinical trials, including the Age-related Eye Disease Study (AREDS) and the natural progression of GA studies by Sunness et al. (AREDS No. 6, Am J Ophthalmol 132(5):668-681, 2001; Sunness et al., Invest Ophthalmol Vis Sci 40(8):1761-1769, 1999). Nevertheless, it can be difficult to distinguish between dead/nonfunctioning retinal pigment epithelium (RPE), living but depigmented RPE (RPE often release melanin granules upon injury), and yellowish coloration caused by large drusen or calcified regressed drusen. Two imaging technologies that seem promising are fundus autofluorescence (FAF) and spectral domain (high resolution) optical coherence tomography (SDOCT). Here we provide an overview of FAF imaging in the setting of age-related macular degeneration (AMD) and GA.

Lifecycles of Individual Subretinal Drusenoid Deposits and Evolution of Outer Retinal Atrophy in Age-Related Macular Degeneration

To characterize inner retinal damage in patients with dry age-related macular degeneration (AMD) using high-resolution spectral domain optical coherence tomography images. Sixty eyes of 60 patients with AMD were categorized using the Age-Related Eye Disease Study (AREDS) severity scale. Spectral domain optical coherence tomography images of these patients were quantified by manually correcting the segmentation of each retinal layer, including the retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer to ensure accurate delineation of layers. The mean ganglion cell complex thickness values (ganglion cell layer + inner plexiform layer + retinal nerve fiber layer) were compared with 30 eyes of 30 healthy subjects. Ninety percent of eyes (81 eyes) required manual correction of segmentation. Compared with healthy subjects, mean ganglion cell complex thicknesses significantly decreased in more advanced dry AMD eyes, and this decrease was predominantly related to a change in inner plexiform layer thickness. There was no significant difference in thickness-related measurements between milder dry AMD (AREDS-2) eyes and healthy eyes (P > 0.05). In patients with dry AMD, automatic optical coherence tomography segmentation algorithms may be erroneous. As the severity of dry AMD increases, the inner plexiform layer layer becomes thinned, suggesting that transsynaptic degeneration may be occurring, as the photoreceptor layer is affected by AMD.

Predictors of AMD Treatment Response

Geographic atrophy (GA) is the atrophic late-stage manifestation of age-related macular degeneration (AMD), which may result in severe vision loss and blindness. The purpose of this study was to develop a reliable, effective approach for GA segmentation in both spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) images using a level set-based approach and to compare the segmentation performance in the two modalities. To identify GA regions in SD-OCT images, three retinal surfaces were first segmented in volumetric SD-OCT images using a double-surface graph search scheme. A two-dimensional (2-D) partial OCT projection image was created from the segmented choroid layer. A level set approach was applied to segment the GA in the partial OCT projection image. In addition, the algorithm was applied to FAF images for the GA segmentation. Twenty randomly chosen macular SD-OCT (Zeiss Cirrus) volumes and 20 corresponding FAF (Heidelberg Spectralis) images were obtained from 20 subjects with GA. The algorithm-defined GA region was compared with consensus manual delineation performed by certified graders. The mean Dice similarity coefficients (DSC) between the algorithm- and manually defined GA regions were 0.87 ± 0.09 in partial OCT projection images and 0.89 ± 0.07 in registered FAF images. The area correlations between them were 0.93 (P < 0.001) in partial OCT projection images and 0.99 (P < 0.001) in FAF images. The mean DSC between the algorithm-defined GA regions in the partial OCT projection and registered FAF images was 0.79 ± 0.12, and the area correlation was 0.96 (P < 0.001). A level set approach was developed to segment GA regions in both SD-OCT and FAF images. This approach demonstrated good agreement between the algorithm- and manually defined GA regions within each single modality. The GA segmentation in FAF images performed better than in partial OCT projection images. Across the two modalities, the GA segmentation presented reasonable agreement.

Choroidal neovascularization (CNV) volume prediction has an important clinical significance to predict the therapeutic effect and schedule the follow-up. In this paper, we propose a Lesion Attention Maps-Guided Network (LamNet) to automatically predict the CNV volume of next follow-up visit after therapy based on 3-dimentional spectral-domain optical coherence tomography (SD-OCT) images. In particular, the backbone of LamNet is a 3D convolutional neural network (3D-CNN). In order to guide the network to focus on the local CNV lesion regions, we use CNV attention maps generated by an attention map generator to produce the multi-scale local context features. Then, the multi-scale of both local and global feature maps are fused to achieve the high-precision CNV volume prediction. In addition, we also design a synergistic multi-task predictor, in which a trend-consistent loss ensures that the change trend of the predicted CNV volume is consistent with the real change trend of the CNV volume. The experiments include a total of 541 SD-OCT cubes from 68 patients with two types of CNV captured by two different SD-OCT devices. The results demonstrate that LamNet can provide the reliable and accurate CNV volume prediction, which would further assist the clinical diagnosis and design the treatment options.

Choroidal Neovascularization Analyzed on Ultrahigh-Speed Swept-Source Optical Coherence Tomography Angiography Compared to Spectral-Domain Optical Coherence Tomography Angiography