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.
With the prospect of available therapy for geographic atrophy in the near future and consequently increasing patient numbers, appropriate management strategies for the clinical practice are needed. ...Optical coherence tomography (OCT) as well as automated OCT analysis using artificial intelligence algorithms provide optimal conditions for assessing disease activity as well as the treatment response for geographic atrophy through a rapid, precise and resource-efficient evaluation.
In patients with age-related macular degeneration (AMD), the risk of progression to late stages is highly heterogeneous, and the prognostic imaging biomarkers remain unclear. We propose a deep ...survival model to predict the progression towards the late atrophic stage of AMD. The model combines the advantages of survival modelling, accounting for time-to-event and censoring, and the advantages of deep learning, generating prediction from raw 3D OCT scans, without the need for extracting a predefined set of quantitative biomarkers. We demonstrate, in an extensive set of evaluations, based on two large longitudinal datasets with 231 eyes from 121 patients for internal evaluation, and 280 eyes from 140 patients for the external evaluation, that this model improves the risk estimation performance over standard deep learning classification models.
To assess retinal function in areas of presumed fibrosis due to neovascular age-related macular degeneration (nAMD), using multimodal imaging and structure-function correlation.
Cross-sectional ...observational study.
30 eyes of 30 consecutive patients with nAMD with a minimum history of one year of anti-vascular endothelial growth factor therapy were included. Each patient underwent microperimetry (MP), color fundus photography (CFP), standard spectral-domain-based OCT (SD-OCT), and polarization sensitive-OCT (PS-OCT) imaging. PS-OCT technology can depict retinal fibrosis based on its birefringence. CFP, SD-OCT, and PS-OCT were evaluated independently for the presence of fibrosis at the corresponding MP stimuli locations. MP results and morphologic findings in CFP, SD-OCT, and PS-OCT were co-registered and analyzed using mixed linear models.
In total, 1350 MP locations were evaluated to assess the functional impact of fibrosis according to a standardized protocol. The estimated means of retinal areas with signs of fibrosis were 12.60 db (95% confidence interval: 10.44-14.76) in CFP, 11.60 db (95% COI: 8.84-14.36) in OCT, and 11.02 db (95% COI 8.10-13.94) in PS-OCT. Areas evaluated as subretinal fibrosis in three (7.2 db) or two (10.1 db) modalities were significantly correlated with a lower retinal sensitivity than a subretinal fibrosis observed in only one (15.3 db) or none (23.3 db) modality (
< 0.001).
CFP, SD-OCT and PS-OCT are all suited to detect areas of reduced retinal sensitivity related to fibrosis, however, a multimodal imaging approach provides higher accuracy in the identification of areas with low sensitivity in MP (i.e., impaired retinal function), and thereby improves the detection rate of subretinal fibrosis in nAMD.
Purpose
To identify the changes in distinct vascular parameters of choroidal neovascularization (CNV) in eyes with treatment‐naïve neovascular age‐related macular degeneration (nAMD) during the ...primary response to anti‐VEGF therapy using aflibercept.
Methods
Patients were prospectively followed during the first 3 months according to a standardized protocol with mandatory visits at days 7 and 14 after each anti‐VEGF treatment up to day 90. Fourteen eyes were seen in addition at days 1 and 3 post‐initial injection. Aflibercept was administered at baseline (BL), day 30 and 60. 6 × 6mm SSOCTA (PlexElite, Zeiss) images were acquired. Using the semi‐automated AngioTool, CNV area, vessel area, vessel density (VD), the number of junctions, junctions density, total vessel length, average vessel length, total number of endpoints and lacunarity were assessed.
Results
Thirty‐two consecutive patients presenting with treatment‐naïve, SSOCTA‐positive CNV lesions were included. Close follow‐up showed a characteristic neovascular response curve with a dynamic decrease in lesion size within days and a reactive increase following 2 weeks after initial treatment. An undulating pattern was seen for all neovascular parameters except for vascular density, with variable statistical significance. Due to a flattening of the therapeutic response as early as after the second treatment, CNV lesion size and most of the related parameters had an increase in activity above baseline values at the end of the loading phase. Lesion size was the leading feature of reactivation by a mean increase of 19.3% after three monthly aflibercept injections. Subgroup analysis based on lesion size revealed a significant correlation between best‐corrected visual acuity and quantitative change in lesion size over time, but not baseline size.
Conclusions
Using SSOCTA, a morphologic neovascular response pattern can be identified in anti‐VEGF treatment of CNV. A synchronized early decrease and consecutive reactivation in a large spectrum of neovascular biomarkers including size and internal structure are visualized in a qualitative and quantitative manner. SSOCTA analyses allow new insights in CNV morphology changes and therapeutic response.
This study aimed to assess a multidisciplinary team (MDT) meeting approach for the management of patients with complex extremity defects, analyze treatment recommendations, and evaluate factors ...influencing non-implementation.
All patients introduced to an MDT meeting for complex extremity defects from 2015 to 2017 were included in a retrospective cohort study. Patients' characteristics and defect causes were evaluated. Treatment recommendations (TR) of MDT meetings and subsequent implementation were reviewed (cohort with implementation of TR versus cohort with non-implementation of TR), and factors associated with non-adherence to recommendations were statistically analyzed using logistic regression.
Fifty-one patients (41 male) with a mean age of 54 years were presented in 27 MDT meetings. Most of the patients (70%) suffered from reconstructive challenging or combined bone- and soft tissue defects, primarily located at the lower extremity (88%). Large skeletal defects, chronic osteomyelitis, and multi-fragmented fractures were present in 65% of cases. Forty-five percent of the patients suffered from peripheral vascular disease, necessitating surgical optimization. Of the 51 MDT decisions, 40 were implemented (78%; (32/40) limb salvage versus 22%; (8/40) limb amputation). Limb salvage was successfully achieved in 91% (29/32) of the cases. Failed limb salvages were due to flap failure (33%; 1/3), recurring periprosthetic joint infections (66%; 2/3) and concomitant reconstructive failure. Patients who underwent limb amputation, as recommended, showed proper stump healing and regained mobility with a prosthesis. Overall the MDT treatment plan was effective in 92.5% (37/40) of the patients, who adhered to the MDT treatment recommendation. In eleven patients (22%; 11/51), the MDT treatment was not implemented. MDT decisions were less likely to be implemented, if amputation was recommended (p = 0.029).
MDT meetings represent a valid tool to formulate individualized treatment plans, avoiding limb amputation in most patients with severe extremity defects. Recommendation for limb amputation is less likely to be implemented than plans for limb salvage.
Retrospectively registered.
To investigate the progression of geographic atrophy secondary to nonneovascular age-related macular degeneration in early and later stage lesions using artificial intelligence–based precision tools.
...Retrospective analysis of an observational cohort study.
Seventy-four eyes of 49 patients with ≥ 1 complete retinal pigment epithelial and outer retinal atrophy (cRORA) lesion secondary to age-related macular degeneration were included. Patients were divided between recently developed cRORA and lesions with advanced disease status.
Patients were prospectively imaged by spectral-domain OCT volume scans. The study period encompassed 18 months with scheduled visits every 6 months. Growth rates of recent cRORA-converted lesions were compared with lesions in an advanced disease status using mixed effect models.
The progression of retinal pigment epithelial loss (RPEL) was considered the primary end point. Secondary end points consisted of external limiting membrane disruption and ellipsoid zone loss. These pathognomonic imaging biomarkers were quantified using validated deep-learning algorithms. Further, the ellipsoid zone/RPEL ratio was analyzed in both study cohorts.
Mean (95% confidence interval CI) square root progression of recently converted lesions was 79.68 (95% CI, −77.14 to 236.49), 68.22 (95% CI, −101.21 to 237.65), and 84.825 (95% CI, −124.82 to 294.47) mm/half year for RPEL, external limiting membrane loss, and ellipsoid zone loss respectively. Mean square root progression of advanced lesions was 131.74 (95% CI, −22.57 to 286.05), 129.96 (95% CI, −36.67 to 296.59), and 116.84 (95% CI, −90.56 to 324.3) mm/half year for RPEL, external limiting membrane loss, and ellipsoid zone loss, respectively. RPEL (P = 0.038) and external limiting membrane disruption (P = 0.026) progression showed significant differences between the 2 study cohorts. Further recent converters had significantly (P < 0.001) higher ellipsoid zone/RPEL ratios at all time points compared with patients in an advanced disease status (1.71 95% CI, 1.12–2.28 vs. 1.14; 95% CI, 0.56–1.71).
Early cRORA lesions have slower growth rates in comparison to atrophic lesions in advanced disease stages. Differences in growth dynamics may play a crucial role in understanding the pathophysiology of nonneovascular age-related macular degeneration and for the interpretation of clinical trials in geographic atrophy. Individual disease monitoring using artificial intelligence–based quantification paves the way toward optimized geographic atrophy management.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
The subsidence of the outer plexiform layer (OPL) is an important imaging biomarker on optical coherence tomography (OCT) associated with early outer retinal atrophy and a risk factor for progression ...to geographic atrophy in patients with intermediate age-related macular degeneration (AMD). Deep neural networks (DNNs) for OCT can support automated detection and localization of this biomarker.PurposeThe subsidence of the outer plexiform layer (OPL) is an important imaging biomarker on optical coherence tomography (OCT) associated with early outer retinal atrophy and a risk factor for progression to geographic atrophy in patients with intermediate age-related macular degeneration (AMD). Deep neural networks (DNNs) for OCT can support automated detection and localization of this biomarker.The method predicts potential OPL subsidence locations on retinal OCTs. A detection module (DM) infers bounding boxes around subsidences with a likelihood score, and a classification module (CM) assesses subsidence presence at the B-scan level. Overlapping boxes between B-scans are combined and scored by the product of the DM and CM predictions. The volume-wise score is the maximum prediction across all B-scans. One development and one independent external data set were used with 140 and 26 patients with AMD, respectively.MethodsThe method predicts potential OPL subsidence locations on retinal OCTs. A detection module (DM) infers bounding boxes around subsidences with a likelihood score, and a classification module (CM) assesses subsidence presence at the B-scan level. Overlapping boxes between B-scans are combined and scored by the product of the DM and CM predictions. The volume-wise score is the maximum prediction across all B-scans. One development and one independent external data set were used with 140 and 26 patients with AMD, respectively.The system detected more than 85% of OPL subsidences with less than one false-positive (FP)/scan. The average area under the curve was 0.94 ± 0.03 for volume-level detection. Similar or better performance was achieved on the independent external data set.ResultsThe system detected more than 85% of OPL subsidences with less than one false-positive (FP)/scan. The average area under the curve was 0.94 ± 0.03 for volume-level detection. Similar or better performance was achieved on the independent external data set.DNN systems can efficiently perform automated retinal layer subsidence detection in retinal OCT images. In particular, the proposed DNN system detects OPL subsidence with high sensitivity and a very limited number of FP detections.ConclusionsDNN systems can efficiently perform automated retinal layer subsidence detection in retinal OCT images. In particular, the proposed DNN system detects OPL subsidence with high sensitivity and a very limited number of FP detections.DNNs enable objective identification of early signs associated with high risk of progression to the atrophic late stage of AMD, ideally suited for screening and assessing the efficacy of the interventions aiming to slow disease progression.Translational RelevanceDNNs enable objective identification of early signs associated with high risk of progression to the atrophic late stage of AMD, ideally suited for screening and assessing the efficacy of the interventions aiming to slow disease progression.
Treatment decisions in neovascular age-related macular degeneration (nAMD) are mainly based on subjective evaluation of OCT. The purpose of this cross-sectional study was to provide a comparison of ...qualitative and quantitative differences between OCT devices in a systematic manner.
Prospective, cross-sectional study.
One hundred sixty OCT volumes, 40 eyes of 40 patients with nAMD.
Patients from clinical practice were imaged with 4 different OCT devices during one visit: (1) Spectralis Heidelberg; (2) Cirrus; (3) Topcon Maestro2; and (4) Topcon Triton. Intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were manually annotated in all cubes by trained human experts to establish fluid measurements based on expert-reader annotations. Intraretinal fluid, SRF, and PED volume were quantified in nanoliters (nL). Bland-Altman plots were created to analyze the agreement of measurements in the central 1 and 6 mm. The Friedman test was performed to test for significant differences in the central 1, 3, and 6 mm.
Intraretinal fluid, SRF, and PED volume.
In the central 6 mm, there was a trend toward higher IRF and PED volumes in Spectralis images compared with the other devices and no differences in SRF volume. In the central 1 mm, the standard deviation of the differences ranged from ± 3 nL to ± 6 nL for IRF, from ± 3 nL to ± 4 nL for SRF, and from ± 7 nL to ± 10 nL for PED in all pairwise comparisons. Manually annotated IRF and SRF volumes showed no significant differences in the central 1 mm.
Fluid volume quantification achieved excellent reliability in all 3 retinal compartments on images obtained from 4 OCT devices, particularly for clinically relevant IRF and SRF values. Although fluid volume quantification is reliable in all 4 OCT devices, switching OCT devices might lead to deviating fluid volume measurements with higher agreement in the central 1 mm compared with the central 6 mm, with highest agreement for SRF volume in the central 1 mm. Understanding device-dependent differences is essential for expanding the interpretation and implementation of pixel-wise fluid volume measurements in clinical practice and in clinical trials.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Drusen volume (DV) and quantitative autofluorescence (qAF) are potential indicators of progression in age-related macular degeneration (AMD). This prospective and observational study examined the ...association between DV and qAF of the retinal pigment epithelium.
Eighty-eight eyes of 52 patients with early and intermediate AMD were included. The mean follow-up was 9.2 ± 5.6 months, resulting in 312 examinations. DV was extracted from 6 × 6-mm spectral-domain optical coherence tomography scans. qAF was measured using a rotated Delori pattern. The associations between qAF and DV, age, sex, and lens status were investigated using linear mixed models.
Patients' mean age was 75.6 ± 5.0 years (range, 61.0-83.4 years). Sixty-eight eyes (77.3%) were from females. No significant association between DV and qAF was found, neither within the total outer Early Treatment Diabetic Retinopathy Study (ETDRS) grid nor for ETDRS segments six to nine (all P > 0.05). Sex and lens status were not associated with qAF (P = 0.429 and P = 0.213, respectively). A significant association between age and qAF (P = 0.025) was found, indicating a decrease of qAF with age.
Quantification of DV and fundus autofluorescence did not reveal any correlation in early and intermediate AMD. qAF decreased with age, whereas DV increased in about half of the patients. This finding is a quantitative corroboration that fundus autofluorescence and the buildup of drusen are not correlated processes in AMD.
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