-
Investigative Ophthalmology & Visual... Oct 2023Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF)...
PURPOSE
Microaneurysm (MA) plays an important role in the pathogenesis of diabetic macular edema (DME) progression and response to anti-vascular endothelial growth factor (VEGF) therapy. This study aimed to investigate the effect of faricimab, a bispecific antibody against angiopoietin-2 and VEGF, on the number of MAs and their turnover in the treatment of DME.
METHODS
We included that patients with DME who underwent three monthly injections of faricimab in one eye, with the other eye as control. We examined central retinal thickness (CRT) based on optical coherence tomography (OCT) and best-corrected visual acuity. Turnover, including loss and newly formed MAs, and the total number of MAs were counted based on merged images of the OCT map and fluorescein angiography.
RESULTS
We enrolled 28 patients with DME. After 3 monthly injections of faricimab, CRT significantly improved, 66.0 ± 16.2% of MAs disappeared, and 6.71 ± 5.6% of new MAs were generated, resulting in total reduction to 40.7 ± 15.2%. In the treated eyes, MA disappearance (P < 0.0001) and turnover (P = 0.007) were significantly greater, and new formation was smaller (P < 0.0001) than in non-treated eyes. The size of the retained MAs decreased after treatment. Microaneurysm turnover was not significantly different between areas with and without edema before treatment.
CONCLUSIONS
In the process of improving edema in DME with faricimab, MAs shrink and disappear, and formation of MAs are inhibited, resulting in decreased total number of MAs. Intravitreal administration of faricimab suppresses vascular permeability and improves vascular structure.
Topics: Humans; Macular Edema; Diabetic Retinopathy; Vascular Endothelial Growth Factor A; Angiogenesis Inhibitors; Microaneurysm; Intravitreal Injections; Edema; Tomography, Optical Coherence; Diabetes Mellitus
PubMed: 37856112
DOI: 10.1167/iovs.64.13.31 -
International Journal of Retina and... Oct 2023This study aimed to develop a deep learning (DL) algorithm that enhances the quality of a single-frame enface OCTA scan to make it comparable to 4-frame averaged scan...
BACKGROUND
This study aimed to develop a deep learning (DL) algorithm that enhances the quality of a single-frame enface OCTA scan to make it comparable to 4-frame averaged scan without the need for the repeated acquisitions required for averaging.
METHODS
Each of the healthy eyes and eyes from diabetic subjects that were prospectively enrolled in this cross-sectional study underwent four repeated 6 × 6 mm macular scans (PLEX Elite 9000 SS-OCT), and the repeated scans of each eye were co-registered to produce 4-frame averages. This prospective dataset of original (single-frame) enface scans and their corresponding averaged scans was divided into a training dataset and a validation dataset. In the training dataset, a DL algorithm (named pseudoaveraging) was trained using original scans as input and 4-frame averages as target. In the validation dataset, the pseudoaveraging algorithm was applied to single-frame scans to produce pseudoaveraged scans, and the single-frame and its corresponding averaged and pseudoaveraged scans were all qualitatively compared. In a separate retrospectively collected dataset of single-frame scans from eyes of diabetic subjects, the DL algorithm was applied, and the produced pseudoaveraged scan was qualitatively compared against its corresponding original.
RESULTS
This study included 39 eyes that comprised the prospective dataset (split into 5 eyes for training and 34 eyes for validating the DL algorithm), and 105 eyes that comprised the retrospective test dataset. Of the total 144 study eyes, 58% had any level of diabetic retinopathy (with and without diabetic macular edema), and the rest were from healthy eyes or eyes of diabetic subjects but without diabetic retinopathy and without macular edema. Grading results in the validation dataset showed that the pseudoaveraged enface scan ranked best in overall scan quality, background noise reduction, and visibility of microaneurysms (p < 0.05). Averaged scan ranked best for motion artifact reduction (p < 0.05). Grading results in the test dataset showed that pseudoaveraging resulted in enhanced small vessels, reduction of background noise, and motion artifact in 100%, 82%, and 98% of scans, respectively. Rates of false-positive/-negative perfusion were zero.
CONCLUSION
Pseudoaveraging is a feasible DL approach to more efficiently improve enface OCTA scan quality without introducing notable image artifacts.
PubMed: 37822004
DOI: 10.1186/s40942-023-00486-5 -
Heliyon Sep 2023One of the major causes of blindness in human beings is the diabetic retinopathy (DR). To prevent blindness, early detection of DR is therefore necessary. In this paper,...
One of the major causes of blindness in human beings is the diabetic retinopathy (DR). To prevent blindness, early detection of DR is therefore necessary. In this paper, a hybrid model is proposed for diagnosing DR from fundus images. A combination of morphological image processing and Inception v3 deep learning techniques are exploited to detect DR as well as to classify healthy, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). The proposed algorithm was carried out in several steps such as segmentation of blood vessels, localization and removal of optic disc, and macula, abnormal features detection (microaneurysms, hemorrhages, and neovascularization), and classification. Microaneurysms and hemorrhages that appear in the retina are the early signs of DR. In this work, we have detected microaneurysms and hemorrhages by applying dynamic contrast limited adaptive histogram equalization and threshold value on overlapping patched images. An overall accuracy of 96.83% is obtained to classify DR into five different stages. The better performance demonstrates the effectiveness and novelty of the proposed work as compared to the recent reported work.
PubMed: 37809795
DOI: 10.1016/j.heliyon.2023.e19625 -
International Journal of General... 2023Controlling the risk factors was the most effective strategy to prevent diabetic retinopathy (DR). This study aimed to recognize the risk factors of DR, and explores...
BACKGROUND AND AIM
Controlling the risk factors was the most effective strategy to prevent diabetic retinopathy (DR). This study aimed to recognize the risk factors of DR, and explores whether the effect of those factors is modified by diabetes mellitus (DM) duration.
METHODS
A total of 1058 DM patients with information about DR assessment were included. DR was measured by a complete ophthalmic examination and was classified as having one or more distinct microaneurysms in the eyes. Data from the lab and clinical factors were gathered. Multivariate logistic analysis was used to examine the risk factors, and the best-fitting model was selected by a backward stepwise based on A1C.
RESULTS
In the current study, 274 (25.9%) patients developed DR. In the entire subjects, baseline age, the level of C-peptide, and urinary creatinine were all presented as protective effects of DR, whose odds ratios (ORs) and 95% confidence intervals (CIs) were 0.79 (0.62, 0.99), 0.75 (0.61, 0.91), and 0.70 (0.52, 0.93), respectively. Conversely, systolic pressure (SBP), urinary albumin, and BUN/Cr ratio were the important risk factors for DR with ORs (95% CIs) 1.21 (1.01, 1.46), 1.55 (1.30, 1.84), and 1.33 (1.11, 1.59), respectively. In stratification analysis, females with higher SBP would be more likely to develop DR in the short-duration group, while C-peptide and urinary creatinine showed protective effects in the long-duration group. BUN/Cr ratio all presented as a risk factor, with ORs 1.38 (p = 0.041) and 1.33 (p = 0.014) in short- and long-duration groups, respectively.
CONCLUSION
Although renal functions presented a significant association with DR in all DM patients, the risk factors of DR varied widely in different disease-duration subjects. Target strategies to prevent DR should be put forward individually, considering the patient's DM duration. Improving the BUN/Cr ratio may be beneficial to delaying DR.
PubMed: 37700740
DOI: 10.2147/IJGM.S420983 -
Ophthalmology. Retina Feb 2024To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time...
Longitudinal Quantitative Ultrawidefield Angiographic Features in Diabetic Retinopathy Treated with Aflibercept from the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement Trial.
OBJECTIVE
To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement (PRIME) diabetic retinopathy (DR) clinical trial.
DESIGN
Post hoc analysis of the PRIME prospective randomized DR clinical trial comparing intravitreal aflibercept treatment based on the DR severity score (DRSS) or quantitative leakage index for DR improvement (ClinicalTrials.gov identifier: NCT03531294).
PARTICIPANTS
Patients were enrolled with a DRSS level of 47A to 71A and best-corrected visual acuity of 20/800 or better. Key exclusion criteria were previous intravitreal injection, panretinal photocoagulation, vitrectomy, central-involving macular edema, or vitreous hemorrhage.
METHODS
A previously validated, machine learning-based qUWFA analysis platform was used for panretinal leakage index assessment and differentiation of generalized and perivascular leakage phenotypes. Additionally, microaneurysm count and ischemic index were quantified in panretinal and macular regions. The trends in these biomarkers and therapeutic response were studied over 1 year.
MAIN OUTCOME MEASURES
Longitudinal trends of qUWFA biomarkers. The impact of these qUWFA metrics on treatment response was assessed by studying their associations with time to 2-step DRSS improvement and number of treatment-free days.
RESULTS
Forty eyes from 40 subjects with DR were enrolled. Lower baseline generalized leakage was noted in eyes that attained the 2-step DRSS improvement in < 16 weeks (1.9% vs. 2.8%; P = 0.026). Baseline macular perivascular-generalized leakage ratio had a significant correlation with the number of treatment-free days (r = 0.4; P = 0.012). At the end of 1 year, therapy significantly reduced the mean panretinal (3.9% vs. 5.8%; P = 0.002) and macular (6.2% vs. 12.2%; P = 0.008) generalized leakage indices compared with baseline, as well as the mean panretinal perivascular leakage index (1.5% vs. 2.3%; P = 0.002). The mean panretinal ischemic index demonstrated a small but likely clinically insignificant decrease from 12.5% at baseline to 11.6% at year 1 (P = 0.016).
CONCLUSIONS
Down-trending leakage indices and microaneurysm counts were demonstrated over 1 year of anti-VEGF therapy. At baseline, DR eyes with lower generalized leakage responded to therapy more rapidly. Eyes with greater perivascular leakage relative to generalized leakage showed a longer-lasting anti-VEGF treatment response.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Diabetic Retinopathy; Angiogenesis Inhibitors; Microaneurysm; Prospective Studies; Treatment Outcome; Tomography, Optical Coherence; Biomarkers; Diabetes Mellitus; Recombinant Fusion Proteins; Receptors, Vascular Endothelial Growth Factor
PubMed: 37696393
DOI: 10.1016/j.oret.2023.09.004 -
Frontiers in Endocrinology 2023This study aimed to observe and compare retinal vein diameter changes and other essential indicators in patients with high-risk proliferative diabetic retinopathy (PDR)...
OBJECTIVE
This study aimed to observe and compare retinal vein diameter changes and other essential indicators in patients with high-risk proliferative diabetic retinopathy (PDR) treated with intravitreal injection of conbercept (IVC) combined with panretinal photocoagulation (PRP) versus PRP monotherapy.
METHODS
A retrospective analysis was conducted on data from patients with high-risk PDR who received specific treatment and were followed up for 24 months. Among 82 patients with high-risk PDR, 50 eyes received PRP combined with IVC, whereas 32 eyes received PRP alone. During the 24-month follow-up period, changes in best-corrected visual acuity (BCVA), central foveal thickness (CFT), retinal vein diameter, number of microaneurysms (MA), neovascularization (NV) area, hard exudate (HE) area, size of the foveal avascular zone (FAZ), superficial capillary plexus (SCP) blood flow density, and adverse effects were recorded and compared between the two groups at baseline and at 6, 12, 18, and 24 months after treatment. The relationship between each observation index and vein diameter was also analyzed.
RESULTS
During the 24-month follow up, significant improvements in the BCVA, CFT, retinal vein diameter, number of MAs, NV area, HE area, FAZ, and SCP were observed in the IVC+PRP group after treatment. The PRP group only showed significant reductions in NV and HE areas. The IVC+PRP group showed significant superiority over the PRP group in improving the vein diameter, number of MA, and HE area. However, no statistically significant difference in NV area reduction was found between the groups.
CONCLUSION
In the treatment of high-risk PDR, IVC+PRP therapy has a significant advantage over PRP monotherapy. IVC+PRP therapy may reverse diabetes-induced retinal vein changes, restoring morphology and function.
Topics: Humans; Diabetic Retinopathy; Cohort Studies; Retinal Vein; Retrospective Studies; Macula Lutea; Light Coagulation; Diabetes Mellitus
PubMed: 37693359
DOI: 10.3389/fendo.2023.1218442 -
Ophthalmology. Retina Feb 2024Microaneurysms (MAs) have distinct, oval-shaped, hyperreflective walls on structural OCT, and inconsistent flow signal in the lumen with OCT angiography (OCTA). Their...
PURPOSE
Microaneurysms (MAs) have distinct, oval-shaped, hyperreflective walls on structural OCT, and inconsistent flow signal in the lumen with OCT angiography (OCTA). Their relationship to regional macular edema in diabetic retinopathy (DR) has not been quantitatively explored.
DESIGN
Retrospective, cross-sectional study.
PARTICIPANTS
A total of 99 participants, including 23 with mild, nonproliferative DR (NPDR), 25 with moderate NPDR, 34 with severe NPDR, and 17 with proliferative DR.
METHODS
We obtained 3 × 3-mm scans with a commercial device (Solix, Visionix/Optovue) in 99 patients with DR. Trained graders manually identified MAs and their location relative to the anatomic layers from cross-sectional OCT. Microaneurysms were first classified as perfused if flow signal was present in the OCTA channel. Then, perfused MAs were further classified into fully and partially perfused MAs based on the flow characteristics in en face OCTA. The presence of retinal fluid based on OCT near MAs was compared between perfused and nonperfused types. We also compared OCT-based MA detection to fundus photography (FP)- and fluorescein angiography (FA)-based detection.
MAIN OUTCOME MEASURES
OCT-identified MAs can be classified according to colocalized OCTA flow signal into fully perfused, partially perfused, and nonperfused types. Fully perfused MAs may be more likely to be associated with diabetic macular edema (DME) than those without flow.
RESULTS
We identified 308 MAs (166 fully perfused, 88 partially perfused, 54 nonperfused) in 42 eyes using OCT and OCTA. Nearly half of the MAs identified in this study straddle the inner nuclear layer and outer plexiform layer. Compared with partially perfused and nonperfused MAs, fully perfused MAs were more likely to be associated with local retinal fluid. The associated fluid volumes were larger with fully perfused MAs compared with other types. OCT/OCTA detected all MAs found on FP. Although not all MAs seen with FA were identified with OCT, some MAs seen with OCT were not visible with FA or FP.
CONCLUSIONS
OCT-identified MAs with colocalized flow on OCTA are more likely to be associated with DME than those without flow.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Diabetic Retinopathy; Retinal Vessels; Microaneurysm; Cross-Sectional Studies; Macular Edema; Retrospective Studies; Tomography, Optical Coherence; Fluorescein Angiography; Retina
PubMed: 37673397
DOI: 10.1016/j.oret.2023.08.019 -
Clinical Ophthalmology (Auckland, N.Z.) 2023To evaluate the agreement between conventional fundus photography (CFP) and multicolor fundus imaging (MFI) for the detection of lesions of diabetic retinopathy (DR) and...
PURPOSE
To evaluate the agreement between conventional fundus photography (CFP) and multicolor fundus imaging (MFI) for the detection of lesions of diabetic retinopathy (DR) and retinal vein occlusion (RVO).
METHODS
Cross-sectional analysis of eyes with DR or RVO who underwent CFP and MFI. All images were independently analyzed by two observers (O1 and O2), and the evaluated lesions were classified as "present" or "absent". Then, a paired comparison between both exams of the same eye was performed, to assess which made it easier to detect the lesions.
RESULTS
Considering DR, the agreement was substantial for cotton wool spots and photocoagulation scars for both observers (O1: =0.75 and =0.67; O2: =0.71 and =0.64, respectively) and for hard exudates for O1 (=0.80). These lesions were detected more frequently on MFI. Regarding RVO, the agreement was considered substantial for venous sheathing by O1 (=0.64) and moderate for optociliary shunts by O2 (=0.60). Optociliary shunts were detected more frequently in CPF by both observers and venous sheathing on MFI by O1. For microaneurysms, retinal hemorrhages, retinal neovascularization, and proliferative membranes, in DR, and retinal hemorrhages, venous engorgement, and retinal neovascularization in RVO, the agreement was almost perfect (>0.82). In the paired analysis, both observers considered that, in DR, microaneurysms and retinal hemorrhages were easier to detect on CFP and that retinal neovascularization, cotton wool spots, and photocoagulation scars were easier to identify on MFI. Regarding RVO, optocilliary shunts were easier to identify on CFP and venous engorgement on MFI.
CONCLUSION
The agreement of MFI and CFP was substantial to almost perfect for most lesions. MFI seems better to detect cotton wool spots and photocoagulations scars in DR and venous sheathing in RVO. Optocilliary shunts seem easier to detect on CFP.
PubMed: 37641738
DOI: 10.2147/OPTH.S414603 -
Indian Journal of Ophthalmology Aug 2023To characterize the relationship between diabetic macular ischemia (DMI) delineated by optical coherence tomography angiography (OCTA) and microaneurysms (MAs)...
PURPOSE
To characterize the relationship between diabetic macular ischemia (DMI) delineated by optical coherence tomography angiography (OCTA) and microaneurysms (MAs) identified by fundus fluorescein angiography (FFA).
METHODS
Patients with diabetic retinopathy (DR) who underwent OCTA and FFA were retrospectively identified. FFA images were cropped and aligned with their respective OCTA images using i2k Align Retina software (Dual-Align, Clifton Park, NY, USA). Foveal avascular zone (FAZ) and ischemic areas were manually delineated on OCTA images, and MAs were marked on the corresponding FFA images before overlaying paired scans for analysis (ImageJ; National Institutes of Health, Bethesda, MD, USA).
RESULTS
Twenty-eight eyes of 20 patients were included. The average number of MAs identified in cropped FFA images was 127 ± 42. More DMI was noted in the superficial capillary plexus (SCP; 36 ± 13%) compared to the deep capillary plexus (DCP; 28 ± 14%, P < 0.001). Similarly, more MAs were associated with ischemic areas in SCP compared to DCP (92.0 ± 35.0 vs. 76.8 ± 36.5, P < 0.001). Most MAs bordered ischemic areas; fewer than 10% localized inside these regions. As DMI area increased, so did associated MAs (SCP: r = 0.695, P < 0.001; DCP: r = 0.726, P < 0.001). Density of MAs surrounding FAZ (7.7 ± 6.0 MAs/mm) was similar to other DMI areas (SCP: 7.0 ± 4.0 MAs/mm, P = 0.478; DCP: 9.2 ± 10.9 MAs/mm, P = 0.394).
CONCLUSION
MAs identified in FFA strongly associate with, and border areas of, DMI delineated by OCTA. Although more MAs are localized to SCP ischemia, the concentration of MAs associated with DCP ischemia is greater. By contrast, few MAs are present inside low-flow regions, likely because capillary loss is associated with their regression.
Topics: Humans; Fluorescein Angiography; Retinal Vessels; Retrospective Studies; Tomography, Optical Coherence; Microaneurysm; Fundus Oculi; Visual Acuity; Diabetic Retinopathy; Diabetes Mellitus
PubMed: 37530285
DOI: 10.4103/IJO.IJO_3155_22