Microaneurysm Counts Research Articles

Earlier smart prediction of diabetic retinopathy from fundus image under innovative ResNet optimization maneuver

AbstractDiabetic retinopathy (DR) is a complication of diabetes that causes blindness and the early detection of diabetics using retinopathy images remains a challenging task. Hence, a novel, earlier smart prediction of diabetic retinopathy from fundus image under Innovative ResNet Optimization is introduced to effectively detect the earlier stage of DR from Fundus image. Initially, the fundus image is scaled during preprocessing and converted into a grayscale format. As the existing studies neglect some deserving unique features that are crucial for predicting the earliest signs of DR, a novel Fractional Radon Transform with Visibility Graph is introduced for extracting the novel features such as microaneurysms count, dot and blot hemorrhages count, statistical measures, and retinal layer thickness, in which a Generalized Cosine Fractional Radon Transform is used to capture the image’s fine-scale texture information thereby effectively capturing the statistical measures, while a weighted Horizontal Visibility Graph is made to examine the apparent spatial relationships between pixel pairs in the image based on the values of the pixels’ gray levels. Further, the existing works failed to identify the small fine dark areas that were ignored throughout the morphological opening process. In order to overcome this issue, a Morphological Black Hat Transform with Optimized ResNet Algorithm is implemented, where segmentation is made through Enriched Black Hat Transform-based Morphological operation to identify fine dark regions among the pixels inside the eye samples, and the classification is done by using ResNet-driven S-GOA (Socio Grasshopper Optimization Algorithm), to optimally predict the stages of DR. The result obtained showed that the proposed model outperforms existing techniques with high performance and accuracy.

Microaneurysm detection using high-speed megahertz optical coherence tomography angiography in advanced diabetic retinopathy.

To compare detection rates of microaneurysms (MAs) on high-speed megahertz optical coherence tomography angiography (MHz-OCTA), fluorescein angiography (FA) and colour fundus photography (CF) in patients with diabetic retinopathy (DR). For this exploratory cross-sectional study, MHz-OCTA data were acquired with a swept-source OCT prototype (A-scan rate: 1.7 MHz), and FA and CF imaging was performed using Optos® California. MA count was manually evaluated on en face MHz-OCTA/FA/CF images within an extended ETDRS grid. Detectability of MAs visible on FA images was evaluated on corresponding MHz-OCTA and CF images. MA distribution and leakage were correlated with detectability on OCTA and CF imaging. 47 eyes with severe DR (n = 12) and proliferative DR (n = 35) were included. MHz-OCTA and CF imaging detected on average 56% and 36% of MAs, respectively. MHz-OCTA detection rate was significantly higher than CF (p < 0.01). The combination of MHz-OCTA and CF leads to an increased detection rate of 70%. There was no statistically significant association between leakage and MA detectability on OCTA (p = 0.13). For CF, the odds of detecting leaking MAs were significantly lower than non-leaking MAs (p = 0.012). Using MHz-OCTA, detection of MAs outside the ETDRS grid was less likely than MAs located within the ETDRS grid (outer ring, p < 0.01; inner ring, p = 0.028). No statistically significant difference between rings was observed for CF measurements. More MAs were detected on MHz-OCTA than on CF imaging. Detection rate was lower for MAs located outside the macular region with MHz-OCTA and for leaking MAs with CF imaging. Combining both non-invasive modalities can improve MA detection.

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

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. 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). 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. 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. 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. 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). 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. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Longitudinal Quantitative Ultrawide-field Fluorescein Angiography Dynamics in the RUBY Diabetic Macular Edema Study

The purpose of this study was to evaluate the longitudinal change in quantitative ultrawide-field angiographic (UWFA) parameters and correlate them with functional outcomes and spectral domain-OCT metrics. This study is a post hoc analysis of the phase II RUBY study: a prospective, randomized trial of patients with diabetic macular edema (DME) treated with either intravitreal aflibercept injection (IAI) or combined IAI/nesvacumab (antiangiopoietin 2 mAb). Subjects with DME that underwent UWFA across all treatment groups (n= 44). A machine learning-enabled feature extraction system generated panretinal quantitative UWFA metrics, including leakage, ischemia, and microaneurysm (MA) burden. Zonal assessments were performed corresponding to the macula, midperiphery, and far periphery. Changes in ischemic area and index (proportion of nonperfusion in analyzable retina), leakage area and index (proportion of leakage in analyzable retina), and MA count at baseline, week 12, week 24, and week 36 were analyzed. Spectral-domain-OCT quantitative metrics, such as central subfield thickness, ellipsoid zone (EZ) integrity parameters, intraretinal fluid (IRF) volume, and subretinal fluid (SRF) volume were extracted via a machine learning-enhanced OCT feature extraction platform and analyzed. Additionally, the effect of these changes on best-corrected visual acuity (BCVA) was evaluated. Mean panretinal leakage index, zonal leakage area, and panretinal MA count improved significantly between baseline and week 36. Panretinal ischemic index decreased between baseline and week 36, with some aspects showing significant improvement. Mean BCVA significantly improved from baseline to week 36. There was a significant inverse correlation between change in BCVA and change in macular leakage area. A direct correlation was observed between both baseline macular leakage area and panretinal leakage index with IRF volume, SRF volume, and EZ disruption on OCT. Assessment of UWFA parameters demonstrates a significant improvement in panretinal leakage index, leakage area, and MA burden in eyes treated with IAI with or without nesvacumab. A numeric reduction in panretinal ischemic index and area was noted. The analysis also shows the critical association of leakage with visual and OCT features. This highlights the potential role of UWFA in disease burden assessment, with leakage parameters serving as a primary end point. Proprietary or commercial disclosure may be found after the references.

Comparison of 24×20 mm2 swept-source OCTA and fluorescein angiography for the evaluation of lesions in diabetic retinopathy

To compare ultra-widefield (24×20 mm2) swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA) in the evaluation of diabetic retinopathy (DR) lesions. Forty-six eyes of 23 patients with treatment-naïve DR were included at Peking University People's Hospital from September 1, 2021, until December 31, 2021, as well as 23 age and gender matched healthy controls. Quantitative assessments of DR lesions on FA and SS-OCTA (superficial capillary plexus, SCP, 24×20 mm2) were performed. Area of fovea avascular zone (FAZ) was larger in DR cases than controls (0.34±0.069 mm2 vs 0.287±0.108 mm2, P=0.006). In DR eyes, the mean FAZ area was 0.34±0.069 and 0.334±0.087 mm2 on SS-OCTA and FA, respectively (P=0.428), while the median FAZ perimeter was 2.382 (IQR, 2.201-2.59) and 2.333 (IQR, 2.138-2.6) mm on SS-OCTA and FA images (P=0.733). There was no significant difference in the size of the non-perfusion area (NPA) between the images on SS-OCTA and FA (12.389, IQR 4.96-28.3 and 11.125, IQR 5-28.31 mm2, P=0.197). The median total microaneurysm (MA) count was 35 (IQR, 19-46) and 73 (IQR, 43-93) on SS-OCTA and FA (P<0.001), respectively. No significant difference in intra-retinal microvascular abnormality (IRMA) and neovascularization (NV) count was found between the two techniques. The intraclass coefficient (ICCs) of all the parameters above indicated stable repeatability. Ultra-widefield SS-OCTA represents a reliable, noninvasive, and quantitative imaging technique in the assessment of microvasculature in DR, which offers a potential substitute for FA in DR evaluation.

Comparison of widefield swept-source optical coherence tomography angiography with ultra-widefield fluorescein angiography for the evaluation of lesions in retinal vein occlusion

BackgroundTo compare widefield swept-source optical coherence tomography angiography (SS-OCTA) with ultra-widefield fundus fluorescein angiography (UWF-FA) for detecting retinal vein occlusion (RVO) lesions.MethodsThirty-four eyes of 32 patients with treatment-naïve RVO were enrolled at Peking University People’s Hospital from September 2021 to March 2022. Patients were imaged with a UWF-FA (200°) and a widefield SS-OCTA using 24 × 20 mm scan single capture. Quantitative assessments of RVO lesions such as foveal avascular zone (FAZ) area and perimeter, non-perfusion areas (NPA), number of microaneurysms (MAs), capillary changes and collateral vessels were performed.ResultsThe measurement of FAZ area and perimeter were comparable between SS-OCTA and UWF-FA (0.373 (range, 0.277–0.48) mm2 vs. 0.370 (range, 0.277–0.48) mm2, P = 0.818 and 2.480 (range, 2.011–2.998) vs. 2.330 (range, 2.027–2.807) mm, P = 0.536, respectively). Intraclass correlation coefficients (ICCs) of FAZ area and perimeter between SS-OCTA and UWF-FA was high (0.999, [0.997–0.999] and 0.996 [0.991–0.996], respectively), suggesting good agreement. The mean NPA area was larger on SS-OCTA than that on UWF-FA (89.977 ± 78.805 mm2vs. 87.944 ± 77.444 mm2, P = 0.037). The ICC of NPA area was also high (0.999, [0.999–1.000]). The median of total MA count was less on SS-OCTA than on UWF-FA (7 (range, 0–19) vs.12 (range, 0–23), P < 0.001). Agreement in detecting MAs between SS-OCTA and UWF-FA was found to be good (ICC = 0.920, [0.555–0.974]).The total capillary changes and collateral vessels count were less on UWF-FA than SS-OCTA (11 ± 9 vs 6 ± 7, P < 0.001 and 4 (range, 0–6) vs 0 (range, 0–0), P < 0.001, respectively). Agreement in detecting capillary changes and collateral vessels between OCTA and UWF-FA was found to be fair (ICC = 0.733, [0.081–0.905] and 0.564, [0.039–0.805], respectively).ConclusionCompared with UWF-FA, widefield SS-OCTA was found comparable or even superior in detecting FAZ, NPA, capillary changes and collateral vessels except MAs in RVO. Widefield SS-OCTA may offer a more efficient alternative to FA for diagnosis and monitoring RVO.

Effect of a Fixed Combination of Curcumin, Artemisia, Bromelain, and Black Pepper Oral Administration on Optical Coherence Tomography Angiography Indices in Patients with Diabetic Macular Edema.

Background: To investigate the effects of a fixed combination of Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) on vascular parameters in mild to moderate diabetic macular edema (DME). Design: Prospective, case-control study. Methods: Fifty-six patients affected by diabetes mellitus type II were enrolled in the study. Twenty-eight patients with DME received 2 tablets/day, before meals of a dietary complementary supplement containing in fixed combination Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) (Intravit®, OFFHEALTH Spa, Firenze, Italy) for 6 months. Twenty-eight age-matched subjects affected by diabetes mellitus type II were given placebo and served as control group. Patients underwent best correct visual acuity (BCVA), swept optical coherence tomography (OCT), and OCT-Angiography (OCTA). OCTA images of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained for each eye. By the end of the follow-up patients were defined responder to the therapy when a decrease of more than 30 μm was registered in central retinal thickness (CRT) measurement, while a poor responder was determined by the absence of reduction or an increase in central retinal thickness at 6 months. We assessed the foveal avascular zone (FAZ) area, vessel density and quantified the number of microaneurysms in each layer. Results: A significant improvement of BCVA and CRT reduction was recorded at 6 months follow-up in the dietary complementary supplementation group compared to control (respectively p = 0.028 and p = 0.0003). VD of the total capillary plexus, microaneurysms count, glycaemia and HbA1c did not vary over the follow-up period between groups. Within the Intravit® group, poor responders tended to show a larger FAZ area, more microaneurysms, and a lower VD in the DCP compared to the good responders group (p < 0.0001). Conclusions: A fixed combination of Curcumin, Artemisia, Bromelain, and Black pepper oral administration may have a positive impact on central retinal thickness, visual acuity, and VD of the DCP in compensated type 2 diabetic patients with mild DME.

Effect of Chinese Patent Medicines on Ocular Fundus Signs and Vision in Calcium Dobesilate-Treated Persons With Non-Proliferative Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

BackgroundDiabetic retinopathy (DR), one of the commonest microvascular complications in diabetic patients, is featured by a series of fundus lesions. Conventional Western medicine therapies for DR are always with modest treatment outcome. This paper is to assess the ocular fundus signs, vision and safety of Chinese patent medicines (CPMs) as an add-on treatment for DR.Method7 electronic databases were searched to determine eligible trials. Randomized controlled trials (RCTs) of non-proliferative diabetic retinopathy (NPDR) in which the intervention group received CPMs combined with calcium dobesilate (CD), and the control group received only CD were included for analysis. Two reviewers extracted the data independently. Results expressing as mean differences (MD) and relative risks (RR) were analyzed with a fixed-effects or random-effects models.Results19 RCTs involved 1568 participants with 1622 eyes met our inclusion criteria. The results suggested that compared with CD alone, CPMs plus CD for NPDR was superior at reducing the microaneurysm volume (MD -3.37; 95% confidence interval [CI], -3.59 to -3.14), microaneurysm counts (MD -2.29; 95%CI -2.97 to -1.61), hemorrhage area (MD -0.79; 95%CI -0.83 to -0.75), and macular thickness (MD -59.72; 95%CI -63.24 to -56.20). Participants in CPMs plus CD group also achieved a better vision. No obvious adverse events occurred.ConclusionCPMs as an add-on therapy for NPDR have additional benefits and be generally safe. This meta‐analysis demonstrated that CPMs combined with CD could improve retinal microaneurysm, hemorrhage, macular thickness, visual acuity, fasting blood glucose (FBG), and glycosylated hemoglobin (HbAlc) compared with CD alone. Further studies are needed to provide more conclusive evidence.Systematic Review RegistrationPROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021257999.

Response to 1-Year Fixed-Regimen Bevacizumab Therapy in Treatment-Naïve DME Patients: Assessment by OCT Angiography.

Purpose To evaluate the effectiveness of intravitreal bevacizumab treatment in patients with diabetic macular edema (DME) by assessing retinal changes using optical coherence tomography angiography (OCT-A). Methods This prospective study was performed in patients with treatment-naïve DME. The eyes of patients were imaged using a swept-source OCT system with a scan area of 6 × 6 mm. The DME patients with a central macular thickness (CMT) of ≥300 μm received nine bevacizumab injections within 12 months. The demographic, systemic, and ocular parameters, including the best-corrected visual acuity (BCVA), CMT, microaneurysm (MA) count, and foveal avascular zone (FAZ) area in both superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as vessel density in SCP, were assessed in the patients. In addition, the response (good or poor) of the DME eyes to bevacizumab treatment and the final visual acuity (BCVA of 75 letters) were analyzed. Results Seventy-seven eyes of DME patients were subjected to the final analysis. Bevacizumab treatment reduced CMT from 425.06 μm (±77.15) to 350.25 μm (±82.04) and improved BCVA by about 8.61 letters (from 64.73 to 73.34) in the patients. The mean number of MAs in SCP decreased from 3.51 ± 2.07 to 2.31 ± 1.15 (p < 0.001) and in DCP from 17.12 ± 11.56 to 12.21 ± 6.99 (p < 0.001), whereas the area of FAZ increased in SCP from 328.22 ± 131.38 to 399.70 ± 156.98 (p < 0.001) and in DCP from 571.13 ± 396.01 to 665.89 ± 412.77 (p = 0.001). The final BCVA letter score and CMT were statistically significant in both poor and good responders, as well as in BCVA < 75 and BCVA ≥ 75 groups. Conclusion The fixed-regimen intravitreal bevacizumab therapy was effective in treating DME. Apart from noninvasive visualization of microvascular damage, OCT-A showed limited usefulness in predicting treatment response. Although the study showed that the number of MAs was significantly reduced during treatment, which is an OCT-A predictor of a good response to bevacizumab treatment at a 12-month visit, commonly observed artifacts may reduce the usefulness of OCT-A.

Comparison between optical coherence tomography angiography and fundus fluorescein angiography for early detection of diabetic retinopathy

Purpose This work studied the ability of optical coherence tomography angiography (OCTA) to detect and analyze microvasculature changes in the retina in early nonproliferative diabetic retinopathy (NPDR) compared with fluorescein angiography (FA) regarding the posterior pole. The study compared two groups of patients with NPDR, a group with diabetic macular edema (DME) and another group without DME, with a group of health individuals as the control. The study compared foveal avascular zone (FAZ) size, capillary perfusion (CP), and vessel density in the superficial capillary plexus (SCP) in both the control and the two groups of patients with NPDR with and without DME. The number of microaneurysms (MAs) was also analyzed in the SCP and deep capillary plexus of OCTA and compared with FA. Patients and methods The study included 40 eyes of patients with NPDR and 20 eyes of volunteers as control. FA, OCT, and OCTA were done for all 40 eyes of NPDR, and only OCTA was done for the control group. OCTA parameters were as follows: ‘vessel density (mm/mm2), CP (%) (in SCP), and FAZ area (mm2) in SCP of macular area.' OCTA was performed using both 3×3 mm and 6 × 6 mm scans of the OCTA and with production of an OCT macular map. Digital color fundus photography and FA photographs were analyzed in relation to NPDR with evaluation of;Deg;MA;Deg;s, FAZ appearance, and late dye leakage. For;Deg;MA;Deg; counting, a 3×3 mm section centered on the fovea was manually delimited on FA images. Results MA count comparison between FA and OCTA (SCP and deep capillary plexus) showed highly a statistically significant differences between them, with P value less than 0.001 in all cases. DMI appeared early in all eyes with NPDR, presented with vessel density, CP, and the FAZ area in the SCP in both groups of patients with NPDR (in group A without DME and in group B with DME), with no significant statistical difference between the two groups of NPDR. Group A had a mean±SD vessel density of 9.95±2.805 mm/mm2, mean±SD of CP 18.97±4.754%, and mean±SD FAZ size of 0.59±0.228 mm2, whereas in group B, mean±SD vessel density was 10.19±3.152 mm/mm2, mean±SD CP was 20.14±6.131%, and mean±SD FAZ size was 0.63±0.270 mm2. When comparing groups A and B of patients with NPDR with the control group (group C), the control group showed a mean±SD vessel density of 13.23±2.454 mm/mm2, mean±SD of CP 27.89±5.627%, and mean±SD FAZ size of 0.36±0.097 mm2. A highly significant difference was found between patients with NPDR (both groups A and B) and healthy participants (group C). Conclusions MAs are more prominent in FA than in OCTA. Superficial vessel density and CP of macular region in NPDR eyes with and without DME are both decreased, in correlation to control group. The FAZ region of patients with NPDR is also enlarged when compared with healthy participants. CP and vessel density cannot be evaluated by FA, which is an advantage of OCTA over FA, but by using FA, we can evaluate the periphery, which cannot be evaluated by OCTA up till now.

The 2-Year Leakage Index and Quantitative Microaneurysm Results of the RECOVERY Study: Quantitative Ultra-Widefield Findings in Proliferative Diabetic Retinopathy Treated with Intravitreal Aflibercept.

Eyes with proliferative diabetic retinopathy (PDR) have been shown to improve in the leakage index and microaneurysm (MA) count after intravitreal aflibercept (IAI) treatment. The authors investigated these changes via automatic segmentation on ultra-widefield fluorescein angiography (UWFA). Forty subjects with PDR were randomized to receive either 2 mg IAI every 4 weeks (Arm 1) or every 12 weeks (Arm 2) through Year 1. After Year 1, Arm 1 switched to quarterly IAI and Arm 2 to monthly IAI through Year 2. By Year 2, the Arm 1 leakage index decreased by 43% from Baseline (p = 0.03) but increased by 59% from Year 1 (p = 0.04). Arm 2 decreased by 61% from Baseline (p = 0.008) and by 31% from Year 1 (p = 0.12). Both cohorts exhibited a significant decline in MAs from Baseline to Year 2 (871 to 410; p < 0.001; 776 to 207; p < 0.001, respectively). Subjects with an improved leakage and MA count showed a more significant improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. Moreover, central subfield thickness (CST) was positively associated with changes in the leakage index. In conclusion, the leakage index and MA counts significantly improved from Baseline following IAI treatment, and monthly injections provided a more rapid and sustained reduction in these parameters compared with quarterly injections.

Association of Subregional Quantitative Ultra-widefield Fluorescence Angiography Characteristics With the Occurrence of Diabetic Macular Edema and Proliferative Diabetic Retinopathy.

Purpose: To explore the relationships of region-specific properties of ultra-widefield fluorescence angiography (UWFFA) images with two adverse outcomes, diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR), and also the severity of diabetic retinopathy (DR).Methods: A cross-sectional observational study was performed to retrospectively analyze UWFFA images of patients with DR. All patients underwent UWFFA and optical coherence tomography examination. Leakage index and microaneurysm (MA) count were measured using Trainable Weka Segmentation, a machine learning algorithm, and ischemic index (ISI) was measured manually. The correlation between UWFFA parameters and severity of DR was analyzed, and receiver operating characteristic curves were used to estimate their diagnostic value for DME and PDR.Results: A total of 108 eyes from 108 patients with DR (mean age of 56.04 ± 8.85 years) were analyzed. As the severity of DR increased, the ISI and leakage index of the panretina and all subregions increased. Panretinal MA count and leakage index were significantly higher in eyes with DME than those without DME (p = 0.044 and 0.001, respectively). Leakage index and ISI were significantly higher in eyes with PDR than those without PDR in both panretinal and subregion-specific measurements (all p < 0.05). Throughout the retina and specifically in the posterior area (PoA), the leakage index had a higher diagnostic value for DME than ISI or MA count (all p < 0.05). The diagnostic value of MA count for PDR was lower than that of ISI and leakage index (all p < 0.05).Conclusion: The ISI, leakage index, and MA count in the PoA and panretina correlated with the severity of DR, especially the posterior parameter. The leakage index was more valuable than ISI and MA count in determining the occurrence of DME. ISI and leakage index were better predictors of PDR.

Exploring the angiographic-biologic phenotype in the IMAGINE study: quantitative UWFA and cytokine expression

BackgroundThis study investigates the association of intraocular cytokine expression and ultrawide-field fluorescein angiography (UWFA) quantitative imaging biomarkers and their association with angiographical feature response after antivascular endothelial growth factor (VEGF)...

Diabetic Macular Edema Treatment with Bevacizumab Does Not Depend on the Retinal Nonperfusion Presence.

This study evaluated the relationship between the retinal nonperfusion area (NPA) presence and the effectiveness of bevacizumab treatment (IVB) in patients with diabetic macular edema (DME). It also tested the prognostic usefulness of ultra-wide-field fluorescein angiography (UWFFA) and OptosAdvance software for diabetic retinopathy monitoring. Eighty-nine patients with DME with a macular central subfield thickness (CST) ≥ 250 μm, with (N = 49 eyes) and without (N = 49 eyes) retinal NPA, underwent nine bevacizumab injections over 12 months. NPA distribution, leakage area distribution, microaneurysm (MA) count, macular CST, diabetic retinopathy severity, and best-corrected visual acuity (BCVA) were assessed. The results show that bevacizumab reduced the macular CST from 420 to 280 μm (p < 0.001) and improved BCVA (p < 0.001) by about 10 ETDRS letters in both groups of patients. Additionally, the therapy reduced total retinal NPA from 29 (14-36) mm2 to 12 (4-18) mm2 (Me (Q1-Q3); p < 0.001) in patients with diagnosed nonperfusion. The effect of the therapy measured with vascular leakage, MA count, BCVArelative, and CSTrelative strongly depended on the zone of the retina and the NPA distribution. We conclude that the bevacizumab treatment had a positive effect on DME and BCVA in both study groups and on the size of retinal NPA in patients with retinal nonperfusion.

Association of macular perfusion status with microvascular parameters up to the far periphery in diabetic retinopathy using multimodal imaging

BackgroundThe aim of our study was to investigate a possible association between macular perfusion status and retinal ischemia and leakage up to far peripheral retinal areas in eyes with early to advanced stages of diabetic retinopathy (DR).MethodsIn a retrospective, cross sectional analysis ultrawide field (UWF) color fundus photos (Optos, Optomap California) were graded for DR severity. Foveal avascular zone (FAZ) and vessel density from the superficial (SCP) and deep capillary plexus (DCP) were assessed on optical coherence tomography angiography (OCTA) scans (Topcon, DRI-OCT Triton). UWF angiography images were used to quantify leakage/ischemic index and number of microaneurysms (MA). Age, gender, disease duration, type of diabetes, HbA1C, hypertension, complications of diabetes and ocular history were recorded. Univariate mixed models and Spearman correlation analysis were used for statistical testing.Results24 eyes of 17 laser-naive diabetic patients with different stages of DR were analyzed. The mean age was 59.56 ± 8.46 years and the mean disease duration 19.65 ± 12.25 years. No statistically significant associations between FAZ size, macular vessel density of SCP/DCP and peripheral retinal ischemia, leakage and MA number were demonstrated. Higher stages of DR were associated with ischemic index (estimate [95% CI]: 13.04 [1.5; 24.5], p = 0.033) and MA count (estimate [95% CI]: 43.7 [15.6; 71.8], p = 0.01), but no association with leakage index was observed. Only weak correlations between DR severity and anamnestic data were found.ConclusionRetinal ischemic index and the amount of MAs assessed on UWFA up to peripheral areas are indicators of DR severity but not related to microvascular perfusion status in the macular region. Significance and timely sequence of macular vessel density in DR progression may need to be re-evaluated in future studies.

The Effect of Anti-Vascular Endothelial Growth Factor on Retinal Microvascular Changes in Diabetic Macular Edema Using Swept-Source Optical Coherence Tomography Angiography.

PurposeThis study evaluates the effect of anti-vascular endothelial growth factor (anti-VEGF) therapy on microaneurysm changes and foveal avascular zone (FAZ) using optical coherence tomography angiography (OCTA) in patients with diabetic macular edema (DME).DesignProspective observational study.Materials and MethodsThis study involved patients with DME undergoing anti-VEGF treatment (aflibercept, ranibizumab, and bevacizumab). Macula OCTA images were obtained before (visit 0) and 1 month after (visit 1) anti-VEGF injection. Microaneurysm counts were performed, and the FAZ was evaluated in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The differences in microaneurysms, FAZ, and clinical correlations were analyzed.ResultsA total of 152 eyes were analyzed. The patients’ mean age was 59 years. Bevacizumab was used in 69.7%, ranibizumab in 15.1%, and aflibercept in 15.1%. There was a significant reduction in the FAZ in the SCP and DCP between visits 0 and 1. All anti-VEGF medications reduced the number of microaneurysms (p<0.01). After treatment, changes in the FAZ in SCP and DCP corresponded with changes in visual acuity (p<0.01).ConclusionMicroaneurysms as detected by OCTA might serve as a biomarker for a clinical response to anti-VEGF treatment in the short term. The FAZ might also predict visual acuity improvement after anti-VEGF injection.Trial RegistrationThai Clinical Trials Registry (TCTR20161010005).

Disparity of microaneurysm count between ultrawide field colour imaging and ultrawide field fluorescein angiography in eyes with diabetic retinopathy

AimsTo compare microaneurysm (MA) counts using ultrawide field colour images (UWF-CI) and ultrawide field fluorescein angiography (UWF-FA).MethodsRetrospective study including patients with type 1 or 2 diabetes mellitus receiving UWF-FA and...

Quantitative Ultra-Widefield Angiographic Features and Associations with Diabetic Macular Edema

To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and microaneurysms. Retrospective image analysis study. Eyes with diabetic retinopathy that had undergone spectral-domain OCT, UWFA, and ultra-widefield fundus photography. OCT images were analyzed to determine the presence or absence of DME, central subfield thickness (CST), and subretinal fluid. Using a semiautomated analysis platform, UWFA images were segmented for ischemia, leakage, and microaneurysms with manual correction as needed. Clinical variables, including age, gender, race, hemoglobin A1C levels, blood pressure, cholesterol levels, use of blood thinners, smoking status, and lens status also were evaluated. Factors associated with the presence and severity of DME. A total of 304 eyes (156 right eyes, 148 left eyes) from 178 diabetic patients were analyzed in the study. Panretinal leakage index, microaneurysm count, and ischemic index were not significantly different between eyes with and without DME in univariate assessment. Zonal assessments of macular microaneurysms and macular leakage index values revealed that eyes with DME showed a significantly higher microaneurysm count (P= 0.001) and leakage index (P < 0.0001) in the posterior pole compared with eyes without DME. Severity of macular thickening (i.e., CST) was associated significantly with macular leakage index and posterior pole microaneurysm count (P= 0.0002 and P= 0.03, respectively). In addition to posterior pole leakage index and microaneurysm count, DME was associated with older age (P < 0.01), higher systolic blood pressure (P < 0.001), and white race (P= 0.03). Multivariate assessment confirmed the independent association of presence of DME with macular leakage index and macular microaneurysm count (P < 0.01). Quantitative measures of leakage index and microaneurysm count in the posterior pole on UWFA images were associated with the presence and severity of DME. Panretinal analyses were not linked to DME as strongly. Additional research is needed to determine the role of quantitative UWFA in predicting DME development and characterizing patient prognosis.

Repeatability of automated leakage quantification and microaneurysm identification utilising an analysis platform for ultra-widefield fluorescein angiography

Background/aimsUltra-widefield fluorescein angiography (UWFA) provides unique opportunities for panretinal assessment of retinal diseases. The objective quantification of UWFA features is a labour-intensive manual process, limiting its utility. The present study...

Quantitative Ultra-Widefield Angiography and Diabetic Retinopathy Severity: An Assessment of Panretinal Leakage Index, Ischemic Index and Microaneurysm Count

To investigate the relationship between the diabetic retinopathy (DR) severity and quantitative ultra-widefield angiographic metrics, including leakage index, ischemic index, and microaneurysm count. Retrospective image analysis study. Eyes with DR that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color photography were identified. All eyes were laser-naive and had not received any intravitreal pharmacotherapy within 6 months of UWFA. Each eye was graded for DR severity. Quantitative angiographic parameters were evaluated with a semiautomated analysis platform with expert reader correction, as needed. Angiographic parameters included panretinal leakage index, ischemic index, and microaneurysm count. Clinical characteristics analyzed included age, gender, race, hemoglobin A1C level, hypertension, systolic blood pressure, diastolic blood pressure, and smoking history. Association of DR severity with panretinal leakage index, ischemic index, and microaneurysm count. Three hundred thirty-nine eyes were included with mean age of 62±13 years. Forty-two percent of eyes were from women and 57.5% were from men. Distribution of DR severity was as follows: mild NPDR in 11.2%, moderate NPDR in 23.9%, severe NPDR in 40.1%, and PDR with 24.8%. Panretinal leakage index [mild NPDR (mean = 0.51%), moderate NPDR mean = 1.20%, severe NPDR (mean = 2.75%), and PDR (mean = 5.84%); P<2×10-16], panretinal ischemic index [mild NPDR (mean = 0.95%, moderate NPDR (mean = 1.37%), severe NPDR (mean = 2.80%), and PDR (mean = 9.53%); P<2×10-16], and panretinal microaneurysm count [mild NPDR (mean = 36), moderate NPDR (mean = 129), severe NPDR (mean = 203), and PDR (mean = 254); P<5×10-7] were strongly associated with DR severity. Multivariate analysis demonstrated that ischemic index and leakage index were the parameters associated most strongly with level of DR severity. Panretinal leakage index, panretinal ischemic index, and panretinal microaneurysm countareassociated with DR severity. Additional research is needed to understand the clinical implications of these parameters related to progression risk, prognosis, and implications for therapeutic response.