Intraretinal Microvascular Abnormalities Research Articles

Diabetic Retinopathy Lesion Types and Distribution on Ultrawide Field Imaging and the Risk of Disease Worsening Over Time.

To evaluate the effect of diabetic retinopathy (DR) lesion type [hemorrhages and/or microaneurysms (H/Ma), intraretinal microvascular abnormalities (IRMA), new vessels elsewhere (NVE), venous beading], severity and distribution on disease worsening based on the Early Treatment Diabetic Retinopathy Study (ETDRS)-Diabetic Retinopathy Severity Scale (DRSS). Post-hoc analysis of a multi-center observational study of 544 eyes with nonproliferative DR and an ETDRS-DRSS score of Level 35-53. Disease worsening was defined as ETDRS-DRSS worsening by ≥2 steps from baseline or receipt of DR treatment over 4 years. DR lesions were evaluated based on the entire visible area in the ultrawide field color (UWF-color) and UWF-fluorescein angiography (UWF-FA) images. A significantly greater risk of disease worsening was associated with the presence of more severe lesion grades outside the ETDRS fields for H/Ma (HR:1.74 [95% CI:1.28-2.36]) on UWF-color; and for H/Ma (1.90 [1.38-2.61]), IRMA (1.68 [1.13-2.49]), and NVE (1.99 [1.36-2.93]) on UWF-FA. These results suggest that features on UWF-color and UWF-FA may provide additional prognostic value in determining the risk of disease worsening. The use of UWF-FA improves identification of DR lesions and disease progression. However, the optimal method of disease risk assessment on UWF imaging still needs to be determined.

ETDRS grading with CLARUS ultra-widefield images shows agreement with 7-fields colour fundus photography

BackgroundTo analyse and compare the grading of diabetic retinopathy (DR) severity level using standard 35° ETDRS 7-fields photography and CLARUS™ 500 ultra-widefield imaging system.MethodsA cross-sectional analysis of retinal images of patients with type 2 diabetes (n = 160 eyes) was performed for this study. All patients underwent 7-fields colour fundus photography (CFP) at 35° on a standard Topcon TRC-50DX® camera, and ultra-widefield (UWF) imaging at 200° on a CLARUS™ 500 (ZEISS, Dublin, CA, USA) by an automatic montage of two 133° images (nasal and temporal). 35° 7-fields photographs were graded by two graders, according to the Early Treatment Diabetic Retinopathy Study (ETDRS). For CLARUS UWF images, a prototype 7-fields grid was applied using the CLARUS review software, and the same ETDRS grading procedures were performed inside that area only. Grading of DR severity level was compared between these two methods to evaluate the agreement between both imaging techniques.ResultsImages of 160 eyes from 83 diabetic patients were considered for analysis. According to the 35° ETDRS 7-fields images, 22 eyes were evaluated as DR severity level 10–20, 64 eyes were evaluated as DR level 35, 41 eyes level 43, 21 eyes level 47, 7 eyes level 53, and 5 eyes level 61. The same DR severity level was achieved with CLARUS 500 UWF images in 92 eyes (57%), showing a perfect agreement (k > 0.80) with the 7-fields 35° technique. Fifty-seven eyes (36%) showed a higher DR level with CLARUS UWF images, mostly due to a better visualization of haemorrhages and a higher detection rate of intraretinal microvascular abnormalities (IRMA). Only 11 eyes (7%) showed a lower severity level with the CLARUS UWF system, due to the presence of artifacts or media opacities that precluded the correct evaluation of DR lesions.ConclusionsUWF CLARUS 500 device showed nearly perfect agreement with standard 35° 7-fields images in all ETDRS severity levels. Moreover, CLARUS images showed an increased ability to detect haemorrhages and IRMA helping with finer evaluation of lesions, thus demonstrating that a UWF photograph can be used to grade ETDRS severity level with a better visualization than the standard 7-fields images.Trial registrationApproved by the AIBILI - Association for Innovation and Biomedical Research on Light and Image Ethics Committee for Health with number CEC/009/17- EYEMARKER.

The effect of long-term hemodialysis on diabetic retinopathy observed by swept-source optical coherence tomography angiography

BackgroundDiabetes can cause chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN). DR and DN can lead to or exacerbate diabetic macular edema (DME). Hemodialysis (HD) is the main treatment method for patients with end-stage kidney disease (ESKD) secondary to DN.PurposeThe aim of this prospective cohort study was to determine the immediate effect of single HD session on retinal and choroidal thickness in DR patients with ESKD and the features of DR and the prevalence of DME in these patients who have received long-term HD.MethodsEighty-five eyes of 44 DR patients with ESKD who underwent long-term HD were examined by swept-source optical coherence tomography angiography (SS-OCTA). Based on OCTA images, the characteristics of DR and the prevalence of DME in these patients were analyzed. Changes in central retinal thickness (CRT), central retinal volume (CRV), subfoveal choroidal thickness (SFCT) and subfoveal choroidal volume (SFCV) within 30 min before and after single HD session were compared. CRT, CRV, SFCT and SFCV were compared before single HD session and before the next single HD session.ResultsThere was no significant difference in the average CRT (251.69 ± 39.21 μm vs. 251.46 ± 39.38 μm, P = 0.286) or CRV (0.15 ± 0.62 μm vs. 0.15 ± 0.63 μm, P = 0.324) between before and after single HD session. After single HD session, SFCT (243.11 ± 77.15 μm vs. 219.20 ± 72.84 μm, P < 0.001) and SFCV (0.15 ± 0.10 μm vs. 0.13 ± 0.90 μm, P < 0.001) significantly decreased. There was no statistically significant difference in CRT (251.69 ± 39.21 μm vs. 251.11 ± 38.47 μm, P = 0.206), CRV (0.15 ± 0.62 μm vs. 0.15 ± 0.61 μm, P = 0.154), SFCT (243.11 ± 77.15 μm vs. 245.41 ± 76.23 μm, P = 0.108), or SFCV (0.15 ± 0.10 μm vs. 0.16 ± 0.10 μm, P = 0.174) before HD and before the next single HD session. On en face OCTA images, eighty-five eyes (100%) had retinal nonperfusion areas, foveal avascular zone (FAZ) enlargement, and abnormal retinal microvasculature. Based on cross-sectional OCTA images, retinal neovascularization (RNV) was confirmed in 42 eyes (49.41%), and intraretinal microvascular abnormalities (IRMAs) were detected in 85 eyes (100%). Seventeen eyes (20%) still had DME, all of which were cystoid macular edema (CME). Among eyes with DME, the epiretinal membrane (ERM) was present in 7 eyes (8.24%).ConclusionsFor DR patients with ESKD who have undergone long-term HD, the choroidal thickness still changes significantly before and after single HD session, which may be related to short-term effects such as reduced blood volume and plasma osmotic pressure caused by single HD session. Although macular features seem to have stabilized in DR patients undergoing long-term dialysis, the DR of patients with ESKD should still be given attention.

Longitudinal Assessment of Intraretinal Microvascular Abnormalities in Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography Angiography.

To longitudinally investigate the changes in intraretinal microvascular abnormalities (IRMAs) over time, employing swept-source optical coherence tomography angiography in eyes with diabetic retinopathy. In this retrospective, longitudinal study, we evaluated 12 × 12-mm swept-source optical coherence tomography angiography centered on the macula at baseline and last available follow-up visit for (1) IRMA changes during follow-up, defined as (a) stable, (b) regressed, (c) obliterated, and (d) progressed; and the (2) development of new neovascularization (NV) and their origins. Competing-risk survival analysis was used to assess the factors associated with these changes. In total, 195 eyes from 131 participants with diabetic retinopathy were included. Stable, regressed, obliterated, and progressed IRMA were observed in 65.1%, 12.8%, 11.3%, and 19% of eyes with diabetic retinopathy, respectively. Anti-VEGF injections during the follow-up periods and a slower increase of foveal avascular zone were associated with IRMA regression (P < 0.001 and P = 0.039). Obliterated IRMA were correlated with previous panretinal photocoagulation (P < 0.001) and a lower deep capillary plexus vessel density at baseline (P = 0.007), as well as with follow-up anti-VEGF injections (P = 0.025). A higher baseline ischemia index (ISI) and panretinal photocoagulation during the follow-up periods were associated with IRMA progression (P = 0.049 and P < 0.001). A faster increase in ISI predicted the development of NV elsewhere (NVE) from veins (P < 0.001). No significant factors were found to be associated with NVE originating from IRMA. Changes in IRMA closely correlated with the severity of retinal ischemia and treatment. Notably, our study confirmed the potential, yet relatively rare, development of NVE from IRMA in a large cohort; however, the risk factors associated with this transformation require further exploration.

OCT angiography 2023 update: focus on diabetic retinopathy.

Optical coherence tomography angiography (OCTA) has become part of the clinical practice and its growing applications are in continuous development. Coherently with the growing concern about the human and economic cost of diabetes, diabetic retinopathy (DR) was the most popular topic for OCTA studies in the past year. The analysis of the literature reveals that applications of OCTA in DR are in continuous growth. In particular, ultrawide field (UWF) OCTA and artificial intelligence (AI) based on OCTA images are affirming as the new frontiers of scientific research in the field. Diagnostic accuracy of AI methods based on OCTA is equal or superior to the one based on OCT methods and also bears potential to detect systemic associations. UWF OCTA is noninvasive method that is reaching similar accuracy of FA in detection of neovascularization and intraretinal microvascular abnormalities (IRMAs) and has allowed better characterization of microvascular peripherical changes in DR. Lastly, deep capillary plexus (DCP) characteristics seem to play a pivotal role in the development of diabetic macular edema (DME) and refinement of biomarkers for different phenotypes of DME and diabetic macular ischemia (DMI) is currently on its way.

Impact of intravitreal anti-VEGF therapy on intraretinal microvascular abnormalities in proliferative diabetic retinopathy.

Impact of intravitreal anti-VEGF therapy on intraretinal microvascular abnormalities in proliferative diabetic retinopathy.

Programmatically Localizing Diabetic Retinopathy Features in 45-Degree Retinal Photographs Using Anatomical Colocation

Background: The aim in this study was to investigate the localization of diabetic retinopathy features at the posterior pole. Methods: This study extracted diabetic retinopathy feature locations from 757 macula-centered 45-degree fundus photographs in the publicly available DDR dataset. Arteriole and venule locations were also extracted from the RITE (n = 35) and IOSTAR (n = 29) datasets. Images were normalized to collocate optic disc and macula positions, and feature positions were collated to generate a frequency distribution matrix. Sørensen–Dice coefficients were calculated to compare the location of different features. Results: Arterioles occurred in two main, distinct arcuate patterns. Venules showed a more diffuse distribution. Microaneurysms were diffusely located around the posterior pole. Hemorrhages and exudates occurred more frequently at the temporal aspect of the macula. Cotton wool spots occurred in a region approximating the radial peripapillary capillaries. Intraretinal microvascular abnormalities and neovascularization were seen throughout the posterior pole, with neovascularization at the disc (n = 65) being more common than neovascularization elsewhere (n = 46). Venous beading occurred primarily between the first and third bifurcations of the venules. Diabetic retinopathy overall was more frequent in the temporal aspect of the macula. The location of cotton wool spots and exudates showed moderate similarity (0.52) when all data were considered, reducing to low similarity (0.18) when areas of low frequency were removed. Conclusions: Diabetic retinopathy occurs throughout the posterior pole but is more frequent in the temporal aspect of the macula. Understanding the location of diabetic retinopathy features may help inform visual search strategies for diabetic retinopathy screening.

Color fundus photography versus fundoscopy in diabetic retinopathy patients: A pilot study

Aims/Purpose: To compare fundoscopy with Color fundus photography (CFP) in identifying diabetic retinopathy (DR) abnormalities.Methods: This is a pilot cross‐sectional study of diabetic patients attending the medical retina clinic for routine examination. All patients underwent dilated indirect ophthalmoscopy and CFP, both performed by the same doctor. The following retinal features were identified in 5 segments during both procedures (CA‐central area, UT‐upper temporal, LT‐lower temporal, UN‐upper nasal, LN‐lower nasal): pre‐retinal/retinal (RH)/vitreous haemorrhages, exudates (EX), intraretinal microvascular abnormalities (IRMA), venous beading (VB), vein loops (VL), cotton wool spots (CWS), retinal neovascularization (NVD/NVE) and ghost vessels (GV).Results: Thirty‐six eyes of 18 patients were included in the study. Overall, CFP recorded more retinal features in comparison with fundoscopy in most segments. In particular, in CFP: RH and VB were identified in 1 extra case but CWS was missed in 2 cases in CA. Imaging in UT segment revealed RH and CWS in 3 and 1 additional cases, respectively. RH, VB, CWS were recorded in 3, 1 and 1 extra cases in LT. RH and EX were documented in 4 and 1 additional cases respectively while CWS and GV were missed in 1 case in UN. In LN, RH and GV were identified in 2 extra cases, but NVD/NVE was missed in 1 case. The main differences were observed in the documentation of RH in all but one segment (apart from CA) as in &gt;3 cases in each segment, RH was missed in fundoscopy. Moreover, in CA, retinal features were similarly identified in both examination techniques.Conclusions: Fundoscopy is part of routine ophthalmic assessment but requires experience and adequate patient cooperation. CFP is a reliable imaging tool that can objectively document diabetic retinopathy lesions. New advances in retina imaging make CFP a promising device for DR assessment patients.

Association of Diabetic Lesions and Retinal Nonperfusion Using Widefield Multimodal Imaging

To evaluate the association of microvascular lesions on ultrawidefield (UWF) color fundus (CF) images with retinal nonperfusion (RNP) up to the midperiphery on single-capture widefield (WF) OCT angiography (OCTA) in patients with diabetic retinopathy (DR). Cross-sectional study. Seventy-five eyes of 50 patients with mild to severe nonproliferative DR (NPDR) and proliferative DR (PDR) were included in this analysis. ETDRS level and presence of predominantly peripheral lesions (PPLs) were assessed on UWF-CF images acquired with a Zeiss Clarus 700. Single-capture 65°-WF-OCTA was performed using a PlexElite prototype (Carl Zeiss Meditec, Inc.). A custom grid consisting of a central ETDRS grid extended by 2 rings reaching up to the midperiphery was overlaid to subdivide retinal areas visible on WF-OCTA en face images. Retinal nonperfusion was measured in each area and in total. Nonperfusion index (NPI) was calculated from total RNP. On UWF-CF images, the number of microaneurysms, hemorrhages, neovascularizations, and areas with intraretinal microvascular abnormalities (IRMAs) were evaluated using the same grid. Association of diabetic lesions with RNP was calculated using Spearman correlations (rs). Median RNP on WF-OCTA was 0 mm2 (0-0.9), 4.9 mm2 (1.9-5.4), 23.4 mm2 (17.8-37), and 68.4 mm2 (40.8-91.7) in mild, moderate, and severe NPDR and PDR, respectively. We found a statistically significant correlation (P < 0.01) of overall RNP (rs= 0.96,) and NPI (rs= 0.97) on WF-OCTA with ETDRS level. Number of grid-fields affected by IRMAs on CF images was highly associated with NPI (rs= 0.86, P < 0.01). Intraretinal microvascular abnormalities and RNPs had similar topographic distributions with high correlations in affected areas. Eyes with PPLs (n= 43 eyes, 57%) on CF images had a significantly higher NPI (P= 0.014) than eyes without PPLs. The combination of UWF-CF imaging and single-capture WF-OCTA allows precise and noninvasive analysis of the retinal vasculature up to the midperiphery in patients with DR. The presence and extent of IRMAs on CF images may serve as an indicator for underlying RNP, which is more pronounced in eyes with PPLs. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Association of Neovascularization With Optical Coherence Tomography Angiography Parameters in Proliferative Diabetic Retinopathy.

We aim to find an association between neovascularization (NVn) and optical coherence tomography angiography (OCTA) parameters in proliferative diabetic retinopathy (PDR). In a prospective study, 41 subjects including 28 (68%) males and 13 (32%) femaleshaving PDR were examined for neovascularization disc (NVD) and neovascularization elsewhere (NVE) clinically and with fundus fluorescein angiography (FFA). A total of 79 eyes were found to be involved. We examined OCTA parameters including foveal avascular zone (FAZ) size, perimeter and circularity, and vessel density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR), outer retinal chorio-capillaries (ORCC), chorio-capillaries (CC), and choroid (C) in these subjects. In eyes with NVD, the central foveal thickness (CFT) (p=0.83) and sub-foveal choroidal thickness (SFCT) (p=0.08) were higher, the FAZ area was significantly larger (p=0.005), and the VD was lower in all retino-choroidal layers. However, it was significantly lower in SCP foveal (p=0.005) and ORCC foveal (p=0.05) than in eyes not having NVD. For NVE, the CFT (p=0.03) and SFCT (p=0.01) were more in affected eyes. The eyes without NVE had a better circularity index (p=0.07) and the highest VD in OR slab (p=0.02) than those eyes that had NVE < ½ disc area (DA) and NVE > ½ DA. On comparing eyes without NVE, NVE < ½ DA, and NVE > ½ DA, the latest had the highest VD in SCP (p=0.59) and lowest VD in DCP (p=0.43) and OR (p=0.02). The VD in ORCC, CC, and choroid was highest in the no NVE group, followed by the NVE > ½ DA and NVE < ½ DA groups in that order. The subjects having vitreous hemorrhage (VH) and intra-retinal microvascular abnormalities (IRMA) had higher values for CFT and SFCT than eyes without these. An increased CFT and SFCT are associated with the appearance of NVD, NVE, VH, and IRMA. The presence of NVD, VH, and IRMA is associated with a larger FAZ area, while that of IRMA and NVE is associated with reduced FAZ circularity. Eyes with NVD, VH, and IRMA had lesser VD in all the retino-choroidal layers. Eyes with NVE > ½ DA had the highest VD in SCP and lowest in DCP and OR; this pattern of VD foretells severer affection in NVE. IRMA was associated with a larger FAZ area, larger FAZ perimeter, and lesser circularity, indicating the presence of central ischemia.

Optical Coherence Tomography Angiography of Volumetric Arteriovenous Relationships in the Healthy Macula and Their Derangement in Disease.

To characterize relative arteriovenous connectivity of the healthy macula imaged by optical coherence tomography angiography (OCTA) using a new volumetric tool. OCTA volumes were obtained for 20 healthy controls (20 eyes). Two graders identified superficial arterioles and venules. We implemented a custom watershed algorithm to identify capillaries most closely connected to arterioles and venules by using the large vessels as seeds to flood the vascular network. We calculated ratios of arteriolar- to venular-connected capillaries (A/V ratios) and adjusted flow indices (AFIs) for superficial capillary plexuses (SCPs), middle capillary plexuses (MCPs), and deep capillary plexuses (DCPs). We also analyzed two eyes with proliferative diabetic retinopathy (PDR) and one eye with macular telangiectasia (MacTel) to evaluate the utility of this method in visualizing pathological vascular connectivity. In healthy eyes, the MCP showed a greater proportion of arteriolar-connected vessels than the SCP and DCP (all P < 0.001). In the SCP, the arteriolar-connected AFI exceeded the venular-connected AFI, but this pattern reversed in the MCP and DCP, with higher venular-connected AFI (all P < 0.001). In PDR eyes, preretinal neovascularization originated from venules, whereas intraretinal microvascular abnormalities were heterogeneous, with some originating from venules and others representing dilated MCP capillary loops. In MacTel, diving SCP venules formed the epicenter of the outer retinal anomalous vascular network. Healthy eyes showed a higher MCP A/V ratio but relatively slower arteriolar vs. venular flow velocity in the MCP and DCP, which may explain deep retinal vulnerability to ischemia. In eyes with complex vascular pathology, our connectivity findings were consistent with histopathologic studies.

Intraretinal Microvascular Abnormalities and Venous Beading Have Different Genetic Profiles in Caucasian Patients with Non-Proliferative Diabetic Retinopathy

Diabetic Retinopathy (DR) is a leading cause of preventable visual impairment in the working age population. Despite the increasing prevalence of DR, there remain gaps in our understanding of its pathophysiology. This is a prospective case-control study comparing the genetic profiles of patients with no DR vs. non-proliferative DR (NPDR) focusing on intraretinal microvascular abnormalities (IRMA) and venous beading (VB) in Caucasians. A total of 596 participants were recruited to the study; 199 with moderate/severe NPDR and 397 with diabetes for at least 5 years without DR. Sixty-four patients were excluded due to technical issues. In total, 532 were analysed; 181 and 351 were in the NPDR group and no DR group, respectively. Those with severe IRMA and VB had distinctly different genetic profiles from each other and from the no DR group, which further supports the theory that these two features of DR might have different etiologies. This also suggests that IRMA and VB are independent risk factors for the development of PDR and may have different pathophysiologies. If these findings are confirmed in larger studies, this could pave the way for personalised treatment options for those more at risk of developing different features of NPDR.

Relationship between Glycosylated Haemoglobin Levels and Macular Thickness on Optical Coherence Tomography in Type 2 Diabetic Patients: A Cross-sectional Study

Introduction: Diabetic Macular Oedema (ME) is the main cause of poor visual acuity due to the breakdown of the inner and/or outer Blood Retinal Barrier (BRB). This can occur at any stage of Diabetic Retinopathy (DR) due to increased vascular permeability from retinal capillaries, as well as from microaneurysms and Intraretinal Microvascular Abnormalities (IRMAs). A high level of Glycosylated Haemoglobin (HbA1c) is a well known risk factor for diabetic ME. Aim: To evaluate the relationship between glycosylated Haemoglobin (Hb) and macular thickness on Optical Coherence Tomography (OCT) in patients with Type 2 Diabetes Mellitus (T2DM). Materials and Methods: A cross-sectional study was in the Department of Ophthalmology at RL Jalappa Hospital, Kolar, Karnataka, India. The study duration was one year and eight months, conducted from January 2021 to September 2022. A total of 162 eyes of 81 patients with Diabetes Mellitus (DM) were included. Patients were assessed for age, gender, duration of diabetes, subfield macular thickness, total macular volume as measured by Optical Coherence Tomography (OCT), and HbA1c levels. Pearson’s correlation and paired t-test were used to identify the mean difference between paired data. A p-value &lt;0.05 was considered statistically significant. Results: Out of 81 patients, 52 (64.2%) were males and 29 (35.8%) were females, with a mean age of 59.36±8.98 years (range 40-81 years) and a duration of diabetes of 14.61±4.2 years. The mean HbA1c level was 8.18±1.47% (range 5.5-12.1). A significant positive correlation was observed between central subfield thickness and total macular volume with HbA1c among both eyes (p-value=0.001). This correlation was more prominent in patients with HbA1c values &gt;8% compared to those with HbA1c values &lt;8% (p-value=0.001). Additionally, a positive correlation was observed between duration of diabetes and right central macular thickness (p-value=0.046) and HbA1c levels (p-value=0.027). Age did not have a major influence on central subfield thickness and total macular volume, but it did show a positive Pearson’s correlation with HbA1c levels (p-value=0.008). Conclusion: A significant positive correlation was observed between central subfield thickness and total macular volume in both eyes with HbA1c levels. Patients with HbA1c levels &gt;8% and a longer duration of diabetes exhibited increased macular thickness and total macular volume as measured by OCT, which was also observed in patients with severe non proliferative DR and proliferative DR.

A Comprehensive Review of Diabetic Retinopathy and Diabetic Macular Edema from an Ayurveda Point of View

Introduction: Diabetes and other related disorders, such as hypertension, are involved in diabetic retinopathy (DR), a chronic, progressive disease of the retinal microvasculature that threatens vision. The retinal pre-capillary arterioles, capillaries, and venules are impacted by DR. Hyperglycemia damages capillary walls, endothelial cells, retinal cells, and capillary pericytes. It also thickens the capillary basement membrane. The blood-retina barrier is broken down by microangiopathy, which can result in retinal edema, bleeding, lipid leakage (hard exudates), micro-aneurysms, hemorrhages, ischemia, and intraretinal microvascular abnormalities. Materials and Methods: Ayurveda classical texts along with the internet sources such as Google Scholar and PubMed were reviewed upon to collect the literature available as per the aims of the present article. Discussion and Conclusion: In Ayurveda, DR can be understood as Pramehajanya Timira. Due to prolonged uncontrolled hyperglycemia, two types of pathology in Madhumeha: Dhatukshayajanya and Avaranajanya play a crucial role in the development of DR. Dhatus are expelled from the body in Dhatukshaya, which leads to several pathogenic events and the development of DME. Attipravritti, Sanga, Siragranthi, and Vimarga Gamana are the four varieties of Srotodusti that are known to be important in the development of DR and macular edema.

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.

Optical coherence tomography angiography analysis of microvascular abnormalities and vessel density in treatment-naïve eyes with diabetic macular edema

BackgroundThe aim of this study was to evaluate the structural retinal vascular integrity using optical coherence tomography angiography (OCTA) in treatment-naïve eyes with diabetic macular edema (DME) and to compare it with findings in diabetic eyes without DME.MethodsIn this prospective study, 70 eyes with diabetic retinopathy were included (37 eyes with DME and 33 eyes without DME). The medical records, including swept-source optical coherence tomography and 9 × 9 mm swept-source OCTA images were reviewed and compared between DME and non-DME groups. Microaneurysms, intraretinal microvascular abnormalities (IRMA), areas of capillary non perfusion, foveal avascular zone (FAZ), and capillary vascular density (CVD) were analyzed in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP).ResultsCompared to the non-DME eyes, DME eyes had more microaneurysms in the SCP and the DCP (p = 0,039 and p = 0,024 respectively), more IRMA in the SCP (p = 0,005), larger areas of capillary non perfusion in the SCP and the DCP (p = 0,026 and p = 0,02 respectively) and larger FAZ in both plexuses (p = 0,048 in the SCP and p = 0,012 in the DCP). The CVD in the DCP was lower in DME eyes compared to non-DME eyes (p = 0,007). The severity of DME was significantly correlated to the number of microaneurysms and to the FAZ surface. Central macular thickness was significantly correlated with the number of microaneurysms in the DCP, the surface of capillary non perfusion areas and the FAZ area in both plexuses.ConclusionsOCTA with a 9 × 9 mm field of view showed that the retinal vascular integrity regarding the number of microaneurysms, the number of IRMA, the surface of capillary non perfusion areas, the FAZ area and the CVD, was significantly more impaired in DME eyes compared to diabetic eyes without DME. The DCP seemed to be more affected in diabetic eyes with and without DME than the SCP.

Automatic Detection of Abnormalities and Grading of Diabetic Retinopathy in 6-Field Retinal Images: Integration of Segmentation Into Classification.

PurposeClassification of diabetic retinopathy (DR) is traditionally based on severity grading, given by the most advanced lesion, but potentially leaving out relevant information for risk stratification. In this study, we aimed to develop a deep learning model able to individually segment seven different DR-lesions, in order to test if this would improve a subsequently developed classification model.MethodsFirst, manual segmentation of 34,075 different DR-lesions was used to construct a segmentation model, with performance subsequently compared to another retinal specialist. Second, we constructed a 5-step classification model using a data set of 31,325 expert-annotated retinal 6-field images and evaluated if performance was improved with the integration of presegmentation given by the segmentation model.ResultsThe segmentation model had higher average sensitivity across all abnormalities compared to the retinal expert (0.68 and 0.62) at a comparable average F1-score (0.60 and 0.62). Model sensitivity for microaneurysms, retinal hemorrhages and intraretinal microvascular abnormalities was higher by 42.5%, 8.8%, and 67.5% and F1-scores by 15.8%, 6.5%, and 12.5%, respectively. When presegmentation was included, grading performance increased by 29.7%, 6.0%, and 4.5% for average per class accuracy, quadratic weighted kappa, and multiclass macro area under the curve, with values of 70.4%, 0.90, and 0.92, respectively.ConclusionsThe segmentation model matched an expert in detecting retinal abnormalities, and presegmentation substantially improved accuracy of the automated classification model.Translational RelevancePresegmentation may yield more accurate automated DR grading models and increase interpretability and trust in model decisions.

Inhibition of Drp1 ameliorates diabetic retinopathy by regulating mitochondrial homeostasis

Diabetic retinopathy (DR) is a potentially blinding complication resulting from diabetes mellitus (DM). Retinal vascular endothelial cells (RMECs) dysfunction occupies an important position in the pathogenesis of DR, and mitochondrial disorders play a vital role in RMECs dysfunction. However, the detailed mechanisms underlying DR-induced mitochondrial disorders in RMECs remain elusive. In the present study, we used High glucose (HG)-induced RMECs in vitro and streptozotocin (STZ)-induced Sprague-Dawley rats in vivo to explore the related mechanisms. We found that HG-induced mitochondrial dysfunction via mitochondrial Dynamin-related protein 1(Drp1)-mediated mitochondrial fission. Drp1 inhibitor, Mdivi-1, rescued HG-induced mitochondrial dysfunction. Protein Kinase Cδ (PKCδ) could induce phosphorylation of Drp1, and we found that HG induced phosphorylation of PKCδ. PKCδ inhibitor (Go 6983) or PKCδ siRNA reversed HG-induced phosphorylation of Drp1 and further mitochondrial dysfunction. The above studies indicated that HG increases mitochondrial fission via promoting PKCδ/Drp1 signaling. Drp1 induces excessive mitochondrial fission and produces damaged mitochondrial, and mitophagy plays a key role in clearing damaged mitochondrial. Our study showed that HG suppressed mitophagy via inhibiting LC3B-II formation and p62 degradation. 3-MA (autophagy inhibitor) aggravated HG-induced RMECs damage, while rapamycin (autophagy agonist) rescued the above phenomenon. Further studies were identified that HG inhibited mitophagy by down-regulation of the PINK1/Parkin signaling pathway, and PINK1 siRNA aggravated HG-induced RMECs damage. Further in-depth study, we propose that Drp1 promotion of Hexokinase II (HK-II) separation from mitochondria, thus inhibiting HK-II-PINK1-mediated mitophagy. In vivo, we found that intraretinal microvascular abnormalities (IRMA), including retinal vascular leakage, acellular capillaries, and apoptosis were increased in STZ-induced DR rats, which were reversed by pretreatment with Mdivi-1 or Rapamycin. Altogether, our findings provide new insight into the mechanisms underlying the regulation of mitochondrial homeostasis and provide a potential treatment strategy for Diabetic retinopathy.

Recommendations for OCT Angiography Reporting in Retinal Vascular Disease: A Delphi Approach by International Experts

Purpose:To develop a consensus nomenclature for reporting OCT angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts.Design:Delphi-based survey.Subjects, Participants, and/or Controls:Twenty-five retinal vascular disease and OCTA imaging experts.Methods, Intervention, or Testing:A Delphi method of consensus development was used, comprising 2 rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The 4 main areas of consensus were: definition of the parameters of “wide-field (WF)” OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study end point was defined by the degree of consensus for each question: “strong consensus” was defined as ≥85% agreement, “consensus” as 80% to 84%, and “near consensus” as 70% to 79%.Main Outcome Measures:Consensus and near consensus on OCTA nomenclature in retinal vascular disease.Results:A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a “large area” of WF-OCTA reduced flow signal should also be defined as ≥30% of the absolute imaged area. The presence of new vessels and intraretinal microvascular abnormalities, the foveal avascular zone parameters, the presence and amount of “no-flow areas,” and the assessment of vessel density in various retinal layers should be added for the staging and classification of diabetic retinopathy. Decreased flow ≥30% of the absolute imaged area should define an ischemic central retinal vein occlusion. Several other items did not meet consensus requirements or were rejected in the final discussion round.Conclusions:This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions.

Comparison of fundus fluorescein angiography and fundus photography grading criteria for early diabetic retinopathy.

To compare the assessment outcomes of the characteristics of mild to moderate non-proliferative diabetic retinopathy (NPDR) established by fundus photography and fundus fluorescein angiography (FFA). The fundus photos and FFA results of 260 patients with diabetes mellitus were reviewed. Diabetic retinopathy (DR) severity was graded based on the international classification standard. The microaneurysms, hemorrhages, and intraretinal microvascular abnormalities (IRMA) in FFA images of patients with mild to moderate NPDR were observed. The differences between the fundus photos and the FFA results were summarized, analyzed, and compared. The counting of intraretinal hemorrhages identified by FFA revealed that only 9 eyes (1.9%) had more than 20 intraretinal hemorrhages in all four quadrants; 15 eyes (3.1%) had more than 20 intraretinal hemorrhages in three quadrants; 26 eyes (5.4%) had over 20 intraretinal hemorrhages in two quadrants; and 37 eyes (7.7%) had more than 20 intraretinal hemorrhages in only one quadrant. Furthermore, the number of IRMAs appeared ≥4 in 17 eyes, 3 in 35 eyes, 2 in 69 eyes, and 1 in 93 eyes. FFA has higher detection accuracy of retinal angiopathy than fundus photography. FFA grading results are helpful for timely detection and proper treatment of lesions easily missed by fundus photography.