Retinal Ischemic Perivascular Lesions are Associated with Multifactorial Disease Burden and Severity of Diabetic Retinopathy.

Studies have not yet determined whether the distribution of lesions in the retinal periphery alters the association between the severity of diabetic retinopathy (DR) and macular vessel density. To evaluate the association of DR lesion distribution with optical coherence tomography angiography (OCTA) metrics and DR severity. This cross-sectional observational study was conducted at a tertiary care center for diabetic eye disease among 225 patients with type 1 or 2 diabetes who had undergone imaging between February 15, 2016, and December 31, 2019. Optical coherence tomography angiography 3 × 3-mm macular scans and ultra-widefield color imaging. Optical coherence tomography angiography vessel density in the superficial capillary plexus, intermediate capillary plexus, and deep capillary plexus and choriocapillaris flow density. The severity of DR and the predominantly peripheral lesions (PPL) were evaluated from ultra-widefield color imaging. The study evaluated 352 eyes (225 patients; 125 men [55.6%]; mean [SD] age, 52.1 [15.1] years), of which 183 eyes (52.0%) had mild nonproliferative diabetic retinopathy (NPDR), 71 eyes (20.2%) had moderate NPDR, and 98 eyes (27.8%) had severe NPDR or proliferative diabetic retinopathy (PDR). In eyes with no PPL (209 [59.4%]), the mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 38.1% [4.7%]; moderate NPDR, 36.4% [4.6%]; severe NPDR or PDR, 34.1% [4.1%]; P < .001) and the deep capillary plexus (mild NPDR, 45.8% [3.0%]; moderate NPDR, 45.8% [2.2%]; severe NPDR or PDR, 44.5% [1.9%]; P = .002), as well as the mean (SD) choriocapillaris flow density (mild NPDR, 69.7% [6.2%]; moderate NPDR, 67.6% [5.6%]; severe NPDR or PDR, 67.1% [5.6%]; P = .01), decreased with increasing DR severity. These associations remained statistically significant even after correcting for age, signal strength index, spherical equivalent, duration of diabetes, type of diabetes, and correlation between eyes of the same patient. In eyes with PPL (143 [40.6%]), mean (SD) vessel density in the superficial capillary plexus (mild NPDR, 34.1% [4.1%]; moderate NPDR, 35.2% [4.1%]; severe NPDR or PDR, 36.0% [4.3%]; P = .42) and the deep capillary plexus (mild NPDR, 44.5% [1.7%]; moderate NPDR, 45.4% [1.4%]; severe NPDR or PDR, 44.9% [1.5%]; P = .81), as well as the mean (SD) choriocapillaris flow density (mild NPDR, 67.1% [5.6%]; moderate NPDR, 69.3% [4.6%]; severe NPDR or PDR, 68.3% [5.6%]; P = .49), did not appear to change with increasing DR severity. These results suggest that central retinal vessel density is associated with DR severity in eyes without, but not with, PPL. These findings suggest a potential need to stratify future optical coherence tomography angiography studies of eyes with DR by the presence or absence of PPL. If DR onset and worsening are associated with the location of retinal nonperfusion, assessment of global retinal nonperfusion using widefield angiography may improve the ability to evaluate DR severity and risk of DR worsening over time.

Toward an Era of Oculomics: Association between Baseline Diabetic Retinopathy Severity and Mortality Risk in a SOURCE Consortium Cohort.

Objective: To assess the effect of diabetic retinopathy (DR) on vision-related quality of life (VRQoL) in patients with type 2 diabetes. Methods: In this cross-sectional study, patients with type 2 diabetes residing in 15 residency communities in Fushun, Liaoning province were enrolled from July 2012 to May 2013. We measured the VRQoL by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). Patients were grouped according to their age, gender, presence of visual impairment, and affected eyes. NEI-VFQ-25 scores were compared between/among groups using the Wilcoxon rank-sum test or Kruskal-Wallis H test. The severity of DR in the eyes was graded into no DR, mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR). Severity scores from both eyes were then summarized to create a single per-person grade ranging from 1 (no DR in either eye) to 7 (bilateral PDR). Generalized linear models were used to assess the linear relationship between NEI-VFQ-25 scores and DR severity. Locally weighted scatterplot smoothing plots were generated to evaluate the possible nonlinear associations between concatenated severity of DR and VRQoL. Results: A total of 1 537 patients were recruited, including 836 (54.4%) with no DR, 479 (31.2%) with mild NPDR, 90 (5.9%) with moderate NPDR, 72 (4.7%) with severe NPDR and 60 (3.9%) with PDR. Compared with patients with unilateral DR, bilaterally involved subjects were statistically significantly compromised in general vision [70.2 (66.5, 72.5) vs. 68.9 (63.9, 71.6), Z=90.222, P=0.038], near activities [90.5 (85.8, 94.0) vs. 88.8 (84.5, 92.5), Z=114.942, P=0.005], dependency [91.1 (85.6, 96.5) vs. 89.3 (83.8, 94.5), Z=91.934, P=0.033], mental health [80.0 (73.4, 84.9) vs. 77.5 (70.8, 82.0), Z=118.388, P=0.003], role difficulties [76.8 (70.1, 82.4) vs. 74.5 (67.6, 80.6), Z =90.791, P=0.036] and NEI-VFQ-25 composite [88.3 (84.2, 91.0) vs. 86.9 (82.8, 90.1), Z=96.207, P=0.024]. Scores on general vision (χ2=85.665), near activities (χ2=78.462), distance activities (χ2=145.489), social function (χ2=53.629), dependency (χ2=86.710), mental health (χ2=68.281), role difficulties (χ2=45.357), color vision (χ2=68.176), peripheral vision (χ2=116.179) and NEI-VFQ-25 composite (χ2=133.291) decreased gradually as DR severity increased (all P<0.001). On role difficulties, locally weighted scatterplot smoothing plots showed significant"turning points"from bilateral mild NPDR to mild NPDR/>mild NPDR (slope m=-4.7) and from moderate NPDR/≥moderate NPDR to severe NPDR/≥severe NPDR (slope m=-12.6). Conclusion: Both greater severity and bilaterality of DR were associated with lower vision-specific VRQoL, particularly role difficulties and mental health.

Classification of Diabetic Retinopathy Severity with Aqueous VEGF Levels: A Prospective, Observational Study

Ultra-Widefield Protocol Enhances Automated Classification of Diabetic Retinopathy Severity with OCT Angiography

Clinically Significant Nonperfusion Areas on Widefield OCT Angiography in Diabetic Retinopathy

To explore the association of choroidal thickness variations in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) at different stages. A total of 161 patients with T2DM were included in this study, from October 2012 to June 2014. According to Early Treatment Diabetic Retinopathy Study (ETDRS) criteria, the patients were divided into 5 groups: non-DR without diabetic macular edema (DME) group(DR-/DME- group, 45 eyes), nonproliferative diabetic retinopathy (NPDR) without DME group(NPDR+/DME- group, 58 eyes), proliferative diabetic retinopathy (PDR) without DME group (PDR+/DME- group, 12 eyes), NPDR with DME group (NPDR+/DME+ group, 41 eyes), PDR with DME group (PDR+/DME+ group, 5 eyes). Meanwhile, 60 normal subjects were enrolled as the control group. All study subjects received optical coherence tomography enhanced depth imaging (EDI-OCT) examination to detect and compare subfoveal choroidal thickness at different stages of DR. Mean SFCT was (271 ± 36), (270 ± 35), (262 ± 38), (244 ± 36), (229 ± 35) µm respectively in control, DR-/DME-, NPDR+/DME-, PDR+/DME-, NPDR+/DME+ groups. The SFCTs of PDR+/DME- and NPDR+/DME+ group were statistically lower than that of control group (P=0.004, P=0.001). The SFCT of PDR+/DME- group was lower than that of DR-/DME- group (P=0.003), and there was also a significant difference of SFCT between NPDR+/DME+ and NPDR+/DME- group (P=0.001). There was linear correlation between SFCT and the logMAR best-corrected visual acuity (r=0.397, P<0.01), but the SFCT was independent of diabetic duration, fasting blood glucose, HbA1c, axial length, diastolic blood pressure (DBP) and systolic blood pressure SBP (r=-0.024, 0.159, 0.089, 0.036, 0.143, 0.057, all P>0.05). There was no significant difference of SFCT among different DME types (F=0.071, P>0.05). The SFCT decreased with increasing severity of DR. To monitor the SFCT in T2DM patients may be helpful to evaluate the severity of DR and provide a new treatment conception.

PurposeEstimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered.Patients and MethodsThis model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data. Changes in DR severity after 2 years, with/without monthly ranibizumab (0.3 or 0.5 mg), were estimated from Phase III clinical trial data (RIDE/RISE) using a 2-dimensional Monte Carlo simulation model. Number of patients over a 2-year period for whom 1) DR severity worsening was avoided, 2) DR severity improved, and 3) selected clinical events related to proliferative DR (PDR) occurred, was estimated.ResultsAn estimated 37,274 US Hispanic and non-Hispanic white persons were projected to have DR with center-involved DME and be eligible for ranibizumab treatment. The number of persons with moderately severe non-proliferative DR (NPDR) or less severe DR at baseline who would worsen to PDR and experience a PDR complication over 2 years would be reduced from 437 with no ranibizumab to 19 with ranibizumab (95% reduction; 95% simulation interval [SI], 79–100%). The number of persons with severe NPDR or less severe DR at baseline who would be expected to improve by ≥2 DR severity levels over 2 years would increase from 1706 with no ranibizumab to 13,042 with ranibizumab (682% increase; 95% SI, 478–967%).ConclusionThis model estimates that ranibizumab treatment in US Hispanic and non-Hispanic white patients with center-involved DME causing vision impairment would potentially reduce the number of patients with worsening DR and potentially increase the number with DR improvements.

PurposeThe purpose of this study was to evaluate differences in optical coherence tomography angiography (OCTA) metrics in the superficial (SCP), intermediate (ICP), and deep (DCP) vascular plexuses across diabetic retinopathy (DR) severity levels.MethodsThis was a cross sectional observational retrospective chart review study. Eligible patients with diabetes who underwent same day RTVue XR Avanti OCTA, spectral-domain optical coherence tomography (SD-OCT), and 200-degree Optos ultrawide field color imaging. SCP, ICP, and DCP vessel density (VD) and vessel length density (VLD) were assessed using 3-D projection artifact removal software (PAROCTA) software.ResultsOf 396 eyes (237 patients), 16.1% had no DR, 26.9% mild nonproliferative DR (NPDR), 21.1% moderate NPDR, 12.1% severe NPDR, 10.1% proliferative DR (PDR) without panretinal photocoagulation (PRP), and 13.4% PDR with PRP. When comparing mild NPDR to no DR eyes, ICP and DCP VD and VLD were significantly lower, but there was no difference for SCP metrics. In eyes with more severe DR, there were significant differences in SCP VD and VLD between DR severity levels (mild versus moderate NPDR: VD 35.45 ± 3.31 vs. 34.14 ± 3.38, P = 0.008 and VLD 17.59 ± 1.83 vs. 16.80 ± 1.83, P = 0.003; moderate versus severe NPDR: VLD 16.80 ± 1.83 vs. 15.79 ± 1.84, P = 0.019), but no significant differences in ICP or DCP.ConclusionsAlthough VD of each of the three individual layers decreases with increasing DR severity, DR severity has a substantially different effect on OCTA parameters within each layer. Vascular changes in eyes with no to early DR were present primarily in the deeper vascular layers, whereas in eyes with advanced DR the opposite was observed. This study highlights the effects of ICP and the importance of assessing SCP and DCP changes independently across each DR severity level.

Introduction: Diabetic retinopathy (DR) remains a visually debilitating disease and is commonly classified according to its severity as non-proliferative DR (NPDR) or proliferative DR (PDR). Those suffering from PDR tend to have worse vascular complications and prognosis. Platelets exposed by vasculopathy caused by DR maybe activated to try to maintain haemostasis. This activity can be illustrated by the mean platelet component (MPC). Therefore, by MPC monitoring we may be able to predict the progression from NPDR into PDR.Purpose: To investigate the difference of MPC in patients with NPDR and PDR.Study design: Cross-sectional.Materials and methods: This study involved 71 DR patients. Preliminary data regarding the patients’ demographic characteristics, diabetes history, related diseases, medication history, and general eye examination were recorded. Fundus photographs were taken after dilating eyedrops and DR was graded by an ophthalmologist. The patients were grouped into NPDR and PDR. Mean platelet component was analyzed using the automatic hematology analyzer ADVIA 120.Results: Mean platelet component (MPC) was 26.69 g/dl (± 1.79) and 25.52 g/dl (± 1.20) in the NPDR and PDR group, respectively (p = 0.002), but was not clinically significant. In depth analysis into the DR grades differed significantly between mild NPDR and high-risk PDR (p = 0.015), and moderate NPDR and high-risk PDR (p = 0.024). Using our definition of mild DR (mild and moderate NPDR) and severe DR (high-risk and advanced PDR), there was a significant difference with mean MPC of 27.01 g/dl (± 1.64) and 25.31 g/dl (± 1.22), respectively (p = 0.001). The proportion of activated platelets was also higher in severe DR. Negative correlations were found between MPC with duration of DM (r = -0.333; p = 0.004) and MPC with systolic blood pressure (r = -0.241; p = 0.043).Conclusion: There was a significant difference in MPC between NPDR and PDR, but the results should be interpreted carefully. Further analysis between the mild and severe form of DR strengthened this finding.

PurposeOsteopontin (OPN) is a proinflammatory cytokine with diverse functions. Increased levels of OPN in vitreous fluid have been reported in patients with diabetic retinopathy (DR); however, studies on circulating OPN levels in DR are limited. We aim to examine the association of plasma OPN levels with the presence and severity of DR in a multiethnic cohort with type 2 diabetes mellitus (type 2 diabetes) in Singapore.MethodsPlasma levels of OPN were measured using enzyme-linked immunosorbent assay. Digital color fundus photographs were assessed for DR. DR severity was categorized into non-proliferative DR (NPDR) and proliferative DR (PDR). Gradable fundus photographs and OPN measurements for 443 patients were used for analysis. A logistic regression model was used to evaluate the association of OPN with DR.ResultsDR was diagnosed in 174 (39.3%) patients, including 132 (75.9%) with NPDR and 42 (24.1%) with PDR. The median of OPN was higher in the patients with DR (64.7 [49.7–89.5] ng/ml) than in the patients without DR (51.7 [38.9–66.9] ng/ml; p<0.001). After adjustment for clinical and biochemical factors, a 1-unit increase in nature logarithm (ln)-transformed OPN was associated with the presence of DR (2.770 [1.599–3.800], p<0.001). The area under the curve (AUC) increased statistically significantly after the addition of OPN (0.805[0.763–0.846] versus 0.825 [0.785–0.865], p=0.011). In the severity analyses, the median of OPN was statistically significantly higher in the patients with PDR (76.8 [55.0–103.6] ng/ml) than in the patients with NPDR (61.7 [47.7–87.3] ng/ml; p=0.017). After adjustment, the 1-unit increase in lnOPN remained associated with NPDR (2.673 [1.519–4.704], p=0.001) and PDR (3.389 [1.254–9.226], p=0.017), respectively (p-trend=0.001).ConclusionsPlasma OPN levels were associated with the presence and severity of DR in patients with type 2 diabetes, suggesting OPN may be useful as a potential biomarker for DR.

The Association Between Diabetic Retinopathy Severity and Dementia Risk: A TriNetX Longitudinal Cohort Study.

Diabetic Retinopathy Severity and Peripheral Lesions Are Associated with Nonperfusion on Ultrawide Field Angiography

The aim of this study was to assess the impact of diabetic retinopathy (DR) severity on the risk of DR progression to proliferative DR (PDR) or clinically significant macular edema (CSME) in patients with diabetes mellitus (DM). This is a prospective, longitudinal, non-interventional, and observational cohort study of patients with DM in the United States based on a database of 7-field color fundus photograph images from primary care visits. Study participants were adults aged ≥ 18 years who underwent DR screening in either eye between January 1999 and December 2016. DR severity was graded according to the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) on 7-field color fundus photographs. The main outcomes were ≥ 2-step DR worsening and development of CSME, PDR, or CSME and PDR together. For all 41,977 eyes evaluated, the proportion of eyes with ≥ 2-step DR worsening was 2.7% at year 2 and 9.6% at year 5. Rate of ≥ 2-step DR worsening was greatest among eyes with moderate-to-severe NPDR with baseline DRSS 43-53 (36.5% at year 5). Analysis of PDR and CSME outcomes showed the presence of 3 distinct clinical phenotypes: 1 subset progressed to CSME (1.24% at year 5), another to PDR (0.49% at year 5), and only a small subset progressed to both vision-threatening forms of DR (0.10% at year 5). The clinical phenotype did not appear to be dependent on baseline DRSS. Overall, the risk of progression to vision-threatening forms of DR was more pronounced in eyes with moderate-to-severe non-proliferative DR at baseline. In addition, we found that distinct DR clinical subtypes progressing to either PDR and/or CSME over a 5-year period are not driven by baseline DR severity, suggesting other factors may contribute.

To analyze the potential role of serum and urinary mindin as biomarkers for diabetic retinopathy (DR) severity in patients with type 2 diabetes mellitus (DM). This prospective, cross-sectional study included 101 participants allocated into four groups: DM without DR (n = 26), DM with non-proliferative DR (n = 25), DM with proliferative DR (n = 25), and non-diabetic healthy controls (n = 25). Serum and 24-hour urinary mindin levels were compared among the groups. Serum mindin levels were significantly lower in Group 3 than in Group 1 and Group 2 (p < 0.001 and p = 0.001, respectively). Twenty-four-hour urinary mindin levels were significantly higher in the diabetic groups (Groups 1, 2, and 3) compared to the non-diabetic control group (p = 0.046 for Group 1, p < 0.001 for Groups 2 and 3). Correlation analysis revealed positive correlations between 24-hour urinary mindin levels and DR severity, HbA1c, proteinuria, and insulin use. Multivariate logistic regression analysis established HbA1c, urinary mindin level, and proteinuria as independent determinants of DR. Conversely, the serum mindin level was not a significant predictor of DR. Twenty-four-hour urinary mindin levels were significantly higher in patients with type 2 DM than in non-diabetic healthy controls. Furthermore, urinary mindin levels increased in correlation with DR severity. In contrast, serum mindin levels were not associated with DR according to multivariate analysis.