Severe Non-proliferative Diabetic Retinopathy Research Articles

Intraretinal Hyper-Reflective Foci Are Almost Universally Present and Co-Localize With Intraretinal Fluid in Diabetic Macular Edema.

In diabetic macular edema (DME), hyper-reflective foci (HRF) has been linked to disease severity and progression. Using an automated approach, we aimed to investigate the baseline distribution of HRF in DME and their co-localization with cystoid intraretinal fluid (IRF). Baseline spectral-domain optical coherence tomography (SD-OCT) volume scans (N = 1527) from phase III clinical trials YOSEMITE (NCT03622580) and RHINE (NCT03622593) were segmented using a deep-learning-based algorithm (developed using B-scans from BOULEVARD NCT02699450) to detect HRF. The HRF count and volume were assessed. HRF distributions were analyzed in relation to best-corrected visual acuity (BCVA), central subfield thickness (CST), and IRF volume in quartiles, and Diabetic Retinopathy Severity Scores (DRSS) in groups. Co-localization of HRF with IRF was calculated in the central 3-mm diameter using the en face projection. HRF were present in most patients (up to 99.7%). Median (interquartile range [IQR]) HRF volume within the 3-mm diameter Early Treatment Diabetic Retinopathy Study ring was 1964.3 (3325.2) pL, and median count was 64.0 (IQR = 96.0). Median HRF volumes were greater with decreasing BCVA (nominal P = 0.0109), and increasing CST (nominal P < 0.0001), IRF (nominal P < 0.0001), and DRSS up to very severe nonproliferative diabetic retinopathy (nominal P < 0.0001). HRF co-localized with IRF in the en face projection. Using automated HRF segmentation of full SD-OCT volumes, we observed that HRF are a ubiquitous feature in DME and exhibit relationships with BCVA, CST, IRF, and DRSS, supporting a potential link to disease severity. The spatial distribution of HRF closely followed that of IRF.

A Case of Rapidly Progressive Proliferative Diabetic Retinopathy in the Setting of Severe Anorexia Nervosa

Purpose: To report a case of rapidly progressive diabetic retinopathy in the setting of admission for severe anorexia nervosa. Methods: Case report Results: A 21-year-old female with type 1 diabetes mellitus and mild nonproliferative diabetic retinopathy of both eyes was admitted for severe anorexia nervosa with a BMI of 12.5 and hemoglobin A1c of 10.6. Three months after admission, the patient reported visual complaints and was found to have severe nonproliferative diabetic retinopathy in the right eye and proliferative diabetic retinopathy with vitreous hemorrhage in the left eye. She was lost to follow-up for 4 months, then presented to clinic with bilateral proliferative diabetic retinopathy and a tractional retinal detachment of the right eye. Conclusion: There is a potential relationship between severe eating disorders and rapid worsening of diabetic retinopathy. Patients with type 1 diabetes who have acute complications due to eating disorders should be evaluated by an ophthalmologist to monitor for rapid progression of retinopathy.

Coexistence of Diabetic Retinopathy and Diabetic Foot in Patients Admitted at Indoor Facility of a Tertiary Care Center

Purpose: To determine frequency of “diabetic retinopathy (DR)” in patients admitted at a tertiary care hospital with diabetic foot. Study Design: Cross sectional study. Place and Duration of Study: HBS medical and dental college, Islamabad from November 2022 to November 2023. Methods: Sixty two patients admitted with “diabetic foot ulcer”(DFU) were included in this study. Severity of DFU was assessed using . Patients were assessed for presence of “diabetic retinopathy (DR)” as well as its severity. Data was analyzed using SPSS 22. Results: Mean age was 49.37 ± 11.02 years. There were 34 (54.84%) males and 28 (45.16%) females. Mean HbA1C% was 9.46 ± 1.11%. Mean duration of diabetes was 10.06 ± 5.53 years. Forty five percent patients had diabetic retinopathy (DR). Amongst these patients diagnosed with DR (n = 45), 6 (13.33%) had mild non-proliferative DR, 20 (44.44%) had moderate non-proliferative DR, 14 (31.11%) had severe non-proliferative DR and 5 (11.11%) had proliferative DR. According to Wagner Grade there were 32 (51.61%), patients with grade 2 DFU, 19 (30.65%) had grade 1 and 11 (17.74%) had grade 3. Coexistence of diabetic retinopathy and diabetic foot in patients admitted at indoor facility was 72.58%. Conclusion: Prevalence of “diabetic retinopathy (DR)” in patients admitted with diabetic foot was 72.58%. Presence of diabetic foot can be considered as strong predictor of presence of concomitant “diabetic retinopathy”.

Epiretinal Macrophage-like Cells on Optical Coherence Tomography: Potential Inflammatory Imaging Biomarker of Severity in Diabetic Retinopathy.

To investigate the clinical value of epiretinal macrophage-like cells (eMLC) in different stages of diabetic retinopathy (DR), including diabetic macular edema (DME). One hundred and seventy-six eyes of 176 patients, including 31 diabetes eyes without retinopathy (NDR), 24 with mild non-proliferative DR (NPDR), 37 with moderate NPDR, 32 with severe NPDR, and 52 with proliferative DR (PDR), were compared to 30 healthy controls. The optic nerve head and macular region were examined using en face optical coherence tomography (OCT) and OCT angiography. A previously described technique was employed to measure the eMLCs on the inner limiting membrane. The optic nerve head (ONH) and macular eMLC densities increased with worsening DR stage and were higher in moderate, severe NPDR and PDR, especially in eyes with DME (all adjusted p<0.01). The ONH and macular eMLC densities in the DME groups were higher than those in their corresponding non-DME groups at the same DR stage (all p<0.05). The average macular thickness was correlated with macular eMLC density (standardized β=0.661, p<0.001) in patients with diabetes. The proportion of eyes with larger and plumper eMLCs increased with worsening DR and was higher in moderate, severe NPDR, PDR and eyes with DME (p=0.018, p<0.001, p<0.001 and p<0.001 respectively). Increased density along with morphological changes of eMLCs are observed beginning with moderate NPDR, and correlate with the progression of DR, including DME.

Sight threatening diabetic retinopathy in patients with macular telangiectasia type 2

PurposeAlthough diabetes is highly prevalent in patients with macular telangiectasia type 2 (MacTel), progression to severe non-proliferative (NPDR) and proliferative diabetic retinopathy (PDR) is rarely reported. We report multimodal imaging features of sight-threatening diabetic retinopathy (STDR) in eyes with MacTel.MethodsRetrospective case series of seven participants of the MacTel Study at the Moorfields Eye Hospital NHS Foundation Trust study site and one patient from the Institute of Retina and Vitreous of Londrina, Brazil. Sight threatening diabetic retinopathy was defined as severe NPDR, PDR or diabetic macular edema.ResultsWe report imaging features of 16 eyes of eight patients (7/8, 87.5% female) with diagnoses of MacTel and type 2 diabetes mellitus with STDR. Mean (SD) age was 56 (8.3) years. Patients were followed-up for a mean time of 9.1 (4.7) years. A total of 10/16 (62.5%) eyes showed PDR and 2/16 (12.5%) eyes presented a macular epiretinal neovascularization.ConclusionsPeople with diabetes mellitus and MacTel may not be protected from STDR as previously reported. Although the two diseases rarely co-exist, regular monitoring for diabetic retinopathy progression is recommended according to baseline retinopathy severity grades in line with established international guidelines. The presence of MacTel may not modify extended screening intervals, but there is no current evidence. The limited case series in the literature support treatment for complications and should follow the standard of care for either condition. Due to dual pathology, reactivation may be difficult to diagnose on standard imaging and multimodal imaging is recommended.

N-glycosylation of disease-specific haptoglobin for the early screening of diabetic retinopathy.

Diabetic retinopathy (DR), as one of the microvascular complications of diabetes, is a leading cause of acquired vision loss. Most DR cases are detected in the advanced stage through fundoscopy, making molecular biomarkers urgently needed for early diagnosis of DR. Serum disease-specific haptoglobin-β (Hp-β) chains of 100 patients with type 2 diabetes mellitus (T2DM) and 156 T2DM patients with non-proliferative diabetic retinopathy (NPDR) were separated using polyacrylamide gel electrophoresis. After in-gel digestion and enrichment, the intact N-glycopeptides were detected by mass spectrometry. Fucosylation of Hp-β was significantly increased and sialylation of Hp-β was significantly decreased in background DR (BDR, an early-stage DR) patients compared with non-diabetic retinopathy patients (p<0.05) and yielded area under curves (AUCs) of 0.801 and 0.829 in training and validation groups, respectively, which had an advantage over glycated hemoglobin A1c (AUC ≤ 0.691). Moreover, a significant increase in sialylated Hp-β was found in severe NPDR patients compared with BDR patients and yielded an AUC of 0.828 to distinguish severe NPDR from BDR. Changes in Hp-β glycosylation are closely related to DR, and may be used for early diagnosis and screening of DR.

Inner retinal oxygen delivery and metabolism in progressive stages of diabetic retinopathy

Previous studies have reported increased retinal venous oxygen saturation and decreased retinal blood flow and oxygen metabolism in non-proliferative diabetic retinopathy (NPDR). The current study aimed to determine alterations in both inner retinal oxygen delivery (DO2) and metabolism (MO2) in proliferative DR (PDR) as well as at stages of NPDR. A total of 123 subjects participated in the study and were categorized into five groups: non-diabetic control (N = 32), diabetic with no diabetic retinopathy (NDR, N = 34), mild NPDR (N = 31), moderate to severe NPDR (N = 17), or PDR (N = 9). Multi-modal imaging was performed to measure oxygen saturation and blood flow, which were used for derivation of DO2 and MO2. There were significant associations of groups with DO2 and MO2. DO2 was lower in PDR and not significantly different in NDR and NPDR stages as compared to the non-diabetic control group. MO2 was decreased in PDR and moderate to severe NPDR as compared to the control group, and not significantly reduced in NDR and mild NPDR. The findings demonstrate reductions in both DO2 and MO2 in PDR and MO2 in moderate to severe NPDR, suggesting their potential as biomarkers for monitoring progression and treatment of DR.

Diabetic retinopathy screening using MII Ret Cam assisted smartphone-based fundus imaging

BackgroundDiabetes Mellitus is a tremendous health implication and is proposed to be the seventh leading cause of death in 2030 by WHO. Diabetic retinopathy is one of the top complications of diabetes leading to preventable blindness. This investigation highlights the importance of timely screening and counseling using MII Ret cCam-assisted smartphone-based fundus imaging. Our study is a boon for bed-ridden and seriously ill patients who could not be evaluated on a fundus camera. MethodsThis is an observational prospective study conducted at the Ophthalmology unit, wards, and intensive care unit (ICU) of a single tertiary teaching hospital between 1 May to 31 November 2022. A total of 268 subjects with diabetes were included. The fundus of all the diabetic patients during the study period were examined by a single-trained ophthalmologist. Those diagnosed with diabetic retinopathy were taken for acquisition of fundus picture with MII Ret Cam. Images were captured using Apple iPhone 5s and 20D mounted in MII Ret Cam device. ResultsOut of 268 subjects (536 eyes) screened during the study period,86 patients (154 eyes) were found to have DR. Maleto Female ratio was 1.4:1. The mean age was 56.37 ± 15.26 years and the mean duration of diabetes was 10.60 ± 6.97 years. Grading of DR revealed proliferative diabetic retinopathy (PDR) to be the topmost (n=84 eyes, 54.5%), followed by mild non-proliferative diabetic retinopathy (NPDR) in 26 eyes (16%) and moderate NPDR in 24 eyes (15%) while severe NPDR was seen in 10 eyes (6.5%) and very severe NPDR was found in 8 eyes (5.2%) and diabetic papillopathy in 2 eyes. Grading of vitreous hemorrhage revealed Grade 1 in one eye (1.8%); Grade 2 in 19 eyes (34.54%); Grade 3 in 33 eyes (60%) and Grade 4 in 2 eyes (3.63%). Grading of macular edema according to the distribution of hard exudates as Grade 1(No Clinically significant macular edema) in 33 eyes (34.37%) and Grade 2 (Clinically significant macular edema) in 63 eyes (65.62%). The duration of diabetes had a direct association with the occurrence of DR, 13patients (15.1%) had a duration of diabetes less than five years; 31patients(36%) had a duration of diabetes between 6 years to 10 years; 28 patients (32.6%) had a duration between 11 years to 20 years. 14 patients (16.3%) had a duration of more than twenty years. The Mean duration of diabetes in Group I was 11.40+/- 7.09 years and was 9.10+/- 6.48 in Group II. The mean HbA1c in Group I is 7.44+/- 1.24 and 6.54 +/- 1.09 in Group II. The mean fasting blood sugar in Group I was 130.87 +/- 29.57 and 106.62+/- 29.85 in Group II. The mean of random blood sugar was 202.15 +/- 60.84 in Group I and 155.13 +/- 55.95 in Group II. Results are suggestive of the association of DR occurrence with fasting, random blood sugar, duration of diabetes, and HbA1c. ConclusionsDiabetic Retinopathy Screening using MII Ret Cam assisted Smartphone-based fundus imaging may be a useful device to screen for referable and vision-threatening diabetic retinopathy. MII Ret Cam is portable equipment and is easily accessible to counsel patients in resource-limited countries.

Comparison of Widefield OCT Angiography Features Between Severe Non-Proliferative and Proliferative Diabetic Retinopathy.

There is a high and ever-increasing global prevalence of diabetic retinopathy (DR) and invasive imaging techniques are often required to confirm the presence of proliferative disease. The aim of this study was to explore the images of a rapid and non-invasive technique, widefield optical coherence tomography angiography (OCT-A), to study differences between patients with severe non-proliferative and proliferative DR (PDR). We conducted an observational longitudinal study from November 2022 to March 2023. We recruited 75 patients who were classified into a proliferative group (28 patients) and severe non-proliferative group (47 patients). Classification was done by specialist clinicians who had full access to any multimodal imaging they required to be confident of their diagnosis, including fluorescein angiography. For all patients, we performed single-shot 4 × 4 and 10 × 10mm (widefield) OCT-A imaging and when possible, the multiple images required for mosaic 17.5 × 17.5mm (ultra widefield) OCT-A imaging. We assessed the frequency with which proliferative disease was identifiable solely from these OCT-A images and used custom-built MATLAB software to analyze the images and determine computerized metrics such as density and intensity of vessels, foveal avascular zone, and ischemic areas. On clinically assessing the OCT-A 10 × 10 fields, we were only able to detect new vessels in 25% of known proliferative images. Using ultra-widefield mosaic images, however, we were able to detect new vessels in 100% of PDR patients. The image analysis metrics of 4 × 4 and 10 × 10mm images did not show any significant differences between the two clinical groups. For mosaics, however, there were significant differences in the capillary density in patients with PDR compared to severe non-PDR (9.1% ± 1.9 in the PDR group versus 11.0% ± 1.9 for severe group). We also found with mosaics a significant difference in the metrics of ischemic areas; average area of ischemic zones (253,930.1 ± 108,636 for the proliferative group versus 149,104.2 ± 55,101.8 for the severe group. Our study showed a high sensitivity for detecting PDR using only ultra-widefield mosaic OCT-A imaging, compared to multimodal including fluorescein angiography imaging. It also suggests that image analysis of aspects such as ischemia levels may be useful in identifying higher risk groups as a warning sign for future conversion to neovascularization.

Incidence of Central Involving Macular Oedema After Cataract Surgery in Diabetic Retinopathy Patients – A Prospective Study

Aim: To study the incidence of central macular oedema at 4, 8 and 12 weeks following cataract surgery in diabetic retinopathy eyes. Materials and Methods: A prospective observational study was conducted over a period of 3 months to investigate the presence of centrally involved macular oedema following cataract surgery in diabetic retinopathy patients. Preoperative OCT scans were performed and patients without centrally involved macular oedema were enrolled. Subfield thickness (central, outer and inner) was measured preoperatively and at 4, 8 and 12 weeks postoperatively. The correlation between diabetic macular oedema (DME) and HbA1c, as well as random blood sugar (RBS) levels at the time of surgery, was analysed. Best.corrected visual acuity (BCVA) was assessed preoperatively and postoperatively, and fundus examinations were conducted each visit to evaluate diabetic retinopathy progression. Results: This study included 80 eyes from 44 patients. Postoperatively, central subfield thickness (CSF) increased significantly at first (14.7 μm), second (26.7 μm) and third (30.3 μm) compared to baseline. Inner subfield thickness (ISF) also increased at first (13.3 μm), second (20.6 μm) and third (24.3 μm) months, while the outer subfield thickness (OSF) showed progression from 6.7 μm to 16.6 μm from the first to third month. A statistically significant shift in DME was observed three months post.cataract surgery. There was a significant association between HbA1c levels and the development of DME, but no correlation with RBS levels. BCVA improved remarkably from preoperative mean log MAR of 0.75 to a mean log MAR of 0.1 at 3 months postoperatively. About 30% had mild non-proliferative diabetic retinopathy (NPDR) preoperatively, and in that group, 60% progressed to moderate NPDR. The status of moderate and severe NPDR remained the same postoperatively at 3 months. Of all patients who progressed to moderate NPDR, 3 cases developed non-central macular oedema, and three cases developed both central and non.central macular oedema postoperatively at 3 months. All eyes with severe NPDR resulted in DME, except for one (9.1%) eye. Conclusion: Preoperatively, 57.5% had no macular oedema, while 42.5% had non.central macular oedema. Postoperatively, 4.4% had central oedema, and 10.9% had both central and non.central oedema among those who initially had no macular oedema. Additionally, 38.2% developed oedema in both central and non.central regions among patients initially presenting with non-central macular oedema. There was also a significant statistical difference with longer duration of diabetes mellitus, severity of diabetic retinopathy and elevated HbA1c values with the development of diabetic macular oedema postoperatively. However, larger sample sizes and longer-term follow-up are essential for assessing retinopathy progression and the incidence of DME.

The Relationship Between Health Insurance Status and Diabetic Retinopathy Progression

ObjectiveTo determine if baseline diabetic retinopathy severity mediates the relationship between health insurance status and diabetic retinopathy progression. DesignRetrospective cohort study Subjects716 patients aged ≥18 years with a diagnosis of type 1 or 2 diabetes mellitus, and a diagnosis of non-proliferative diabetic retinopathy (NPDR) were identified from the electronic health record (EHR) of a tertiary academic center between 6/2012 and 2/2022. MethodsNPDR severity at baseline was the proposed mediator in the relationship between insurance status and PDR progression. Logistic regression was used to determine the association between insurance status and NPDR severity at baseline, and Cox proportional hazards regression was used to assess the association between insurance status and time to PDR progression. To analyze the mediation effect of NPDR severity at baseline, a counterfactual approach, which decomposes a total effect into a natural direct effect and a natural indirect effect was applied. Main Outcome MeasuresTime to progression from first NPDR diagnosis to first PDR diagnosis. ResultsOf the 716 patients, 581 (81%) had Medicare or private insurance, 107 (15%) had Medicaid, and 28 (4.0%) were uninsured at their baseline eye visit. Uninsured or Medicaid patients had a higher proportion of moderate or severe NPDR at their baseline eye visit, and a higher proportion of progression to PDR. After adjusting for confounders and NPDR severity at baseline, uninsured patients had significantly greater risk of progression to PDR compared to Medicare/private insurance patients (HR 2.63, 95% CI 1.10 – 6.25). Medicaid patients also had an increased risk of progression to PDR compared to Medicare/private insurance patients, although not statistically significant (HR 1.53, 95% CI 0.81 – 2.89). NPDR severity at baseline mediated 41% of the effect of insurance status (uninsured vs Medicare/private insurance) on PDR progression. ConclusionsUninsured patients were more likely to have an advanced stage of NPDR at their baseline eye visit and were at significantly greater risk of progression to PDR compared with Medicare or privately insured patients. Mediation analysis revealed that differences in baseline NPDR severity by insurance explained a significant proportion of the relationship between insurance status and diabetic retinopathy progression.

Implementation of a Teleophthalmology Screening Program for Diabetic Retinopathy in New York City.

Purpose: To examine the implementation of a teleophthalmology program for diabetic retinopathy (DR) screening at a metropolitan hospital system and identify the challenges that the clinical teams encountered using the program. Methods: The study was conducted in 2 parts. The first was a pilot retrospective chart review of 300 consecutive patients screened for DR by the teleophthalmology screening program. The baseline variables, DR capture rate and staging, and continuity of care for those diagnosed with DR were analyzed. The second was a web-based survey identifying the barriers encountered by 36 physicians and clinical staff as they participated in the teleophthalmology screening program. Results: Part 1: Of the patients evaluated, 57 (19.0%) were diagnosed with DR; 42 (73.7%) had mild nonproliferative DR (NPDR), 7 (12.3%) had moderate NPDR, none had severe NPDR, and 8 (14.0%) had PDR. Thirty-one patients (54.4%) with retinopathy diagnoses were referred for an in-person follow-up at the clinic while the rest continued monitoring via the program. Of this subset, 22 (71.0%) completed the follow-up visit. Part 2: The survey respondents comprised 28 physicians (77.8%), 6 licensed nurse practitioners (16.7%), and 2 medical assistants (5.6%). Twenty-two providers (71.0%) preferred initiating referrals for in-person annual examinations over teleophthalmology screening referrals. The most common barriers described were related to workflow interruption, time constraints, and staff shortages. Conclusions: The teleophthalmology DR screening program allowed identification of early or absent DR at clinics in an urban setting (New York City). The findings suggest areas for targeted improvement in the screening program to better complement internal referral practices' workflows.

Study of OCT based biomarkers as a predictor of visual outcome in diabetic macular edema

To determine the association between optical coherence tomography (SD-OCT) based biomarkers and visual acuity (VA) in diabetic macular edema (DME). This cross-sectional study was conducted at a tertiary care teaching hospitalbetweenJanuary 2021 and July 2022.The study included 54 eyes (30 patients) with DME. Based on the early treatment diabetic retinopathy study (ETDRS) grading system, these were classified as mild (n=1), moderate (n=31), severe (n=14), and very severe (n=8) non-proliferative diabetic retinopathy (NPDR). The demographics, VA recorded using ETDRS chart and ETDRS scoring system, slit lamp biomicroscopy findings, colour fundus pictures and biomarkers determined using macular scans on SD-OCT were noted. Six eyes with proliferative diabetic retinopathy (n-4) and considerable media opacity (n-2) were excluded. The data was entered into Microsoft Excel spreadsheet 2021and IBM's SPSS 26 statistical program was used to calculate the results.VA and biomarkers, which included central macular thickness, disorganisation of retinal inner layers (DRIL), ellipsoid zone disruption (EZD), choroidal thickness were measured on SD-OCT.: The mean age was 59.4±9.4 years, and male to female ratio was 1.3:1. Mean uncorrected and best corrected VA were 46 and 61 letters, 55.12±1.76 and 67.25±10.05 letters for moderate NPDR, 43.07±3.95 and 52.14±17.83 letters for severe NPDR, and 26.50±16.53 and 36±16.38 letters for very severe NPDR, respectively. VA deteriorated with increasing disease severity. Poorer VA was associated with increased average foveal and macular thickness and increased mean horizontal disruption of the inner retinal layers (DRIL). Average choroidal thickness positively correlated with increasing DR severity. : Poorer VA was associated with increasing DR severity, increased central retinal thickness, increased mean horizontal DRIL and increased average foveal choroidal thickness. We found no statistically significant correlation between VA and ellipsoid zone disruption.

The effect of hypothyroidism on the risk of diabetes and its microvascular complications: a Mendelian randomization study.

Several observational studies have found that hypothyroidism is associated with diabetes and its microvascular complications. However, the cause and effect have not been clarified. The aim of the study was to examine the causality of such associations by a Mendelian randomization study. Two-sample Mendelian randomization analysis was conducted to investigate the associations. Summary statistics for hypothyroidism were from the UK Biobank, and diabetes and its microvascular complications were from the largest available genome-wide association studies. MR-Egger, weighted median, inverse variance weighted, simple mode and weighted mode were used to examine the causal associations, and several sensitivity analyses were used to assess pleiotropy. Inverse variance weighted estimates suggested that hypothyroidism was associated with type 1 diabetes and type 1 diabetes with renal complications (β= 9.059926, se= 1.762903, P = 2.76E-07 and β= 10.18375, se= 2.021879, P = 4.73E-07, respectively) but not type 2 diabetes and type 2 diabetes with renal complications. In addition, hypothyroidism was positively associated with severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy (β= 8.427943, se= 2.142493, P = 8.36E-05 and β= 3.100939, se= 0.74956, P=3.52E-05, respectively). The study identified the causal roles of hypothyroidism in diabetes and its microvascular complications. Hypothyroidism can lead to type 1 diabetes, type 1 diabetes with renal complications, severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy.

Evaluation of Quality of Life and Emotional Disturbances in Patients with Diabetic Retinopathy.

The purpose of this study was to evaluate the association of Diabetic Retinopathy (DR) and diabetic macular edema with vision-related quality of life, as well as the potential association between the disease's severity, emotional status of patients and the manifestation of anxiety and psychological features. Patients with fundoscopic findings had significantly lower scores in all VFQ-25 subscales, indicating worse quality of life in comparison to patients without DR. Severity of DR, greater levels of anxiety, daily sitting time, unemployment and lower education level, were all found to be significantly, negatively associated with a worse quality of life. Regarding emotional status, more years of suffering from diabetes, treatment with insulin and the hours being idle per day were associated with an increased burden of anxiety. In addition, the presence of a concomitant disease, findings in fundoscopy, diabetic macular edema and treatment with anti-VEFG injections, as well as the number of doses, were significantly associated with greater anxiety. Multivariate analysis showed that having Severe Non-Proliferative Diabetic Retinopathy or having Proliferative Diabetic Retinopathy and receiving insulin therapy (alone or in combination with another treatment), were significantly associated with higher levels of anxiety. The well-established impact of DR on the patients' well-being, quality of life and emotional status render DR and CME prevention, stabilization or delaying progression as a necessity in order to protect patients from developing psychiatric symptoms. On the other hand, the speculated bi-directional association between emotional problems and DR progression highlights the importance of acknowledging and dealing with psychological issues with the aim of delaying DR progression.

Prevalence and Risk Factors of Retinopathy in Type 1 Diabetes: A Cross-Sectional Study.

Introduction Diabetic retinopathy (DR) is a severe complication of diabetes. It remains a major cause of visual impairment and blindness, especially in young people. It is a silent affection that only becomes symptomatic at the onset of complications. Our study aimed to estimate the prevalence of retinopathy in patients with type 1 diabetes mellitus (T1DM) and evaluate the associated risk factors in our population. Materials and methods A descriptive and analytical study, with a cross-sectional study involving 359 patients with type 1 diabetes, was followed up in the Department of Endocrinology, Diabetology, and Nutrition of the University Hospital Center Mohammed VI Oujda, Morocco. Data were collected from medical records and analyzed by binary logistic regression using IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp. Results The average age of our patients was 24.2 ± 11.4 years. The mean duration of diabetes was 11.8±4.4 years. The average glycated hemoglobin (HbA1c) at admission was 10.1 ± 2.4%. DR was found in 30% of patients, including 28.6% with minimal non-proliferative diabetic retinopathy (NPDR), 19.1% with moderate NPDR, 19.1% with severe NPDR, and 33.3% with proliferative DR. Patients with diabetic retinopathy appear to have a longer duration of diabetes (13.05±9.05 vs. 10.6±8.07 years). The longer duration of diabetes, neuropathy, and nephropathy was significantly associated with diabetic retinopathy (p=0.02, p=0.002, and p=0.0001, respectively). Conclusion The frequency of diabetic retinopathy increases with age, poor glycemic control, and the duration of diabetes. Therefore, cooperation between diabetologists and ophthalmologists is essential for making an early diagnosis and providing early treatment.

Ocular and Systemic Risk Factors for Disease Worsening Among Patients with NPDR: Post Hoc Analysis of the PANORAMA Trial

PurposeIdentify baseline systemic and ocular characteristics associated with nonproliferative diabetic retinopathy (NPDR) worsening, and the impact of intravitreal aflibercept injection (IAI) on these associations. DesignPost hoc analysis of PANORAMA. ParticipantsPatients with moderately severe to severe NPDR enrolled in the prospective PANORAMA phase 3 trial. MethodsAssociations between baseline systemic and ocular factors with events indicative of NPDR worsening at Week 100 were evaluated by multivariable analysis in sham-treated eyes. NPDR worsening was defined as development of (1) vision-threatening complications (VTCs; comprising PDR and/or anterior segment neovascularization), (2) center-involved diabetic macular edema (CI-DME), or (3) ≥ 2-step Diabetic Retinopathy Severity Scale (DRSS) worsening. Impact of IAI on identified baseline factors was evaluated using univariable analysis in combined IAI groups. Main Outcomes MeasuresBaseline systemic and ocular factors associated with events indicative of NPDR worsening at Week 100. The cumulative incidence and risk of developing such events at Week 100 among sham versus IAI-treated eyes. ResultsUsing multivariable analyses among sham-treated eyes, 5 baseline factors associated with increased risk of NPDR worsening were identified: fluorescein leakage, retinal nonperfusion area, thicker central subfield thickness, eosinophil level, and proteinuria. Considering baseline fluorescein leakage area as a prognostic indicator in detail, the risk of developing VTCs alone, VTCs and/or CI-DME, or ≥ 2-step DRSS worsening increased with increasing fluorescein leakage area in the sham group (all P < 0.05). Considering baseline retinal nonperfusion area as a prognostic indicator in detail, the risk of developing VTCs alone, CI-DME alone, or VTCs and/or CI-DME increased with increasing baseline retinal nonperfusion area in the sham group (all P < 0.05). In contrast, among IAI-treated eyes, increasing baseline fluorescein leakage or retinal nonperfusion areas did not increase the risks of NPDR worsening. ConclusionsWithin the PANORAMA trial, increased areas of fluorescein leakage and retinal nonperfusion at baseline were identified as key ocular biomarkers associated with events indicative of NPDR worsening among sham-treated patients. IAI treatment appeared to mitigate the effect of these baseline risk factors and reduced the likelihood of NPDR worsening.

Association between macrophage-like cell density and ischemia metrics in diabetic eyes

We previously showed that macrophage-like cells (MLCs) are increased in eyes with advanced diabetic retinopathy (DR). Here, we hypothesized that MLC density was correlated with ischemia using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography (UWF-FA). Treatment-naïve diabetic eyes were prospectively imaged with repeated OCTA (average 5.3 scans per eye) and UWF-FA imaging. OCTA images were registered and averaged to generate a superficial capillary plexus (SCP), deep capillary plexus (DCP), and MLC slab. We calculated geometric perfusion deficit (GPD), vessel length density, and vessel density for the SCP and DCP. MLC density was quantified by two masked graders and averaged. Ischemia on UWF-FA was measured to generate a non-perfusion area (NPA) and index (NPI). Since MLC density was non-parametrically distributed, MLC density was correlated with ischemia metrics using Spearman correlations. Forty-five treatment-naïve eyes of 45 patients (59 ± 12 years of age; 56% female) were imaged. We included 6 eyes with no DR, 7 eyes with mild non-proliferative DR (NPDR), 22 moderate NPDR, 4 severe NPDR, and 6 PDR eyes. MLC density between graders was highly correlated (r = 0.9592, p < 0.0001). MLC density was correlated with DCP GPD (r = 0.296, p = 0.049), but no other OCTA ischemia metrics. MLC density was also correlated with UWF-FA NPA (r = 0.330, p = 0.035) and NPI (r = 0.332, p = 0.034). MLC density was correlated with total ischemia on UWF-FA and local DCP GPD. Since both UWF-FA and DCP non-perfusion are associated with higher risk for DR progression, MLC density could be another potential biomarker for DR progression.

A Prediction Model for Sight-Threatening Diabetic Retinopathy Based on Plasma Adipokines among Patients with Mild Diabetic Retinopathy.

Accumulating evidence has suggested a link between adipokines and diabetic retinopathy (DR). This study is aimed at investigating the risk factors for sight-threatening DR (STDR) and establishing a prognostic model for predicting STDR among a high-risk population of patients with type 2 diabetes mellitus (T2DM). Plasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. In the case-control set, principal component analysis (PCA) was performed to select optimal predictive cytokines for STDR, involving severe nonproliferative DR (NPDR) and proliferative DR. Support vector machine (SVM) was used to examine the possible combination of baseline plasma adipokines to discriminate the patients with mild NPDR who will later develop STDR. An individual prospective cohort with a follow-up period of 3 years was used for the external validation. In both training and testing sets, involving 306 patients with T2DM, median levels of plasma adiponectin (APN), leptin, and fatty acid-binding protein 4 (FABP4) were significantly higher in the STDR group than those in mild NPDR. Except for adipsin, the other three adipokines, FABP4, APN, and leptin, were selected by PCA and integrated into SVM. The accuracy of the multivariate SVM classification model was acceptable in both the training set (AUC = 0.81, sensitivity = 71%, and specificity = 91%) and the testing set (AUC = 0.77, sensitivity = 61%, and specificity = 92%). 110 T2DM patients with mild NPDR, the high-risk population of STDR, were enrolled for external validation. Based on the SVM, the risk of each patient was calculated. More STDR occurred in the high-risk group than in the low-risk group, which were grouped by the median value of APN, FABP4, and leptin, respectively. The model was validated in an individual cohort using SVM with the AUC, sensitivity, and specificity reaching 0.77, 64%, and 91%, respectively. Adiponectin, leptin, and FABP4 were demonstrated to be associated with the severity of DR and maybe good predictors for STDR, suggesting that adipokines may play an important role in the pathophysiology of DR development.

THE ROLE OF E-SELECTIN IN THE DEVELOPMENT OF MACULAR EDEMA IN DIABETIC RETINOPATHY DURING TYPE 2 DIABETES

Background. Diabetic retinopathy (DR) and diabetic macular edema (DME) are frequent complications of type 2 diabetes (T2D). Implementation of their effective diagnosis and prognosis by identifying new biomarkers is an important task of modern ophthalmology.&#x0D; Aim: is to establish the role of E-selectin in the development of DME in DR of various degrees in patients with T2D.&#x0D; Materials and methods. The study included 124 patients (124 eyes) with T2D who had mild (29 eyes, group 1), moderate or severe (35 eyes, group 2) non-proliferative DR and proliferative DR (31 eyes, 3rd group); the control group consisted of 29 eyes without diabetes. All patients underwent standard ophthalmological examinations, spectral domain optical coherence tomography (OCT) with determination of central retinal thickness (CRT, μm). The DME set more values of the regulatory database on the ETDRS fields of the spectral-domain OKT software when the CRT is increased. The content of E-selectin in the blood was determined by the immunoenzymatic method (Invitrogen ThermoFisher Scientific, USA). MedStat and MedCalc v.15.1 software packages (MedCalc Software bvba) were used for statistical research.&#x0D; Results. The content of E-selectin in the blood in DR and T2D was significantly increased in all stages of DR (1.2-1.3 times; p&lt;0.01), with a maximum in proliferative DR, which directly correlated with indicators that reflected glycemic control (HbA1c), retinal edema (CRT) and visual acuity deterioration. The content of E-selectin when dividing patients according to the presence of DMN was higher than without it (1.3 times; p&lt;0.001), which was preserved for all stages of DR. The existence of a pathogenetic connection between an increase in the content of E-selectin and the development of DME and the possibility of its use as a biomarker of DME was confirmed in a univariate regression analysis: an increase in the DME risk with an increase in the content of E-selectin was found (OR=1.19; 95% CI 1.12-1.26). The model had satisfactory performance criteria - AUC=0.89 (95% CI 0.83-0.94) with a sensitivity of 89.8% and a specificity of 80.0%.&#x0D; Conclusion. The results of the study confirmed the concept of the significant importance of increasing the content of E-selectin in the blood for the development of DME in DM and T2D.