Baseline Diabetic Retinopathy Research Articles

Deep Capillary Nonperfusion on OCT Angiography Predicts Complications in Eyes with Referable Nonproliferative Diabetic Retinopathy

To evaluate the ability of capillary nonperfusion parameters on OCT angiography (OCTA) to predict the development of clinically significant outcomes in eyes with referable nonproliferative diabetic retinopathy (NPDR). Prospective longitudinal observational study. In total, 59 patients (74 eyes) with treatment-naive moderate and severe (referable) NPDR. Patients were imaged with OCTA at baseline and then followed-up for 1 year. We evaluated 2 OCTA capillary nonperfusion metrics, vessel density (VD) and geometric perfusion deficits (GPDs), in the superficialcapillary plexus, middle capillary plexus (MCP), and deep capillary plexus (DCP). We compared thepredictive accuracy of baseline OCTA metrics for clinically significant diabetic retinopathy (DR) outcomes at1year. Significant clinical outcomes at 1 year, defined as 1 or more of the following-vitreous hemorrhage, center-involving diabetic macular edema, and initiation of treatment with pan-retinal photocoagulation or anti-VEGF injections. Overall, 49 patients (61 eyes) returned for the 1-year follow-up. Geometric perfusion deficits and VD in the MCP and DCP correlated with clinically significant outcomes at 1 year (P < 0.001). Eyes with these outcomes had lower VD and higher GPD, indicating worse nonperfusion of the deeper retinal layers than those that remained free from complication. These differences remained significant (P= 0.046 to < 0.001) when OCTA parameters were incorporated into models that also considered sex, baseline corrected visual acuity, and baseline DR severity. Adjusted receiver operating characteristic curve for DCP GPD achieved an area under the curve (AUC) of 0.929, with sensitivity of 89% and specificity of 98%. In a separate analysis focusing on high-risk proliferative diabetic retinopathy outcomes, MCP and DCP GPD and VD remained significantly predictive with comparable AUC and sensitivities to the pooled analysis. Evidence of deep capillary nonperfusion at baseline in eyes with clinically referable NPDR can predict short-term DR complications with high accuracy, suggesting that deep retinal ischemia has an important pathophysiologic role in DR progression. Our results suggest that OCTA may provide additional prognostic benefit to clinical DR staging in eyes with high risk.

Course of Diabetic Retinopathy in Untreated Fellow Eyes in RIDE and RISE: A Post Hoc Analysis.

To characterize diabetic retinopathy (DR) progression without therapy. This post hoc analysis of the phase 3 RIDE and RISE trials examined the association between baseline DR severity on rates of ≥ 2-step DR progression and improvement in untreated fellow eyes (n = 530) and ranibizumab-treated study eyes (n = 369). Kaplan-Meier analyses estimated progression to proliferative DR (PDR) over 2 years in eyes with nonproliferative DR (NPDR) at baseline. At month 24, 28.8% of untreated fellow eyes with moderately severe to severe NPDR at baseline experienced ≥ 2-step DR progression, versus 10.3% of eyes with absent to moderate NPDR and 0 eyes with mild- to high-risk proliferative DR. Of the untreated fellow eyes with moderately severe to severe NPDR, 18.9% achieved ≥ 2-step DR improvement, compared with 88.4% of ranibizumab-treated eyes. Without treatment, patients with moderately severe to severe NPDR are at risk of rapid disease progression and vision loss. [Ophthalmic Surg Lasers Imaging Retina. 2022;53(4):202-207.].

Cardiac autonomic neuropathy predicts diabetic retinopathy progression in Asian population with type 2 diabetes mellitus.

To investigate the role of cardiac autonomic neuropathy (CAN), vascular condition, and sensory function in diabetic retinopathy (DR) progression. This 3-year cohort study conducted in a community hospital included 4850 patients over 20 with type 2 diabetes mellitus. Participants were assessed in 2017 at baseline and were followed up in 2020. Patients were divided into two groups based on whether they had DR progression or not and were compared using the chi-square test or two-sample t-test. Beta coefficient and odds ratio (OR) with 95% confidence intervals were calculated using binary logistic regression. The receiver operating characteristic (ROC) curve of various independent variables for DR progression was provided with C-statistics. Abnormal hemoglobin A1c (HbA1c) level/variation, estimated glomerular filtration rate, urine albumin-to-creatinine ratio, R-R interval variation, standard deviation of the average NN intervals, autonomic nervous system function, power of high-frequency (HF) bands, balance, cardio-ankle vascular index (CAVI), and warm stimulation (WS) were associated with DR progression. Average HbA1c, HF, and proliferative diabetic retinopathy were independent factors for patients developing DR progression. The top three areas under the curve of ROCs were HF + baseline DR grading, WS + baseline DR grading, and CAVI + baseline DR grading. These variable combinations were the most reliable predictors of DR progression. CAN, abnormal vascular condition, and sensory function are associated with DR progression. The combination of HF, WS, and CAVI with baseline DR grading provides the most accurate predictive model for DR progression. Early detection of these factors is important to prevent DR progression.

Alterations in the Choroidal Sublayers in Relationship to Severity and Progression of Diabetic Retinopathy: A Swept-Source OCT Study.

PurposeTo examine the association of baseline choroidal sublayers metrics with the risk of diabetic retinopathy (DR) progression over 2 years, with adjustment for confounding factors that affect choroidal measurements.DesignProspective, observational cohort study.ParticipantsOne hundred three eyes from 62 patients with diabetes mellitus (DM).MethodsPatients were followed up at 6-month intervals for at least 2 years. Choroidal metrics including choroidal area, choroidal thickness (CT), and choroidal vascularity index were measured for both (1) the choriocapillaris plus Sattler’s layer and (2) the Haller’s layer within the subfoveal and parafoveal region. Cox proportional models were constructed to estimate the relationship between baseline choroidal metrics and DR progression, adjusted for intereye correlation, established risk factors (i.e., duration of DM, glycated hemoglobin [HbA1c] level, body mass index [BMI], use of insulin, and mean arterial blood pressure [MABP]) and confounding factors of choroidal measurements (i.e., age and axial length). Additional predictive value of choroidal metrics was assessed using the C-statistic.Main Outcome MeasuresHazard ratios (HRs) calculated by Cox proportional hazards model to demonstrate the associations between baseline choroidal metrics and DR progression.ResultsAfter adjusting for age, axial length, and intereye correlation, choroidal metrics in Haller’s layer at baseline that were associated with a higher risk of DR progression included increases in subfoveal choroidal area (HR, 2.033; 95% confidence interval [CI], 1.179–3.505; P = 0.011), subfoveal plus parafoveal choroidal area (HR, 1.909; 95% CI, 1.096–3.326; P = 0.022), subfoveal CT (HR, 2.032; 95% CI, 1.181–3.498; P = 0.010), and subfoveal plus parafoveal CT (HR, 1.908; 95% CI, 1.097–3.319; P = 0.022). These associations remained statistically significant after additionally adjusting for duration of DM, HbA1c level, BMI, use of insulin, and MABP. Addition of these choroidal metrics significantly improved the discrimination for DR progression when compared with established risk factors alone (e.g., duration of DM and HbA1c; increase in C-statistic ranged from 8.08% to 9.67% [P < 0.05]).ConclusionsEyes with a larger choroidal area and CT in Haller’s layer at baseline were associated with a higher risk of DR progression over 2 years.

Longitudinal associations of ocular biometric parameters with onset and progression of diabetic retinopathy in Chinese adults with type 2 diabetes mellitus

AimsTo investigate the associations of ocular biometric parameters with incident diabetic retinopathy (DR), incident vision-threatening DR (VTDR) and DR progression.MethodsThis community-based prospective cohort study recruited participants with type 2 diabetes...

Graph Adversarial Transfer Learning for Diabetic Retinopathy Classification

Diabetic retinopathy (DR) is an essential factor that has caused vision loss and even blindness in middle-aged and older adults. A system that can automatically perform DR diagnosis can help ophthalmologists save a lot of tedious work, such as DR grading or lesion detection. At the same time, patients can find their diseases earlier and perform the correct treatment. However, most of the existing methods require many DR annotations to train the model, and the DR data will vary to different degrees due to various shooting tools. The above problems lead to the inefficient use of existing data in the experiment, limiting actual deployment. To alleviate this problem, we propose a novel Graph Adversarial Transfer Learning (GATL) for DR diagnosis in a deep model through transfer learning, including intra-domain alignment and inter-domain alignment. The proposed GATL enjoys several merits. First, our GATL adopts the self-supervised training to save the annotating cost in the target domain thus this domain adaptation method can significantly reduce annotation cost compared to the supervised approaches. Second, we introduce the graph neural network to extract potential features between unknown samples. Third, to enhance the robustness of the model, we use adversarial training to perform both inter-domain and intra-domain alignment to further improve the model’s classification accuracy. GATL achieved 94.3%, 97.5%, and 91.1% in accuracy, sensitivity, and specificity in the APTOS dataset and 92.7%, 95.7%, and 89.7% in the EyePACS dataset, respectively. Extensive experimental results on two challenging benchmarks, including APTOS 2019 and EyePACS, demonstrate that the proposed GATL performs favorably against baseline DR classification methods.

Review of the management of sight-threatening diabetic retinopathy during pregnancy.

Diabetes mellitus (DM) is a noncommunicable disease reaching epidemic proportions around the world. It affects younger individuals, including women of childbearing age. Diabetes can cause diabetic retinopathy (DR), which is potentially sight threatening when severe nonproliferative DR (NPDR), proliferative DR (PDR), or sight-threatening diabetic macular oedema (STDME) develops. Pregnancy is an independent risk factor for the progression of DR. Baseline DR at the onset of pregnancy is an important indicator of progression, with up to 10% of women with baseline NPDR progressing to PDR. Progression to sight-threatening DR (STDR) during pregnancy causes distress to the patient and often necessitates ocular treatment, which may have a systemic effect. Management includes prepregnancy counselling and, when possible, conventional treatment prior to pregnancy. During pregnancy, closer follow-up is required for those with a long duration of DM, poor baseline control of blood sugar and blood pressure, and worse DR, as these are risk factors for progression to STDR. Conventional treatment with anti-vascular endothelial growth factor agents for STDME can potentially lead to foetal loss. Treatment with laser photocoagulation may be preferred, and surgery under general anaesthesia should be avoided. This review provides a management plan for STDR from the perspective of practising ophthalmologists. A review of strategies for maintaining the eyesight of diabetic women with STDR with emphasis on prepregnancy counselling and planning, monitoring and safe treatment during pregnancy, and management of complications is presented.

Urinary peptidome and diabetic retinopathy in the DIRECT-Protect 1 and 2 trials.

Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively. Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792subjects in two randomized controlled trials, DIRECT-Protect 1 and 2, respectively. End points were two-step (RET2) and three-step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT-Protect 1. The identified peptides were then validated cross-sectionally in the remaining 1/3 from DIRECT-Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT-Protect 1 and 2 cohorts and significant peptides were tested longitudinally. Follow-up ranged 4.0-4.7years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: -.223, p<0.001 and Rho: -.141, p=0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types. We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR.

430-P: Urinary Proteome and Diabetic Retinopathy in the Direct-Protect 1 and 2 Trials

Background: Given the association of diabetic retinopathy (DR) to diabetic kidney disease, we investigated the urinary proteome to the presence and deterioration of DR in type 1 and type 2 diabetes in a post-hoc analysis of studies investigating the effect of candesartan on the progression of DR. Methods: Baseline urinary proteomic analysis was performed in 783 and 792 randomly chosen subjects from two RCTs: DIRECT-Protect 1 and 2. Endpoints were two-step and three-step change in DR score according to the Early Treatment of Diabetic Retinopathy Study protocol. Peptide levels were correlated to baseline DR score, using Spearman rank correlation (association presented as Rho), in a discovery set of 2/3 of participants in DIRECT-Protect 1. Identified peptide fragments were then tested cross-sectionally in a validation set of the remaining 1/3 in DIRECT-Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT-Protect 1 and 2 cohorts in relation to baseline DR. Finally, peptides validated in the entire cohorts were tested longitudinally. Adjustment included sex, age, diabetes duration, smoking, total cholesterol, HbA1c, SBP, UAER, serum creatinine, and randomization group. Results: Follow-up ranged from 4.0-4.7 years. 24 out of 427 investigated peptide fragments were associated with baseline DR in the discovery set after adjustment for multiple testing. Two of these (COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were also associated to baseline DR in the validation set (Rho: -0.22, p&amp;lt;0.001 and Rho: -0.14, p=0.024). Neither was associated with the development of endpoints. Investigating the discovered fragments in the full cohorts, several collagen fragments were associated with baseline DR and endpoints, in both type 1 and type 2 diabetes, however without overlap. Conclusions: Several urinary peptide fragments (mainly collagen) were associated with the presence of DR, however, they were not conclusively associated with worsening of DR. Disclosure V. Rotbain curovic: None. P. Magalhães: None. T. He: Employee; Self; Mosaiques Diagnostics GmbH. T. W. Hansen: Stock/Shareholder; Self; Novo Nordisk A/S. H. Mischak: Stock/Shareholder; Self; Mosaiques Diagnostics. P. Rossing: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Merck KGaA, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Vifor Pharma Management Ltd.

1103-P: Risk Factors for Visit Cancellations in a Tertiary Care Referral Clinic Specializing in Diabetic Eye Disease

Patient cancellations of scheduled visits may result in missed opportunities for timely treatment and counseling and adversely impact quality of patient care. Identification of risk factors for cancellations might allow clinicians to define subgroups more likely to miss visits and interventions that prevent lapses in care. The purpose of this study was to identify patient factors associated with visit cancellations in patients followed at a tertiary care referral center for diabetes eye care. A retrospective review of the Joslin Diabetes Center’s Beetham Eye Institute electronic medical record was performed for patients with a first visit in 2016 and subsequent follow-up data. Analyses adjusted for repeated measures from the same patient. A total of 1,785 patients with diabetes (46.5% type 1, 53.5% type 2) were evaluated with baseline mean ± SD diabetes duration 24.5 ± 0.6 yrs, A1c 8.0 ± 0.1; 44.0% were female, 64.7% White, 10.3% Black and 4.0% Asian. Baseline diabetic retinopathy (DR) severity in the eye with more advanced disease was no DR in 40.3%, nonproliferative DR in 40.8% and proliferative DR (PDR) in 19.0%. Over the study time period, 333/13,085 (2.5%) visits were cancelled by patients. Bivariate analyses revealed increased cancellations were associated with older age (OR:1.00, p = 0.02), Asian versus White race (OR:3.77, p = 0.003), longer DM duration (OR:1.01, p &amp;lt; 0.05), the presence of DM complications (OR:1.43, p = 0.02), not being insured by Medicare (OR:1.29, p = 0.01), and the presence of PDR (OR:2.28, p = 0.004). After backwards elimination analysis, only PDR remained significantly associated with cancellations. These findings suggest that patient cancellations may be associated with DR severity. Future studies should explore this relationship in expanded patient datasets and the relationship of cancelled to missed visits in order to better understand potential barriers to follow up for patients undergoing diabetes eye care. Disclosure C. Gilbert: None. W. Fickweiler: None. A. Adam: None. J. Sun: Other Relationship; Self; Novo Nordisk, Roche Pharma, Research Support; Self; Adaptive Sensory Technology, Boehringer Ingelheim Pharmaceuticals, Inc., KalVista Pharmaceuticals, Optovue, Roche Pharma. Funding Massachusetts Lions Eye Research Fund

Racial, Ethnic, and Insurance-Based Disparities Upon Initiation of Anti–Vascular Endothelial Growth Factor Therapy for Diabetic Macular Edema in the US

This study characterizes the association of risk factors including race, ethnicity, and insurance status with presenting visual acuity (VA) and diabetic retinopathy (DR) severity in patients initiating treatment with anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME). Retrospective, cross-sectional study. The Academy Intelligent Research in Sight (IRIS) Registry database was queried for patients who initiated anti-VEGF injection treatment for DME between 2012 and 2020 (n= 203 707). Multivariate regression analyses were conducted to understand how race, ethnicity, insurance status, and geographic location were associated with baseline features. Visual acuity and DR severity. Patients on Medicare and private insurance presented with higher baseline VA compared with patients on Medicaid (median of 2.31 and 4.17 greater Early Treatment Diabetic Retinopathy Scale [ETDRS] letters, respectively P < 0.01). White and non-Hispanic patients presented with better VA compared with their counterparts (median of 0.68 and 2.53 greater ETDRS letters, respectively; P < 0.01). Black and Hispanic patients presented with a worse baseline DR severity compared with White and non-Hispanic patients (odds ratio, 1.23 and 1.71, respectively; P < 0.01). There are ethnic and insurance-based disparities in VA and disease severity upon initiation of anti-VEGF therapy for DME treatment. Public health initiatives could improve timely initiation of treatment.

Diabetic Retinopathy, Visual Impairment, and the Risk of Six-Year Death: A Cohort Study of a Rural Population in China

Purpose: The aim of this study was to explore the association between diabetic retinopathy (DR) and the risk of 6-year death, as well as the association between visual impairment (VI) and the risk of 6-year death in a rural Chinese population of age ≥30 years. Methods: This was a population-based cohort study. In 2006–2007, 6,830 subjects aged ≥30 years were recruited from 13 villages in Northern China through clustered randomization. In 2012–2013, a 6-year follow-up was further done. Six different proportional hazards models, with different confounders adjusted, were used to explore the association between baseline DR and risk of death. Results: 5,570 subjects were included in this study by our inclusion and exclusion criteria. Four hundred and ten (7.36%) subjects died by follow-up. The median ages of the dead subjects and survived subjects were 67 (interquartile range [IQR]: 58–72) years and 52 (IQR: 42–58) years (Z = 21.979, p < 0.001). Male accounted for 62.20 and 44.92% among the dead and survived subjects (χ² = 45.591, p < 0.001). Besides, compared with those survived, the dead were found to be with lower education (χ² = 109.981, p < 0.001), lower marriage rate (χ² = 101.341, p < 0.001), lower income (χ² = 123.763, p < 0.001), higher proportion of smoking (χ² = 8.869, p = 0.003), higher systolic blood pressure (Z = 10.411, p < 0.001), lower body mass index (Z = −3.302, p = 0.001), larger spherical equivalent error (Z = 4.248, p < 0.001), lower intraocular pressure (Z = −4.912, p < 0.001), smaller anterior chamber depth (Z = −9.186, p < 0.001), larger length thickness (Z = 11.069, p < 0.001), higher fast blood glucose level (Z = 5.650, p < 0.001), higher total cholesterols (Z = 2.015, p = 0.044), higher low-density lipoprotein (Z = 2.024, p = 0.043), and higher proportion of drug usage (χ² = 56.108, p < 0.001). Besides, the dead subjects were more likely to be with VI, glaucoma, cataract, age-related macular degeneration, diabetes, and DR. Hundred and forty-eight subjects were diagnosed with DR at baseline, and 33 (22.30%) of them were dead before follow-up. By adjusting all relative confounders in a proportional hazards model, DR was found to be a risk factor of 6-year death, the hazard ratio was 1.739 (95% confidence intervals: 1.080, 2.803). Another 5 different statistical models with different confounders adjusted also revealed a statistically significant association between DR and 6-year death. The association between VI and 6-year death was not statistically significant. Conclusions: DR increased the risk of 6-year death in a rural Chinese population aged ≥30 years, while VI did not.

Baseline Factors Associated with Diabetic Retinopathy Improvement in RIDE/RISE

Abstract In a retrospective post hoc analysis of RIDE/RISE, baseline diabetic retinopathy severity and retinal nonperfusion were predictive of at least 2-step diabetic retinopathy severity improvement at month 24 in response to ranibizumab.

Predictors of Early Diabetic Retinopathy Regression with Ranibizumab in the RIDE and RISE Clinical Trials.

PurposeTo investigate the predictors of early diabetic retinopathy (DR) improvement in the RIDE/RISE (NCT00473382/NCT00473330) clinical trials.Patients and MethodsIn RIDE/RISE, adult patients with vision loss due to diabetic macular edema (DME) were randomized to monthly intravitreal ranibizumab 0.3 or 0.5 mg (n=502 total) or sham (n=257). DR severity was graded (using the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale). In this post hoc analysis of RIDE/RISE, eyes with baseline DR score ≥35 were evaluated for ≥2-step improvements, and eyes with baseline DR score ≥43 were evaluated for ≥3-step improvements. The characteristics associated with ≥2- or ≥3-step DR improvement at months 3 or 6 were assessed using univariate and/or multivariable analyses.ResultsThe percentage of eyes with a ≥2- or ≥3-step DR improvement was 20.1% and 3.7% at month 3 and 31.2% and 5.8% at month 6. Odds of ≥2-step DR improvement at months 3 or 6 were significantly greater in eyes with moderately severe to severe nonproliferative DR (NPDR) at baseline versus less severe or more severe DR (both P<0.0001). At month 6, odds of ≥2-step DR improvement were significantly greater in eyes with no DME at month 3 (P=0.008). Most patients with ≥3-step DR improvement at months 3 or 6 had proliferative DR (PDR) at baseline (83.3% and 66.7%).ConclusionThe strongest predictors of DR response to ranibizumab at month 6 were baseline DR severity and DME quiescence at month 3. Eyes with the most robust early improvements had moderately severe or severe NPDR or PDR at baseline.

564-P: Differences in Diabetic Retinopathy Prevalence and Progression between Aboriginal and Anglo-Celt Australians: The Fremantle Diabetes Study Phase II

Background: There are limited contemporary data on the prevalence and progression of diabetic retinopathy (DR) in urban-dwelling Aboriginal Australians. We therefore compared the prevalence of DR and cumulative incidence of new/worsening DR (NWDR) between Aboriginal and Anglo-Celt Australians with type 2 diabetes (T2D) in the representative community-based Fremantle Diabetes Study Phase II (FDS2). Methods: From 2008 to 2011, 932 Anglo-Celt and Aboriginal FDS2 participants with T2D underwent comprehensive baseline assessments and were invited to biennial reviews. Ethnic status was based on self-selection, country/countries of birth and parents’ birth, language(s) spoken at home, and country of grandparents’ birth. Fundus photographs were graded according to the Early Treatment Diabetic Retinopathy Study protocol. Prevalence of DR and cumulative incidence of NWDR for each ethnic group, and unadjusted and adjusted odds ratios (ORs), were calculated. Results: Baseline DR data was available for 911 (97.7%) participants (mean age 66.0 years, median T2D duration 8.4 years, 49.7% males). There were 817 Anglo-Celt and 94 Aboriginal participants. Of these, 56% had follow-up data. Baseline prevalence of any DR was 33.0% in Anglo-Celts and 52.1% in Aboriginals (P&amp;lt;0.001). During 4.2±0.4 years’ follow-up, the cumulative incidence of NWDR was 6.7% and 23.5%, respectively (P&amp;lt;0.001). The unadjusted OR (95% CI) for Aboriginals for any DR and NWDR were 2.21 (1.43-3.39) and 4.32 (1.33-13.98), respectively. These ORs were attenuated after age and sex adjustment (1.21 (1.10-1.33) and 4.1 (1.2-14.1), respectively) but were no longer significant after adjusting for other DR risk factors including HbA1c and systolic blood pressure. Conclusions: Urban dwelling Aboriginal Australians have substantial DR prevalence and progression, highlighting the need for better access to culturally appropriate management. Disclosure J.J. Drinkwater: None. W.A. Davis: Advisory Panel; Spouse/Partner; Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Spouse/Partner; Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Mylan, Novo Nordisk A/S, Sanofi-Aventis. Other Relationship; Self; Proteomics International. Other Relationship; Spouse/Partner; Proteomics International. A.W. Turner: None. T. Davis: Advisory Panel; Self; Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. Speaker’s Bureau; Spouse/Partner; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Mylan, Novo Nordisk A/S, Sanofi-Aventis. Other Relationship; Self; Protemics International. Other Relationship; Spouse/Partner; Protemics International. Funding University of Western Australia; Australian Government Training Program; National Health and Medical Research Council of Australia

Extended-Zone Retinal Vascular Caliber and Risk of Diabetic Retinopathy in Adolescents with Type 1 Diabetes

Retinal vascular caliber has been linked to diabetic retinopathy (DR). Newer imaging technologies allow analysis of retinal vascular caliber beyond the standard areas surrounding the optic disc. We investigated the vascular caliber in extended zones in prediction of DR in adolescents with type 1 diabetes. Prospective, longitudinal study. Adolescents (n = 904) who attended the diabetes complications assessment service at the Children's Hospital at Westmead. Retinal caliber was assessed from baseline retinal photographs with a semiautomated computer software Singapore I Vessel Assessment: standard zone retinal vessel calibers were summarized as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), and extended-zone vessels (>2 disc diameters from the optic disc margin) were summarized as mean width of arterioles (MWa) and mean width of venules (MWv). Retinal vessel calibers at baseline (upper 3 quartiles vs. lowest quartiles [Q2-4 vs. Q1]) and moderate DR (stage 3 or more) were analyzed using multivariate generalized estimating equations, with results expressed as odds ratios (OR) and 95% confidence intervals (CIs). Among the 904 participants, baseline mean age ± standard deviation was 14.0 ± 1.5 years, hemoglobin A1C (HbA1C) level was 8.5 ± 1.3%, and median diabetes duration 4.6 years. After a median 3-year follow-up, 15% of adolescents demonstrated moderate DR. Wider extended-zone retinal arteriolar caliber (MWa; OR, 3.6 [95% CI, 2.06-6.1], comparing Q2-4 vs. Q1) and venular caliber (MWv; OR, 4.2 [95% CI, 2.2-7.5]) predicted moderate DR after adjusting for HbA1C and blood pressure. Standard zone CRAE and CRVE were not associated with moderate DR. Extended-zone retinal vessel caliber predicts moderate DR in adolescents with type 1 diabetes.

Diabetic Population-Based Model to Estimate Impact of Ranibizumab on Diabetic Retinopathy Severity in Patients with Diabetic Macular Edema.

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.

Optical Coherence Tomography Angiography Avascular Area Association With 1-Year Treatment Requirement and Disease Progression in Diabetic Retinopathy

To assess the association between optical coherence tomography angiography (OCTA)-quantified avascular areas (AAs) and diabetic retinopathy (DR) severity, progression, and treatment requirement in the following year. Prospective cohort study. We recruited patients with diabetes from a tertiary academic retina practice and obtained 3-mm× 3-mm macular OCTA scans with the AngioVue system and standard 7-field color photographs at baseline and at a 1-year follow-up visit. A masked grader determined the severity of DR from the color photographs using the Early Treatment of Diabetic Retinopathy scale. A custom algorithm detected extrafoveal AA (EAA) excluding the central 1-mm circle in projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Of 138 patients, 92 (41 men, ranging in age from 26-84 years [mean 59.4 years]) completed 1 year of follow-up. At baseline, EAAs for SVC, ICP, and DCP were all significantly correlated with retinopathy severity (P < .0001). DCP EAA was significantly associated with worse visual acuity (r=-0.24, P= .02), but SVC and ICP EAA were not. At 1 year, 11 eyes progressed in severity by at least 1 step. Multivariate logistic regression analysis demonstrated the progression was significantly associated with baseline SVC EAA (odds ratio= 8.73, P= .04). During the follow-up period, 33 eyes underwent treatment. Multivariate analysis showed that treatment requirement was significantly associated with baseline DCP EAA (odds ratio= 3.39, P= .002). No baseline metric was associated with vision loss at 1 year. EAAs detected by OCTA in diabetic eyes are significantly associated with baseline DR severity, disease progression, and treatment requirement over 1 year.

Risk factors associated with progression to referable retinopathy: a type 2 diabetes mellitus cohort study in the Republic of Ireland

To determine factors associated with progression to referable diabetic retinopathy in people with type 2 diabetes in the Republic ofIreland. The study was conducted in a dynamic cohort of 2770 people with type 2 diabetes, recruited between April 2005 and July 2013. Systemic factors (systolic and diastolic blood pressure, HbA1c , lipid levels, BMI) and baseline diabetic retinopathy grading results were evaluated at 4-monthly and yearly intervals, respectively. Associations between risk factors (most recently recorded value, and rate of change in value between pairs of consecutive systemic evaluations) and development of referable diabetic retinopathy were estimated using Cox proportional hazards models. There was a fourfold increased risk of progression to referral when retinopathy was present at baseline vs no retinopathy at baseline (hazard ratio 4.02, 95% CI 2.80-5.78; P<0.001). Higher current values of HbA1c (hazard ratio 1.22, 95% CI 1.11-1.34; P<0.001), systolic blood pressure (hazard ratio 1.29, 95% CI 1.15-1.45; P<0.001) and triglycerides (hazard ratio 1.10, 95% CI 1.03-1.18; P=0.004) were associated with increased risk of referral. Higher current BMI (hazard ratio 0.83, 95% CI 0.73-0.95; P=0.007) and diastolic blood pressure (hazard ratio 0.91, 95% CI 0.85-0.97; P=0.006) were associated with reduced risk of referral. Presence of retinopathy at baseline was strongly associated with increased risk of referral. Modest associations between systemic factors and risk of progression to referable retinopathy were detected.

Profile of non-responder and late responder patients treated for diabetic macular edema: systemic and ocular factors.

Diabetic macular edema (DME) treatment represents a challenge for the ophthalmologists, and several aspects of real treatment expectancy are still being discussed and not yet fully elucidated. A univocal definition of responsiveness to treatment has not been reached. How the clinicians can evaluate the therapeutic success? The evaluation of systemic and ocular factors should help in this complex management. The age influences the long-term outcomes, and the role of glycemic control is confounded by contrasting correlations between hemoglobin glycated A1c and DME. Long-term treatment success is influenced by baseline best-corrected visual acuity (BCVA), central macular thickness (CMT) and early BCVA response. Also baseline diabetic retinopathy severity scale score is useful to evaluate the chances of improvement before and during treatments. The time-switching was influenced by early BCVA response, however considering a delayed response in a percentage of patients. Several structural optical coherence tomography (OCT) findings could predict long-term success, as the presence of serous retinal detachment, hyperreflective retinal spots, the disruption of external limiting membrane and ellipsoid zone, the disorganization of inner retinal layers and continued increase in CMT were considered predictors of poor response to treatment. Foveal avascular zone enlargement, high number of microaneurysms (Mas), lower vessel density (VD) in deep capillary plexus and lower parafoveal VD in superficial capillary plexus were considered as OCT angiography biomarkers of poor responsiveness. The aim of this review is to report the factors that could influence the response to treatment of DME patients.