Muhammad Bayu Sasongko

Alterations in Retinal Microvascular Geometry in Young Type 1 Diabetes

OBJECTIVE To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes (aged 12–20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. RESULTS Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P ≤ 0.001) and increased arteriolar optimality deviation (P = 0.018), higher A1C was associated with increased arteriolar tortuosity (>8.5 vs. ≤8.5%, P = 0.008), higher SBP was associated with decreased arteriolar LDR (P = 0.002), and higher total cholesterol levels were associated with increased arteriolar LDR (P = 0.044) and decreased venular optimality deviation (P = 0.044). These associations remained after controlling for A1C, retinal vessel caliber, and retinopathy status and were seen in subjects without retinopathy. CONCLUSIONS Key diabetes-related factors affect retinal microvascular geometry in young type 1 diabetes, even in those without evidence of retinopathy. These early retinal alterations may be markers of diabetes microvascular complications.

Serum Apolipoprotein AI and B Are Stronger Biomarkers of Diabetic Retinopathy Than Traditional Lipids

OBJECTIVE To describe and compare the associations of serum lipoproteins and apolipoproteins with diabetic retinopathy. RESEARCH DESIGN AND METHODS This was a cross-sectional study of 224 diabetic patients (85 type 1 and 139 type 2) from a diabetes clinic. Diabetic retinopathy was graded from fundus photographs according to the Airlie House Classification system and categorized into mild, moderate, and vision-threatening diabetic retinopathy (VTDR). Serum traditional lipids (total, LDL, non–HDL, and HDL cholesterol and triglycerides) and apolipoprotein AI (apoAI), apolipoprotein B (apoB), and the apoB-to-apoAI ratio were assessed. RESULTS Diabetic retinopathy was present in 133 (59.4%) individuals. After adjustment for age, sex, diabetes duration, A1C, systolic blood pressure, and diabetes medications, the HDL cholesterol level was inversely associated with diabetic retinopathy (odds ratio 0.39 [95% CI 0.16–0.94], highest versus lowest quartile; Ptrend = 0.017). The ApoAI level was inversely associated with diabetic retinopathy (per SD increase, 0.76 [95% CI 0.59–0.98]), whereas apoB (per SD increase, 1.31 [1.02–1.68]) and the apoB-to-apoAI ratio (per SD increase, 1.48 [1.13–1.95]) were positively associated with diabetic retinopathy. Results were similar for mild to moderate diabetic retinopathy and VTDR. Traditional lipid levels improved the area under the receiver operating curve by 1.8%, whereas apolipoproteins improved the area by 8.2%. CONCLUSIONS ApoAI and apoB and the apoB-to-apoAI ratio were significantly and independently associated with diabetic retinopathy and diabetic retinopathy severity and improved the ability to discriminate diabetic retinopathy by 8%. Serum apolipoprotein levels may therefore be stronger biomarkers of diabetic retinopathy than traditional lipid measures.

Differential Association of Serum Lipids with Diabetic Retinopathy and Diabetic Macular Edema

PURPOSE To assess the association of serum lipids with diabetic retinopathy (DR), diabetic macular edema (DME), and macular thickness in adults with diabetes. METHODS Diabetic patients aged ≥ 18 years were prospectively recruited from specialized eye clinics in Melbourne, Australia. Fasting total-C (cholesterol), triglyceride, HDL-C, non-HDL-C, and LDL-C were assessed. DR was graded from fundus photographs and classified into mild, moderate, severe nonproliferative, and proliferative DR and separately graded for the presence of DME, including clinically significant macular edema (CSME). Macular thickness was assessed using optical coherence tomography (OCT). RESULTS A total of 500 participants (median age, 65 years) were examined. DR, DME, and CSME were present in 321 (66.2%), 149 (33.0%), and 68 (15.0%) patients, respectively. Serum lipid levels were not related to DR or DME. In multivariate models adjusted for traditional risk factors and lipid medications, persons with higher total-, LDL-, and non-HDL-C were more likely to have CSME (odds ratio of 1.54, 1.49, and 1.63 per 1-SD increase, respectively; all P < 0.05). No association was found for serum lipids with macular thickness, as assessed by OCT. The pattern of these associations remained similar in both type 1 and type 2 diabetes, although it was statistically significant only in type 2 diabetes. CONCLUSIONS Serum lipids are independently associated with the CSME, but not with DR, mild or moderate DME, or macular thickness. These data reflect the different impact of hyperlipidemia in the pathogenesis of DR and DME and may explain the discrepancies in previous studies.

Retinal Vascular Geometry Predicts Incident Retinopathy in Young People With Type 1 Diabetes A prospective cohort study from adolescence

OBJECTIVE To examine the association between retinal vascular geometry and subsequent development of incident retinopathy in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS A prospective cohort study of 736 people with type 1 diabetes aged 12 to 20 years, retinopathy-free at baseline, attending an Australian tertiary care hospital. Retinopathy was determined from seven-field retinal photographs according to the modified Airlie House Classification. Retinal vascular geometry, including length/diameter ratio (LDR) and simple tortuosity (ST), was quantified in baseline retinal photographs. Generalized estimating equations were used to determine risk of retinopathy associated with baseline LDR and ST, adjusting for other factors. RESULTS After a median 3.8 (interquartile range 2.4–6.1) years of follow-up, incident retinopathy developed in 287 of 736 (39%). In multivariate analysis, lower arteriolar LDR (odds ratio 1.8 [95% CI 1.2–2.6]; 1st vs. 4th quartile) and greater arteriolar ST (1.5 [1.0–2.2]; 4th vs. 1st quartile) predicted incident retinopathy after adjusting for diabetes duration, sex, A1C, blood pressure, total cholesterol, and BMI. In subgroup analysis by sex, LDR predicted incident retinopathy in male and female participants (2.1 [1.1–4.0] and 1.7 [1.1–2.7]; 1st vs. 4th quartiles, respectively) and greater arteriolar ST predicted incident retinopathy in male participants (2.4 [1.1–4.4]; 4th vs. 1st quartile) only. CONCLUSIONS Lower arteriolar LDR and greater ST were independently associated with incident retinopathy in young people with type 1 diabetes. These vascular geometry measures may serve as risk markers for diabetic retinopathy and provide insights into the early structural changes in diabetic microvascular complications.

Retinal Arteriolar Changes: Intermediate Pathways Linking Early Life Exposures to Cardiovascular Disease?

Microcirculation (2010) 17, 21–31. doi: 10.1111/j.1549‐8719.2009.00007.x

Systemic associations of dynamic retinal vessel analysis: a review of current literature.

Endothelial dysfunction is a key pathogenic mechanism of CVD. The retinal microvascular network offers a unique, non‐invasive window to study endothelial function. Recently, dynamic measurement of retinal vessel caliber using flicker light stimulation has been used to evaluate potential endothelial dysfunction and other mechanisms in CVD. A variety of studies now indicate that retinal vasodilation during flicker light simulation is reduced in diabetes, hypertension, hyperlipidemia and obesity, and may be influenced by age and race/ethnicity. These data suggest that flicker light‐induced retinal vasodilation may be a unique and non‐invasive measure of endothelial dysfunction. This review focuses recent studies on systemic associations of flicker light‐induced retinal vasodilation, and discusses the potential for future research in this area.

Does Retinal Vascular Geometry Vary with Cardiac Cycle

PURPOSE Changes in retinal vascular parameters have been shown to be associated with systemic vascular diseases. In this study, we assessed the physiologic variations in retinal vascular measurements during the cardiac cycle. METHODS Fundus images were taken using electrocardiogram-synchronized retinal camera at nine distinct cardiac points from 15 healthy volunteers (135 images). Analyses of retinal vessel geometric measures, including retinal vessel caliber (individual and summary), tortuosity, branching angle, length-diameter ratio (LDR), and optimality deviation, were performed using semiautomated computer software. Repeated-measures ANOVAs were used to obtain the means and to estimate the variation of each cardiac point compared with cardiac point 1. RESULTS There was a significant variation of the caliber of the individual arteriolar and venular vessels. However, there was no significant variation found for vessel caliber summary, represented by the central retinal arteriolar equivalent (CRAE) and the central retinal venular equivalent (CRVE). There was also no significant variation found for tortuosity and branching angle, and LDR showed none or very little variations at different cardiac points: variations in caliber ranges between 0 and 4.1%, tortuosity 0 and 1.5%, branching angle 0 and 3.5%, and LDR 0 and 2%; all values for variations, P > 0.1; linear trend, P > 0.5; and nonlinear trend, P > 0.8. CONCLUSIONS This study showed that there were minimal variations in the CRAE, CRVE, tortuosity, and branching angle that are clinically used for two-dimensional measures of retinal vascular geometry during cardiac cycles. However, there was significant variation in the caliber of the individual vessels over the cardiac cycle.

Longer Axial Length Is Protective of Diabetic Retinopathy and Macular Edema

PURPOSE To assess the association of ocular biometric parameters and refractive error with diabetic retinopathy (DR) and diabetic macular edema (DME) in persons with diabetes. DESIGN Cross-sectional, clinic-based study. PARTICIPANTS Patients with diabetes aged 18 years or more from the Royal Victorian Eye and Ear Hospital, Victoria, Australia. METHODS Spherical equivalent (SE) refraction was assessed using objective autorefraction. Axial length (AL), corneal curvature (CC), and anterior chamber depth (ACD) were measured using the IOLMaster (Carl Zeiss Meditech AG, Jena, Germany). Diabetic retinopathy was graded from 2-field retinal photographs using the modified Airlie House classification system. Diabetic macular edema was defined as absent or present from fundus photographs and confirmed by optical coherence tomography (Stratus, Carl Zeiss Meditech AG). MAIN OUTCOME MEASURES Severity of DR was grouped as no DR, mild DR (Early Treatment of Diabetic Retinopathy Study [ETDRS] = 20), moderate DR (ETDRS = 31-43), and severe DR (ETDRS >43). Diabetic macular edema severity was classified as mild, moderate, or severe. RESULTS A total of 208 of 630 eyes (33.0%) had DR. In multivariate models, eyes with longer AL were less likely to have mild (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.41-0.83; P = 0.006 per mm increase), moderate (OR, 0.73; 95% CI, 0.60-0.88; P = 0.002), and severe DR (OR, 0.67; 95% CI, 0.53-0.85; P=0.01), and had a lesser risk of mild (OR, 0.70; 95% CI, 0.56-0.86; P < 0.001) and moderate DME (OR, 0.72; 95% CI, 0.56-0.93; P=0.002) but not severe DME. No association was found for SE, ACD, and CC with DR. CONCLUSIONS In persons with diabetes, eyes with longer ALs are less likely to have DR and DME.

Retinal Vascular Geometry Predicts Incident Renal Dysfunction in Young People With Type 1 Diabetes

OBJECTIVE To examine the relationship between retinal vascular geometry parameters and development of incident renal dysfunction in young people with type 1 diabetes. RESEARCH DESIGN AND METHODS This was a prospective cohort study of 511 adolescents with type 1 diabetes of at least 2 years duration, with normal albumin excretion rate (AER) and no retinopathy at baseline while attending an Australian tertiary-care hospital. AER was quantified using three overnight, timed urine specimen collections and early renal dysfunction was defined as AER >7.5 μg/min. Retinal vascular geometry (including length-to-diameter ratio [LDR] and simple tortuosity [ST]) was quantified from baseline retinal photographs. Generalized estimating equations were used to examine the relationship between incident renal dysfunction and baseline venular LDR and ST, adjusting for age, diabetes duration, glycated hemoglobin (A1C), blood pressure (BP), BMI, and cholesterol. RESULTS Diabetes duration at baseline was 4.8 (IQR 3.3–7.5) years. After a median 3.7 (2.3–5.7) years follow-up, 34% of participants developed incident renal dysfunction. In multivariate analysis, higher retinal venular LDR (odds ratio 1.7, 95% CI 1.2–2.4; quartile 4 vs. 1–3) and lower venular ST (1.6, 1.1–2.2; quartile 1 vs. 2–4) predicted incident renal dysfunction. CONCLUSIONS Retinal venular geometry independently predicted incident renal dysfunction in young people with type 1 diabetes. These noninvasive retinal measures may help to elucidate early mechanistic pathways for microvascular complications. Retinal venular geometry may be a useful tool to identify individuals at high risk of renal disease early in the course of diabetes.

Novel versus traditional risk markers for diabetic retinopathy

Aims/hypothesisTo explore the relative contribution of novel and traditional risk markers for diabetic retinopathy (DR).MethodsA clinic-based study of 224 diabetic patients (85 type 1, 139 type 2) from a diabetes clinic was performed. DR was graded from fundus photographs according to the Airlie House Classification system and classified as absent or present (at least ETDRS level 14). Novel risk markers assessed included serum apolipoprotein (Apo) AI and B, skin microvascular responses to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) iontophoresis, flicker-light-induced retinal vasodilation and retinal vascular tortuosity. Relative contribution was determined by semi-partial correlation coefficient generated from a logistic regression model containing all traditional and novel risk markers simultaneously.ResultsThere were 144 (64.3%) participants with DR. Of the novel markers, ApoAI, flicker-light-induced vasodilation and retinal arteriolar tortuosity were significantly associated with DR, independently of traditional measures (all p < 0.03). Diabetes duration contributed most (51%) to the risk of DR, followed by ApoAI (16%), systolic blood pressure (13%), retinal arteriolar tortuosity (8%) and flicker-light-induced venular and arteriolar dilation (3% and 0.5%, respectively).Conclusions/interpretationApoAI and retinal arteriolar tortuosity made considerable contributions to DR risk, independently of traditional risk markers. Findings from this study suggest that serum ApoAI and retinal arteriolar tortuosity may be novel and independent risk markers of DR.