Prevalence of Glaucoma Following Paediatric Cataract Surgery in an Australian Tertiary Referral Centre.

Purpose: Secondary glaucoma following childhood cataract surgery remains the most common complication in the paediatric population. This study aimed to determine the incidence, time to progression and risk factors associated with the development of secondary glaucoma following childhood cataract surgery in a paediatric population. Outcome measures were the detection of secondary glaucoma, postoperative time frame to development of glaucoma and risk factors in its development. Patients and Methods: A retrospective case series was conducted between 2003 and 2017 at a tertiary children's hospital in Sydney. The patient population included those 16 years or less of age who underwent congenital cataract extraction, with or without an intraocular lens implantation and who had been followed up for a minimum of six months following surgery. Patients were excluded if they had cataract aetiology other than congenital idiopathic cataract. Multivariate Cox Regression analysis was used to determine relevant risk factors. Results: A total of 320 eyes in 216 patients were included in the study. Secondary glaucoma developed in 11.9% of eyes. In those that developed secondary glaucoma, the average time to onset from surgery was 3.2 years (median 2.75 years). The mean age of diagnosis of secondary glaucoma was 4.58 years (median 3.5 years, range 2.5 months to 13.23 years). Microcornea was the only adverse characteristic significantly associated with an increased risk of secondary glaucoma (HR 6.30, p 0.003). Conclusion: Despite modern surgical techniques, glaucoma remains a significant long-term sequela in children following cataract surgery.

Optimal Frequency of Retinopathy Screening in Adolescents With Type 1 Diabetes: Markov Modeling Approach Based on 30 Years of Data.

OBJECTIVE: Current guidelines recommend biennial diabetic retinopathy (DR) screening commencing at the age of 11 years and after 2-5 years' duration of type 1 diabetes. Growing evidence suggests less frequent screening may be feasible. RESEARCH DESIGN AND METHODS: Prospective data were collected from 2,063 youth with type 1 diabetes who were screened two or more times between 1990 and 2019. Baseline (mean ± SD) age was 13.3 ± 1.8 years, HbA1c was 8.6 ± 1.3% (70.1 ± 14.7 mmol/mol), diabetes duration was 5.6 ± 2.8 years, and follow-up time was 4.8 ± 2.8 years. DR was manually graded from 7-field retinal photographs using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Markov chain was used to calculate probabilities of DR change over time and hazard ratio (HR) of DR stage transition. RESULTS: The incidence of moderate nonproliferative DR (MNPDR) or worse was 8.6 per 1,000 patient-years. Probabilities of transition to this state after a 3-year interval were from no DR, 1.3%; from minimal DR, 5.1%; and from mild DR, 22.2%, respectively. HRs (95% CIs) for transition per 1% current HbA1c increase were 1.23 (1.16-1.31) from no DR to minimal NPDR, 1.12 (1.03-1.23) from minimal to mild NPDR, and 1.28 (1.13-1.46) from mild to MNPDR or worse. HbA1c alone explained 27% of the transitions between no retinopathy and MNPDR or worse. The addition of diabetes duration into the model increased this value to 31% (P = 0.03). Risk was also increased by female sex and higher attained age. CONCLUSIONS: These results support less frequent DR screening in youth with type 1 diabetes without DR and short duration. Although DR progression to advanced stages is generally slow, higher HbA1c greatly accelerates it.

Thirty-Year Time Trends in Diabetic Retinopathy and Macular Edema in Youth With Type 1 Diabetes.

OBJECTIVE: To examine trends in diabetic retinopathy (DR) and diabetic macular edema (DME) in adolescents with type 1 diabetes between 1990 and 2019. RESEARCH DESIGN AND METHODS: We analyzed 5,487 complication assessments for 2,404 adolescents (52.7% female, aged 12-20 years, diabetes duration >5 years), stratified by three decades (1990-1999, 2000-2009, 2010-2019). DR and DME were graded according to the modified Airlie House classification from seven-field stereoscopic fundal photography. RESULTS: Over three decades, the prevalence of DR was 40, 21, and 20% (P < 0.001) and DME 1.4, 0.5, and 0.9% (P = 0.13), respectively, for 1990-1999, 2000-2009, and 2010-2019. Continuous subcutaneous insulin infusion (CSII) use increased (0, 12, and 55%; P < 0.001); mean HbA1c was bimodal (8.7, 8.5, and 8.7%; P < 0.001), and the proportion of adolescents meeting target HbA1c <7% did not change significantly (8.3, 7.7, and 7.1%; P = 0.63). In multivariable generalized estimating equation analysis, DR was associated with 1-2 daily injections (odds ratio 1.88, 95% CI 1.42-2.48) and multiple injections in comparison with CSII (1.38, 1.09-1.74); older age (1.11, 1.07-1.15), higher HbA1c (1.19, 1.05-1.15), longer diabetes duration (1.15, 1.12-1.18), overweight/obesity (1.27, 1.08-1.49) and higher diastolic blood pressure SDS (1.11, 1.01-1.21). DME was associated with 1-2 daily injections (3.26, 1.72-6.19), longer diabetes duration (1.26, 1.12-1.41), higher diastolic blood pressure SDS (1.66, 1.22-2.27), higher HbA1c (1.28, 1.03-1.59), and elevated cholesterol (3.78, 1.84-7.76). CONCLUSIONS: One in five adolescents with type 1 diabetes had DR in the last decade. These findings support contemporary guidelines for lower glycemic targets, increasing CSII use, and targeting modifiable risk factors including blood pressure, cholesterol, and overweight/obesity.

Fractal Dimension Analysis of Transient Visual Evoked Potentials: Optimisation and Applications.

PURPOSE: The visual evoked potential (VEP) provides a time series signal response to an external visual stimulus at the location of the visual cortex. The major VEP signal components, peak latency and amplitude, may be affected by disease processes. Additionally, the VEP contains fine detailed and non-periodic structure, of presently unclear relevance to normal function, which may be quantified using the fractal dimension. The purpose of this study is to provide a systematic investigation of the key parameters in the measurement of the fractal dimension of VEPs, to develop an optimal analysis protocol for application. METHODS: VEP time series were mathematically transformed using delay time, τ, and embedding dimension, m, parameters. The fractal dimension of the transformed data was obtained from a scaling analysis based on straight line fits to the numbers of pairs of points with separation less than r versus log(r) in the transformed space. Optimal τ, m, and scaling analysis were obtained by comparing the consistency of results using different sampling frequencies. The optimised method was then piloted on samples of normal and abnormal VEPs. RESULTS: Consistent fractal dimension estimates were obtained using τ = 4 ms, designating the fractal dimension = D2 of the time series based on embedding dimension m = 7 (for 3606 Hz and 5000 Hz), m = 6 (for 1803 Hz) and m = 5 (for 1000Hz), and estimating D2 for each embedding dimension as the steepest slope of the linear scaling region in the plot of log(C(r)) vs log(r) provided the scaling region occurred within the middle third of the plot. Piloting revealed that fractal dimensions were higher from the sampled abnormal than normal achromatic VEPs in adults (p = 0.02). Variances of fractal dimension were higher from the abnormal than normal chromatic VEPs in children (p = 0.01). CONCLUSIONS: A useful analysis protocol to assess the fractal dimension of transformed VEPs has been developed.

Strategies for the Management of Congenital Iris Cysts.

Iris cysts can arise from iris pigment epithelium or stroma. We present 3 cases of iris cysts which have been managed in different ways. In a one-month neonate, cyst was punctured with keratome and gentle diode laser endophotocoagulation was applied to the base. A2.5-month infant presented with watering and blepharospasm since birth. Clear fluid was aspirated from the cyst with a 27-gauge needle and Ethanol 96% (ETOH) was injected into the cyst and then aspirated. It was followed by injection/aspiration of 0.3 ml of balanced salt solution thrice. Cyst wall was excised. A13-month toddler presented with 4-month history of intermittent irritation and photophobia. The cyst was aspirated with a 25-gauge needle and the cyst walls were nibbled with 20-gauge vitrectomy cutter. Excision is better than injection of sclerosing solutions. The aim is to remove the whole cyst to avoid recurrence and to prevent amblyopia.

Association Between HbA1c Variability and Risk of Microvascular Complications in Adolescents With Type 1 Diabetes.

CONTEXT: There is a paucity of data regarding the association between glycosylated hemoglobin (HbA1c) variability and risk of microvascular complications in adolescents with type 1 diabetes (T1D). OBJECTIVE: To investigate the association between HbA1c variability and risk of microvascular complications in adolescents with T1D. DESIGN: Prospective cohort study from 1990 to 2014 (median follow-up, 8.1 y). SETTING: Tertiary pediatric hospital. PARTICIPANTS: A total of 1706 adolescents (aged 12-20 minimum diabetes duration 5 y) with median age of 15.9 years (interquartile range, 14.3-17.5) and diabetes duration of 8.1 years (6.3-10.8). MAIN OUTCOME MEASURES: Glycemic variability was computed as the SD of all HbA1c measurements (SD-HbA1c) after diagnosis. Retinopathy was detected using 7-field fundal photography, renal function assessed using albumin excretion rate, peripheral neuropathy detected using thermal and vibration threshold testing, and cardiac autonomic neuropathy (CAN) detected using time- and frequency-domain analyses of electrocardiogram recordings. Generalized estimating equations were used to examine the relationship between complications outcomes and HbA1c variability, after adjusting for known risk factors, including HbA1c, diabetes duration, blood pressure, and lipids. RESULTS: In multivariable analysis, SD-HbA1c was associated with early retinopathy (odds ratio [OR] 1.32; 95% confidence interval, 1.00-1.73), albuminuria (OR 1.81; 1.04-3.14), increased log10 albumin excretion rate (OR 1.10; 1.05-1.15) and CAN (OR 2.28; 1.23-4.21) but not peripheral neuropathy. CONCLUSIONS: Greater HbA1c variability predicts retinopathy, early nephropathy, and CAN, in addition to established risk factors, in adolescents with T1D. Minimizing long term fluctuations in glycemia may provide additional protection against the development of microvascular complications.

Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality.

OBJECTIVE: To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI). RESEARCH DESIGN AND METHODS: Prospective cohort of 989 patients (aged 12-20 years; diabetes duration >5 years) treated with CSII or MDI for >12 months. Microvascular complications were assessed from 2000-14: early retinopathy (seven-field fundal photography), peripheral nerve function (thermal and vibration threshold testing), autonomic nerve abnormality (heart rate variability analysis of electrocardiogram recordings) and albuminuria (albumin creatinine ratio/timed overnight albumin excretion). Generalized estimating equations (GEE) were used to examine the relationship between treatment and complications rates, adjusting for socio-economic status (SES) and known risk factors including HbA1c and diabetes duration. RESULTS: Comparing CSII with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7), retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07), peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45-0.95, p = 0.029) and peripheral nerve abnormality (OR 0.63, 95% CI 0.42-0.95, p = 0.026), but not albuminuria (OR 0.46, 95% CI 0.10-2.17, p = 0.33). SES was not associated with any of the complication outcomes. CONCLUSIONS: In adolescents, CSII use is associated with lower rates of retinopathy and peripheral nerve abnormality, suggesting an apparent benefit of CSII over MDI independent of glycemic control or SES.

Primary congenital glaucoma outcomes: lessons from 23 years of follow-up.

PURPOSE: To determine in primary congenital glaucoma whether age of presentation influences surgical success, the degrees of angle surgery needed to achieve glaucoma control, and whether there are critical ages where glaucoma progresses, requiring further surgical management. DESIGN: Retrospective cohort study. METHODS: The medical records of patients with primary congenital glaucoma over a 23-year period were reviewed: 192 procedures were performed on 117 eyes (70 patients). The number and age of angle procedures and final visual acuity was analyzed. Surgical success was defined as stable intraocular pressure and optic disc appearance. RESULTS: Procedures involving 83 of the 110 eyes (75.5%) undergoing angle surgery were successful, with 2-, 4-, 6-, and 10-year success rates of 92%, 86%, 84%, and 75%, respectively. Subgroup analysis (<3 months; 3-6 months; >6 months) comparing age of diagnosis to visual outcome (<20/200, 20/200-20/40, >20/40) was significant (P = .04). The age at first operation (P = .94), the number of angle operations (P = .43), and their effect on angle surgery success was not significant. Seven of 192 operations were performed after the age of 8 years (3.6%). After the initial angle surgeries within the first year of life, the third procedure occurred at a median age of 2.4 years (interquartile ratio [IQR] 0.6-3.8 years) and the fourth procedure occurred at a median age of 5.3 years (IQR 2.5-6.1 years). CONCLUSIONS: Children diagnosed at <3 months of age had a visual outcome of <20/200 despite successful glaucoma control. Age of presentation did not affect surgical success. A total of 78.9% of cases undergoing primary trabeculotomy were controlled with 1 operation: 4 clock hours of angle (120 degrees). Analysis of glaucoma progression suggests critical ages where further glaucoma surgery is required at around 2 and 5 years of age.

Plantar fascia thickness is longitudinally associated with retinopathy and renal dysfunction: a prospective study from adolescence to adulthood.

AIM: The aim was to study the longitudinal relationship between plantar fascia thickness (PFT) as a measure of tissue glycation and microvascular (MV) complications in young persons with type 1 diabetes (T1DM). METHODS: We conducted a prospective longitudinal cohort study of 152 (69 male) adolescents with T1DM who underwent repeated MV complications assessments and ultrasound measurements of PFT from baseline (1997-2002) until 2008. Retinopathy was assessed by 7-field stereoscopic fundal photography and nephropathy by albumin excretion rate (AER) from three timed overnight urine specimens. Longitudinal analysis was performed using generalized estimating equations (GEE). RESULTS: Median (interquartile range) age at baseline was 15.1 (13.4-16.8) years, and median follow-up was 8.3 (7.0-9.5) years, with 4 (3-6) visits per patient. Glycemic control improved from baseline to final visit [glycated hemoglobin (HbA1c) 8.5% to 8.0%, respectively; p = .004]. Prevalence of retinopathy increased from 20% to 51% (p < .001) and early elevation of AER (>7.5 µg/min) increased from 26% to 29% (p = .2). A greater increase in PFT (mm/year) was associated with retinopathy at the final assessment (ΔPFT 1st vs. 2nd-4th quartiles, χ(2) = 9.87, p = .02). In multivariate GEE, greater PFT was longitudinally associated with retinopathy [odds ratio (OR) 4.6, 95% confidence interval (CI) 2.0-10.3] and early renal dysfunction (OR 3.2, CI 1.3-8.0) after adjusting for gender, blood pressure standard deviation scores, HbA1c, and total cholesterol. CONCLUSIONS: In young people with T1DM, PFT was longitudinally associated with retinopathy and early renal dysfunction, highlighting the importance of early glycemic control and supporting the role of metabolic memory in MV complications. Measurement of PFT by ultrasound offers a noninvasive estimate of glycemic burden and tissue glycation.

Continued reduction in the prevalence of retinopathy in adolescents with type 1 diabetes: role of insulin therapy and glycemic control.

OBJECTIVE: To examine trends in microvascular complications in adolescents with type 1 diabetes between 1990 and 2009 in Sydney, Australia. RESEARCH DESIGN AND METHODS: We used analysis of complications in 1,604 adolescents (54% female, aged 12-20 years, median duration 8.6 years), stratified by four time periods using Generalized Estimation Equations as follows: T1 (1990-1994), T2 (1995-1999), T3 (2000-2004), and T4 (2005-2009). Early retinopathy was detected using seven-field fundal photography, albumin excretion rate (AER) using timed overnight urine collections, and albumin-to-creatinine ratio (ACR) and peripheral nerve function using thermal and vibration threshold. RESULTS: Retinopathy declined (53, 38, 23, and 12%; P < 0.001), as did borderline elevation of AER/ACR (45, 30, 26, and 30%; P < 0.001) and microalbuminuria (8, 4, 3, and 3%; P = 0.006). Multiple daily injections (MDI)/continuous subcutaneous insulin infusion (CSII) use increased (17, 54, 75, and 88%; P < 0.001), median HbA(1c) decreased (9.1, 8.9, 8.5, and 8.5%; P < 0.001), and severe hypoglycemia was unchanged (6, 8, 10, and 7%; P = 0.272). Retinopathy was associated with diabetes duration (odds ratio [OR] 1.12 [95% CI 1.08-1.17]), age (1.13 [1.06-1.20]), HbA(1c) (1.16 [1.08-1.25]), systolic blood pressure (BP) SDS (1.31 [1.16-1.48]), socioeconomic disadvantage (1.42 [1.04-1.95]), and 1 to 2 injections per day (vs. MDI/CSII; 1.35 [1.05-1.73]); borderline AER/ACR with male sex (1.32 [1.02-1.70]), age (1.19 [1.12-1.26]), HbA(1c) (1.18 [1.08-1.29]), weight SDS (1.31 [1.21-1.53]), insulin dose per kilograms (1.64 [1.13-2.39]), 1 to 2 injections per day (1.41 [1.08-1.84]), and socioeconomic disadvantage (1.68 [1.23-2.31]); and microalbuminuria with age (1.14 [1.01-1.29]), HbA(1c) (1.20 [1.05-1.37]), diastolic BP SDS (1.76 [1.26-2.46]), and 1 to 2 injections per day (1.95 [1.11-3.41]). CONCLUSIONS: The decline in retinopathy supports contemporary guidelines that recommend lower glycemic targets and use of MDI/CSII in children and adolescents with type 1 diabetes.

Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes.

OBJECTIVE: To examine the hypothesis that vitamin D deficiency (VDD) is associated with an increased prevalence of microvascular complications in young people with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a cross-sectional study of 517 patients, 25-hydroxyvitamin D was measured. Retinopathy was assessed by 7-field stereoscopic retinal photography, peripheral neuropathy by thermal and vibration threshold testing, and microalbuminuria by albumin excretion rate or albumin-to-creatinine ratio. RESULTS: Retinopathy prevalence was higher in cases with VDD versus sufficiency (18 vs. 9%, P = 0.02); deficiency was not associated with microalbuminuria or neuropathy. In logistic regression, retinopathy was associated with VDD (odds ratio 2.12 [95% CI 1.03-4.33]), diabetes duration (1.13, 1.05-1.23), and HbA(1c) (1.24, 1.02-1.50). CONCLUSIONS: VDD is associated with an increased prevalence of retinopathy in young people with type 1 diabetes. The inflammatory and angiogenic effects of VDD may contribute to early retinal vascular damage; however, further investigations are warranted.

Microvascular complications assessment in adolescents with 2- to 5-yr duration of type 1 diabetes from 1990 to 2006.

OBJECTIVE: Microvascular complications occur in adolescents with type 1 diabetes, although guidelines vary as to when screening should commence and prevalence data for those with ≤5-yr duration are limited. We therefore investigated trends in prevalence of early microvascular complications over 17 yr. RESEARCH DESIGN AND METHODS: 819 adolescents (54% female) aged 11-17 yr with 2- to 5-yr diabetes duration were assessed for complications at a tertiary pediatric diabetes clinic between 1990 and 2006. Early retinopathy was detected using seven-field fundal photography, albumin excretion rate (AER) by timed overnight urine collections and peripheral nerve function by thermal/vibration threshold at the foot. Results were analyzed by age, time period of assessment, and duration. RESULTS: Early retinopathy declined from 1990 to 2002 (16-7%, p < 0.01), then remained unchanged until 2006. Early elevation of AER (≥7.5 µg/min) and microalbuminuria (≥20 µg/min) did not change over time, whereas peripheral nerve abnormalities increased (14-28%, p < 0.01). Median hemoglobin A1c improved (8.7-8.2%, p < 0.01), in parallel with increased total daily insulin dose and injections per day (p < 0.01). Body mass index standard deviation score increased over time (0.55-0.79, p < 0.01). In multivariate logistic regression, early retinopathy was associated with earlier time period [odds ratio (OR) 0.68, confidence interval (CI) 0.55-0.85, p < 0.01] and older age (OR 1.19, CI 1.02-1.39, p = 0.03). AER ≥ 7.5 µg/min was associated with older age (1.19, 1.06-1.34, p < 0.01) and longer diabetes duration (OR 1.28, CI 1.02-1.62, p = 0.04) and height-adjusted peripheral nerve abnormalities with later time period (OR 1.26, CI 1.05-1.50, p = 0.01). CONCLUSIONS: Early complications are not uncommon in adolescents with 2- to 5-yr diabetes duration, despite more intensive management in recent years.

Role of blood pressure in development of early retinopathy in adolescents with type 1 diabetes: prospective cohort study.

OBJECTIVE: To examine the relation between blood pressure and the development of early retinopathy in adolescents with childhood onset type 1 diabetes. DESIGN: Prospective cohort study. SETTING: Diabetes Complications Assessment Service at the Children's Hospital at Westmead, Sydney, Australia. PARTICIPANTS: 1869 patients with type 1 diabetes (54% female) screened for retinopathy with baseline median age 13.4 (interquartile range 12.0-15.2) years, duration 4.9 (3.1-7.0) years, and albumin excretion rate of 4.4 (3.1-6.8) microg/min plus a subgroup of 1093 patients retinopathy-free at baseline and followed for a median 4.1 (2.4-6.6) years. MAIN OUTCOME MEASURES: Early background retinopathy; blood pressure. RESULTS: Overall, retinopathy developed in 673 (36%) participants at any time point. In the retinopathy-free group, higher systolic blood pressure (odds ratio 1.01, 95% confidence interval 1.003 to 1.02) and diastolic blood pressure (1.01, 1.002 to 1.03) were predictors of retinopathy, after adjustment for albumin excretion rate (1.27, 1.13 to 1.42), haemoglobin A(1c) (1.08, 1.02 to 1.15), duration of diabetes (1.16, 1.13 to 1.19), age (1.13, 1.08 to 1.17), and height (0.98, 0.97 to 0.99). In a subgroup of 1025 patients with albumin excretion rate below 7.5 microg/min, the cumulative risk of retinopathy at 10 years' duration of diabetes was higher for those with systolic blood pressure on or above the 90th centile compared with those below the 90th centile (58% v 35%, P=0.03). The risk was also higher for patients with diastolic blood pressure on or above the 90th centile compared with those below the 90th centile (57% v 35%, P=0.005). CONCLUSIONS: Both systolic and diastolic blood pressure are predictors of retinopathy and increase the probability of early retinopathy independently of incipient nephropathy in young patients with type 1 diabetes.

Plantar fascia thickness, a measure of tissue glycation, predicts the development of complications in adolescents with type 1 diabetes.

OBJECTIVE: Direct measurement of collagen glycation requires skin biopsy, which is invasive. We hypothesized that measurement of plantar fascia thickness (PFT) by ultrasound is an alternative index of tissue glycation and a marker of microvascular disease. RESEARCH DESIGN AND METHODS: This was a prospective longitudinal study of microvascular complications in 344 adolescents with type 1 diabetes, whose PFT was assessed by ultrasound at baseline. Retinopathy was assessed by seven-field fundal photography, albumin excretion rate (AER) measured from three consecutive timed overnight urine specimens, autonomic neuropathy by pupillometry and cardiovascular tests, and peripheral neuropathy by vibration and thermal thresholds. Longitudinal analysis was performed using generalized estimating equations with baseline PFT, duration, and A1C as explanatory variables. RESULTS: At first assessment, median (interquartile range) age was 15.1 (13.5-17.2) years and diabetes duration was 8.5 (6.0-11.5) years. Median follow up was 3.2 (2.1-4.5) years with a median of 4 (2-13) complications assessments per patient. In multivariate analysis, baseline PFT (abnormal in 132 subjects, 38%) predicted subsequent development of retinopathy (odds ratio 2.4 [95% CI 1.1-5.0]), elevated AER (2.24 [1.05-5.11]), peripheral neuropathy (2.3 [1.2-4.41]), and autonomic neuropathy (4.94 [2.46-9.91]). Limited joint mobility was present in only 4%. CONCLUSIONS: PFT is a significant predictor of the subsequent development of complications in type 1 diabetes, suggesting that glycation and oxidation of collagen in soft tissues may be independent risk factors for microvascular complications.

Autonomic nerve testing predicts the development of complications: a 12-year follow-up study.

OBJECTIVE: Cardiac autonomic nerve tests have predicted increased mortality in adults with diabetes, predominantly due to nephropathy, cardiac disease, and hypoglycemia. The significance of subclinical autonomic nerve test abnormalities has not been systematically studied in adolescents. We aimed to reassess an adolescent cohort, whose autonomic nervous system had been tested 12 years earlier by both pupillometry and cardiovascular tests. RESEARCH DESIGN AND METHODS: From 1990 to 1993, adolescents with type 1 diabetes (n = 335) were assessed for autonomic neuropathy (median age 14.7 years [interquartile range 13.0-16.8], duration of diabetes 6.3 years [4.0-9.6], and A1C 8.3% [7.5-9.4]). Between 2003 and 2005, contact was made with 59% of the original group. Individual assessment 12 years later included completion of a validated hypoglycemia unawareness questionnaire (n = 123) and urinary albumin-to-creatinine ratio (n = 99) and retinal (n = 102) screening, as well as analysis of reports from external doctors (n = 35). RESULTS: At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n = 137) and those who did not participate (n = 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P = 0.031). At 12 years of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32 (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no microalbuminuria. Small pupil size at baseline was independently associated with the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32-14.42], P = 0.016) and retinopathy (4.83 [1.3-17.98], P = 0.019) but not with the development of hypoglycemia unawareness. There was no association with baseline cardiovascular tests and the development of complications 12 years later. CONCLUSIONS: In this study, we found an association between baseline pupillometry tests and the presence of microalbuminuria and retinopathy at 12 years of follow-up. This suggests that pupillometry abnormalities may be early indicators of patients who are at high risk of future microvascular disease.

Retinal vascular caliber and risk of retinopathy in young patients with type 1 diabetes.

OBJECTIVE: To examine the relationship between retinal vascular caliber and incident retinopathy in children and adolescents with type 1 diabetes mellitus. DESIGN: Hospital-based case-control study with prospective outcomes. PARTICIPANTS: Cases and controls were selected from a cohort of children and adolescents 12 to 20 years old with type 1 diabetes followed up at a tertiary diabetes clinic. Cases were patients who developed incident diabetic retinopathy (n = 166) after at least 1 year of follow-up (> or =2 clinic visits), and controls were patients who had not developed retinopathy (n = 165) after > or =2 years of follow-up (> or =3 clinic visits). Baseline retinal photographs of cases and controls were digitized, and retinal vascular calibers were measured using a computer-assisted program by a grader masked to case-control status. These measurements were combined into summary indices reflecting the average arteriolar and venular calibers. MAIN OUTCOME MEASURE: Development of diabetic retinopathy. RESULTS: Incident retinopathy cases had retinal arteriolar calibers (mean +/- standard deviation [SD], 206.5+/-18.4 microm) significantly larger than those of controls (200.2+/-16.5 microm) (P = 0.004) but similar retinal venular calibers (329.1+/-14.7 microm in cases vs. 326.4+/-15.1 microm in controls, P = 0.312). After adjusting for age, gender, diabetes duration, glycated hemoglobin levels, blood pressure, body mass index, and pubertal stage, larger arteriolar caliber was predictive of risk of diabetic retinopathy (odds ratio, 1.44 per SD increase in arteriolar caliber; 95% confidence interval, 1.11-1.86). CONCLUSION: Larger retinal arteriolar caliber predicts incident retinopathy in children and adolescents with type 1 diabetes, independent of conventional risk factors for retinopathy. Measurement of retinal vascular caliber may provide prognostic information regarding the subsequent risk of diabetic retinopathy.