Diurnal Refractive Error Fluctuations in Diabetic and Control Subjects

Purpose: Refractive error has been shown to fluctuate in poorly controlled diabetic patients. The purpose of this study was to measure acute diurnal fluctuations in refractive error and blood glucose levels (BGLs) in diabetic and control subjects. Methods: Twenty-one type 2 diabetic subjects (age 56 ± 11 years), 20 type 1 diabetic subjects (age 38 ± 15 years) and 20 non-diabetic controls (age 49 ± 23 years) took part in the study. Refractive error was measured with an OPD ARK-10000 autorefractometer (Nidek) and BGLs were measured using a finger stick test (Hemocue). All measurements were taken six times during the day, between 8AM and 8PM at approximately twohourly intervals. Using power vector analysis the variability in refractive error was mapped against time of day and related to BGLs, HbA1c, diabetic status and duration of disease. Results: Refractive error was similar between groups (p=0.96) and did not fluctuate significantly during the day in any of the three groups (ANOVA p>0.05). The mean ± SD values for BGLs during the day were 10.4 ± 4.40mM/l in DM type 2, 10.3 ± 5.30mM/l in DM type 1, and 5.4 ± 1.04mM/l in control subjects. BGLs changed significantly during the day and between groups (ANOVA p0.05). Multiple regression analysis showed that neither BGLs, HbA1c, diabetic status, nor duration of disease had a significant effect on diurnal refractive error measurements. (p>0.05). Conclusions: Diurnal changes in BGLs do not result in significant acute refractive error fluctuations in diabetic patients, as measured with an autorefractometer. CR: C. O’Donnell, None; H. Workman, None; S.L. Hosking, None; B. Huntjens, None. Support: Supported by a PhD studentship from Lein Applied Diagnostics Ltd

Does the Swedish Interactive Threshold Algorithm (SITA) accurately map visual field loss attributed to vigabatrin?

Purpose Vigabatrin (VGB) is an anti-epileptic medication which has been linked to peripheral constriction of the visual field. Documenting the natural history associated with continued VGB exposure is important when making decisions about the risk and benefits associated with the treatment. Due to its speed the Swedish Interactive Threshold Algorithm (SITA) has become the algorithm of choice when carrying out Full Threshold automated static perimetry. SITA uses prior distributions of normal and glaucomatous visual field behaviour to estimate threshold sensitivity. As the abnormal model is based on glaucomatous behaviour this algorithm has not been validated for VGB recipients. We aim to assess the clinical utility of the SITA algorithm for accurately mapping VGB attributed field loss. Methods The sample comprised one randomly selected eye of 16 patients diagnosed with epilepsy, exposed to VGB therapy. A clinical diagnosis of VGB attributed visual field loss was documented in 44% of the group. The mean age was 39.3 years ± 14.5 years and the mean deviation was -4.76 dB ±4.34 dB. Each patient was examined with the Full Threshold, SITA Standard and SITA Fast algorithm. Results SITA Standard was on average approximately twice as fast (7.6 minutes) and SITA Fast approximately 3 times as fast (4.7 minutes) as examinations completed using the Full Threshold algorithm (15.8 minutes). In the clinical environment, the visual field outcome with both SITA algorithms was equivalent to visual field examination using the Full Threshold algorithm in terms of visual inspection of the grey scale plots , defect area and defect severity. Conclusions Our research shows that both SITA algorithms are able to accurately map visual field loss attributed to VGB. As patients diagnosed with epilepsy are often vulnerable to fatigue, the time saving offered by SITA Fast means that this algorithm has a significant advantage for use with VGB recipients

Diurnal Fluctuations in Higher-Order Aberrations in Patients with Diabetes Mellitus

Purpose: The purpose of this study was to investigate diurnal fluctuations in aberrations and blood glucose levels (BGLs) in diabetic patients and control subjects. Methods: Twenty-one type 2 diabetic subjects (age 56 ± 11 years), 20 type 1 diabetic subjects (age 38 ± 15 years) and 20 non-diabetic controls (age 49 ± 23 years) took part in the study. The distribution of refractive errors was similar between groups (p=0.96). Aberrations were measured with an OPD autorefractometer (NIDEK) and analysed for a 5mm pupil diameter. BGLs were measured using a finger stick test (Hemocue). All measurements were taken six times during the day, between 8AM and 8PM at approximately two-hourly intervals. Results: The coefficients of third order coma, fourth order spherical aberration, and higher-order RMS error were found to be higher in the diabetic compared to the control group. The mean variation in the third and fourth order aberrations over the twelve-hour period was found to be higher in the diabetic when compared to the control group; however, these differences were not statistically significant. The higher-order RMS error showed a negative correlation with time in the diabetic group compared to a positive correlation in the control group (gradient: -6.4 x 10-3 in type 2 diabetes, -24.4 x 10-3 in type 1 diabetes and 74.9 x 10-3 in control group; ANOVA p=0.025). In diabetic patients, increasing BGLs showed a negative trend with the third order horizontal coma (p=0.44) and fourth order spherical aberration coefficients (p= 0.61), while a positive trend was observed between BGLs and the third order vertical coma (p=0.58) and higher order RMS (p=0.47). Conclusions: Compared to controls, diabetic patients exhibit greater variation in higher order aberrations. Ocular aberration coefficients varied during the day, with fluctuating BGLs. The variation in ocular aberration coefficients is possibly due to the effect of large fluctuations in BGLs leading to hydration effects on the diabetic crystalline lens. CR: B. Huntjens, None; H. Radhakrishnan, None; H. Workman, None; S.L. Hosking, None; C. O’Donnell, None. Support: Supported by a PhD studentship from Lein Applied Diagnostics Lt

Evidence for energy conservation during pubertal growth. A 10-year longitudinal study (EarlyBird 71)

BACKGROUND: Diabetes is closely linked to obesity, and obesity rates climb during adolescence for reasons that are not clear. Energy efficiency is important to obesity, and we describe a temporary but substantial fall in absolute energy expenditure, compatible with improved energy efficiency, during the rapid growth phase of puberty. METHODS: In a longitudinal cohort study lasting 10 years, we measured voluntary energy expenditure as physical activity (PA) by accelerometry, involuntary energy expenditure as resting energy expenditure (REE) by oxygen consumption, body mass index (BMI) and body composition by dual energy X-ray absorptiometry annually on 10 occasions from 7 to 16 years in the 347 children of the EarlyBird study. We used mixed effects modelling to analyse the trends in REE and their relationship to BMI, lean mass (LM), fat mass (FM), age, PA and pubertal stage. RESULTS: Relative REE and total PA fell during puberty, as previously described, but the longitudinal data and narrow age-range of the cohort (s.d.±4m) revealed for the first time a substantial fall in absolute REE during the period of maximum growth. The fall became clearer still when adjusted for FM and LM. The fall could not be explained by fasting insulin, adiponectin, leptin, luteinising hormone or follicle stimulating hormone. CONCLUSIONS: There appears to be a temporary but substantial reduction in energy expenditure during puberty, which is unrelated to changes in body composition. If it means higher energy efficiency, the fall in REE could be advantageous in an evolutionary context to delivering the extra energy needed for pubertal growth, but unfavourable to weight gain in a contemporary environment.International Journal of Obesity advance online publication, 4 October 2016; doi:10.1038/ijo.2016.158.We are grateful to the Bright futures trust, Fountain Foundation, BUPA Foundation, EarlyBird Diabetes Trust and countless individual donors who made this study possible

Estimation of conditional laws given an extreme component

Let $(X,Y)$ be a bivariate random vector. The estimation of a probability of the form $P(Y\leq y \mid X >t)$ is challenging when $t$ is large, and a fruitful approach consists in studying, if it exists, the limiting conditional distribution of the random vector $(X,Y)$, suitably normalized, given that $X$ is large. There already exists a wide literature on bivariate models for which this limiting distribution exists. In this paper, a statistical analysis of this problem is done. Estimators of the limiting distribution (which is assumed to exist) and the normalizing functions are provided, as well as an estimator of the conditional quantile function when the conditioning event is extreme. Consistency of the estimators is proved and a functional central limit theorem for the estimator of the limiting distribution is obtained. The small sample behavior of the estimator of the conditional quantile function is illustrated through simulations.Comment: 32 pages, 5 figur

Ogre and Pythia: An Invariance Proof Method for Weak Consistency Models

We design an invariance proof method for concurrent programs parameterised by a weak consistency model. The calculational design of the invariance proof method is by abstract interpretation of a truly parallel analytic semantics. This generalises the methods by Lamport and Owicki-Gries for sequential consistency. We use cat as an example of language to write consistency specifications of both concurrent programs and machine architectures