Retinal nerve fibre layer thinning associated with diabetic peripheral neuropathy

Aims
To investigate the relationship between retinal nerve fibre layer thickness and peripheral neuropathy in patients with Type 2 diabetes, particularly in those who are at higher risk of foot ulceration.

Methods
Global and sectoral retinal nerve fibre layer thicknesses were measured at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). The level of neuropathy was assessed in 106 participants (82 with Type 2 diabetes and 24 healthy controls) using the 0–10 neuropathy disability score. Participants were stratified into four neuropathy groups: none (0–2), mild (3–5), moderate (6–8), and severe (9–10). A neuropathy disability score ‡ 6 was used to define those at higher risk of foot ulceration. Multivariable regression analysis was performed to assess the effect of neuropathy disability scores, age, disease duration and retinopathy on RNFL thickness.

Results
Inferior (but not global or other sectoral) retinal nerve fibre layer thinning was associated with higher neuropathy disability scores (P = 0.03). The retinal nerve fibre layer was significantly thinner for the group with neuropathy disability scores ‡ 6 in the inferior quadrant (P < 0.005). Age, duration of disease and retinopathy levels did not significantly influence retinal nerve fibre layer thickness. Control participants did not show any significant differences in thickness measurements from the group with diabetes and no neuropathy (P > 0.24 for global and all sectors).

Conclusions
Inferior quadrant retinal nerve fibre layer thinning is associated with peripheral neuropathy in patients with Type 2 diabetes, and is more pronounced in those at higher risk of foot ulceration.

Visual sensitivity loss in the central 30° of visual field is associated with diabetic peripheral neuropathy

Aims/hypothesis
Impaired central vision has been shown to predict diabetic peripheral neuropathy (DPN). Several studies have demonstrated diffuse retinal neurodegenerative changes in diabetic patients prior to retinopathy development, raising the prospect that non-central vision may also be compromised by primary neural damage. We hypothesise that type 2 diabetic patients with DPN exhibit visual sensitivity loss in a distinctive pattern across the visual field, compared with a control group of type 2 diabetic patients without DPN.

Methods
Increment light sensitivity was measured by standard perimetry in the central 30° of visual field for two age-matched groups of type 2 diabetic patients, with and without neuropathy (n = 40/30). Neuropathy status was assigned using the neuropathy disability score. Mean visual sensitivity values were calculated globally, for each quadrant and for three eccentricities (0–10°, 11–20° and 21–30°). Data were analysed using a generalised additive mixed model (GAMM).

Results
Global and quadrant between-group visual sensitivity mean differences were marginally but consistently lower (by about 1 dB) in the neuropathy cohort compared with controls. Between-group mean differences increased from 0.36 to 1.81 dB with increasing eccentricity. GAMM analysis, after adjustment for age, showed these differences to be significant beyond 15° eccentricity and monotonically increasing. Retinopathy levels and disease duration were not significant factors within the model (p = 0.90).

Conclusions/interpretation
Visual sensitivity reduces disproportionately with increasing eccentricity in type 2 diabetic patients with peripheral neuropathy. This sensitivity reduction within the central 30° of visual field may be indicative of more consequential loss in the far periphery.

Exploring retinal and functional markers of diabetic neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most debilitating complications of diabetes. DPN is a major cause of foot ulceration and lower limb amputation. Early diagnosis and management are key factors in reducing morbidity and mortality. Current techniques for clinical assessment of DPN are relatively insensitive for detecting early disease or involve invasive procedures such as skin biopsies. There is a need for less painful, non-invasive, safe evaluation methods. Eye-care professionals already play an important role in the management of diabetic retinopathy but recent studies have indicated that the eye may also be an important site for the diagnosis and monitoring of neuropathy. Corneal nerve morphology is a promising marker of diabetic neuropathy occurring elsewhere in the body. Emerging evidence tentatively suggests that retinal anatomical markers and a range of functional visual indicators could similarly provide useful information regarding neural damage in diabetes, although this line of research is less well established. This review outlines the growing body of evidence supporting a potential diagnostic role for retinal structure and visual functional markers in the diagnosis and monitoring of peripheral neuropathy in diabetes.

Corneal markers of diabetic neuropathy

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Enhancing predictive accuracy of cardiac autonomic neuropathy using blood biochemistry features and iterative multitier ensembles

Blood biochemistry attributes form an important class of tests, routinely collected several times per year for many patients with diabetes. The objective of this study is to investigate the role of blood biochemistry for improving the predictive accuracy of the diagnosis of cardiac autonomic neuropathy (CAN) progression. Blood biochemistry contributes to CAN, and so it is a causative factor that can provide additional power for the diagnosis of CAN especially in the absence of a complete set of Ewing tests. We introduce automated iterative multitier ensembles (AIME) and investigate their performance in comparison to base classifiers and standard ensemble classifiers for blood biochemistry attributes. AIME incorporate diverse ensembles into several tiers simultaneously and combine them into one automatically generated integrated system so that one ensemble acts as an integral part of another ensemble. We carried out extensive experimental analysis using large datasets from the diabetes screening research initiative (DiScRi) project. The results of our experiments show that several blood biochemistry attributes can be used to supplement the Ewing battery for the detection of CAN in situations where one or more of the Ewing tests cannot be completed because of the individual difficulties faced by each patient in performing the tests. The results show that AIME provide higher accuracy as a multitier CAN classification paradigm. The best predictive accuracy of 99.57% has been obtained by the AIME combining decorate on top tier with bagging on middle tier based on random forest. Practitioners can use these findings to increase the accuracy of CAN diagnosis.

Postural control and functional balance in individuals with diabetic peripheral neuropathy

A Neuropatia diabética periférica (NDP) cursa com redução somatossensitiva que pode levar a alterações no controle postural. O objetivo do estudo foi avaliar o controle postural na postura ereta, em diferentes condições, e o equilíbrio funcional em indivíduos com NDP, correlacionar os resultados obtidos na avaliação do controle postural com os valores do teste do equilíbrio funcional e comparar os resultados obtidos no grupo neuropata com o grupo controle, verificando as possíveis diferenças entre as condições de avaliação em ambos os grupos. Participaram do estudo 13 mulheres com NDP (GN) e 17 mulheres não diabéticas (GC). A avaliação do controle postural foi realizada por cinemetria nas condições: olhos abertos (OA), olhos fechados (OF) e semi tandem (ST). Após processamento no MATLAB, foram geradas as variáveis: amplitude média de oscilação (AMO) na direção ântero-posterior (AP) e médio-lateral (ML); e velocidade média de oscilação (VMO) na direção AP e ML. O equilíbrio funcional foi avaliado pelo Timed Up and Go Test. Houve diferença significante entre os grupos (p<0,005) na AMO-AP OA e OF, AMO-ML of e ST e VMO-ML ST. Houve diferença entre as condições OA e ST (p<0,005) e of e ST (p<0,005) para as variáveis AMO-ML e VMO-ML, com maior prejuízo para o GN, que também apresentou um menor equilíbrio funcional (p=0,001). A instabilidade ML foi correlacionada positivamente com o desequilíbrio funcional. Os resultados nos mostram uma alteração no sistema de controle postural na NDP, o que pode levar estes indivíduos a um maior risco a quedas e prejuízos funcionais.

Mechanisms for consideration for intervention in the development of organophosphorus-induced delayed neuropathy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Organophosphorus-induced delayed neuropathy: A simple and efficient therapeutic strategy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Neurophysiological patterns of ulnar nerve neuropathy in leprosy reactions

Background: Leprosy neuropathy, despite being primarily demyelinating, frequently leads to axonal loss. Neurophysiological examination of the nerves during Type 1 (T1R) and Type 2 reactions (T2R) may give some insight into the pathophysiological mechanisms.Methods: Neurophysiological examinations were performed in 28 ulnar nerves during a clinical trial of steroid treatment effectiveness, 19 patients with T1R and nine with T2R. The nerves were monitored during a period of 6 months; there were eight assessments per nerve, for a total of 224 assessments. Nine neurophysiological parameters were assessed at three sites of the ulnar nerve. The compound motor action potential amplitudes elicited at wrist, elbow and above, as well as the conduction velocity and temporal dispersion across the elbow, were chosen to focus on the changes occurring in the parameters at the elbow tunnel.Results and Conclusion: Neurophysiological changes indicating axonal and demyelinating processes during both T1R and T2R were detected across the elbow. Changes in demyelination, i.e. a Conduction Block, as a primary event present during T2R, occurring as an acute phenomenon, were observed regularly; in T1R Temporal Dispersion, a subacute phenomenon, was seen. During treatment remyelination occurred after both types of reactions.