Latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy.

AIM: To assess if latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy. METHODS: Participants with LADA (n=31), Type 2 diabetes (n=31) and healthy control participants without diabetes (n=31) underwent a detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, skin biopsy and corneal confocal microscopy. RESULTS: The groups were matched for age (healthy control without diabetes: 53.5±9.1 vs. Type 2 diabetes: 58.0±6.5 vs. LADA: 53.2±11.6 years), duration of diabetes (Type 2 diabetes: 10.0±8.3 vs. LADA: 11.0±9.1 years) and blood pressure. However, BMI (P=0.01) and triglycerides (P=0.0008) were lower and HbA1c (P=0.0005), total cholesterol (P=0.01) and HDL (P=0.002) were higher in participants with LADA compared with Type 2 diabetes. Peroneal motor nerve conduction velocity (P=0.04) and sural sensory nerve conduction velocity (P=0.008) were lower in participants with latent autoimmune diabetes in adults compared with Type 2 diabetes. Intra-epidermal nerve fibre density (P=0.008), corneal nerve fibre density (P=0.003) and corneal nerve branch density (P=0.006) were significantly lower in participants with LADA compared with Type 2 diabetes. There were no significant differences in the other neuropathy parameters. CONCLUSIONS: Despite comparable age and duration of diabetes, participants with LADA demonstrate more severe neuropathy and particularly small fibre neuropathy, compared with participants with Type 2 diabetes.

Visual complications in diabetes mellitus: beyond retinopathy.

Diabetic retinopathy is the most common cause of vision loss in people with diabetes mellitus; however, other causes of visual impairment/loss include other retinal and non-retinal visual problems, including glaucoma, age-related macular degeneration, non-arteritic anterior ischaemic optic neuropathy and cataracts. Additionally, when a person with diabetes complains of visual disturbance despite a visual acuity of 6/6, abnormalities in refraction, contrast sensitivity, straylight and amplitude of accommodation should be considered. We review and highlight these visual problems for physicians who manage people with diabetes to ensure timely referral and treatment to limit visual disability, which can have a significant impact on daily living, especially for those participating in sports and driving.

NerveCheck: An inexpensive quantitative sensory testing device for patients with diabetic neuropathy.

AIMS: Sensory neuropathy is central to the development of painful neuropathy, and foot ulceration in patients with diabetes. Currently, available QST devices take considerable time to perform and are expensive. NerveCheck is the first inexpensive ($500), portable QST device to perform both vibration and thermal testing and hence evaluate diabetic peripheral neuropathy (DPN). This study was undertaken to establish the reproducibility and diagnostic validity of NerveCheck for detecting neuropathy. METHODS: 130 subjects (28 with DPN, 46 without DPN and 56 control subjects) underwent QST assessment with NerveCheck; vibration perception and thermal testing. DPN was defined according to the Toronto criteria. RESULTS: NerveCheck's intra correlation coefficient for vibration, cold and warm sensation testing was 0.79 (95% LOA: -4.20 to 6.60), 0.86 (95% LOA: -1.38 to 2.72) and 0.71 (95% LOA: -2.36 to 3.83), respectively. The diagnostic accuracy (AUC) for vibration, cold and warm sensation testing was 86% (SE: 0.038, 95% CI 0.79-0.94), 79% (SE: 0.058, 95% CI 0.68-0.91) and 72% (SE: 0.058, 95% CI 0.60-0.83), respectively. CONCLUSIONS: This study shows that NerveCheck has good reproducibility and comparable diagnostic accuracy to established QST equipment for the diagnosis of DPN.

Correlation between Central Corneal Thickness and Intraocular Pressure Measured by Goldmann Applanation Tonometry or Pascal Dynamic Contour Tonometry.

PURPOSE: The aim of this study was to investigate the relationship between central corneal thickness and intraocular pressure measured by Goldmann applanation tonometry and Pascal dynamic contour tonometry. PATIENTS AND METHODS: The study included 45 persons (90 eyes), divided into 4 groups: a) 10 normal volunteers (20 eyes); b) 16 patients (32 eyes) with primary open-angle glaucoma; c) 8 patients (16 eyes) with normal-tension glaucoma; and d) 11 patients (22 eyes) with ocular hypertension. Intraocular pressure was measured by Goldmann applanation tonometry and Pascal dynamic contour tonometry, and central corneal thickness was measured by ultrasound pachymetry. The relationship between intraocular pressure and central corneal thickness was evaluated. RESULTS: Intraocular pressure was correlated positively but not strongly enough with central corneal thickness when it was measured by Goldmann applanation tonometry. On the contrary, there was no correlation between intraocular pressure and central corneal thickness when intraocular pressure was measured by Pascal dynamic contour tonometry. CONCLUSION: Central corneal thickness is an important variable in the evaluation of intraocular pressure by Goldmann applanation tonometry. This factor does not interfere with the intraocular pressure measurements taken by Pascal dynamic contour tonometry.

Clinical and diagnostic features of small fiber damage in diabetic polyneuropathy.

Small fiber neuropathy represents a significant component of diabetic sensorimotor polyneuropathy (DSPN) which has to date been ignored in most recommendations for the diagnosis of DSPN. Small fibers predominate in the peripheral nerve, serve crucial and highly clinically relevant functions such as pain, and regulate microvascular blood flow, mediating the mechanisms underlying foot ulceration. An increasing number of diagnostic tests have been developed to quantify small fiber damage. Because small fiber damage precedes large fiber damage, diagnostic tests for DSPN show good sensitivity but moderate specificity, because the gold standard which is used to define DSPN is large fiber-weighted. Hence new diagnostic algorithms for DSPN should acknowledge this emerging data and incorporate small fiber evaluation as a key measure in the diagnosis of DSPN, especially early neuropathy.

The diagnostic accuracy of Neuropad for assessing large and small fibre diabetic neuropathy.

AIMS: Neuropad is a simple visual indicator test, with moderate diagnostic performance for diabetic peripheral neuropathy. As it assesses sweating, which is a measure of cholinergic small nerve fibre function, we compared its diagnostic performance against established measures of both large and, more specifically, small fibre damage in patients with diabetes. METHODS: One hundred and twenty-seven participants (89 without diabetic peripheral neuropathy and 38 with) aged 57 ± 9.7 years underwent assessment with Neuropad, large nerve fibre assessments: Neuropathy Disability Score, vibration perception threshold, peroneal motor nerve conduction velocity; small nerve fibre assessments: neuropathy symptoms (Diabetic Neuropathy Symptoms score) corneal nerve fibre length and warm perception threshold. RESULTS: Neuropad has a high sensitivity but moderate specificity against large fibre neuropathy assessments: Neuropathy Disability Score (> 2) 70% and 50%, vibration perception threshold (> 14 V) 83% and 53%, and peroneal motor nerve conduction velocity (< 42 m/s) 81% and 54%, respectively. However, the diagnostic accuracy of Neuropad was significantly improved against corneal nerve fibre length (< 14 mm/mm2) with a sensitivity and specificity of 83% and 80%, respectively. Furthermore, the area under the curve for corneal nerve fibre length (85%) was significantly greater than with the Neuropathy Disability Score (66%, P = 0.01) and peroneal motor nerve conduction velocity (70%, P = 0.03). For neuropathic symptoms, sensitivity was 78% and specificity was 60%. CONCLUSIONS: The data show the improved diagnostic performance of Neuropad against corneal nerve fibre length. This study underlines the importance of Neuropad as a practical diagnostic test for small fibre neuropathy in patients with diabetes.

Ocular pulse amplitude measurement using pascal dynamic contour tonometer in glaucoma patients.

AIM: This study aims to measure and compare the ocular pulse amplitude using Pascal dynamic contour tonometry in normal persons and in glaucoma patients. PATIENTS AND METHODS: 20 patients (40 eyes) with primary open angle glaucoma (Group A), 8 patients (16 eyes) with normal tension glaucoma (Group B), and 12 patients (24 eyes) with ocular hypertension (Group C) were included in the study. Control group (Group D) comprised 25 normal volunteers (50 eyes). Intraocular pressure was measured using both Goldmann applanation tonometry in the slit-lamp and Pascal dynamic contour tonometry. Ocular pulse amplitude was evaluated with Pascal dynamic contour tonometry. Statistical evaluation of the differences in ocular pulse amplitude and intraocular pressure among the different groups was performed using Student's t-test. RESULTS: Mean ocular pulse amplitude values expressed in mmHg were 3.66 ± 1.00, 2.46 ± 0.60, 4.04 ± 1.47, and 2.52 ± 0.52, for Groups A, B, C, and D, respectively. The ocular pulse amplitude was significantly higher in Group A (primary open angle glaucoma) and Group C (ocular hypertension) when compared with Group D (control group) and Group B (normal tension glaucoma). No statistically significant difference was detected between Group D (control group) and Group B (normal tension glaucoma). CONCLUSIONS: Although we can measure the intraocular pressure with Goldmann applanation tonometry, no information can be derived regarding the ocular pulse amplitude. The use of Pascal dynamic contour tonometry in intraocular pressure estimation provides useful clinical information also about the magnitude of the ocular pulse amplitude in different types of glaucoma. Pascal dynamic contour tonometry discloses an elevation of ocular pulse amplitude in primary open angle glaucoma and ocular hypertension patients. On the contrary, the ocular pulse amplitude is within normal limits in normal tension glaucoma patients.

Impact of preoperative and intraoperative factors in cataract surgery.

BACKGROUND: Cataract surgery is the most common procedure in ophthalmology. However the surgical outcome depends on various factors. The impact of preoperative and intraoperative factors on the surgical procedure were investigated. PATIENTS AND METHODS: Prospective consecutive study of eyes that underwent cataract surgery. The studied parameters included: age, body mass index (BMI), medical history, type of anaesthesia, preoperative patient's anxiety level (scale from 0 to 10), spherical equivalent (SE), keratometry, axial length (AL), time and percentage of ultrasounds (US), intraoperative complications, duration of surgery. The eyes were separated into two groups: the "no complication group" and the "complication group". RESULTS: 529 eyes were included. Age averaged 75.5 years old (44; 100), mean BMI (kg/m2) was 26.3 (13.7; 45.2), patients had cardiovascular history in 61.05% of cases, the type of anaesthesia used was topical in 93.4%, subtenon in 4.7% and general in 1.9% of cases. Mean preoperative anxiety was 4.04 (0; 10), mean preoperative SE was -0.12 (-10; 7.5), mean keratometry (diopters) was 43.88 (39.5; 49), mean AL (mm) was 23.29 (20.91; 29.78), mean time of US (minutes) was 1.89 (0.08; 9.2), mean percentage of US was 10.5 (2; 30) and mean surgical duration (minutes) was 17.15 (5; 50). There was a statistically significant difference (p < 0.0001 in all cases) between both groups in the preoperative anxiety, the time of US and the duration of surgery. The "complication group" had higher scores in all cases as well as more proportion of patients with cardiovascular history. There was no statistically significant difference between both groups for the BMI, SE, AL, keratometry and percentage of US. CONCLUSIONS: The preoperative anxiety level and a cardiovascular medical history together with a prolonged time of US and a longer surgical duration seem to provide more complications during the surgery. The BMI, SE, AL and keratometry did not influence the surgical procedure.

Central foveal thickness before and after cataract surgery in normal and in diabetic patients without retinopathy.

BACKGROUND: This study aims to evaluate and compare central foveal thickness (CFT) changes after cataract surgery between normal and diabetic patients without retinopathy, using optical coherence tomography (OCT). PATIENTS AND METHODS: Ninety-eight patients (49 patients with type 2 diabetes and 49 healthy controls, sex- and age-matched) undergoing phacoemulsification in one eye were included. The presence of retinopathy was an exclusion criterion. The OCT examination was performed preoperatively as well as one, three, six and twelve months postoperatively. CFT was evaluated and compared between groups. RESULTS: Preoperative CFT showed no significant difference between the two groups (normals: 205 ± 18 µm vs. diabetics: 202 ± 23 µm, p > 0.1). Postoperative CFT in diabetics at all time-points of the follow-up period was significantly increased when compared to controls (first month, normals: 215 ± 28 µm vs. diabetics: 262 ± 33 µm, p < 0.05; third month, normals: 211 ± 19 µm vs. diabetics: 250 ± 27 µm, p < 0.05; sixth month, normals: 208 ± 12 µm vs. diabetics: 266 ± 13 µm, p < 0.05; and twelfth month, normals: 209 ± 13 µm vs. diabetics: 280 ± 11 µm, p < 0.05). The incidence of cystoid macular edema (CME) was 4.0 % and 28.6 % for the control group and the diabetic group, respectively, at the end of the follow-up period (p < 0.05). CONCLUSION: Eyes of diabetic patients without retinopathy present higher CFT and a higher incidence of CME after cataract surgery on OCT examination compared to eyes of healthy controls. This may explain the unsatisfactory visual acuity following cataract surgery in these patients.

Should central serous chorioretinopathy be added to the list of ocular side effects of phosphodiesterase 5 inhibitors?

INTRODUCTION: Rare cases of central serous chorioretinopathy (CSC) associated with the intake of sildenafil citrate have been reported, although CSC is not included in the list of phosphodiesterase 5 (PDE5) inhibitor side effects. MATERIALS AND METHODS: We present a review of the literature and 2 cases of CSC in 2 men taking PDE5 inhibitors (vardenafil and tadalafil) for erectile dysfunction. In both cases chorioretinopathy appeared after intake of the inhibitor, resolved once the latter was discontinued, reappeared when the inhibitor was restarted and resolved once again after the inhibitor had been discontinued for the second time. DISCUSSION: PDE5 inhibitors used for male erectile dysfunction have been associated with ocular side effects including lid edema, hyposphagma, photophobia, mydriasis, dyschromatopsia, and nonarteritic anterior ischemic optic neuropathy. CSC was previously described in patients taking sildenafil citrate. Very recently, a case of CSC after tadalafil intake was reported. The relevant literature is reviewed and possible pathophysiologic mechanisms are discussed. CONCLUSION: The 2 presented cases of CSC after intake of vardenafil or tadalafil with positive dechallenge, rechallenge and second dechallenge reactions provide important arguments for considering CSC as a rare PDE5 inhibitor class-specific side effect.

Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging.

Diabetic peripheral neuropathy (DPN) is one of the most common long term complications of diabetes. Corneal confocal microscopy (CCM) image analysis is a novel non-invasive technique which quantifies corneal nerve fibre damage and enables diagnosis of DPN. This paper presents an automatic analysis and classification system for detecting nerve fibres in CCM images based on a multi-scale adaptive dual-model detection algorithm. The algorithm exploits the curvilinear structure of the nerve fibres and adapts itself to the local image information. Detected nerve fibres are then quantified and used as feature vectors for classification using random forest (RF) and neural networks (NNT) classifiers. We show, in a comparative study with other well known curvilinear detectors, that the best performance is achieved by the multi-scale dual model in conjunction with the NNT classifier. An evaluation of clinical effectiveness shows that the performance of the automated system matches that of ground-truth defined by expert manual annotation.

Dual-model automatic detection of nerve-fibres in corneal confocal microscopy images.

Corneal Confocal Microscopy (CCM) imaging is a non-invasive surrogate of detecting, quantifying and monitoring diabetic peripheral neuropathy. This paper presents an automated method for detecting nerve-fibres from CCM images using a dual-model detection algorithm and compares the performance to well-established texture and feature detection methods. The algorithm comprises two separate models, one for the background and another for the foreground (nerve-fibres), which work interactively. Our evaluation shows significant improvement (p approximately 0) in both error rate and signal-to-noise ratio of this model over the competitor methods. The automatic method is also evaluated in comparison with manual ground truth analysis in assessing diabetic neuropathy on the basis of nerve-fibre length, and shows a strong correlation (r = 0.92). Both analyses significantly separate diabetic patients from control subjects (p approximately 0).

Intravitreal l-Arginine injection reverses the retinal arteriolar vasoconstriction that occurs after experimental acute branch retinal vein occlusion.

To investigate the effect of l-Arginine on the retinal arteriolar diameter following acute branch retinal vein occlusion (BRVO) in minipigs. Under general anesthesia, 10 eyes of 10 minipigs were evaluated. Two hours after BRVO, an intravitreal juxta-arteriolar micro-injection of 30 microl l-Arginine 1 mM (pH = 7.4) was performed in 7 eyes. Three eyes received a micro-injection of 30 microl of the solvent (pH = 7.4) that was used to prepare the solution of l-Arginine and served as controls. Retinal arteriolar diameter changes were measured using a Retinal Vessel Analyzer. Overall (n = 10), 2 h after BRVO there was a 10.5 +/- 1.9% decrease in the retinal arteriolar diameter in the affected territories compared to baseline (p < 0.001). An increase of 16.0 +/- 3.0% (p = 0.001) and 21.0 +/- 7.0% (p = 0.013) of the arteriolar diameter was evidenced 10 and 15 min respectively after l-Arginine injection (n = 7) compared to the diameter prior to l-Arginine injection. Thereafter, the vasodilatory effect of l-Arginine started to decrease but persisted and remained significant at the end of the study period (5.0 +/- 1.5% at 30 min, p = 0.007). Micro-injection of the solvent alone (n = 3) did not produce any significant effect on the retinal arterioles, which remained constricted at all time-points (p > 0.1). These findings demonstrate a significant arteriolar vasodilation after intravitreal juxta-arteriolar l-Arginine micro-injection in eyes with experimental BRVO in the affected territories. l-Arginine micro-injection can reverse the arteriolar vasoconstriction that occurs in acute experimental BRVO by stimulating nitric oxide production.

Effect of brimonidine/timolol fixed combination on preventing the short-term intraocular pressure increase after intravitreal injection of ranibizumab.

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of brimonidine 0.2 % and timolol 0.5 % instillation as a fixed combination (Combigan, Allergan Inc.) to prevent acute intraocular pressure (IOP) increase occurring after intravitreal injection of ranibizumab (Lucentis, Novartis Pharma AG). PATIENTS AND METHODS: A prospective double-blind placebo-controlled study was carried out. One eye of 88 consecutive normotensive age-related macular degeneration patients receiving Lucentis was randomized into placebo drops (artificial tears, 44 patients) or Combigan drops (44 patients) given twice a day the day before and the day of injection. IOP was measured before and 5, 10, 15 minutes and 1 hour after the intravitreal injection. RESULTS: The placebo group had the higher mean IOP at all time points after injection. Maximum IOP increase for both groups occurred at the 5-minutes time point. Mean post-injection IOP in the placebo group was 34.1 +/- 2.7 mmHg at 5 minutes post-injection versus 28.4 +/- 1.1 mmHg in the Combigan group (P < 0.001). IOP decreased to 24.9 +/- 1.8 mmHg (placebo group) and 19.9 +/- 1.1 mmHg (Combigan group) at 10 minutes post-injection. At 15 minutes post-injection, IOP was below 20 mmHg in all eyes of the Combigan group (100 %), whereas at the same time point these IOP levels were reached only by 34 % of the eyes of the placebo group (15 eyes). All eyes of both groups had a normal IOP 1 hour post-injection. No systemic or ocular side effect was recorded in either group. CONCLUSIONS: The use of Combigan drops twice a day the day before and the day of injection in eyes scheduled for intravitreal injection of Lucentis is a safe and effective prophylaxis to reduce the acute IOP spikes of the post-injection period.