Retinal blood flow velocity measured by retinal function imaging in retinitis pigmentosa.

BACKGROUND: To measure the retinal blood flow velocity in patients with retinitis pigmentosa using the retinal function imaging technique. METHODS: The clinical observational investigation included a study group of five eyes of five patients (age: 55.7 ± 8.6 years) with retinitis pigmentosa (RP) and a control group of five eyes of five healthy subjects. We used a randomly chosen eye of the RP patients, and compared its results to the normal subjects using a mixed linear model, correcting for heart rate, age, and gender. RESULTS: The mean blood velocity in the narrow retinal veins (1.7 ± 0.35 cm/s versus 3.0 ± 0.35 cm/s; P < 0.001) and wide retinal veins (1.5 ± 0.35 cm/s versus 3.1 ± 0.30 cm/s; P < 0.001) was significantly lower in the study group than in the control group not correcting for heart rate, age or gender. Correspondingly, the arterial blood flow velocity was significantly lower in the study group than in the control group for the narrow arterial vessels (2.3 ± 0.55 versus 4.2 ± 0.5; P = 0.006) and for the wide retinal arteries (2.5 ± 1.05 cm/s versus 4.8 ± 1.0 cm/s; P < 0.001). CONCLUSIONS: Using the retinal function imaging technology revealed significantly lower retinal blood flow velocities in the small and large retinal vessels in patients with retinitis pigmentosa than in healthy subjects. This corresponds with the known decrease in the retinal vessel diameters as observed upon ophthalmoscopy in patients with retinitis pigmentosa. Retinal function imaging technology may hold promise for measurements of retinal blood flow parameters.

Repeatability and reproducibility of corneal biomechanical parameters derived from Corvis ST.

INTRODUCTION: The aim of this study was to evaluate repeatability and reproducibility of newly calculated biomechanical parameters of the cornea, developed by our research group. METHODS: One eye from each of the 23 healthy subjects was measured three times consecutively, three times at different daytimes and on three different days. The within-subject standard deviation and coefficient of variation, as well as the intraclass correlation coefficient, were calculated for every parameter in each group. RESULTS: Excellent repeatability and reproducibility (coefficient of variation < 5%, intraclass correlation coefficient > 0.75) was found for corrected values measured at A1, HC, and A2 time points (2nd A2 Time, 2nd A1 Time, 2nd HC Time, 2nd HC Def Amp and 2nd A1 Def Amp). Corneal-specific stiffness parameters, which showed good repeatability and reliability, were DA_cor (coefficient of variation = 4.02%, intraclass correlation coefficient = 0.919), KcLinear (coefficient of variation = 4.03%, intraclass correlation coefficient = 0.895), areaForceCornea (coefficient of variation = 3.34%, intraclass correlation coefficient = 0.853) and E2 (coefficient of variation = 4.1%, intraclass correlation coefficient = 0.78). Overall, most parameters fell into the category of good reliability (high intraclass correlation coefficient) and poor reproducibility (low coefficient of variation), including all the parameters describing extraocular deformation (DA_ext, AEPvED, AUC EDef, areaForceExtra, Kg and µg). Comparing the coefficient of variation values for intrasession, intersession and daytime measurements, there were no indices for diurnal changes. CONCLUSION: Most parameters showed good repeatability and reliability. The extraocular stiffness parameters showed poor reproducibility. KcLinear can serve as a very reliable and repeatable indicator of corneal stiffness.

Function of the tryptophan metabolite, L-kynurenine, in human corneal endothelial cells.

PURPOSE: Penetrating keratoplasty has been the mainstay for the treatment of blindness and is the most common form of tissue transplantation worldwide. Due to significant rates of rejection, treatment of immunological transplant reactions is of wide interest. Recently in a mouse model, the overexpression of indoeleamine 2,3 dioxigenase (IDO) was led to an extension in corneal allograft survival. L-kynurenine is a tryptophan metabolite, which may render activated T-cells apoptotic and therefore might modulate an allogenous transplant reaction. The function of L-kynurenine in the human cornea remains unclear. We analyzed the expression levels of IDO in human corneal endothelial cells (HCECs) and downstream tryptophan/kynurenine mechanisms in cell culture. METHODS: An immunological activation profile was determined in proliferation assays of monocytes from healthy donors. Reversed-phase high pressure liquid chromatography (HPLC), western blot, real time polymerase chain reaction (PCR), and microarray analyses were used. The expression of IDO and immunological infiltration of rejected human corneal allografts (n=12) were analyzed by immunohistochemistry. RESULTS: We found IDO and an associated tryptophan/kynurenine transporter protein exchange mechanism upregulated by inflammatory cytokines in HCECs. The inhibition of T-cell proliferation might depend on rapid delivery of the tryptophan metabolite, L-kynurenine, to the local corneal environment. Microarray analysis gives evidence that the large amino acid transporter 1 (LAT1) transporter protein is responsible for this mechanism. CONCLUSIONS: Our data support that adequate levels of functional L-kynurenine might contribute to the maintenance of a relative immune privilege in the ocular anterior chamber, thereby contributing to the preservation of corneal allogeneic cells.

Paroxysmal nocturnal hemoglobinuria may cause retinal vascular occlusions.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the classic triad of haemolytic anaemia, thrombophilia and cytopenia with the majority of cases occurring in adulthood. PNH constitutes a nonmalignant clonal disease of hematopoietic stem cells harboring somatic mutations in the X-linked phosphatidyl inositol glycan complementation group-A (PIG-A) gene. METHODS: We report for the first time retinal venous vascular occlusion as the primary manifestation of PNH. A patient of untypical age for retinal vascular occlusions presented with a history of 4 weeks of progressive reduction in visual acuity. RESULTS: The screening tests for thrombophilia were not successful. However, elevated LDH was detected, leading to the diagnosis of PNH. CONCLUSIONS: To date, no report shows retinal vascular occlusion as the primary symptom leading to the diagnosis PNH. This article describes, for the first time, that this rare disease needs to be considered in the differential diagnosis of retinal vascular occlusions.

Vitamins inhibit oxidant-induced apoptosis of corneal endothelial cells.

PURPOSE: To determine the effects of vitamins A, C, and E supplementation on lipid peroxidation and apoptosis in corneal endothelial cells. METHODS: Murine corneal endothelial cells were maintained in tissue culture medium supplemented with free iron ions, known to lead to increased lipid peroxidation. The concentration of antioxidative vitamins (ascorbic acid, tocopherol, and retinoic acid) in the cells and supernatant was determined using reversed-phase high-performance liquid chromatography. Apoptosis was assessed by quantification of caspase-3-like activity, using annexin-V/propidium iodide stains for flow cytometry. Lipid peroxidation was assessed using the malondialdehyde method. Supplementation of antioxidative vitamins was tested in the setting of apoptosis. RESULTS: Increasing levels of free iron led to a rapid loss of antioxidative vitamins in the supernatant and corneal endothelial cells. This was correlated with rising levels of malondialdehyde and increased apoptosis. Supplementation with ascorbic acid or alpha-tocopherol alone was not sufficient to prevent lipid peroxidation in the cells, whereas a combination of vitamins C and E was able to do so. In contrast, supplementation with vitamin A alone significantly reduced oxidative stress and apoptosis. CONCLUSIONS: We present an in vitro model to test the direct influence of vitamin supplementation on corneal endothelial cells with regard to lipid peroxidation and apoptosis. We show that supplementation with antioxidative vitamins of corneal endothelial cells significantly prevents the generation of free-radical injury, lipid peroxidation, and consequent apoptosis.

Clinical and experimental evidence of prostaglandin E1-induced angiogenesis in the myocardium of patients with ischemic heart disease.

OBJECTIVE: Prostaglandin E1 (PGE-1) is a potent vasodilative agent which has been used to bridge patients with chronic heart failure listed for heart transplantation (HTX). In various experimental settings PGE-1 appears to stimulate angiogenesis by inducing vascular endothelial growth factor expression. This observational clinical study sought to investigate the angiogenic effects of PGE-1 in the failing human heart. METHODS: Neovascularization was investigated in 14 explanted hearts from patients with ischemic cardiomyopathy (ICMP) who had been bridged to HTX with PGE-1 (8+/-1 mg/kg/min, 97+/-75.6 days) and compared with 14 hearts who did not receive PGE-1 prior to HTX. In three sectional areas obtained from the left ventricular wall CD34, von Willebrand factor (vWf), nuclear Ki67 (MIB-1), and VEGF were quantified by immunohistochemistry to estimate capillary density and endothelial cell proliferation. Additionally, to investigate a possible angiogenic effect of PGE-1 in vitro, cultured human coronary artery smooth muscle cells (HCASMCs) were treated with PGE-1. RESULTS: PGE-1-treated patients had significantly more CD34- and vWf-positive cells in the subepicardium (both P<0.01), myocardium (both P<0.0001) and subendocardium (P<0.01 and P<0.001) as compared to the nonPGE-1 group. Proliferative endothelial activity expressed by the presence of MIB-1- and VEGF-positive cells (both P<0.0001 in all layers) was increased more than twofold. Addition of PGE-1 to HCASMCs in cell culture resulted in a significant increase in VEGF production (164.0+/-19.7 pg/10(5) cells/24 h, P<0.005) as compared to the control cell line (66.6+/-8.7 pg/10(5) cells/24 h, P<0.005). CONCLUSIONS: Our data demonstrate that PGE-1 is a potent stimulator of angiogenesis via upregulation of VEGF expression. The induction of therapeutic angiogenesis in patients with severe ICMP might explain the favorable clinical outcome in PGE-1 treated patients until HTX.

CROP - The Clinico-Radiologico-Ophthalmological Paradox in Multiple Sclerosis: Are Patterns of Retinal and MRI Changes Heterogeneous and Thus Not Predictable?

BACKGROUND: To date, no direct scientific evidence has been found linking tissue changes in multiple sclerosis (MS) patients, such as demyelination, axonal destruction or gliosis, with either steady progression and/or stepwise accumulation of focal CNS lesions. Tissue changes such as reduction of the retinal nerve fiber layer (RNFL) and the total macular volume (TMV), or brain- and spinal cord atrophy indicates an irreversible stage of tissue destruction. Whether these changes are found in all MS patients, and if there is a correlation with clinical disease state, remains controversial. The objective of our study was to determine, whether there was any correlation between the RNFL or TMV of patients with MS, and: (1) the lesion load along the visual pathways, (2) the ratios and absolute concentrations of metabolites in the normal-appearing white matter (NAWM), (3) standard brain atrophy indices, (4) disease activity or (5) disease duration. METHODS: 28 MS patients (RRMS, n = 23; secondary progressive MS (SPMS), n = 5) with moderately-high disease activity or long disease course were included in the study. We utilised: (1) magnetic resonance imaging (MRI) and (2) -spectroscopy (MRS), both operating at 3 Tesla, and (3) high-resolution spectral domain-OCT with locked reference images and eye tracking mode) to undertake the study. RESULTS: There was no consistency in the pattern of CNS metabolites, brain atrophy indices and the RNFL/TMV between individuals, which ranged from normal to markedly-reduced levels. Furthermore, there was no strict correlation between CNS metabolites, lesions along the visual pathways, atrophy indices, RNFL, TMV, disease duration or disability. CONCLUSIONS: Based on the findings of this study, we recommend that the concept of 'clinico-radiologico paradox' in multiple sclerosis be extended to CROP-'clinico-radiologico-ophthalmological paradox'. Furthermore, OCT data of MS patients should be interpreted with caution.

Corrigendum: "High-Resolution Spectral Domain-Optical Coherence Tomography in Multiple Sclerosis, Part II - The Total Macular Volume. The First Follow-Up Study Over 2 Years".

[This corrects the article on p. 20 in vol. 5, PMID: 24605107.].

Quantitative analysis of peroxisome proliferator-activated receptor gamma (PPARgamma) expression in arteries and hearts of patients with ischaemic or dilated cardiomyopathy.

PPARgamma, a nuclear transcription factor, is expressed in various cells within the vasculature and in cardiomyocytes. It has been suggested that PPARgamma is involved in atherogenesis and in cardiac hypertrophy. Therefore, we sought to quantify PPARgamma mRNA in coronary arteries, the aorta and left ventricular specimens from patients with ischaemic (CHD) and dilated cardiomyopathy (CMP). Using real-time PCR, we were able to demonstrate the expression of PPARgamma in all of the human specimens. The lowest expression of PPARgamma was detected in the aorta specimens of both groups (this was set to one). In comparison, the expression in coronary arteries was 2.32-fold in CHD- and 3.78-fold in CMP specimens and in the left ventricle specimens, 2.12-fold in CHD- and 3.51-fold in CMP. Samples from CHD patients showed a higher expression of PPARgamma in all of the samples compared to those from CMP patients (aorta: 1.99-fold; coronary arteries: 1.35; left ventricles: 1.23). PPARgamma levels were not significantly correlated to CD 36 expression values in any group, suggesting that higher levels of PPARgamma are not principally due to increased PPARgamma expression in macrophages. This was confirmed by immunohistochemical analysis, which showed that PPARgamma is also located in the smooth muscle layer and in cardiomyocytes. In conclusion, our observations of increased PPAR mRNA expression in the coronary arteries and left ventricles from CHD and CMP patients suggest an important function of this nuclear receptor in the pathogenesis of heart disease.

Elevated homocysteine serum level is associated with low enrichment of homocysteine in coronary arteries of patients with coronary artery disease.

In the present study, we sought to investigate whether elevated serum levels of homocysteine (Hcy), predisposing to endothelial dysfunction during progression of atherosclerosis, were paralleled by increased Hcy concentrations in human coronary arteries. Paraffin sections of coronary arteries were obtained from explanted hearts of cardiac transplant recipients suffering from coronary artery disease (CAD, n=32, mean age=56.6+/-6.8), and from heart donors where transplantation was not performed due to organization-related circumstances (Co, n=6, mean age 25.0+/-10.6), and characterized immunohistochemically for Hcy, CD68, and smooth muscle alpha-actin. Although the CAD group presented with high serum Hcy levels (27.7+/-12.8 micromol/l), the media and intimal layers containing the endothelium showed the lowest enrichment of Hcy (media: 20.8+/-4.4%; intima: 6.1+/-2.3%). Surprisingly, the control group revealed an extensive Hcy enrichment, co-localizing with vascular smooth cells (media: 32.3+/-14.0%; intima: 7.0+/-2.0%). In conclusion, we have provided evidence for a reverse relation between Hcy serum concentration and enrichment of Hcy in coronary arteries of patients with severe CAD, suggesting that Hcy is not likely to be involved directly in atheromatosis development of coronary arteries.

Clinical benefit of prostaglandin E1-treatment of patients with ischemic heart disease: stimulation of therapeutic angiogenesis in vital and infarcted myocardium.

New evidence suggests that Prostaglandin E1 (PGE-1) stimulates myocardial angiogenesis in human chronic ischemic myocardium. We sought to investigate whether PGE-1 may participate in the process of neoangiogenesis within the myocardial infarct scar. Neovascularization was investigated in 14 explanted hearts from patients with ischemic cardiomyopathy, who had been bridged to heart transplantation (HTX) with PGE-1 and compared with 14 hearts from patients who did not receive PGE-1 prior to HTX. In transmural sections obtained from the left ventricular wall and containing myocardial scar tissue, CD34 and vascular endothelial growth factor (VEGF) were quantified immunohistochemically to estimate capillary density and amount of angiogenesis. Additionally, to assess the hypoxic state of myocardium of the infarct border zone, hypoxia inducible factor 1-alpha (HIF-1alpha) was determined by immunohistochemistry and quantified by means of planimetric analysis. PGE-1-treated patients had significantly more CD34-and VEGF-positive cells in infarct areas as compared to nonPGE-1 group, respectively (CD34: 116.7 +/- 5.9 vs. 45.1 +/- 5.2 capillary profiles/mm(2), P < 0.001, and VEGF: 48.3 +/- 4.9 vs. 22.9 +/- 4.7 capillary profiles/mm(2)). HIF-1alpha enrichment (in %) as well as staining intensity (in estimated units (eU)) was significantly decreased in PGE-1-treated as compared to non-treated controls (enrichment: 11.3 +/- 2.5% vs. 19.4 +/- 4.36%; staining intensity: 0.95 +/- 0.3 vs. 1.97 +/- 0.44 eU). Our data demonstrate that PGE-1 stimulates neoangiogenesis in infarct areas adjacent to viable myocardium, via upregulation of VEGF expression. The induction of therapeutic angiogenesis along with the improved hypoxic state of chronic ischemic myocardial tissue might explain the favorable clinical outcome in PGE-1 treated patients.

Revascularization of myocardial scar tissue following prostaglandin E1-therapy in patients with ischemic heart disease.

Prostaglandin E1 (PGE-1) treatment has proved to stimulate angiogenesis in vital non-infarcted myocardium of patients with ischemic cardiomyopathy (ICMP). We investigated infarcted myocardial tissue for a possible angiogenic response to PGE-1. Neovascularization was investigated in infarcted areas of 12 hearts explanted from patients with ICMP who had been treated with PGE-1 before heart transplantation (HTX). In transmural sections containing myocardial scar tissue, CD34 and VEGF were immunohistochemically quantified to estimate capillary density and the extent of angiogenesis. To investigate a possible effect of PGE-1 on collagen turnover, the collagen content was determined in myocardial scar tissue by assessing the intensity of the area positively stained with sirius red. PGE-1-treated patients had significantly more CD34- and VEGF-positive cells in infarcted areas, and showed a significant reduction in collagen content as compared with the non-PGE-1 group (CD34: 120.3 +/- 6.1 vs. 47.7 +/- 6.1 capillary profiles/mm2; VEGF: 52.8 +/- 5.6 vs. 24.0 +/- 4.8 capillary profiles/mm2, and collagen content: 2.18 +/- 0.4 eU vs. 3.59 +/- 0.38 eU). Our data demonstrate that PGE-1 stimulates angiogenesis by upregulating VEGF expression, and reduces fibrosis in cardiac scar tissue of ischemic origin. The induction of therapeutic angiogenesis in vital and at sites of putative dead myocardial scar tissue, along with the hemodynamic improvement in patients with severe ICMP, might explain the favorable clinical outcome in PGE-1-treated patients before HTX.

Low dose-ethanol modulates toxic effect of iron-overloading in the liver.

UNLABELLED: The oxidant properties of iron-overload and simultaneous ethanol consumption have received much interest, due to evidence reporting from hereditary hemochromatosis (HC). The full form of this disease is often associated with chronic alcoholism. An additive effect of toxicity of iron and ethanol was assumed. In this study, we examined nutritively iron-loaded Wistar rats (n = 59) (TMH-Ferrocene) additionally fed with ethanol up to 8% in drinking water for 36 wk. METHODS: By reverse-phase HPLC we measured the concentration of ascorbic acid, tocopherole and retinol in serum and liver homogenates as well as transaminases in the serum. Lipid peroxidation was assessed utilizing the ethane-exhalation method. Iron concentration in the liver was measured with the Bathophenanthrolin-method. Liver histology was performed to investigate the iron deposits and the organ damage (H.E., Azan and Berlin-blue-stainings). RESULTS: 1. Vitamin C: A linear decrease of the concentration of vitamin C in serum and liver was found independent of alcohol and iron uptake. 2. Vitamin E: Animals fed iron and alcohol showed elevated vitamin E concentrations in the serum but not in the liver. 3. Vitamin A: Elevated levels in serum but strongly decreasing levels in liver could be measured. 4. HISTOLOGY: All iron-fed animals showed massive deposits of iron in the liver. Iron diet caused liver cirrhosis, while an additional administration of ethanol could prevent this. 5. Lipid peroxidation increased in animals fed ethanol and iron, but was significantly lower in animals only receiving an iron diet. CONCLUSION: Evidence indicates that the additional exposition to ethanol in iron-loaded animals could modulate the organ damage and oxidative stress. The biochemical findings are positively correlated to the histology.

Comparison of VEP with contrast sensitivity and other measurements of central visual function.

PURPOSE: In order to evaluate alternative visual acuity testing techniques, especially to discriminate between small changes and for high visual acuity, we conducted a study covering several state-of-the-art techniques. METHODS: In this cross-sectional study, a homogeneous cohort of healthy and young patients (n = 33; 66 eyes) underwent ETDRS vision acuity (VA) testing, testing for contrast sensitivity (CS), VA determination with spatial frequency sweep visual evoked potentials (VEP) and a series of examinations of perifoveal retinal nerve fibre layer thickness (RNFLT) using Spectralis SD-OCT. To simulate the effect of artificial media opacity, CS, and VEP were repeated with Bangerter foils. RESULTS: We found that Bangerter foils can be used to reduce VA effectively measured by VA testing and VEP VA. CS correlated significantly with VA (correlation coefficients ranging from 0.54 to 0.77). VEP may be used to estimate VA; nevertheless, we found no significant correlation. RNFLT did not correlate significantly with VA. CONCLUSION: CS seems to correlate well with VA when used for high VA. All other used examinations seem to have difficulties distinguishing between small differences in VA or when the VA is high.

Detection of Retinal Nerve Fiber Layer Defects in Alzheimer's Disease Using SD-OCT.

INTRODUCTION: Our aim is to examine the clinical value of spectral-domain optical coherence tomography (Spectralis OCT) to detect retinal nerve fibre layer defects in patients with clinically defined Alzheimer's disease (AD). MATERIAL AND METHODS: This cross-sectional study included 22 patients with AD (mean age: 75.9 ± 6.1 years) and 22 healthy age- and sex-matched controls. Neuro-ophthalmologic examinations and a series of high-resolution OCT examinations of the peripapillary retinal nerve fiber layer (RNFL) thickness using the Spectralis 3.5-mm circle scan protocol with ART-Modus and eye tracking were obtained, and compared to age- and sex-matched healthy control subjects. RESULTS: Patients with AD showed a significant decrease in RNFL thickness in the nasal superior sector compared to the control group (101.0 ± 18.18 µm versus 122.8 ± 28.08 µm; P < 0.0001). In all other sectors, independently of disease duration, no significant difference in RNFL thickness compared to controls was detected. Using the advanced age- and gender-matched measurement model, 32 out of 42 eyes (76.19%) as pathologic with 67 abnormal sectors were detected. DISCUSSION: As examined by spectral-domain OCT, patients with mild to moderate stages of AD showed a significant reduction of RNFL thickness in the nasal superior sector. Nevertheless, successive studies are needed.

High-Resolution Spectral Domain-Optical Coherence Tomography in Multiple Sclerosis, Part II - the Total Macular Volume. The First Follow-Up Study over 2 Years.

BACKGROUND: Recent studies investigating the use of optical coherence tomography (OCT) in multiple sclerosis (MS) patients have resulted in wide-ranging and often contradictory outcomes. This is mainly due to the complex etiology and heterogeneity of MS, physiological variations in the retinal nerve fiber layer (RNFL) and/or total macular volume (TMV), and limitations in methodology. It remains to be discovered whether any retinal changes in MS develop continuously or in a stepwise fashion, and whether these changes occur in all or a subset of patients. High-resolution spectral domain-OCT devices (SD-OCT) would be required to detect subtle retinal changes and longitudinal studies would have to be carried out to investigate retinal changes over time. In addition, if the hypothesis is correct, then retinal and global brain tissue changes should be detected in a substantial majority of MS patients and detection should be possible with a high degree of disease activity and/or long disease course. METHODOLOGY: In order to address the factors above, 37 MS patients (relapsing-remitting, n = 27; secondary progressive, n = 10) were examined prospectively on two occasions with a median interval of 22.4 ± 0.5 months [range 19-27]. SD-OCT was utilized with the Spectralis 3.5 mm circle scan protocol (with locked reference images and eye-tracking mode). None of the patients had optic neuritis 12 months prior to study entry or during the observation period. PRINCIPAL FINDINGS: The initial TMV pattern differed between study participants, but remained relatively unchanged over the 2-year observation period despite high disease activity or long disease course. The TMV correlated well with the RNFL. CONCLUSION: The significance of differences in TMV (and RNFL) between study participants remains unclear. Until these differences have been explored further, OCT data in MS patients should be interpreted with caution.

Comparison of visual evoked potentials and retinal nerve fiber layer thickness in Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a long term progressive neurodegenerative disease and might affect the retinal nerve fiber layer thickness (RNFLT) of the eye. There is increasing evidence that visual evoked potentials (VEP), which are an objective way to indicate visual field loss, might be affected by the disease as well. MATERIALS AND METHODS: About 22 patients (mean age: 75.9 ± 6.1 years; 14 women) with mild-to-moderate AD and 22 sex-matched healthy patients were examined. We compared the use of VEP and RNFLT using the latest high-resolution spectral domain optical coherence tomography with eye-tracking capabilities for optimized peripapillary scan centering for the first time in AD patients. RESULTS: The mean MMSE score was 22.59 ± 5.47 in the AD group, and did not significantly correlate with the VEP latencies. We found no significant difference between the VEP latencies of the AD patients and those of the control patients. No peripapillary sector of the retina had a RNFLT significantly correlated with the VEP latencies. DISCUSSION: We demonstrated that pattern VEP did not show any significant correlation despite subtle loss in RNFLT. It remains open whether additional flash VEP combined with RNFLT analysis may be useful in diagnosing AD, particularly for mild-to-moderate stages of the disease.

Interpretation of RNFLT values in multiple sclerosis-associated acute optic neuritis using high-resolution SD-OCT device.

PURPOSE: Optical coherence tomography (OCT) has emerged as the technique of choice in measuring the retinal nerve fibre layer (RNFL) quantitatively. It is suggested that RNFL reduction may correlate with lesion burden and diffuse axonal degeneration in the whole CNS of patients with multiple sclerosis (MS). However, RNFL changes because of optic neuritis (ON) must be taken into account. METHODS: Twenty-three patients with acute ON (46 eyes) associated with clinical definite MS (23 ON eyes, 23 fellow eyes) and 23 sex- and age-matched healthy controls were studied. Retinal nerve fibre layer thickness (RNFLT) was measured at baseline, using a high-resolution spectral domain OCT (SD-OCT) applying circular, peripapillary OCT scans with a novel eye-tracking mechanism. RESULTS: The internal OCT software was able to identify RNFL atrophy in three out of five of the acute ON eyes and one out of four of the fellow eyes with previous ON episodes. Retinal nerve fibre layer thickness of two ON (8.7%) and five fellow eyes (21.7%) was overestimated, thus located within the 95% and 5% confidence interval of the company standard values (not marked pathologic). In contrast, our comparison with age- and sex-matched controls revealed RNFL atrophy suggestive of prior, clinically silent RNFL loss in ON and fellow eyes (30.4%). CONCLUSION: Retinal nerve fibre layer thickness measurements at a single time-point seem to have a limited role in detecting prior clinically silent optic nerve injury. Our data suggest that affected eyes should be compared with the fellow eyes and a sufficient number of age- and sex-matched controls to allow the detection of even subtle RNFL changes at baseline. The role of OCT for disease monitoring of MS must be evaluated in detail, as ON is often the initial symptom of MS.

Assessment of central corneal thickness using OCT, ultrasound, optical low coherence reflectometry and Scheimpflug pachymetry.

PURPOSE: Accurate measurement of central corneal thickness (CCT) is essential in refractive surgery and advanced glaucoma diagnostics. The gold standard for pachymetry is full-contact ultrasound-based pachymetry. As this method is associated with potential sources of error, noncontact methods have been introduced. The aim of this study was to compare CCT results measured using 4 different techniques. METHODS: In this analysis of 20 patients (40 eyes) at the University Eye Hospital Heidelberg, Germany, we compared a slit-lamp-mounted optical coherence tomography (OCT) system (SL-OCT, Heidelberg Engineering, Heidelberg, Germany), conventional ultrasound pachymetry (IOPac, Heidelberg Engineering), optical low coherence reflectometry (OLCR, Haag-Streit, Germany), and scanning-slit pachymetry (Orbscan). RESULTS: Comparison among the 4 groups did not show significant differences, except the comparison of OLCR to Orbscan; the mean was significantly different (p=0.0247) and the Orbscan detected slightly thicker values than the other methods. CONCLUSIONS: Orbscan, SL-OCT, and OLCR provide non-touch technology, without the need for local anesthesia, and limiting the risk of infection or artifacts. Extreme care must be used interpreting the results obtained from Orbscan, as this technique may overestimate the CCT significantly.