[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
PLoS ONE 11/2015; 10(11):e0142272. DOI:10.1371/journal.pone.0142272 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose To transfer the neutral density filter test to perimetry; i.e. to show that the diagnostic battery can be supplemented by low luminance visual fields, if the standard procedures yield unsatisfactory information.Methods The Goldmann perimeter uses one single incandescent light source for both stimulus and background illumination (BI). By dimming the luminance was reduced by 0.6 log units. The accompanying change in colour temperature was ignored. The i) Twinfield and ii) Tübingen automatic perimeters were modified to low luminance conditions using neutral grey filters i) in front of the eye, or ii) in the stimulus and the BI light paths. Special attention was paid to perform glaucoma fields at normal IOP level as proven by GAT and/or by Corvis tonometry (the latter to avoid affection of the tear film by anesthetics).Results Low luminance perimetry produces more pronounced scotomas in kinetic, and more distinct loss of sensitivity in static perimetry than otherwise identical perimetric procedures in standard luminance. Cases concern inflammatory, ischemic and compressive optic nerve diseases, glaucoma, and ischemic and diabetic retinopathies. Results in hereditary, dystrophic and toxic retinal conditions vary depending on whether the rods and the scotopic system are mainly affected, or the cones and the photopic system. Cone diseases lack visual field deterioration in low luminance and instead may show improvement.Conclusion Low luminance perimetry is a supplementary diagnostic tool which may add helpful diagnostic information, particularly if standard results are insignificant. Commercial interest
[Show abstract][Hide abstract] ABSTRACT: 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.
Frontiers in Psychiatry 02/2014; 5:22. DOI:10.3389/fpsyt.2014.00022
[Show abstract][Hide abstract] ABSTRACT: 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.
Frontiers in Neurology 02/2014; 5:20. DOI:10.3389/fneur.2014.00020
[Show abstract][Hide abstract] ABSTRACT: 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.
Frontiers in Neurology 12/2013; 4:203. DOI:10.3389/fneur.2013.00203
[Show abstract][Hide abstract] ABSTRACT: Purpose To emphasize the significance of photopsias and positive scotomas as subjective indicators of occult retinopathy. Methods The patient’s depiction of his photopsias led to a diagnostic work-up by white and red static and kinetic perimetry, OCT, and visual electrophysiology. Results Within the OD lower visual field our patient encountered a rapid loss of color vision. In dark environs, coloured photopsias showed up in this region, in bright environs, a positive black scotoma developped over time. Kinetic perimetry revealed a relative lower hemifield scotoma by white and an absolute one by red targets. On static perimetry, a distinct lower hemifield scotoma improved for white but persisted for red stimuli during 3 years of follow up. Retinal origin of the scotoma was proven by mf ERG. Serology for anti-retinal antibodies remained negative. Difficult to detect by ophthalmoscopy, an affection of the OS / RPE layer in the corresponding fundus area was proven by SD OCT. Conclusion Coloured photopsias in dark, a black positive scotoma in bright envorons are salient symptoms of this upper hemifield occult retinopathy. OCT, visual fields and electrodiagnostic findings point towards a variant of AZOOR (acute zonal occult outer retinopathy).
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Dendritic cell (DC) modification is a potential strategy to induce clinical transplantation tolerance. We compared two DC modification strategies to inhibit allogeneic T-cell proliferation. In the first strategy, murine DCs were transduced with a lentiviral vector expressing CTLA4-KDEL, a fusion protein which prevents surface CD80/86 expression by retaining the costimulatory molecules within the endoplasmic reticulum. In the second approach, DCs were transduced to express the tryptophan-catabolising enzyme indoleamine 2,3-dioxygenase (IDO). CTLA4-KDEL-expressing DCs induced anergy in alloreactive T cells and generated both CD4(+) CD25(+) and CD4(+) CD25(-) Treg cells (with direct and indirect donor allospecificity and capacity for linked suppression) both in vitro and in vivo. In contrast, T-cell unresponsiveness induced by IDO(+) DCs lacked donor specificity. In the absence of any immunosuppressive treatment, intravenous administration of CTLA4-KDEL-expressing DCs resulted in long-term survival of corneal allografts only when the DCs were capable of indirect presentation of alloantigen. This study demonstrates the therapeutic potential of CTLA4-KDEL-expressing DCs in tolerance induction.
European Journal of Immunology 03/2013; 43(3). DOI:10.1002/eji.201242914 · 4.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To measure the retinal blood flow velocity in patients with retinitis pigmentosa using the retinal function imaging technique.
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.
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).
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.
Albrecht von Graæes Archiv für Ophthalmologie 08/2011; 249(12):1855-8. DOI:10.1007/s00417-011-1757-y · 1.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: "Non-invasive, faster and less expensive than MRI" and "the eye is a window to the brain" are recent slogans promoting optical coherence tomography (OCT) as a new surrogate marker in multiple sclerosis (MS). Indeed, OCT allows for the first time a non-invasive visualization of axons of the central nervous system (CNS). Reduction of retina nerve fibre layer (RNFL) thickness was suggested to correlate with disease activity and duration. However, several issues are unclear: Do a few million axons, which build up both optic nerves, really resemble billions of CNS neurons? Does global CNS damage really result in global RNFL reduction? And if so, does global RNFL reduction really exist in all MS patients, and follow a slowly but steadily ongoing pattern? How can these (hypothesized) subtle global RNFL changes be reliably measured and separated from the rather gross RNFL changes caused by optic neuritis? Before generally being accepted, this interpretation needs further critical and objective validation.
We prospectively studied 37 MS patients with relapsing remitting (n = 27) and secondary progressive (n = 10) course on two occasions with a median interval of 22.4±0.5 months [range 19-27]. We used the high resolution spectral domain (SD-)OCT with the Spectralis 3.5 mm circle scan protocol with locked reference images and eye tracking mode. Patients with an attack of optic neuritis within 12 months prior to the onset of the study were excluded.
Although the disease was highly active over the observation period in more than half of the included relapsing remitting MS patients (19 patients/32 relapses) and the initial RNFL pattern showed a broad range, from normal to markedly reduced thickness, no significant changes between baseline and follow-up examinations could be detected.
These results show that caution is required when using OCT for monitoring disease activity and global axonal injury in MS.
PLoS ONE 05/2011; 6(5):e19843. DOI:10.1371/journal.pone.0019843 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
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.
European journal of ophthalmology 03/2011; 21(2):132-7. DOI:10.5301/EJO.2010.1093 · 1.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Axonal loss is considered a key prognostic factor in diagnosing and monitoring the progress of multiple sclerosis (MS). The purpose of our research was to determine whether the measurement of retinal nerve fibre layer thickness (RNFLT) as measured with high-resolution spectral-domain optical coherence tomography (SD-OCT) differs between optic nerve injury following acute optic neuritis (ON) or following unregistered subclinical axonal damage in patients with MS.
High-resolution SD-OCT measurements of RNFLT were initially carried out in the acute phase of ON and again after 3 months, in 25 patients with clinical definite MS and 25 sex- and age-matched healthy controls, all at the University Eye Hospital, Vienna.
Conventional OCT-based RNFLT analysis correctly identified all three patients with initial RNFL swelling. However, only two of three acute ON eyes with a history of ON were registered with RNFLT decrease in seven peripapillary sectors (PPs). The remaining have only been revealed using RNFLT symmetry comparison. Two of 22 (9%) first-episode ON eyes were labelled as pathologic. The number and metric RNFL values of pathologically labelled PPs remained unchanged after 3 months. Our age- and sex-match-based measurement model, with patients with MS being plotted individually and towards the fellow eye, identified all acute ON eyes (with a history of prior ON) with RNFLT reduction in 11 PPs. A global RNFL loss was registered in 36.4% (eight of 22 eyes). However, in 72%, or 16 of 22 ON eyes presenting with first episode of acute ON, a segmental RNFL loss was initially registered in 39 PPs upon baseline examination. The number of PPs with identified axonal decrease increased to a total of 48 PPs within the observational period.
Spectral-domain optical coherence tomography imaging of identical scanning locations, combined with an optimized scan centring around the optic disc, offers the technological potential of detecting prior, subtle, clinically unregistered optic nerve injury within MS individuals. Significant discrepancy in RNFLT to the potential ON eye may be achieved by comparing OCT metrics with the fellow eye and a sufficient number of age and sex-matched controls.
[Show abstract][Hide abstract] ABSTRACT: To assess retinal blood flow in patients with central serous chorioretinopathy (CSR).
The hospital-based observational comparative study included a study group with 12 patients (age: 45 ± 13 years) with an acute onset of CSR and a control group of 12 subjects matched for age and gender with the study group. The diagnosis was substantiated by fluorescein angiography and optical coherence tomography. All study participants underwent measurement of retinal blood perfusion using the retinal function imager (RFI).
The retinal blood flow velocity in the retinal veins was significantly lower in the study group than in the control group (2.76 ± 0.53 mm/s versus 3.33 ± 0.76 mm/s; p = 0.03).The difference between the study group and control group was more marked for the larger retinal veins (2.87 ± 0.51 mm/s versus 3.47 ± 0.48 mm/s; p = 0.001) than for the smaller veins (2.69 ± 0.53 mm/s versus 3.42 ± 1.05 mm/s; p = 0.04). Both groups did not differ significantly in the data of the retinal arterial flow velocities.
The data suggest an abnormal retinal venous blood flow regulation in patients with active CSR.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate measurements of the central corneal thickness using OLCR and ultrasound pachymetry (IOPac).
In a retrospective observational study, fifty patients were assessed. Central corneal thickness was measured using OLCR and ultrasound.
The IOPac system shows results for the central corneal thickness between 419 µm and 613 µm. The OLCR values ranged between 421 and 598 µm. The coefficient of variation was 1.12 % in the case of the IOPac and 0.97 % in the case of the OLCR. The paired Student's t-test showed no significant differences between the two methods. The agreement between the two methods was high with r = 0.929.
The agreement between the results for the central corneal thickness using OLCR and ultrasound is high. The OLCR is a non-touch technology that does not require local anaesthesia, thus further reducing the risk of infection or mechanical trauma. Especially in surgical applications or glaucoma assessments, movement artefacts need to be ruled out, which potentially could cause wrong values and thus lead to wrong decisions.
[Show abstract][Hide abstract] ABSTRACT: Recently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction of RNFL be detected in all MS patients, even in early disease courses and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along the visual pathways, which are both very common in MS, limit the predication of diffuse axonal degeneration in the whole CNS? The purpose of our study was to determine the baseline characteristics of clinical definite relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT technique.
Forty-two RRMS and 17 SPMS patients with and without history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls were analysed prospectively with the high resolution spectral-domain OCT device (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference images and eye tracking mode. Furthermore we performed tests for visual and contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color vision (Lanthony D-15), the Humphrey visual field and visual evoked potential testing (VEP).
All 4 groups (RRMS and SPMS with or without ON) showed significantly reduced RNFL globally, or at least in one of the peripapillary sectors compared to age-/sex-matched healthy controls. In patients with previous ON additional RNFL reduction was found. However, in many RRMS patients the RNFL was found within normal range. We found no correlation between RNFL reduction and disease duration (range 9-540 months).
RNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels).
PLoS ONE 11/2010; 5(11):e13877. DOI:10.1371/journal.pone.0013877 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Conventional time-domain OCT technology for detection of retinal nerve fibre layer (RNFL) neurodegeneration suffers from technical inaccuracy owing to a lack of exact scan centring around the optic disc as well as a true follow-up possibility. In this study, the authors evaluated a novel high-resolution spectral-domain OCT device (SD-OCT) with an incorporated eye-tracking feature in its ability to objectively measure the RNFL thickness (RNFLT) by testing intraobserver reproducibility in a series of healthy volunteers.
Triplicate circumferential RNFL scans of six peripapillary sectors were obtained from both eyes of all 31 participants. The authors compared the measurements of RNFLT during three separate examination days under miotic (Mi) and mydriatic (My) pupil conditions using a high-speed (HS) and high-resolution (HR) scan-acquisition mode. To examine the intersession reproducibility of the SD-OCT measurements, the mean, SD and coefficient of variation (COV) were calculated.
No significant differences were found in all groups, independent of the mode of image acquisition and examination day (p always >0,05). Under all conditions, low COVs between 0.545% and 3.97% (intrasession COV on baseline) were found. The intersession COV with activated follow-up mode ranged between 0.29% and 1.07%. In both settings, the temporal sector showed the highest COV values.
True follow-up measurement of identical peripapillary regions may enable clinicians to detect discrete levels of retinal thickness change over time. This constitutes a crucial prerequisite for a reliable monitoring of subtle RNFL changes in neurodegenerative disorders.
The British journal of ophthalmology 11/2010; 95(6):804-10. DOI:10.1136/bjo.2010.186221 · 2.98 Impact Factor