Andreas Reitner

High Resolution Spectral Domain Optical Coherence Tomography (SD-OCT) in Multiple Sclerosis: The First Follow Up Study over Two Years

Background “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. Methodology 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. Principal Findings 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. Conclusions These results show that caution is required when using OCT for monitoring disease activity and global axonal injury in MS.

Reproducibility of high-resolution optical coherence tomography measurements of the nerve fibre layer with the new Heidelberg Spectralis optical coherence tomography

Aim 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. Methods 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. Results 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. Conclusions 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.

Glare and halo phenomena after laser in situ keratomileusis

Purpose: To simulate and measure subjectively observed glare and halos after laser in situ keratomileusis (LASIK). Setting: University of Vienna, Medical School, Department of Ophthalmology, Vienna, Austria. Methods: In 16 eyes of 10 patients, the best corrected visual acuity (BCVA) and subjectively observed glare and halo size under mesopic conditions were measured before LASIK and 1, 3, and 6 months postoperatively. Infrared pupillography was used to ensure that all patients had a larger ablation zone than the measured pupil size under mesopic conditions. Results: Preoperatively, the mean Snellen BCVA was 0.88 ± 0.17 (SD) and the mean glare and halo size was 1.97 ± 1.20 square degrees (sqd) before the treatment. One month after LASIK, the BCVA was 0.83 ± 0.29 and the mean glare and halo size, 2.61 ± 3.14 sqd. Three months after LASIK, the mean values were 0.90 ± 0.26 and 1.88 ± 2.37 sqd, respectively. Six months after LASIK treatment, they were 0.85 ± 0.28 and 1.30 ± 1.63 sqd, respectively. The 95% confidence interval for the difference between preoperative glare and halo and glare and halo at 6 months was −1.56 to + 0.51 sqd. Conclusion: Subjectively observed glare and halo size after LASIK reached a peak after 1 month and decreased in the following postoperative period.

Heterogeneous Pattern of Retinal Nerve Fiber Layer in Multiple Sclerosis. High Resolution Optical Coherence Tomography: Potential and Limitations

Background 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. Methodology 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). Principal Findings 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). Conclusions RNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels).

Apoplexy of a pituitary macroadenoma with reversible third, fourth and sixth cranial nerve palsies following administration of hypothalamic releasing hormones : MR features

Pituitary apoplexy in patients with pituitary macroadenomas can occur either spontaneously or following various interventions. We present a case of a 71-year-old woman who developed third, fourth, and sixth cranial nerve palsies following administration of the four hypothalamic releasing hormones for routine preoperative testing of pituitary function. The MR examination showed interval tumor growth with impression of the floor of the third ventricle. There were also changes in signal intensity characteristics of the mass, suggestive of intratumoral bleeding. A transsphenoidal surgery with subtotal resection of the pituitary adenoma was performed. Microscopical examination revealed large areas of necrosis and blood surrounded by adenomatous tissue. Third, fourth, and sixth cranial nerve palsies completely resolved within 4 months. We conclude that MR imaging is useful in the demonstration of pituitary apoplexy following preoperative stimulation tests, but we suggest that these tests should be abandoned in patients with pituitary macroadenomas.

Rapid Communication The Mydriatic Effect of Tropicamide and its Diagnostic Use in Alzheimer's Disease

The mydriatic effect of topically administered tropicamide was investigated as a possible diagnostic indicator for Alzheimers disease. Although an initial series seemed to show a correlation between hypersensitivity to tropicamide and intellectual impairment, subsequent testing showed a greater inter- and intra-individual variation than that between the normal group and the group of patients with intellectual impairment. This procedure seems, therefore, to lack sufficient specificity to be useful for such a diagnostic purpose.

A new colour vision arrangement test to detect functional changes in diabetic macular oedema

AIM A study was undertaken to investigate the correlation between colour discrimination tests and the presence of macular oedema in patients with type I diabetes to find a sensitive diagnostic tool for the detection of early functional changes. METHODS The study was performed in 39 type I diabetic patients, 10 with and 29 without macular oedema. The examination included biomicroscopy, fundus photography of the macula, videofluorescein angiography, the LogMAR visual acuity chart, Farnsworth-Lanthony desaturated D-15 test, and the new Mollon-Reffin “Minimalist” test for colour vision deficiencies version 6.0. RESULTS A highly significant correlation was found between the tritan value of the Mollon test and the presence of clinically significant macular oedema (p<0.0015), with a high sensitivity (88.9%) and specificity (93.3%). The DD-15 test was not significant (p=0.345) and showed low sensitivity for the presence of macular oedema (36%). All variables concerning the grading of macular oedema showed a highly significant association with the tritan values of the Mollon test (p<0.0001). CONCLUSION The results suggest that the Mollon-Reffin “Minimalist” test version 6.0 is the best colour discrimination test for detecting macular oedema, with higher specificity and sensitivity than the other methods used in the study.

RNFL thickness in MS-associated acute optic neuritis using SD-OCT: critical interpretation and limitations.

Purpose:  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.

Mortality and incidence of renal replacement therapy in people with type 1 diabetes mellitus--a three decade long prospective observational study in the Lainz T1DM cohort.

CONTEXT AND OBJECTIVE We investigated long term mortality, requirement for renal replacement therapy (RRT), and incidence of other late diabetic complications in an observational cohort study of 641 people with type 1 diabetes (T1DM). DESIGN Prospective observational cohort study. SETTING The study was conducted at a Tertiary Diabetes Centre in Vienna, Austria. PATIENTS A cohort with all people with T1DM (n = 641, 47% females, 30 ± 11 years) attending their annual diabetes review was created in 1983-1984. Biomedical data were collected. MAIN OUTCOME MEASURES In 2013 we investigated mortality rates and incidence rates of RRT by record linkage with national registries and incidence of other major diabetes complications by questionnaire. RESULTS 156 (24%) patients died [mortality rate: 922 (95%CI: 778-1066) per 100 000 person years]. Fifty-five (8.6%) received RRT [incidence rate: 335 (95%CI: 246-423) per 100 000 person years]. The 380 questionnaires (78% return rate) recorded cardiac events, strokes, limb amputations, and/or blindness, affecting 21.8% of survivors. Mortality and incidence of RRT increased in each quartile of baseline HbA1c, with the lowest rates in the quartile with HbA1c ≤ 6.5% (48 mmol/mol) (P < .05). CONCLUSIONS In people with established type 1 diabetes who were observed for almost three decades, the overall mortality was 24% and the incidence of renal replacement therapy was 8.6%, with a 21.8% combined incidence rate of the other hard endpoints in the surviving people. A clear linear relationship between early glycemic control and the later development of end stage renal disease and mortality has been found.

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.