The use of intravenous methylprednisolone in giant cell arteritis-a population-based study.

OBJECTIVES: To determine clinical characteristics, outcome, and occurrence of comorbidities in patients with biopsy-confirmed giant cell arteritis (GCA) treated with intravenous methylprednisolone (IVMP) vs those receiving oral glucocorticoids (OGC) only. METHODS: A retrospective study included patients with GCA diagnosed from 2004 through 2019. Clinical and laboratory characteristics, and cumulative GC dose were compared in patients receiving IVMP vs OGCs. Changes in visual acuity (VA), occurrence of comorbidities after GCA diagnosis, and mortality were analysed. RESULTS: Four-hundred-nineteen patients (69% female) were included. One-hundred-eleven patients were initially treated with IVMP, 104 (94%) of whom showed visual manifestations at onset, and 308 received OGCs only. Ninety patients (21.5%) exhibited visual involvement at onset, verified by an ophthalmologist. Compared with OGC, patients receiving IVMP exhibited lower inflammatory response at presentation. There was a tendency for improvement in VA with the use of IVMP, but the results were not statistically significant (OR 1.19, 95% CI 0.35-4.01). Patients treated with IVMP had a higher risk of newly diagnosed diabetes mellitus within a year of GCA diagnosis (OR 2.59, 95% CI 1.19-5.63). This risk remained elevated after adjusting for cumulative OGC dose at three months (adjusted OR 3.30, 95% CI 1.29-8.43). There was no difference in survival between treatment groups. CONCLUSIONS: Our study found no evidence supporting any benefit of using IVMP in improving VA or survival. IVMP may increase diabetes risk within a year of GCA diagnosis. Further studies are needed to evaluate the value IVMP in GCA.

Comparison of perimetric 24-2 and 30-2 test patterns in detecting visual field defects in patients with tumours in the pituitary region.

PURPOSE: Automated perimetry provides a standardized method of measuring the visual field. The Humphrey Field Analyser (HFA) uses the 24-2 test pattern to cover 24 degrees centrally or the 30-2 test pattern to cover a slightly broader region of 30 degrees. The aim of this study was to determine whether the 24-2 test pattern provides comparable information to the 30-2 test pattern in detecting visual field defects in patients with tumours in the pituitary region. METHODS: A retrospective cohort study was carried out on patients with tumours in the pituitary region and radiologically confirmed compression of the visual pathway. Included patients (79 of 133) had been examined using the Humphrey 30-2 visual field test, after which the 30-2 test patterns were reduced into corresponding 24-2 test patterns. The location of visual field defects, visual acuity and the perimetric parameters mean deviation (MD) and visual field index (VFI) were also recorded. RESULTS: No patient was classified differently when evaluated with the 24-2 test pattern, compared to the 30-2 test pattern. Interestingly, although the majority of patients had visual field defects located in the temporal visual field of each eye, a significant minority did not. In addition, it was found that a large proportion of patients had normal visual acuity (≥0.8). CONCLUSIONS: The use of the HFA 24-2 test pattern reliably detected visual field defects in patients with tumours in the pituitary region. The present study indicates that MD and VFI are not reliable parameters for evaluating visual field defects due to compression.

Visual acuity in patients with non-functioning pituitary adenoma: Prognostic factors and long-term outcome after surgery.

Background: Visual acuity (VA) and visual field defects (VF) are evaluated in the preoperative management of non-functioning pituitary adenoma (NFPA). The former is less studied than the latter. Research question: To analyze preoperative factors, including adenoma volumetry, associated with reduced VA and postoperative improvement of VA over five years after surgery. Methods: Eighty-seven patients who had primary surgery for NFPA were retrospectively reviewed. Eyes were categorized by best/worse preoperative VA. Ophthalmology review was performed before surgery, at three months, one to two years, and five years post-surgery. Results: Reduced VA in any eye was present in 55%. VA of the worse eye improved in 77% and normalized in 54%. The majority improved within three months. Additional cases with VA improvement were seen at 1-2 years after surgery. No further improvement was seen five years after surgery. Fifty percent of patients with, per definition, normal preoperative VA showed improved VA postoperatively. Tumor height above the sella in the sagittal plane was the best radiological predictor of reduced VA. Volumetry did not add to accuracy. Age, sagittal tumor height and visual field defects were risk factors of preoperative reduced VA. No predictors of postoperative recovery were identified. Conclusion: Half of patients with reduced VA recover fully. All patients, independent of age and degree of VA reduction, may improve. No predictors of recovery were found. Early improvement is common and improvement beyond two years is unlikely. The frequency of reduced VA is underestimated. The present results could be of value in pre- and postoperative counseling.

Mapping the architecture of the temporal artery with photoacoustic imaging for diagnosing giant cell arteritis.

Photoacoustic (PA) imaging is rapidly emerging as a promising clinical diagnostic tool. One of the main applications of PA imaging is to image vascular networks in humans. This relies on the signal obtained from oxygenated and deoxygenated hemoglobin, which limits imaging of the vessel wall itself. Giant cell arteritis (GCA) is a treatable, but potentially sight- and life-threatening disease, in which the artery wall is infiltrated by leukocytes. Early intervention can prevent complications making prompt diagnosis of importance. Temporal artery biopsy is the gold standard for diagnosing GCA. We present an approach to imaging the temporal artery using multispectral PA imaging. Employing minimally supervised spectral analysis, we produce histology-like images where the artery wall is clearly discernible from the lumen and further differentiate between PA spectra from biopsies diagnosed as GCA- and GCA+ in 77 patients.

Waveform characterisation and comparison of nystagmus eye-tracking signals.

OBJECTIVE: Pathological nystagmus is a symptom of oculomotor disease where the eyes oscillate involuntarily. The underlying cause of the nystagmus and the characteristics of the oscillatory eye movements are patient specific. An important part of clinical assessment in nystagmus patients is therefore to characterise different recorded eye-tracking signals, i.e. waveforms. APPROACH: A method for characterisation of the nystagmus waveform morphology is proposed. The method extracts local morphologic characteristics based on a sinusoidal model, and clusters these into a description of the complete signal. The clusters are used to characterise and compare recordings within and between patients and tasks. New metrics are proposed that can measure waveform similarity at different scales; from short signal segments up to entire signals, both within and between patients. MAIN RESULTS: The results show that the proposed method robustly can find the most prominent nystagmus waveforms in a recording. The method accurately identifies different eye movement patterns within and between patients and across different tasks. SIGNIFICANCE: In conclusion, by allowing characterisation and comparison of nystagmus waveform patterns, the proposed method opens up for investigation and identification of the underlying condition in the individual patient, and for quantifying eye movements during tasks.

Photoacoustic imaging for non-invasive examination of the healthy temporal artery - systematic evaluation of visual function in healthy subjects.

PURPOSE: Photoacoustic (PA) imaging has the potential to become a non-invasive diagnostic tool for giant cell arteritis, as shown in pilot experiments on seven patients undergoing surgery. Here, we present a detailed evaluation of the safety regarding visual function and patient tolerability in healthy subjects, and define the spectral signature in the healthy temporal artery. METHODS: Photoacoustic scanning of the temporal artery was performed in 12 healthy subjects using 59 wavelengths (from 680 nm to 970 nm). Visual function was tested before and after the examination. The subjects' experience of the examination was rated on a 0-100 VAS scale. Two- and three-dimensional PA images were generated from the spectra obtained from the artery. RESULTS: Photoacoustic imaging did not affect the best corrected visual acuity, colour vision (tested with Sahlgren's Saturation Test or the Ishihara colour vision test) or the visual field. The level of discomfort was low, and only little heat and light sensation were reported. The spectral signature of the artery wall could be clearly differentiated from those of the subcutaneous tissue and skin. Spectral unmixing provided visualization of the chromophore distribution and overall architecture of the artery. CONCLUSIONS: Photoacoustic imaging of the temporal artery is well tolerated and can be performed without any risk to visual function, including the function of the retina and the optic nerve. The spectral signature of the temporal artery is specific, which is promising for future method development.

Modeling and quality assessment of nystagmus eye movements recorded using an eye-tracker.

Mathematical modeling of nystagmus oscillations is a technique with applications in diagnostics, treatment evaluation, and acuity testing. Modeling is a powerful tool for the analysis of nystagmus oscillations but quality assessment of the input data is needed in order to avoid misinterpretation of the modeling results. In this work, we propose a signal quality metric for nystagmus waveforms, the normalized segment error (NSE). The NSE is based on the energy in the error signal between the observed oscillations and a reconstruction from a harmonic sinusoidal model called the normalized waveform model (NWM). A threshold for discrimination between nystagmus oscillations and disturbances is estimated using simulated signals and receiver operator characteristics (ROC). The ROC is optimized to find noisy segments and abrupt waveform and frequency changes in the simulated data that disturb the modeling. The discrimination threshold, 𝜖, obtained from the ROC analysis, is applied to real recordings of nystagmus data in order to determine whether a segment is of high quality or not. The NWM parameters from both the simulated dataset and the nystagmus recordings are analyzed for the two classes suggested by the threshold. The optimized 𝜖 yielded a true-positive rate and a false-positive rate of 0.97 and 0.07, respectively, for the simulated data. The results from the NWM parameter analysis show that they are consistent with the known values of the simulated signals, and that the method estimates similar model parameters when performing analysis of repeated recordings from one subject.

A robust method for calibration of eye tracking data recorded during nystagmus.

Eye tracking is a useful tool when studying the oscillatory eye movements associated with nystagmus. However, this oscillatory nature of nystagmus is problematic during calibration since it introduces uncertainty about where the person is actually looking. This renders comparisons between separate recordings unreliable. Still, the influence of the calibration protocol on eye movement data from people with nystagmus has not been thoroughly investigated. In this work, we propose a calibration method using Procrustes analysis in combination with an outlier correction algorithm, which is based on a model of the calibration data and on the geometry of the experimental setup. The proposed method is compared to previously used calibration polynomials in terms of accuracy, calibration plane distortion and waveform robustness. Six recordings of calibration data, validation data and optokinetic nystagmus data from people with nystagmus and seven recordings from a control group were included in the study. Fixation errors during the recording of calibration data from the healthy participants were introduced, simulating fixation errors caused by the oscillatory movements found in nystagmus data. The outlier correction algorithm improved the accuracy for all tested calibration methods. The accuracy and calibration plane distortion performance of the Procrustes analysis calibration method were similar to the top performing mapping functions for the simulated fixation errors. The performance in terms of waveform robustness was superior for the Procrustes analysis calibration compared to the other calibration methods. The overall performance of the Procrustes calibration methods was best for the datasets containing errors during the calibration.

Clinical Translation of a Novel Photoacoustic Imaging System for Examining the Temporal Artery.

The objective was to provide a clinical setup for photoacoustic imaging (PAI) of the temporal artery in humans and to describe the challenges encountered and methods of overcoming them. The temporal artery was examined in seven patients with suspect giant-cell arteritis (GCA), both in vivo and ex vivo, and the results were compared to that of histology. To adapt PAI to the human studies, the transducer was fixed to an adjustable arm to reduce motion artifacts, and a stepping motor was developed to enable 3-D scanning. Risks associated with the use of lasers, ultrasound, and electrical equipment were evaluated by measuring energy levels, and safety precautions were undertaken to prevent injury to the patients and staff. The PAI spectra obtained clearly delineated the artery wall, both in vivo and ex vivo, although the latter was of high quality due to the lack of artifacts. The results could be compared to that of histology. The involved energy levels were found to be below the limits given in regulatory standards. Eye protectors prevented irradiation of the patient's eyes, and visual function after the procedure was found not to be affected. The patients reported no discomfort during the investigations. PAI provides images of the temporal artery wall that may be used for the future diagnosis of GCA in humans. The technique could be further refined by addressing the specific problems of motion artifacts and interference from blood and other chromophores. This study paves the way for other clinical applications of PAI.

Visual outcome is similar in optic neuritis patients treated with oral and i.v. high-dose methylprednisolone: a retrospective study on 56 patients.

BACKGROUND: To investigate visual recovery after treatment of acute optic neuritis (ON) with either oral or intravenous high-dose methylprednisolone, in order to establish the best route of administration. METHODS: Retrospective analysis of patients treated with oral or intravenous high-dose (≥500 mg per day) methylprednisolone for acute ON of unknown or demyelinating etiology. Twenty-eight patients were included in each treatment group. Visual acuity was measured with the Snellen letter chart, color vision with Boström-Kugelberg pseudo-isochromatic plates, and visual field with a Humphrey Field Analyzer. RESULTS: The treatment results were similar in the two groups at follow-up, with no significant difference in visual acuity (p = 0.54), color vision (p = 0.18), visual field mean deviation (p = 0.39) or the number of highly significantly depressed test points (p = 0.46). CONCLUSIONS: The results show no clinical disadvantage of using oral high-dose corticosteroids compared to intravenous administration in the treatment of acute ON, which would facilitate the clinical management of these patients.