Changes in Visual Function and Correlations with Inner Retinal Structure in Acute and Chronic Leber's Hereditary Optic Neuropathy Patients after Treatment with Idebenone.

Progressive impairment and degeneration of retinal ganglion cells (RGC) and nerve fibers in Leber's hereditary optic neuropathy (LHON) usually cause permanent visual loss. Idebenone is currently the only approved treatment. However, its therapeutic potential in different stages of LHON has not been definitely clarified. We aimed to investigate the changes in visual function and correlations with retinal structure in acute and in chronic LHON patients after treatment with idebenone. Twenty-three genetically confirmed LHON patients were followed during treatment using logMAR charts, automated perimetry and optical coherence tomography (OCT). Mean visual acuity improved significantly in acute patients treated within 1 year from onset (-0.52 ± 0.46 logMAR from nadir), in early chronic patients who started after 1-5 years (-0.39 ± 0.27 logMAR from baseline), and in late chronic patients with treatment initiation after >5 years (-0.33 ± 0.28 logMAR from baseline, p < 0.001 all groups). In acute and in chronic patients, strong correlations between OCT and visual function parameters were present only after treatment. This and the sustained visual recovery after treatment may indicate a reactivated signal transduction in dysfunctional RGC that survive the acute phase. Our results support previous evidence that idebenone has therapeutic potential in promoting visual recovery in LHON.

Anti-Neuronal IgG4 Autoimmune Diseases and IgG4-Related Diseases May Not Be Part of the Same Spectrum: A Comparative Study.

Background: IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features. Methods: We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD. Results: A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women (p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4+ plasma cells, which are diagnostic hallmarks of IgG4-RLD. Conclusion: Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities.

Visual function in chronic Leber's hereditary optic neuropathy during idebenone treatment initiated 5 to 50 years after onset.

PURPOSE: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by a subacute and progressive impairment and subsequent degeneration of retinal ganglion cells (RGCs). In most cases, it results in optic nerve atrophy and permanently reduced visual acuity (VA). Idebenone has recently been approved in Europe for treating LHON. However, published clinical data has only focused on efficacy in patients within the first years after disease onset. The present study is the first to evaluate possible effects of idebenone treatment in patients with LHON when initiated after more than 5 years from disease onset. METHODS: Oral treatment with idebenone 300 mg tid was started in seven patients 5 to 51 years after LHON onset. All patients had genetically confirmed primary LHON mutations (m11778G>A, m14484T>C, and m13051G>A). Visual function of all fourteen eyes was tested every 3 months using logarithmic reading charts and automated static threshold perimetry. The obtained clinical data were analyzed retrospectively using a multivariate analysis for VA and the Wilcoxon signed-rank test for visual field data. RESULTS: Before treatment, VA was 0.78 ± 0.38 logMAR (range 0.24 to 1.50 logMAR). During the first year of therapy, VA improved significantly by an average of - 0.20 ± 0.10 logMAR or 10 ± 5 ETDRS letters (P = 0.002; VA range 0.06 to 1.30 logMAR). Seven of fourteen eyes showed an improvement of 2 or more lines. Visual field mean deviation increased from - 8.02 ± 6.11 to - 6.48 ± 5.26 dB after 12 months, but this change was not statistically significant (P = 0.056). CONCLUSIONS: The increase in VA of patients who have had LHON for more than 5 years observed soon after start of treatment may not constitute a coincidental spontaneous recovery. We hypothesize that the treatment response in chronic LHON was the result of a reactivated signal transduction in surviving dysfunctional RGCs. The results of this study indicate a beneficial effect of idebenone on improvement of visual function in LHON patients with established optic atrophy.

Two Cases of Pediatric AQP4-Antibody Positive Neuromyelitis Optica Spectrum Disorder Successfully Treated with Tocilizumab.

B cell depletion with the anti-CD20-antibody rituximab is widely considered treatment of choice for long-term immunotherapy in aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD). However, up to 30% of patients suffer from relapses despite complete B cell depletion. In these cases, the IL6 (interleukin-6)-receptor blocking antibody tocilizumab has been suggested as an alternative. We report two female adolescents with AQP4-antibody positive NMOSD who relapsed under rituximab treatment and clinically stabilized after switching to monthly administrations of tocilizumab. Our data suggest that early escalation of therapy with tocilizumab may lead to stabilization of disease activity in pediatric NMOSD patients who relapse under B cell depletion.

Veins in plaques of multiple sclerosis patients - a longitudinal magnetic resonance imaging study at 7 Tesla.

OBJECTIVE: To monitor the venous volumes in plaques of patients with multiple sclerosis (MS) compared to an age-matched control group over a period of 3.5 years. METHODS: Ten MS patients underwent an annual neurological examination and MRI. Susceptibility-weighted imaging (SWI) combined with fluid-attenuated inversion recovery (FLAIR) or FLAIR-like contrast at 7 Tesla (7 T) magnetic resonance imaging (MRI) was used for manual segmentation of veins in plaques, in the normal-appearing white matter (NAWM) and in location-matched white matter of 9 age-matched controls. Venous volume to tissue volume ratio was assessed for each time point in order to describe the dynamics of venous volumes in MS plaques over time. RESULTS: MS plaques, which were newly detected during the study period, showed significantly higher venous volumes compared to the preplaque area 1 year before plaque detection and the corresponding NAWM regions. Venous volumes in established MS plaques, which were present already in the first scans, were significantly higher compared to the NAWM and controls. CONCLUSIONS: Our data underpin a relation of veins and plaque development in MS and reflect increased apparent venous calibers due to increased venous diameters or increased oxygen consumption in early MS plaques. KEY POINTS: • Longitudinal 7 T Magnetic Resonance Imaging study of intralesional veins in MS patients. • Venous volumes are significantly increased in newly detected and established MS plaques. • Venous volumes in established MS plaques show a trend to decrease with time.

Hypofractionated stereotactic photon radiotherapy of posteriorly located choroidal melanoma with five fractions at ten Gy--clinical results after six years of experience.

PURPOSE: To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10 Gy each in patients with centrally located choroidal melanoma. MATERIALS AND METHODS: Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6 MV photon beams with 5 fractions at 10 Gy each. Examinations were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and yearly thereafter. Median follow-up was 37.8 months (IQR 19.2-49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. RESULTS: Initial tumor base diameters, height and volume were 11.20mm (IQR 9.10-13.70), 9.80 mm (IQR 7.80-11.70), 4.53 mm (IQR 3.33-6.43) and 253.8mm(3) (IQR 127.5-477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5 years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p<0.001). The most common toxicities (any grade) were radiation retinopathy (n=39), optic neuropathy (n=32), radiogenic cataract (n=21), neovascular glaucoma (n=15) and dry eye syndrome (n=10). The 5 year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. CONCLUSION: Hypofractionated stereotactic photon radiotherapy with a total dose of 50 Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile.

Effectiveness of averaging strategies to reduce variance in retinal nerve fibre layer thickness measurements using spectral-domain optical coherence tomography.

BACKGROUND: Automated detection of subtle changes in peripapillary retinal nerve fibre layer thickness (RNFLT) over time using optical coherence tomography (OCT) is limited by inherent image quality before layer segmentation, stabilization of the scan on the peripapillary retina and its precise placement on repeated scans. The present study evaluates image quality and reproducibility of spectral domain (SD)-OCT comparing different rates of automatic real-time tracking (ART). METHODS: Peripapillary RNFLT was measured in 40 healthy eyes on six different days using SD-OCT with an eye-tracking system. Image brightness of OCT with unaveraged single frame B-scans was compared to images using ART of 16 B-scans and 100 averaged frames. Short-term and day-to-day reproducibility was evaluated by calculation of intraindividual coefficients of variation (CV) and intraclass correlation coefficients (ICC) for single measurements as well as for seven repeated measurements per study day. RESULTS: Image brightness, short-term reproducibility, and day-to-day reproducibility were significantly improved using ART of 100 frames compared to one and 16 frames. Short-term CV was reduced from 0.94 ± 0.31 % and 0.91 ± 0.54 % in scans of one and 16 frames to 0.56 ± 0.42 % in scans of 100 averaged frames (P ≤ 0.003 each). Day-to-day CV was reduced from 0.98 ± 0.86 % and 0.78 ± 0.56 % to 0.53 ± 0.43 % (P ≤ 0.022 each). The range of ICC was 0.94 to 0.99. Sample size calculations for detecting changes of RNFLT over time in the range of 2 to 5 µm were performed based on intraindividual variability. CONCLUSION: Image quality and reproducibility of mean peripapillary RNFLT measurements using SD-OCT is improved by averaging OCT images with eye-tracking compared to unaveraged single frame images. Further improvement is achieved by increasing the amount of frames per measurement, and by averaging values of repeated measurements per session. These strategies may allow a more accurate evaluation of RNFLT reduction in clinical trials observing optic nerve degeneration.

In vivo identification of alteration of inner neurosensory layers in branch retinal artery occlusion.

BACKGROUND/AIMS: To characterise the extension and progression of alteration of neurosensory layers following acute and chronic branch retinal artery occlusion (BRAO) in vivo using spectral-domain optical coherence tomography. METHODS: In this observational case series, eight eyes with acute BRAO and nine eyes with chronic BRAO were analysed using a Spectralis Heidelberg Retina Angiograph (HRA)+optical coherence tomography system including eye tracking. Patients with acute BRAO were examined within 36±5 h after primary event and at weekly/monthly intervals thereafter. Segmentation measurements of all individual neurosensory layers were performed on single A-scans at six locations in affected and corresponding non-affected areas. The thickness values of the retinal nerve fibre layer together with the ganglion cell layer (NFL/GCL), inner plexiform layer (IPL), inner nuclear layer together with outer plexiform layer (INL/OPL), outer nuclear layer (ONL), and photoreceptor layers together with the retinal pigment epithelium (PR/RPE) were measured and analysed. RESULTS: Segmentation evaluation revealed a distinct increase in thickness of inner neurosensory layers including the NFL/GCL (35%), IPL (80%), INL/OPL (48%) and mildly the ONL by 21% in acute ischaemia compared with corresponding layers in non-ischaemic areas. Regression of intraretinal oedema was followed by persistent retinal atrophy with loss of differentiation between IPL and INL/OPL at month 2. In contrast, the ONL and subjacent PR/RPE retained their physiological thickness in patients with chronic BRAO. CONCLUSION: In vivo assessment of retinal layer morphology allows a precise identification of the pathophysiology in retinal ischaemia.

Radiogenic side effects after hypofractionated stereotactic photon radiotherapy of choroidal melanoma in 212 patients treated between 1997 and 2007.

PURPOSE: To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. PATIENTS AND METHODS: Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy. Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. RESULTS: One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. CONCLUSION: In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.

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.

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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Local tumor control, visual acuity, and survival after hypofractionated stereotactic photon radiotherapy of choroidal melanoma in 212 patients treated between 1997 and 2007.

PURPOSE: To evaluate long-term local tumor control, visual acuity, and survival after hypofractionated linear accelerator-based stereotactic photon radiotherapy in patients with choroidal melanoma. METHODS AND MATERIALS: Between 1997 and 2007, 212 patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at a linear accelerator with 6-MV photon beams at the Medical University of Vienna in five fractions over 7 days. Twenty-four patients received a total dose of 70 Gy (five fractions of 14 Gy), 158 a total dose of 60 Gy (five fractions of 12 Gy) and 30 patients a total dose of 50 Gy (five fractions of 10 Gy) applied on the 80% isodose. Ophthalmologic examinations were performed at baseline and every 3 months in the first 2 years, every 6 months until 5 years, and once a year thereafter until 10 years after radiotherapy. Assessment of visual acuity, routine ophthalmologic examinations, and measurement of tumor base dimension and height using standardized A-scan and B-scan echography were done at each visit. Funduscopy and fluorescein angiography were done when necessary to document tumor response. RESULTS: Median tumor height and volume decreased from 4.8 mm and 270.7 mm3 at baseline to 2.6 mm and 86.6 mm3 at the last individual follow-up, respectively (p<0.001, p<0.001). Median visual acuity decreased from 0.55 at baseline to hand motion at the last individual follow-up (p<0.001). Local tumor control was 95.9% after 5 years and 92.6% after 10 years. Thirty-two patients developed metastatic disease, and 22 of these patients died during the follow-up period. CONCLUSION: Hypofractionated stereotactic photon radiotherapy with 70 to 50 Gy delivered in five fractions in 7 days is sufficient to achieve excellent local tumor control in patients with malignant melanoma of the choroid. Disease outcome and vision are comparable to those achieved with proton beam radiotherapy. Decreasing the total dose below 60 Gy seems to be possible.

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).

Ocular haemodynamic changes after single treatment with photodynamic therapy assessed with non-invasive techniques.

PURPOSE: To investigate in patients with neovascular age-related macular degeneration (ARMD) the changes in ocular perfusion caused by single treatment with photodynamic therapy (PDT) by different non-invasive methods; to evaluate correlations between relative changes of ocular haemodynamic parameters after PDT among each other and compared to morphological parameters; and to assess this in relation to early changes of visual acuity. STUDY POPULATION: 17 consecutive patients with subfoveal choroidal neovascularization (CNV) caused by ARMD scheduled for PDT without previous PDT treatment (four patients with predominantly classic CNV and 13 patients with occult CNV). OBSERVATION PROCEDURES: best-corrected visual acuity (before PDT, 6 and 8 weeks after PDT), fundus photography, fluorescein angiography, haemodynamic measurements with laser Doppler flowmetry (LDF), laser interferometry and ocular blood flow (OBF) tonometry (baseline and 1, 2, 6 and 8 weeks after treatment). MAIN OUTCOME MEASURES: choroidal blood flow (CHBF), fundus pulsation amplitude (FPA), pulsatile ocular blood flow (POBF), visual acuity. Changes smaller than 20% were considered clinically irrelevant. RESULTS: Ocular haemodynamic parameters did not change significantly in the follow-up period. Changes of haemodynamic parameters showed no correlation to treatment spot, morphological changes or visual acuity. Changes of visual acuity were comparable to results of earlier studies. CONCLUSION: Single treatment with PDT did not modify ocular blood flow parameters above 20% as assessed with different non-invasive methods.

Ocular blood flow and systemic blood pressure in patients with primary open-angle glaucoma and ocular hypertension.

PURPOSE: There is evidence that altered optic nerve head (ONH) blood flow may play a role in the development and progression of glaucoma. In the present study, the baseline characteristics were examined in a study population participating in a clinical trial in which the ocular hemodynamic effects of timolol and dorzolamide were compared. METHODS: One hundred forty patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) were included in this trial and their baseline parameters compared with those of a group of 102 age-matched control subjects. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the ONH. Pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. In addition, hemodynamic parameters and mean arterial pressure were calculated in both groups. RESULTS: All ocular hemodynamic parameters were significantly lower in the POAG/OHT group compared with the healthy control group (P < 0.001 each). In addition, a significant positive correlation between laser Doppler flowmetry readings and mean arterial pressure was observed in patients with glaucoma but not in healthy control subjects. Likewise, the correlation coefficient between fundus pulsation amplitude and mean arterial pressure was higher in patients with glaucoma than in healthy control subjects. CONCLUSIONS: The present study indicates reduced ONH and choroidal blood flow and an abnormal association between blood pressure and ocular perfusion in patients with primary open-angle glaucoma or ocular hypertension, independent of topical antiglaucoma medication. Hence, vascular dysregulation appears to be an early manifestation in glaucoma that is not caused by pharmacologic intervention.

Topical fundus pulsation measurement in patients with active central serous chorioretinopathy.

OBJECTIVE: To determine regional pulsatile choroidal blood flow using laser interferometry in patients with active central serous chorioretinopathy (CSC). METHOD: The study compared an equally sized age-, sex-, and refractive error-matched control group of healthy volunteers obtained from the Department of Clinical Pharmacology with 18 consecutive patients who had newly diagnosed active, unilateral CSC obtained from the University of Vienna Eye Clinic, Vienna, Austria. MAIN OUTCOME MEASURES: Regional fundus pulsation amplitude as assessed using laser interferometry. RESULTS: The median age of the patients was 40 years; the male-female ratio was 16:2. Foveal fundus pulsation amplitude was significantly higher in eyes with CSC (mean [SD], 5.5 [1.7] micro m) than in the eyes of the control subjects (4.1 [1.1] micro m; P =.005). In addition, eyes with CSC had a significantly higher variability in fundus pulsation amplitude (mean [SD], 48% [20%]) assessed at different fundus locations around the leak than the controls did (20% [9%]; P<.001). CONCLUSIONS: To our knowledge, this is the first study that measures topical fundus pulsations in patients who have active, unilateral CSC. These data indicate a generally increased foveal pulsatile choroidal blood flow and an abnormal distribution of fundus pulsation amplitude in the area close to the leak. Whether these findings reinforce the concept that choroidal perfusion abnormalities play a role in the pathogenesis of CSC remains to be established.

Chlamydia pneumoniae in central retinal artery occlusion.

PURPOSE: There is increasing evidence that the common respiratory human pathogen Chlamydia pneumoniae has a causative role in atherosclerosis. We investigated the association of this pathogen with acute central retinal artery occlusion (CRAO). PATIENTS AND METHODS: Sera of 14 consecutive patients with CRAO and of 14 age- and sex-matched control subjects were examined. Antibodies against chlamydial lipopolysaccharide (LPS) and outer membrane proteins of C. pneumoniae were determined by an enzyme-linked immunosorbent assay (ELISA). RESULTS: In the CRAO group, seven patients (50%) were found to be IgA positive, 12 (86%) were IgG positive and one (7%) was IgM positive for chlamydial LPS antibodies. In the control group 36%, 79% and 14% were IgA, IgG and IgM positive, respectively. The results showed no significant difference between the groups. In the CRAO group, IgA, IgG and IgM antibodies to C. pneumoniae were found in 43%, 79% and 0% of subjects, respectively. These findings did not differ significantly from those pertaining to matched controls. CONCLUSIONS: These data do not support an association between acute CRAO and current C. pneumoniae infection.

Effect of age on antibody titer to Mycoplasma pneumoniae.

Between January 1996 and September 1999, 13,650 serum samples from 12,337 patients were examined for antibodies to Mycoplasma pneumoniae at the Institute of Hygiene, University Hospital Vienna in the course of routine diagnosis. Antibody determination was performed by means of the microparticle agglutination assay Serodia Myco II. Overall, positive results (antibody titer > or = 1:40) were obtained in 2028 patients (16.4%). Age details were available for analysis in 2016 positive patients. Young children (< or = 9 y) who tested positive showed a geometric mean titer of 1:137.9 (95% confidence interval: 117.7-161.4). The geometric mean titers of positive patients decreased significantly with age (Spearman's correlation coefficient -0.20; p < 0.0001). Only 1/87 patients with serological evidence of M. pneumoniae infection aged > or = 70 y showed a titer of > or = 1:320. These data highlight the fact that, in the elderly, acute M. pneumoniae infection has to be considered in cases with slightly elevated antibody titers, which are usually referred to as borderline in children and young adults.

Chlamydia in anterior ischemic optic neuropathy.

There is an increasing body of evidence linking the common respiratory human pathogen Chlamydia pneumoniae with atherosclerosis and other vascular disorders. Our research was designed to investigate the association of this organism with anterior ischemic optic neuropathy (AION), representing an acute ischemic disorder of the optic nerve head. Sera were examined of 14 consecutive patients with AION and of 14 age- and sex-matched control subjects with noncardiovascular, nonpulmonary disorders. Antibodies against chlamydial lipopolysaccharide (LPS) and outer membrane proteins of C. pneumoniae were determined by ELISA. Further, nucleic acid amplification tests were done in order to detect C. pneumoniae-specific nucleotide sequences. Four patients (29%) were IgA positive, 11 (79%) were IgG positive and 1 (7%) was IgM positive for chlamydial LPS antibodies. In the control group, 36, 79 and 7% were IgA, IgG and IgM positive and showed no significant difference. IgA, IgG and IgM antibodies to C. pneumoniae were found in 43, 79 and 0% and did not differ from matched controls. By the nucleic acid amplification test, specific C. pneumo niae sequences were neither detected in the AION patients nor in the control group. These data do not support the association of AION with previous C. pneumoniae infection. However, it remains unclear whether Chlamydia actually initiates atherosclerotic injury, facilitates its progression or plays another role in other vascular disorders.