The 2-global flash mfERG in glaucoma: attempting to increase sensitivity by reducing the focal flash luminance and changing filter settings

Purpose: To test a new 2-flash multifocal electroretinogram (mfERG) paradigm in glaucoma using a reduced light intensity of the m-frame flash as opposed to the global flash, as it has been suggested that this may increase the responses induced by the global flash, which has been the part of the mfERG response where most changes have been noted in glaucoma. Methods: A mfERG was recorded from one eye of 22 primary open angle glaucoma (POAG) patients [16 normal tension glaucoma (NTG), 6 high tension glaucoma (HTG)] and 20 control subjects. A binary m-sequence (2^13-1, L max 100cd/m2, L min <1cd/m2), followed by two global flashes (L max 200cd/m2) at an interval of 26ms (VERIS 6.0™, FMSIII), was used. The stimulus array consisted of 103 hexagons. Retinal signals were amplified (gain=50K) and bandpass filtered at 1-300Hz. For each focal response, the root mean square was calculated. We analyzed 5 larger response averages (central 15° and 4 adjoining quadrants) as well as 8 smaller response averages (central 10° and 7 surrounding response averages of approximately 7° radius each). Three epochs were analyzed: the direct component at 15-45ms (DC) and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 45-75ms (IC-1) and at 75-105ms (IC-2). Statistical analysis was performed using linear mixed effects models adjusted for age. Results: Responses differed significantly between POAG patients and controls in all central response averages. This difference was larger for the central 10° than for the response average of the central 15°. While these observations held true for all response epochs analyzed, the DC differed least and the IC-1 most when POAG was compared to control. For POAG, the most sensitive differential measure was IC-1 of the central 10° with an area under the ROC curve of 0.78. With a cutoff value of 12.52nV/deg2, 80% of the POAG patients (100% HTG, 69% NTG) were correctly classified as abnormal, while 77% of the control subjects were correctly classified as normal. When the results of the mfERG were compared to the visual fields, there was a tendency for the mfERG to decrease as the mean defect increased. However, this correlation was only significant in the superior nasal quadrant when the IC-1 of the mfERG was compared to the corresponding area of the visual field. Conclusion: When compared to findings from previous studies, reducing the luminance of the m-frame flash in the 2-global flash paradigm did not increase the sensitivity and specificity of the mfERG to detect glaucoma furthe

Comparison of Two Different OCT Systems: Retina Layer Segmentation and Impact on Structure-Function Analysis in Glaucoma

Purpose. To compare two different spectral-domain optical coherence tomography (OCT) systems in regard to full macular thickness (MT) and ganglion cell layer-inner plexiform layer (GCIPL) measures and in regard to structure-function correlation when compared to standard automated perimetry (SAP). Methods. Seventeen primary open angle glaucoma patients and 16 controls (one eye per subject) were enrolled. MT and GCIPL thicknesses were measured by Cirrus and Spectralis OCTs. Octopus Perimeter 101 (G2 protocol) reports sensitivity in mean defect (dB). Differences between measurements were assessed with Student’s t-test and Bland Altman. Diagnostic performance was also compared between each parameter calculating the areas under the operator receiver (ROC). Linear models were used to investigate structure-function association between OCT and SAP. Results. Disagreement between OCTs in both MT and GCIPL values was significant. Spectralis values were thicker than Cirrus. Average difference between OCTs was 21.64 μm (SD 4.5) for MT and 9.8 μm (SD 5.4) for GCIPL (p<0.001). Patients differed significantly from controls in both OCTs, in both measurements. MT and GCIPL were negatively associated with MD (p<0.001). Conclusions. Although OCT values were not interchangeable, both machines differentiated patients from controls with statistical significance. Structure-function analysis results were comparable, when either OCT was compared to SAP

Characterization of excitation-contraction coupling components in human extraocular muscles

Excitation-contraction coupling (ECC) is the physiological mechanism whereby an electrical signal detected by the dihydropyridine receptor, is converted into an increase in [Ca2+], via activation of ryanodine receptors (RyRs). Mutations in RYR1, the gene encoding RyR1, are the underlying cause of various congenital myopathies including central core disease, multiminicore disease (MmD), some forms of centronuclear myopathy (CNM) and congenital fibre-type disproportion. Interestingly, patients with recessive, but not dominant, RYR1 mutations show a significant reduction in RyR protein in muscle biopsies as well as ophthalmoplegia. This specific involvement of the extraocular muscles (EOMs) indicates that this group of muscles may express different amounts of proteins involved in ECC compared with limb muscles. In the present paper, we report that this is indeed the case; in particular the transcripts encoding RyR3, cardiac calsequestrin (CSQ2) and the alpha 1 subunit of the cardiac dihydropyridine receptor are up-regulated by at least 100-fold, whereas excitation-coupled Ca2+ entry is 3-fold higher. These findings support the hypothesis that EOMs have a unique mode of calcium handling

Excitation-Contraction Coupling in Human Extraocular Muscles:There is more than Meets the Eye

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Characterization of excitation-contraction coupling components in human extraocular muscles

Excitation-contraction coupling (ECC) is the physiological mechanism whereby an electrical signal detected by the dihydropyridine receptor, is converted into an increase in [Ca2+], via activation of ryanodine receptors (RyRs). Mutations in RYR1, the gene encoding RyR1, are the underlying cause of various congenital myopathies including central core disease, multiminicore disease (MmD), some forms of centronuclear myopathy (CNM) and congenital fibre-type disproportion. Interestingly, patients with recessive, but not dominant, RYR1 mutations show a significant reduction in RyR protein in muscle biopsies as well as ophthalmoplegia. This specific involvement of the extraocular muscles (EOMs) indicates that this group of muscles may express different amounts of proteins involved in ECC compared with limb muscles. In the present paper, we report that this is indeed the case; in particular the transcripts encoding RyR3, cardiac calsequestrin (CSQ2) and the alpha 1 subunit of the cardiac dihydropyridine receptor are up-regulated by at least 100-fold, whereas excitation-coupled Ca2+ entry is 3-fold higher. These findings support the hypothesis that EOMs have a unique mode of calcium handling

Belastungsabhängige vertikale Doppelbilder und Ptosis

A 43-year-old patient presented to our department because her left eyelid had exhibited drooping to varying extents for 2-3 months. Furthermore, in extreme positions or after rapid eye movement, she perceived diplopic images and was sensitive to light. The diagnosis of sphenoid meningioma was reached. Subsequently two rounds of radiopeptide therapy with (90)Y-DOTATOC (somatostatin analog) were administered within 3 months. This treatment approach led to a reduction of tumor volume in our patient as well as clinical improvement followed by stabilization

Applying a New Automated Perimetry Pattern Based on the Stimulus Distribution of the Multifocal ERG to Improve Structure-Function Investigation in Glaucoma

Purpose. To validate a new automated perimetry pattern (mf103 pattern) for the investigation of retinal structure-function relationships in glaucoma in comparison to the standard G2 pattern and to relate either field’s performance to optical coherence tomography (OCT). Methods. Automated perimetry data from the mfERG103 pattern were compared with the standard G2 pattern in glaucoma patients (18) and controls (15). The results of both (mean defect (MD) and mean sensitivity (MS)) were compared with optical coherence tomography (OCT): retinal nerve fiber layer (RNFL) thickness, macular thickness (mT), and ganglion cell analysis (GCIPL). Nine patients were followed up after one year. Results. G2 pattern and mf103 pattern did not differ significantly in MD or MS. The mf103 pattern associated significantly with more RNFL sectors in both MD and MS (p<0.01 and p<0.05, resp.). GCIPL thickness was not significantly associated with either SAP protocols. Both protocols remained comparable after one-year follow-up. Conclusions. G2 and mf103 pattern can both differentiate patients from controls with no significant difference in performance. RNFL thickness defects correlated better with mf103 than G2 with POAG. The mfERG-103 perimetry pattern can be used to establish structure-function correlations in glaucoma and may enable a more direct comparison with objective electrophysiological data