MfERG responses to long-duration white stimuli in glaucoma patients

The intent of our study was to evaluate whether the response to a long-duration white stimulus in the multifocal electroretinogram (mfERG) is sufficiently sensitive to detect early retinal dysfunction in glaucoma. On-off mfERGs were recorded from 15 NTG and 15 HTG patients and compared with 14 control subjects. Recording parameters were the following: LED stimulus screen (RETIscan™), 100-ms stimulus duration, 200-ms stimulus interval, 11-min total recording time, stimulus matrix of 61 elements, frame rate: 70Hz, Lmax: 180cd/m2, Lmin: 0cd/m2, and filter setting: 1-200Hz. The second negative response following stimulus onset (N2-on), as well as following stimulus offset (N2-off), was analyzed as an overall response and in quadrants, as well as in 4 small central and four adjoining peripheral areas per quadrant. The latency of the N2-on was significantly delayed in HTG in all response averages tested, while in NTG this was only seen in the overall response and in the small central response averages (P<0.05). The most sensitive measure in HTG was the latency of the N2-on of the small peripheral response average of the superior temporal quadrant with an area under the ROC curve of 0.881. For NTG, the most representative measure was the latency of the N2-on of the small central response average of the inferior nasal quadrant with an area under the ROC curve of 0.793. Our results showed that in stimulation with long-duration flashes, the second negative response following the on response, representative of the early PhNR, is affected in glaucoma where N2-on showed a latency delay in POAG patients. The latency delay of the N2-on was more prominent for HTG than for NT

A Comparison of the Fast Stimulation Multifocal-ERG in Patients with an IOL and Control Groups of Different Age

Purpose: It has been shown that a cataract significantly reduces mfERG responses in the central 4-14°. Removing the cataract, leads to a significant increase in the response of the central 4°. In this study we compare the mfERG of Woerdehoff etal.'s patients' [Doc Ophthalmol 2004; 108(1): 67-75] following cataract surgery to a healthy control group in order to assess whether, in the elderly, further influences of age need to be considered in addition to optical effects. Methods: Eighteen patients with an IOL following cataract surgery and 29 healthy volunteers (without clouding of the media or retinal changes) underwent testing of the mfERG (103 hexagons stimulating the central 50°, M-sequence 215, Lmax: 200cd/m2, Lmin <1cd/m2). For the first order response component we compared the latencies of N1,P1 and N2 as well as the natural logarithm (ln) of the amplitudes N1P1 and P1N2 for four group averages: I. the central 4°, II. 4-7°, III. 7-10° and IV. 10-15°. Results: Mean age was 67years (SD 10.1) for the IOL patients, 28.5years (SD 5.6) for a young group of controls (n=15) and 60.2years (SD 9.2) for the older control group (n=14). Patients with an IOL did not differ in latency from either control group (ANOVA, Tukey). Interestingly, at 10-15° eccentricity, the latency of N2 differed significantly between the younger (41.4ms, SD 1.4) and the older (43.0ms, SD 1.9) control group. In the central 4° LnN1P1 amplitudes were significantly lower in the IOL group (mean: 3.7, SD 0.2) than either the younger (mean: 3.9, SD 3.3) or the older (mean: 4.0, SD 0.3) control group. In all other amplitude measures, the older control group had slightly larger mean amplitudes than the younger control group and significantly larger amplitudes than the patients with an IOL, whose amplitudes were lowest. Discussion: Both, primarily optical but also neural phenomena have been described to affect the mfERG changes observed with age. Our results, are in support of this, as the improvement of the mfERG response following cataract surgery does not seem to reach the level of a healthy control group of equal age. Thus, our results suggest, that a control group with an IOL should be used when retinal function is tested in subjects with an IO

Function and morphology in macular retinoschisis associated with optic disc pit in a child before and after its spontaneous resolution

Optic disc pit (ODP) is a rare congenital defect within the optic nerve head. Macula elevation associated with ODP develops in 75-93% of the adult patients. Macular involvement in children with optic disc pit is rare, and only a few cases have been published to date. In the present case, we have observed morphology and function of the central retina in a child with ODP-associated macular detachment and following its spontaneous resolution. An 8-year-old white boy diagnosed with a macular detachment in an eye with an ODP. Optical coherent tomography (OCT) and multifocal electroretinography (mfERG), as well as visual acuity and visual field, were performed in the follow-up of the unilateral schisis—like retinal detachment. A large retinoschisis associated with ODP in a child showed a tendency to spontaneously resolve at 3months, which was confirmed on OCT. At this time, an mfERG revealed markedly reduced responses. Despite morphologic reattachment at follow-up and improvement in visual acuity, increased mfERG responses were still not the same as in the fellow healthy eye. In contrast to the OCT which is very helpful to assess the extent of the neurosensory detachment, the mfERG offers an additional tool for follow-up of retinal function in this disorder. The good visual outcome in our patient shows that in the presence of residual retinal function on mfERG and in the absence of further lesions on OCT, follow-up is a valid option in children with an ODP-associated macular detachmen

LED-generated Multifocal ERG On- and Off-responses in Complete Congenital Stationary Night Blindness - A Case Report

We report on the application of a light emitting diode (LED) screen to elicit multifocal ERG on- and off-responses in a patient presenting with the complete type of congenital stationary night blindness (cCSNB): A 63-years old woman was diagnosed with cCSNB by means of standard ERG procedures and dark adaptometry. To confirm this diagnosis and to investigate topographical differences of on- and off-responses a multifocal approach employing long-duration stimuli was added. Results of mfERG-testing were averaged in three groups (a central area of 7.5°, a ring area of 7.5-21.9° and a peripheral ring of 21.9-31.1°). When compared to normal controls (n = 4) on-responses (P1-amplitudes) were severely reduced symmetrically at all eccentricities, while off-responses showed no reduction resulting in an increased off/on-ratio. Furthermore on-latencies of P1 were delayed symmetrically at all eccentricities, whereas off-latencies were normal. To our knowledge this is the first report of multifocal on- and off-responses in a CSNB-patient. Stimulus-generation with a LED-screen provides the advantage of a stable luminance during the long-duration on-phas

30Hz-flicker mfERG in primary open-angle glaucoma patients: 30Hz-flicker-mfERG in POAG

Purpose: This study was performed in an attempt to gain more information on whether the 30Hz-flicker mfERG indeed provides a sensitive measure of dysfunction in patients with primary open-angle glaucoma (POAG) as has been suggested previously. Methods: Eighteen POAG patients with visual field defects (MD>2.2dB) and glaucomatous optic neuropathies as well as 10 control subjects underwent mfERG recording as follows: 30Hz-flicker mfERG, LED stimulus screen, 61 hexagons, L max: 180cd/m2, L min: 0cd/m2, recording time: ∼5min, filter setting: 10-200Hz. The 30Hz response (also called the fundamental or the first harmonic response (1HW) and the second harmonic wave at 60Hz (2HW) were analysed as an overall response and in quadrants, as well as in 4 small neighbouring areas per quadrant. The patients' mfERGs were compared to those of the control group and to the mean defect values (MD) of the corresponding quadrants of the Octopus perimetry. Results: Neither in the overall response, nor in the quadrants, nor in the smaller areas examined did amplitudes and phases of the 1HW and the 2HW or the amplitude ratio of the 2HW to the 1HW (DFT-ratio) differ from the controls (P>0.05—ANOVA). There was no significant correlation between mfERG values and the MD (Spearman-test, Bonferroni). Conclusion: Thus, the 30Hz-flicker mfERG does not seem to be sensitive enough to separate glaucoma patients from norma

Functional characterization of orbicularis oculi and extraocular muscles

The orbicularis oculi are the sphincter muscles of the eyelids and are involved in modulating facial expression. They differ from both limb and extraocular muscles (EOMs) in their histology and biochemistry. Weakness of the orbicularis oculi muscles is a feature of neuromuscular disorders affecting the neuromuscular junction, and weakness of facial muscles and ptosis have also been described in patients with mutations in the ryanodine receptor gene. Here, we investigate human orbicularis oculi muscles and find that they are functionally more similar to quadriceps than to EOMs in terms of excitation-contraction coupling components. In particular, they do not express the cardiac isoform of the dihydropyridine receptor, which we find to be highly expressed in EOMs where it is likely responsible for the large depolarization-induced calcium influx. We further show that human orbicularis oculi and EOMs express high levels of utrophin and low levels of dystrophin, whereas quadriceps express dystrophin and low levels of utrophin. The results of this study highlight the notion that myotubes obtained by explanting satellite cells from different muscles are not functionally identical and retain the physiological characteristics of their muscle of origin. Furthermore, our results indicate that sparing of facial and EOMs in patients with Duchenne muscular dystrophy is the result of the higher levels of utrophin expression

The ‘two global flash' mfERG in high and normal tension primary open-angle glaucoma

Purpose: To analyse the sensitivity of the ‘2 global flash' multifocal electroretinogram (mfERG) to detect glaucomatous dysfunction in normal tension (NTG) and high tension primary open angle glaucoma (POAG) patients. Methods: MfERGs were recorded from 20 NTG and 20 POAG patients and compared to those of 20 controls. The mfERG array consisted of 103 hexagons. Each m-sequence step started with a focal flash that could be either dark or light (m-sequence: 2^13, L max: 200cd/m2, L min: 1cd/m2), followed by two global flashes (L max: 200cd/m2) at an interval of ∼26ms. Focal scalar products (SP) were calculated using focal templates derived from the control recordings (VERIS 4.8). We analyzed 5 response averages (central 7.5 degrees and 4 adjoining quadrants) of the response to the focal flash, the direct component at 10-40 ms (DC) and the following two components induced by the effects of the preceding focal flash on the response to the global flashes at 40-70ms (IC-1) and at 70-100 ms (IC-2). Results: Both NTG and POAG patients differed from controls in the IC-1 response to the superior quadrants, and POAG patients also differed from controls in the centre. The most sensitive parameter was the IC-1 of the superior temporal quadrant with an area under the ROC curve of 0.82 for POAG and 0.79 for NTG. The DC and the IC-2 did not differ significantly between the groups. When all five response averages of the IC-1 were taken into consideration 90% of the NTG patients and 85% of the POAG patients were correctly classified as abnormal while 80% of the control subjects were correctly classified as normal. Conclusions: This stimulus sequence holds promise for the diagnosis of early functional changes in POAG. A new finding is that both NTG, as well as POAG can be differentiated from control subject

Y-Split Recession of the Medial Rectus Muscle as a Secondary and/or Unilateral Procedure in the Treatment of Esotropia with Distance/Near Disparity

Introduction. In esotropia with larger angles > near than at distance, splitting of the medial rectus muscle has been suggested as a treatment option. Previous reports of bilateral medial rectus Y-splitting as a first intervention showed a reduction of the distance/near disparity with fewer side effects compared to posterior fixation surgery. We address whether a medial rectus Y-splitting as a secondary and/or a unilateral procedure also reduce distance/near disparity. Materials and Methods. We retrospectively reviewed the charts of four patients undergoing Y-split recession as a second and/or unilateral surgery. Main outcomes were distance/near disparity and squint angles. Results and Discussion. Three of the four patients had undergone unilateral Y-splitting of the medial rectus as a secondary surgery, three as a unilateral procedure. Mean distance/near disparity was reduced from 17 PD preoperatively to zero at the final follow-up (FU). Preoperative angles ranged from 45 PD to 66 PD at near and from 25 PD to 55 PD at distance. At the final FU, these angles ranged from 0 PD to 20 PD at near and at distance. Mean FU was 42 months (range: 12–60 months). Conclusion. Y-split recession as a secondary and/or unilateral surgery for distance/near esotropia can reduce distance/near disparity with good long-term results. Residual esotropia can be corrected by adding resection of the lateral rectus muscle

Slow-stimulated Multifocal ERG in High- and Normal-tension Glaucoma

Purpose: To study the ability and sensitivity of the slow stimulation multifocal ERG (mfERG) to detect glaucomatous damage. Methods: Right eyes of 20 patients with normal-tension glaucoma (NTG), 15 patients with high-tension glaucoma (HTG) and 15 healthy volunteers underwent testing with the mfERG (VERIS 4.1TM). The central 50 degrees of the retina were stimulated by 103 hexagons (m-sequence: 213-1, Lmax: 100cd/m2, Lmin: 1cd/m2, background: 50cd/m2). Each m-sequence step was followed by 3 black frames (Lmax: < 1cd/m2). Five response averages of the first order response component (KI) were analyzed: the central 7.5 degrees and the 4 adjoining quadrants. The amplitudes from the first minimum, N1, to the first maximum, P1, and from P1 to the second minimum, N2, were analyzed as well as the latencies of N1, P1, N2 and the latencies of 3 multifocal oscillatory potentials (mfOPs) with their maxima at about 73, 80 and 85ms. Results: For each parameter the percentage of deviation from the mean of the control group was calculated. These values were then added for each individual to form a deviation index (DI). Seventeen patients (85.0%) with NTG and 3 patients (20.0%) with HTG showed a DI outside the normal range. The major changes were observed in the mfOPs of the NTG patients. MfOPs were then selectively filtered at 100-300Hz and their scalar product was analyzed over an epoch of 68-105ms. This confirmed that mfOPs differed significantly from the control in the central 7.5° and, for NTG, in the nasal field. With a logistic regression analysis the mfOPs had a sensitivity to differentiate 85% of the NTG patients and 73% of the HTG patients from normal. Conclusions: Under these conditions, the slow-stimulated mfERG can detect glaucomatous dysfunction in NTG (85.0%). The differences observed between NTG and HTG are in support of a different underlying pathomechanis

Idiopathic intracranial hypertension: a possible association with Imatinib

Idiopathic intracranial hypertension (IIH) is characterized by an increased intracranial pressure in the absence of a tumor and in the absence of a venous thrombosis. Associated risk factors include obesity and several medications such as tetracyclines. We report a 60-year-old patient who developed IIH under treatment with imatinib. To our knowledge such a possible connection has not been reported in the literature, even though intracranial hypertension is now listed as a rare possible side effect of treatment with imatinib in the Swiss List of Medications Arzneimittelkompendium. It remains to be seen, if further case reports will support this observation