M-sequences in ophthalmic electrophysiology.

The aim of this review is to use the multimedia aspects of a purely digital online publication to explain and illustrate the highly capable technique of m-sequences in multifocal ophthalmic electrophysiology. M-sequences have been successfully applied in clinical routines during the past 20 years. However, the underlying mathematical rationale is often daunting. These mathematical properties of m-sequences allow one not only to separate the responses from different fields but also to analyze adaptational effects and impacts of former events. By explaining the history, the formation, and the different aspects of application, a better comprehension of the technique is intended. With this review we aim to clarify the opportunities of m-sequences in order to motivate scientists to use m-sequences in their future research.

ISCEV standard for clinical pattern electroretinography (PERG): 2012 update.

The pattern electroretinogram (PERG) is a retinal response evoked by a contrast-reversing pattern, usually a black and white checkerboard, which provides information about macular and retinal ganglion cell function. This document from the International Society for Clinical Electrophysiology of Vision (www.iscev.org) is a scheduled revision of the ISCEV PERG Standard, which updates and replaces the 2007 update and all earlier versions. The standard defines a single minimum stimulus and recording protocol for clinical PERG testing to assist practitioners in obtaining good quality responses and to facilitate inter-laboratory comparison. The present revision tightens stimulus specifications, expands on steady-state PERG recording, addresses visual stimulus display distinctions (CRT vs. LCD), and provides a more explicit definition of response components.

Intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration.

PURPOSE: To investigate the benefit of adding bevacizumab to intravitreal recombinant tissue plasminogen activator (rTPA) and gas as initial therapy in subretinal hemorrhage and choroidal neovascularization because of age-related macular degeneration. METHODS: Thirty-eight consecutive patients with recent (1-31 days) subretinal hemorrhage who were treated with intravitreal rTPA and gas (26 patients) or with intravitreal bevacizumab, rTPA, and gas (12 patients) were included in this retrospective analysis. In all patients, a standardized antivascular endothelial growth factor therapy was followed. Testing of best-corrected visual acuity, biomicroscopy, and fundus examination were performed at 4 weeks and 7 months. RESULTS: The mean pretreatment best-corrected visual acuity in the rTPA/gas group was 0.08 ± 0.09 and 0.12 ± 0.13 in the bevacizumab/rTPA/gas group. After 4 weeks, it was significantly higher in the bevacizumab/rTPA/gas group (0.25 ± 0.26) than in the rTPA/gas (0.08 ± 0.1) group (P < 0.05). Also, after 7 months, best-corrected visual acuity was significantly higher in the bevacizumab/rTPA/gas group (0.07 ± 0.07 vs. 0.24 ± 0.35; P < 0.05). Reading vision could be restored in 0% (rTPA/gas) versus 50% (bevacizumab/rTPA/gas). Stabilization (0 ± 2 lines) or improvement of best-corrected visual acuity was obtained in 62% (rTPA/gas) versus 84% (bevacizumab/rTPA/gas). CONCLUSION: From our retrospective pilot study, there is a strong indication that the addition of intravitreal bevacizumab is safe and superior to the displacement of submacular hemorrhages alone with rTPA and gas.

Comparison of bevacizumab and triamcinolone for treatment of macular edema secondary to central retinal vein occlusion--a matched-pairs analysis.

PURPOSE: Our aim was to evaluate differences in the outcome of bevacizumab or triamcinolone acetate (TA) treatment in patients with macular edema (ME) after central retinal vein occlusion (CRVO). PROCEDURES: In a retrospective assessment 9 bevacizumab-treated patients and 9 TA-treated ones with ME after CRVO were pair-matched according to initial best-corrected visual acuity (BCVA) and central macular thickness (CMT) as measured by Stratus optical coherence tomography. BCVA and CMT were the main endpoints. RESULTS: The initial BCVA of 0.15 +/- 0.1 increased not significantly by 1.0 +/- 3.1 lines in the bevacizumab-treated patients after a mean of 10 months. The initial BCVA of 0.17 +/- 0.1 decreased by -1.0 +/- 5.2 lines after a mean of 13 months following initial TA injection. The only significant decrease in mean CMT by 239 +/- 209 microm occurred 8 weeks after initial bevacizumab injection. CONCLUSIONS: Both substances are able to stabilize CMT and BCVA in ME after CRVO, but only bevacizumab was devoid of unfavorable intraocular pressure elevation.

Comparison of bevacizumab and triamcinolone for treatment of macular edema secondary to branch retinal vein occlusion in a pair-matched analysis.

BACKGROUND: To compare the outcome of bevacizumab or triamcinolone acetate (TA) treatment in patients with macular edema (ME) after branch retinal vein occlusion (BRVO). METHODS: In a retrospective assessment, 10 bevacizumab-treated patients and 10 TA-treated with ME after BRVO were pair-matched according to initial best-corrected visual acuity (BCVA) and central macular thickness (CMT) as measured by Stratus optical coherence tomography (OCT). BCVA and CMT were the main endpoints. RESULTS: The initial BCVA was 0.2 +/- 0.13 in bevacizumab-treated patients and 0.2 +/- 0.16 in TA-treated patients, with a CMT of 497 +/- 102 microm and 517 +/- 88 microm, respectively. Following bevacizumab, the mean final BCVA increased by 2.8 +/- 4 lines, and by 0.6 +/- 3.5 lines in patients receiving TA. The mean final CMT was 238 +/- 118 microm and 195 +/- 243 microm in the respective treatment groups. CONCLUSIONS: Both treatments decreased the CMT, but only bevacizumab induced an improvement in BCVA from baseline, which was significant 8 weeks after treatment, but no longer significant after 13 months.

Optimizing electrode positions and analysis strategies for multifocal VEP recordings by ROC analysis.

The multifocal visual evoked potential (mfVEP) is an important tool to test visual pathway function. The aim of this study was to optimize electrode positions in mfVEP recordings. For analysis we applied a receiver operating characteristic (ROC), a method that inherently corrects for multiple testing. We found that a combination of two perpendicular derivations-both straddling the inion-was the most effective recording setup. Adding more than two derivations did not significantly increase the sensitivity. Thus optimal mfVEP detection can be achieved with a fairly simple recording setup which may facilitate mfVEP recordings in basic research and clinical routine.

[Adaptive estimation of contrast thresholds using the visual evoked potential (VEP)]. / Die adaptive Bestimmung von Kontrastschwellen mit dem visuell evozierten Potenzial (VEP).

The visual evoked potential (VEP) can be used to objectively estimate sensory thresholds. Recently, we developed an adaptive procedure for this threshold estimation based on a Fourier analysis of steady-state responses during the recording. In this study we quantified the reduction in recording time of this adaptive procedure. Steady-state VEPs to pattern reversal (f = 8.3 Hz) of checkerboards with 8 contrast values between 0.64% and 82% were recorded monocularly. Adaptive and non-adaptive recordings were performed for full correction (fc) and for blurred stimulus patterns (+1.5 D and +3.0D). VEP contrast thresholds were defined by the lowest contrast condition that showed a significant response. An ANOVA of the VEP thresholds showed significant effects (p < 0.0001) of the factors "procedure" (psychophysics, adaptive VEP, non-adaptive VEP) and "correction" (fc, fc + 1.5D, fc + 3.0D). Compared to non-adaptive recordings, adaptive recordings showed thresholds that were significantly reduced and closer to psychophysical contrast thresholds. By applying the adaptive procedure the recording time can be reduced by a factor of about 2 when compared to the non-adaptive procedure. The new adaptive VEP procedure may help to improve the correlation of electrophysiological and psychophysical estimates of sensory thresholds and may accelerate functional testing in the clinical routine.

Clinical findings in a multigeneration family with autosomal dominant central areolar choroidal dystrophy associated with an Arg195Leu mutation in the peripherin/RDS gene.

OBJECTIVE: To characterize clinical findings associated with a mutation in codon 195 (Arg195Leu) of the peripherin/RDS gene in a large multigeneration family of European decent. METHODS: Sixteen members from 2 generations underwent ophthalmologic examination, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. All affected family members underwent Farnsworth Panel-D15 color testing. Five selected family members with early stages of the disease underwent multifocal electroretinography. Full-field electroretinography was performed in 2 family members with more advanced fundus changes. Finally, former patients' records and fundus images were analyzed to determine the course of the disease in affected individuals. RESULTS: Nine family members in 2 generations were diagnosed as having autosomal dominant central areolar choroidal dystrophy. The family demonstrated an age-dependent increase of central granular fundus abnormalities with progressive development of geographic atrophy. Interindividual phenotypic variability was apparent and ranged from predominantly drusenlike depositions to single perifoveal pigment clumps. Age of onset of visual disturbances varied between 27 and 48 years. All individuals who manifested signs of disease were found to carry an Arg195Leu mutation in the peripherin/RDS gene. CONCLUSIONS: Age of onset, progression of the disease, and characteristic fundus abnormalities share similarities to previous reports on families with central areolar choroidal dystrophy associated with peripherin/RDS gene mutations in codons 172, 142, and 195, respectively. However, striking variability in individual phenotypic findings and age of onset in our family suggests that additional factors that modify the defined peripherin/RDS gene mutation Arg195Leu likely influence the severity of the disease. CLINICAL RELEVANCE: Caution should be advised in predicting the clinical course and severity of the disease based solely on a specific mutation in the peripherin/RDS gene.

Late-onset central areolar choroidal dystrophy caused by a heterozygous frame-shift mutation affecting codon 307 of the peripherin/RDS gene.

Mutations in the peripherin/RDS gene have been identified in families with various retinopathies including those affecting primarily the macula and those restricted to the retinal periphery. Here, we describe the clinical findings of two sisters with late-onset central areolar choroidal dystrophy (CACD). The two siblings underwent genetic testing and were found to be carriers of a heterozygous frame-shift mutation 920delT affecting codon 307 of the peripherin/RDS gene and resulting in a truncated, likely functionless, protein with an altered C-terminus (Leu307fsX83). The identical mutation has previously been reported to cause slowly progressive autosomal dominant retinitis pigmentosa. In our two patients, the Leu307fsX83 mutation accounts for an unusually mild form of retinal degeneration.

ISCEV standard for clinical pattern electroretinography--2007 update.

The pattern electroretinogram (PERG) is a retinal response evoked by viewing a temporally alternating pattern, usually a black and white checkerboard or grating. The PERG is important in clinical and research applications because it provides information both about retinal ganglion cell function and, because the stimulus is customarily viewed with central fixation, the function of the macula. The PERG can therefore facilitate interpretation of an abnormal pattern VEP by revealing the retinal responses to a similar stimulus to that used for the VEP. However, practitioners may have difficulty choosing between the different techniques for recording the PERG that have been described in the literature. The International Society for Clinical Electrophysiology of Vision published a standard for clinical PERG recording in 2000 to assist practitioners in obtaining good quality reliable responses and to facilitate inter-laboratory communication and comparison. This document is the scheduled revision of that standard.

Can subthreshold summation be observed with the Ehrenstein illusion?

Subthreshold summation between physical target lines and illusory contours induced by edges such as those produced in the Kanizsa illusion has been reported in previous studies. Here, we investigated the ability of line-induced illusory contours, using Ehrenstein figures, to produce similar subthreshold summation. In the first experiment, three stimulus conditions were presented. The target line was superimposed on the illusory contour of a four-arm Ehrenstein figure, or the target was presented between two dots (which replaced the arms of the Ehrenstein figure), or the target was presented on an otherwise blank screen (control). Detection of the target line was significantly worse when presented on the illusory contour (on the Ehrenstein figure) than when presented between two dots. This result was consistent for both curved and straight target lines, as well as for a 100 ms presentation duration and unlimited presentation duration. Performance was worst in the control condition. The results for the three stimulus conditions were replicated in a second experiment in which an eight-arm Ehrenstein figure was used to produce a stronger and less ambiguous illusory contour. In the third experiment, the target was either superimposed on the illusory contour, or was located across the central gap (illusory surface) of the Ehrenstein figure, collinear with two arms of the figure. As in the first two experiments, the target was either presented on the Ehrenstein figure, or between dots, or on a blank screen. Detection was better in the dot condition than in the Ehrenstein condition, regardless of whether the target was presented on the illusory contour or collinear with the arms of the Ehrenstein figure. These three experiments demonstrate the ability of reduced spatial uncertainty to facilitate the detection of a target line, but do not provide any evidence for subthreshold summation between a physical target line and the illusory contours produced by an Ehrenstein figure. The incongruence of these results with previous findings on Kanizsa figures is discussed.

The dependency of simultaneously recorded retinal and cortical potentials on temporal frequency.

To optimize the simultaneous recording of retinal and cortical potentials, we tried to identify the most sensitive condition for pattern-electroretinogram (PERG) and pattern visual evoked potential (VEP) concerning the temporal frequency. In the same session PERGs and VEPs were elicited by checkerboard patterns with 5 temporal frequencies ranging from 8 rps to 33 rps. For data analysis the steady-state responses were Fourier analysed. We evaluated whether a statistically significant response was present, estimated the magnitude of the response at the stimulus frequencies tested and estimated it's significance. For PERG less dependence on temporal frequency was evident compared to VEP. The magnitude of the VEP response was larger than that of the PERG. However the rate of statistically significant responses for the PERG compared to that of the VEP was similar for the small checksize and even higher for the large checksize. The results permit a simultaneous recording in the range of temporal frequencies, where high responses are acquired from both levels, retinal and cortical.