[Functional and Morphological Microstructural Changes in SD-OCT in Long-Term Treatment for Neovascular AMD with Ranibizumab - Monotherapy Versus Combination Therapy with PDT]. / Funktionelle und morphologische mikrostrukturelle Veränderungen in der SD-OCT bei der Langzeitbehandlung der neovaskulären AMD mit Ranibizumab-Monotherapie versus Kombinationstherapie mit PDT.

Background: Intravitreal anti-VEGF therapy is the gold standard in the treatment of neovascular age-related macular degeneration (nAMD). In recent literature, the benefit of additional photodynamic therapy (PDT) has been debated. The aim of our study was to compare the functional and structural effects of long-term combination therapy with PDT plus ranibizumab with monotherapy with ranibizumab. Material and Methods: In a retrospective study, patients suffering from nAMD were followed up for at least 42 months. Patients were assigned to group A (monotherapy with ranibizumab according to pro re nata [PRN]) or group B (combination therapy with one-time PDT plus ranibizumab according to PRN). The best-corrected visual acuity (BVCA) was evaluated at the starting and end points, together with central retinal thickness (CRT), maximal retinal thickness (MRT) and the maximal diameter of the base of the subretinal plaque in spectral-domain optical coherence tomography (SD-OCT), at the first measurement and at the end point. Results: Group A consisted of 21 eyes (17 patients) and group B consisted of 12 eyes (11 patients). The average follow-up from starting to end point was 64 months and 47 months, from the first measurement of SD-OCT to the end point. Within this period, patients in group A received 19 ± 14 intravitreal injections, and patients in group B received 22 ± 10 intravitreal injections. BCVA at the starting point was 0.31 ± 0.26 in group A and 0.31 ± 0.17 in group B. At the end point, BCVA in group A was 0.29 ± 0.25 (p = 0.405), and in group B 0.25 ± 0.20 (p = 0.142). CRT decreased in group A by 72 ± 178 µm (p = 0.024) and group B by 28 ± 98 (p = 0.1335). MRT decreased in group A by 25 ± 135 µm (p = 0.166) and in group B by 2 ± 118 µm (p = 0.421). The base of the subretinal plaque increased in group A by 32 ± 1468 µm (p = 0.242) and in group B by 748 ± 1024 (p = 0.025). Conclusion: In a long-term follow-up of 5.3 years, patients with nAMD in both groups exhibited good stabilisation of visual acuity. In both groups, retinal thickness decreased and the base of the subretinal plaque increased. With respect to SD-OCT morphological criteria, patients in group A (monotherapy) responded slightly better to therapy than patients in group B (combination group).

[Morphological Characteristics in SD-OCT and Fundus Autofluorescence in Different Ischaemic Retinopathies - Characterisation of a New, Temporary Hyperreflective Band]. / Morphologische Charakteristika im hochauflösenden OCT und in der Fundusautofluoreszenz bei verschiedenen ischämischen Retinopathien - Beschreibung einer zusätzlichen, temporären hyperreflektiven Bande.

BACKGROUND: The aim of this study was to investigate alterations in the neurosensory retinal morphology secondary to acute retinal ischaemic conditions. The observations were documented by spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering) and fundus autofluorescence (FAF) imaging. In addition, the occurrence of an additional hyperrefelctive band in the outer corneal layers is described. This observation was made during the evaluation of OCT images of patients with an acute loss of vision due to retinal ischaemia. PATIENTS/METHOD: SD-OCT images and FAF were used to observe the retinal structure of 26 subjects (36 to 96 years) with acute monocular visual impairment due to central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), anterior ischaemic optic neuropathy (AION) or impending central retinal vein occlusion were included. The main focus of attention was set on the transition of the outer nuclear layer (ONL) to outer plexiform layer (OPL). Furthermore measurements of the retinal thickness at the fovea, parafoveal and within the retinal layers were acquired and compared to corresponding points of the non-affected eyes. SD-OCT images were acquired with a combined SD-OCT and scanning laser ophthalmoscope (cSLO) imaging system using a linear cross hair scan and a 6 line radial scan of 6 mm length (ART mode on; average of 20 frames). RESULTS: SD-OCT revealed an additional highly reflective band located within the OPL. Morphological characteristics of this hyperdense band were a decreasing intensity with distance from the fovea, partially segmental occurrence and manifestation limited in time. FAF showed areas of increased and decreased signal intensity within the vessel arcade at the posterior pole. The regions of decreased FAF corresponded to perivenous regions and resemble the "frosted branches" sign seen in fluorescein angiography in patients with ocular ischaemia. CONCLUSIONS: The additional hyperreflective band observed in SD-OCT could represent a marker for retinal ischaemia in subjects without the presence of a complete vascular occlusion. The mid retinal localisation of the band within the OPL is situated at the locus of transition from retinal to choroidal oxygen supply where oxygen diffusion is weakest. Histopathologically the observed structure could represent activated microglial tissue induced by the hypoxia driven upregulation of inflammatory molecules aimed at ischaemia repair.

[Vitreomacular Traction Syndrome (VMTS)]. / Vitreomakuläres Traktionssyndrom (VMTS).

In vitreomacular traction syndrome (VMTS) an anomalous posterior vitreous detachment (APVD) with persistant symptomatic vitreoretinal adhesion is seen. The adhesion leads to a thickened macula, to macular oedema and a reduction of BCVA. Modern imaging techniques like spectral domain OCT (SD-OCT) allow a detailed imaging of the retinal microstructure and the vitreoretinal interface. Vitreomacular adhesions and their effect on the retina can be visualised. Until now, the treatment option for VMTS was and is vitreoretinal surgery. In studies pharmacological vitreolysis has shown a therapeutic effect in patients with symptomatic adhesion and traction. The results of these studies represent an important step towards a pharmacological treatment of VMTS.

[Transconjunctival sutureless pars plana vitrectomy and Brilliant Peel (BP)-assisted ILM peeling in patients with macular holes]. / Transkonjunktivale nahtlose Pars-plana-Vitrektomie und Brilliant-Blau-G-assistiertes ILM-Peeling bei Patienten mit Makulaforamen.

PURPOSE: The aim of this study was to evaluate the visual and anatomic outcome after 23-gauge transconjunctival sutureless pars plana vitrectomy and Brilliant Peel (BP)-assisted ILM peeling in patients with macular holes. METHODS: In a consecutive retrospective study in 41 eyes of 41 patients with macular holes a standardised 23-G transconjunctival sutureless pars plana vitrectomy with ILM-peeling and gas tamponade was performed. All patients underwent preoperative measurements of visual acuity (VA), the maximum hole diameter, basis, height, and intraretinal changes using high resolution optical coherence tomography (SD-OCT; Spectralis; Heidelberg Engineering). Main outcome measures included visual acuity 1, 3, and 6 months after surgery and the closure rate. We also evaluated photoreceptor inner/outer segment (IS/OS) integrity as seen in SD-OCT for correlation with visual outcomes after macular hole surgery. RESULTS: At baseline the mean best corrected visual acuity (BCVA) was 0.2 (0.77 logMAR). BCVA improved significantly to 0.4 (0.46 logMAR) after 1 month, to 0.44 (0.41 logMAR) after 3 months and to 0.58 (0.28 logMAR) after 6 months, respectively. A closure rate of 95.1 % was achieved. The morphological parameter photoreceptor IS/OS integrity was measured semiquantitatively and showed a positive correlation to BCVA. CONCLUSION: Transconjunctival sutureless pars plana vitrectomy and Brilliant Peel (BP)-assisted ILM peeling in patients with macular holes is a very safe procedure and leads to good functional and anatomic results. The integrity of the IS/OS segment is a good predictive parameter for BCVA improvement after macular hole surgery.

[Choroidal neovascularisation in pathological myopia: epidemiological data from a health services research study conducted in Germany]. / Choroidale Neovaskularisation (CNV) bei pathologischer Myopie (PM): epidemiologische Daten aus einer Versorgungsforschungsstudie bei Ophthalmologen in Deutschland.

BACKGROUND: Pathological myopia (PM) or high myopia is defined as excessive short-sightedness (more than -6 dioptres) caused by a strong dilation of the bulbus oculi, that can induce the development of new and unstable vessel structures [choroidal neovascularisation (CNV)]. Since there are only limited epidemiological data available on PM, this health services research study was conducted. PATIENTS AND METHODS: A health services survey with ophthalmologists throughout Germany was undertaken. Physicians were asked to complete a 51-item questionnaire on CNV in PM as well as on its early stages in their daily practice, diagnosis, control and treatment, patient numbers and evaluation of health care situation. Statistical analyses were entirely descriptive. RESULTS: Of 7,500 ophthalmologists, a representative sample of 800 was randomly selected; 340 physicians took part. The mean prevalence rates/year/practice were 1,765.5 ± 1,218.1 with myopia, 230.7 ± 278.6 patients with high myopia, subdivided into 129.3 ± 242.8 patients with PM without macular degeneration (MD), 39.6 ± 64.8 patients with PM and MD, and 13.3 ± 30.3 patients with PM and CNV. Data on diagnosis and control show a lack of clearly defined standardisation. With regard to treatment of CNV in PM the data show the current discrepancy of guideline recommendations and approved treatment options. CONCLUSION: The prevalence and incidence data collected in this study vary considerably between physicians. This may be explained by the various grades of specialisation as well as to possibly existing uncertainties regarding the definition and nomenclature of PM/high myopia and their different stages of the disease that should be harmonised. A generally accepted definition of severity grades, recommendations on diagnosis as well as detailed information and continuous training programmes on this disease is necessary.

[Acute loss of vision during therapy of chronic hepatitis C]. / Akute Visusminderung während der Therapie einer chronischen Hepatitis C.

A patient undergoing combined therapy of chronic hepatitis C with pegylated interferon-α-2a (PEG-IFN-α-2a) and ribavirin suddenly developed severe loss of visual acuity. A central vein occlusion with macular edema was found and intravitreal injections of bevacizumab were initiated. Retinal occlusion is a known complication of therapy with pegylated interferon-α-2a and ribavirin. An interdisciplinary assessment of patients treated for a chronic hepatitis C as well as an early anti-VEGF administration can be helpful in the therapy of this complication of chronic hepatitis C.

[Early emulsification of silicone oil (2000 cs) in minimally invasive transconjunctival vitreoretinal surgery]. / Frühe Emulsifikation des 2000er-Silikonöls nach minimalinvasiver transkonjunktivaler vitreoretinaler Chirurgie.

BACKGROUND: The highly purified polydimethylsiloxane (PDMS) with a viscosity of 5000 centistokes (cs) is the preferred silicone oil endotamponade in vitreoretinal surgery (20 gauge) and shows high stability. In contrast in transconjunctival minimally invasive surgery (23 gauge) the application of 5000 cs. silicone oil shows substantial disadvantages because of time-consuming and difficult application procedure due to the small lumen of the used surgical equipment. Consequently silicone oils with lower viscosity like the 2000 cs silicone oil are being increasingly used in transconjunctival surgery. PATIENTS: We present two cases of early emulsification of the 2000 cs silicone oil (Siluron 2000 ©, Fluoron, Neu-Ulm, Germany) consisting of highly purified PDMS in the course of minimally invasive transconjunctival vitreoretinal surgery. In both cases 23 gauge vitrectomy with application of 2000 cs silicone oil was performed without any complication. The first case is a 34-year-old female with proliferative diabetic retinopathy who had already experienced several vitreoretinal operations. The present indication for vitrectomy was a persistent macular hole and vitreous haemorrhage. The second case is a 55-year-old pseudophakic patient with a retinal detachment after vitrectomy with gas endotamponade following rhegmatogenous retinal detachment. RESULTS: In the first case emulsification of silicone oil was seen on the second postoperative day. In the second case emulsification was discovered two weeks postoperatively. In both cases high intraocular pressure did not occur. CONCLUSION: With emerging performance of minimally invasive vitrectomy techniques the use of silicone oil with low viscosity in patients with conceivable endurance of the endotamponade appears to be beneficial. Up to now 10 patients have undergone 23 gauge vitrectomy with application of 2000 cs silicone oil without any complications in our clinic. In contrast, two cases demonstrated early emulsification of the 2000 cs silicone oil. To the best of our knowledge this complication has not been described before.

[Intravitreal Ranibizumab Injection for the Treatment of Occult and Classic CNV in Exsudative AMD]. / Ranibizumab intravitreal zur Behandlung okkulter und klassischer choroidaler Neovaskularisation (CNV) bei AMD.

BACKGROUND: Double-blind, randomised, placebo-controlled and multicentre studies have proven an increase in visual acuity in one-third of the patients receiving Ranibizumab (0.5 mg) injections, who suffer from exsudative AMD. The purpose of this study was to evaluate the early effects of intravitreal Ranibizumab therapy in patients with mainly occult neovascular AMD in clinical applications. PATIENTS AND METHODS: In a retrospective cohort study, 91 eyes with occult and classic neovascular AMD were treated with intravitreal injections of Ranibizumab (0.5 mg) at 30-day intervals. The treatment effects were evaluated according to best corrected visual acuity, optical coherence tomography (OCT) and intraocular pressure at baseline as well as 1, 3 and 6 months after the beginning of therapy. Furthermore, fluorescein angiography (FLA) was performed at baseline as well as 3 and 6 months after therapy. RESULTS: 74 % of the patients lost fewer than 15 letters on the EDTRS-scale 6 months after the beginning of therapy. Visual acuity improved by more than 15 letters in 11 % of the patients. Central retinal thickness, measured by OCT, decreased statistically significantly in each control compared to baseline (1 month: p = 0.045; 3 months: p = 0.001; 6 months: p = 0.006). Leakage and membranes, evaluated in FA, worsened in 31 % of the patients; in 67 % the findings were stable. No increase in intraocular pressure was detected. CONCLUSIONS: Intravitreal application of Ranibizumab was safe and well tolerated. In the clinical situation, visual acuity was stabilised in the short term. As opposed to phase-III studies, no improvement in visual acuity could be accomplished. Cental retinal thickness decreased and findings in fluorescein angiography were stable within a 6-month follow-up period. It is necessary to perform monthly controls and proceed with VA- and OCT-based injections in order to maintain the therapeutic effect. Futher clinical evaluations of Ranibizumab will be necessary to evaluate its long-term treatment effects.

[Epi-LASIK with a 1000 hertz excimer laser]. / EpiLASIK mit einem 1000 Hertz Excimer-Laser.

PURPOSE: The aim of this study was to evaluate the safety, stability and efficacy of Epi-LASIK with a 1000 hertz excimer laser system. METHODS: 40 eyes of 23 patients underwent an Epi-LASIK procedure using the Gebauer EpiLift and the WaveLight Concept System 1000. Preoperatively as well as 1 month, and 3 months postoperatively, a complete ophthalmic examination, including objective and subjective refraction (UCVA, BCVA) and topography, was performed. RESULTS: The mean preoperative spherical equivalent (SE) was -4.07 D (SD ± 1.89 D). 1 month after surgery, the spherical equivalent was + 0.01 D (SD ± 0.33 D), and 3 months after surgery -0.06 D (SD ± 0.28 D). 3 months after the Epi-LASIK procedure, 90 % of the patients were within ± 0.5 D of the intended correction, and 97.5 % were within ± 1.0 D of the intended correction. The astigmatism was reduced from -0.77 D (SD ± 0.68 D) to -0.24 D (SD ± 0.29 D) 3 months after surgery. 34 of the 40 eyes had a clear cornea 3 months after surgery, and 6 of the 40 eyes presented with haze grade 0.5. CONCLUSIONS: In our pilot series of 40 eyes, the use of the 1000 hertz excimer laser did not reveal any specific clinical side effects potentially associated with the use of a high repetition rate. These first results with Epi-LASIK and the WaveLight Concept System 1000 are very promising.

[Sutureless encircling band - clinical experience]. / Nahtlose Cerclage mit Skleratunnelfixation.

PURPOSE: In cases with multiple retinal breaks and in combination with vitrectomy in eyes with proliferative vitreoretinopathy (PVR) often an encircling band is used for retinal detachment surgery. Usually the encircling band is fixed with non-resorbable sutures. METHODS: A fixation method for an encircling band in retinal detachment surgery with one scleral tunnel in each of the 4 quadrants is reported. After 50 consecutive operations on 50 patients, we describe our experience and biomechanical calculations of this fixation technique. RESULTS: In comparison to conventional fixation technique we found the following advantages. No suture is necessary, this means that no additional foreign body can produce irritations. The scleral tunnel is safe and the preparation under the microscope can be performed rapidly and under good control. According to our biomechanical calculations, the same tension of the encircling band produces less myopic shift with this technique. Scleral tunnel fixation is very comfortable in combination with a vitrectomy. CONCLUSIONS: After a short learning curve, the operating time is as short as with conventional suture fixation of the encircling band. There is less perforating risk, less irritation and less patient discomfort postoperatively. A sutureless encircling band with scleral tunnel fixation is a very useful operative technique in clinical routine.

[Wavefront-guided and wavefront-optimised LASEK--comparison of clinical results]. / Wellenfrontgestützte und wellenfrontoptimierte LASEK--Vergleich der klinischen Ergebnisse.

PURPOSE: The aim of this study was to compare refractive outcomes and wavefront results in eyes undergoing wavefront-optimised and wavefront-guided LASEK. METHODS: In this contralateral eye study wavefront-guided LASEK and wavefront-optimised LASEK have been carried out on 30 eyes each. Preoperatively, 1 month, 3 months and 6 months after surgery a full ophthalmological examination was carried out. Preoperatively and 6 months postoperatively additional wavefront measurement have been carried out on all patients. RESULTS: The mean preoperative refraction in the wavefront-guided group was -4.41 D (SD 1.38 D) and in the wavefront-optimised group -4.62 D (SD 1.86 D). The postoperative refraction was very good in both groups (wavefront-guided -0.06 D, SD 0.18 D; wavefront-optimised -0.03 D, SD 0.21 D). In both groups RMS of higher orders were increased slightly (wavefront-guided from 0.26 to 0.31 microm, wavefront-optimised from 0.27 to 0.32 microm) and also spherical aberrations increased slightly (wavefront-guided from 0.18 to 0.23 microm, wavefront-optimised from 0.16 to 0.21 microm). CONCLUSIONS: The refractive results with the Concept System 500 in patients with preoperatively low amounts of higher order aberrations after wavefront-guided and wavefront-optimised LASEK are comparable. As good wavefront measurements need a lot of experience and take a lot of time, there is no advantage of wavefront-guided ablation in patients with low preoperative aberrations.

[Photodynamic therapy with verteporfin combined with intravitreal injection of ranibizumab for occult and classic CNV in AMD]. / Photodynamische Therapie mit Verteporfin kombiniert mit intravitrealer Injektion von Ranibizumab zur Behandlung okkulter und klassischer choroidaler Neovaskularisationen bei AMD.

PURPOSE: The aim of this study is to discuss the effect and outcome of a combined photodynamic therapy and intravitreal injection of ranibizumab (0.5 mg) in occult CNV with recent disease progression and in classic choroidal neovascularization (CNV) due to AMD. METHODS: In a pilot study in 28 patients (17 classic, 11 occult CNV) an intravitreal injection of ranibizumab was administered within 12 to 24 hours after standard PDT, followed by 2 injections of ranibizumab after 1 and 2 months. Before as well as 3 and 6 months after treatment visual acuity, OCT examinations (retinal thickness) and fluorescein angiography were performed. RESULTS: Mean visual acuity was significantly improved compared to baseline after 3 months (VA baseline 20/80, after 3 months 20/50, and 20/63 after 6 months). We found no choroidal hypoperfusion and no RPE rip. OCT and fluorescein angiography in patients with occult and classic choroidal neovascularisation after the combination therapy showed a reduced retinal thickness (baseline: 307 microm, after 1 month: 210 microm, after 3 months: 228 microm and after 6 months 281 microm) and a reduction of leakage compared to baseline. CONCLUSIONS: Photodynamic therapy combined with injection of intravitreal ranibizumab was well tolerated and is effective. We found a stabilisation of VA in 96% of patients. Our short-term results are very promising. Further studies are necessary to show the long-term effect of the PDT and anti-VEGF combination therapy.

[Cut quality of a new femtosecond laser system]. / Schnittqualität eines neuen Femtosekundenlasers.

OBJECTIVE: The aim of this study was to evaluate the cut quality and the cellular damage when using a new 200 kHz femtosecond laser. METHODS: 20 porcine eyes and 3 human eyes, not suitable for transplantation, were used for this study. The WaveLight UltraFlap femtosecond laser was used for flap creation. The surface of the cornea, the structure and ultrastructure of the corneal cells and stroma were evaluated thoroughly using light microscopy (HE-, PAS- and Picrosirius red staining), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). RESULTS: In all eyes, the flap could be lifted very easily and the flap appeared very smooth. Structural and ultrastructural evaluation with light and transmission electron microscopy on epithelium and endothelium showed no side effects of the laser application. The area around the flap cut was minimally affected and the keratocytes and collagen fibres showed minimal alteration due to laser treatment. Scanning electron microscopy revealed in all cases smooth surfaces and precise sidecuts. CONCLUSIONS: Precise corneal flaps can easily be created with this new femtosecond laser. At the same time, no structural and thermal side effects on corneal epithelium, stroma and endothelium appeared. Hence with this new femtosecond laser corneal flaps could be created easily without noteworthy side effects.

On and Off magnetic auditory evoked responses in early infancy: a possible marker of brain immaturity.

OBJECTIVE: To follow the development of the auditory evoked on- and off-responses in early infancy. METHODS: The subjects were healthy infants, studied at conceptional age (CA) 39-66 weeks. Serial auditory evoked responses (AERs) were recorded in 17 subjects in response to tones of frequency 1.5 kHz and duration 1.0 s in order to follow the development of the AERs. Two small substudies were performed to examine off-responses evoked by tones of varying duration. The first used 0.2, 0.3, 0.4, and 0.5s tones; the second used 0.5, 1.0, and 2.0 s tones. RESULTS: For the 1.0 s tones, the on- and off-responses consisted of three components: P250, P400, and N750 m. The on- and off-responses had similar amplitude, in contrast to adult AERs in which the on-responses are typically much larger. Prior to about CA 47 weeks, the on-responses were actually smaller on average than the off-responses, and in infants born prior to CA 38 weeks the AERs were dominated by the off-response. Off-responses were seen for tones as brief as 0.2 s; however, the P400m component was often absent in the off-responses for tone durations < or = 0.5 s. An interaction was observed in which the N750 m-On component was strongly suppressed when it overlapped the P250 m-Off. CONCLUSIONS: Off-responses are much more prominent in infant than in adult AERs, especially in pre-term infants and at early CAs. On- and off-responses also exhibit more complex behavior in infants than in adult; the individual components can interact and behave independently. SIGNIFICANCE: Measurement of auditory off-responses can improve the assessment of infant neurodevelopment, potentially providing a marker of brain immaturity.

MEG sleep pattern dependence of auditory evoked fields in young infants.

We recorded magnetic auditory evoked responses (AERs) to brief 1 kHz tones in infants ranging in age from 1.5-8.5 weeks. Long continuous MEG recordings were collected with a 37-channel sensor and were classified into one of four patterns: low-amplitude irregular, high-amplitude slow, mixed, and REM-like sleep. The AERs were characterized by a monophasic deflection with nominal latency 250 msec, followed by a broader peak with opposite polarity and approximate latency 600 msec. No strong dependences on MEG sleep pattern were observed. The latency of the 250 msec component decreased with age, but the 600 msec component showed variable latency. The signal topography of both components was compatible with a source in the auditory cortex. We conclude that sleep state does not appreciably confound recording of the AER in young infants.

Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes.

Hey genes (Hey1, Hey2 and HeyL) encode a new group of basic helix-loop-helix transcription factors that are related to the hairy/Enhancer of split genes. In the present study, we cloned and characterized the promoter region of the human and mouse Hey1 gene. The transcription initiation site was located 138 nucleotides upstream of the start codon. There is a minimal sequence element (nt -30 to -247) that is essential and important for basal transcription in three different cell types. Further upstream, a highly conserved sequence block (nt -324 to -646; approximately 90% human/mouse similarity) could be identified that contains several putative binding sites for transcription factors and likely represents an important regulatory region for this gene. Cotransfection experiments demonstrated that the mHey1 promoter activity is up-regulated by the activated form of all four mammalian Notch receptors via two functional RBP-Jkappa binding sites. The other members of the Hey gene family, Hey2 and HeyL, also possess RBP-Jkappa binding sites and they are similarly responsive to Notch signaling. Thus, our data clearly demonstrate that Hey genes form a new class of Notch signal transducers that should prove to be relevant in various developmental processes.

Nonlinear functional modeling of scalp recorded auditory evoked responses to maximum length sequences.

The purpose of this study was to model the adult human's scalp recorded evoked response to auditory pulses separated by varying inter pulse intervals (IPIs). The responses modeled probably reflect auditory nerve and brainstem generators. The subjects were 10 young adult humans with normal hearing. They were presented pseudo random sequences of pulses (maximum length sequences, MLSs) in order to characterize their system response. For the stimuli and the responses modeled accounting for temporal nonlinearities (interactions among the pulses) improved model performance only marginally. Nonlinear contributions to the models decreased with increasing interval between the input pulses. Increasing the memory of the model beyond 20 ms did not increase modeled performance dramatically. Model performance varied as a function of minimum IPI (MIPI) of the MLSs. At the shortest MIPI overall model performance deteriorated (due, in part, to a decrease in SNR), but nonlinear effects became relatively more important. At the longest MIPI performance also deteriorated, possibly due to the increasing influence of longer latency, more variable evoked potential components. Modeled performance generalized to responses recorded in the same recording session to the same and different MLSs. This study confirms the similarity between MLS linear kernels and conventionally averaged evoked responses--both are adapted responses reflecting the IPIs of the evoking stimuli.

Auditory evoked brain stem responses to trains of stimuli in human adults.

OBJECTIVE: This study describes the effect of train length, interstimulus interval, intertrain interval (ITI), and stimulus duration on the transition from the unadapted to the adapted wave V auditory evoked brain stem response (ABR). DESIGN: ABRs were recorded to stimuli presented at two different rates: a slow rate characterizing the unadapted response and a fast rate characterizing the adapted response. Trains of stimuli (a sequence of stimuli separated by intervals of silence) also were presented. Different stimulus parameters defining the trains were varied. RESULTS: Given a sufficiently long ITI, the latency prolongation to the first three or four stimuli in a train was rapid. It was similar for trains differing in number of stimuli. After the first three or four stimuli, there was a more gradual latency prolongation as a function of stimulus number. Shorter ITIs had the effect of prolonging the latencies to all the stimuli in the trains, reducing the rate of latency prolongation over the first few stimuli, and causing responses to trains of different length to differ (e.g., two click train responses were shorter latency than four click train responses). An unexpected result was the latency prolongation of wave Vs after the presentation of the stimulus trains. CONCLUSIONS: In response to a train of clicks, there seems to be a rapid increase in wave V latency to the first few clicks in the train followed by a more gradual latency prolongation to subsequent clicks in the train.

The effects of lead on otoacoustic emissions and auditory evoked potentials in monkeys.

Auditory functioning was assessed in two groups of adult rhesus monkeys (11 years of age). One (n = 11) received modest exposure to lead early in life and the other (n = 8) served as controls and did not receive any lead supplementation. Two lead-exposed monkeys had abnormal distortion product otoacoustic emissions (DPEs) and smaller amplitude or absent evoked potentials. These monkeys had abnormal distortion product otoacoustic emission (DPEs) and smaller amplitude or absent evoked potentials. These monkeys had the highest blood levels recorded in their respective groups. For the remaining lead-exposed monkeys there was little difference between their DPEs and the DPEs of the control monkeys with one exception. DPE amplitudes of the control monkeys increased more rapidly as a function of stimulus level than those of the lead-exposed monkeys at most frequencies. There was also a significant but modest effect of lead exposure on the auditory brain stem evoked responses (ABRs) of these lead-exposed monkeys. There was no apparent effect on the middle latency evoked responses (MLRs), although that result could be due to the relatively greater variability of the MLR.