Nerve Fiber Analyzer Research Articles

Nerve repair by means of vein filled with muscle grafts. II. Morphological analysis of regeneration.

The morphological features of regeneration in long-distance (3 cm) muscle-vein-combined grafts were experimentally investigated in the rat sciatic nerve by means of light and electron microscopy. In the early phases of regeneration (14 days after surgery), many regenerating nerve fibers were detected along the muscle-vein-combined graft. Six months after surgery, quantitative morphometrical analysis of myelinated nerve fibers showed that both the total number and density of myelinated nerve fibers were significantly greater in regenerated nerves than in control nerves. The contrary appeared true for the mean fiber size, with fiber size significantly smaller in regenerated nerves. Ultrastructural observations allowed the description of some peculiar aspects of the relationship between muscle fibers, nerve fibers, and Schwann cells in both early and late phases of regeneration.

The Human Recurrent Laryngeal Nerve during the Aging Process

After a morphometric analysis of nerve fibers of the human recurrent laryngeal nerve, which is connected with phonation, the authors discovered several changes occurring in the axon during the aging process. These changes are mainly the disappearance of large axons and a slenderization of all remaining axons. This is the first time that such observation has been made.

Unmyelinated nerve fibre analysis of the human lesser splanchnic nerve.

The aim of the present study is to analyse unmyelinated nerve fibres of the human lesser splanchnic nerve in relation to the ageing process. With the help of an image-analyser, we examined 30 human lesser splanchnic nerves. The analysis was conducted with the use of a new staining method that makes it possible to discriminate various structures of the nervous tissue. Our report provides for the first time information on the ageing process of the human lesser splanchnic nerve fibres. The results indicate that a decrease in transverse area and perimeter of unmyelinated axons is one of the important changes occurring in the human lesser splanchnic nerve during the ageing process.

Unmyelinated Nerve Fiber Analysis of the Human Oculomotor Nerve

Unmyelinated nerve fibers of the oculomotor nerve have occasionally been observed in experimental animals with the use of electron microscopes, but no details concerning normal oculomotor nerves in humans have been published. We measured and analyzed unmyelinated nerve fibers in the human oculomotor nerve with an image analyzer and a computer, using a new staining method, the Luxol fast blue-periodic acid-Schiff-hematoxylin (LPH) discriminative staining method which is the only one suitable for morphometric research on nervous tissues. We studied the numbers and transverse areas of unmyelinated fibers of the oculomotor nerve in 20 cadavers. The number of unmyelinated axons did not change with age, but the mean transverse area decreased with age. These fibers were distributed diffusely in the transverse area of the oculomotor nerve, not localized in any part of the nerve. These findings may be important for the analysis of clinical and neurological signs in relation to aging and ophthalmologic functions.

A uniform format for ocular imaging devices.

To develop a uniform file format of ocular imaging data, including, but not limited to, ultrasound biomicroscopy, optical coherence tomography, and nerve fiber analyzer, capable of being transmitted via Internet or intranet for collaborative research and telemedicine use. File filters were developed as dynamic link libraries (DLLs). These can read the original raw data format of each ocular imaging device. A data file format was also designed to describe these raw data uniformly in three different types of compression: noncompressed, run length compression, and differential pulse code modulation (DPCM). These three file formats were then tested in the following aspects: file size, speed of reading, and speed of writing. Run length compression failed to compress raw data, while DPCM compressed raw data successfully (< or =35.5%). The speed of reading and writing files was slowest in DPCM. However, the actual time of reading and writing was fast enough (<0.6 s) for daily work regardless of file compression methods. The format designed has robust potential to be the standard file format for transmission of any ocular imaging raw data.

Scanning laser polarimetry via intravitreal silicone oil.

To investigate whether scanning laser polarimetry, a promising new technique for early detection of glaucomatous nerve fiber loss, is a suitable method to measure retinal nerve fiber layer thickness in eyes with intravitreal silicone oil. Eleven eyes of 11 consecutive patients two days to 16 months after successful vitrectomy and intravitreal silicone oil injection and 12 eyes of 12 consecutive subjects, who never had any vitreoretinal surgery were examined using the GDx Nerve Fiber Analyzer. Three individual images were computed to a mean image using the software in each case. "Variance", a software-provided parameter, which represents the differences between the individual images used to calculate the mean image was higher in the "silicone oil" group (unpaired t test for different variances, p = 0.02). Good-quality mean images with a "Variance" value similar to that of the control eyes were obtained in seven of the 11 cases. Characteristic artifacts caused by intravitreal silicone oil were observed in five of the 11 cases. Successful scanning laser polarimetry is possible after vitrectomy and intravitreal silicone oil injection, and may help to monitor the retinal nerve fiber layer of these eyes in case of silicone oil induced glaucoma.

Effects of contact lenses on scanning laser polarimetry of the peripapillary retinal nerve fiber layer

PURPOSE: To determine the effects of contact lenses on scanning laser polarimetry of the peripapillary nerve fiber layer. METHODS: In a prospective study using the Nerve Fiber Analyzer (Laser Diagnostic Technologies, San Diego, California), retinal nerve fiber layer thickness in 22 subjects (51 eyes) was imaged with and without contact lenses (disposable and nondisposable daily wear soft and rigid gas permeable). Measurements of the circumference and of each quadrant were compared using paired Student t test. RESULTS: Nerve Fiber Analyzer measurements with and without contact lenses were not significantly different for any of the contact lens types tested ( P ≥ .11), using either hyperopic (to +4 diopters) or myopic (to −8.5 diopters) lenses. CONCLUSION: Contact lens wear and refractive power of the eye within the range tested do not significantly affect scanning laser polarimetry of the peripapillary nerve fiber layer.

Laser scanning topography and polarimetry with implantation of intraocular lenses before and after cataract surgery

In the last years, scanning laser measurements were established in glaucoma diagnostics. Techniques of special interest are scanning laser topometry (SLT) for exact measurements of the optic disc and its cup and scanning laser polarimetry (SLP) for precise assessment of the retinal nerve fiber layer thickness. As glaucoma patients often suffer from a cataract, too, and a trabeculectomy additionally favors the advance of lens opacities, in the follow up of glaucoma patients cataract surgery is often necessary. The influence of cataract surgery in phacotechnique with intraocular lens implantation (31 PMMA-IOLs, Pharmacia/Upjohn, model 811 B, and 25 HEMA/MMA-IOLs, Technomed, Memory Lens) on SLT and SLP was evaluated before and 3 to 4 weeks after cataract surgery in 56 eyes of otherwise healthy patients. Lens opacities were classified according to LOCS III. For SLT, we applied a TopSS, and for SLP a Nerve Fiber Analyzer II and a GDx (LDT, USA). Our results show that SLT and SLP are mostly performable at lens opacities with visual acuity reductions down to 0.16. In SLT, we usually found no big differences in the assessed parameters before and after cataract surgeries with IOL implantation. Standard deviations between three single measurements were mostly smaller postop. In SLP, nerve fiber layer patterns were very similar before and after cataract surgeries with IOL implantation whereas total nerve fiber layer thickness values postoperatively were slightly higher. Our results indicate that cataract surgeries with IOL-implantation have only mild influence on SLT and SLP. These findings seem to be of clinical interest especially in the follow up of glaucoma patients.

Retinal nerve fiber layer measurement by nerve fiber analyzer in normal subjects and patients with glaucoma

Objective To identify the pattern of retinal nerve fiber layer (RNFL) loss in glaucoma using the Nerve Fiber Analyzer (NFA). Design Case-control study. Participants A total of 80 normal and 75 age- and race-matched chronic open-angle glaucoma subjects were recruited. Intervention The RNFL thickness was assessed with a scanning laser polarimeter (Nerve Fiber Analyzer GDX, Laser Diagnostic Technologies Inc., San Diego, CA). Analysis of variance was used to compare the corresponding RNFL measurement indices of the different groups. Main outcome measures Superior/nasal (S/N) and inferior/nasal (I/N) ratios of NFA are sensitive parameters to differentiate between glaucoma and nonglaucoma subjects. Results Peripapillary RNFL measurements at the superior and inferior regions were significantly lower in the glaucoma group ( P < 0.001) but were similar in temporal and nasal regions ( P > 0.05). Using nasal value as reference, S/N and I/N ratios were significantly lower in the glaucoma groups ( P < 0.001) and also decreased with increasing severity of glaucoma. Conclusions In glaucoma, RNFL was more susceptible to loss in the superior and inferior regions than in the nasal and temporal regions. The S/N and I/N ratio parameters provided by the NFA appeared to give further discriminating ability in early glaucoma.

Estimation of the retinal nerve fibre layer thickness in the papillomacular area of long standing stage IV macular holes

AIMTo compare the thickness of the retinal nerve fibre layer (RNFL) in the papillomacular area of patients with long standing stage IV macular holes with age matched controls, using a...

Study of the optic papilla and nerve fiber layer in glaucoma

For diagnosis and follow-up of glaucoma an exact evaluation of the optic nerve disc and the nerve fiber layer is necessary. The slit-lamp evaluation of the optic nerve disc and nerve fiber layer is presented as well as the evaluation with the Nerve Fiber Analyzer and the Heidelberg Retina Tomograph. Signs of a glaucomatous optic disc include a difference of more than 0.2 in the vertical cup to disc (CD) ratio between the eyes, a vertical CD ratio exceeding more than 0.1 the horizontal, larger CD ratios in small optic discs, notching of the neuroretinal rim, an enlarged zone beta of parapapillary chorioretinal atrophy, and peripapillary hemorrhages. Atrophy of the nerve fiber layer may be localized or diffuse. Both types of atrophy may be present at the same time. Knowledge of all signs of the glaucomatous optic disc and forms of nerve fiber layer atrophy allows an earlier diagnosis of glaucoma and an earlier recognition of progression.

The effect of excimer laser photorefractive keratectomy for myopia on nerve fiber layer thickness measurements as determined by scanning laser polarimetry

Objective Scanning laser polarimetry measures the retardation of polarized laser light as it passes through the birefringent retinal nerve fiber layer (RNFL). Because retardation is directly proportional to the number of retinal nerve fibers, indirect measurements of the RNFL thickness are obtained. A fixed compensatory mechanism is used to correct for retardation attributed to birefringence in the cornea and anterior segment. Excimer laser photorefractive keratectomy (PRK) corrects myopia by ablating tissue from the cornea. This study was conducted to determine the effect of this ablation on RNFL measurements. Design Prospective comparative case series. Participants Eighteen patients. Methods Patients undergoing PRK had RNFL measurements performed with the GDx Nerve Fiber Analyzer (Laser Diagnostic Technologies, San Diego, CA), a scanning laser polarimeter, in both eyes before and 90 days after PRK in the first eye. Main outcome measures Fourteen different GDx parameters were analyzed for statistically significant differences preoperatively and 3 months postoperatively in the treated and untreated eye using Hotelling’s T-squared generalized means test. Results Eighteen patients underwent PRK in the nondominant eye first. Preoperative refractions averaged −3.8 ± 1.6 diopters (D), with an average correction of 3.4 ± 1.9 D, corresponding to 49.7 ± 20.5 microns of ablation. There were no statistically significant preoperative differences between the fellow eyes in refractive error ( P = 0.65). Postoperatively, there were no statistically significant changes in any GDx parameter in the treated eye compared with the untreated control eye ( P = 0.21). Conclusions Excimer laser PRK for moderate myopia has no significant effect on RNFL thickness measurements as determined by scanning laser polarimetry.

Morphometric nerve fiber analysis and aging process of the human vestibular nerve.

Myelinated and unmyelinated nerve fibers of the human vestibular nerve were analyzed with the use of a new staining method that makes it possible to discriminate various structures of the nervous tissue. An image-analyzing digitizer, a microscope with a drawing tube and a personal computer for storing data and performing statistical analyses were employed in this study. We measured the axonal numbers and transverse areas of myelinated vestibular nerve fibers in 20 cadavers, and of unmyelinated fibers in 14 cadavers. The average number of myelinated axons and unmyelinated axons were 20,318 and 2,782, and the average transverse area of their axons were 3.46 and 0.49 micron 2, respectively. The transverse areas of myelinated axons decreased with age, although the numbers of their axons did not change. However, in the case of unmyelinated axons, both the transverse areas and the numbers did not change.

Differentiating patients with glaucoma from glaucoma suspects and normal subjects by nerve fiber layer assessment with scanning laser polarimetry 1,2

Purpose A study was conducted to determine normative data for nerve fiber layer measurements as obtained by scanning laser polarimetry with the Laser Diagnostic Technologies Nerve Fiber Analyzer II, identify factors affecting the measurements, and identify parameters capable of differentiating normal subjects from patients with glaucoma and patients suspected of having glaucoma because of ocular hypertension or because of a large cup-to-disc ratio (GS-disc). Design A case series. Participants Four hundred normal subjects, 35 patients with ocular hypertension, 42 patients with glaucoma, and 17 glaucoma suspects based on optic disc appearance participated. Methods Nerve fiber layer thickness assessments were determined in normal subjects (with normal appearing optic nerves and normal visual fields). The results were compared to measurements from samples of age-matched patients with ocular hypertension (with normal visual fields), patients suspected of having glaucoma based on enlarged cup-to-disc ratios, and patients with open-angle glaucoma who had visual field loss. Results The majority of the parameters derived from the measurements showed no significant relationship to age, although some parameters tended to decrease with increasing age. Multiple parameters showed statistically significant differences between normal subjects and patients with glaucoma. In particular, the intraellipse sector variability, an indirect measure of the shape of the nerve fiber layer in an ellipse surrounding the nerve head, showed statistically significant differences between normal subjects and patients with glaucoma as well as between glaucoma suspects and normal subjects. Similar results were seen with the superior maxima, the average thickness assessment value of the 1500 thickest points in the superior bundle. Conclusions Assessments of nerve fiber layer thickness as determined by scanning laser polarimetry can differentiate patients with glaucoma from normal subjects and may identify otherwise undetected damage in glaucoma suspects.

THE NERVE FIBER ANALYZER

The Nerve Fiber Analyzer (NFA; Laser Diagnostic Technologies, San Diego, CA) is a scanning laser polarimeter that was developed to measure the thickness of the human retinal nerve fiber layer (NFL) in vivo. Because glaucoma is associated with thinning of the NFL, the instrument potentially could be used for the detection and follow-up of glaucoma. The NFA came onto the market in 1993, and has been upgraded several times since then. The first results were promising but not altogether satisfactory, partly because the reproducibility of measurements was poor and very operatordependent. The authors were able to improve the reproducibility of measurements of the first version of the in~trument.’~ A sensitivity and specificity for detecting glaucoma was established that was unrivalled by any other single technique.25 The first version of the instrument was followed by the NFA I1 and later by the NFA GDx (or GDx), which both represented large revisions in hardware and software. Some of these revisions have further improved the reproducibility of measurements. The GDx version contains a large normative database and a statistical software package that allow comparison of an individual’s data with those of age-matched normal subjects of the same ethnic origin. An individual’s data may be stored for future reference to

Retinal nerve fibre layer polarimetry: histological and clinical comparison

AIMSTo compare histological thickness of the retinal nerve fibre layer in the primate with retardation measurements obtained in vivo using the Mark II Nerve Fiber Analyzer (NFA, Laser Diagnostic Technologies,...

QUANTITATIVE METHODS FOR EVALUATING THE RETINAL NERVE FIBER LAYER IN GLAUCOMA

Primary open angle glaucoma is a leading cause of blindness in the United States. It is estimated that more than 2 million Americans have glaucoma and that 80,000 are legally blind from the disease. Currently, there is no uniform definition of glaucoma, particularly in the earliest stages of the disease. Glaucoma is diagnosed by identifying structural damage (characteristic optic nerve damage) or functional damage (characteristic visual field loss). Most glaucoma patients also have high intraocular pressure, a major risk factor for the disease. Defects in the retinal nerve fiber layer (RNFL) are an early sign of glaucoma. In some subjects, RNFL defects can be detected before changes in the optic nerve head 1 or visual field 22,29,32 are identified. Retinal ganglion cell atrophy cannot be visualized with clinical examinations, but can be detected indirectly as diffuse or focal RNFL defects. In diffuse loss, retinal vessels, which are embedded within the RNFL, may become clearer as retinal ganglion cell dropout increases focally with progressive glaucoma. In focal loss, a wedge-shaped defect widens with increasing distance from the disc margin. Delineation of early structural change in the peripapillary retinal nerve fibers might facilitate their diagnosis and improve the monitoring of progressive glaucomatous damage. Unfortunately, RNFL defects can be difficult to identify during clinical examination. Photographic documentation of the RNFL is often hard to obtain and is only routine at a few academic centers. In addition, photographic methods require full dilation and qualitative review at the patient's next clinic visit. Three new diagnostic instruments, the Heidelberg Retina Tomograph (Heidelberg Engineering, Heidelberg, Germany), the Nerve Fiber Analyzer II (Laser Diagnostics Technology, San Diego, CA), and the Optical Coherence Tomograph (OCT; Humphrey Instruments, San Leandro, CA) have the ability to provide real-time quantitative and objective assessments of the RNFL in vivo. Each of these instruments is based on different optical principles. The clinical use of an instrument depends on the reproducibility and accuracy of the results, and its ability to differentiate between normal and glaucoma eyes and to monitor disease progression. This article summarizes the current literature addressing each of these topics and compares RNFL measurements using these three instruments in normal, glaucoma, and glaucoma suspect eyes.

Measuring nerve fiber thickness with laser scanning polarimetry in aging

In glaucoma, visual field defects are a late sign of retinal nerve fiber layer damage. Scanning laser polarimetry directly quantifies nerve fiber layer thickness (NFLT) and may allow early detection of defects and progression during follow-up. The NFLT of 54 healthy eyes of 54 subjects (age range from 14 to 83 years) was measured with a scanning laser polarimeter (Nerve Fiber Analyzer II). Measurements were performed along an ellipse 1.75 disc diameters away from the disc margin. For each subject an average image was calculated from three measurements. The ellipse was divided into four sectors by the internal software. All measurements were performed by the same examiner. All examined eyes had a normal ophthalmological examination, normal eye pressure and a normal computerized perimetry. The mean NFLT was thicker in the superior (91.3 microns +/- 16.7 microns) and inferior sector (90.8 microns +/- 15.6 microns) as compared to the temporal (53.7 microns +/- 15.4 microns) and nasal sector (60.0 microns +/- 14.8 microns). There was an inverse linear correlation between age and NFLT (Pearson's correlation-coefficient r = -0.30, p < 0.025). On the average, the mean NFLT decreased by 2.5 microns for each decade of age. The interindividual variation of the NFLT (mean standard deviation (s) = 16.1 microns) was, even after correction for age, much larger than the intraindividual variation (s = 6.6 microns). In normal subjects the NFLT decreases with age. The interindividual NFLT variation is, even after correction for age, much larger than the intraindividual. Therefore, scanning laser polarymetry might be especially useful for follow-up of NFLT.

Peripapillary Nerve Fiber Layer Thickness Measurement Reproducibility Using Scanning Laser Polarimetry

The authors assess the reproducibility of retinal nerve fiber layer (RNFL) thickness measurements using scanning laser polarimetry. The right eyes of five healthy individuals were scanned by two trained operators (S.T.H., H.I.) using the Nerve Fiber Analyzer II (Laser Diagnostic Technologies, Inc., San Diego, CA, U.S.A.). Each participant was scanned six consecutive times per session for five sessions carried out over separate days within a two-week period. Intra- and interoperator measurement reproducibility was assessed. Intraoperator reproducibility was high. Mean coefficients of variation for total RNFL thickness measurements were 4.48 +/- 1.76% and 4.92 +/- 2.32% for operators 1 and 2, respectively. Interoperator reproducibility was high (p = 0.20-0.93) if a single ellipse was applied to the images of both examiners. However, measurement reproducibility worsened if each operator created his own measurement ellipse (p < or = 0.05 for 3 out of 5 participants). Interoperator error in image analysis can be minimized by using a single ellipse for the baseline and all subsequent scans even if subsequent scans are acquired by different operators.

Unmyelinated nerve fiber analysis of the human abducent nerve.

Unmyelinated nerve fibers of the abducent nerve have occasionally been observed with electron microscopes, but, to our knowledge, they have never been evaluated from the morphometric point of view. We analyzed the aging process of the unmyelinated nerve fibers in the human abducent nerve with the help of a new staining method suitable for morphometric research on the nervous system. We studied numbers and transverse areas of unmyelinated fibers of the abducent nerve in 10 cadavers. Our findings were that (1) these fibers were distributed diffusely, (2) their number decreased with age, and (3) the mean transverse area did not change with age. Most of the unmyelinated axons were thinner than the myelinated axons. These results may be important for analysis of clinical signs in relation to aging and ophthalmologic functions.