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Multimodal macula mapping: a new approach to study diseases of the macula.

Multimodal macula mapping is presented as a combination of a variety of diagnostic tools and techniques to examine the macular region in order to obtain information on its structure and function in a clinical environment. Foundations of macular mapping are reviewed and discussed. New methodologies for multimodal macula mapping based on a combination of scanning laser angiography, retinal leakage analysis, retinal thickness analysis, and visual field testing are presented, demonstrating the potential of macula mapping. Other available detection devices are briefly reviewed considering their potential to be included and utilized in future developments of multimodal macula mapping. Multimodal macula mapping appears to offer unique perspectives and insights that are expected to contribute to improved diagnosis and better understanding of macular diseases.

Diagnostic Techniques, Ophthalmological↗

Ultrasonic absorption in polymer gel dosimeters.

Ultrasonic absorption in polymer gel dosimeters was investigated. An ultrasonic interferometer was used to study the frequency (f) dependence of the absorption coefficient (alpha) in a polyacrylamide gel dosimeter (PAG) in the frequency range 5-20 MHz. The frequency dependence of ultrasonic absorption deviated from that of an ideal viscous fluid. The presence of relaxation mechanisms was evidenced by the frequency dependence of alpha/f(2) and the dispersion in ultrasonic velocity. It was concluded that absorption in polymer gel dosimeters is due to a number of relaxation processes which may include polymer-solvent interactions as well as relaxation due to motion of polymer side groups. The dependence of ultrasonic absorption on absorbed dose and formulation was also investigated in polymer gel dosimeters as a function of pH and chemical composition. Changes in dosimeter pH and chemical composition resulted in a variation in ultrasonic dose response curves. The observed dependence on pH was considered to be due to pH induced modifications in the radiation yield while changes in chemical composition resulted in differences in polymerisation kinetics.

Acrylic Resins↗

Computer generated optical holographic fringe patterns for the analysis of vibrating structures.

Optical holographic interference fringe patterns on rods and bars vibrating in ultrasonic resonance (standing waves) are predicted by computer simulations. The simulations are based on a combination of finite element calculations with calculations based on the theory of holographic interference fringe generation. The hypothetical fringe patterns are then compared to holographic fringe images obtained by the experiment (time average holograms). The holographic arrangement and the mechanical part of the ultrasonic system (transducer, horn and specimen) were fixed on a commercial rigid optical table supported on air bags to isolate it from ground vibrations. Thus it is shown that the scope of the study can be reached with a minimum of experimental effort, i.e., with basic laser optical equipment. It is shown that provided the system operates in the desired mode, good agreement between the theoretical and the real image is given. Finally examples of the possible influence of defects or of parasitic modes of vibration on the appearance of the fringe patterns are given.

Computer Simulation↗

The shape of the aging human lens: curvature, equivalent refractive index and the lens paradox.

Scheimpflug slit images of the crystalline lens are distorted due to the refracting properties of the cornea and because they are obliquely viewed. We measured the aspheric curvature of the lens of 102 subjects ranging in age between 16 and 65 years and applied correction for these distortions. The procedure was validated by measuring an artificial eye and pseudophakic patients with intraocular lenses of known dimensions. Compared to previous studies using Scheimpflug photography, the decrease of the radius of the anterior lens surface with age was smaller, and the absolute value for the radius of the anterior and posterior lens surface was significantly smaller. A slight decrease of the posterior lens radius with age could be demonstrated. Generally, front and back surfaces were hyperbolic. Axial length was measured of 42 subjects enabling calculation of the equivalent refractive index of the lens, which showed a small, but highly significant decrease with age. These new findings explain the lens paradox and may serve as a basis for modelling the refractive properties of the lens.

Adolescent↗

In vivo pachymetry in normal eyes of rats, mice and rabbits with the optical low coherence reflectometer.

The aim of this study was to determine the central corneal thickness (CCT) in living rats, mice and rabbits using a non-contact, high-speed optical low coherence reflectometer (OLCR) mounted on a regular slit lamp. Both eyes of eight male Wistar rats, eight male balb-c mice and eight male Japanese rabbits were measured. Each eye was measured twice (one measurement consists of 20 scans), the average calculated. Additionally, CCT was measured in rabbits using an ultrasound pachymeter. The mean CCT was: RATS: 159.08 microm (SD+/-14.99 microm), MICE: 106.0 microm (SD+/-3.45 microm) and RABBITS: 356.11 microm (SD+/-14.34 microm). With the use of OLCR we were able to accurately measure the CCT of rats, mice and rabbits in vivo. This technique may prove useful in further refractive, pharmacological and glaucoma studies.

Animals↗

Quantitative cytochemistry of glycogen in blood cells. Methods and clinical application.

Quantitative glycogen determinations can be made in single blood and bone marrow cells, using microspectrophotometry or microfluorometry after staining with variants of the periodic acid--Schiff (PAS) reaction. These PAS variant reactions generally do not indicate the presence of non-glycogen PAS-positive substances, known to be prevalent in various hematopoietic cells, possibly due to masking of reactive groups. The specificity of the reaction in blood cells was ascertained by alpha-amylase digestion, which removed more than 95% of the PAS-positive material. Calibration of the PAS reaction was undertaken with a microdroplet model of pure leukocyte glycogen. The glycogen amounts in the droplets were determined by microinterferometry, the droplets were stained with a variant PAS reaction, and the total extinction of the reaction product in the stained droplets was determined by microspectrophotometry. The extinction coefficient (k) was obtained from the equation k equals Etot divided by M where (Etot) is the total extinction as determined by microspectrophotometry and (M) the dry glycogen amount as determined by microinterferometry. The microinterferometric dry mass determinations were calibrated by X-ray absorption in order to obtain the absolute amounts of glycogen. For practical purposes a reference system was made of normal neutrophil leukocytes. The glycogen content in the reference neutrophils was first determined with the micromodel. These neutrophils, now with a known glycogen amount, were stained with the PAS reagents and measured microspectrophotometrically in parallel with cells containing an unknown glycogen amount. Alternatively, the staining was made with a fluorescent PAS reaction, and the glycogen content determined by microfluorometry. Both methods appeared suitable for determining the glycogen content of blood cells from patients with various diseases, though the microfluorometric method was preferable for measurements of small amounts of inhomogeneously distributed glycogen. The mean glycogen content of normal neutrophil leukocytes was found to be 13.6 times 10(-12) g. The content was increased in infectious diseases such as pneumonia and tonisillitis, as well as in polycythemia vera and myelofibrosis, while low amounts were found in untreated chronic myelocytic leukemia. In chronic myelocytic leukemia in remission, the glycogen content of mature neutrophils had completely normalized. Erythroblasts normally do not contain detectable amounts of glycogen. However, in certain diseases such as beta-thalassemia and Di Guglielomo's syndrome, appreciable amounts of glycogen accumulate in the erythropoietic precursor cells. In beta-thalassemia this was associated with an arrest in the proliferation of early polychromatic erythroblasts, which accumulate glycogen in the G1 phase of the cell cycle. In all these diseases quantitative glycogen determinations in the blood cells have diagnostic importance.

Autoradiography↗

FTIR/ATR for protein adsorption to biomaterial surfaces.

It is now well accepted that the initial rapid adsorption of blood proteins to biomaterial surfaces is important in the long-term performance of the implant. Cells that interact with the implant will be reacting to a layer (single or multiple) of adsorbed protein. The parameters of importance in a study of protein adsorption to surfaces of biomaterial interest include total amounts of different adsorbed proteins and the conformation and orientation of these adsorbed proteins. Researchers have developed a number of techniques with which we can now address all these questions. In this paper, we have discussed how Fourier transform infrared (FTIR) attenuated total internal reflection (ATR) techniques can be used for the study of biomaterial surfaces and events at biomaterial surfaces such as protein adsorption. FTIR spectroscopy offers higher signal-to-noise and speeds than spectrometers that use gratings and hence offers the capability of observing the critical early events when proteins interact with surfaces. Perhaps the biggest advantage of the FTIR technique over dispersive spectrometers is wavelength precision. This allows the subtraction of water, a strong infrared absorber, from the spectra of proteins in aqueous solutions. This review starts with an introduction of how ATR can be used to provide information about proteins on surfaces. Equations to calculate the amount of proteins adsorbed to surfaces from analysis of ATR spectra are presented. A discussion of the kinds of surfaces that can be analyzed by FTIR/ATR and difficulties with the subtraction of H2O is given. The rest of the review deals with how information of interest to biomaterials researchers such as kinetics of protein adsorption, changes in protein secondary structure and orientation upon adsorption to surfaces can be obtained by FTIR/ATR.

Adsorption↗

The laser interferometer in predicting efficacy of secondary posterior capsulotomy.

Twenty eyes with posterior chamber intraocular lens implants that required secondary capsulotomies were evaluated with the laser interferometer. The interferometric measured preoperative retinal acuity is a good indication as to what the postoperative Snellen visual acuity can be after capsulotomy. Preoperative retinal visual acuity testing is also valuable in helping to decide when a capsulotomy is indicated.

Aged↗

Predicting acuities in capsulotomy patients: interferometers and potential acuity meter.

Using the Lotmar moiré fringe interferometer and the potential acuity meter, I predicted the postoperative Snellen visual acuities in 30 implanted eyes that required secondary capsulotomies. The Lotmar interferometer was within one line of the postoperative visual acuity in 29 eyes (96.6%); the potential acuity meter prediction was within one line in 10 eyes (33.3%). An earlier study defined seven clinical conditions that produced false positive results with the laser interferometer. The same results occurred with the Lotmar interferometer. When the potential acuity meter was used, six of the seven conditions produced false positive results.

False Positive Reactions↗

The Haag-Streit Lotmar Visometer for determining macular potential prior to cataract surgery.

The Haag-Streit Lotmar Visometer was evaluated to determine its accuracy in predicting macular potential prior to cataract removal in 101 cases. Overall, the instrument was reasonably reliable in 73% of cases. The results were analyzed from several standpoints to determine what data obtained during routine preoperative examination might help predict the reliability of the instrument in a given case.

Cataract Extraction↗

A comparison of optical coherence tomography and retinal nerve fiber layer photography for detection of nerve fiber layer damage in glaucoma.

PURPOSE: To compare optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements with established methods for assessment of glaucomatous damage using RNFL photography and visual field testing. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-eight eyes of 58 healthy volunteer ocular hypertensive patients, glaucoma suspect patients, and glaucoma patients were included. METHODS: Optical coherence tomography 3.4-mm diameter circular scans were obtained within 3 months of RNFL photography and standard achromatic visual field testing. Three independent observers graded RNFL photographs using two standardized protocols. For each method, superior and inferior arcuate bundles were scored separately, and interobserver and intraobserver variation was measured. Standard achromatic visual field mean deviation in the superior and inferior hemifields was compared with RNFL damage as assessed by photography and OCT RNFL thickness measurements. MAIN OUTCOME MEASURES: Visual field mean deviation and severity of glaucomatous RNFL damage as assessed by photography. RESULTS: Optical coherence tomography RNFL thickness decreased with increasing RNFL damage as assessed by photography using both methods of photographic assessment. Standard achromatic perimetry mean deviation was significantly associated with OCT RNFL thickness (R(2) = 35%-43%) and RNFL photography severity score (R(2) = 18%-29%). CONCLUSIONS: These results suggest that the OCT shows promise for providing quantitative measures of RNFL thickness for diagnosing and monitoring glaucoma.

Adult↗

Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography.

OBJECTIVE: To evaluate the reproducibility of optical coherence tomograph (OCT) retinal nerve fiber layer (RNFL) measurements in normal and glaucomatous eyes by means of the commercially available OCT 2000 instrument (Humphrey Systems, Dublin, CA). DESIGN: Prospective instrument validation study. PARTICIPANTS: One eye each from 10 normal subjects and 10 glaucoma patients. METHODS: Twenty subjects underwent a total of eight scanning sessions during two independent visits. In each session, five circular scans centered on the optic nerve head were performed. The first two sessions were performed by two experienced technicians. Followed by a 30-minute break, a third and a fourth session was completed by the same technicians. This sequence was duplicated on a second visit. Intrasession, intersession, intervisit, and interoperator reproducibility of quadrant and global RNFL measurements were calculated by use of a components of variance model. MAIN OUTCOME MEASURES: RNFL thickness. RESULTS: The coefficient of variation for the mean RNFL thickness was significantly smaller (P = 0.02) in normal eyes (6.9%) than in glaucoma eyes (11.8%). The estimated root mean squared error based on the statistical model using three scans per patient was 5.8 and 8.0 micrometer for normal and glaucoma eyes, respectively. A components of variance model showed most of the variance (79%) to be due to differences between patients. Only a modest contribution to variability was found for session (1%), visit (5%), and operator (2%). CONCLUSION: With the commercially available OCT, our results indicate that the RNFL measurements are reproducible for both normal and glaucomatous eyes.

Adult↗

Foveal pseudocyst as the first step in macular hole formation: a prospective study by optical coherence tomography.

OBJECTIVE: To establish the natural history of a series of impending macular holes presenting as foveal pseudocysts using optical coherence tomography (OCT). DESIGN: In a prospective observational case series, patients exhibiting a foveal pseudocyst on biomicroscopy were examined with OCT and were followed up for 3 to 26 months (mean, 9.4 months) PARTICIPANTS: Twenty-two eyes of 20 consecutive patients examined for a macular hole in the fellow eye or reporting visual symptoms in only one eye, in whom a foveal pseudocyst was diagnosed on OCT. METHODS: In all cases, fundus biomicroscopy and OCT findings were compared. MAIN OUTCOME MEASURES: Biomicroscopic fundoscopy, OCT scans, and visual acuity. RESULTS: Eight foveal pseudocysts occurred in the fellow eye of an eye with a macular hole, and 14 were diagnosed in patients with unilateral visual symptoms. In four of the 22 eyes, the macula was considered normal on biomicroscopy. In the 18 others, biomicroscopy detected a foveal pseudocyst, radial striae, a yellow spot or ring, or a combination of these findings. No posterior vitreous detachment was seen on biomicroscopy in any of the eyes. On OCT, the cystoid space occupied the inner part of the foveal tissue in the stage 1A impending hole; a stage 1B impending hole corresponded to a cystoid space that extended posteriorly, disrupting the outer retinal layer. During the follow-up period, three pseudocysts evolved into full-thickness macular holes, four turned into lamellar holes, seven resolved completely after detachment of the posterior hyaloid, and eight remained unchanged for a long time. CONCLUSIONS: Foveal pseudocysts are a specific entity occurring either as a primary ocular involvement or in the fellow eye of an eye with a macular hole. Foveal pseudocysts are the first step of full thickness macular hole formation, but they also may evolve into a lamellar hole, may persist unchanged for months, or may resolve completely. Foveal pseudocyst formation may be the result of the incomplete separation of the vitreous cortex at the foveal center and the particular structure of the foveal Müller cells.

Aged↗

Correlation between optical coherence tomography, pattern electroretinogram, and visual evoked potentials in open-angle glaucoma patients.

OBJECTIVE: [corrected] To correlate the nerve fiber layer (NFL) thickness and the visual function evaluated by electrophysiologic retinal and cortical responses assessed in open-angle glaucoma (OAG) eyes. DESIGN: Prospective case-control study. PARTICIPANTS: Thirty glaucoma patients (mean age, 47.1 +/- 7.15 years; refractive error range, +/- 2 spherical equivalent) with a mean deviation of computerized static perimetry (24/2 Humphrey, Dublin, CA) from -5 to -28 dB and intraocular pressure less than 21 mmHg on pharmacologic treatment and 14 age-matched control participants. METHODS: Nerve fiber layer thickness was measured by optical coherence tomography. Retinal and visual pathway function was assessed by simultaneously recording pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) using high-contrast (80%) checkerboard stimuli (the single check edges subtend 15 minutes of the visual arc) reversed at the rate of two reversals per second. Linear regression analyses were adopted to establish the correlation between NFL thickness and PERG and VEP parameters. MAIN OUTCOME MEASURES: Nerve fiber layer thickness measurements in each quadrant (superior, inferior, nasal, and temporal) were taken and then averaged (12 values averaged) and identified as NFL overall, whereas the data obtained in the temporal quadrant only (three values averaged) were identified as NFL temporal. PERG P50 implicit time and P50-N95 amplitude and VEP P100 implicit time and N75-P100 amplitude were also measured. RESULTS: In OAG eyes, we found a significant (P < 0.01) reduction in NFL thickness in both NFL overall and NFL temporal evaluations with respect to the values observed in control eyes. PERG and VEP parameters showed a significant (P < 0.01) delay in implicit time and a reduction in peak-to-peak amplitude. In OAG eyes, the NFL overall and NFL temporal values were significantly correlated (P < 0.01) with the PERG P50 implicit time and P50-95 peak-to-peak amplitude. No correlations (P > 0.01) between NFL values and VEP parameters were found. CONCLUSIONS: There is a correlation between PERG changes and NFL thickness, but there is no correlation between VEP changes and NFL thickness in patients affected by OAG.

Adult↗

Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study.

PURPOSE: To investigate the use of intravitreal injection of triamcinolone acetonide (TA) for the treatment of refractory uveitic cystoid macular edema (CME). DESIGN: Prospective, nonrandomized, self-controlled comparative trial. PARTICIPANTS: Six patients with chronic CME resistant to treatment with systemic steroids, orbital floor steroids, and cyclosporine A. Three patients were followed for more than 1 year, and the other three for between 3 and 9 months. INTERVENTION: Injection of 2 mg of TA into the vitreous cavity. TESTING: Optical coherence tomography scanning of the fovea before and after injection and logarithmic minimal angle of resolution visual acuity. MAIN OUTCOME MEASURES: Visual acuity, retinal thickness, cystoid space height, and intraocular pressure. RESULTS: There was complete anatomic resolution of CME in five of the six cases within 1 week after injection. Cystoid spaces began to return between 6 weeks and 3 months after injection. Two patients with longer term follow-up responded to further orbital floor steroid injection and had no CME 1 year later. One patient had raised intraocular pressure develop, requiring a trabeculectomy. Mean improvement in visual acuity after 12 months was 0.27 (range, 0.14-0.42). CONCLUSIONS: Complete anatomic and, to some extent, functional recovery can be induced by intravitreal TA despite long-term refractory inflammatory CME. Optical coherence tomography aids in the management of these cases.

Adult↗

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