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Biomedical subjects

D van Norren

Publications and source records attributed to D van Norren.

At least 55 records · Page 3Linked to original sources

Imaging retinal densitometry with a confocal Scanning Laser Ophthalmoscope.

We describe a novel use of the Scanning Laser Ophthalmoscope (SLO), viz. as an imaging retinal densitometer. In our SLO a helium-neon or an argon laser beam is moved in a raster pattern over the retina; the reflected light is descanned (confocal SLO) and collected by a photomultiplier. Images of the fundus subtending 22 by 18 deg are displayed on a TV monitor. Single frames taken with 514 nm light were stored in a computer in arrays of 256 by 256 pixels and density differences between dark adapted and bleached images were calculated. With a full bleach density differences of about 0.35 were found in the center of the fovea; at retinal eccentricities of 15-20 deg we found 0.15. After selective bleaching with 633 nm light substantial density differences were only seen in the foveal area. We conclude that the confocal SLO is a very suitable instrument for imaging fundus reflectometry.

Densitometry↗

Retinal damage in macaque after white light exposures lasting ten minutes to twelve hours.

We induced photochemical damage in small parts of the retinas of anesthetized macaques after light exposures of varying intensity, lasting between 10 min and 12 hr. Damage was assessed both with funduscopy and densitometry at several periods after exposure. Damage was most extensive 2 days post-exposure, with similar thresholds for both methods. Reciprocity between exposure time and irradiance was found for all exposures at a threshold irradiant dose of 230 J/cm2. This is in good agreement with part of the literature data on monkeys, yet contradicts another report (Sykes et al) in which a much lower threshold dose was found. The latter data probably concern a different class of damage. It remains unclear what critical factors distinguish the two classes. Observations more than 70 days post-exposure show a divergence between funduscopic and densitometric thresholds. Although the appearance of funduscopic lesions had changed, the threshold dose remained 230 J/cm2. Densitometry showed full recovery of the amount of visual pigment for doses below 600 J/cm2.

Animals↗

Retinal densitometry in acute posterior multifocal placoid pigment epitheliopathy.

Cone photopigment kinetics were investigated by retinal densitometry in six patients with acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Our goal was to document the course of cone impairment during a period of at least 12 months following the onset of the disease process. During the active stage, we found that the amount of pigment measurable by densitometry (the density difference) was reduced and that the time constant of pigment regeneration was unmeasurable. Following resolution of the fundus lesions, the densitometric parameters gradually improved in eight of ten eyes. In patients who maintained foveal fixation (five eyes), the density difference and the time constant of pigment regeneration improved simultaneously, though with individual differences in time course. Photopigment kinetics returned to normal in all these patients but the density difference remained lower than normal in four of the five eyes. In patients with parafoveal fixation (five eyes), photopigment kinetics were slow, possibly reflecting mixed cone and rod contributions. With time, the density difference improved to a level comparable to that measured in normal observers at a similar retinal location, but the photopigment regeneration time constant remained abnormal or unmeasurable. Recovery was variable, with one eye changing from parafoveal to foveal fixation, and no improvement noted in two eyes with extreme parafoveal fixation. Our findings demonstrate a large interpatient variation associated with APMPPE.

Color Perception↗

Kinetics of human cone photopigments explained with a Rushton-Henry model.

Densitrometric measurements of the regeneration of cone visual photopigments have shown effects that cannot be explained by the existing quantitative models. Regeneration from a fully bleached state seems to depend on how this state has been reached and the shape of the regeneration curve cannot be produced by a first order reaction. Rushton and Henry (1968) proposed a store of 11-cis-retinal to explain rapid regeneration after a short bleach. We elaborated this idea into a quantitative model. Regeneration after three different bleach histories and steady state behaviour of the pigments was measured using the Utrecht densitometer. The Rushton-Henry model gives a good fit to the data and is clearly superior to the classical Rushton model in describing densitometric measurements.

Animals↗

Contribution of electroretinography to diagnosis of color vision deficiencies.

The role that electroretinography (ERG) has played in the past and might play in the future in the study of color vision deficiencies is discussed in this paper. First, an example is given of how Copenhaver and Gunkel concluded in 1958 the absence of the green cone system in deuteranopia before Rushton, with the more direct method of densitometry, reached the same conclusion. Padmos and van Norren showed in 1971 that chromatic adaptation did not change a dichromat's spectral sensitivity curve, which fits the model of a loss system. A comparison between dichromats' spectral sensitivity curves based on the rapid off-response and recent data on single monkey receptors showed a slight but systematic discrepancy, indicative of a rod contribution in the off-response method. Carriers of color vision deficiencies might be more readily detected with an ERG than with a psychophysical method. The early receptor potential (ERP) seems a less suitable means to study color vision deficiencies. The blue cones form an interesting subject of study since they seem to be the most vulnerable cone type. With an ERG method a localization of acquired tritan deficiencies is possible. A recent finding is that blue cones are substantially more sensitive to light damage than either rods, or red or green cones.

Color Vision Defects↗

Density of foveal cone pigments at older age.

We investigated foveal cone photopigment kinetics by retinal densitometry in 34 eyes of 29 healthy subjects with clear optical media and good visual acuity, ranging in age from 39 to 79 years. Our aim was to assess possible senile disturbances of foveal cones. To assess the effects of ocular straylight, we measured not only in subjects with a clear crystalline lens, but also in pseudophakia and aphakia. In a limited number of subjects color vision was assessed with a Nagel anomaloscope; no systematic changes with age were found. A significant decrease in two-way density and in time constant of regeneration was found to occur only after age 60, with large individual variations. There was no indication that results for subjects with their natural crystalline lens, in aphakia, or in pseudophakia were different. We argue that a reduction in the number of cones with age, rather than an increase in ocular stray light is the most likely explanation of our findings.

Adult↗

Foveal densitometry as a diagnostic technique in Stargardt's disease.

Foveal densitometry was performed in eight patients with Stargardt's disease. Their visual acuities were between 20/200 and 20/16. All eight had low two-way densities, ranging from 0.07 to less than or equal to 0.01 (mean value for a control group, 0.32 +/- 0.03). Two patients had poor visual acuities combined with ophthalmoscopically normal maculas. Because two-way densities were very low in these patients, ranging between 0.04 and less than or equal to 0.01, foveal densitometry may be a useful diagnostic technique in the diagnosis of Stargardt's disease. Foveal densitometry was also performed in two patients with fundus flavimaculatus and good visual acuities for the sake of comparison. Two-way densities were between 0.09 and 0.24. One patient with cone dystrophy and poor visual acuity had low two-way densities (0.02 bilaterally). Three patients with vitelliform dystrophy and vitelliform cysts on ophthalmoscopy had two-way densities between 0.07 and 0.14 and increased half-times of regeneration (between 90 and 126 seconds). One patient with a vitelliform cyst in one eye showed only fine pigmentations in the other eye, which had a normal two-way density (0.32).

Adolescent↗

Minimum procedures for visual electrodiagnostic testing.

A set of procedures for the electroretinogram, electrooculogram, and pattern and luminance visual evoked cortical potentials was defined by representatives from all Dutch University Eye Clinics in order to promote standardization of procedures for routine diagnostic testing. The procedures have been selected to obtain an answer to most electrodiagnostic questions of frequent occurrence with a minimum of equipment and examination time. An individual examiner may add other procedures to the proposed program to extend and diagnostic possibilities.

Electrodiagnosis↗

Origin of the fast oscillation in the electroretinogram of the macaque.

To investigate the origin of the fast oscillation, a phenomenon in the electroretinogram evoked with stimulus frequencies of about 8 mHz (a period time of about 2 min), we recorded responses from retina and pigment epithelium in the macaque. Micropipettes were placed in the subretinal space and in the vitreous close to the retina; the reference electrode was in the orbit behind the eye. Thus, simultaneous recordings were obtained of the trans-epithelial, the trans-retinal and the trans-tissue (vitreal) potential. At 10 mHz the trans-retinal and the trans-epithelial responses are of about equal magnitude but of opposite phase, resulting in a small and rather variable vitreal potential. The origin of the fast oscillation evoked with repetitive stimuli lies in subtle differences between retinal and pigment epithelial potentials, in which a pigment epithelial event plays an important role. For single stimuli lasting 60 s again the trans-epithelial and trans-retinal responses were of equal magnitude and opposite polarity. The epithelial responses were found to return more quickly towards the baseline than the retinal responses. In vitreal recordings this causes a trough between the c-wave and the light peak which is referred to as the "trough" fast oscillation. Most of the "trough" fast oscillation is caused by a pigment epithelial event. In view of the complexity of the fast oscillation evoked with repetitive stimuli it might be difficult to relate pathology to specific neuro-epithelial structures.

Animals↗

Intensity and polarization of light scattered at small angles from the human fovea.

We have investigated the equivalent reflectance and the degree of preservation of polarization of light scattered at the human fundus in vivo. Measurements are performed at various angles of incidence and reflectance with both a bleached and unbleached state of the visual pigment. In the light that is scattered from the fovea two components were distinguished. First, a wide angle scattered component whose behavior in terms of equivalent reflectance and degree of polarization is independent of the angle of incidence and reflectance. Also, its reflectance is only moderately affected by the density of the visual pigment. Second, a directional component that is most prominent in a bleached state of the visual pigment and with a central position of the entrance and exit light path. The degree of preservation of polarization is about 90% at short wavelengths and decreases to about 40% for red light. Polarization is almost invariant for the angle of incidence and reflectance and the density of the visual pigment. To explain the results a model is proposed in which the scattering of both components is assumed to take place at the same layer. A consequence of this model is that a significant amount of light leaks between the receptor outer segments.

Fixation, Ocular↗

Origin of the electroretinogram in the intact macaque eye--I. Principal component analysis.

Responses to 400 msec flashes of white light were recorded at various depths in the retina of the intact macaque eye. A statistical technique, principal component analysis (PCA), was used to isolate independent components from the LERG, using the changing contribution of a cell's response to the LERG with retinal depth. Two approaches were evaluated: first, PCA was performed on the complete LERG waveforms and, second, on small sections of the LERG. The first method yielded a component strongly resembling the receptor response, apart from some inconsistencies in the proximal layers, and a component in which the b-wave was the most prominent feature, but which still contained some other responses. Hence, the components were not suitable to describe the LERG in terms of responses of specific cell types. The second method uses PCA to determine whether or not the potential change within a small time window is accounted for by a single component. This method, which essentially uses the knowledge that different cell types respond with different delay times, yielded three components. These were identified as the receptor component, the b-wave and the d.c.-component. The voltage-depth profiles of these components were assessed.

Animals↗

Origin of the electroretinogram in the intact macaque eye--II. Current source-density analysis.

Local electroretinograms (LERGs), evoked by 400 msec flashes of white light, were recorded as a function of retinal depth with a microelectrode in the intact eye of a macaque monkey. Retinal resistivity was measured as the potential difference between the tips of a bipolar microelectrode, resulting from a 300 msec current pulse which was passed through the retina. From the light evoked potentials and the resistivity the local currents in the retina were calculated. Current sources and sinks were localised for three LERG components. The receptor component had a current source in the outer segments (90% depth) and a sink in the ONL (70% depth). Both the b-wave and the d.c.-component had a source around 40% depth and a sink around 70% depth. The distribution of b-wave sources and sinks in primate seems to deviate from that in lower species, since no large current source is found in the most proximal layers.

Animals↗

Origin of the oscillatory potentials in the primate retina.

The current source and sink profiles of the oscillatory potentials (OPs) of the primate (macaque) electroretinogram (ERG) were studied. The intraretinal local ERG (LERG) and the local resistivity were recorded with a bipolar microelectrode in the intact macaque eye in response to a 10 deg and full field stimulus. A statistical method, a principle component analysis, was performed on high pass digitally filtered LERGs to extract and more closely study the oscillatory components of the LERG's at a number of electrode depths in the retina. The OPs were found to represent radial current flow and to have a current distribution different from those of the receptor and b-wave components. They are generated more proximal than the a- and b-waves, most probably by the bipolar cells. However, the interplexiform cell cannot be excluded as a generator. If so, the OPs should represent activity in a feed-back neural pathway in the inner part of the retina, also in the primate. The OPs can be used to monitor the inner neuronal layer but further differentiation in depth regarding consecutive peaks is not possible.

Animals↗

Density of human cone photopigments as a function of age.

The density difference between fully bleached and fully dark-adapted retinas was assessed for 77 eyes (47 subjects) in the age group 13-50 yr. No significant change in density was found as a function of age. The time constant of pigment regeneration was also found to show no age effects up to the age of 50 yr. These findings are at odds with another study on the density of foveal cones.

Adult↗

User friendly system for electrodiagnosis.

A laboratory built computer system for clinical electrophysiology of vision is described to illustrate how modern technology may ease the task of handling otherwise rather complicated electronic equipment and of elaborating the data obtained. An example is given of a procedure for clinical electroretinography in which the task of the operator is virtually confined to using a single command letter, which is specified in continuously updated instructions displayed on a monitor. After the patient has left, the operator checks and if necessary corrects the automatically defined maxima of a and b waves of the electroretinogram. The print-out consists of graphs of amplitude and latency versus stimulus intensity in which the normal range is indicated. The task of the operator during an EOG measurement is confined to checking the collaboration of the patient, since the complete procedure including the elaboration of the data is automated.

Computers↗

Foveal densitometry in central serous choroidopathy.

We evaluated foveal cone photopigment kinetics by retinal densitometry in 14 patients (12 men and two women, ranging in age from 30 to 54 years) with central serous choroidopathy. At the initial examinations when 12 of the 14 patients showed active leaks, the measured two-way density of pigment was low and the time-course of regeneration was slow. At later examinations, we found low two-way densities with normal regeneration times in five patients without active leakage. Near normal two-way densities occurred only in three patients who had complete clinical recoveries.

Choroid↗

Contact lenses in the military service.

This paper discusses contact lenses in a military environment and reports the results of a literature survey, an extensive questionnaire sent to 1400 spectacle and contact lens wearers, and a short questionnaire given to soldiers taking part in a large scale and long military maneuver. Only a small number of publications were found concerning the relation between adverse environmental conditions and contact lens wearing. In Vietnam dust and poor hygiene often led to eye irritations that precluded the wearing of contact lenses by soldiers. Nevertheless, persons in the army are often in favor of contact lenses. In the air force and navy, wearing contact lenses seems compatible with nearly all military duties. A questionnaire was sent to all known contact lens wearers in the Dutch army and air force and to about an equal number of spectacle wearers. The responses indicate that the proportion of contact lens wearers is 1.8%. The distribution of hard vs. soft lenses was 60 and 40%, respectively. Military personnel wore their lenses during nearly all daily activities. Most contact lens wearers were of the opinion that in military conditions contact lenses have advantages over spectacles. To obtain more information on field exercises, a second questionnaire was handed out immediately after a large-scale NATO field maneuver. Twenty percent of the contact lens wearers had decided in advance not to wear their lenses, but another 30% ceased wearing their lenses during the exercise. It was recommended that for nearly all functions and/or conditions, wearing of contact lenses should be allowed, but that during extended field exercises wearing of hard contact lenses should be discouraged.

Adult↗