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Biomedical subjects

D van Norren

Publications and source records attributed to D van Norren.

At least 19 recordsLinked to original sources

Foveal densitometry in adult-onset diffuse drusen.

We compared the results of foveal densitometry with results of other retinal function tests in five asymptomatic subjects with adult-onset diffuse drusen. All results of routine retinal function tests, including visual acuity, Rayleigh equation color matches, multiple static perimetry, electroretinography, and electro-oculography, were normal. All five subjects had decreased foveal cone photopigment density with densitometry, indicating an early dysfunction at the level of the foveal cone photoreceptors. Several functional defects may be responsible for the densitometric results in adult-onset diffuse drusen, including retinal pigment epithelium dysfunction, foveal cone photoreceptor misalignment, and a reduction of the in situ foveal cone photopigment.

Adult

Spectral transmittance of the rat lens.

The spectral transmittance of the isolated rat lens for radiation of wavelengths from 300 to 700 nm was measured using a spectrophotometer. Transmittance decreased from 93-95% at 700 nm, to 70-80% at 400 nm, 50-60% at 360 nm, 4-18% at 320 nm, and to < 2% at 310-300 nm. These results indicate that the rat lens is remarkably transparent for UVA radiation, which has consequences for rat vision, and for interpretation of earlier studies on retinal light damage.

Animals

Foveal photopigment kinetics--abnormality: an early sign in myotonic dystrophy?

Twelve subjects with minimal expression of the myotonic dystrophy (MyD) gene were investigated by retinal densitometry, a technique which has been used to study the properties of photopigments in the living eye and to detect photoreceptor abnormalities. Other investigations included slit-lamp examination, funduscopy, raleigh matches with the anomaloscope, tonometry, and neurological examination, including electroretinography (ERG) and pattern visual evoked potentials recording. Foveal densitometry demonstrated reduced values of the macular photopigment density difference with normal photopigment kinetics in early phases of the disease, even in asymptomatic individuals. The densitometric values correlated with decreased amplitudes of the photopic ERG a-wave. These findings may be explained by loss or dysfunction of the outer segments of foveal receptors. It is yet unknown whether or not these changes are secondary to other observed neuroretinal abnormalities in MyD. The most likely explanation might be an abnormality of the Na, Ca:K exchanger at the level of the outer segments of the photoreceptors whether or not in combination with a dysfunction of voltage generation systems, involving both photoreceptors and retinal pigment epithelium.

Adolescent

Effect of body temperature on threshold for retinal light damage.

Body temperature is known to influence the threshold for retinal light damage, but the magnitude of the effect has varied substantially between previous studies. The purpose of the present study was to establish a quantitative relation between body temperature in the range of 30-42 degrees C and dose of radiation for a just visible change in fundo. Anesthetized pigmented rats were exposed to 380 nm radiation for 10 min. Four intensities were simultaneously presented. Funduscopic changes were noted 2-3 d after exposure. At 30 degrees C, threshold dose was 6 J/cm2; at 42 degrees C, it was about 1 J/cm2. A fair fit to the data could be obtained with a linear regression between log threshold dose and temperature. The slope was -0.067. In an additional experiment, threshold dose at 500 nm and 41 degrees C body temperature was established at 400 J/cm2. These results agree with data in monkey and rabbit, but they vary from earlier data in rats that show a slope of -0.8. Exposure time, damage criterion, and the chromophores involved in retinal light damage are possible factors in the discrepancy.

Animals

Mizuo phenomenon in X-linked retinoschisis. Pathogenesis of the Mizuo phenomenon.

Four unrelated males with X-linked retinoschisis and a golden fundus reflex had Mizuo-Nakamura phenomenon, which, to our knowledge, has been described only in Oguchi's disease and X-linked cone dystrophy. These findings, together with experimental observations and data from the literature, led us to hypothesize that the Mizuo-Nakamura phenomenon is caused by an excess of extracellular potassium in the retina as a result of a decreased potassium scavenging capacity of retinal Müller cells.

Adult

Rod densitometry in the aging human eye.

Retinal densitometry is a noninvasive physiologic technique used to examine the visual pigments in living human eyes. To assess possible age-related disturbances of rod photopigment kinetics, retinal densitometry was done in 44 eyes of 44 healthy subjects (age range, 12-78 yr). With progressing age, a significant but small increase in photopigment density difference (bleached versus dark adapted eye) and an increase in the time constant of rhodopsin regeneration was found. The increased density difference in rods was consistent with morphologic findings of increased rod outer segment diameter and disc content in older subjects. To explain this change in terms of the decreased specular reflections at the level of the inner limiting membrane was inadequate because age effects were independent of wavelength in the region of 450-550 nm. To control for the effects of ocular stray light from the lens, subjects older than 40 yr with a clear crystalline lens were measured and compared with those with pseudophakia. No statistically significant difference was found between the two groups. Increased rod density difference contrasts sharply with an earlier reported decrease in this parameter for foveal cones. The slowing of the regeneration rate is a phenomenon common to rods and cones. It may be a result of a gradual metabolic dysfunction of the retinal pigment epithelium in older subjects.

Adolescent

Color matching and foveal densitometry in patients and carriers of an X-linked progressive cone dystrophy.

We describe a family with an as yet undescribed form of X-linked progressive cone dystrophy in a five-generation pedigree, from which we report here the results of 17 male patients and 31 obligate and 13 possible female carriers. The affected males showed the characteristic picture of cone dystrophy. Foveal cone photopigment density was impaired (judged from anomaloscope settings and foveal densitometry), even at an early stage of the disease. The carriers showed no fundus abnormalities, except occasional changes due to myopia. The anomaloscope demonstrated mild pseudoprotanomaly in 27 of 31 obligate carriers and in six of 13 possible carriers. Foveal densitometry findings performed in 11 carriers always agreed with the anomaloscope findings. We conclude that the findings of pseudoprotanomaly and abnormal density differences in females of this family were the only ocular abnormalities and thus are indicative of the carrier state.

Adult

Blue light hazard in rat.

Rats have been extensively used in light damage studies. Retinal damage threshold for white light were found at 1-10 J/cm2, and the action spectrum resembled the absorption spectrum of visual pigment. We wished to answer the question whether a different class of light damage, the "blue light hazard", with white light damage thresholds at about 300 J/cm2, and an action spectrum peaking in the ultra-violet, could also be demonstrated in rat. To that purpose 5 deg patches of retina were exposed to white xenon light with exposure times between 10 sec and 1 hr. We found that for funduscopic threshold damage the product of irradiance and exposure time was constant at a level of 315 J/cm2. Thereafter, the action spectrum was measured by exposing rat eyes to narrow band spectral lights. Threshold irradiant dose ranged from 4 J/cm2 at 379 nm to 2000 J/cm2 at 559 nm. Thus, susceptibility for damage sharply increased towards the ultra-violet, just like in earlier monkey studies. We conclude that in similar experimental conditions susceptibility to photic injury in rat is comparable to that in primates. Rat is the first species for which two different action spectra of photochemical damage have been established.

Animals

Retinal densitometer with the size of a fundus camera.

This paper describes a small, user-friendly fundus reflection densitometer. All optics and part of the electronics are contained in a box with the size of a fundus camera. A personal computer is used for control and on-line display of output. A single 30 W halogen lamp provides bleaching and measuring light. A chopper wheel generates 24 light pulses in 100 msec time frames: 16 pulses of measuring light at different wavelengths covering the spectrum, four pulses of bleaching light (optionally), and four dark pulses for assessing the dark current of the photomultiplier. The fundus can be viewed when the bleaching light is on. The measuring field has four widths ranging from 1.6 to 5.4 deg; the bleaching light is fixed at 25 deg. A fixation aid may be positioned anywhere in the bleaching field. A microprocessor sorts the quanta, detected by the photomultiplier after reflection from the fundus, in 16 channels labeled with wavelength information. Real-time changes in spectral reflection can be viewed on a monitor. Due to optimal design of entrance and exit pupils foveal density differences of up to 0.5 were recorded in human subjects. This is higher than ever reported before with retinal densitometry.

Adult

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