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Biomedical subjects

D van Norren

Publications and source records attributed to D van Norren.

At least 37 records · Page 2Linked to original sources

The pathways of light measured in fundus reflectometry.

We measured the spectral reflectance of the fovea of ten normal subjects in four conditions, i.e. under dark-adapted and bleached conditions and at two retinal angles of incidence. The objective was to study optical pathways through the photoreceptor layer, resulting in a model that simultaneously explains spectral, directional and bleaching properties of the fovea. On theoretical grounds, we propose that small reflections from the stack of discs in the cone outer segments are the origin of the directional component of foveal reflection. Non-directional reflection occurs at the inner limiting membrane and at all layers posterior to the outer segments. With four reflectance spectra as input, the model allows determination of the density of the photostable absorbers, the lens, macular pigment, melanin and blood. Because of the simplified modeling of the layers posterior to the photoreceptor layer, the values for the density of melanin and blood are not necessarily comparable to physiological data. The density of the visual pigment calculated with this model is consistent with psychophysical data, with estimates for the ten subjects ranging from 0.41 to 0.80. The long wavelength sensitive cone fraction is calculated as 0.56.

Blood↗

Scanning laser densitometry in visual acuity loss of unknown origin.

AIM: To assess foveal cone photoreceptor function in patients with unexplained loss of central visual acuity. METHODS: Testing of foveal cone photoreceptor function was performed using scanning laser densitometry, colour matching (Rayleigh equation), and pattern electroretinography (ERG). Standard tests included full field ERG, electrooculography, visual evoked potentials, static perimetry, and fluorescein angiography. RESULTS: Decreased foveal cone photopigment density and abnormal pattern ERG were found in three patients. Results of colour matching were not unequivocal. CONCLUSION: Testing of foveal cone photoreceptor function using scanning laser densitometry may determine the location of pathological changes in certain patients with unexplained visual loss.

Adolescent↗

Origin of tapetal-like reflexes in carriers of X-linked retinitis pigmentosa.

PURPOSE: To determine the origin of the tapetal-like reflex (TLR) in carriers of X-linked retinitis pigmentosa. METHODS: Spectral fundus reflectance of carriers of X-linked retinitis pigmentosa was measured and compared with that of normal subjects. The influence of visual pigment was determined by measuring the density difference, that is, the difference between the logarithmically scaled spectra of a bleached and a dark-adapted retina. In addition, fundus reflectance maps at 514 nm were made with a scanning laser ophthalmoscope in a bleached and a dark-adapted condition. Finally, the optical Stiles-Crawford effect was measured to determine the angular sensitivity of the TLR. RESULTS: The tapetal-like reflex showed its spectral fingerprint in a high reflectance for wave-lengths smaller than 600 nm. The density difference measured at retinal sites of TLR was significantly larger than in normals, but the shape of the spectrum was similar. The optical Stiles-Crawford effect showed a similar peakedness for all retinal positions. However, in the TLR region, the amplitude of the directionally dependent part was increased dramatically. For the foveal region, no differences were observed. CONCLUSIONS: An increase in reflectance of the outer segments of the photoreceptors in heterozygotes compared to normals can explain both the high-density difference and the large amplitude of the Stiles-Crawford effect. An earlier suggestion that only cones contribute to the TLR is unlikely.

Adult↗

Reversible cone photoreceptor injury in commotio retinae of the macula.

PURPOSE: To examine the foveal cone photopigment kinetics in two patients with commotio retinae of the posterior pole (Berlin edema). METHODS: A noninvasive technique, called fundus reflection densitometry, was used to provide a measure of the amount of visual photopigment at the foveal area and the time constant of photopigment regeneration. RESULTS: Strongly impaired foveal cone photopigment kinetics were found in two patients during the acute stage of commotio retinae. Complete recovery occurred within 3 months in both patients. CONCLUSION: Retinal opacification in Berlin edema is accompanied by a traumatic lesion at the level of the photoreceptor-retinal pigment epithelium (RPE) complex. These results support recent histopathologic data on commotio retinae, which revealed moderate photoreceptor outer segment disruption and retinal pigment epithelium damage. According to our data, such damage might be reversible.

Adult↗

Ultraviolet and green light cause different types of damage in rat retina.

PURPOSE: To assess the influence of wavelength on retinal light damage in rat with funduscopy and histology and to determine a detailed action spectrum. METHODS: Adult Long Evans rats were anesthetized, and small patches of retina were exposed to narrow-band irradiations in the range of 320 to 600 nm using a Xenon arc and Maxwellian view conditions. After 3 days, the retina was examined with funduscopy and prepared for light microscopy. RESULTS: The dose that produced a change just visible in fundo was determined for each wavelength. This threshold dose for funduscopic damage increased monotonically from 0.35 J/cm2 at 320 nm to 1600 J/cm2 at 550 nm. At 600 nm, exposure of more than 3000 J/cm2 did not cause funduscopic damage. Morphologic changes in retinas exposed to threshold doses at wavelengths from 320 to 440 nm were similar and consisted of pyknosis of photoreceptors. Retinas exposed to threshold doses of 470 to 550 nm had different morphologic appearances. Retinal pigment epithelial cells were swollen, and their melanin had lost the characteristic apical distribution. Some pyknosis was found in photoreceptors. CONCLUSIONS: Damage sensitivity in rat increases enormously from visible to ultraviolet wavelengths. Compelling evidence is presented that two morphologically distinct types of damage occur in the rat retina, depending on the wavelength. Because two types also have been described in monkey, a remarkable similarity seems to exist across species.

Animals↗

Serial foveal densitometry and visual function after retinal detachment surgery with macular involvement.

PURPOSE: Fundus reflection densitometry was used as an objective means for monitoring the recovery of foveal cone photopigments in nine patients who underwent anatomically successful surgery of a rhegmatogenous retinal detachment with macular involvement. METHODS: Postoperative assessment of foveal densitometry, visual acuity, color matching, and the Amsler grid were performed at repeated intervals for up to 14 months. RESULTS: Gradual recovery of foveal cone photopigments was found in all patients 1 to 14 months after surgery, with considerable interindividual variation. Maximal recovery to values equalling those in the fellow eye was found in only one patient with a macular detachment duration of 5 days. All other patients had final photopigment densities below those of the fellow eye. The length of the preoperative detachment period was inversely related to the recovery of photopigment. The recovery of photopigment seems to increase further in the second year after surgery. Visual acuity increased rapidly in all patients during the first 6 months after surgery, to levels ranging between 20/67 and 20/25; thereafter, visual acuity did not change. A return to normal color matching after an episode of pseudoprotanomaly was found in four of nine patients, whereas pseudoprotanomaly remained in five patients. Complete resolution of metamorphopsia after surgery was seen only in the patient who had the shortest detachment duration. Metamorphopsia was consistent with decreased foveal cone photopigment densities. CONCLUSION: Foveal densitometry shows a slow recovery of the cone photopigments after reattachment, probably because of regrowth and realignment of the cone photoreceptor outer segments and metabolic recovery of the retinal pigment epithelium-cone photoreceptor complex. Recovery of photopigment, color matching, and metamorphosia follow a slower time course than recovery of visual acuity.

Adult↗

Does color vision deficiency in the endoscopist influence the accuracy of endoscopic diagnosis? An anonymous study with Dutch gastrointestinal endoscopists.

Colors play a major role in the endoscopic diagnosis of many gastrointestinal conditions. Gastrointestinal endoscopists in the Netherlands are predominantly male (> 90%), and from population data it is to be expected that approximately 8% will have a color vision deficiency. The present study was designed to assess the prevalence of color vision deficiencies amongst Dutch gastrointestinal endoscopists and to determine whether color vision deficiency affects an endoscopist's diagnostic skill. One hundred and thirty-nine gastroenterologists and physicians of internal medicine took an F2 color vision test and assessed nine videofragments of endoscopies. Color vision deficiencies were detected in 8% of Dutch gastrointestinal endoscopists. In one out of the nine video excerpts of endoscopies, a statistically significant difference was detected between test subjects with and without a color vision deficiency. However, this video excerpt showed a green pea, which could not be mistaken for a polyp at polypectomy. The study therefore does not show any effect of color vision deficiencies on endoscopic skills, nor does it show any deviant prevalence of color vision deficiencies amongst Dutch gastrointestinal endoscopists.

Adult↗

Scanning laser densitometry in multiple evanescent white dot syndrome.

A 28-year-old man with multiple evanescent white dot syndrome (MEWDS) in the left eye was examined with a scanning laser densitometer. The first measurements were taken in the acute stage, and repeat examinations were performed during the process of recovery. Fundus pictures were obtained from a 20 degrees retinal field, in dark and light adapted stages. From these images visual pigment density maps were derived. In the acute stage of the disease, maps revealed small round areas of absent visual pigment, which did not always correspond with the visible white dots. The areas of absent visual pigment density were also larger than the white dots seen on funduscopic examination. Single spot densitometry at the fovea was also performed and showed no significant density difference of the foveal cones. Rod density difference measured at a locus 16 degrees in the temporal retina was much lower than normal with an increased time constant of rhodopsin regeneration. Ten weeks after the onset of the disease, no white dot lesions were visible on funduscopic examination. Rod density difference and regeneration time had become normal again, but with scanning laser densitometry the abnormal areas of no pigment were still faintly visible. It is concluded that these findings, completed with data of electroretinography, anomaloscopic testing, and perimetry, are in agreement with a metabolic disturbance at the level of the retinal pigment epithelium-photoreceptor complex.

Acute Disease↗

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↗