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Biomedical subjects

J A van Best

Publications and source records attributed to J A van Best.

At least 19 recordsLinked to original sources

Effect of morphological abnormalities on blood retinal barrier permeability in diabetic retinopathy.

The morphological base for the impaired function of the blood retinal barrier was studied in 50 eyes of 10 insulin dependent and 21 non-insulin dependent patients with various levels of diabetic retinopathy. The permeability of the blood retinal barrier (PBRB) was determined by vitreous fluorophotometry with correction for autofluorescence, lens transmission and non-protein bound plasma fluorescein concentration. Morphological abnormalities of diabetic retinopathy assessed by fundus photography and fluorescein angiography were individually scored on a decimal scale and related to the PBRB by multiple regression analysis. The PBRB was not correlated to morphological abnormalities of non-proliferative retinopathy [(1) microaneurysms, (2) hard exudates, (3) soft exudates, (4) intraretinal hemorrhages, (5) fluorescein leakage, and (6) capillary closure, p greater than 0.3]. The PBRB was correlated to morphological abnormalities of (pre)proliferative retinopathy [(1) intraretinal microvascular abnormalities (SIRMA) and (2) new vessels (Sneo): PBRB = A+B.SIRMA + C.Sneo with PBRB in nm/sec, A = 1.5 +/- 0.5, B = 0.9 +/- 0.2 and C = 1.7 +/- 0.4, R2 = 0.65, p less than 0.0001]. It can be concluded that the increased blood retinal barrier permeability in diabetic patients is mainly due to (pre)proliferative abnormalities and not to non-proliferative abnormalities.

Blood-Retinal Barrier

Toxicity of 1-(beta-D-arabinofuranosyl)cytosine after intravitreal injection in the rabbit eye.

The retinal toxicity of intravitreally injected 1-(beta-D-arabinofuranosyl)cytosine (cytarabine) was examined in 7 chinchilla rabbits to determine if cytarabine can be used as local therapy for vitreoretinal non-Hodgkin's lymphoma. Fractionated dose of 600 micrograms, 1500 micrograms, and 2700 micrograms cytarabine in stabilized saline were given intravitreally in one eye (2 x 300 micrograms, 5 x 300 micrograms, and 3 x 900 micrograms, respectively, with an interval time of 24 h) and stabilized saline in the other eye as control. Toxic effects were evaluated with biomicroscopy, direct ophthalmoscopy, fluorophotometry, electroretinography, light, and electron microscopy. Toxic effects were found with the 1500 micrograms and 2700 micrograms doses only. They consisted of a temporary impairment of the blood retina barrier function for fluorescein as measured by fluorophotometry and an irreversible change of the b-wave in the electroretinograms. No histopathologic changes were seen under the light microscope. Electron microscopic examination showed aberrations in the synaptic pedicles of the photoreceptor cells at a dose of 1500 micrograms cytarabine. The results suggest that the cytarabine dose that is expected to be therapeutic for vitreoretinal non-Hodgkin's lymphoma (about 90 micrograms given in three doses of 30 micrograms) is non-toxic for ocular structures.

Animals

Fluorophotometric assessment of tear turnover under rigid contact lenses.

To examine the effect of rigid contact lens design on tear turnover the left and right eyes of 25 healthy volunteers were randomly fitted with either a spherical or an aspherical contact lens. Tear turnover is defined as the percentage of decrease of fluorescein concentration in the tear film per minute as a result of tear flow after instillation of fluorescein and can be determined with a fluorophotometer. A drop of fluorescein (1 microliter, 2%) was instilled in each contact lens-wearing eye, whereafter the decrease of the fluorescein was measured for about 30 min. The test was repeated without contact lenses. No statistically significant difference was found between the tear turnover in the spherical, the aspherical, and the non-contact lens-wearing eyes (mean values +/- SD: 15.2 +/- 4.9, 15.6 +/- 5.9, and 16.9 +/- 6.8%/min, p > 0.20).

Adult

Blood-retinal barrier dysfunction at the pigment epithelium induced by blue light.

Exposure to low-intensity white light can induce dysfunction of the blood-retinal barrier (BRB) at the retinal pigment epithelium (RPE). To determine whether the shorter wavelengths white light are responsible for this dysfunction, rabbit retinas were exposed to blue light (400-520 nm) or yellow light (510-740 nm). The permeability of the BRB, a parameter for the integrity of the barrier, was quantified with vitreous fluorophotometry. Morphologically, the barrier at the RPE was visualized on light and electron microscopy using horseradish peroxidase (HRP) as a tracer. Seventeen pigmented rabbits were exposed to blue light and 11 were exposed to yellow light. Vitreous fluorescein leakage increased with the exposure energy according to a power function (correlation coefficient > 0.79). The threshold energy for an increase in BRB permeability was 50 J/cm2 (0.014 W/cm2 for 1 hr) after blue and 1600 J/cm2 after yellow light. HRP tracing demonstrated that after blue light exposure, a significant fluorescein leakage on fluorophotometry corresponded to the presence of HRP in the RPE cells and in the subretinal space. After yellow light exposures of < 3700 J/cm2 and in rabbits with no significant fluorescein leakage, the HRP was limited to the choroidal capillaries and Bruch's membrane. These results demonstrate that the blue component of white light causes dysfunction of the BRB at the RPE 30 times more effectively than the longer wavelength fraction of white light. As a result, a blue light blocking filter should be used in ocular surgery on humans when an operating microscope is being used (light power 0.1-0.9 W/cm2).

Animals

Basal tear turnover and topical timolol in glaucoma patients and healthy controls by fluorophotometry.

To assess the effect of glaucoma and timolol on tear secretion, basal tear turnover was measured with fluorophotometry in 13 open-angle glaucoma patients not using any ophthalmic medication, 24 patients using timolol medication daily, and 41 healthy control subjects. Basal tear turnover is defined as the tear turnover at the lowest level of reflex lacrimation possible under physiologic conditions. Tear turnover was calculated from the decay of the tear fluorescence after instillation of fluorescein. Minimal influence of reflex lacrimation was obtained by instilling 1 microliter of 2% fluorescein without touching the eye and by discarding measurements performed in the first 5 min. Minimization was confirmed by a monophasic decay of tear fluorescence. The values of patients who used timolol and those who did not use timolol were significantly lower than those of healthy control subjects (mean values in percent/minute +/- standard deviation: 10.1 +/- 3.2, 12.3 +/- 4.1, and 15.6 +/- 5.4, respectively; Student's t-test: P < 0.02). The values of patients who used timolol were significantly lower compared to those of patients who did not use timolol (P = 0.03). The tear film break up time values of patients who used timolol were significantly shorter than those of patients who did not use timolol and healthy control subjects (Fisher exact test: P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical

Corneal autofluorescence: an indicator of diabetic retinopathy.

The metabolic disorder in diabetics often results in progressive retinopathy with severe visual impairment. Changes in metabolism can influence corneal autofluorescence. This has led to speculation that diabetic retinopathy might be associated with changes in corneal autofluorescence. Corneal autofluorescence of both eyes was determined by fluorophotometry in 94 insulin-dependent diabetes mellitus patients and in 46 healthy controls to evaluate its correlation with diabetic retinopathy. The modified Airlie House classification was used for grading diabetic retinopathy: (1) no or negligible retinopathy; (2) minimal background retinopathy; (3) background retinopathy; and (4) (pre-) proliferative retinopathy. The corneal autofluorescence values of grade 1 retinopathy patients did not differ significantly from those of the healthy controls (mean +/- standard deviation in ng equivalent fluorescein/ml: 11.6 +/- 3.0 and 11.4 +/- 2.8, respectively; P = 0.8). The means of grade 2, 3, and 4 retinopathy patients (mean +/- standard deviation in ngEq fluorescein/ml: 16.2 +/- 4.4, 16.7 +/- 4.3, 20.9 +/- 5.4, respectively) were significantly higher than the means of grade 1 patients and healthy controls (P less than 0.004). The mean values of patients with grade 4 were significantly higher than those of patients with grades 2 and 3 (P less than 0.01). The sensitivity and specificity of corneal autofluorescence as a screening test for diabetic retinopathy were 80% and 76%, respectively; the positive predictive value for the presence of retinopathy was 90%. The values for screening on (pre-) proliferative diabetic retinopathy were 68%, 72%, and 58%, respectively. These data show corneal autofluorescence to be an adequate indicator of diabetic retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Determination of basal tear turnover in insulin-dependent diabetes mellitus patients by fluorophotometry.

The tear turnover was determined by fluorophotometry in 25 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy and 29 IDDM patients with (pre-)proliferative retinopathy. The results were compared with those in 34 healthy controls, to investigate the lacrimal gland function in diabetic patients. The tear turnover was calculated from the decay of the relative tear fluorescein concentration values measured after instillation of one microliters of fluorescein. The tear turnover values in both patient groups did not correlate significantly with age or diabetes duration (linear correlation coefficients: r less than 0.3). The tear turnover values in patients both without retinoplathy and with (pre-)proliferative retinopathy did not differ significantly from those in healthy controls (mean +/- SD in %/min: 13.7 +/- 4.5, 14.7 +/- 5.8 and 15.5 +/- 5.1, respectively; P greater than 0.16). The tear turnover was significantly decreased in eyes having a BUT shorter than 10 seconds compared with eyes having a BUT longer than 10 seconds (P less than 0.05). The tear turnover values correlated significantly with the HbA1c and Schirmer-test values in patients with (pre-)proliferative retinopathy (r = 0.7 and r = 0.4, respectively; P less than 0.02) and with the blood glucose values in patients without retinopathy (r = 0.41, P = 0.04). Since the tear turnover was not significantly decreased in IDDM patients in comparison with healthy controls the corneal disorders which are more frequently seen in these patients than in a healthy population may not be attributed to a decrease in tear production.

Adult

Xenon arch photocoagulator used for transpupillary hyperthermia.

The technique of near-infrared irradiation to obtain tumour necrosis in experimental pigmented melanomas is described. The xenon arch photocoagulator was modified and adapted for hyperthermia treatment. The adaptations included: filtering the light and changing the electronics, the aiming beam and the diameter of the beam.

Animals

Epithelial permeability in corneal grafts by fluorophotometry.

The epithelial permeability to fluorescein of 27 clear corneal grafts in 23 patients was determined by fluorophotometry at greater than 1 year after penetrating keratoplasty (PKP) so as to study the recovery of corneal epithelial function. The mean epithelial permeability of the corneal grafts did not differ significantly from that of normal corneas (0.042 +/- 0.016 and 0.038 +/- 0.017 nm/s, respectively; P greater than 0.3). Multiple linear regression analysis showed that permeability correlated with recipient age but not with donor age (permeability increase, 0.00054 nm/s per year; r = 0.6, P less than 0.005 and r = 0.1, P greater than 0.5, respectively). These results indicate that corneal grafts can regain a normal epithelial barrier function and that recovery of epithelial function is better in young than in old recipients.

Adult

The effect of white light exposure on the rabbit eye lens as measured by fluorophotometry and spectrophotometry.

Fluorophotometry and spectrophotometry of the rabbit lens were performed after white light exposure to detect possible changes in the lens before damage could be seen by biomicroscopic slit lamp examination. In nine rabbits the lens of one eye was exposed to white light and that of the fellow eye was used as a control. The incident light power was 240 mW for 90 min on a lenticular area of 3 mm2. Slit lamp examination of lens and cornea prior to, 1 hr after and 2 days after light exposure did not reveal any sign of damage. The mean in vivo autofluorescence ratio between exposed lens and non-exposed fellow lens was found to increase significantly from 1.0 +/- 0.08 S.D. (n = 9) before exposure to 3.3 +/- 0.8 S.D. (n = 9; P less than 0.004) 1 hr after exposure and hereafter to decay exponentially with a half time of 0.8 days to the ratio before exposure (correlation coefficient: -0.97, P = 0.0013). Three additional rabbits were exposed as described above with subsequent in vitro spectrophotometry of the lenses between 400 and 800 nm revealing an absorbance peak at 468 nm with a half width of 10 nm. The ratio between the absorbance peak of exposed lens and non-exposed fellow lens was found to increase from 1.1 before exposure to 2.8 1 hr after exposure and then to decrease to 1.4 at 1 day after exposure. The corresponding autofluorescence ratios measured in vivo before spectrophotometry were 0.93, 2.6 and 1.5, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Topical administration of leukotriene antagonists in immunogenic keratitis.

Antagonists of leukotriene D4 (LTD4), 3-[7-(2-n-propyl-3-hydroxy-4-acetyl- phenoxy)-propoxy-2-methyl-3,4-dihydro-4-8-n-propyl-2H-1-benzopyran- 2-yl]-propionic acid (SC-39070) and 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy- propoxy]-4-methyl- 2-oxo-2H-1-benzopyran-3-acetic acid (FPL-60319) were locally administered to eyes of rabbits with immunogenic keratitis. The period of circular leukocyte infiltration (Wessely's ring) in the cornea was markedly decreased. Edema and neovascularization of the cornea were not influenced.

Administration, Topical

Corneal epithelial barrier function after oxybuprocaine provocation in diabetics.

Corneal epithelial permeability for fluorescein was determined after provocation by a local anesthetic in 18 non-insulin-dependent diabetes mellitus (NIDDM) patients, 23 insulin-dependent diabetes mellitus (IDDM) patients, and 22 healthy controls to evaluate the corneal epithelial barrier function in diabetes. All volunteers had Oxybuprocaine instilled into one eye and saline into the other eye. The epithelial permeability values were determined by fluorophotometry, and the ratio between both eyes was calculated for each individual. The mean permeability values of the saline-instilled eyes in the diabetic patients did not differ significantly from those in the healthy controls (P greater than 0.2). The individual ratios between Oxybuprocaine- and saline-instilled eyes in the NIDDM and IDDM patients differed significantly from those in the healthy controls (mean ratios: 2.6, 1.9, and 1.0, respectively; P less than 0.002). The permeability ratios and the percentage glycosylated hemoglobin (HbAlc) were linearly correlated in the NIDDM patients but not in the IDDM patients (r = 0.73, P less than 0.001, and r = 0.09, P greater than 0.68, respectively). The results showed that the corneal epithelial barrier function in the diabetic patients was not impaired compared with that in the healthy controls. After provocation by a local anesthetic, the barrier function was impaired in the diabetic patients only.

Adolescent

Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry.

At first it was verified that the major part of the fluorophotometer signal obtained when measuring corneal autofluorescence originated from fluorescence and not from scatter of excitation light at the corneal surface. The minimum percentage of the signal which can be attributed to fluorescence was determined using a fluorescence blocking filter placed in the excitation and fluorescence light path, respectively. The minimum percentages in two healthy controls, two diabetic patients and two patients after penetrating keratoplasty ranged from 75% to 93% (mean 84%). Then the corneal autofluorescence was determined in 22 healthy controls, 18 non-insulin-dependent diabetes mellitus (NIDDM). 23 insulin-dependent diabetes mellitus (IDDM) and 21 penetrating keratoplasty patients in order to detect a possible difference in autofluorescence as a result of diabetes or penetrating keratoplasty. The means of the corneal peak autofluorescence values in the NIDDM, IDDM and penetrating keratoplasty patient groups were significantly higher than that in the healthy control group (mean values in ng equivalent fluorescin ml-1: 18.0 +/- 4.2 S.D., 20.6 +/- 5.1 S.D., 17.9 +/- 5.5 S.D. and 13.7 +/- 3.7 S.D., respectively; P less than 0.01). The mean values in the NIDDM and IDDM patients did not differ significantly (P = 0.09). The autofluorescence values were independent of age in all four groups (linear correlation coefficient: r less than 0.47). The corneal peak autofluorescence was linearly correlated with the diabetes duration in the NIDDM and IDDM patients [r = 0.6, P = 0.02; increase: 0.36 ng equiv. fluorescein ml-1 yr diabetes-1]. Our results show that corneal autofluorescence is an easily obtained parameter which can be of assistance in evaluating corneal metabolism.

Adolescent

Fluorophotometric assessment of blood-retinal barrier function after white light exposure in the rabbit eye.

Fluorophotometry was performed in 14 rabbits after exposure of one eye to white light with an energy insufficient to cause visible phototoxic retinal damage as determined by ophthalmoscopy and fundus photography. Fluorescence measurements in the vitreous were performed before and 1 hr after i.v. injection of fluorescein. Ratios between the fluorescein concentrations in the exposed and in the non-exposed fellow eye were calculated after correction for the autofluorescence. The average ratio directly after light exposure had significantly increased (P = 0.005) as compared to pre-exposure values and was maximal one day after exposure (P less than 0.005). Four days after exposure the ratios had returned to pre-exposure values (P greater than 0.05). A significant linear correlation between age and the ratios directly after exposure was found (r = -0.67; P less than 0.01). Signs of phototoxic retinal damage were not found on ophthalmoscopy and fundus photography, nor on light and electron microscopic examination of the retinal pigment epithelium, neuro-retina or retinal capillaries 1 and 4 days after light exposure. A fluorophotometric assessment of the blood-retinal barrier (BRB) function after white light exposure appeared to be a more sensitive parameter of light-induced damage than morphological examination since light exposures at retinal irradiance levels below the threshold for ultrastructural damage resulted in a temporary BRB dysfunction that could be detected by fluorophotometry but not by the other methods.

Animals

Tumor destruction by intermediate level hyperthermia.

The tumoricidal effect of hyperthermia was studied in Greene's amelanotic hamster melanoma transplanted into the anterior chamber of rabbit eyes. To achieve optimal depth penetration, hyperthermia was induced with near infrared light of 820-870 nm, during 15 minutes, at a beam diameter of 2.5-6.0 mm resulting in an intermediate level hyperthermia of 45-60 degrees C. At 45 degrees C no tumor destruction occurred, at 50 degrees C the effect varied from no destruction to total thickness tumor destruction. At 55-60 degrees C total tumor destruction with additional lens damage occurred. In comparison photocoagulation with white light revealed only necrosis up to half the tumor thickness.

Animals

Bacteriochlorin a, a new photosensitizer in photodynamic therapy. In vivo results.

The photosensitizing properties of bacteriochlorin a (BCA), a nontoxic derivative of bacteriochlorophyll a, were investigated in vivo. BCA has an absorption band at a wavelength at which tissue penetration is optimal (760 nm), and it shows preferential tumor retention in Greene melanoma implanted in the anterior chamber of rabbit eyes. A dose of 20 mg/kg BCA was administered IV at 4-7 mm tumor diameter; 24 hr later the tumor was irradiated with near-infrared light (30 min, 760 nm, 150-280 J/cm2). On the day after the irradiation it appeared that tumor growth had stopped: fluorescein angiography showed nonperfusion of the tumor. Histopathology after enucleation showed subtotal tumor necrosis with occasionally small clusters of viable cells around a blood vessel and at the tumor periphery. Neither BCA nor light alone had any effect on the eye or melanoma.

Animals

The permeability of the corneal epithelium of Graves' ophthalmopathy as determined by fluorophotometry.

The function of the corneal epithelium was evaluated in 30 patients with Graves' ophthalmopathy in whom no signs of corneal disease were observed. This function was evaluated by determining the permeability values of the corneal epithelium for fluorescein using fluorophotometry. The permeability values of the patients were compared with those of 46 healthy individuals. A significant increase in the permeability values was seen in 11 (37%) patients and in two (4%) controls (p less than 0.05). The difference in the mean permeability values between patients en controls was statistically significant (0.053 nm/sec. +/- 0.043 SD and 0.038 nm/sec. +/- 0.017 SD, respectively, p less than 0.05). No relation was found between the permeability values of the corneal epithelium and the NOSPECS classification or the duration of the disease. There was a tendency for increased permeability values in patients having an exophthalmos larger than 20 mm. (correl. coeff. = + 0.3, p less than 0.05).

Adult