Biomedical subjects

B Khoobehi

Publications and source records attributed to B Khoobehi.

At least 37 records · Page 2Linked to original sources

PubMed1992

Laser-triggered repetitive fluorescein angiography.

Liposome-encapsulated fluorescent dye has been altered to allow full fundus angiography after a single laser shot. By exposing the retinal arteries to laser energy where they emerge at the optic disc nerve head, dye release is elicited simultaneously in all four quadrants of the retina, without choroidal fluorescence, allowing visualization of the retinal microcirculation. Because the quantity of dye release is limited, recirculation does not increase background fluorescence. The procedure can be repeated many times without delay with consistent results. Increasing the laser spot size to 1.5 mm allows consistent dye release at energy densities from 0.5 J/cm2 to 3.4 J/cm2. This refinement will allow direct comparison in primates of this technique and conventional fluorescein angiography. The laser energy delivered to the retina is below suggested levels that may be tolerated by the optic nerve.

Animals↗

PubMed1992

Encapsulation of sodium fluorescein for dye release studies.

Recent investigations have detailed a selective dye release technique in which a pulse of laser light induces the release of a fluorescent dye from temperature-sensitive liposomes circulating in the retinal vasculature. This dye release technique has made possible a new method for measuring ocular blood flow in the retina and has spurred the development of repetitive, site-specific angiography. However, sodium fluorescein, the dye employed clinically for angiography of the retina, has not been employed in the aforementioned studies because of its rapid efflux from liposomes. This report outlines a method for stable encapsulation of sodium fluorescein in temperature-sensitive liposomes. Heat-induced leakage of the dye from liposomes in vitro was similar to that previously seen with other fluorescent dyes. Furthermore, after intravenous injection of encapsulated fluorescein in a nonhuman primate, dye released by a pulse of laser light allowed excellent visualization of the retinal architecture. These results indicate that sodium fluorescein, a dye that has proven to be the agent of choice for sensitive detection of leakage of vessels of the retina, can be released at a specific site in the retinal vasculature. Direct comparisons of the diagnostic capability of free and encapsulated sodium fluorescein are now possible.

Animals↗

PubMed1991

Effect of piroxicam on the blood-retina barrier in experimentally induced diabetes in rats.

The effect of piroxicam on the blood-retina barrier was evaluated in rats with experimentally induced diabetes. Diabetes was induced in rats by intraperitoneal injection of streptozocin (STZ). Diabetic rats were divided into two equal groups: those treated with piroxicam, a long-acting platelet inhibitor, and an untreated control group. Vitreous fluorophotometry (VFP) was performed both before and two weeks after induction of diabetes and piroxicam intake. Streptozocin-induced diabetes caused an alteration in the blood-retinal barrier evidenced by an increase in vitreous fluorescein concentration in diabetic rats compared with normal rats. Piroxicam intake did not lead to significant change in vitreous fluorescein concentrations. However, the examination had to be terminated at two weeks because of cataract formation. The piroxicam treated group showed less incidence of lens opacity formation (59.1% compared to 81.8% in the untreated group, p = 0.0006). Piroxicam administration appears to protect the diabetic rat eye against lens opacification.

Animals↗

PubMed1991

Long-term effect of erbium-YAG laser (2.9 microns) on the primate cornea.

An erbium-YAG (2.9 microns) laser was used in the primate eye to irradiate the anterior surface of the cornea in one group and the midstroma in another group after temporary lamellar keratectomy. The eyes were observed clinically up to a period of eight months, when the animals were sacrificed. The initial opacification of the cornea caused by the erbium laser application gradually disappeared over the observation period and was replaced by a faint haze. The healing process was faster in Group II (midstromal laser ablation). Some degree of flattening of the cornea after laser ablation was seen in both groups by photokeratoscopy. At the end of the observation period, the irradiated corneas demonstrated normal appearing corneal structure without significant damage to the corneal epithelium, stroma, or endothelial cells. Further experimental studies are needed to improve the laser delivery system and reduce the degree of corneal damage produced by long laser pulses.

Animals↗

PubMed1991

The effect of aminoguanidine on the blood-retinal barrier in streptozocin-induced diabetic rats.

The effect of aminoguanidine hydrochloride (AG) on the blood-retinal barrier was studied in rats with streptozocin-induced diabetes. Half of the rats were given AG (100 mg/kg/day) while the remainder received no treatment. Vitreous fluorophotometry was performed on all rats before STZ injection and 2 weeks after induction of diabetes mellitus. Two weeks after STZ injection the mean 60-minute vitreous fluorescein concentration following dye injection had increased more in the nontreated group than in the AG-treated group, suggesting that AG may have some beneficial effect on the breakdown of the blood-retinal barrier.

Animals↗

PubMed1991

Effect of pyridoxine on the blood-retina barrier in experimentally induced hyperglycemia in rats.

We studied the effects on the blood-retina barrier of pyridoxal S phosphate, the biologically active form of vitamin B6 (pyridoxine), in 23 male Long-Evans rats in which hyperglycemia had been induced by means of intraperitoneal injection of streptozocin. Twelve rats were treated with pyridoxine, and 11 rats served as the control group. Vitreous fluorophotometry was used to quantitatively evaluate the effect of pyridoxine. The procedure was done before and 2 weeks after the induction of hyperglycemia, readings being taken 5 and 60 minutes after injection of the dye. In both groups the mean vitreous fluorescein levels after hyperglycemia was induced were significantly higher than those before hyperglycemia was induced (p less than 0.05). The mean levels before hyperglycemia was induced were not significantly different between the two groups. The mean level 60 minutes after injection of the dye after hyperglycemia was induced was lower in the treated group than in the untreated group, although not significantly so. The incidence of lens opacities at 5 weeks was higher in the untreated group than in the treated group (p less than 0.01). We conclude that administration of pyridoxine to hyperglycemic rats for 5 weeks has no significant effect on the permeability of the blood-retina barrier.

Animals↗

PubMed1991

Clearance of sodium fluorescein incorporated into microspheres from the vitreous after intravitreal injection.

The clearance of microsphere-bound fluorescein from the vitreous was studied in rabbits to evaluate microspheres as a controlled-release drug delivery system. Microspheres of different combinations of copolymers of lactic and glycolic acid were injected intravitreally in three groups of rabbits. High concentrations were detected in the vitreous of all groups within 24 hours. By 5 days, the levels had gradually decreased, but they remained measurable up to 16 days in the rabbits in which lactide microspheres had been injected. Clearance was more rapid in the lactide/glycolide combination group than in the lactide group.

Animals↗

PubMed1990

Assessment of laser-induced release of drugs from liposomes: an in vitro study.

We evaluated the characteristics of laser-induced release of an antimetabolite (cytosine arabinoside) from temperature-sensitive liposomes. Previous work had shown that a laser would induce breakdown of liposomes when a dye was encapsulated within the liposomes. The present investigation was performed to determine if release could be induced from liposomes that did not contain dye. In vitro, dynamic studies of the release of the drug from liposomes diluted in blood (flowing in a capillary tube at 40 microns/min) were conducted using an argon dye laser operating either in the blue-green mode (488/514 nm) or in the dye mode (577 nm). A radio-labeled marker was used to monitor the drug release. The results showed that the drug could indeed be released from liposomes that did not contain dye, at energy levels that are not likely to be harmful to the tissue. At identical power levels, the release of the drug was greater at 577 nm than at 488/514 nm, probably owing to the greater light absorbance of hemoglobin at the longer wavelength. The results indicate the potential for the site-specific release of a variety of molecules in the ocular vasculature.

Animals↗

PubMed1990

Study of the mechanisms of laser-induced release of liposome-encapsulated dye.

To differentiate the contributing factors (blood or encapsulated dye) leading to the release of encapsulated dyes from liposomes after laser exposure, we initiated an in vitro experimental study. The release of encapsulated calcein was quantified under various experimental conditions in whole blood and in buffered solution containing high-density lipoprotein. Generally, the amount of dye release improved with an increase in laser power, with a maximum release of approximately 80% of encapsulated dye. Because the laser exposure was not continuous, only 80% of each sample was actually exposed. Therefore, 80% release may be thought of as total release. In a lipoprotein/buffer mixture, the 488 nm wavelength caused greater dye release than the 577 nm wavelength, because the maximum absorption of calcein is near 488 nm. The laser wavelength at 577 nm, however, caused greater release in the blood mixture, reflecting the peak absorption of hemoglobin at near 577 nm. At a 3 x higher liposome concentration, the differences in the effects of wavelengths on the release of dye from liposomes were insignificant. Although the 577 nm wavelength is an optimum wavelength for dye and drug delivery in the presence of blood, the 488 nm wavelength might also be suitable for the release of dye from the liposomes.

Animals↗

PubMed1990

Determination of retinal blood velocity with respect to the cardiac cycle using laser-triggered release of liposome-encapsulated dye.

A system of selective angiography has been developed for measuring blood velocity in retinal arteries and veins. It uses a liposome-encapsulated fluorescent dye that is released by application of laser energy in a specific retinal vessel. The method is shown to be able to distinguish between peak systolic velocity and minimum diastolic velocity. In the cynomolgus monkey, the two values were found to differ by approximately a factor of three. It is known that many ocular and systemic diseases affect retinal circulation, and therefore a method of blood velocity measurement with such sensitivity may prove highly valuable in the practice of ophthalmology. As an example, the velocity in a retinal vein was measured before and after partial occlusion by photocoagulation. The two values obtained were significantly different, and the blood velocity was found to return to the value prior to occlusion when measured at 18 days.

Animals↗

PubMed1990

Calcein angiography: a preliminary report on an experimental dye.

Calcein is a new experimental dye for fundus angiography. Injected intravenously, calcein shares most of the characteristics of sodium fluorescein, but it also has some advantages over fluorescein because it lasts longer in the circulatory system. Calcein may be useful in experimental and clinical angiography of the fundus. This study gives the results of angiograms taken with a standard fundus camera after calcein injection.

Animals↗

PubMed1990

Measurement of circulation time in the retinal vasculature using selective angiography.

Retinal circulation times (RCT) and mean circulation time (MCT) in the retinal vasculature have been used to determine the effect of ocular disease on retinal circulation. Both RCT and MCT are usually determined by measuring dye dilution curves during a traditional fluorescein angiogram. The authors present a variation of the dye dilution technique. The primary difference is that a fluorescent dye (carboxyfluorescein or calcein) was encapsulated in liposomes at a very high concentration. The dye was then released at a specific site in a retinal artery by the application of a laser pulse delivered through the pupil of the eye. The heat pulse produced by the laser lysed the liposomes in the targeted vessel, causing a stream of dye to be released. The time it took the dye front to pass through the artery and return through the vein (RCT) was then measured. To clarify the situation, two times were actually measured, the shortest path the dye traveled from the exposure site to a corresponding site on the vein (short RCT) and the longest path through the periphery to venous filling (long RCT). The measurements were made in both cynomolgus monkeys and squirrel monkeys. The local dye release achieved with this method was found to produce a more distinct dye front than traditional angiography while also eliminating the problem of recirculation. Choroidal background fluorescence, a factor that often obscures the dye front in traditional angiography, was minimal. Furthermore, it was possible to make individual measurements on each of the four arteries and to repeat the measurements several times.

Animals↗

PubMed1990

Clearance of fluorescein incorporated into microspheres from the cornea and aqueous after subconjunctival injection.

The clearance of sodium fluorescein from the cornea and aqueous humor of albino rabbits was quantitated after subconjunctival injection of fluorescein entrapped in lactide/glycolide (group 1) and lactide (group 2) microspheres. Seven hours after injection, approximately equal concentrations of fluorescein were measured in both groups in the cornea and aqueous. Fluorescein concentrations in the cornea were more than three times those found in the aqueous. Fluorescein concentrations in both groups decreased at 22 hours, and remained constant at 46 hours. Corneal fluorescein levels in group 2 were slightly higher than in group 1 at 22 and 46 hours. All eyes showed conjunctival inflammatory reaction at the injection sites after 6 days. One eye showed conjunctival necrosis at the injection site after 13 days.

Animals↗

PubMed1990

Comparative study of three fluorescent dyes for angiography: sodium fluorescein, carboxyfluorescein, and calcein.

To compare the characteristics of carboxyfluorescein (CF) and calcein (Calc) with those of sodium fluorescein (Naf), the only fluorescent dye currently in clinical use, we performed angiography in rabbits and primates using these three dyes. The circulation decay time of all dyes was longer in primates than in rabbits. In primates, CF and Calc had longer decay times than Naf. Calc produced the greatest contrast between the choroidal and retinal vasculature. Tissue staining and dye leakage into the vitreous immediately after retinal photocoagulation were minimal with Calc, moderate with CF, and marked with Naf. The limited leakage and longer circulation time of Calc may permit simultaneous angiography and photocoagulation therapy without obscuring the fundus view with leaking dye from the photocoagulated structure.

Angiography↗

PubMed1989

Evaluation of liposome-encapsulated clindamycin in Staphylococcus aureus endophthalmitis.

We investigated the effects of liposome-encapsulated clindamycin in Staphylococcus aureus endophthalmitis induced in rabbits. Clindamycin was encapsulated into liposomes, and suspended in two concentrations: 1 mg/0.1 ml and 2 mg/0.1 ml of clindamycin phosphate. Seven eyes received an intravitreal injection (0.1 ml volume) containing 1 mg of liposome-encapsulated clindamycin and seven eyes received 2 mg. Three control rabbits (six eyes) received drug-free liposomes (three eyes) and no treatment (three eyes). All but one eye treated with clindamycin recovered. All control eyes, including those treated with empty liposomes, were lost to infection.

Animals↗

PubMed1989

External limbal sclerostomy with contact Nd:YAG laser versus surgical knife.

An ab externo limbal sclerostomy was made into the anterior chamber using either a contact neodymium: yittrium aluminum garnet (Nd:YAG) laser probe or a surgical superblade. 5-fluorouracil was injected subconjunctivally as an antiproliferative agent to prevent or decrease cell proliferation and scar formation. The contact Nd:YAG laser use was accompanied by minimal complications. The intraocular pressure was lowered for a longer period in the contact Nd:YAG group compared with the other (knife) group. External sclerostomy with an Nd:YAG laser may offer an alternative in the surgical management of recurrent or intractable glaucoma.

Animals↗

PubMed1989

Corneal ablation in rabbits using an infrared (2.9-microns) erbium: YAG laser.

The authors used a 2.9-microns infrared erbium:YAG (ER:YAG) laser to ablate the central corneas (a 3.5-mm wide, 180-microns deep area) of ten albino rabbits. In group 1 (10 eyes), the central epithelium was removed by mechanical scrubbing to ablate the anterior stroma. In group 2 (10 eyes), a central anterior corneal cap was removed to ablate the midstroma. In group 1, epithelial wound healing occurred in 2 to 3 days. A mild anterior haze was observed with the slit lamp, but it gradually cleared in most eyes of both groups. Histologic specimens were obtained immediately and at 2 and 6 months after ablation for light and transmission and scanning electron microscopy. This acute histopathologic study did not show any endothelial damage even after ablations at 300-microns depth, although there was thermal damage more prominent at the borders of the ablated area for an extension of 40 microns. After 2 months, in the group 1 eyes, the regenerated epithelium appeared normal except for a thickening at the margins of the ablated area. Six months postoperatively there was still epithelial thickening at the margins of the remodeled zone. The basement membrane was present with anchoring filaments and hemidesmosomes. The healing of the anterior (group 1) and midstroma (group 2) occurred with some degree of disorganization of the lamellae and an increase in the population of keratocytes. The density of keratocytes at the ablated areas at 6 months was reduced in comparison with the 2-month observation. By photokeratoscopy, the corneas were smooth and slightly flattened. The authors conclude that corneal ablation using an ER: YAG laser at 2.9 microns may meet the criteria for photorefractive keratectomy (PRK).

Animals↗

PubMed1989

Measurement of retinal blood velocity and flow rate in primates using a liposome-dye system.

A recently developed liposome-dye method was used to make quantitative measurements of blood velocity and volumetric flow rates in the retina of the rhesus monkey. After systemic injection of a liposome-encapsulated fluorescent dye (calcein), the release of a bolus of the dye in the retina was triggered by an ophthalmic argon laser. Initially, calcein was entrapped at a high concentration and the fluorescence of the dye in the lipid vesicle was quenched. After laser exposure, the liposomes released a bolus of dye at the laser exposure site in a specific vessel of the retina. The released dye formed a well-defined, fluorescent wavefront in the exposed artery or vein. By measuring the distance the dye traveled in the vein over a set time interval, it was possible to measure blood velocity in retinal vessels of various diameters, and to calculate volumetric flow rates in those vessels.

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