Biomedical subjects

B Khoobehi

Publications and source records attributed to B Khoobehi.

At least 55 records · Page 3Linked to original sources

PubMed1989

Tissue plasminogen activator in the treatment of experimental retinal vein occlusion.

The thrombolytic effect of recombinant tissue plasminogen activator was studied in 28 randomly selected rabbit eyes to lyse photochemically induced retinal vein occlusion. Occlusion was confirmed histologically and assessed by fluorescein angiography. Sixteen eyes were treated with recombinant tissue plasminogen activator given intravenously and 12 control eyes were given similar volumes of normal saline solution. Fluorescein angiography was performed before and at various intervals after treatment. Four hours after treatment, the retinal vein was patent in 16 eyes (100%) treated with recombinant tissue plasminogen activator, as opposed to one eye (8.3%) treated with normal saline. The results indicate that tissue plasminogen activator is effective in lysing experimentally induced retinal vein thrombi.

Animals↗

PubMed1989

Repetitive, selective angiography of individual vessels of the retina.

Recent experiments have shown the feasibility of using laser or microwave energy for the externally controlled release of both dyes and drugs from temperature-sensitive liposomes (lipid vesicles). In the present study, calcein, a fluorescent dye, was used to improve the in vivo capabilities of this controlled release system. In vitro studies showed that the encapsulation efficiency was improved when compared to carboxyfluorescein, the fluorescent dye used previously. The improved liposome and dye system was used to obtain repetitive, "selective angiograms" in isolated segments of the retina in rabbits and in a nonhuman primate (Macaca mulatta) over a period of up to 2 hours after a single liposome injection. Conventional fluorescein angiography of the primate retina one week after the end of the experiments showed no visible damage, even after more than 400 individual laser exposures.

Angiography↗

PubMed1989

Toxicity and clearance of a combination of liposome-encapsulated ganciclovir and trifluridine.

New Zealand albino rabbits were given intravitreal injections of liposome-encapsulated ganciclovir and trifluridine. Preoperatively and postoperatively, the eyes were evaluated by indirect ophthalmoscopy at different time intervals up to 14 days after injection. At intervals up to 14 days postinjection, the animals were sacrificed, the eyes enucleated, vitreous antiviral levels determined in one group of eyes, and histopathological examination conducted in the other group. The results of this study demonstrated prolonged intravitreal drug levels above the mean inhibitory dose for many strains of virus belonging to the herpes simplex virus family. No evidence of gross retinal toxicity was found by clinical or light microscopic examination of the treated eyes.

Animals↗

PubMed1989

Hyperthermia and temperature-sensitive liposomes: selective delivery of drugs into the eye.

Experiments were performed to quantitate the delivery of two drugs into the eye following hyperthermia. The drugs, cytosine arabinoside and 5-fluorouridine, were encapsulated in temperature-sensitive liposomes. After systemic injection of the liposome-encapsulated drug, microwave hyperthermia was applied to the superior limbus of rabbit eyes in an attempt to locally release the drug. Samples of aqueous humor and vitreous showed significantly higher drug levels in the heated versus the unheated eyes. Histology of the heated eyes showed no significant damage to ocular structures at the power level used to release the entrapped drug. Heating at higher power levels did damage the eye, confirming earlier studies. The potential uses and limitations of this drug delivery modality are discussed.

Animals↗

PubMed1989

Feasibility of blood flow measurement by externally controlled dye delivery.

We are developing a new method of delivering substances locally and repeatedly in the retinal vasculature under external control. This delivery system is based on encapsulating the substance in heat-sensitive lipsomes, which are injected intravenously and lysed by a heat pulse delivered by a laser. The feasibility of using this system with dyes and creating a sharp dye front was tested in vitro and in vivo. The results indicate that the background fluorescence of intact liposomes is minimal but in contrast a dramatic increase in fluorescence is achieved where the dye is released. In vivo tests indicated that only the selected vascular branch fluoresced. Moreover, a sharp dye front could be obtained repeatedly and preserved over significant distances. The presence of a sharp dye front allowed measurements, in vitro, of blood velocity which correlated well (r = 0.985, P less than 0.001) with the average blood velocity values calculated from the known flow rate.

Animals↗

PubMed1989

Reduced toxicity of intravitreally injected liposome-encapsulated cytarabine.

Cytarabine has been demonstrated to be a more potent inhibitor of fibroblast proliferation than fluorouracil. It is, however, more toxic to the retina. We evaluated the ocular toxicity of liposome-encapsulated cytarabine in vitrectomized and nonvitrectomized rabbit eyes by ophthalmic and histopathologic examination. In the vitrectomized group, doses of up to 26 micrograms were nontoxic to the retina. In nonvitrectomized eyes, doses of up to 55 micrograms were nontoxic. Doses of 85 micrograms resulted in loss of ganglion cells and disorganization of photoreceptor cells. The results obtained in this study demonstrated a substantial reduction in ocular toxicity of liposome-encapsulated cytarabine, as compared with a previous study which employed free drug. By virtue of its reduced toxicity, cytarabine in a liposomal vehicle may be of value in the treatment of ocular proliferative disorders.

Animals↗

PubMed1989

Efficacy of liposome-bound amphotericin B for the treatment of experimental fungal endophthalmitis in rabbits.

The efficacy of intravitreally administered amphotericin B was evaluated. Experimental fungal infections were produced by inoculation of Candida albicans organisms into the vitreous cavities of 46 rabbit eyes. After 72 hr, eight eyes received intravitreal injections of 10 micrograms of free amphotericin B; and ten eyes each received 10 micrograms, 20 micrograms, and 40 micrograms of liposome-bound amphotericin B. The remaining eight eyes served as controls: four eyes received dextrose solution and four eyes received empty liposomes. Histopathologic examination 8 weeks after inoculation showed clear vitreous without retinal damage in groups treated with either 10 micrograms free amphotericin B or 20 micrograms of liposome-bound drug. All eyes in the control group and six eyes (60%) in the group treated with 10 micrograms of liposome-bound amphotericin B developed vitreous abscesses with evidence of fungal infection. In eyes treated with 40 micrograms of liposome-bound amphotericin B, fungal infection was successfully eradicated, but retinal damage was detected in all eyes by light microscopy. It is proposed that a reduced toxicity of intravitreally injected liposome-bound drugs is accompanied by reduced efficacy. In the treatment of fungal endophthalmitis, an increased dosage of liposome-bound amphotericin B (above that dosage of free drug which would be required) is suggested.

Amphotericin B↗

PubMed1989

Feasibility test of a new method to measure retinal thickness noninvasively.

There are many devastating ocular diseases that are directly related to an alteration of the retinal or nerve fiber layer thickness, such as glaucoma and macular edema. To diagnose these diseases earlier and to monitor their therapy more sensitively, an accurate measurement of the tissue thickness is needed. Since no clinical method is currently available, we developed and tested a new method capable of measuring noninvasively the retinal thickness. The separation between the images of the anterior and posterior intersections is quantitated by an optoelectronic system. The theoretical performance of the method has been calculated. Tests of the method in a model eye indicated that the measurements were basically diffraction limited, their reproductivity was +/- 9 microns, and their accuracy was 5.5 microns. Tests performed in vivo indicated that two intersections between the laser and the retina are present and correspond to the anterior and posterior surfaces of the retina. These intersections can be resolved and analyzed to yield quantitative data. These encouraging results indicate that this method is feasible and could yield sensitive measurements of the retinal thickness.

Calibration↗

PubMed1988

Intravitreal liposome-encapsulated drugs: a preliminary human report.

Intravitreal liposome-encapsulated antibiotics and antiviral drugs were used in patients with acute toxoplasmosis retinochoroiditis, presumed propionibacterium acne endophthalmitis after cataract surgery, and presumed cytomegalovirus retinitis associated with AIDS. A single intravitreal dose was effective in the treatment of all the conditions. Intravitreal liposomes may prove to be an advantageous drug delivery system for the treatment of chronic intraocular inflammatory disorders.

Acyclovir↗

PubMed1988

Liposome-bound cyclosporine: aqueous and vitreous level after subconjunctival injection.

The concentration of cyclosporine in the aqueous and vitreous humors of albino rabbits was measured, using HPLC at intervals of 24, 48, 96, and 192 hours after subconjunctival injections of 2.5 mg of free or liposome-bound cyclosporine. The aqueous concentration was reasonably high in both groups until day 4: 1050 nanograms per milliliter in the group receiving free cyclosporine, and 1438 nanograms per milliliter in the group receiving liposome-bound cyclosporine. The vitreous concentration was very low in both groups.

Animals↗

PubMed1988

Liposome-bound cyclosporine: retinal toxicity after intravitreal injection.

The retinal toxicity of intraocular liposome-bound cyclosporine was studied in albino rabbits by means of electrophysiology and histopathology. During a followup period of one month, no histopathological or electroretinographic changes were noted using concentrations of 100, 200 and 500 micrograms injected intravitreally.

Animals↗

PubMed1988

Liposome-bound cyclosporine: clearance after intravitreal injection.

The concentration of cyclosporine in the vitreous after intravitreal injection of 100 micrograms of either free or liposome-bound cyclosporine was studied in albino rabbits. We found that the half-life of free cyclosporine was about 6 hours and that of liposome-bound cyclosporine was about 3 days. The finding indicates that liposome-bound cyclosporine prolongs the availability of the drug.

Animals↗

PubMed1988

Externally triggered release of dye and drugs from liposomes into the eye. An in vitro and in vivo study.

Temperature-sensitive liposomes were made with carboxyfluorescein (CF) (100 mM) entrapped in the aqueous compartment. This liposome dye system was used in vitro to evaluate the feasibility of using microwaves as a triggering mechanism for the release of drugs in the anterior chamber of the eye. The in vitro study demonstrated that CF can be released from liposomes in response to a localized temperature rise induced by microwave irradiation. In an in vivo study in rabbits, CF and the antineoplastic agent, cytosine arabinoside, were administered intravenously and selectively released by increasing the temperature of the ciliary body with microwaves. In the eyes receiving liposome-encapsulated dye, the average concentration of CF in the anterior chamber of the heated eyes was 8.0 times higher than in the contralateral unheated control eyes. In the eyes receiving liposome-encapsulated drug, the average concentration of cytosine arabinoside in the aqueous of the heated eyes was 4.1 times higher than the concentration in the contralateral unheated control eyes. The importance of this finding lies in the potential for a new method of targeting the delivery of dyes and drugs to specific sites in the eye.

Animals↗

PubMed1988

Liposome-encapsulated 5-fluorouracil in the treatment of proliferative vitreoretinopathy.

Liposomes, small bilayer vesicles composed of phospholipids, can entrap and thus slow the release of drugs. We investigated the use of liposome-encapsulated 5-fluorouracil (5-FU), an antiproliferative agent, in the treatment of proliferative vitreoretinopathy (PVR) in an animal model. Doses of up to 1.6 mg administered intravitreally in rabbits demonstrated no retinal toxicity by histologic or electroretinographic criteria. In an experimental animal model of PVR, intravitreal injection of homologous rabbit corneal fibroblasts caused tractional retinal detachments in 90% of eyes after 4 weeks. The addition of 1.6 mg of liposome-encapsulated 5-FU decreased the rate of detachment to 32%, compared with 55% for 1 mg of free 5-FU. Thus, liposomal encapsulation of an anti-proliferative agent such as 5-FU may be a valuable adjunct to conventional vitreous surgery in managing PVR.

Animals↗

PubMed1988

A potential method for local drug and dye delivery in the ocular vasculature.

We propose a new drug and dye delivery system that would allow repeated release of substances in the ocular vasculature by an externally controlled mechanism. The substances are encapsulated in heat-sensitive liposomes, which are lysed by locally applying a heat pulse produced by an argon laser. The system was tested by investigating the release of carboxyfluorescein encapsulated in the liposomes. The liposome suspension was incubated at 37 degrees or 38.5 degrees C and irradiated at different powers and pulse durations. The amount of dye released was monitored by fluorophotometry and compared with the concentration obtained when the liposomes were lysed at their transition temperature of 41 degrees C. The results showed that 85% of the encapsulated substance can be released. Moreover, a dramatic contrast was observed between the fluorescence before and after the lysis. Presently the energy density is higher than but close to the maximal permissible exposure for humans. The release mechanism with the short laser pulse appeared to be similar to that present when liposomes were heated slowly.

Coloring Agents↗

PubMed1987

Contact application of Nd:YAG laser through a fiberoptic and a sapphire tip.

We evaluated the effects of Nd:YAG laser energy directly applied to ocular tissue through a fiberoptic and a sapphire tip. All ocular tissue could be easily cut with the maximum 4 watts of energy. The coagulated borders extended 20 to 200 mu into the healthy tissue depending on the speed with which the cutting was performed.

Aluminum Oxide↗

PubMed1987

Intravitreal liposome-encapsulated trifluorothymidine in a rabbit model.

Two groups of albino rabbits received an intravitreal injection of liposome-encapsulated trifluorothymidine. One group underwent a clearance study using high-performance liquid chromatography. The results of this study demonstrated a prolonged vitreal drug level within the range of ID50 for many strains of herpesvirus and human cytomegalovirus (CMV) at 28 days after injection. The eyes of another group were evaluated with preoperative and postoperative indirect ophthalmoscopy, electroretinography, and histologic examination. No retinal toxicity was found.

Animals↗

PubMed1987

Intravitreal injection of liposome-encapsulated ganciclovir in a rabbit model.

The authors determined the intravitreal clearance of liposome-encapsulated ganciclovir. Liposome-encapsulated ganciclovir (84.1 micrograms/0.1 ml) was injected into the vitreous cavity of New Zealand rabbits, which were killed at 24 hours and 7, 14, and 28 days after injection. Total ganciclovir concentrations in the vitreous, up to 28 days, were higher than ID50 (50% inhibitory dose) for different clinical and laboratory strains of viruses belonging to the herpes simplex family.

Acyclovir↗