Tissue plasminogen activator(tPA) is a fibrin-specific fibrinolytic agent that has recently been shown to be effective in accelerating the clearance of hyphema. Intravitreal injection of tPA can promote rapid lysis of experimental intravitreal fibrin clots. The purpose of this study was to investigate the efficacy of intravitreal tPA injection for the treatment of vitreous hemorrhage in normal phakic non-vitrectomized rabbit eyes. Vitreous hemorrhages were produced by intravitreal injections of 0.05 ml of autologous whole blood in 25 rabbit eyes with intact vitreous. The injection of 25 or 100 micrograms of tPA in 15 eyes resulted in the clearance of vitreous hemorrhage in 99 +/- 19 or 34 +/- 6.5 days, respectively. This was significantly faster than in the control eyes in which the clearance was not seen until 131 +/- 17 days later. No tractional retinal detachment was observed.
Animals ; Rabbits ; Retina/drug effects ; Tissue Plasminogen Activator/*therapeutic use ; Vitreous Body/drug effects ; Vitreous Hemorrhage/*drug therapy

Our previous experimental work with tissue plasminogen activator (TPA) suggested the possibility of the clearance of vitreous hemorrhage by repetitive injections of low-dose TPA. We therefore investigated in rabbits the effect of both repeated injections of TPA and the change of the integrity of the vitreous body on the clearance of vitreous hemorrhage. Vitreous hemorrhage was produced by intravitreal injection of 0.05 ml of autologous whole blood in the pigmented rabbit eyes with intact vitreous or gas-compressed vitreous. Three intravitreal injections of 3-g TPA (total dose of 9 microgram), separated by 7-day intervals, were performed. The endpoint for vitreous hemorrhage clearance was defined as clear visualization of the posterior central retina of the rabbits. Regardless of whether gas compression vitrectomy was performed, repeated injections of low-dose TPA resulted in rapid clearance of fresh vitreous hemorrhage in approximately two to three weeks after the last TPA injection. No evidence of retinal toxicity was seen in all experimental groups. Repetitive injections of low-dose TPA may be effective in the treatment of fresh vitreous hemorrhage.
Animals ; Disease Models, Animal ; Injections ; Rabbits ; Tissue Plasminogen Activator/*administration & dosage/therapeutic use ; Vitreous Body/drug effects ; Vitreous Hemorrhage/*drug therapy

OBJECTIVETo evaluate the experimental induction of posterior vitreous detachment (PVD) by intravitreous injection of hyaluronidase and perfluoroethane (C(2)F(6)).

METHODSFifteen rabbits (30 eyes) were divided into 3 experimental groups,the contralateral eyes in same animals served as the controls. Eyes in group A and B were received two vitreous injections of 15 IU of hyaluronidase at an interval of 5 d. The eyes in group C and all control eyes were injected with balanced salt solution (BSS). Seven days after injection, the experimental eyes in group A and C were received 0.5 ml of Fifteen rabbits (30 eyes) were divided into 3 experimental groups, the contralateral eyes in same animals served as the controls. Eyes in group A and B were received two vitreous injections of 15 IU of hyaluronidase at an interval of 5 d. The eyes in group C and all control eyes were injected with balanced salt solution (BSS). Seven days after injection,the experimental eyes in group A and C were received 0.5 ml of C(2)F(6) injection. The ocular and retinal signs were examined for 8 following weeks and then killed for histological examination.

RESULTFive eyes in group A (100.0%) showed complete separation of the vitreous cortex from the retina (PVD), three eyes in group B(60.0%) showed partial PVD, and no PVD was detected in group C and all control eyes. On electroretinogram no significant difference was found in amplitude and latency of a-(or b-) wave in both experimental and control eyes, between before and after experiments. No evidence of ocular or retinal toxicity was revealed by light or scanning electronic microscopy in all eyes.

CONCLUSIONVitreous injection of hyaluronidase combined with perfluoroethane, as a safety method, can induce posterior vitreous detachment without mechanical vitrectomy.

Animals ; Electroretinography ; Female ; Fluorocarbons ; pharmacology ; Hyaluronoglucosaminidase ; pharmacology ; Male ; Ophthalmologic Surgical Procedures ; methods ; Rabbits ; Vitreous Body ; drug effects ; surgery ; ultrastructure ; Vitreous Detachment ; etiology

The aim was to investigate the proteolytic activity of plasmin and its long-term complications. Plasmin was injected into the vitreous cavity of rabbits' eyes. Slit lamp biomicroscopy and electroretinography were performed. Rabbits were serially sacrificed at four months, and globes fixated and prepared for light and transmission electron microscopy. In both the plasmin-injected and control eyes, electroretinography showed a transient decrease in the amplitude, but this recovered to the baseline level in a week. Under the light microscope, the plasmin-treated eyes had a smooth retinal surface, implying separation of the vitreous cortex from the retina. In the control eyes, the collagen fibers remained on the retinal surface. By transmission electron microscopy, the plasmin-treated eyes showed a vitreous-free retinal surface, but no vitreoretinal separation was observed in the control eyes. Plasmin induces a cleavage between the vitreous and the internal limiting membrane, with no long-term complications, so may be a useful pharmacologic adjunct to vitrectomy.
Animals ; Electroretinography ; Fibrinolysis/*drug effects ; Fibrinolytic Agents/*pharmacology ; Injections ; Plasmin/*pharmacology ; Rabbits ; Research Support, Non-U.S. Gov't ; Retina/drug effects/physiology ; Vitreous Body/*drug effects ; Vitreous Detachment/*chemically induced/pathology

Intravitreal fibrin clots were produced by intravitreal injection of 0.2 ml of autologous plasma in 62 rabbit eyes. The intravitreal injection of 0.25 micrograms or more of tissue plasminogen activator(tPA) resulted in a total clearing of intravitreal fibrin within one day in all treated eyes. This was significantly faster than in the control eyes, in which complete clearing was not seen until 8 days later. This represents the plateau on the dose-response curve in doses ranging from 0.25 to 200 micrograms. With light microscopy and transmission electron microscopy, retinal toxicity was demonstrated in eyes enucleated seven days after injection of 25 micrograms or more of tPA. This study demonstrates that tPA was effective and safe at 12.5 micrograms or less in clearing intravitreal fibrin in an experimental model. These results suggest that low dosages of tPA, probably of 3 micrograms or less, may be useful in the treatment of severe postvitrectomy fibrin formation seen clinically.
Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Fibrinolysis/*drug effects ; Rabbits ; Retina/drug effects/pathology ; Tissue Plasminogen Activator/*toxicity ; *Vitreous Body

To simulate the posterior vitreous detachment (PVD) in the rabbit, 1 IU hyaluronidase and/or 0.2 ml of perfluoropropane gas was intravitreally injected. Ophthalmoscopic, light microscopic examination prepared by cryotechnique, electron microscopic examination, and electroretinogram were done on the 3rd and 28th postoperative days. As a result, the eyes undergone simultaneous intravitreal injection of 1 IU hyaluronidase and 0.2 ml perfluoropropane gas showed membranous structure split from the internal limiting membrane of the superior retina in 3 days after injection. The eyes also demonstrated membranous structure separated from the superior retina after 28 days, simulating vitreous detachment. On the contrary, neither agent alone induced vitreous detachment. No toxic retinal changes associated with simultaneous intravitreal injection of 1 IU hyaluronidase and 0.2 ml perfluoropropane gas were observed. Therefore, with a future support by histologic examination other than cryotechnique and by immunohistochemical analysis, the simultaneous intravitreal injection of perfluoropropane gas and hyaluronidase would be a promising method to induce vitreous detachment in non-vitrectomized eye.
Animals ; Drug Combinations ; Electroretinography ; Eye Diseases/chemically induced/pathology ; Fluorocarbons/*toxicity ; Hyaluronoglucosaminidase/*toxicity ; Injections ; Rabbits ; Retina/drug effects/physiology ; Vitreous Body/*drug effects/pathology

BACKGROUNDManganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI.

METHODSForty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices.

RESULTSBetween the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2+ were 5087 ± 666 ng/ml, 22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups.

CONCLUSIONSThe corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body.

Administration, Topical ; Animals ; Aqueous Humor ; drug effects ; metabolism ; Cornea ; drug effects ; metabolism ; Epithelium, Corneal ; drug effects ; metabolism ; Magnetic Resonance Imaging ; methods ; Male ; Manganese ; administration & dosage ; pharmacokinetics ; pharmacology ; Rabbits ; Visual Pathways ; drug effects ; Vitreous Body ; drug effects ; metabolism

This study was designed to determine the maximal safe drug concentration of intravitreal ciprofloxacin in phakic rabbit eyes. Twenty-two eyes of New Zealand pigmented rabbits received midvitreal ciprofloxacin of 100, 200, 400, 600 or 800 microgram in BSS Plus, or BSS Plus only. Retinal toxicity was dose-dependent as determined with electroretinography, light microscopy, and transmission electron microscopy. At a dose of greater than 400 microgram, disorganization of the outer segments was a main pathological finding in transmission electron microscopy. We evaluated retinal function by measuring the electroretinograms for a graded series of flash intensities and by fitting electroretinogram b-wave amplitudes to the Naka-Rushton equation. At a dose of greater than 600 microgram, Rmax was significantly decreased and log K was significantly increased. N-value tended to decrease. A decrease of b-wave amplitudes caused by retinal toxicity could be detected very sensitively with lower luminance stimuli. Determination of retinal toxicity with lower luminance electroretinography revealed a significant decrease of b-wave amplitudes at a dose of greater than 400 microgram. We concluded that a safe dose of intravitreal ciprofloxacin in phakic rabbit eyes was 200 microgram in phakic eyes.
Animals ; Ciprofloxacin/administration & dosage/*toxicity ; Dose-Response Relationship, Drug ; Electroretinography/drug effects ; Injections ; Lens, Crystalline ; Photic Stimulation ; Rabbits ; Retina/*drug effects/pathology/physiopathology ; Rod Cell Outer Segment/drug effects/pathology ; Vitreous Body

Acetates ; pharmacology ; Animals ; Bicarbonates ; pharmacology ; Drug Combinations ; Endothelium, Corneal ; drug effects ; pathology ; Female ; Glutathione ; pharmacology ; Hydrogen-Ion Concentration ; Minerals ; pharmacology ; Ophthalmic Solutions ; pharmacology ; Rabbits ; Retina ; drug effects ; pathology ; Sodium Chloride ; pharmacology ; Vitreous Body ; drug effects

PURPOSE: This study investigated firstly the change of intraocular pressure (IOP) after injection of intravitreal triamcinolone acetonide (IVTA) for the treatment of macular edema and secondly the factors that influence these changes. METHODS: A prospective, non-comparative study was performed in 60 patients at Kangnam Sacred Heart Hospital from October 2003 to September 2004. All the patients received 4-mg IVTA injection. RESULTS: Mean IOP was elevated from the day after injection and peaked at 20.5 mmHg after 2 months (p=0.000). Twenty-six eyes (43.3%) showed significant IOP elevation. IOP was not controlled despite full glaucoma medication in 7 (11.7%) eyes. Two eyes underwent filtering surgery. Younger age was a statistically significant predictive factor for IOP elevation (p=0.009). CONCLUSIONS: In this study, patients who needed filtering surgery developed an IOP spike within one week after the injection. Therefore, clinicians should consider checking IOP at the end of the first week. Furthermore, greater cautions is mandatory with relatively younger patients.
Adult ; Aged ; Aged, 80 and over ; Female ; Glucocorticoids/*administration & dosage/*adverse effects/therapeutic use ; Humans ; Injections ; Intraocular Pressure/*drug effects ; Macular Edema, Cystoid/*drug therapy/*physiopathology ; Male ; Middle Aged ; Prospective Studies ; Triamcinolone Acetonide/*administration & dosage/*adverse ; Vitreous Body