摘要:

ABSTRACTWe wished to determine the stability of frozen, refrigerated, and room temperature topical cyclosporine 1% in artificial tears (Tears Plus®). Cyclosporine 1% eye drops were made in artificial tears prior to the manufacturers recommendations of using a lipid soluble vehicle, such as olive oil. Patients preferred the artificial tears preparation over the oil based cyclosporine product. Because of the good clinical response and the reluctance of patients to change to the oil vehicle product, we determined the stability of cyclosporine 1% in artificial tears. Cyclosporine 1% was prepared in artificial tears (polyvinyl alcohol 1.4% and povidone 0.6%) by adding 1 ml of the injectable (50mg/ml) cyclosporine into 4 ml of the artificial tears solution. Each bottle was frozen at −20° C for one month and then the cyclosporine concentration was determined after thawing and refrigeration or storage at room temperature. Refrigerated stability was determined after thawing for up to 28 days and room temperature stability was determined for up to 1 week after thawing. Cyclosporine concentration was determined by HPLC analysis. None of the samples exhibited any significant loss of cyclosporine at any time period. Frozen cyclosporine appears stable when frozen in a 1% solution for one month. Cyclosporine 1% in artificial tears is stable for up to 28 days in the refrigerator or at least 7 days at room temperature. Because of the ease of preparation, the proven clinical effectiveness of the product and better patient acceptance, we continue to make this prod

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.1

年代:1996

数据来源: MAL

摘要:

ABSTRACTControlled release ocular inserts have been found to increase the amount of drug which is absorbed into the aqueous humour when compared to eyedrops. Systemic absorption following delivery using a controlled release insert has been found to be dependent on the release rate of the insert. The objective of this study was to determine if ocular inserts affect drug absorption into other ocular tissues such as the conjunctiva and iris-ciliary body. Ocular absorption studies were performed using albino rabbits and ethylene-vinyl acetate controlled release devices containing timolol maleate. A compartmental model previously developed to simulate ocular absorption following eyedrop administration was modified and used to simulate these experiments.The conjunctival absorption coefficient calculated by the model and the AUC of the conjunctiva per μmol of delivered drug were found to be 2.7 and 42 times higher, respectively, for the ocular insert as compared to eyedrop administration. The increased conjunctiva absorption was likely the result of reduced tear mixing, which caused a high local concentration of timolol between the insert and the conjunctiva. The AUC of the iris-ciliary body per μmol of delivered drug was found to be 24 times higher for the ocular inserts as compared to eyedrop administration. The AUC of the iris-ciliary body was found to be 1.4 times higher than the AUC of the aqueous humour for eyedrop administration, but 9 times greater for delivery via the ocular inserts. Thus, the increased absorption into the iris-ciliary body and aqueous humour observed for ocular inserts is partially the result of an increase in the amount of drug which enters these tissues via penetration across the conjunctiva and scler

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.5

年代:1996

数据来源: MAL

摘要:

ABSTRACTThe production of 12-hydroxyeicosatetraenoic acid by the corneal epithelium of several species has been extensively reported yet the controversy over the exclusive production of the (S) epimer (a lipoxygenase-derived metabolite) endures. Incubation of calf corneal epithelial microsomes (3 mg/ml) with arachidonic acid and NADPH resulted in the formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE). The synthesis of 12-HETE was inhibited by SKF-525A and clotrimazole, selective inhibitors of cytochrome P450 dependent activities, but not by indomethacin or BW-755C, inhibitors of cyclooxygenase and lipoxygenase activities, respectively. Chiral analysis revealed the presence of both enantiomers; however, the R isomer was the predominant one, i.e., 91±5% vs. 9±5% for the R and S enantiomers, respectively. Since the R enantiomer is the product of a cytochrome P450-mediated reaction, it suggests that the major metabolic activity in these microsomes is cytochrome P450-dependent and supports the claim for cytochrome P450 reactions in this ocular tissu

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.19

年代:1996

数据来源: MAL

摘要:

ABSTRACTThe protective efficacy of sodium hyaluronate (Na-HA) on the corneal endothelium against the damage induced by sonication was investigated using enucleated rabbit eyes and Na-HA fluorescence labeled with 5-aminofluorescein (FA-HA). The anterior chamber was reformed by injecting a 1 % solution of FA-HA, and then sonication, irrigation and aspiration were performed in the anterior chamber using a phaco-needle attached to phacoemulsification and aspiration (PEA) equipment. The protective efficacy was evaluated by the area of damaged corneal endothelium. When the anterior chamber was reformed by the solution of FA-HA with a molecular weight of 2010 × 103(FA-HA (2010 × 103) group), most of the FA-HA was eliminated within 20 seconds after starting the irrigation and aspiration, and the area of damaged endothelium was the same with the case when the FA-HA was not pre-injected (Control group). On the other hand, when the anterior chamber was reformed by the solution of FA-HA with a molecular weight of 1130 × 103(FA-HA (1130 × 103) group), the FA-HA was gradually eliminated after mixing with an irrigating solution, and the area of damaged endothelium was significantly smaller than those of the Control and FA-HA (2010 × 103) groups. These results suggest that the corneal endothelial damage induced by PEA can be avoided by pre-injecting a viscoelastic material which can remain in the anterior chamber during

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.27

年代:1996

数据来源: MAL

摘要:

ABSTRACTIntracameral injection (ICI) of antibiotics and steroid is an effective method to deliver drugs into eyeballs, and rapidly achieve therapeutic concentrations. The high intraocular concentrations, however, that occur by such injections can harm the corneal endothelium. The MTT assay, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], has been used to test cytotoxicity of five antibiotics (including amphotericin-B, colistin-M, sulbenicillin, amikacin, cephradine) and a steroid, betamethasone, to cultured porcine corneal endothelial cells.The third passage of porcine corneal endothelial cells were plated into 96-well microtitration plates for drugs exposure. Cytotoxicities of the six drugs in different concentrations were compared, using exposure time as an independent variable.In its original and 10-fold ICI dose, only amphotericin-B among the six tested drugs showed significant cytotoxicity; the other drugs were considered safe. In a 100-fold ICI dose, amphotericin-B, colistin-M, and sulbenicillin were all toxic.Although a cell culture system utilizing the MTT assay is anin vitromethod of testing for drug toxicity to the corneal endothelium, it nevertheless offers the advantages overin vivomethods. It is rapid, convenient, and economical. Large numbers of toxic compounds can be compared simultaneously, so that relative toxicities among different drugs and concentrations can be obtained, and be a guide for determining ICI dose, or as a reference for furtherin vivotesting.

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.35

年代:1996

数据来源: MAL

摘要:

ABSTRACTThe pathogenesis of myopia and the mechanism of atropine in preventing myopic progression have long been widely discussed. Recent studies with animals have pointed to the possible role of the muscarinic receptor of the retina itself in regulating eye growth. This paper stresses that, for myopia in humans, the importance of accommodation still holds. Twenty-five recovered cases of previous traumatic hyphema, occurring under age 16, were collected. For four or more years, the patients were examined for ocular refraction, axial length, intraocular pressure, gonioscopy and accommodation time; the latter was measured with an accommodopolyrecorder. Data from injured eyes and fellow eyes were compared and analyzed. The results indicated that, in the injured eyes the refractive status was invariably less myopic than in the fellow eye, and was not related to intraocular pressure. In injured eyes the accommodation time was highly correlated with the extent of angle recess. And the difference of anisometropia was also related to the extent of angle recess. These observations showed that there was a significant correlation between the degree of myopic anisometropia and the impairment of accommodation.

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.45

年代:1996

数据来源: MAL

摘要:

ABSTRACTThe concentration of neuropeptide Y in the aqueous humor (NPYaq) did not change during the circadian cycle in rabbits. However, NPYaqalso did not decrease after superior cervical ganglionectomy or preganglionic section of the cervical sympathetic trunk (decentralization). Nor did NPYaqchange after either stimulation, with para-aminoclonidine, or blockade, with rauwolscine, of prejunctional ocular α2-adrenergic receptors. Therefore, NPYaqdoes not reflect NPY release from ocular sympathetic nerves in rabbits

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.51

年代:1996

数据来源: MAL

摘要:

ABSTRACTSustained intravitreal levels of dexamethasone may be useful in the treatment of proliferative vitreoretinopathy (PVR). The preparation and evaluation of an implantable system for intravitreal sustained release of dexamethasone is described. Pellets of dexamethasone were coated in biocompatible, nonerodible polymers and the release rate tested in vitro. Devices were then implanted in the rabbit vitreous and the in vivo release rate and corresponding steady state vitreous concentration determined. Toxicity was also evaluated by histopathology and electrographic examination.Devices released dexamethasone at approximately 1 ug/hrin vitroand 1.5 ug/hrin vivo. When implanted into the vitreous intravitreal concentrations of approximately 2.5 +/− 1.2 ug/hr were maintained for over 3 months. Devices were well tolerated with no evidence of inflammation or retinal abnormalitie

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.57

年代:1996

数据来源: MAL

摘要:

ABSTRACTThe retina contains a high amount of taurine which suggests a role in retinal function. The mongolian gerbil is well studied in stroke because of its incomplete circle of Willis. Two groups of gerbils were used: one served as control and the other was subjected to unilateral left carotid occlusion during 30 minutes, followed by 60 minutes of reperfusion. Gerbils were selected by ocular fundus and only sensitive gerbils were retained for the experimentation. We studied the level of taurine in gerbil retina of different ages: 3, 9, 15 and 24 months old (sham operated and ischemic groups).Level of taurine was determined by HPLC/electrochemical method.Compared to sham operated groups, level of taurine was significantly increased in ischemic groups for all ages studied.In the sham operated groups, level of taurine was low at birth, reached a plateau, and then decreased with aging.In the ischemic groups, level of taurine regularly increased from 3 to 24 months of age.With comparison evaluated for each age (modification ischemic versus sham operated groups expressed in percentage), level of taurine was quite equal at 3 and 9 months of age, but increased in 15 and 24 months old gerbils.

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.65

年代:1996

数据来源: MAL

摘要:

ABSTRACTWe determined the effects of endothelin-1 on optic nerve head (ONH) blood flow in anesthetized cats. Endothelin-1 (50-2500 pmol) injected into the vitreous produced a dose-related and sustained decrease (22 ± 6% by 500 pmol and 36 ± 11% by 2500 pmol) in the ONH blood flow. Blood pressure (BP) and heart rate (HR) remained, however, unchanged. In contrast, intravenous (i.v.) injected endothelin-1 (0.004-0.4 nmol kg−1) produced a dose-related and short-lasting increase in the ONH blood flow; its maximum increase by 0.4 nmol kg−1 was 135 ± 34%. Endothelin-1, at 0.4 nmol kg−1, i.v., produced a transient decrease followed by a more sustained increase in BP, but had no remarkable effect on HR. The increase in ONH blood flow by i.v. injection of endothelin-1 was abolished by NG-nitro-L-arginine methyl ester (L-NAME, 5 mg kg−1min−1, i.v.). The suppresion of blood flow by L-NAME was reversed by the addition of L-arginine (50 mg kg−1min−1). Pressor responses to endothelin-1 (0.4 nmol kg−1, i.v.) were augmented in the presence of L-NAME, but reversed in combination with L-arginine. These findings suggest that i.v. injection of endothelin-1 causes NO release from endothelial cells which increases ONH blood flow, whereas intravitreal injection of endothelin-1 decreases ONH blood flow by its vasoconstrictive effect. Different populations of ET receptors on vascular smooth muscles or endothelial cells would reflect the opposing effec

ISSN:8756-3320    

DOI:10.1089/jop.1996.12.75

年代:1996

数据来源: MAL