Comparison of the topical ocular antiallergic efficacy of emedastine 0.05% ophthalmic solution to ketorolac 0.5% ophthalmic solution in a clinical model of allergic conjunctivitis.

PURPOSE: To compare the clinical efficacy of emedastine ophthalmic solution to that of ketorolac ophthalmic solution using a conjunctival allergen challenge model. METHODS: The conjunctival allergen challenge model was used in this randomized, double-masked, single center, crossover study. The titer of allergen that elicited a positive allergic reaction was selected. After at least 14 days, 36 subjects were randomized into two groups of 18 to receive either emedastine in one eye and placebo in the contralateral eye, or ketorolac in one eye and placebo in the contralateral eye. Ten minutes after drug instillation, subjects were challenged with antigen. At 3, 10 and 20 minutes following challenge subjects graded ocular itching and were assessed for hyperemia in conjunctival, ciliary, and episcleral vessel beds. Approximately 14 days later, subjects received the alternate treatment in one eye and placebo in the contralateral eye. They were again challenged with allergen and their responses were rated in the same manner. Ocular discomfort was assessed by the subjects after administration of each study drug. RESULTS: Emedastine significantly (p < 0.05) inhibited ocular itching and redness in vascular beds following topical ocular administration. In contrast, ketorolac failed to significantly inhibit ocular itching or redness in this study. Patient assessment of comfort indicated emedastine was significantly (p < 0.05) more comfortable than ketorolac upon topical ocular administration. CONCLUSION: Emedastine is superior to ketorolac in controlling itching and redness, the cardinal symptom and sign of allergic conjunctivitis.     

Perinatal ocular physiology and ROP in the experimental animal model

In order to overcome the scarcity of premature human ocular tissues and the enormous obstacles to direct examination of immature human ocular vasculatures, a number of animal models have been employed by investigators in order to study various aspects of ROP. A variety of factors may influence selection of the particular model used, but ultimately it is the faithfulness with which the model mimics human ROP that is most important. The validity of the models has been and remains a controversial subject, but evidence appears strong in favor of the beagle puppy model for studying physiology of the ocular vasculatures during perinatal development. Human ROP pathology usually is defined in terms of static morphological state, physiological dysfunction being considerably more difficult to assess. Most of the animal models fall short of mimicking the pathological lesions found in human eyes, especially those associated with severe, or end-stage ROP, yet they do fairly well in terms of mimicking the retinal vascular physiological changes associated with onset of the disease. Unfortunately, where the physiological aspects of ROP are concerned, focus is primarily on the effects of hyperoxia; other physiological factors as well as the potential role of the choroid are essentially ignored. This paper discusses the potential of physiological changes which occur during the perinatal period to play a role in ROP pathogenesis.     

Late-phase reaction in topically induced ocular anaphylaxis in the rat

A cellular late-phase reaction is described in a rat model of topically induced ocular anaphylaxis. Rats were immunized with dinitrophenylated Ascaris suum extract and alum and were tested for active cutaneous anaphylaxis on day 13. Rats with a strong skin test response were selected for ocular challenge with di-DNP-lysine. Macroscopic observation and histologic evaluation were performed at 1, 6, and 24 h. In rats showing a moderate macroscopic ocular response at 1 h, mast cell degranulation was significantly increased at 1 h; no significant increase in eosinophils, neutrophils or lymphocytes was found in the conjunctive of these animals. In rats showing a marked macroscopic ocular response at 1 h, mast cell degranulation was significantly increased at 1 and 6 h; the number of eosinophils was significantly increased at 1 and 6 h, and of neutrophils at 6 h only. At 24 h, neutrophil and eosinophil numbers returned to baseline levels. There was no macroscopic evidence of a late-phase response in either group of animals. Our results suggest that, in keeping with earlier observations in human skin, a strong early response to antigen is required for the development of a late-phase ocular response in the rat.     

Topically induced ocular anaphylaxis in rats immunized with egg albumin

A model of topically induced ocular anaphylaxis was developed. Male Sprague-Dawley rats were immunized by intraperitoneal injections of egg albumin (EA) and alum and topically challenged with EA. Application of EA induced clinical (conjunctival edema) and histologic (mast cell degranulation) signs of anaphylaxis, when the antigen was preceded by topical application of dithiothreitol (DTT), a mucolytic agent. Rats challenged by four EA applications did not differ significantly in clinical edema or mast cell degranulation from those challenged by one EA application at the same (0.1 M DTT) pretreatment level, but there was significantly greater histologically assessed edema in the eyes challenged four times.     

Worm antigen-induced ocular anaphylaxis in rats infected with Nippostrongylus brasiliensis

A model of topically induced conjunctival anaphylaxis has been developed. Male Sprague-Dawley rats were immunized by infection with 3000 Nippostrongylus brasiliensis larvae and challenged topically on the eye 4 weeks later. Application of worm antigen alone did not induce clinical (conjunctival edema) or histologic (mast-cell degranulation) signs of anaphylaxis. Topical challenge with antigen 15 min after topical application of dithiothreitol (DTT), a mucolytic agent, elicited conjunctival edema and mast-cell degranulation within the first hour after challenge. At 6 and 24 hr, no clinical change was evident and conjunctival mast cells had again become granulated. At none of the three intervals (1, 6 and 24 hr) was there a significant increase in neutrophils, lymphocytes, eosinophils or macrophages in tissues from DTT-pretreated, antigen-eyes. The present model of ocular anaphylaxis resembles the ocular component of human hay fever in that sensitization prior to challenge is essential, the antigen is presented topically to the ocular tissues, conjunctival edema is the clinical manifestation and mast cell degranulation characterizes the histologic changes.     

Vitrectomy in penetrating ocular trauma: an experimental study using rabbits

To study the value and the proper timing of vitrectomy in cases of ocular trauma involving the posterior segment, 24 rabbit eyes were traumatized by introducing a steel foreign body and autogenous blood into the vitreous. Twelve eyes underwent vitrectomy, 6 in the first week after trauma ("early") and 6 in the fourth week ("late"). The other 12 eyes, which underwent removal of the foreign body but not vitrectomy, served as controls. Traction retinal detachment did not develop in the 6 early-vitrectomy eyes, but it did occur before vitrectomy in 4 of the 6 eyes of the late-vitrectomy group and in 6 of the 12 control eyes. Iatrogenic cataract and retinal breaks were twice as frequent in the late as in the early group. The data seem to favor early vitrectomy in eyes with posterior-segment trauma. However, in routine clinical practice we advise prompt primary repair and exploration to evaluate the extent of posterior-segment damage, and vitrectomy within 14 days after injury.     

应用于眼表的缓释药物

眼结膜囊内滴滴眼液是眼科疾病常用的治疗方法 ,除住院患者外 ,大部分患者自我用药。所以用药的依从性、点眼液方法的正确性都会影响用药效果。而且眼睛有其自然的保护机制 ,包括眨眼、反应性流泪和泪水从鼻泪管排出。此外 ,还有诸如结膜囊容量小 (结膜囊最多容纳 10 μL 液体而不致溢出 [1 ] )、活跃的泪液分泌 (泪液更新率约 16 %· min- 1 )和角膜屏障作用。一般滴眼液容器每滴容量为 2 5～ 70μL ,很显然超过 80 %的所用滴眼液会溢出 ,加上泪液更新 90 %以上眼结膜囊的局部用药经泪液的稀释、冲洗渗出眼外或经鼻泪道和粘膜而全身吸收。…     

Late-phase reaction and tear fluid cytology in the rat ocular anaphylaxis

Tear fluid cytology is described for the early and late phases of ocular anaphylaxis in actively immunized Sprague-Dawley rats. Tears were collected from both eyes of the rats before challenge and at 1, 2, 4, 6, 8, 10, 12, 24, and 48 h after topical challenge with di-DNP-lysine in one eye and PBS in the fellow eye. Results showed a statistically significant increase in the Aggregate Cell Rating, which represents the aggregate scores in neutrophil, eosinophil, lymphocyte, and atypical epithelial cell levels, in antigen-treated vs control eyes. This report is the first to use a cytologic study of tear film to detect the late phase of ocular anaphylaxis in the rat. Cytology of the tear film could be applied to the study of allergic conjunctivitis in both animals and humans.     

Comparison of ketorolac tromethamine, diclofenac sodium, and loteprednol etabonate in an animal model of ocular inflammation.

PURPOSE: The aim of this study was to compare the anti-inflammatory activities of ketorolac tromethamine 0.4% and 0.1%; diclofenac sodium 0.1%; and loteprednol etabonate 0.5% suspension in an animal model of ocular inflammation. METHODS: An ocular inflammatory response was induced in New Zealand White rabbits by the intravenous (i.v.) administration of 10 microg/kg lipopolysaccharide (LPS). In study animals, 1 eye was treated topically with 50 microL of study medication (n = 8 animals per drug) and the other eye was treated topically with a 50-microL vehicle (buffered saline). In control animals (n = 8), both eyes were treated with vehicle. All animals were treated twice: 2 h and 1 h before LPS challenge. The breakdown of the blood-aqueous barrier in the anterior chamber was measured by fluorophotometry (FITC-dextran 30 mg/kg, i.v. given immediately after LPS challenge). Aqueous prostaglandin E(2) (PGE(2)) levels were measured using an enzyme-linked immunosorbent assay (ELISA) immunoassay. RESULTS: Ketorolac 0.4% resulted in a nearly complete inhibition of endotoxin-induced increases in FITC-dextran and PGE(2) synthesis (P < 0.001 vs. vehicle). Diclofenac 0.1% had much less of an effect on these parameters (P < 0.01 vs. ketorolac 0.4%). Loteprednol 0.5% was no more effective than vehicle at inhibiting increases in FITC-dextran. CONCLUSIONS: Ketorolac has greater anti-inflammatory effects than diclofenac and loteprednol.     

Toxic ocular effects of two fibrinolytic drugs. An experimental electroretinographic study on albino rabbits

The toxic effects on rabbit eyes of 2 intravitreally injected fibrinolytic substances at different concentrations were studied with repeated clinical observations and registrations of the DC ERG. The fellow, control eye of each animal was injected with saline. Urokinase (Ukidan, Serono) (13 rabbits) initially produced aqueous flare (64%), iris hyperaemia (36%) vitreous opacities (27%) and small retinal haemorrhages (18%). 2-3 months after the injection cataract (50%), vitreous opacities (25%) and retinal changes (13%) were observed. The highest dose (10 000 Ploug units) caused reduction of the ERG b-wave, as a sign of retinal toxicity. Tissue activator (D-44, Centre d'immunologie et de biologie Pierre Fabre) (10 rabbits) produced marked aqueous flare (initially 100%, after 2 weeks 50%) and pronounced, persistent vitreous opacities (25% after 2-3 months). At the late stage corneal blood vessels (38%) and cataract (38%) were also found, but only in eyes injected with the highest dose (1000 units), which was retinotoxic as judged by the ERG (reduced b- and c-waves).     

Characterization of ocular and metastatic uveal melanoma in an animal model

PURPOSE: To characterize, in detail, tumor development, malignant cell dissemination, and metastasis in a 10-week animal model of uveal melanoma. METHODS: One million 92.1 human primary uveal melanoma cells were injected into the suprachoroidal space of the right eye of 27 immunosuppressed albino rabbits. Intraocular tumor growth was monitored weekly by fundoscopy and by ultrasonography at the end of the experiment. To document the progression of the disease, one animal per week was killed. The enucleated eyes, lungs, and livers were macroscopically examined and histopathologically studied by hematoxylin and eosin, periodic acid-Schiff, and immunohistochemistry. Mononuclear layers isolated from the rabbits' blood samples were cultured. RESULTS: Histopathology showed intraocular tumors in 89% of the animals. Tumor growth was found 1 week after cell inoculation, and by the end of the experiment large tumor masses were observed. Microscopic pulmonary metastatic foci were first observed 4 weeks after cell injection. By the end of the experiment, all the animals had metastasis to the lungs. Interestingly, 18% of the animals also had micrometastasis to the liver. Viable adherent uveal melanoma cells were successfully isolated from peripheral blood and grown in vitro. CONCLUSIONS: In this study, most rabbits developed intraocular tumors followed by lung metastasis, and some of these rabbits later developed liver micrometastases. This novel source of research material warrants a follow-up longer than 10 weeks to further explore the pathophysiologic bases of liver involvement commonly encountered in humans. The success in the isolation and culture of circulating malignant cells in this animal model suggests that it might be worthwhile to explore the application of this technique to the management of patients with primary uveal melanoma.