Abelson M, Howes J, George M
Ophthalmic Research Associates, North Andover, Massachusetts, USA.
J Ocul Pharmacol Ther. 1998 Dec;14(6):533-42. doi: 10.1089/jop.1998.14.533.
Two studies were conducted using the conjunctival provocation test (CPT) model of ocular allergy. The objective of the first study was to evaluate the sensitivity of the CPT model to a topical corticosteroid. Selected was loteprednol etabonate 0.5%, previously found effective in the treatment of ocular allergy and inflammation. The study was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.5% (LE), b.i.d. or q.i.d. Sixty subjects who had a minimum pre-determined allergic response received LE in one eye and placebo in the fellow eye for 28 days from Day 7 to Day 35. Antigen challenges were carried out on Days 0, 7 (baseline), 21 and 35. The primary endpoints were interocular differences in itching and mean redness (the average of ciliary, conjunctival and episcleral vessel beds). LE (either b.i.d. or q.i.d.) was significantly more effective than placebo for reducing mean redness and itching. No clinical or statistically significant changes in intraocular pressure were observed. Based upon the results of Study 1, we used the CPT model to aid in the selection of a concentration of loteprednol etabonate for subsequent studies in environmental seasonal allergic conjunctivitis. This was a randomized double-masked, placebo-controlled, paired-comparison of loteprednol etabonate 0.1%, 0.2% and 0.3%, q.i.d. in 88 subjects. The dosing and testing regimen was similar to the first portion of the study. Loteprednol etabonate, 0.1%, 0.2% and 0.3%, was numerically superior to the placebo in reducing mean redness and itching. At the 20-minute post allergen challenge, the 0.1% concentration was significantly superior (p < 0.05) to the placebo on Visit 4 (2 and 4 hour challenge) in reducing the mean redness; however, LE was only numerically superior in relieving itching. The 0.2% concentration was significantly superior (p < 0.05) to the placebo in the reduction of mean redness and itching on Visit 3 (Day 21) and in reduction of mean redness on Visit 4 (4 hour challenge). The 0.3% concentration was significantly superior (p < 0.05) to the placebo in the reduction of mean redness on all visits, and statistically significant in the reduction of itching on Visit 4 (4 hour challenge). While there were some elevations of IOP with LE 0.2%, they were not clinically significant. In conclusion, the CPT model of ocular allergy is useful in the evaluation of corticosteroids. Furthermore, based upon a dose-response study in this model, 0.2% loteprednol etabonate was selected for further evaluation in environmental seasonal allergic conjunctivitis studies.
两项研究采用眼部过敏的结膜激发试验（CPT）模型进行。第一项研究的目的是评估CPT模型对局部用皮质类固醇的敏感性。选用的是0.5%的氯替泼诺依碳酸酯，此前发现其对治疗眼部过敏和炎症有效。该研究是一项随机双盲、安慰剂对照、配对比较的试验，比较0.5%氯替泼诺依碳酸酯（LE），每日两次或每日四次给药。60名具有最低预定过敏反应的受试者，从第7天至第35天，一只眼睛接受LE治疗，另一只眼睛接受安慰剂治疗，为期28天。在第0天、第7天（基线）、第21天和第35天进行抗原激发试验。主要终点是双眼在瘙痒和平均充血（睫状体、结膜和巩膜上血管床的平均值）方面的差异。LE（每日两次或每日四次）在减轻平均充血和瘙痒方面显著优于安慰剂。未观察到眼压有临床或统计学上的显著变化。基于研究1的结果，我们使用CPT模型来辅助选择氯替泼诺依碳酸酯的浓度，用于后续环境性季节性过敏性结膜炎的研究。这是一项随机双盲、安慰剂对照、配对比较的试验，88名受试者每日四次使用0.1%、0.2%和0.3%的氯替泼诺依碳酸酯。给药和测试方案与研究的第一部分相似。0.1%、0.2%和0.3%的氯替泼诺依碳酸酯在减轻平均充血和瘙痒方面在数值上优于安慰剂。在过敏原激发后20分钟，0.1%浓度在第4次就诊（2小时和4小时激发）时减轻平均充血方面显著优于安慰剂（p<0.05）；然而，LE在缓解瘙痒方面仅在数值上更优。0.2%浓度在第3次就诊（第21天）减轻平均充血和瘙痒以及在第4次就诊（4小时激发）减轻平均充血方面显著优于安慰剂（p<0.05）。0.3%浓度在所有就诊时减轻平均充血方面显著优于安慰剂，在第4次就诊（4小时激发）减轻瘙痒方面具有统计学显著性。虽然0.2%的LE有一些眼压升高，但无临床意义。总之，眼部过敏的CPT模型在评估皮质类固醇方面有用。此外，基于该模型的剂量反应研究，选择0.2%的氯替泼诺依碳酸酯用于环境性季节性过敏性结膜炎研究的进一步评估。
