Prager T C, Kellaway J, Zou Y, Urso R G, McIntyre S, Bedikian A Y
Department of Ophthalmology and Visual Science, University of Texas Health Science Center, Houston 77030, USA.
Anticancer Drugs. 1998 Jul;9(6):515-24.
Ninety-six patients with metastatic melanoma treated with two consecutive tirapazamine-cisplatin combination chemotherapy regimens were followed for signs of therapy-related ocular toxicity. Baseline and follow-up data were obtained such that each patient acted as his own control. A battery of vision-related tests was performed. These included: best corrected visual acuity, color vision, retinal fundus examination and electro-oculograms (EOG). A brief health-related quality of vision test was administered at each follow-up visit to detect and evaluate self-perceived changes in visual status. In the first study, 48 patients received i.v. tirapazamine over 2 h at 260 mg/m2 (group 1) while in the second study 48 patients (group 2) received i.v. tirapazamine at 390 mg/m2. Visual system assessment was conducted at three timepoints: first at baseline, then at 6 weeks post-baseline, i.e. after two courses of chemotherapy and visit two upon discontinuation of therapy. There was no difference in visual acuity between group 1 and group 2 at baseline, follow-up 1 or at follow-up 2. Grouped data indicate that visual acuity was not affected by either dosage of chemotherapy. Group 1 at baseline found 15% below the normal EOG cutoff point, increasing to 23% at follow-up 1 and increasing at follow-up visit 2 to 33%. Group 2 demonstrated the same EOG findings, but the results were more magnified: baseline, 24%; follow-up 1, 44%; and follow-up 2, 44%. After eliminating those with abnormal color vision baselines, 21% (nine of 42) group 1 patients demonstrated abnormal color vision total error scores at follow-up 1 and 16.7% (four of 24) at follow-up 2. Few individuals showed changes in the higher dosage group. With the exception of one person in each dosage group, all changes were along the blue-yellow (tritan) axis, which is associated with acquired color defects. Of 96 patients examined, proven fundus changes were found in only four subjects. These fundus findings included retinal hemorrhages, retinal nerve fiber layer infarcts (cotton wool spots) and small retinal pigment epithelium detachments. There was no systematic statistical significant difference among the various measures of visual system outcome between groups or test times. Data from all tests for individual patients in both groups reveals a sporadic distribution of changes in visual system tests. If toxicity were pronounced, one would expect consistency in the findings and all or most of the assessment tests would be abnormal for a particular patient. However, patients who were abnormal on one measure of acuity were not necessarily abnormal on the other measures.
96例接受连续两个疗程替拉扎明-顺铂联合化疗方案治疗的转移性黑色素瘤患者，接受了与治疗相关的眼部毒性体征的随访。获取了基线和随访数据，使每位患者作为自身对照。进行了一系列与视力相关的检查。这些检查包括：最佳矫正视力、色觉、视网膜眼底检查和眼电图（EOG）。在每次随访时进行一项简短的与健康相关的视力质量测试，以检测和评估自我感知的视力状态变化。在第一项研究中，48例患者以260mg/m²的剂量静脉注射替拉扎明2小时（第1组），而在第二项研究中，48例患者（第2组）以390mg/m²的剂量静脉注射替拉扎明。在三个时间点进行视觉系统评估：首先在基线时，然后在基线后6周，即两个疗程化疗后以及治疗结束时的第二次就诊。第1组和第2组在基线、随访1或随访2时的视力无差异。分组数据表明，视力不受任何一种化疗剂量的影响。第1组在基线时发现15%的患者EOG低于正常临界值，随访1时增至23%，随访2时增至33%。第2组也有相同的EOG结果，但结果更为明显：基线时为24%；随访1时为44%；随访2时为44%。在排除色觉基线异常的患者后，第1组42例患者中有21%（9例）在随访1时色觉总误差评分异常，随访2时为16.7%（4例）。高剂量组中很少有人出现变化。除每个剂量组各有1人外，所有变化均沿蓝黄色（三原色）轴，这与后天性色觉缺陷有关。在接受检查的96例患者中，仅4例发现有眼底改变。这些眼底改变包括视网膜出血、视网膜神经纤维层梗死（棉絮斑）和小的视网膜色素上皮脱离。两组之间或不同测试时间的视觉系统结果的各种测量指标之间没有系统性的统计学显著差异。两组中个体患者的所有检查数据显示，视觉系统检查结果呈散在分布。如果毒性明显，人们会预期结果具有一致性，并且特定患者的所有或大多数评估检查都会异常。然而，在一项视力测量指标上异常的患者在其他指标上不一定异常。
