Framme Carsten, Schuele Georg, Roider Johann, Birngruber Reginald, Brinkmann Ralf
University Eye Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany.
Lasers Surg Med. 2004;34(3):206-15. doi: 10.1002/lsm.20022.
The therapeutic effect of laser treatment for macular diseases is related to the damage to the retinal pigment epithelium (RPE) and the subsequent restoration of the defect due to RPE proliferation. In contrast to conventional laser treatment, it is possible to damage the RPE selectively and to spare the photoreceptors by using repetitive microsecond laser pulses. It was the aim of the study to investigate the influence of pulse duration and number of pulses on angiographically and ophthalmoscopically visible retinal damage thresholds in order to optimize treatment modalities.
STUDY DESIGN/MATERIALS AND METHODS: In total, 625 laser lesions with various parameters were applied to the retina in 11 eyes of 6 Chinchilla breed rabbits using an experimental laser system (Nd:YLF at 527 nm). Pulse duration (1.7 microseconds and 200 nanoseconds) and number of pulses (100, 10, and 1 pulses) were varied at a constant repetition rate of 100 Hz. Damage thresholds were determined in terms of ophthalmoscopic and fluorescein angiographic visibility, and the therapeutic window (TW; angiographic ED(50) vs. ophthalmoscopic ED(50)) as well as the safety range (SR; angiographic ED(84) vs. ophthalmoscopic ED(16)) between both thresholds were calculated. Selected laser lesions were evaluated by histology.
Generally, the ED(50) radiant exposure for angiographic visibility decreases for shorter laser pulses and with an increase in the number of pulses. The TW for both pulse durations (1.7 microseconds and 200 nanoseconds) was wider with 100 pulses than with single pulses. The widest TW was found for 100 pulses at 200 nanoseconds pulse duration (5.9-fold above the angiographic threshold), and the smallest TW with a factor of 1.6 was found for 1.7 microseconds single pulses. In terms of SR, only irradiation with 100 pulses at 200 nanoseconds pulse duration was associated with a ratio >2. Independently of pulse duration, histological examination of laser sites 1 hour after irradiation revealed widely intact photoreceptors, while the underlying RPE was damaged.
Pulse duration and number of pulses have a significant influence on RPE damage thresholds and consecutively on TW and SR. Because fundus pigmentation in humans may vary intra- and interindividually by a factor of 2, a large TW and ideally also a large SR should be ensured in a clinical treatment context. In rabbits, the safety range with 200 nanoseconds pulses is higher than with the pulse duration of 1.7 microseconds currently in clinical use. These findings suggest the need for clinical pilot studies to prove whether these results can be transposed to the situation in humans.
激光治疗黄斑疾病的疗效与视网膜色素上皮（RPE）损伤以及随后因RPE增殖而修复缺损有关。与传统激光治疗不同，使用重复微秒激光脉冲有可能选择性地损伤RPE并使光感受器免受损伤。本研究的目的是调查脉冲持续时间和脉冲数量对血管造影和检眼镜可见的视网膜损伤阈值的影响，以优化治疗方式。
研究设计/材料与方法：使用实验激光系统（527nm的Nd:YLF）对6只龙猫品种兔子的11只眼睛的视网膜总共施加了625个具有不同参数的激光损伤。在100Hz的恒定重复率下改变脉冲持续时间（1.7微秒和200纳秒）和脉冲数量（100、10和1个脉冲）。根据检眼镜和荧光素血管造影的可见性确定损伤阈值，并计算治疗窗口（TW；血管造影ED(50)与检眼镜ED(50)）以及两个阈值之间的安全范围（SR；血管造影ED(84)与检眼镜ED(16)）。对选定的激光损伤进行组织学评估。
一般来说，对于较短的激光脉冲以及随着脉冲数量的增加，血管造影可见性的ED(50)辐射曝光量会降低。两种脉冲持续时间（1.7微秒和200纳秒）下，100个脉冲时的TW比单个脉冲时更宽。在200纳秒脉冲持续时间下100个脉冲时发现的TW最宽（比血管造影阈值高5.9倍），而在1.7微秒单个脉冲时发现的TW最小，为1.6倍。就SR而言，只有在200纳秒脉冲持续时间下100个脉冲的照射其比值>2。与脉冲持续时间无关，照射后1小时对激光部位的组织学检查显示光感受器广泛完整，而其下方的RPE受损。
脉冲持续时间和脉冲数量对RPE损伤阈值有显著影响，进而对TW和SR也有显著影响。由于人类眼底色素沉着在个体内和个体间可能相差2倍，在临床治疗中应确保有较大的TW，理想情况下也应有较大的SR。在兔子中，200纳秒脉冲的安全范围高于目前临床使用的1.7微秒脉冲持续时间。这些发现表明需要进行临床前期研究，以证明这些结果是否可以应用于人类情况。
