Department of Ophthalmology, St. Franziskus Hospital, Münster, 48145, Germany.
Graefes Arch Clin Exp Ophthalmol. 2011 May;249(5):639-44. doi: 10.1007/s00417-010-1524-5. Epub 2010 Oct 3.
In phase III trials, the therapeutic efficacy of anti-VEGF therapy with ranibizumab (Lucentis) in patients with choroidal neovascularization due to AMD was demonstrated in a 24-month period with monthly injections. Other studies and models suggested that flexible reinjection regimens can provide similar visual results. The aim of the present study was to evaluate the flexible, predominantly visual acuity-driven ranibizumab retreatment regimen in clinical practice in Germany.
Best-corrected visual acuity (VA, logMAR) and central retinal thickness (CRT) were recorded initially and every 4-6 weeks during follow-up (mean follow-up 75.5 weeks) from 152 eyes. All eyes were treated initially 3 times with ranibizumab at 4-weekly intervals, and retreated with another three injections if visual acuity decreased and/or CRT increased (>100 μm), and/or if new angiographic leakage and/or new retinal hemorrhages developed. Visual acuity development was analyzed in the whole group. A quartile analysis was also performed, and visual course was correlated with CRT. In all groups, numbers and times of reinjections within the first year were registered and analyzed.
An increase in mean VA of 0.14 (SD 0.22) logMAR could be observed after 3 months, but during follow-up from months 3 to 12 the mean visual acuity decreased again by 0.14 (SD 0.24) logMAR, and was similar to the initial VA despite several reinjections (mean five injections). Stratification of patients according to the visual effect after 3 months (quartile analysis) demonstrated a differentiation of the visual course. Quartile 1, with the largest increase in VA after 3 months and reduction of the retinal edema, lost this positive effect during follow-up (100% of eyes received further injections). In contrast, quartile 2, with a minor increase, and quartile 3 demonstrated a stabilized response during follow-up (80% reinjections), while quartile 4 demonstrated a further loss in VA despite reinjections initially and during follow-up (60% reinjections).
The flexible, predominantly visual acuity-driven ranibizumab retreatment regimen employed in clinical practice in Germany generally resulted in a loss of initially gained VA during 12 months of follow-up. Subgroup analysis showed that this negative effect was especially present in patients with relatively bad VA at treatment entry as well as the highest visual gain. Because this result demonstratse that a visual acuity-related retreatment regimen can not preserve the initial positive treatment effects with ranibizumab in exudative AMD, a revision of this schematic retreatment regimen used in Germany and adaptation to more sensitive retreatment parameters is recommended.
在三期临床试验中，雷珠单抗（Lucentis）的抗 VEGF 治疗在 AMD 引起的脉络膜新生血管患者中，通过每月注射一次，在 24 个月的时间内显示出了治疗效果。其他研究和模型表明，灵活的再注射方案可以提供类似的视力结果。本研究的目的是评估在德国临床实践中灵活的、主要基于视力的雷珠单抗再治疗方案。
从 152 只眼中最初记录最佳矫正视力（VA，logMAR）和中心视网膜厚度（CRT），并在随访期间每 4-6 周记录一次（平均随访 75.5 周）。所有患者最初均以 4 周的间隔接受 3 次雷珠单抗治疗，如果视力下降和/或 CRT 增加（>100μm），和/或如果出现新的血管造影渗漏和/或新的视网膜出血，则再进行三次注射。对整个组别的视力发展进行了分析。还进行了四分位数分析，并将视力过程与 CRT 相关联。在所有组中，都记录并分析了第一年的再注射次数和次数。
在 3 个月后，可以观察到平均 VA 增加 0.14（SD 0.22）logMAR，但在 3 至 12 个月的随访期间，平均视力再次下降 0.14（SD 0.24）logMAR，尽管多次再注射（平均 5 次注射），但仍与初始 VA 相似。根据 3 个月后的视力效果进行分层（四分位数分析），显示出视力过程的分化。四分位数 1 在 3 个月后 VA 增加最大，视网膜水肿减轻，但在随访期间失去了这种积极的效果（100%的患者接受了进一步的注射）。相比之下，四分位数 2 和三分位数在随访期间表现出稳定的反应（80%的再注射），而四分位数 4 尽管最初和随访期间进行了再注射，但 VA 仍进一步下降（60%的再注射）。
在德国临床实践中使用的灵活的、主要基于视力的雷珠单抗再治疗方案，在 12 个月的随访期间，通常会导致最初获得的 VA 丧失。亚组分析表明，这种负面影响尤其存在于治疗开始时 VA 相对较差以及 VA 增加最高的患者中。因为这个结果表明，一种基于视力的再治疗方案不能在渗出性 AMD 中保持雷珠单抗的初始积极治疗效果，所以建议修订德国使用的这种示意性的再治疗方案，并适应更敏感的再治疗参数。
