Riechardt Aline I, Pilger Daniel, Cordini Dino, Seibel Ira, Gundlach Enken, Hager Annette, Joussen Antonia M
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health; Department of Ophthalmology, Campus Benjamin Franklin, Berlin, Germany.
BerlinProtonen am Helmholtz-Zentrum Berlin für Materialien und EnergieCharité Universitätsmedizin Berlin, Lise-Meitner-Campus, Berlin, Germany.
Graefes Arch Clin Exp Ophthalmol. 2017 Nov;255(11):2263-2269. doi: 10.1007/s00417-017-3737-3. Epub 2017 Jul 18.
To analyze the risk factors for the development of neovascular glaucoma (NVG) of patients with choroidal melanoma after proton beam therapy (PBT).
Clinical case series, retrospective study. We evaluated 629 consecutive patients receiving proton beam therapy for the treatment of a choroidal melanoma at the oncology service at Charité, Berlin and Helmholtz-Zentrum, Berlin between 05/1998 and 11/2008 regarding the development and risk factors of NVG. Patients with tumor resection, salvage proton beam therapy for recurrent disease and known glaucoma of other origin were excluded from the cohort.
Of the 629 patients matching the inclusion criteria, 20.8% developed neovascularization of the iris after a mean time of 2.0 years (range 0.45 to 8.4 years) after PBT. Forty-seven percent of the patients with a neovascularization of the iris developed NVG after a mean time of 2.0 years after PBT, ranging from 5 months to 11.6 years. Univariate analysis revealed tumor height [p < 0.001, hazard ratio (HR): 2.71, 95% confidence interval (CI): 1.36-5.35 for tumors >6 mm ≤9 mm and 11.32 (4.03-31.73) for tumors >9 mm], distance of the tumor to the optic disc (p < 0.001, HR: 0.43, 95% CI: 0.24-0.77 for >0 mm ≤3 mm and HR: 0.13, 95% CI: 0.04-0.37 for >3 mm), dose to the ciliary body (p < 0.001, HR: 9.21, 95% CI: 5.08-16.71 (21-40 cobalt gray equivalents (CGE), HR 27.23, 95% CI: 6.33-116.97 (41-60 CGE)), dose to the optic disc (p < 0.001, HR: 3.53, 95% CI: 1.11-11.27 (21-40CGE), HR: 5.37, 95% CI: 2.72-10.63 (41-60CGE)), the irradiated length of the optic nerve (p < 0.001, HR: 4.48, 95% CI: 2.47-8.13) and diabetes mellitus (p < 0.05, HR: 2.53, 95% CI: 1.4-4.5) were found to be risk factors for the development of NVG. Multivariate regression analysis identified the dose to the ciliary body [p < 0.001, HR: 4.39, 95% CI: 2.28-8.44 (21-40 CGE), HR: 11.04, 95% CI: 1.97-61.69 (41-60 CGE)], the irradiated length of the optic nerve (p < 0.001, HR: 3.88, 95% CI: 2.11-7.16), the existence of diabetes mellitus (p < 0.01, HR: 1.28, 95% CI: 1.24-4.21) and tumor height [p < 0.05, HR: 2.28, 95% CI: 1.17-4.83 (>6 mm ≤9 mm), HR: 3.74, 95% CI: 1.05-13.23, (>9 mm)] to be independent risk factors for the development of NVG.
In the present analysis we found tumor height, dose to the ciliary body, irradiated length of the optic nerve and diabetes mellitus to be risk factors for the development of NVG. Whenever possible, critical structures of the anterior and posterior segment should be spared by beam shaping or changing of the beam entry angle.
分析质子束治疗(PBT)后脉络膜黑色素瘤患者发生新生血管性青光眼(NVG)的危险因素。
临床病例系列,回顾性研究。我们评估了1998年5月至2008年11月期间在柏林夏里特医院肿瘤科和柏林亥姆霍兹中心接受质子束治疗脉络膜黑色素瘤的629例连续患者,观察NVG的发生情况和危险因素。队列排除了接受肿瘤切除术、复发性疾病的挽救性质子束治疗以及已知其他原因导致青光眼的患者。
在符合纳入标准的629例患者中,20.8%在PBT后平均2.0年(范围0.45至8.4年)出现虹膜新生血管。虹膜新生血管患者中有47%在PBT后平均2.0年(范围5个月至11.6年)发生NVG。单因素分析显示,肿瘤高度[p < 〇.〇〇1,风险比(HR):2.71,95%置信区间(CI):肿瘤>6mm≤9mm时为1.36 - 5.35,肿瘤>9mm时为11.32(4.03 - 31.73)]、肿瘤与视盘的距离(p < 〇.〇〇1,HR:肿瘤>0mm≤3mm时为0.43,95%CI:0.24 - 0.77;肿瘤>3mm时为0.13,95%CI:0.04 - 0.37)、睫状体剂量(p < 〇.〇〇1,HR:21 - 40钴灰当量(CGE)时为9.21,95%CI:5.08 - 16.71;41 - 60CGE时为27.23,95%CI:6.33 - 116.97)、视盘剂量(p < 〇.〇〇1,HR:21 - 40CGE时为3.53,95%CI:1.11 - 11.27;41 - 60CGE时为5.37,95%CI:2.72 - 10.63)、视神经照射长度(p < 〇.〇〇1,HR:4.48,95%CI:2.47 - 8.13)和糖尿病(p < 〇.〇5,HR:2.53,95%CI:1.4 - 4.5)是NVG发生的危险因素。多因素回归分析确定睫状体剂量[p < 〇.〇〇1,HR:21 - 40CGE时为4.39,95%CI:2.28 - 8.44;41 - 60CGE时为11.04,95%CI:1.97 - 61.69]、视神经照射长度(p < 〇.〇〇1,HR:3.88,95%CI:2.11 - 7.16)、糖尿病的存在(p < 〇.〇1,HR:1.28,95%CI:1.24 - 4.21)和肿瘤高度[p < 〇.〇5,HR:肿瘤>6mm≤9mm时为2.28,95%CI:1.17 - 4.83;肿瘤>9mm时为3.74,95%CI:1.05 - 13.23]是NVG发生的独立危险因素。
在本分析中,我们发现肿瘤高度、睫状体剂量、视神经照射长度和糖尿病是NVG发生的危险因素。只要有可能,应通过束流整形或改变束流入射角来避免前后节关键结构受照射。