Effect of prolonged photodynamic therapy irradiation time combined with intravitreal injection of ranibizumab in the treatment of circumscribed choroidal hemangioma_Chinese Journal of Ocular Fundus Diseases

Authors：

Liang Siying ,  Chen Qingshan , Hu Chenli , Li Zhi , Ma Dahui

Shenzhen Eye Hospital Affiliated to Jinan University, Shenzhen 518000, China;

Corresponding author：

Chen Qingshan, Email: cqs1967@sina.com

Keywords：

Photochemotherapy; Choroid neoplasms/therapy; Hemangioma/therapy; Angiogenesis inhibitors/therapeutic use

DOI：

10.3760/cma.j.issn.1005-1015.2020.02.006

Video：

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Objective To observe the clinical effect of prolonged photodynamic therapy (PDT) irradiation time combined with intravitreal injection of ranibizumab in the treatment of circumscribed choroidal hemangioma (CCH).Methods A retrospective clinical study. From March 2012 to March 2018, 51 eyes of 51 patients diagnosed in Shenzhen Eye Hospital were included in the study. Among the patients, the tumor of 36 eyes were located in macular area, of 15 eyes were located outside macular area (near center or around optic disc). All patients underwent BCVA, color fundus photography, FFA, ocular B-scan ultrasonography and OCT examinations. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logMAR visual acuity. OCT showed 48 eyes with macular serous retinal detachment. of 36 eyes with tumor located in macular area, the logMAR BCVA was 0.05±0.05, the tumor thickness was 4.5±2.2 mm, the diameter of tumor was 9.7±3.6 mm. Of 15 eyes with tumor located outside macular area, the logMAR BCVA was 0.32±0.15, the tumor thickness was 3.8±1.4 mm, the diameter of tumor was 7.7±1.9 mm. PDT was performed for all eyes with the irradiation time of 123 s. After 48 h, all patients received intravitreal injections of 0.5 mg ranibizumab (0.05 ml). At 1, 3 and 6 months after treatment, the same equipment and methods before treatment were used for related examination. BCVA, subretinal effusion (SRF), tumor leakage and size changes were observed. BCVA, tumor thickness and diameter before and after treatment were compared by t test.Results At 6 months after treatment, the tumor was becoming smaller without scar formation. FFA showed that the blood vessels in the tumor were sparse compared with those before treatment, and the fluorescence leakage domain was reduced. OCT showed 43 eyes of macular serous detachment were treated after the combined treatment. The logMAR BCVA were 0.16±0.15 and 0.55±0.21 of the eyes with tumor located in or outside macular area, respectively. The difference of logMAR BCVA between before and after treatment was significant (t=－2.511, －2.676; P=0.036, 0.040). Both the tumor thickness (t=3.416, 3.055; P=0.011, 0.028) and diameter (t=4.385, 4.171; P=0.002, 0.009) of CCH patients were significantly reduced compared with that before treatment.Conclusion The tumor of CCH can be reduced by prolonged PDT irradiation time combined with intravitreal injection of ranibizumab.

Citation： Liang Siying, Chen Qingshan, Hu Chenli, Li Zhi, Ma Dahui. Effect of prolonged photodynamic therapy irradiation time combined with intravitreal injection of ranibizumab in the treatment of circumscribed choroidal hemangioma. Chinese Journal of Ocular Fundus Diseases, 2020, 36(2): 116-120. doi: 10.3760/cma.j.issn.1005-1015.2020.02.006 Copy

1.	Sharma T, Krishnan T, Gopal L, et al. Transpupillary thermotherapy for circumscribed choroidal hemangioma:clinical profile and treatment outcome[J]. Ophthalmic Surg Laser Imaging, 2011, 42(5): 360-368. DOI: 10.3928/15428877-20110707-01.
2.	Karimi S, Nourinia R, Mashayekhi A, et al. Circumscribed choroidal hemangioma[J]. J Ophthalmic Vis Res, 2015, 10(3): 320-328. DOI: 10.4103/2008-322X.170353.
3.	吴又凯, 张清, 卜菊芬, 等. 氪红激光透热治疗视网膜下新生血管及脉络膜血管瘤的疗效分析[J]. 中国实用眼科杂志, 2003, 21(3): 213-215. DOI: 10.3760/cma.j.issn.1006-4443.2003.03.018.Wu YK, Zhang Q, Bu JF, et al. Krypton red laser transpupil thermotherapy for retina neovascularization and uveal aneurysms[J]. Chin J Pract Ophthalmol, 2003, 21(3): 213-215. DOI: 10.3760/cma.j.issn.1006-4443.2003.03.018.
4.	高汝龙, 张国明, 王燕, 等. 孤立性脉络膜血管瘤合并视网膜脱离的治疗[J]. 中国实用眼科杂志, 2000, 18(2): 81-82. DOI: 10.3760/cma.j.issn.1006-4443.2000.02.007.Gao RL, Zhang GM, Wang Y, et al. Treatment the hemangioma of choroid accompanied by retinal detachment[J]. Chin J Pract Ophthalmol, 2000, 18(2): 81-82. DOI: 10.3760/cma.j.issn.1006-4443.2000.02.007.
5.	Cerman E, Çekiç O. Clinical use of photodynamic therapy in ocular tumors[J]. Surv Ophthalmol, 2015, 60(6): 557-574. DOI: 10.1016/j.survophthal.2015.05.004.
6.	Rezaei KA, Toma HS, Cai J, et al. Reduced choroidal neovascular membrane formation in cyclooxygenase-2 null mice[J]. Invest Ophtahlmol Vis Sci, 2011, 52(2): 701-707. DOI: 10.1167/iovs.10-6319.
7.	Ho YF, Chao A, Chen KJ, et al.Clinical outcomes and predictors of response to photodynamic therapy in symptomatic circumscribed choroidal hemangioma: aretrospective case series[J/OL]. PLoS One, 2018, 13(5): 0197088[2018-05-31].https://doi.org/10.1371/journal.pone.0197088. DOI:10.1371/journal.pone.0197088.
8.	史伟, 姜娜, 崔宏宇. 光动力疗法治疗68例脉络膜血管瘤的疗效及安全性[J]. 中国肿瘤临床与康复, 2016, 23(7): 821-824. DOI: 10.13455/j.cnki.cjcor.2016.07.15.Shi W, Jiang N, Cui HY. Analysis of the efficacy and safety of photodynamic therapy in the treatment of 68 cases of choroidal hemangioma[J]. Chin J Clin Oncol Rehabil, 2016, 23(7): 821-824. DOI: 10.13455/j.cnki.cjcor.2016.07.15.
9.	Battaglia Parodi M, La Spina C, Berchicci L, et al. Photosensitizers and photodynamic therapy: verteporfin[J]. Dev Ophthalmol, 2016, 55: 330-336. DOI: 10.1159/000434704.
10.	Sagong M, Lee J, Chang W, et al. Application of intravitreal bevacizumab for circumscribed choroidal hemangioma[J]. Korean J Ophthalmol, 2009, 23(2): 127-131. DOI: 10.3341/kjo.2009.23.2.127.
11.	Hsu CC, Yang CS, Peng CH, et al. Combination photodynamic therapy and intravitreal bevacizumab used to treat circumscribed choroidal hemangioma[J]. J Chin Med Assoc, 2011, 74(10): 473-477. DOI: 10.1016/j.jcma.2011.08.020.
12.	刘月明, 延艳妮, 李洋, 等. 国产敷贴器治疗孤立性脉络膜血管瘤的临床效果[J]. 中华眼视光学与视觉科学杂志, 2019, 21(8): 576-580. DOI: 10.3760/cma.j.issn.1674-845X.2019.08.003.Liu MY, Yan YN, Li Y, et al. The safety and efficacy of a domestic radioactive applicator for the treatment of circumscribed choroidal hemangioma[J]. Chin J Ophthalmol Vis Sci, 2019, 21(8): 576-580. DOI: 10.3760/cma.j.issn.1674-845X.2019.08.003.
13.	李骥, 王胜资, 徐格致, 等. 放射疗法治疗难治性脉络膜血管瘤的疗效观察[J]. 中华眼底病杂志, 2014, 30(5): 470-472. DOI: 10.3760/cma.j.issn.1005-1015.2014.05.010.Li J, Wang SZ, Xu G, et al. Radiotherapy for refractory choroidalhemangioma[J]. Chin J Ocul Fundus Dis, 2014, 30(5): 470-472. DOI: 10.3760/cma.j.issn.1005-1015.2014.05.010.
14.	田晓燕, 王小芳, 邹晶, 等. 倍频532nm激光光凝治疗孤立性脉络膜血管瘤的临床观察[J]. 眼科新进展, 2013, 33(5): 450-452. DOI: 10.13389/j.cnki.rao.2013.05.002.Tian XY, Wang XF, Zou J, et al. Clinical efficacy of photocoagulation with 532 nm frequency-doubled laser on circum-scribed choroidal hemangioma[J]. Rec Adv Ophthalmol, 2013, 33(5): 450-452. DOI: 10.13389/j.cnki.rao.2013.05.002.
15.	王光璐, 王明扬, 魏文斌, 等. 经瞳孔温热疗法治疗局限性脉络膜血管瘤[J]. 中华眼科杂志, 2012, 48(4): 318-322. DOI: 10.3760/cma.j.issn.0412-4081.2012.04.007.Wang GL, Wang MY, Wei WB, et al. Transpupillary thermotherapy for circumscribed choroidal hemangiomas[J]. Chin J Ophthalmol, 2012, 48(4): 318-322. DOI: 10.3760/cma.j.issn.0412-4081.2012.04.007.
16.	宋艳萍, 徐东强, 丁琴, 等. 光动力疗法与经瞳孔温热疗法治疗孤立型脉络膜血管瘤的疗效观察[J]. 中华眼底病杂志, 2009, 25(4): 279-282. DOI: 10.3760/cma.j.issn.1005-1015.2009.04.09.Song YP, Xu DQ, Ding Q, et al. Therapeutic effect of photodynamic therapy and transpupillary thermotherapy on circumscribed choroid hemangioma[J]. Chin J Ocul Fundus Dis, 2009, 25(4): 279-282. DOI: 10.3760/cma.j.issn.1005-1015.2009.04.09.
17.	黄乐乐, 陈雷, 胡悦东, 等. 两种方法治疗孤立性脉络膜血管瘤疗效对比[J]. 国际眼科杂志, 2014, 14(3): 499-502. DOI: 10.3980/j.issn.1672-5123.2014.03.33.Huang LL, Chen L, Hu YD, et al. Clinical therapeutic effect of two therapies on circumscribed choroidal hemangioma[J]. Int Eye Sci, 2014, 14(3): 499-502. DOI: 10.3980/j.issn.1672-5123.2014.03.33.
18.	Lasave AF, Serrano MA, Arevalo JF. Photodynamic therapy with verteporfin plus intravitreal bevacizumab for circumscribed choroidal hemangioma: 4 years of follow-up[J/OL].Retin Cases Brief Rep, 2017, 2017: E1[2017-11-22]. http://europepmc.org/article/MED/29176523. DOI:10.1097/ICB.0000000000000677. [published online ahead of print].
19.	Subirà O, Brosa H, Lorenzo-Parra D, et al. Choroidal haemangioma and photodynamic therapy: a natomical and functional response of patients with choroidal hemangioma treated with photodynamic therapy[J]. Arch Soc Esp Oftalmol, 2017, 92(6): 257-264. DOI: 10.1016/j.oftal.2016.11.013.
20.	张军军. 孤立性脉络膜血管瘤的治疗[J]. 中华眼底病杂志, 2004, 20(1): 47. DOI: 10.3760/j.issn.1005-1015.2004.01.037.Zhang JJ. The treatment of circumscribed choroidal hemangioma[J]. Chin J Ocul Fundus Dis, 2004, 20(1): 47. DOI: 10.3760/j.issn.1005-1015.2004.01.037.
21.	Mitry D, Bunce C, Charteris D. Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion[J/CD].Cochrane Database Syst Rev, 2013(1): CD009510. DOI: 10.1002/14651858.CD009510.pub2.
22.	Schmidt-Erfurth U. Clinical safety of ranibizumab in age-related macular degeneration[J]. Expert Opin Drug Saf, 2010, 9(1): 149-165. DOI: 10.1517/14740330903418422.
23.	薛雨顺, 周海燕, 杨乐, 等. PDT联合玻璃体内注射雷珠单抗治疗孤立性脉络膜血管瘤[J]. 国际眼科杂志, 2017, 17(2): 341-343. DOI: 10.3980/j.issn.1672-5123.2017.2.38.Xue YS, Zhou HY, Yang L, et al. Effect of photodynamic therapy combined with intravitreal ranibizumab injection on circumscribed choroidal hemangioma[J]. Int Eye Sci, 2017, 17(2): 341-343. DOI: 10.3980/j.issn.1672-5123.2017.2.38.
24.	Blassi MA, Tiberti AC, Scopola A, et al. Photodynamic therapy with verteperfin for symptomatic circumscribed choroidal hemangioma[J]. Ophthalmology, 2010, 117(8): 1630-1637. DOI: 10.1016/j.ophtha.2009.12.033.
25.	Boixadera A, García-Arumí J, Martínez-Castillo V, et al. Prospective clinical trial evaluating the efficacy of photodynamic therapy for symptomatic circumscribed choroidal hemangioma[J]. Ophthalmology, 2009, 116(1): 100-105. DOI: 10.1016/j.ophtha.2008.08.029.

1. Sharma T, Krishnan T, Gopal L, et al. Transpupillary thermotherapy for circumscribed choroidal hemangioma:clinical profile and treatment outcome[J]. Ophthalmic Surg Laser Imaging, 2011, 42(5): 360-368. DOI: 10.3928/15428877-20110707-01.
2. Karimi S, Nourinia R, Mashayekhi A, et al. Circumscribed choroidal hemangioma[J]. J Ophthalmic Vis Res, 2015, 10(3): 320-328. DOI: 10.4103/2008-322X.170353.
3. 吴又凯, 张清, 卜菊芬, 等. 氪红激光透热治疗视网膜下新生血管及脉络膜血管瘤的疗效分析[J]. 中国实用眼科杂志, 2003, 21(3): 213-215. DOI: 10.3760/cma.j.issn.1006-4443.2003.03.018.Wu YK, Zhang Q, Bu JF, et al. Krypton red laser transpupil thermotherapy for retina neovascularization and uveal aneurysms[J]. Chin J Pract Ophthalmol, 2003, 21(3): 213-215. DOI: 10.3760/cma.j.issn.1006-4443.2003.03.018.
4. 高汝龙, 张国明, 王燕, 等. 孤立性脉络膜血管瘤合并视网膜脱离的治疗[J]. 中国实用眼科杂志, 2000, 18(2): 81-82. DOI: 10.3760/cma.j.issn.1006-4443.2000.02.007.Gao RL, Zhang GM, Wang Y, et al. Treatment the hemangioma of choroid accompanied by retinal detachment[J]. Chin J Pract Ophthalmol, 2000, 18(2): 81-82. DOI: 10.3760/cma.j.issn.1006-4443.2000.02.007.
5. Cerman E, Çekiç O. Clinical use of photodynamic therapy in ocular tumors[J]. Surv Ophthalmol, 2015, 60(6): 557-574. DOI: 10.1016/j.survophthal.2015.05.004.
6. Rezaei KA, Toma HS, Cai J, et al. Reduced choroidal neovascular membrane formation in cyclooxygenase-2 null mice[J]. Invest Ophtahlmol Vis Sci, 2011, 52(2): 701-707. DOI: 10.1167/iovs.10-6319.
7. Ho YF, Chao A, Chen KJ, et al.Clinical outcomes and predictors of response to photodynamic therapy in symptomatic circumscribed choroidal hemangioma: aretrospective case series[J/OL]. PLoS One, 2018, 13(5): 0197088[2018-05-31].https://doi.org/10.1371/journal.pone.0197088. DOI:10.1371/journal.pone.0197088.
8. 史伟, 姜娜, 崔宏宇. 光动力疗法治疗68例脉络膜血管瘤的疗效及安全性[J]. 中国肿瘤临床与康复, 2016, 23(7): 821-824. DOI: 10.13455/j.cnki.cjcor.2016.07.15.Shi W, Jiang N, Cui HY. Analysis of the efficacy and safety of photodynamic therapy in the treatment of 68 cases of choroidal hemangioma[J]. Chin J Clin Oncol Rehabil, 2016, 23(7): 821-824. DOI: 10.13455/j.cnki.cjcor.2016.07.15.
9. Battaglia Parodi M, La Spina C, Berchicci L, et al. Photosensitizers and photodynamic therapy: verteporfin[J]. Dev Ophthalmol, 2016, 55: 330-336. DOI: 10.1159/000434704.
10. Sagong M, Lee J, Chang W, et al. Application of intravitreal bevacizumab for circumscribed choroidal hemangioma[J]. Korean J Ophthalmol, 2009, 23(2): 127-131. DOI: 10.3341/kjo.2009.23.2.127.
11. Hsu CC, Yang CS, Peng CH, et al. Combination photodynamic therapy and intravitreal bevacizumab used to treat circumscribed choroidal hemangioma[J]. J Chin Med Assoc, 2011, 74(10): 473-477. DOI: 10.1016/j.jcma.2011.08.020.
12. 刘月明, 延艳妮, 李洋, 等. 国产敷贴器治疗孤立性脉络膜血管瘤的临床效果[J]. 中华眼视光学与视觉科学杂志, 2019, 21(8): 576-580. DOI: 10.3760/cma.j.issn.1674-845X.2019.08.003.Liu MY, Yan YN, Li Y, et al. The safety and efficacy of a domestic radioactive applicator for the treatment of circumscribed choroidal hemangioma[J]. Chin J Ophthalmol Vis Sci, 2019, 21(8): 576-580. DOI: 10.3760/cma.j.issn.1674-845X.2019.08.003.
13. 李骥, 王胜资, 徐格致, 等. 放射疗法治疗难治性脉络膜血管瘤的疗效观察[J]. 中华眼底病杂志, 2014, 30(5): 470-472. DOI: 10.3760/cma.j.issn.1005-1015.2014.05.010.Li J, Wang SZ, Xu G, et al. Radiotherapy for refractory choroidalhemangioma[J]. Chin J Ocul Fundus Dis, 2014, 30(5): 470-472. DOI: 10.3760/cma.j.issn.1005-1015.2014.05.010.
14. 田晓燕, 王小芳, 邹晶, 等. 倍频532nm激光光凝治疗孤立性脉络膜血管瘤的临床观察[J]. 眼科新进展, 2013, 33(5): 450-452. DOI: 10.13389/j.cnki.rao.2013.05.002.Tian XY, Wang XF, Zou J, et al. Clinical efficacy of photocoagulation with 532 nm frequency-doubled laser on circum-scribed choroidal hemangioma[J]. Rec Adv Ophthalmol, 2013, 33(5): 450-452. DOI: 10.13389/j.cnki.rao.2013.05.002.
15. 王光璐, 王明扬, 魏文斌, 等. 经瞳孔温热疗法治疗局限性脉络膜血管瘤[J]. 中华眼科杂志, 2012, 48(4): 318-322. DOI: 10.3760/cma.j.issn.0412-4081.2012.04.007.Wang GL, Wang MY, Wei WB, et al. Transpupillary thermotherapy for circumscribed choroidal hemangiomas[J]. Chin J Ophthalmol, 2012, 48(4): 318-322. DOI: 10.3760/cma.j.issn.0412-4081.2012.04.007.
16. 宋艳萍, 徐东强, 丁琴, 等. 光动力疗法与经瞳孔温热疗法治疗孤立型脉络膜血管瘤的疗效观察[J]. 中华眼底病杂志, 2009, 25(4): 279-282. DOI: 10.3760/cma.j.issn.1005-1015.2009.04.09.Song YP, Xu DQ, Ding Q, et al. Therapeutic effect of photodynamic therapy and transpupillary thermotherapy on circumscribed choroid hemangioma[J]. Chin J Ocul Fundus Dis, 2009, 25(4): 279-282. DOI: 10.3760/cma.j.issn.1005-1015.2009.04.09.
17. 黄乐乐, 陈雷, 胡悦东, 等. 两种方法治疗孤立性脉络膜血管瘤疗效对比[J]. 国际眼科杂志, 2014, 14(3): 499-502. DOI: 10.3980/j.issn.1672-5123.2014.03.33.Huang LL, Chen L, Hu YD, et al. Clinical therapeutic effect of two therapies on circumscribed choroidal hemangioma[J]. Int Eye Sci, 2014, 14(3): 499-502. DOI: 10.3980/j.issn.1672-5123.2014.03.33.
18. Lasave AF, Serrano MA, Arevalo JF. Photodynamic therapy with verteporfin plus intravitreal bevacizumab for circumscribed choroidal hemangioma: 4 years of follow-up[J/OL].Retin Cases Brief Rep, 2017, 2017: E1[2017-11-22]. http://europepmc.org/article/MED/29176523. DOI:10.1097/ICB.0000000000000677. [published online ahead of print].
19. Subirà O, Brosa H, Lorenzo-Parra D, et al. Choroidal haemangioma and photodynamic therapy: a natomical and functional response of patients with choroidal hemangioma treated with photodynamic therapy[J]. Arch Soc Esp Oftalmol, 2017, 92(6): 257-264. DOI: 10.1016/j.oftal.2016.11.013.
20. 张军军. 孤立性脉络膜血管瘤的治疗[J]. 中华眼底病杂志, 2004, 20(1): 47. DOI: 10.3760/j.issn.1005-1015.2004.01.037.Zhang JJ. The treatment of circumscribed choroidal hemangioma[J]. Chin J Ocul Fundus Dis, 2004, 20(1): 47. DOI: 10.3760/j.issn.1005-1015.2004.01.037.
21. Mitry D, Bunce C, Charteris D. Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion[J/CD].Cochrane Database Syst Rev, 2013(1): CD009510. DOI: 10.1002/14651858.CD009510.pub2.
22. Schmidt-Erfurth U. Clinical safety of ranibizumab in age-related macular degeneration[J]. Expert Opin Drug Saf, 2010, 9(1): 149-165. DOI: 10.1517/14740330903418422.
23. 薛雨顺, 周海燕, 杨乐, 等. PDT联合玻璃体内注射雷珠单抗治疗孤立性脉络膜血管瘤[J]. 国际眼科杂志, 2017, 17(2): 341-343. DOI: 10.3980/j.issn.1672-5123.2017.2.38.Xue YS, Zhou HY, Yang L, et al. Effect of photodynamic therapy combined with intravitreal ranibizumab injection on circumscribed choroidal hemangioma[J]. Int Eye Sci, 2017, 17(2): 341-343. DOI: 10.3980/j.issn.1672-5123.2017.2.38.
24. Blassi MA, Tiberti AC, Scopola A, et al. Photodynamic therapy with verteperfin for symptomatic circumscribed choroidal hemangioma[J]. Ophthalmology, 2010, 117(8): 1630-1637. DOI: 10.1016/j.ophtha.2009.12.033.
25. Boixadera A, García-Arumí J, Martínez-Castillo V, et al. Prospective clinical trial evaluating the efficacy of photodynamic therapy for symptomatic circumscribed choroidal hemangioma[J]. Ophthalmology, 2009, 116(1): 100-105. DOI: 10.1016/j.ophtha.2008.08.029.

Chinese Journal of Ocular Fundus Diseases

Effect of prolonged photodynamic therapy irradiation time combined with intravitreal injection of ranibizumab in the treatment of circumscribed choroidal hemangioma

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