A prospective case-control study of intravitreal injection of anti-vascular endothelial factor drugs in the treatment of Coats disease_Chinese Journal of Ocular Fundus Diseases

Authors：

Ruan Lu , Ju Yuqiao , Zhang Juan , Jiang Chen , Yang Qian ,  Huang Xin

Department of Ophthalmology, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China;

Corresponding author：

Huang Xin, Email: huangxin2007@aliyun.com

Keywords：

Retinal telangiectasis; Angiogenesis inhibitors; Laser coagulation; Subretinal fluid; Macular edema

DOI：

10.3760/cma.j.cn511434-20220520-00314

Video：

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Objective To investigate the efficacy and safety of traditional laser photocoagulation, laser combined with intravitreal injection of anti-vascular endothelial factor (anti-VEGF) drugs and intravitreal injection of anti-VEGF drugs alone in Coats disease. Methods The patients diagnosed as Coats disease stage 2B-3A2 in Department of Ophthalmology, Eye and ENT Hospital of Shanghai Medical College of Fudan University from December 2016 to November 2019 were included in this study. Patients were divided into three groups, including laser group, combined group and drug group, according to the different treatment. In the laser group, the initial treatment was traditional laser photocoagulation alone. In the drug group, the anti-VEGF drug was injected into vitreous once a month for three months. The initial treatment of the eyes in the combined group was laser combined with intravitreal injection of anti-VEGF drugs, or laser treatment within 1 week after anti-VEGF drug treatment. The follow-up time was more than 6 months, and best-corrected visual acuity (BCVA), ultra-wide-angle fundus photography, and fluorescein fundus angiography were performed during follow-up. The treatment efficiency, subretinal fluid (SRF), macular edema, BCVA and complications were compared among the three groups. Results Among 60 patients (60 eyes), there were 55 males (55 eyes) and 5 females (5 eyes), with the mean age of 17.1±2.0 years. Among 60 eyes, there were 26 eyes in 2B stage, 23 eyes in 3A1 stage, and 11 eyes in 3A2 stage. Twenty patients (20 eyes) was in the laser group, combined group and drug group, respectively. After the initial treatment of all eyes in the drug group, the abnormal blood vessels did not regress significantly; the absorption and increase of SRF were 4 (20.0%, 4/20) and 5 (25.0%, 5/20) eyes, respectively. Supplementary laser therapy was given to 16 eyes, and vitrectomy (PPV) was given to 4 eyes. Among the 16 eyes treated by laser, 10 eyes were effective (50.0%, 10/20); vitreous hemorrhage, fibrous membrane hyperplasia, and complicated cataract occurred in 1, 1, and 2 eyes during the treatment, respectively, and PPV was given again in all eyes. Recurrent and persistent macular edema occurred in 4 and 1 eyes, respectively. Among the eyes in the combined group, treatment were effective in 11 eyes (55.0%, 11/20); 5, 2, and 2 eyes had SRF, fibrous membrane hyperplasia, and complicated cataract during the treatment, and PPV was given again; the edema was repeated and persisted in 1 eye, respectively. Among the affected eyes in the laser group, 15 eyes (75.0%, 15/20) were treated effectively; 2, 2, and 1 eyes developed a large number of vitreous hemorrhage, fibrous membrane hyperplasia, and complicated cataract during the treatment, and PPV was given again. Conclusions Anti-VEGF drugs alone are ineffective in the treatment of Coats disease, and ablation of other abnormal blood vessels is needed. In the treatment of Coats disease, anti-VEGF drugs can not only promote the absorption of SRF, but also may lead to its increase, and the application should be cautious.

Citation： Ruan Lu, Ju Yuqiao, Zhang Juan, Jiang Chen, Yang Qian, Huang Xin. A prospective case-control study of intravitreal injection of anti-vascular endothelial factor drugs in the treatment of Coats disease. Chinese Journal of Ocular Fundus Diseases, 2022, 38(7): 556-561. doi: 10.3760/cma.j.cn511434-20220520-00314 Copy

1.	Shields JA, Shields CL, Honavar SG, et al. Classification and management of Coats disease: the 2000 Proctor Lecture[J]. Am J Ophthalmol, 2001, 131(5): 572-583. DOI: 10.1016/s0002-9394(01)00896-0.
2.	Shields JA, Shields CL, Honavar SG, et al. Clinical variations and complications of Coats disease in 150 cases: the 2000 Sanford Gifford Memorial Lecture[J]. Am J Ophthalmol, 2001, 131(5): 561-571. DOI: 10.1016/s0002-9394(00)00883-7.
3.	Gomez Morales A. Coats' disease. Natural history and results of treatment[J]. Am J Ophthalmol, 1965, 60(5): 855-865. DOI: 10.1016/0002-9394(65)92006-4.
4.	Ruben M, Yaghy A, Park CH, et al. Neglected Coats disease[J/OL]. J Pediatr Ophthalmol Strabismus, 2020, 57: e82-e85[2020-10-20]. https://www.ncbi.nlm.nih.gov/pubmed/33090232. DOI: 10.3928/01913913-20200818-01.
5.	Karacorlu M, Hocaoglu M, Sayman Muslubas I, et al. Long-term anatomical and functional outcomes following vitrectomy for advanced Coats disease[J]. Retina, 2017, 37(9): 1757-1764. DOI: 10.1097/IAE.0000000000001415.
6.	Mano F, Matsushita I, Kondo H, et al. Vitrectomy and external drainage of subretinal fluid containing high concentration of vascular endothelial growth factor for advanced Coats disease[J/OL]. Sci Rep, 2021, 11(1): 19333[2021-09-29]. https://pubmed.ncbi.nlm.nih.gov/34588604/. DOI: 10.1038/s41598-021-98968-9.
7.	Zhao Q, Peng XY, Chen FH, et al. Vascular endothelial growth factor in Coats' disease[J/OL]. Acta Ophthalmol, 2014, 92(3): e225-e228[2013-06-13]. https://pubmed.ncbi.nlm.nih.gov/23764089/. DOI: 10.1111/aos.12158.
8.	Zhang J, Jiang C, Ruan L, et al. Associations of cytokine concentrations in aqueous humour with retinal vascular abnormalities and exudation in Coats' disease[J]. Acta Ophthalmol, 2019, 97(3): 319-324. DOI: 10.1111/aos.13971.
9.	Jiang L, Qin B, Luo XL, et al. Three-year follow-up of Coats disease treated with conbercept and 532-nm laser photocoagulation[J]. World J Clin Cases, 2020, 8(24): 6243-6251. DOI: 10.12998/wjcc.v8.i24.6243.
10.	Zhang L, Ke Y, Wang W, et al. The efficacy of conbercept or ranibizumab intravitreal injection combined with laser therapy for Coats' disease[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(7): 1339-1346. DOI: 10.1007/s00417-018-3949-1.
11.	Li S, Deng G, Liu J, et al. The effects of a treatment combination of anti-VEGF injections, laser coagulation and cryotherapy on patients with type 3 Coat's disease[J]. BMC Ophthalmol, 2017, 17(1): 76. DOI: 10.1186/s12886-017-0469-4.
12.	Yang Q, Wei W, Shi X, et al. Successful use of intravitreal ranibizumab injection and combined treatment in the management of Coats' disease[J]. Acta Ophthalmol, 2016, 94(4): 401-406. DOI: 10.1111/aos.13067.
13.	Zheng XX, Jiang YR. The effect of intravitreal bevacizumab injection as the initial treatment for Coats' disease[J]. Graefe's Arch Clin Exp Ophthalmol, 2014, 252(1): 35-42. DOI: 10.1007/s00417-013-2409-1.
14.	阮露, 黄欣, 江睿, 等. 间接检眼镜下激光光凝治疗青少年型Coats病[J]. 中华眼底病杂志, 2014, 30(1): 42-45. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.011.Ruan L, Huang X, Jiang R, et al. Juvenile Coats disease successfully managed with green diode laser using indirect ophthalmoscope[J]. Chin J Ocul Fundus Dis, 2014, 30(1): 42-45. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.011.
15.	Reichstein DA, Recchia FM. Coats disease and exudative retinopathy[J]. Int Ophthalmol Clin, 2011, 51(1): 93-112. DOI: 10.1097/IIO.0b013e318200de51.
16.	Schefler AC, Berrocal AM, Murray TG. Advanced Coats' disease. Management with repetitive aggressive laser ablation therapy[J]. Retina, 2008, 28: S38-41. DOI: 10.1097/IAE.0b013e318163cd7c.
17.	Giannakopoulos M, Drimtzias E, Panteli V, et al. Intravitreal ranibizumab as an adjunctive treatment for Coats disease (6-year follow-up)[J]. Retin Cases Brief Rep, 2017, 11(4): 339-343. DOI: 10.1097/ICB.0000000000000363.
18.	Wang Y, Fan H, Gao K, et al. Levels of cytokines in the aqueous humor guided treatment of refractory macular edema in adult-onset Coats' disease[J]. BMC Ophthalmol, 2020, 20(1): 261. DOI: 10.1186/s12886-020-01474-1.
19.	Kam AW, Hui M, Cherepanoff S, et al. Rapid "epiretinal membrane" development following intravitreal bevacizumab for Coats' disease[J]. Am J Ophthalmol Case Rep, 2018, 11: 75-77. DOI: 10.1016/j.ajoc.2018.06.002.
20.	Ramasubramanian A, Shields CL. Bevacizumab for Coats' disease with exudative retinal detachment and risk of vitreoretinal traction[J]. Br J Ophthalmol, 2012, 96(3): 356-359. DOI: 10.1136/bjophthalmol-2011-300141.
21.	Levinson JD, Hubbard GB, 3rd. 577-nm yellow laser photocoagulation for Coats disease[J]. Retina, 2016, 36(7): 1388-1394. DOI: 10.1097/IAE.0000000000000874.
22.	Shapiro MJ, Chow CC, Karth PA, et al. Effects of green diode laser in the treatment of pediatric Coats disease[J]. Am J Ophthalmol, 2011, 151(4): 725-731. DOI: 10.1016/j.ajo.2010.10.024.
23.	Nowara M, Fouad YA, Abdel Aziz I, et al. Experience with intravitreal ranibizumab as an adjunct to ablation therapy in eyes with exudative Coats' disease[J]. Clin Ophthalmol, 2021, 15: 367-373. DOI: 10.2147/OPTH.S293030.

1. Shields JA, Shields CL, Honavar SG, et al. Classification and management of Coats disease: the 2000 Proctor Lecture[J]. Am J Ophthalmol, 2001, 131(5): 572-583. DOI: 10.1016/s0002-9394(01)00896-0.
2. Shields JA, Shields CL, Honavar SG, et al. Clinical variations and complications of Coats disease in 150 cases: the 2000 Sanford Gifford Memorial Lecture[J]. Am J Ophthalmol, 2001, 131(5): 561-571. DOI: 10.1016/s0002-9394(00)00883-7.
3. Gomez Morales A. Coats' disease. Natural history and results of treatment[J]. Am J Ophthalmol, 1965, 60(5): 855-865. DOI: 10.1016/0002-9394(65)92006-4.
4. Ruben M, Yaghy A, Park CH, et al. Neglected Coats disease[J/OL]. J Pediatr Ophthalmol Strabismus, 2020, 57: e82-e85[2020-10-20]. https://www.ncbi.nlm.nih.gov/pubmed/33090232. DOI: 10.3928/01913913-20200818-01.
5. Karacorlu M, Hocaoglu M, Sayman Muslubas I, et al. Long-term anatomical and functional outcomes following vitrectomy for advanced Coats disease[J]. Retina, 2017, 37(9): 1757-1764. DOI: 10.1097/IAE.0000000000001415.
6. Mano F, Matsushita I, Kondo H, et al. Vitrectomy and external drainage of subretinal fluid containing high concentration of vascular endothelial growth factor for advanced Coats disease[J/OL]. Sci Rep, 2021, 11(1): 19333[2021-09-29]. https://pubmed.ncbi.nlm.nih.gov/34588604/. DOI: 10.1038/s41598-021-98968-9.
7. Zhao Q, Peng XY, Chen FH, et al. Vascular endothelial growth factor in Coats' disease[J/OL]. Acta Ophthalmol, 2014, 92(3): e225-e228[2013-06-13]. https://pubmed.ncbi.nlm.nih.gov/23764089/. DOI: 10.1111/aos.12158.
8. Zhang J, Jiang C, Ruan L, et al. Associations of cytokine concentrations in aqueous humour with retinal vascular abnormalities and exudation in Coats' disease[J]. Acta Ophthalmol, 2019, 97(3): 319-324. DOI: 10.1111/aos.13971.
9. Jiang L, Qin B, Luo XL, et al. Three-year follow-up of Coats disease treated with conbercept and 532-nm laser photocoagulation[J]. World J Clin Cases, 2020, 8(24): 6243-6251. DOI: 10.12998/wjcc.v8.i24.6243.
10. Zhang L, Ke Y, Wang W, et al. The efficacy of conbercept or ranibizumab intravitreal injection combined with laser therapy for Coats' disease[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(7): 1339-1346. DOI: 10.1007/s00417-018-3949-1.
11. Li S, Deng G, Liu J, et al. The effects of a treatment combination of anti-VEGF injections, laser coagulation and cryotherapy on patients with type 3 Coat's disease[J]. BMC Ophthalmol, 2017, 17(1): 76. DOI: 10.1186/s12886-017-0469-4.
12. Yang Q, Wei W, Shi X, et al. Successful use of intravitreal ranibizumab injection and combined treatment in the management of Coats' disease[J]. Acta Ophthalmol, 2016, 94(4): 401-406. DOI: 10.1111/aos.13067.
13. Zheng XX, Jiang YR. The effect of intravitreal bevacizumab injection as the initial treatment for Coats' disease[J]. Graefe's Arch Clin Exp Ophthalmol, 2014, 252(1): 35-42. DOI: 10.1007/s00417-013-2409-1.
14. 阮露, 黄欣, 江睿, 等. 间接检眼镜下激光光凝治疗青少年型Coats病[J]. 中华眼底病杂志, 2014, 30(1): 42-45. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.011.Ruan L, Huang X, Jiang R, et al. Juvenile Coats disease successfully managed with green diode laser using indirect ophthalmoscope[J]. Chin J Ocul Fundus Dis, 2014, 30(1): 42-45. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.011.
15. Reichstein DA, Recchia FM. Coats disease and exudative retinopathy[J]. Int Ophthalmol Clin, 2011, 51(1): 93-112. DOI: 10.1097/IIO.0b013e318200de51.
16. Schefler AC, Berrocal AM, Murray TG. Advanced Coats' disease. Management with repetitive aggressive laser ablation therapy[J]. Retina, 2008, 28: S38-41. DOI: 10.1097/IAE.0b013e318163cd7c.
17. Giannakopoulos M, Drimtzias E, Panteli V, et al. Intravitreal ranibizumab as an adjunctive treatment for Coats disease (6-year follow-up)[J]. Retin Cases Brief Rep, 2017, 11(4): 339-343. DOI: 10.1097/ICB.0000000000000363.
18. Wang Y, Fan H, Gao K, et al. Levels of cytokines in the aqueous humor guided treatment of refractory macular edema in adult-onset Coats' disease[J]. BMC Ophthalmol, 2020, 20(1): 261. DOI: 10.1186/s12886-020-01474-1.
19. Kam AW, Hui M, Cherepanoff S, et al. Rapid "epiretinal membrane" development following intravitreal bevacizumab for Coats' disease[J]. Am J Ophthalmol Case Rep, 2018, 11: 75-77. DOI: 10.1016/j.ajoc.2018.06.002.
20. Ramasubramanian A, Shields CL. Bevacizumab for Coats' disease with exudative retinal detachment and risk of vitreoretinal traction[J]. Br J Ophthalmol, 2012, 96(3): 356-359. DOI: 10.1136/bjophthalmol-2011-300141.
21. Levinson JD, Hubbard GB, 3rd. 577-nm yellow laser photocoagulation for Coats disease[J]. Retina, 2016, 36(7): 1388-1394. DOI: 10.1097/IAE.0000000000000874.
22. Shapiro MJ, Chow CC, Karth PA, et al. Effects of green diode laser in the treatment of pediatric Coats disease[J]. Am J Ophthalmol, 2011, 151(4): 725-731. DOI: 10.1016/j.ajo.2010.10.024.
23. Nowara M, Fouad YA, Abdel Aziz I, et al. Experience with intravitreal ranibizumab as an adjunct to ablation therapy in eyes with exudative Coats' disease[J]. Clin Ophthalmol, 2021, 15: 367-373. DOI: 10.2147/OPTH.S293030.

Chinese Journal of Ocular Fundus Diseases

A prospective case-control study of intravitreal injection of anti-vascular endothelial factor drugs in the treatment of Coats disease

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