Application of an improved subretinal injection system in the treatment of submacular hemorrhage: a single-center, retrospective study_Chinese Journal of Ocular Fundus Diseases

Authors：

He Ying ¹ , Zhao Xufeng ² , Wei Liwei ¹ , Zhang Zheng ¹ , Zhang Shengjie ¹ , Liu Li ¹ , Chen Youxin ² , Yu Weihong ² , Min Hanyi ³ ,  Wang Huizhen ¹

1. Department of Operating Room, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China;
2. Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China;
3. Aier Eye Hospital, Tianjin University, Tianjin 300190, China;

Corresponding?author：

Wang Huizhen, Email: whzhen72@126.com

Keywords：

Submacular hemorrhage; Polypoidal choroidal vasculopathy; Subretinal injection; Vitreoretinal surgery

DOI：

10.3760/cma.j.cn511434-20250120-00031

Video：

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Objective To develop a simple and effective subretinal injection pipeline system to enhance the accuracy and precision of subretinal injection volume control. Methods A retrospective case series study. From May to October 2023, 18 patients (18 eyes) with submacular hemorrhage (SMH) who continuously received modified subretinal injection treatment in Department of Ophthalmology of Peking Union Medical College Hospital were included in the study. Among them, there were 10 males and 8 females. The mean age was (60.00±7.41) years. The primary causes included polypoid choroidal vasculopathy (14 cases), retinal macroaneurysm (2 cases), traumatic retinopathy (1 case), and Valsalva retinopathy (1 case). Hemorrhage affected 14 eyes of the fovea centralis. All affected eyes underwent standard three-channel 25G vitrectomy via the flat part of the ciliary body combined with modified subretinal injection of recombinant tissue plasminogen activator. The improved injection system consisted of a 1 ml syringe, a Q-Syte^TM connector, a 41G subretinal microinjection needle, a converter and a viscoelastic substance control pipeline. The drug preparation time for subretinal injection (i.e., the time consumed by the system connection step), the injection time, whether bubbles occur during the injection process, and the perioperative complications were recorded and analyzed. Results The preparation time prior to drug injection ranged from 230 to 335 seconds, while the injection completion time varied between 43 and 75 seconds. Both times decreased progressively as operator proficiency improved. Among the treated eyes, five received a target injection dose of 0.05 ml and thirteen received 0.10 ml, with all eyes achieving the preset dose accurately. No subretinal bubbles were observed during the injection procedure. Additionally, no intraoperative complications such as retinal hemorrhage or tear secondary to mechanical trauma at the injection site were recorded. Postoperatively, one eye developed anterior chamber hemorrhage, which resolved following intraocular pressure-lowering treatment. No other postoperative complications, including hemorrhage, rhegmatogenous retinal detachment, or infection, were observed in the remaining eyes. Conclusion The retinal drug injection system developed in this study has a simple structure, safe and stable operation, can achieve precise drug injection, and effectively avoid the formation of bubbles.

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2.	Diaconita V, Uhlman K, Mao A, et al. Survey of occupational musculoskeletal pain and injury in Canadian ophthalmology[J]. Can J Ophthalmol, 2019, 54(3): 314-322. DOI: 10.1016/j.jcjo.2018.06.021.
3.	Zhang Z, Wang L, Wei Y, et al. The preliminary experiences with three-dimensional heads-up display viewing system for vitreoretinal surgery under various status[J]. Curr Eye Res, 2019, 44(1): 102-109. DOI: 10.1080/02713683.2018.1526305.
4.	Nariai Y, Horiguchi M, Mizuguchi T, et al. Comparison of microscopic illumination between a three-dimensional heads-up system and eyepiece in cataract surgery[J]. Eur J Ophthalmol, 2021, 31(4): 1817-1821. DOI: 10.1177/1120672120929962.
5.	Saito-Uchida S, Inoue M, Koto T, et al. Vitrectomy combined with subretinal injection of tissue plasminogen activator for successful treatment of massive subretinal hemorrhage[J]. Eur J Ophthalmol, 2021, 31(5): 2588-2595. DOI: 10.1177/1120672120970404.
6.	Kimura S, Morizane Y, Hosokawa MM, et al. Outcomes of vitrectomy combined with subretinal tissue plasminogen activator injection for submacular hemorrhage associated with polypoidal choroidal vasculopathy[J]. Jpn J Ophthalmol, 2019, 63(5): 382-388. DOI: 10.1007/s10384-019-00679-2.
7.	Waizel M, Todorova MG, Rickmann A, et al. Efficacy of vitrectomy combined with subretinal rtPA injection with gas or air tamponade[J]. Klin Monbl Augenheilkd, 2017, 234(4): 487-492. DOI: 10.1055/s-0042-121575.
8.	Al-Hity A, Steel DH, Yorston D, et al. Incidence of submacular haemorrhage (SMH) in Scotland: a Scottish Ophthalmic Surveillance Unit (SOSU) study[J]. Eye (Lond), 2019, 33(3): 486-491. DOI: 10.1038/s41433-018-0239-4.
9.	張霜, 張杰, 徐鑫彥, 等. 組織型纖溶酶原激活劑、雷珠單抗聯合C₃F₈治療息肉樣脈絡膜血管病變并發早期黃斑下出血的療效觀察[J]. 中華眼底病雜志, 2018, 34(5): 448-452. DOI: 10.3760/cma.j.issn.1005-1015.2018.05.007.Zhang S, Zhang J, Xu XY, et al. The efficacy of intravitreal injection of tissue plasminogen activator, ranibizumab and C₃F₈ in the treatment of early submacular hemorrhage induce to polypoid choroid vasculopathy[J]. Chin J Ocul Fundus Dis, 2018, 34(5): 448-452. DOI: 10.3760/cma.j.issn.1005-1015.2018.05.007.
10.	安廣琪, 金學民, 戴方方, 等. 組織型纖溶酶原激活劑在黃斑下出血治療中的應用[J]. 中華眼外傷職業眼病雜志, 2020, 42(3): 237-240. DOI: 10.3760/cma.j.cn116022-20191024-00303.An GQ, Jin XM, Dai FF, et al. Application of tissue plasminogen activator in the treatment of submacular hemorrhage[J]. Chin J Ocul Traum Occupat Eye Dis, 2020, 42(3): 237-240. DOI: 10.3760/cma.j.cn116022-20191024-00303.
11.	Wakabayashi T, Hara C, Shiraki A, et al. Simultaneous intravitreal aflibercept and gas injections for submacular hemorrhage secondary to polypoidal choroidal vasculopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2023, 261(6): 1545-1552. DOI: 10.1007/s00417-022-05922-0.
12.	中華醫學會眼科學分會眼底病學組, 中國醫師協會眼科醫師分會眼底病專業委員會. 中國視網膜下基因治療藥物注射術操作規范推薦專家共識(2022)[J]. 中華實驗眼科雜志, 2022, 40(10): 887-893. DOI: 10.3760/cma.j.cn115989-20220808-00366.Fundus Disease Group of Chinese Medical Association Ophthalmology Branch, Fundus Disease Committee of Chinese Medical Doctor Association Ophthalmology Branch. Expert consensus on surgical technique for subretinal injection of gene therapy in China (2022)[J]. Chin J Exp Ophthalmol, 2022, 40(10): 887-893. DOI: 10.3760/cma.j.cn115989-20220808-00366.
13.	Feltgen N. Submacular hemorrhage[J]. Ophthalmologe, 2012, 109(7): 633-634. DOI: 10.1007/s00347-012-2562-7.
14.	Novelli FJD, Preti RC, Monteiro MLR, et al. A new method of subretinal injection of tissue plasminogen activator and air in patients with submacular hemorrhage[J]. Retina, 2017, 37(8): 1607-1611. DOI: 10.1097/IAE.0000000000001491.
15.	Shi T, Xie H, Chen H. Modified device for subretinal injection[J]. Retina, 2022, 42(1): 224-226. DOI: 10.1097/IAE.0000000000003342.
16.	Chernecky C, Waller J. Comparative evaluation of five needleless intravenous connectors[J]. J Adv Nurs, 2011, 67(7): 1601-1613. DOI: 10.1111/j.1365-2648.2010.05598.x.
17.	Raingeard E, Delcroix C, Lavainne F, et al. Impact of the use of luer access devices on the quality of chronic hemodialysis[J]. Nephrol Ther, 2012, 8(6): 451-455. DOI: 10.1016/j.nephro.2012.06.002.
18.	王春霞. 分隔膜無針密閉式輸液接頭在CRRT股靜脈血管通路應用的效果觀察[J]. 護理研究, 2014(18): 2237-2238. DOI: 10.3969/j.issn.10096493.2014.18.031.Wang CX. Observation on effect of separating film needleless closed transfusion connector in CRRT femoral vein vascular access[J]. Chinese Nursing Reasearch, 2014(18): 2237-2238. DOI: 10.3969/j.issn.10096493.2014.18.031.
19.	孫穎, 杜靜, 呂冬梅, 等. Q-SyteTM分隔膜無針接頭在術后留置中心靜脈導管患者中的應用[J]. 中華現代護理雜志, 2012, 18(23): 2824-2826. DOI: 10.3760/cma.j.issn.1674-2907.2012.23.034.Sun Y, Du J, Lyu DM, et al. Application of Q-SyteTM split septum needleless connector in patients with detained central venous catheter after surgery[J]. Chin J Mod Nurs, 2012, 18(23): 2824-2826. DOI: 10.3760/cma.j.issn.1674-2907.2012.23.034.
20.	Adams D, Karpanen T, Worthington T, et al. Infection risk associated with a closed luer access device[J]. J Hosp Infect, 2006, 62(3): 353-357. DOI: 10.1016/j.jhin.2005.09.016.
21.	Pohl F, Hartmann W, Holzmann T, et al. Risk of infection due to medical interventions via central venous catheters or implantable venous access port systems at the middle port of a three-way cock: luer lock cap vs. luer access split septum system (Q-Syte)[J/OL]. BMC Infect Dis, 2014, 14: 41[2014-01-25]. https://pubmed.ncbi.nlm.nih.gov/24460652/. DOI: 10.1186/1471-2334-14-41.

1. JH Cho, NK Ryoo, KH Cho, et al. Incidence rate of massive submacular hemorrhage and its risk factors in polypoidal choroidal vasculopathy[J]. Am J Ophthalmol, 2016, 169: 79-88. DOI: 10.1016/j.ajo.2016.06.014.
2. Diaconita V, Uhlman K, Mao A, et al. Survey of occupational musculoskeletal pain and injury in Canadian ophthalmology[J]. Can J Ophthalmol, 2019, 54(3): 314-322. DOI: 10.1016/j.jcjo.2018.06.021.
3. Zhang Z, Wang L, Wei Y, et al. The preliminary experiences with three-dimensional heads-up display viewing system for vitreoretinal surgery under various status[J]. Curr Eye Res, 2019, 44(1): 102-109. DOI: 10.1080/02713683.2018.1526305.
4. Nariai Y, Horiguchi M, Mizuguchi T, et al. Comparison of microscopic illumination between a three-dimensional heads-up system and eyepiece in cataract surgery[J]. Eur J Ophthalmol, 2021, 31(4): 1817-1821. DOI: 10.1177/1120672120929962.
5. Saito-Uchida S, Inoue M, Koto T, et al. Vitrectomy combined with subretinal injection of tissue plasminogen activator for successful treatment of massive subretinal hemorrhage[J]. Eur J Ophthalmol, 2021, 31(5): 2588-2595. DOI: 10.1177/1120672120970404.
6. Kimura S, Morizane Y, Hosokawa MM, et al. Outcomes of vitrectomy combined with subretinal tissue plasminogen activator injection for submacular hemorrhage associated with polypoidal choroidal vasculopathy[J]. Jpn J Ophthalmol, 2019, 63(5): 382-388. DOI: 10.1007/s10384-019-00679-2.
7. Waizel M, Todorova MG, Rickmann A, et al. Efficacy of vitrectomy combined with subretinal rtPA injection with gas or air tamponade[J]. Klin Monbl Augenheilkd, 2017, 234(4): 487-492. DOI: 10.1055/s-0042-121575.
8. Al-Hity A, Steel DH, Yorston D, et al. Incidence of submacular haemorrhage (SMH) in Scotland: a Scottish Ophthalmic Surveillance Unit (SOSU) study[J]. Eye (Lond), 2019, 33(3): 486-491. DOI: 10.1038/s41433-018-0239-4.
9. 張霜, 張杰, 徐鑫彥, 等. 組織型纖溶酶原激活劑、雷珠單抗聯合C₃F₈治療息肉樣脈絡膜血管病變并發早期黃斑下出血的療效觀察[J]. 中華眼底病雜志, 2018, 34(5): 448-452. DOI: 10.3760/cma.j.issn.1005-1015.2018.05.007.Zhang S, Zhang J, Xu XY, et al. The efficacy of intravitreal injection of tissue plasminogen activator, ranibizumab and C₃F₈ in the treatment of early submacular hemorrhage induce to polypoid choroid vasculopathy[J]. Chin J Ocul Fundus Dis, 2018, 34(5): 448-452. DOI: 10.3760/cma.j.issn.1005-1015.2018.05.007.
10. 安廣琪, 金學民, 戴方方, 等. 組織型纖溶酶原激活劑在黃斑下出血治療中的應用[J]. 中華眼外傷職業眼病雜志, 2020, 42(3): 237-240. DOI: 10.3760/cma.j.cn116022-20191024-00303.An GQ, Jin XM, Dai FF, et al. Application of tissue plasminogen activator in the treatment of submacular hemorrhage[J]. Chin J Ocul Traum Occupat Eye Dis, 2020, 42(3): 237-240. DOI: 10.3760/cma.j.cn116022-20191024-00303.
11. Wakabayashi T, Hara C, Shiraki A, et al. Simultaneous intravitreal aflibercept and gas injections for submacular hemorrhage secondary to polypoidal choroidal vasculopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2023, 261(6): 1545-1552. DOI: 10.1007/s00417-022-05922-0.
12. 中華醫學會眼科學分會眼底病學組, 中國醫師協會眼科醫師分會眼底病專業委員會. 中國視網膜下基因治療藥物注射術操作規范推薦專家共識(2022)[J]. 中華實驗眼科雜志, 2022, 40(10): 887-893. DOI: 10.3760/cma.j.cn115989-20220808-00366.Fundus Disease Group of Chinese Medical Association Ophthalmology Branch, Fundus Disease Committee of Chinese Medical Doctor Association Ophthalmology Branch. Expert consensus on surgical technique for subretinal injection of gene therapy in China (2022)[J]. Chin J Exp Ophthalmol, 2022, 40(10): 887-893. DOI: 10.3760/cma.j.cn115989-20220808-00366.
13. Feltgen N. Submacular hemorrhage[J]. Ophthalmologe, 2012, 109(7): 633-634. DOI: 10.1007/s00347-012-2562-7.
14. Novelli FJD, Preti RC, Monteiro MLR, et al. A new method of subretinal injection of tissue plasminogen activator and air in patients with submacular hemorrhage[J]. Retina, 2017, 37(8): 1607-1611. DOI: 10.1097/IAE.0000000000001491.
15. Shi T, Xie H, Chen H. Modified device for subretinal injection[J]. Retina, 2022, 42(1): 224-226. DOI: 10.1097/IAE.0000000000003342.
16. Chernecky C, Waller J. Comparative evaluation of five needleless intravenous connectors[J]. J Adv Nurs, 2011, 67(7): 1601-1613. DOI: 10.1111/j.1365-2648.2010.05598.x.
17. Raingeard E, Delcroix C, Lavainne F, et al. Impact of the use of luer access devices on the quality of chronic hemodialysis[J]. Nephrol Ther, 2012, 8(6): 451-455. DOI: 10.1016/j.nephro.2012.06.002.
18. 王春霞. 分隔膜無針密閉式輸液接頭在CRRT股靜脈血管通路應用的效果觀察[J]. 護理研究, 2014(18): 2237-2238. DOI: 10.3969/j.issn.10096493.2014.18.031.Wang CX. Observation on effect of separating film needleless closed transfusion connector in CRRT femoral vein vascular access[J]. Chinese Nursing Reasearch, 2014(18): 2237-2238. DOI: 10.3969/j.issn.10096493.2014.18.031.
19. 孫穎, 杜靜, 呂冬梅, 等. Q-SyteTM分隔膜無針接頭在術后留置中心靜脈導管患者中的應用[J]. 中華現代護理雜志, 2012, 18(23): 2824-2826. DOI: 10.3760/cma.j.issn.1674-2907.2012.23.034.Sun Y, Du J, Lyu DM, et al. Application of Q-SyteTM split septum needleless connector in patients with detained central venous catheter after surgery[J]. Chin J Mod Nurs, 2012, 18(23): 2824-2826. DOI: 10.3760/cma.j.issn.1674-2907.2012.23.034.
20. Adams D, Karpanen T, Worthington T, et al. Infection risk associated with a closed luer access device[J]. J Hosp Infect, 2006, 62(3): 353-357. DOI: 10.1016/j.jhin.2005.09.016.
21. Pohl F, Hartmann W, Holzmann T, et al. Risk of infection due to medical interventions via central venous catheters or implantable venous access port systems at the middle port of a three-way cock: luer lock cap vs. luer access split septum system (Q-Syte)[J/OL]. BMC Infect Dis, 2014, 14: 41[2014-01-25]. https://pubmed.ncbi.nlm.nih.gov/24460652/. DOI: 10.1186/1471-2334-14-41.

Chinese Journal of Ocular Fundus Diseases

Latest ArticlesApplication of an improved subretinal injection system in the treatment of submacular hemorrhage: a single-center, retrospective study

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