Anti-vascular endothelial growth factor treatment in X-linked retinoschisis with vitreous hemorrhage_Chinese Journal of Ocular Fundus Diseases

Authors：

Ma Jing , Li Songfeng , Liu Jinghua , Deng Guangda , Li Liang , Yuan Mingzhen , Zhou Dan ,  Lu Hai

Beijing Tongren Hospital, Capital Medical University, Beijing Tongren Eye Center, Key Laboratory of Beijing Ophthalmology and Visual Science, Beijing 100730, China;

Corresponding author：

Lu Hai, Email: trdr_luhai@163.com

Keywords：

X-linked retinoschisis; Vitreous hemorrhage; Angiogenesis inhibitors; Ranibizumab

DOI：

10.3760/cma.j.cn511434-20220512-00296

Video：

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Objective To review the outcome of intravitreous anti-vascular endothelial growth factor (VEGF) treatment in patients with X-linked retinoschisis (XLRS) complicated with vitreous hemorrhage (VH). Methods A retrospective clinical study. From March 1, 2016 to April 1, 2022, 18 patients (19 eyes) diagnosed with XLRS complicated with vitreous hemorrhage in Beijing Tongren Hospital, Capital Medical University of Eye Center were included. All the patients were male, with a median age of 7.05±3.8 years. Best corrected visual acuity (BCVA) and wide-angle fundus photography were performed in all the patients. BCVA was carried out using international standard visual acuity chart, and converted into logarithm of minimum resolution angle (logMAR) in statistics analysis. According to whether the patients received intravitreal injection of ranibizumab (IVR), the patients were divided into injection group and observation group, with 11 eyes in 10 cases and 8 eyes in 8 cases, respectively. In the injection group, 0.025 ml of 10 mg/ml ranibizumab (including 0.25 mg of ranibizumab) was injected into the vitreous cavity of the affected eye. Follow-up time after treatment was 24.82±20.77 months. The VH absorption time, visual acuity changes and complications were observed in the injection group after treatment. Paired sample t test was used to compare BCVA before and after VH and IVR treatment. Independent sample t test was used to compare the VH absorption time between the injection group and the observation group. Results LogMAR BCVA before and after VH were 0.73±0.32 and 1.80±0.77, respectively. BCVA decreased significantly after VH (t=－3.620, P=0.006). LogMAR BCVA after VH and IVR were 1.87±0.55 and 0.62±0.29, respectively. BCVA was significantly improved after IVR treatment (t=6.684, P＜0.001). BCVA records were available in 5 eyes before and after IVR, and the BCVA values after VH and IVR were 0.58±0.31 and 0.48±0.20, respectively, with no statistically significant difference (t=1.000, P=0.374). BCVA increased in 1 eye and remained unchanged in 4 eyes after treatment. BCVA records were available in 5 eyes before VH and after VH absorption in the 8 eyes of the observation group. LogMAR BCVA before VH and after VH absorption were 0.88±0.28 and 0.90±0.26, respectively, with no significant difference (t=－1.000, P=0.374). After VH absorption, BCVA remained unchanged in 4 eyes and decreased in 1 eye. The absorption time of VH in the injection group and the observation group were 1.80±1.06 and 7.25±5.04 months, respectively. The absorption time of VH was significantly shorter in the injection group than in the observation group, the difference was statistically significant (t=－3.005, P=0.018). Multivariate linear regression analysis showed that IVR treatment was significantly correlated with VH absorption time (B=－6.66, 95% confidence interval －10.93-－2.39, t=－3.40, P=0.005). In the injection group, VH recurrence occurred in 1 eye after IVR treatment. Vitrectomy (PPV) was performed in one eye. In the 8 eyes of the observation group, VH recurrence occurred in 2 eyes, subsequent PPV in 1 eye. The rate of VH recurrence and PPV was lower in the injection group, however, the difference was not statistically significant(P=0.576, 1.000). In terms of complications, minor subconjunctival hemorrhage occurred in 2 eyes and minor corneal epithelial injury occurred in 1 eye in the injection group, and all recovered spontaneously within a short time. In the injection group, 9 eyes had wide-angle fundus photography before and after IVR treatment. There was no significant change in the range of peripheral retinoschisis after treatment. No obvious proliferative vitreoretinopathy, infectious endophthalmitis, retinal detachment, macular hole, complicated cataract, secondary glaucoma or other serious complications were found in all the treated eyes, and there were no systemic complications. Conclusion Intravitreous anti-VEGF treatment may accelerate the absorption of vitreous hemorrhage in patients with XLRS. No impact is found regarding to the peripheral retinoschisis.

Citation： Ma Jing, Li Songfeng, Liu Jinghua, Deng Guangda, Li Liang, Yuan Mingzhen, Zhou Dan, Lu Hai. Anti-vascular endothelial growth factor treatment in X-linked retinoschisis with vitreous hemorrhage. Chinese Journal of Ocular Fundus Diseases, 2023, 39(1): 34-40. doi: 10.3760/cma.j.cn511434-20220512-00296 Copy

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2.	Rao P, Dedania VS, Drenser KA. Congenital X-linked retinoschisis: an updated clinical review[J]. Asia Pac J Ophthalmol (Phila), 2018, 7(3): 169-175. DOI: 10.22608/APO.201803.
3.	Xiao S, Sun W, Xiao X, et al. Clinical and genetic features of retinoschisis in 120 families with rs1 mutations[J/OL]. Br J Ophthalmol, 2021, 13: bjophthalmol-2021-319668[2021-10-13]. https://pubmed.ncbi.nlm.nih.gov/34645606/. DOI: 10.1136/bjophthalmol-2021-319668.
4.	Pearson R, Jagger J. Sex linked juvenile retinoschisis with optic disc and peripheral retinal neovascularisation[J]. Br J Ophthalmol, 1989, 73(4): 311-313. DOI: 10.1136/bjo.73.4.311.
5.	Ranchod TM, Faia LJ, Drenser KA. Peripapillary choroidal neovascularization in congenital retinoschisis[J]. Retin Cases Brief Rep, 2011, 5(4): 336-338. DOI: 10.1097/ICB.0b013e3181ff0960.
6.	Ando A, Takahashi K, Sho K, et al. Histopathological findings of X-linked retinoschisis with neovascular glaucoma[J]. Graefe's Arch Clin Exp Ophthalmol, 2000, 238(1): 1-7. DOI: 10.1007/s004170050001.
7.	Parra MM, Hartnett ME. Vitreous hemorrhage in X-linked retinoschisis[J/OL]. Am J Ophthalmol Case Rep, 2022, 25: 101395[2022-02-03].https://pubmed.ncbi.nlm.nih.gov/35198819/. DOI: 10.1016/j.ajoc.2022.101395.
8.	Luo M, Du H, Ding H, et al. Peripheral retinal neovascularization secondary to highly myopic superficial retinoschisis: a case report[J]. BMC Ophthalmol, 2020, 20(1): 25. DOI: 10.1186/s12886-020-1308-6.
9.	Campo RV, Reeser FH, Flindall RJ. Vascular leakage, neovascularization, and vitreous hemorrhage in senile bullous retinoschisis[J]. Am J Ophthalmol, 1983, 95(6): 826-832. DOI: 10.1016/0002-9394(83)90073-9.
10.	Wu AL, Wu WC. Anti-VEGF for ROP and pediatric retinal diseases[J]. Asia Pac J Ophthalmol (Phila), 2018, 7(3): 145-151. DOI: 10.22608/APO.201837.
11.	Hu QR, Huang LZ, Chen XL, et al. Genetic analysis and clinical features of X-linked retinoschisis in chinese patients[J/OL]. Sci Rep, 2017, 7: 44060[2017-03-08]. https://pubmed.ncbi.nlm.nih.gov/28272453/. DOI: 10.1038/srep44060.
12.	Fahim AT, Ali N, Blachley T, et al. Peripheral fundus findings in X-linked retinoschisis[J]. Br J Ophthalmol, 2017, 101(11): 1555-1559. DOI: 10.1136/bjophthalmol-2016-310110.
13.	Lewis TL, Maurer D. Multiple sensitive periods in human visual development: evidence from visually deprived children[J]. Dev Psychobiol, 2005, 46(3): 163-183. DOI: 10.1002/dev.20055.
14.	Regillo CD, Tasman WS, Brown GC. Surgical management of complications associated with X-linked retinoschisis[J]. Arch Ophthalmol, 1993, 111(8): 1080-1086. DOI: 10.1001/archopht.1993.01090080076021.
15.	Berenberg TL, Van Tassel SH, Patel SN, et al. Juvenile X-linked retinoschisis: a comparison of imaging modalities and review of angiographic findings[J/OL]. Retina, 2016, 36(12): e117-119[2016-12-01]. https://pubmed.ncbi.nlm.nih.gov/27164547/. DOI: 10.1097/IAE.0000000000001046.
16.	Ferrara N, Gerber HP, Lecouter J. The biology of vegf and its receptors[J]. Nat Med, 2003, 9(6): 669-676. DOI: 10.1038/nm0603-669.
17.	Green JL Jr, Jampol LM. Vascular opacification and leakage in X-linked (juvenile) retinoschisis[J]. Br J Ophthalmol, 1979, 63(5): 368-373. DOI: 10.1136/bjo.63.5.368.
18.	Chatziralli I, Loewenstein A. Intravitreal anti-vascular endothelial growth factor agents for the treatment of diabetic retinopathy: a review of the literature[J/OL]. Pharmaceutics, 2021, 13(8): 1137[2021-07-26]. https://pubmed.ncbi.nlm.nih.gov/34452097/. DOI: 10.3390/pharmaceutics13081137.
19.	Moradian S, Ahmadieh H, Malihi M, et al. Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2008, 246(12): 1699-1705. DOI: 10.1007/s00417-008-0914-4.
20.	Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy[J/OL]. Ophthalmology, 2006, 113(10): 1695[2006-10-01]. https://pubmed.ncbi.nlm.nih.gov/17011951/. DOI: 10.1016/j.ophtha.2006.05.064.
21.	Smith JM, Ward LT, Townsend JH, et al. Rhegmatogenous retinal detachment in children: clinical factors predictive of successful surgical repair[J]. Ophthalmology, 2019, 126(9): 1263-1270. DOI: 10.1016/j.ophtha.2018.11.001.
22.	Wu WC, Drenser KA, Capone A, et al. Plasmin enzyme-assisted vitreoretinal surgery in congenital X-linked retinoschisis: surgical techniques based on a new classification system[J]. Retina, 2007, 27(8): 1079-1085. DOI: 10.1097/IAE.0b013e31806196d0.
23.	Belin PJ, Lee AC, Greaves G, et al. The use of bevacizumab in pediatric retinal and choroidal disease: a review[J]. Eur J Ophthalmol, 2019, 29(3): 338-347. DOI: 10.1177/1120672119827773.
24.	Jeffrey BG, Cukras CA, Vitale S, et al. Test-retest intervisit variability of functional and structural parameters in x-linked retinoschisis[J]. Transl Vis Sci Technol, 2014, 3(5): 5. DOI: 10.1167/tvst.3.5.5.
25.	Verbakel SK, Van De Ven JP, Le Blanc LM, et al. Carbonic anhydrase inhibitors for the treatment of cystic macular lesions in children with X-linked juvenile retinoschisis[J]. Invest Ophthalmol Vis Sci, 2016, 57(13): 5143-5147. DOI: 10.1167/iovs.16-20078.
26.	Zhou Y, Yang S, Yuan Y, et al. Progression and new onset of macular retinoschisis in myopic choroidal neovascularization eyes after conbercept therapy: a post-hoc analysis[J]. Eye (Lond), 2020, 34(3): 523-529. DOI: 10.1038/s41433-019-0516-x.
27.	Ternant D, Paintaud G. Pharmacokinetics and concentration-effect relationships of therapeutic monoclonal antibodies and fusion proteins[J]. Expert Opin Biol Ther, 2005, 5(Suppl 1): S37-47. DOI: 10.1517/14712598.5.1.s37.
28.	Wu WC, Lien R, Liao PJ, et al. Serum levels of vascular endothelial growth factor and related factors after intravitreous bevacizumab injection for retinopathy of prematurity[J]. JAMA Ophthalmol, 2015, 133(4): 391-397. DOI: 10.1001/jamaophthalmol.2014.5373.

1. Molday RS, Kellner U, Weber BH. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms[J]. Prog Retin Eye Res, 2012, 31(3): 195-212. DOI: 10.1016/j.preteyeres.2011.12.002.
2. Rao P, Dedania VS, Drenser KA. Congenital X-linked retinoschisis: an updated clinical review[J]. Asia Pac J Ophthalmol (Phila), 2018, 7(3): 169-175. DOI: 10.22608/APO.201803.
3. Xiao S, Sun W, Xiao X, et al. Clinical and genetic features of retinoschisis in 120 families with rs1 mutations[J/OL]. Br J Ophthalmol, 2021, 13: bjophthalmol-2021-319668[2021-10-13]. https://pubmed.ncbi.nlm.nih.gov/34645606/. DOI: 10.1136/bjophthalmol-2021-319668.
4. Pearson R, Jagger J. Sex linked juvenile retinoschisis with optic disc and peripheral retinal neovascularisation[J]. Br J Ophthalmol, 1989, 73(4): 311-313. DOI: 10.1136/bjo.73.4.311.
5. Ranchod TM, Faia LJ, Drenser KA. Peripapillary choroidal neovascularization in congenital retinoschisis[J]. Retin Cases Brief Rep, 2011, 5(4): 336-338. DOI: 10.1097/ICB.0b013e3181ff0960.
6. Ando A, Takahashi K, Sho K, et al. Histopathological findings of X-linked retinoschisis with neovascular glaucoma[J]. Graefe's Arch Clin Exp Ophthalmol, 2000, 238(1): 1-7. DOI: 10.1007/s004170050001.
7. Parra MM, Hartnett ME. Vitreous hemorrhage in X-linked retinoschisis[J/OL]. Am J Ophthalmol Case Rep, 2022, 25: 101395[2022-02-03].https://pubmed.ncbi.nlm.nih.gov/35198819/. DOI: 10.1016/j.ajoc.2022.101395.
8. Luo M, Du H, Ding H, et al. Peripheral retinal neovascularization secondary to highly myopic superficial retinoschisis: a case report[J]. BMC Ophthalmol, 2020, 20(1): 25. DOI: 10.1186/s12886-020-1308-6.
9. Campo RV, Reeser FH, Flindall RJ. Vascular leakage, neovascularization, and vitreous hemorrhage in senile bullous retinoschisis[J]. Am J Ophthalmol, 1983, 95(6): 826-832. DOI: 10.1016/0002-9394(83)90073-9.
10. Wu AL, Wu WC. Anti-VEGF for ROP and pediatric retinal diseases[J]. Asia Pac J Ophthalmol (Phila), 2018, 7(3): 145-151. DOI: 10.22608/APO.201837.
11. Hu QR, Huang LZ, Chen XL, et al. Genetic analysis and clinical features of X-linked retinoschisis in chinese patients[J/OL]. Sci Rep, 2017, 7: 44060[2017-03-08]. https://pubmed.ncbi.nlm.nih.gov/28272453/. DOI: 10.1038/srep44060.
12. Fahim AT, Ali N, Blachley T, et al. Peripheral fundus findings in X-linked retinoschisis[J]. Br J Ophthalmol, 2017, 101(11): 1555-1559. DOI: 10.1136/bjophthalmol-2016-310110.
13. Lewis TL, Maurer D. Multiple sensitive periods in human visual development: evidence from visually deprived children[J]. Dev Psychobiol, 2005, 46(3): 163-183. DOI: 10.1002/dev.20055.
14. Regillo CD, Tasman WS, Brown GC. Surgical management of complications associated with X-linked retinoschisis[J]. Arch Ophthalmol, 1993, 111(8): 1080-1086. DOI: 10.1001/archopht.1993.01090080076021.
15. Berenberg TL, Van Tassel SH, Patel SN, et al. Juvenile X-linked retinoschisis: a comparison of imaging modalities and review of angiographic findings[J/OL]. Retina, 2016, 36(12): e117-119[2016-12-01]. https://pubmed.ncbi.nlm.nih.gov/27164547/. DOI: 10.1097/IAE.0000000000001046.
16. Ferrara N, Gerber HP, Lecouter J. The biology of vegf and its receptors[J]. Nat Med, 2003, 9(6): 669-676. DOI: 10.1038/nm0603-669.
17. Green JL Jr, Jampol LM. Vascular opacification and leakage in X-linked (juvenile) retinoschisis[J]. Br J Ophthalmol, 1979, 63(5): 368-373. DOI: 10.1136/bjo.63.5.368.
18. Chatziralli I, Loewenstein A. Intravitreal anti-vascular endothelial growth factor agents for the treatment of diabetic retinopathy: a review of the literature[J/OL]. Pharmaceutics, 2021, 13(8): 1137[2021-07-26]. https://pubmed.ncbi.nlm.nih.gov/34452097/. DOI: 10.3390/pharmaceutics13081137.
19. Moradian S, Ahmadieh H, Malihi M, et al. Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy[J]. Graefe's Arch Clin Exp Ophthalmol, 2008, 246(12): 1699-1705. DOI: 10.1007/s00417-008-0914-4.
20. Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy[J/OL]. Ophthalmology, 2006, 113(10): 1695[2006-10-01]. https://pubmed.ncbi.nlm.nih.gov/17011951/. DOI: 10.1016/j.ophtha.2006.05.064.
21. Smith JM, Ward LT, Townsend JH, et al. Rhegmatogenous retinal detachment in children: clinical factors predictive of successful surgical repair[J]. Ophthalmology, 2019, 126(9): 1263-1270. DOI: 10.1016/j.ophtha.2018.11.001.
22. Wu WC, Drenser KA, Capone A, et al. Plasmin enzyme-assisted vitreoretinal surgery in congenital X-linked retinoschisis: surgical techniques based on a new classification system[J]. Retina, 2007, 27(8): 1079-1085. DOI: 10.1097/IAE.0b013e31806196d0.
23. Belin PJ, Lee AC, Greaves G, et al. The use of bevacizumab in pediatric retinal and choroidal disease: a review[J]. Eur J Ophthalmol, 2019, 29(3): 338-347. DOI: 10.1177/1120672119827773.
24. Jeffrey BG, Cukras CA, Vitale S, et al. Test-retest intervisit variability of functional and structural parameters in x-linked retinoschisis[J]. Transl Vis Sci Technol, 2014, 3(5): 5. DOI: 10.1167/tvst.3.5.5.
25. Verbakel SK, Van De Ven JP, Le Blanc LM, et al. Carbonic anhydrase inhibitors for the treatment of cystic macular lesions in children with X-linked juvenile retinoschisis[J]. Invest Ophthalmol Vis Sci, 2016, 57(13): 5143-5147. DOI: 10.1167/iovs.16-20078.
26. Zhou Y, Yang S, Yuan Y, et al. Progression and new onset of macular retinoschisis in myopic choroidal neovascularization eyes after conbercept therapy: a post-hoc analysis[J]. Eye (Lond), 2020, 34(3): 523-529. DOI: 10.1038/s41433-019-0516-x.
27. Ternant D, Paintaud G. Pharmacokinetics and concentration-effect relationships of therapeutic monoclonal antibodies and fusion proteins[J]. Expert Opin Biol Ther, 2005, 5(Suppl 1): S37-47. DOI: 10.1517/14712598.5.1.s37.
28. Wu WC, Lien R, Liao PJ, et al. Serum levels of vascular endothelial growth factor and related factors after intravitreous bevacizumab injection for retinopathy of prematurity[J]. JAMA Ophthalmol, 2015, 133(4): 391-397. DOI: 10.1001/jamaophthalmol.2014.5373.

Chinese Journal of Ocular Fundus Diseases

Anti-vascular endothelial growth factor treatment in X-linked retinoschisis with vitreous hemorrhage

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