Biomarkers of Myopic Choroidal Neovascularization in Women, Determining the Clinical Course and Response to Anti-VEGF Therapy

Aim: to identify clinical and laboratory biomarkers that determine the nature of the course of myopic choroidal neovascularization (mCNV) and the response to anti-VEGF therapy in women.

Material and methods. A prospective non-randomized study was conducted in 52 patients (52 eyes) with active mCNV, treated with ranibizumab intravitreally, 0.5mg. After 12months, the suppression of CNV activity, the number of injections and the fellow eye inclusion in the pathological process were taken into account. There were 2 groups: with a favorable clinical course (n = 31, age – 33,0 ± 5,1 years, anterior-posterior axis (APA) 28,5 ± 0,3 mm) and an unfavorable clinical course (n = 21, age – 34,0 ± 4,1 years, APA – 29,01 ± 0,1 mm). Structural retinal changes, choroid thickness, retinal blood flow, and heart rate were evaluated using OCT and OCTA protocols (Optovue XR Avanti, USA). Studies were conducted before the start of therapy and then one time per month. The concentration of sex and pituitary hormones (ELISA analyzer “Immunohem-2100”), lipoprotein A, Apo B/Apo A (Accent 200 Cormay, Poland), coagulogram data (Helena C-2, UK), and the concentration of highly sensitive C-reactive protein in blood serum before the start of antiangiogenic therapy were studied once.

Results. In the first group, 1.4 ± 0.7 ranibizumab injections were administered to suppress the CNV activity. In the opposite group – 3.5 ± 2.1 injections, in 73.7 % of cases, relapses were diagnosed, in 3 cases – primary CNV in the fellow eye. Clinical and laboratory biomarkers of the unfavorable clinical course of mCNV were identified: extreme choroidal thinning, highly organized membranes of a large area, dome-shaped deformation of the posterior pole, excess of the reference values of lipoprotein A, fibrinogen and highly sensitive C-reactive protein by two or more times, an imbalance of sex and pituitary hormones (excess of the reference values of prolactin, follicle stimulating hormone, cortisol, progesterone concentration decrease), a predominant change in the menstrual-ovarian cycle according to the type of amenorrhea and opsomenorrhea.

Conclusion. Myopic CNV biomarkers in women allow predicting the response to anti-VEGF therapy, the formation of relapses and the inclusion of the fellow eye in the pathological process. 

1. Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global Prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. 2016; 123(5): 1036-1042. doi: 10.1016/j.ophtha.2016.01.006

2. Wong Y-L, Saw S-M. Epidemiology of pathologic myopia in Asia and worldwide. Asia Pac J Ophthalmol (Phila). 2016; 5(6): 394-402. doi: 10.1097/APO.0000000000000234

3. Wong Y-L, Sabanayagam Ch, Ding Y, Wong Ch-W, Yeo ACh-H, Cheung Y-B, et al. Prevalence, risk factors, and impact of myopic macular degeneration on visual impairment and functioning among adults in Singapore. Invest Ophthalmol Vis Sci. 2018; 59(11): 4603-4613. doi: 10.1167/iovs.18-24032

4. Fang Y, Yokoi T, Nagaoka N, Shinohara K, Onishi Y, Ishida T, et al. Progression of myopic maculopathy during 18-year follow-up. Ophthalmology. 2018; 125(6): 863-877. doi: 10.1016/j.ophtha.2017.12.005

5. Wong TY, Ferreira A, Hughes R, Carter G, Mitchell P. Epidemiology and disease burden of pathologic myopia and myopic choroidal neovascularization: An evidence-based systematic review. Am J Ophthalmol. 2014; 157(1): 9-25.e12. doi: 10.1016/j.ajo.2013.08.010

6. Wong Y-L, Sabanayagam Ch, Wong Ch-W, Cheung Y-B, Man REK, Yeo AC-H, et al. Six-year changes in myopic macular degeneration in adults of the Singapore epidemiology of eye diseases study. Invest Ophthalmol Vis Sci. 2020; 61(4): 14. doi: 10.1167/iovs.61.4.14

7. Yoshida T, Ohno-Matsui K, Yasuzumi K, Kojima A, Shimada N, Futagami S, et al. Myopic choroidal neovascularization: A 10-year follow-up. Ophthalmology. 2003; 110(7): 1297-1305. doi: 10.1016/S0161-6420(03)00461-5

8. Wakabayashi T, Ikuno Y, Oshima Y, Hamasaki T, Nishida K. Aqueous concentrations of vascular endothelial growth factor in eyes with high myopia with and without choroidal neovascularization. J Ophthalmol. 2013; 2013: 257381. doi: 10.1155/2013/257381

9. Shchuko AG, Zaitseva NV, Iureva TN, Chernykh ER, Mikhalevich IM, Grigorieva AV. Role of immunological factors in the development of myopic choroidal neovascularization. The Russian Annals of Ophthalmology. 2016; 132(5): 5-14. doi: 10.17116/oftalma201613255-14. (In Russ.)

10. Wolf S, Balciuniene VJ, Laganovska G, Menchini U, Ohno-Matsui K, Sharma T, et al. RADIANCE: A randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology. 2014; 121(3): 682-92.e2. doi: 10.1016/j.ophtha.2013.10.023

11. Wong TY, Ohno-Matsui K, Leveziel N, Holz FG, Lai TY, Yu HG, et al. Myopic choroidal neovascularisation: Current concepts and update on clinical management. Br J Ophthalmol. 2015; 99(3): 289-296. doi: 10.1136/bjophthalmol-2014-305131

12. Sayanagi K, Uematsu S, Hara C, Wakabayashi T, Fukushima Y, Sato S, et al. Effect of intravitreal injection of aflibercept or ranibizumab on chorioretinal atrophy in myopic choroidal neovascularization. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2019; 257: 749-757. doi: 10.1007/s00417-018-04214-w

13. Silva R. Myopic maculopathy: A review. Ophthalmologica. 2012; 228(4): 197-213. doi: 10.1159/000339893

14. Ruiz-Moreno JM, Roura M. Cost of myopic patients with and without myopic choroidal neovascularization. Arch Soc Esp Oftalmol. 2016; 91(6): 265-272. doi: 10.1016/j.oftal.2016.01.013

15. Grigorieva AV, Iureva TN, Kursakova JuV, Ivanova EI. The role of changes in hormonal status in the formation of myopic chorioretinal neovascularization. Sovremennye tekhnologii v oftal’mologii. 2017; 4: 61-64. (In Russ.)

16. Tanemura M, Miyamoto N, Mandai M, Kamizuru H, Ooto S, Yasukawa T, et al. The role of estrogen and estrogen receptorbeta in choroidal neovascularization. Mol Vis. 2004; 10: 923-932.

17. Hormel TT, Jia Y, Jian Y, Hwang ThS, Bailey ST, Pennesi ME, et al. Plexus-specific retinal vascular anatomy and pathologies as seen by projection-resolved optical coherence tomographic angiography. Prog Retin Eye Res. 2021; 80: 100878. doi: 10.1016/j. preteyeres.2020.100878

18. Von der Burchard C, Treumer F, Ehlken Ch, Koinzer S, Purtskhvanidze K, Tode J, et al. Retinal volume change is a reliable OCT biomarker for disease activity in neovascular AMD. Graefes Arch Clin Exp Ophthalmol. 2018; 256(9): 1623-1629. doi: 10.1007/s00417-018-4040-7

19. Coscas GJ, Lupidi M, Coscas F, Cagini C, Souied EH. Optical coherence tomography angiography versus traditional multimodal imaging in assessing the activity of exudative age-related macular degeneration: A new diagnostic challenge. Retina. 2015; 35(11): 2219-2228. doi: 10.1097/IAE.0000000000000766