Abstract
Purpose
To investigate the effect of vitreomacular traction (VMT) on vitreous vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels in patients with active neovascular age-related macular degeneration (nAMD).
Design
A prospective, interventional, case-control study.
Methods
The study included a total of 70 patients from whom vitreous samples were obtained. The patients were categorized into four group: 10 patients with active nAMD accompanying VMT, 17 patients with VMT, 24 patients with active nAMD and 19 healthy patients without any diagnosis other than cataract. VEGF and PlGF levels were measured.
Results
The mean vitreous VEGF level was 34.7 ± 4.98 pg/ml in the nAMD and VMT group, 32.36 ± 4.55 pg/ml in the VMT group, 34.02 ± 3.79 pg/ml in the nAMD group, and 32.33 ± 2.4 pg/ml in the healthy control group. The mean vitreous PlGF level was 58.92 ± 20.83 pg/ml in the nAMD and VMT group, 46.29 ± 3.45 pg/ml in the VMT group, 54.64 ± 16.88 pg/ml in the nAMD group, and 53.66 ± 19.35 pg/ml in the healthy control group. No significant differences were observed in terms of vitreous VEGF and PlGF concentrations among the groups (p > 0.05 and p > 0.05, respectively). Aqueous humour VEGF and PlGF levels were significantly higher than vitreous levels in nAMD patients (p = 0.005 and p = 0.005, respectively).
Conclusion
The present study found no increases in vitreous VEGF and PlGF levels in both VMT + nAMD and VMT cases. Furthermore, patients with nAMD had significantly higher levels of PlGF and VEGF in aqueous humour compared to vitreous levels.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Data availability
Available if requested. All persons named in the Acknowledgment section provided written permission to be named.
References
Duker JS, Kaiser PK, Binder S, de Smet MD, Gaudric A, Reichel E, et al. The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology. 2013;120:2611–9.
Chang LK, Fine HF, Spaide RF, Koizumi H, Grossniklaus HE. Ultrastructural correlation of spectral-domain optical coherence tomographic findings in vitreomacular traction syndrome. Am J Ophthalmol. 2008;146:121–7.
Lee EK, Lee SY, Lee JY, Heo JW, Yu HG, Chung H. Anatomical configurations of vitreomacular traction syndrome: influence on clinical course and surgical outcomes. Graefes Arch Clin Exp Ophthalmol. 2019;257:1631–9.
Klein R, Peto T, Bird A, Vannewkirk MR. The epidemiology of age-related macular degeneration. Am J Ophthalmol. 2004;137:486–95.
Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2:e106–116.
Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984;102:1640–2.
Bressler SB. Introduction: Understanding the role of angiogenesis and antiangiogenic agents in age-related macular degeneration. Ophthalmology. 2009;116:S1–7.
Das A, McGuire PG. Retinal and choroidal angiogenesis: pathophysiology and strategies for inhibition. Prog Retin Eye Res. 2003;22:721–48.
McLeod DS, Taomoto M, Otsuji T, Green WR, Sunness JS, Lutty GA. Quantifying changes in RPE and choroidal vasculature in eyes with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2002;43:1986–93.
Grunwald JE, Hariprasad SM, DuPont J, Maguire MG, Fine SL, Brucker AJ, et al. Foveolar choroidal blood flow in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1998;39:385–90.
Campochiaro PA. Retinal and choroidal neovascularization. J Cell Physiol. 2000;184:301–10.
Amin R, Puklin JE, Frank RN. Growth factor localization in choroidal neovascular membranes of age-related macular degeneration. Invest Ophthalmol Vis Sci. 1994;35:3178–88.
Lopez PF, Sippy BD, Lambert HM, Thach AB, Hinton DR. Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes. Invest Ophthalmol Vis Sci. 1996;37:855–68.
Krebs I, Brannath W, Glittenberg C, Zeiler F, Sebag J, Binder S. Posterior vitreomacular adhesion: a potential risk factor for exudative age-related macular degeneration? Am J Ophthalmol. 2007;144:741–6.
Mojana F, Cheng L, Bartsch DU, Silva GA, Kozak I, Nigam N, et al. The role of abnormal vitreomacular adhesion in age-related macular degeneration: spectral optical coherence tomography and surgical results. Am J Ophthalmol. 2008;146:218–27.
Reese AB, Jones IS, Cooper WC. Macular changes secondary to vitreous traction. Am J Ophthalmol. 1967;64:544–9. Suppl
Suzuma I, Hata Y, Clermont A, Pokras F, Rook SL, Suzuma K, et al. Cyclic stretch and hypertension induce retinal expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2: potential mechanisms for exacerbation of diabetic retinopathy by hypertension. Diabetes. 2001;50:444–54.
Kinoshita H, Suzuma K, Maki T, Maekawa Y, Matsumoto M, Kusano M, et al. Cyclic stretch and hypertension increase retinal succinate: potential mechanisms for exacerbation of ocular neovascularization by mechanical stress. Invest Ophthalmol Vis Sci. 2014;55:4320–6.
Suzuma I, Suzuma K, Ueki K, Hata Y, Feener EP, King GL, et al. Stretch-induced retinal vascular endothelial growth factor expression is mediated by phosphatidylinositol 3-kinase and protein kinase C (PKC)-zeta but not by stretch-induced ERK1/2, Akt, Ras, or classical/novel PKC pathways. J Biol Chem. 2002;277:1047–57.
Krishnan R, Arora R, De Salvo G, Stinghe A, Severn PS, Pal B, et al. Vitreomacular Traction Affects Anti-Vascular Endothelial Growth Factor Treatment Outcomes For Exudative Age-Related Macular Degeneration. Retina. 2015;35:1750–6.
Ciulla TA, Ying GS, Maguire MG, Martin DF, Jaffe GJ, Grunwald JE, et al. Influence of the Vitreomacular Interface on Treatment Outcomes in the Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology. 2015;122:1203–11.
Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, Liu JJ, et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express. 2012;20:4710–25.
Boyer DS, Antoszyk AN, Awh CC, Bhisitkul RB, Shapiro H, Acharya NR. Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology. 2007;114:246–52.
Rotsos T, Sagoo MS, daCruz L, Andrews R, Dowler J. Intravitreal anti-VEGF treatment in eyes with combined choroidal neovascularisation and vitreomacular traction syndrome. Br J Ophthalmol. 2010;94:1205–10.
Spaide RF. Measurement of the posterior precortical vitreous pocket in fellow eyes with posterior vitreous detachment and macular holes. Retina. 2003;23:481–5.
Aiello LP, Northrup JM, Keyt BA, Takagi H, Iwamoto MA. Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol. 1995;113:1538–44.
Tsilimbaris MK, López-Gálvez MI, Gallego-Pinazo R, Margaron P, Lambrou GN. Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD. J Ophthalmol. 2016;2016:4367631.
Seko Y, Seko Y, Fujikura H, Pang J, Tokoro T, Shimokawa H. Induction of vascular endothelial growth factor after application of mechanical stress to retinal pigment epithelium of the rat in vitro. Invest Ophthalmol Vis Sci. 1999;40:3287–91.
Rakic JM, Lambert V, Devy L, Luttun A, Carmeliet P, Claes C, et al. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2003;44:3186–93.
Anderson DH, Mullins RF, Hageman GS, Johnson LV. A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol. 2002;134:411–31.
Donoso LA, Kim D, Frost A, Callahan A, Hageman G. The role of inflammation in the pathogenesis of age-related macular degeneration. Surv Ophthalmol. 2006;51:137–52.
Nussenblatt RB, Ferris F 3rd. Age-related macular degeneration and the immune response: implications for therapy. Am J Ophthalmol. 2007;144:618–26.
Lommatzsch A, Hermans P, Müller KD, Bornfeld N, Bird AC, Pauleikhoff D. Are low inflammatory reactions involved in exudative age-related macular degeneration? Morphological and immunhistochemical analysis of AMD associated with basal deposits. Graefes Arch Clin Exp Ophthalmol. 2008;246:803–10.
Waldstein SM, Wright J, Warburton J, Margaron P, Simader C, Schmidt-Erfurth U. Predictive Value of Retinal Morphology for Visual Acuity Outcomes of Different Ranibizumab Treatment Regimens for Neovascular AMD. Ophthalmology. 2016;123:60–9.
Maggio E, Polito A, Guerriero M, Prigione G, Parolini B, Pertile G. Vitreomacular Adhesion and the Risk of Neovascular Age-Related Macular Degeneration. Ophthalmology. 2017;124:657–66.
Holekamp NM, Bouck N, Volpert O. Pigment epithelium-derived factor is deficient in the vitreous of patients with choroidal neovascularization due to age-related macular degeneration. Am J Ophthalmol. 2002;134:220–7.
Mitamura Y, Tashimo A, Nakamura Y, Tagawa H, Ohtsuka K, Mizue Y, et al. Vitreous levels of placenta growth factor and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Diabetes Care. 2002;25:2352.
Holekamp NM. Vitreomacular adhesion in active and end-stage age-related macular degeneration. Am J Ophthalmol. 2010;149:171–2.
Kovacs K, Marra KV, Yu G, Wagley S, Ma J, Teague GC, et al. Angiogenic and Inflammatory Vitreous Biomarkers Associated With Increasing Levels of Retinal Ischemia. Invest Ophthalmol Vis Sci. 2015;56:6523–30.
Tsai DC, Charng MJ, Lee FL, Hsu WM, Chen SJ. Different plasma levels of vascular endothelial growth factor and nitric oxide between patients with choroidal and retinal neovascularization. Ophthalmologica. 2006;220:246–51.
Author information
Authors and Affiliations
Contributions
Concept: THC, KS. Design: THC, KS. Data collection/ processing: THC, KS, GK. Analysis/ interpretation: THC, KS, GK. Literature review: THC, KS. Writing the article: THC. Critical review: THC, KS. References and fundings: THC, KS. Materials: THC, KS, GK.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Horozoglu Ceran, T., Sonmez, K. & Kirtil, G. The impact of vitreomacular traction on vitreous vascular endothelial growth factor and placental growth factor levels in neovascular age-related macular degeneration patients. Eye 39, 373–378 (2025). https://doi.org/10.1038/s41433-024-03456-9
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41433-024-03456-9
