Abstract
Purpose
To evaluate the tear level of VEGF and the quantity of tear film in type 2 diabetic patients.
Methods
Thirty patients with diabetic retinopathy (DR group) and 30 patients with no DR (NDR group), and 30 healthy subjects with age and gender matching were enrolled in this prospective comparative study. The tear samples were collected using the Schirmer strips, and the amount of moisture absorbed by the strips was used to determine the quantitative level of the tear film. The concentration of VEGF in the tear samples was measured using the enzyme-linked immunosorbent assay method. The variables were compared with an independent t-test and covariance analysis.
Results
Mean tear level of VEGF was significantly higher in DR group (235.42 pg/ml) compared to NDR (75.11 pg/ml) and control (58.77 pg/ml) groups (P ≤ 0.001). There was no significant difference in the mean of VEGF between NDR and control patients (P = 1.00). Mean quantitative tear film levels were 7.15%, 9.72%, and 15.11% in DR, NDR, and healthy subjects, respectively (P < 0.05). The pairwise analysis showed significant differences in the level of VEGF between DR and both NDR (P = 0.001) and normal (P = 0.017) groups. However, there was no significant difference observed between NDR and normal eyes (P = 0.743).
Conclusion
The VEGF level in tear was higher in diabetic patients with DR, independent of tear volume. The tear VEGF measurement can be used as a valuable predictor to prevent DR in diabetic patients.
Similar content being viewed by others
References
Shukla UV, Tripathy K (2023). Diabetic retinopathy. In: StatPearls. Treasure island (FL): StatPearls publishing; available from: https://www.ncbi.nlm.nih.gov/books/NBK560805/
Teo ZL, Tham YC, Yu M, Chee ML, Rim TH, Cheung N, Bikbov MM, Wang YX, Tang Y, Lu Y, Wong IY, Ting DSW, Tan GSW, Jonas JB, Sabanayagam C, Wong TY, Cheng CY (2021) Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology 128(11):1580–1591. https://doi.org/10.1016/j.ophtha.2021.04.027
Cheung N, Mitchell P, Wong TY (2010) Diabetic retinopathy. Lancet 376(9735):124–136. https://doi.org/10.1016/s0140-6736(09)62124-3
Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME (2008) Vascular endothelial growth factor in eye disease. Prog Retin Eye Res 27(4):331–371. https://doi.org/10.1016/j.preteyeres.2008.05.001
Ang WJ, Zunaina E, Norfadzillah AJ, Raja-Norliza RO, Julieana M, Ab-Hamid SA, Mahaneem M (2019) Evaluation of vascular endothelial growth factor levels in tears and serum among diabetic patients. PLoS ONE 14(8):e0221481. https://doi.org/10.1371/journal.pone.0221481
Costagliola C, Romano V, De Tollis M, Aceto F, dell’Omo R, Romano MR, Pedicino C, Semeraro F (2013) TNF-alpha levels in tears: a novel biomarker to assess the degree of diabetic retinopathy. Mediators Inflamm 2013:629529. https://doi.org/10.1155/2013/629529
Wirostko B, Wong TY, Simó R (2008) Vascular endothelial growth factor and diabetic complications. Prog Retin Eye Res 27(6):608–621. https://doi.org/10.1016/j.preteyeres.2008.09.002
Kaštelan S, Orešković I, Bišćan F, Kaštelan H, Gverović Antunica A (2020) Inflammatory and angiogenic biomarkers in diabetic retinopathy. Biochem Med (Zagreb) 30(3):030502. https://doi.org/10.11613/bm.2020.030502
Vujosevic S, Benetti E, Massignan F, Pilotto E, Varano M, Cavarzeran F, Avogaro A, Midena E (2009) Screening for diabetic retinopathy: 1 and 3 nonmydriatic 45-degree digital fundus photographs vs 7 standard early treatment diabetic retinopathy study fields. Am J Ophthalmol 148(1):111–118. https://doi.org/10.1016/j.ajo.2009.02.031
Kumari S, Venkatesh P, Tandon N, Chawla R, Takkar B, Kumar A (2022) Selfie fundus imaging for diabetic retinopathy screening. Eye (Lond) 36(10):1988–1993. https://doi.org/10.1038/s41433-021-01804-7
Maturi RK, Glassman AR, Josic K, Antoszyk AN, Blodi BA, Jampol LM, Marcus DM, Martin DF, Melia M, Salehi-Had H, Stockdale CR, Punjabi OS, Sun JK (2021) Effect of intravitreous anti-vascular endothelial growth factor vs sham treatment for prevention of vision-threatening complications of diabetic retinopathy: the protocol w randomized clinical trial. JAMA Ophthalmol 139(7):701–712. https://doi.org/10.1001/jamaophthalmol.2021.0606
Park KS, Kim SS, Kim JC, Kim HC, Im YS, Ahn CW, Lee HK (2008) Serum and tear levels of nerve growth factor in diabetic retinopathy patients. Am J Ophthalmol 145(3):432–437. https://doi.org/10.1016/j.ajo.2007.11.011
Derakhshan A, Abrishami M, Khajedaluee M, Omidtabrizi A, Moghaddam SG (2019) Comparison between tear film osmolar cocentration and other tear film function parameters in patients with diabetes mellitus. Korean J Ophthalmol 33(4):326–332. https://doi.org/10.3341/kjo.2013.0146
Jiao X, Lu D, Pei X, Qi D, Huang S, Song Z, Gu J, Li Z (2020) Type 1 diabetes mellitus impairs diurnal oscillations in murine extraorbital lacrimal glands. Ocul Surf 18(3):438–452. https://doi.org/10.1016/j.jtos.2020.04.013
Pontelli RCN, Souza MCO, Fantucci MZ, de Andrade M, Rocha EM (2019) The role of endocrine disruptors in ocular surface diseases. Med Hypotheses 122:157–164. https://doi.org/10.1016/j.mehy.2018.11.009
Johnson ME, Murphy PJ (2004) Changes in the tear film and ocular surface from dry eye syndrome. Prog Retin Eye Res 23(4):449–474. https://doi.org/10.1016/j.preteyeres.2004.04.003
Enríquez-de-Salamanca A, Castellanos E, Stern ME, Fernández I, Carreño E, García-Vázquez C, Herreras JM, Calonge M (2010) Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease. Mol Vis 16:862–873
Zhang X, Saaddine JB, Chou CF, Cotch MF, Cheng YJ, Geiss LS, Gregg EW, Albright AL, Klein BE, Klein R (2010) Prevalence of diabetic retinopathy in the United States, 2005–2008. JAMA 304(6):649–656. https://doi.org/10.1001/jama.2010.1111
Organization WH (2020) Diagnosis and management of type 2 diabetes (HEARTS-D). World Health Organization, Geneva, Switzerland
Rifai N (2017) Tietz textbook of clinical chemistry and molecular diagnostics. Elsevier, Health Sciences
Ixcamey M, Palma C (2021) Diabetic macular edema. Dis Mon 67(5):101138. https://doi.org/10.1016/j.disamonth.2021.101138
Ljubimov AV, Huang ZS, Huang GH, Burgeson RE, Gullberg D, Miner JH, Ninomiya Y, Sado Y, Kenney MC (1998) Human corneal epithelial basement membrane and integrin alterations in diabetes and diabetic retinopathy. J Histochem Cytochem 46(9):1033–1041. https://doi.org/10.1177/002215549804600907
Kasza M, Balogh Z, Biro L, Ujhelyi B, Damjanovich J, Csutak A, Várdai J, Berta A, Nagy V (2015) Vascular endothelial growth factor levels in tears of patients with retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 253(9):1581–1586. https://doi.org/10.1007/s00417-015-3030-2
Wang J-Y, Kwon J-S, Hsu S-M, Chuang H-S (2020) Sensitive tear screening of diabetic retinopathy with dual biomarkers enabled using a rapid electrokinetic patterning platform. Lab Chip 20(2):356–362. https://doi.org/10.1039/C9LC00975B
Pieczyński J, Szulc U, Harazna J, Szulc A, Kiewisz J (2021) Tear fluid collection methods: review of current techniques. Eur J Ophthalmol 31(5):2245–2251. https://doi.org/10.1177/1120672121998922
Matthews DR, Stratton IM, Aldington SJ, Holman RR, Kohner EM (2004) Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Arch Ophthalmol 122(11):1631–1640. https://doi.org/10.1001/archopht.122.11.1631
Domngang C, Noutchie AL, Chuisseu PD, Simo FN, Galani BT, Mekieje PT, Nzounji FU, Djahmeni EN, Guewo-Fokeng M, Kagmeni G (2020) Level of VEGF-A and interleukin 6 in lacrimal fluid of patients with diabetic retinopathy. Int J Biol Chem Sci 14(3):664–673
The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop (2007) Ocul Surf 5 (2):75–92. https://doi.org/10.1016/s1542-0124(12)70081-2
Zhang X, Zhao L, Deng S, Sun X, Wang N (2016) Dry eye syndrome in patients with diabetes mellitus: prevalence, etiology, and clinical characteristics. J Ophthalmol 2016:8201053. https://doi.org/10.1155/2016/8201053
Manaviat MR, Rashidi M, Afkhami-Ardekani M, Shoja MR (2008) Prevalence of dry eye syndrome and diabetic retinopathy in type 2 diabetic patients. BMC Ophthalmol 8:10. https://doi.org/10.1186/1471-2415-8-10
Saini JS, Mittal S (1996) Graded corneal sensitivity for screening of diabetic retinopathy. Indian J Ophthalmol 44(4):219–223
Salami MO, Aribaba OT, Musa KO, Rotimi-Samuel A, Onakoya AO (2020) Relationship between corneal sensitivity and diabetic retinopathy among diabetics attending a Nigerian Teaching Hospital. Int Ophthalmol 40(10):2707–2716. https://doi.org/10.1007/s10792-020-01456-8
Nepp J, Abela C, Polzer I, Derbolav A, Wedrich A (2000) Is there a correlation between the severity of diabetic retinopathy and keratoconjunctivitis sicca? Cornea 19(4):487–491. https://doi.org/10.1097/00003226-200007000-00017
Błochowiak KJ, Trzybulska D, Olewicz-Gawlik A, Sikora JJ, Nowak-Gabryel M, Kocięcki J, Witmanowski H, Sokalski J (2018) Levels of EGF and VEGF in patients with primary and secondary Sjögren’s syndrome. Adv Clin Exp Med 27(4):455–461. https://doi.org/10.17219/acem/70800
Rentka A, Hársfalvi J, Berta A, Köröskényi K, Szekanecz Z, Szücs G, Szodoray P, Kemény-Beke Á (2015) Vascular endothelial growth factor in tear samples of patients with systemic sclerosis. Mediators Inflamm 2015:573681. https://doi.org/10.1155/2015/573681
Acknowledgements
The authors received no financial support for the research, authorship, and/or publication of this article. The authors declare that there is no conflict of interest.
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by ZH, HH, HA, ZR, and AA. The first draft of the manuscript was written by ZH and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interests
The authors have no financial interests.
Ethical approval
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Mazandaran University of Medical Sciences.
Consent to participate
Informed consent was obtained from all individual participants included.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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
Hashemi, H., Ahmadi, H., Rostami, Z. et al. The role of endothelial growth factor and tear levels in diabetic retinopathy in type 2 diabetes. Int Ophthalmol 44, 143 (2024). https://doi.org/10.1007/s10792-024-03064-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10792-024-03064-2