Retinal biomarkers associated with iron deficiency anemia and beta-thalassemia in children
DOI: 10.32364/2311-7729-2026-26-1-7
S.V. Yanchenko1, N.F. Saidova1, A.V. Malyshev2,3, E.N. Khairova4, Sh.Zh. Teshaev1, G.R. Odilova1, S.S. Davlatov1
1Bukhara State Medical Institute, Bukhara, Republic of Uzbekistan
2Scientific Research Institute — Regional Clinical Hospital No. 1, Krasnodar, Russian Federation
3Maykop State University of Technology, Maykop, Russian Federation
4ROSBIOTECH, Moscow, Russian Federation
Aim: to study retinal parameters in children with iron deficiency anemia (IDA) and beta-thalassemia (BT) by optical coherence tomography-angiography (OCTA) and to identify biomarkers of preclinical retinopathy (PR).
Materials and Methods: 90 children, 36 boys and 54 girls aged 7–18 years old (30 healthy volunteers (controls), 30 patients with IDA and 30 patients with BT major without ophthalmoscopic signs of retinopathy), were examined. Design: a prospective observational single-step case-control study. A standard ophthalmological examination, OCTA, and hematological parameter assessment were performed.
Results: children with IDA demonstrated a significant decrease in circularity index (CI) of foveal avascular zone (FAZ) and vascular density (VD) of the superficial retinal capillary plexus (SRCP) to 0.5±0.05 (p<0.001) and 37.3±0.95% (p=0.001), respectively, as compared with controls (0.63±0.05 and 38.5±1.1%, respectively) that may highlight retinal microcirculatory changes without ophthalmoscopic signs of retinopathy. FAZ CI is the most sensitive biomarker of PR in children with IDA (cut-off value — 0.55; sensitivity — 73.33%, specificity — 70%). Children with BT without ophthalmoscopic signs of retinopathy showed an increase in FAZ area (0.34±0.09 mm2; p=0.001) and perimeter (2.7±0.48 mm; p=0.001); a decrease in FAZ CI (0.45±0.06 RU; p<0.001), SRCP VD (36.15±1.69%; p<0.001) and DRCP (deep retinal capillary plexus) VD (39.03±2.61%; p=0.003) as compared with controls (0.27±0.05 mm2; 2.35±0.44 mm; 0.63±0.05 RU; 38,5±1,1%; 41,29±1,87%). This indicates more pronounced retinal microcirculatory changes than those associated with IDA. SRCP VD was the most sensitive biomarker of PR in children with BT (cut-off value — 37.5%; sensitivity — 76.67%, specificity — 83.3%).
Conclusion: OCTA revealed retinal microcirculatory changes in children with anemia without ophthalmoscopic signs of retinopathy. In patients with IDA and BT major, decreased FAZ CI and SRCP VD, respectively, may be biomarkers of PR. To minimize risks of clinical manifestation of retinopathy in these patients, retinoprotective therapy based on a complex of retinal water-soluble polypeptide fractions, added to stabilization of hematological parameters, seems to be a promising approach which requires further research.
Keywords: optical coherence tomography-angiography, iron deficiency anemia, beta-thalassemia, biomarkers, preclinical retinopathy, retinoprotection, retinalamin.
For citation: Yanchenko S.V., Saidova N.F., Malyshev A.V., Khairova E.N., Teshaev Sh.Zh., Odilova G.R., Davlatov S.S. Retinal biomarkers associated with iron deficiency anemia and beta-thalassemia in children. Russian Journal of Clinical Ophthalmology. 2026;26(1):45–51 (in Russ.). DOI: 10.32364/2311-7729-2026-26-1-7
ABOUT THE AUTHORS:
Sergey V. Yanchenko — Dr. Sc. (Med.), Professor of the Department of Ophthalmology, Bukhara State Medical Institute; 10, Gidzhuvanskaya st., Bukhara, 200126, Republic of Uzbekistan; ORCID iD 0000-0002-7371-689X
Nigora F. Saidova — Postgraduate Student, Department of Ophthalmology, Bukhara State Medical Institute; 10, Gidzhuvanskaya st., Bukhara, 200126, Republic of Uzbekistan; ORCID iD 0009-0001-7312-3541
Alexey V. Malyshev — Dr. Sc. (Med.), Head of the Department of Ophthalmology, Scientific Research Institute — Regional Clinical Hospital No. 1; 167, 1 Maya st., Krasnodar, 350000, Russian Federation; Head of the Department of Ophthalmology, Maykop State University of Technology, 191, Pervomaiskaya str., Maykop, Republic of Adygea, 385000, Russian Federation; ORCID iD 0000-0002-1448-9690
Elena N. Khairova — Dr. Sc. (Med.), Associate Professor, Professor of the Department of Therapy with a Course of Pharmacology and Pharmacy, at the ROSBIOTECH Medical Institute of Continuous Education; 11, Volokolamskoe road, Moscow, 125080, Russian Federation; ORCID iD 0000-0003-2954-8996
Shukhrat Zh. Teshaev — Dr. Sc. (Med.), Professor, Rector of Bukhara State Medical Institute; 10, Gidzhuvanskaya st., Bukhara, 200126, Republic of Uzbekistan; ORCID iD 0009-0002-1996-4275
Gulzhamol R. Odilova — Dr. Sc. (Med.), Assistant Professor, Head of the Department of Ophthalmology, Bukhara State Medical Institute; 10, Gidzhuvanskaya st., Bukhara, 200126, Republic of Uzbekistan; ORCID iD 000-0001-8825-8134
Salim S. Davlatov — Dr. Sc. (Med.), Assistant Professor, Head of the Quality Control Department, Bukhara State Medical Institute; 10, Gidzhuvanskaya st., Bukhara, 200126, Republic of Uzbekistan; ORCID iD 0000-0002-3268-7156
Contact information: Sergey V. Yanchenko, e-mail: eye2105sv@gmail.com
There is no conflict of interest.
Received 01.12.2025.
Revised 22.12.2025.
Accepted 26.01.2026.
2. Safiri S., Kolahi A.A., Noori M. et al. Burden of anemia and its underlying causes in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. J Hematol Oncol. 2021;14(1):185. DOI: 10.1186/s13045-021-01202-2
3. Means R.T. Iron Deficiency and Iron Deficiency Anemia: Implications and Impact in Pregnancy, Fetal Development, and Early Childhood Parameters. Nutrients. 2020;12(2):447. DOI: 10.3390/nu12020447
4. Kumar A., Sharma E., Marley A. et al. Iron deficiency anaemia: pathophysiology, assessment, practical management. BMJ Open Gastroenterol. 2022;9(1):e000759. DOI: 10.1136/bmjgast-2021-000759
5. Kattamis A., Kwiatkowski J.L., Aydinok Y. Thalassaemia. Lancet. 2022;399(10343):2310–2324. DOI: 10.1016/S0140-6736(22)00536-0
6. Baig R., Zahid N., Kausar F. et al. Burden of ocular abnormalities in patients with beta thalassaemia: a cross-sectional study. BMJ Open Ophthalmol. 2023;8(1):e001293. DOI: 10.1136/bmjophth-2023-001293
7. Heydarian S., Jafari R., Dailami K.N. Ocular abnormalities in beta thalassemia patients: prevalence, impact, and management strategies. Int Ophthalmol. 2020;40(2):511–527. DOI: 10.1007/s10792-019-01189-3
8. Jian T., Xu F., Li G. et al. Quantitative detection of macular microvascular abnormalities identified by optical coherence tomography angiography in different hematological diseases. Sci Rep. 2024;14:25433. DOI: 10.1038/s41598-024-76753-8
9. Güvenç U., Ünlü N., Yarali H.N., Özbek N.Y. Does thalassemia truly cause microvascular changes without us noticing? An optical coherence tomography angiography study of the children with beta-thalassemia. Int Ophthalmol. 2023;43(10):3755–3765. DOI: 10.1007/s10792-023-02786-z
10. Стулова А.Н., Семенова Н.С., Железнякова А.В. и др. Современные подходы к выявлению доклинических признаков диабетической ретинопатии с помощью ОКТ-ангиографии. Офтальмология. 2022;19(2):391–398. DOI: 10.18008/1816-5095-2022-2-391-398Stulova A.N., Semenova N.S., Zheleznyakova A.V. et al. OCT-Angiography in Detecting Preclinical Diabetic Retinopathy. Ophthalmology in Russia. 2022;19(2):391–398 (in Russ.). DOI: 10.18008/1816-5095-2022-2-391-398
11. Шпак А.А. Вопросы статистического анализа в российских офтальмологических журналах. Офтальмохирургия. 2016;(1):73–77. DOI: 10.25276/0235- 4160-2016-1-73-77Shpak A.A. Issues of the statistical analysis in the Russian ophthalmic journals. The Fyodorov Journal of Ophthalmic Surgery. 2016;(1):73–77 (in Russ.). DOI: 10.25276/0235-4160-2016-1-73-77
12. Wu Y., Wang D., Wu X. et al. Optical coherence tomography angiography for the characterisation of retinal microvasculature alterations in pregnant patients with anaemia: a nested case–control study. Br J Ophthalmol. 2023;108(1):117–123. DOI: 10.1136/bjo-2022-321781
13. Korkmaz M.F., Can M.E., Kazancı E.G. Effects of iron deficiency anemia on peripapillary and macular vessel density determined using optical coherence tomography angiography on children. Graefes Arch Clin Exp Ophthalmol. 2020;258(9):2059–2068. DOI: 10.1007/s00417-020-04633-8
14. Koca S., Bozkurt E., Eroğul Ö. et al. Evaluation of macular and optic disc radial peripapillary vessel density with optical coherence tomography angiography in iron deficiency anemia. Photodiagnosis Photodyn Ther. 2022;38:102744. DOI: 10.1016/j.pdpdt.2022.102744
15. Inanc M., Tekin K., Kiziltoprak H. Changes in retinal microcirculation precede the clinical onset of diabetic retinopathy in children with type 1 diabetes mellitus. Am J Ophthalmol. 2019;207:37–44. DOI: 10.1016/j.ajo.2019.04.011
16. Петрачков Д.В., Будзинская М.В. Биомаркеры диабетической ретинопатии, полученные при помощи оптической когерентной томографии в режиме ангиографии. Вестник офтальмологии. 2020;136(4):344–353. DOI: 10.17116/oftalma2020136042344Petrachkov D.V., Budzinskaya M.V. Biomarkers of diabetic retinopathy on optical coherence tomography angiography. Russian Annals of Ophthalmology. 2020;136(4):344–353 (in Russ.). DOI: 10.17116/oftalma2020136042344
17. Нероев В.В., Охоцимская Т.Д., Фадеева В.А. Оценка микрососудистых изменений сетчатки при сахарном диабете методом ОКТ-ангиографии. Российский офтальмологический журнал. 2017;10(2):40–45. DOI: 10.21516/2072-0076-2017-10-2-40-45Neroev V.V., Okhotsimskaya T.D., Fadeeva V.A. An account of retinal microvascular changes in diabetes acquired by OCTangiography. Russian Ophthalmological Journal. 2017;10(2):40–45 (in Russ.). DOI: 10.21516/2072-0076-2017-10-2-40-45
18. Haase V.H. Regulation of erythropoiesis by hypoxia inducible factors. Blood Rev. 2013;27(1):41–53. DOI: 10. 1016/j.blre.2012.12.003
19. Simsek A., Tekin M. et al. Evaluation of choroidal thickness in children with iron deficiency anemia. Invest Ophthalmol Vis Sci. 2016;57(14):5940–5944. DOI: 10.1167/iovs.15-18713
20. Celik Dulger S., Cevik Kaya S., Fen T., Teke M.Y. Effects of hemoglobin concentration on retinochoroidal vascular plexuses: an optical coherence tomography angiography study. Int Ophthalmol. 2024;44(1):117. DOI: 10.1007/s10792-024-03029-5
21. Niestrata-Ortiz M., Fichna P., Stankiewicz W. et al. Enlargement of the foveal avascular zone detected by optical coherence tomography angiography in diabetic children without diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2019;257(4):689–697. DOI: 10.1007/s00417-019-04264-8
22. Cennamo G., Montorio D., Mazzella G. et al. Retinal and Choriocapillaris Vascular Changes in Patients Affected by Different Clinical Phenotypes of β-Thalassemia: An Optical Coherence Tomography Angiography Study. Biology. 2021;10:276. DOI: 10.3390/ biology10040276
23. Türkyilmaz K., Oner V., Ozkasap S. et al. Peripapillary retinal nerve fiber layer thickness in children with iron deficiency anemia. Eur J Ophthalmol. 2013;23(2):217–222. DOI: 10.5301/ejo.5000206. PMID: 23112037
24. Ghasemi M., Ghasemi A., Khorasani S. et al. Characteristics of optical coherence tomography in patients with iron deficiency anemia: a systematic review and meta-analysis. BMC Ophthalmol. 2024;24(1):483. DOI: 10.1186/s12886-024-03751-9
25. Firdous M., Umer M.F., Chandran S.P. Optical coherence tomography findings in beta-thalassemia major: a systematic review and Meta-analysis. Int J Ophthalmol. 2025;18(6):1113–1122. DOI: 10.18240/ijo.2025.06.19
26. Верлов Н.А., Доротенко А.Р., Гулина Л.С. и др. Исследование лиганд-рецепторного взаимодействия и биораспределения при различных режимах введения лекарственного средства, содержащего полипептиды сетчатки глаз скота. Вестник офтальмологии. 2021;137(5):88–95. DOI: 10.17116/oftalma202113705188Verlov N.A., Dorotenko A.R., Gulina L.S. et al. Study of ligand-receptor interaction and biodistribution under various modes of administration of a medicine containing polypeptides from the livestock eyes retina. The Russian Annals of Ophthalmology. 2021;137(5):88–95 (in Russ.). DOI: 10.17116/oftalma202113705188
27. Fosgerau K., Hoffmann T. Peptide therapeutics: current status and future directions. Drug Discovery Today. 2015;20(1):122–128. DOI: 10.1016/j.drudis.2014.10.003
28. Lau J.L., Dunn M.K. Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorg Med Chem. 2018;26:2700–2707. DOI: 10.1016/j.bmc.2017.06.052
29. Даниличев В.Ф., Максимов И.Б. Травмы и заболевания глаз: применение ферментов и пептидных биорегуляторов. Минск: Наука и техника; 1994.Danilichev V.F., Maximov I.B. Eye injuries and diseases: the use of enzymes and peptide bioregulators. Minsk: Nauka i tehnika; 1994 (in Russ.).
30. Хасанова Н.Х., Беляева А.В. Результаты применения Ретиналамина при заболеваниях сетчатки. РМЖ. Клиническая офтальмология. 2008;9(3):77–82.Khasanova N.Kh., Belyaeva A.V. Results of Retinalamin usage in retinal diseases. RMJ. Clinical Ophthalmology. 2008;9(3):77–82 (in Russ.).
31. Егоров Е.А., Оганезова Ж.Г., Егорова Т.Е. Возможности применения Ретиналамина в терапии дистрофических заболеваний глаза (обзор клинических исследований). РМЖ. Клиническая офтальмология. 2009;10(2):57–58.Egorov E.A., Oganezova Zh.G., Egorova T.E. Possibilities of Retinalamin usage in treatment of dystrophic eye diseases (literary review). RMJ. Clinical Ophthalmology. 2009;10(2):57–58 (in Russ.).
32. Еричев В.П., Петров С.Ю., Волжанин А.В. Метаанализ клинических исследований эффективности ретинопротекторной терапии «сухой» формы ВМД с применением препарата Ретиналамин® по динамике остроты зрения. РМЖ. Клиническая офтальмология. 2017;4:219–226.Erichev V.P., Petrov S.Yu., Volzhanin A.V. Efficiency of retinoprotective dry AMD therapy with Retinalamin®: a randomized clinical trials metanalysis based on the dynamics of visual acuity. RMJ. Clinical ophthalmology. 2017;4:219–226 (in Russ.).
33. Малышев А.В., Янченко С.В., Саверская Е.Н. и др. Диабетическая ретинопатия: возможности и перспективы ретинопротекции. Офтальмология. 2024;21(2):256–263. DOI: 10.18008/1816509520242256263Malishev A.V., Yanchenko S.V., Saverskaya E.N. et al. Diabetic Retinopathy: Possibilities and Prospects for Retinoprotection. Ophthalmology in Russia. 2024;21(2):256–263 (in Russ.). DOI: 10.18008/1816509520242256263

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