Retinal and Choriocapillaris Vascular Changes in Patients Affected by Different Clinical Phenotypes of β-Thalassemia: An Optical Coherence Tomography Angiography Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Spectral Domain Optical Coherence Tomography
2.3. Optical Coherence Tomography Angiography
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Vichinsky, E.P. Changing patterns of thalassemia worldwide. Ann. N. Y. Acad. Sci. 2005, 1054, 18–24. [Google Scholar] [CrossRef]
- Liaska, A.; Petrou, P.; Georgakopoulos, C.D.; Diamanti, R.; Papaconstantinou, D.; Kanakis, M.G.; Georgalas, I. β-Thalassemia and ocular implications: A systematic review. BMC Ophthalmol. 2016, 16, 102. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grosso, M.; Amendolara, M.; Rescigno, G.; Danise, P.; Todisco, N.; Izzo, P.; Amendola, G. Delayed decline of gamma-globin expression in infant age associated with the presence of Ggamma-158 (C-->T) polymorphism. Int. J. Lab. Hematol. 2008, 30, 191–195. [Google Scholar] [CrossRef] [PubMed]
- Pepe, A.; Meloni, A.; Pistoia, L.; Cuccia, L.; Gamberini, M.R.; Lisi, R.; D’Ascola, D.G.; Rosso, R.; Allò, M.; Spasiano, A.; et al. MRI multicentre prospective survey in thalassaemia major patients treated with deferasirox versus deferiprone and desferrioxamine. Br. J. Haematol. 2018, 183, 783–795. [Google Scholar] [CrossRef] [Green Version]
- Ricchi, P.; Ammirabile, M.; Spasiano, A.; Costantini, S.; Cinque, P.; Di Matola, T.; Pagano, L.; Prossomariti, L. Combined chelation therapy in thalassemia major with deferiprone and desferrioxamine: A retrospective study. Eur. J. Haematol. 2010, 85, 36–42. [Google Scholar] [CrossRef]
- Capolongo, G.; Zacchia, M.; Beneduci, A.; Costantini, S.; Cinque, P.; Spasiano, A.; De Luca, G.; Di Pietro, M.E.; Ricchi, P.; Trepiccione, F.; et al. Urinary Metabolic Profile of Patients with Transfusion-Dependent β-Thalassemia Major Undergoing Deferasirox Therapy. Kidney Blood Press Res. 2020, 45, 455–466. [Google Scholar] [CrossRef]
- Rund, D.; Rachmilewitz, E. Beta-thalassemia. N. Engl. J. Med. 2005, 353, 1135–1146. [Google Scholar] [CrossRef]
- Taneja, R.; Malik, P.; Sharma, M.; Agarwal, M.C. Multiple transfused thalassemia major: Ocular manifestations in a hospital-based population. Indian J. Ophthalmol. 2010, 58, 125–130. [Google Scholar]
- Wu, C.H.; Yang, C.P.; Lai, C.C.; Wu, W.C.; Chen, Y.H. Deferoxamine retinopathy:spectral domain-optical coherence tomography findings. BMC Ophthalmol. 2014, 2, 88–90. [Google Scholar] [CrossRef] [Green Version]
- Rahi, A.H.; Hungerford, J.L.; Ahmed, A.I. Ocular toxicity of desferrioxamine: Light microscopic histochemical and ultrastructural findings. Br. J. Ophthalmol. 1986, 70, 373–381. [Google Scholar] [CrossRef]
- Arden, G.B.; Wonke, B.; Kennedy, C.; Huehns, E.R. Ocular changes in patients undergoing long-term desferrioxamine treatment. Br. J. Ophthalmol. 1984, 68, 873–877. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aessopos, A.; Farmakis, D.; Loukopoulos, D. Elastic tissue abnormalities resembling pseudoxanthoma elasticum in beta thalassemia and the sickling syndromes. Blood 2002, 99, 30–35. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rund, D.; Rachmilewitz, E. Pathophysiology of alpha- and beta-thalassemia: Therapeutic implications. Semin. Hematol 2001, 38, 343–349. [Google Scholar] [CrossRef]
- Karimi, M.; Cohan, N.; De Sanctis, V.; Mallat, N.S.; Taher, A. Guidelines for diagnosis and management of Beta-thalassemia intermedia. Pediatr. Hematol. Oncol. 2014, 31, 583–596. [Google Scholar] [CrossRef]
- Haase, V.H. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev. 2013, 27, 41–53. [Google Scholar] [CrossRef] [Green Version]
- Kassab-Chekir, A.; Laradi, S.; Ferchichi, S.; Khelil, A.H.; Feki, M.F.; Amri, F.; Selmi, H.; Bejaoui, M.; Miled, A. Oxidant, antioxidant status and metabolic data in patients with betathalassemia. Clin. Chim. Acta 2003, 338, 79–86. [Google Scholar] [CrossRef] [PubMed]
- Savastano, M.C.; Lumbroso, B.; Rispoli, M. In vivo characterization of retinal vascularization morphology using optical coherence tomography angiography. Retina 2015, 35, 2196–2203. [Google Scholar] [CrossRef] [PubMed]
- Spaide, R.F. Choriocapillaris Flow Features Follow a Power Law Distribution: Implications for Characterization and Mechanisms of Disease Progression. Am. J. Ophthalmol. 2016, 170, 58–67. [Google Scholar] [CrossRef] [PubMed]
- Cennamo, G.; Montorio, D.; Velotti, N.; Sparnelli, F.; Reibaldi, M.; Cennamo, G. Optical coherence tomography angiography in pre-perimetric open-angle glaucoma. Graefes Arch Clin. Exp. Ophthalmol. 2017, 255, 1787–1793. [Google Scholar] [CrossRef]
- Jia, Y.; Tan, O.; Tokayer, J.; Potsaid, B.; Wang, Y.; Liu, J.J.; Kraus, M.F.; Subhash, H.; Fujimoto, J.G.; Hornegger, J.; et al. Split spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt. Express 2012, 20, 4710–4725. [Google Scholar] [CrossRef] [Green Version]
- Huang, D.; Jia, Y.; Gao, S.S.; Lumbroso, B.; Rispoli, M. Optical Coherence Tomography Angiography Using the Optovue Device. Dev. Ophthalmol. 2016, 56, 6–12. [Google Scholar]
- Rao, H.L.; Pradhan, Z.S.; Weinreb, R.N.; Reddy, H.B.; Riyazuddin, M.; Dasari, S.; Palakurthy, M.; Puttaiah, N.K.; Rao, D.A.; Webers, C.A. Regional Comparisons of Optical Coherence Tomography Angiography Vessel Density in Primary Open-Angle Glaucoma. Am. J. Ophthalmol. 2016, 171, 75–83. [Google Scholar] [CrossRef] [PubMed]
- Moein, H.R.; Novais, E.A.; Rebhun, C.B.; Cole, E.D.; Louzada, R.N.; Witkin, A.J.; Baumal, C.R.; Duker, J.S.; Waheed, N.K. Optical coherence tomography angiography to detect macular capillary ischemia in patients with inner retinal changes after resolved diabetic. Retina 2018, 38, 2277–2284. [Google Scholar] [CrossRef] [PubMed]
- Filosa, A.; Valgimigli, L.; Pedulli, G.F.; Sapone, A.; Maggio, A.; Renda, D.; Scazzone, C.; Malizia, R.; Pitrolo, L.; Lo Pinto, C.; et al. Quantitative evaluation of oxidative stress status on peripheral blood in beta-thalassaemic patients by means of electron paramagnetic resonance spectroscopy. Br. J. Haematol. 2005, 131, 135–140. [Google Scholar] [CrossRef] [PubMed]
- Connor, J.R.; Menzies, S.L. Relationship of iron to oligodendrocytes and myelination. Glia 1996, 17, 83–93. [Google Scholar] [CrossRef]
- Lozoff, B. Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction. J. Nutr. 2011, 141, 740–746. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dhawan, V.; Kumar, K.H.R.; Marwaha, R.K.; Ganguly, N.K. Antioxidant status in children with homozygous beta thalassemia. Indian Pediatr. 2005, 42, 1141–1145. [Google Scholar] [PubMed]
- Aksoy, A.; Aslan, L.; Aslankurt, M.; Eser, O.; Garipardic, M.; Okumus, S.; Kaya, G. Retinal fiber layerthickness in children with thalessemia major and iron deficiency anemia. Semin. Ophthalmol. 2014, 29, 22–26. [Google Scholar] [CrossRef]
- Nemeth, E. Hepcidin in beta-thalassemia. Ann. N. Y. Acad. Sci. 2010, 1202, 31–35. [Google Scholar] [CrossRef] [PubMed]
- Uzun, F.; Karaca, E.E.; Yıldız Yerlikaya, G.; Fındık, H.; Akın, M. Retinal nerve fiber layer thickness in children with β-thalassemia major. Saudi. J. Ophthalmol. 2017, 31, 224–228. [Google Scholar] [CrossRef] [PubMed]
- Turkyilmaz, K.; Oner, V.; Ozkasap, S.; Sekeryapan, B.; Dereci, S.; Durmus, M. Peripapillary retinal nerve fiber layer thickness in children with iron deficiency anemia. Eur. J. Ophthalmol. 2013, 23, 217–222. [Google Scholar] [CrossRef]
- Acer, S.; Balci, Y.I.; Pekel, G.; Ongun, T.T.; Polat, A.; Çetin, E.N.; Yağcı, R. Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor. SAGE Open Med. 2016, 4, 2050312116661683. [Google Scholar] [CrossRef]
- Aggeli, C.; Antoniades, C.; Cosma, C.; Chrysohoou, C.; Tousoulis, D.; Ladis, V.; Karageorga, M.; Pitsavos, C.; Stefanadis, C. Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major. Int. J. Cardiol. 2005, 105, 80–84. [Google Scholar] [CrossRef] [PubMed]
- Campbell, J.P.; Zhang, M.; Hwang, T.S.; Bailey, S.T.; Wilson, D.J.; Jia, Y.; Huang, D. Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography. Sci. Rep. 2017, 7, 42201. [Google Scholar] [CrossRef] [Green Version]
- Samara, W.A.; Say, E.A.; Khoo, C.T.; Higgins, T.P.; Magrath, G.; Ferenczy, S.; Shields, C.L. Correlation of Foveal Avascular Zone Size with Foveal Morphology in Normal Eyes Using Optical Coherence Tomography Angiography. Retina 2015, 35, 2188–2195. [Google Scholar] [CrossRef] [PubMed]
- Güler Kazancı, E.; Korkmaz, M.F.; Can, M.E. Optical coherence tomography angiography findings in young β-thalassemia patients. Eur. J. Ophthalmol. 2020, 30, 600–607. [Google Scholar] [CrossRef] [PubMed]
- Georgalas, I.; Makris, G.; Papaconstantinou, D. A Pilot Optical Coherence Tomography Angiography Study on Superficial and Deep Capillary Plexus Foveal Avascular Zone in Patients with Beta-Thalassemia Major. Investig. Ophthalmol. Vis. Sci. 2019, 60, 3887–3896. [Google Scholar] [CrossRef] [PubMed]
- Pichi, F.; Sarraf, D.; Morara, M.; Mazumdar, S.; Neri, P.; Gupta, V. Pearls and pitfalls of optical coherence tomography angiography in the multimodal evaluation of uveitis. J. Ophthalmic. Inflamm. Infect. 2017, 7, 20. [Google Scholar] [CrossRef]
- Vujosevic, S.; Martini, F.; Cavarzeran, F.; Pilotto, E.; Midena, E. Macular and peripapillary choroidal thickness in diabetic patients. Retina 2012, 32, 1781–1790. [Google Scholar] [CrossRef]
- Bhoiwala, D.L.; Dunaief, J.L. Retinal abnormalities in β-thalassemia major. Surv. Ophthalmol. 2016, 6, 33–50. [Google Scholar] [CrossRef] [Green Version]
- Van Bol, L.; Alami, A.; Benghiat, F.S.; Rasquin, F. Spectral domain optical coherence tomography findings in early deferoxamine maculopathy: Report of two cases. Retin. Cases Brief Rep. 2014, 8, 97–102. [Google Scholar] [CrossRef] [PubMed]
- Viola, F.; Barteselli, G.; Dell’Arti, L.; Vezzola, D.; Mapelli, C.; Villani, E.; Ratiglia, R. Multimodal imaging in deferoxamine retinopathy. Retina 2014, 34, 1428–1438. [Google Scholar] [CrossRef] [PubMed]
- Viola, F.; Barteselli, G.; Dell’arti, L.; Vezzola, D.; Villani, E.; Mapelli, C.; Zanaboni, L.; Cappellini, M.D.; Ratiglia, R. Abnormal fundus autofluorescence results of patients in long-term treatment with deferoxamine. Ophthalmology 2012, 119, 1693–1700. [Google Scholar] [CrossRef] [PubMed]
Control Group | TDT | NTDT | β-Thalassemia Minor | p Value | |
---|---|---|---|---|---|
Eye (n.) | 40 | 42 | 34 | 48 | - |
Age (years) | 44 ± 5.3 | 45.2 ± 3.6 | 43.88 ± 5.4 | 44.91 ± 7.5 | 0.855 |
Gender (male/female) | 8/12 | 8/13 | 4/13 | 14/10 | 0.158 † |
BCVA (logMAR) | 0.05 ± 0.08 | 0.06 ± 0.06 | 0.05 ± 0.06 | 0.03 ± 0.05 | 0.765 |
Hemoglobin (g/dL) | 12.02 ± 0.90 | 10 ± 0.42 | 9.67 ± 0.86 | 11.58 ± 1.39 | <0.001 |
Ferritin (nmol/L) | 72.85 ± 26.36 | 1459.05 ± 1745.27 | 485.35 ± 416.89 | 161.52 ± 192.92 | <0.001 |
Control Group | TDT | p Value | NTDT | p Value * | β-Thalassemia Minor | p Value † | Anova | |
---|---|---|---|---|---|---|---|---|
GCC (µm) | ||||||||
Average | 103.07 ± 7.69 | 97.50 ± 9.23 | 0.011 | 101.35 ± 5.98 | 0.465 | 102.37 ± 8.30 | 0.851 | 0.008 |
Superior | 105.87 ± 7.61 | 98.73 ± 8.74 | 0.001 | 104.17 ± 7.50 | 0.758 | 105.10 ± 9.76 | 0.994 | 0.001 |
Inferior | 104.47 ± 7.87 | 96.59 ± 7.50 | <0.001 | 100.02 ± 5.82 | 0.053 | 103.33 ± 7.15 | 0.742 | <0.001 |
RNFL (µm) | ||||||||
Average | 110.80 ± 7.58 | 99.73 ± 8.48 | <0.001 | 113.05 ± 7.24 | 0.819 | 110.25 ± 6.03 | 1 | <0.001 |
Superior | 112.85 ± 6.72 | 101.04 ± 7.47 | <0.001 | 114.20 ± 6.79 | 0.784 | 111.20 ± 6.20 | 0.865 | <0.001 |
Inferior | 108.30 ± 7.75 | 98.47 ± 7.70 | <0.001 | 109.29 ± 7.68 | 0.811 | 106.62 ± 6.82 | 0.892 | <0.001 |
Control Group | TDT | p Value | NTDT | p Value * | β-Thalassemia Minor | p Value † | Anova | |
---|---|---|---|---|---|---|---|---|
SCP (%) | ||||||||
Whole image | 50.72 ± 3.39 | 46.78 ± 4.37 | <0.001 | 50.78 ± 3.51 | 1 | 52.10 ± 4.12 | 0.603 | <0.001 |
Parafovea | 52.56 ± 6.37 | 48.22 ± 6.42 | 0.006 | 53.87 ± 3.97 | 0.936 | 54.30 ± 5.66 | 0.999 | <0.001 |
Fovea | 23.55 ± 5.33 | 18.60 ± 4.03 | <0.001 | 22.77 ± 5.25 | 0.945 | 21.20 ± 6.81 | 0.291 | <0.001 |
DCP (%) | ||||||||
Whole image | 55.74 ± 6.31 | 50.40 ± 7.47 | 0.007 | 50.96 ± 7.53 | 0.034 | 55.76 ± 7.79 | 1 | <0.001 |
Parafovea | 58.07 ± 7.18 | 53.47 ± 6.24 | 0.022 | 53.58 ± 7.68 | 0.043 | 58.16 ± 7.14 | 1 | 0.001 |
Fovea | 40.89 ± 5.82 | 36.55 ± 5.03 | 0.002 | 37.15 ± 5.55 | 0.022 | 40.88 ± 5.29 | 1 | <0.001 |
CC (%) | ||||||||
Whole image | 73.78 ± 3.39 | 71.18 ± 4.25 | 0.019 | 72.98 ± 4.80 | 0.875 | 73.35 ± 3.30 | 1 | 0.016 |
Parafovea | 71.73 ± 4.19 | 68.62 ± 4.42 | 0.007 | 70.48 ± 4.68 | 0.922 | 71.81 ± 3.90 | 1 | 0.002 |
Fovea | 71.63 ± 5.40 | 68.75 ± 4.92 | 0.048 | 71.23 ± 4.59 | 1 | 72.73 ± 4.63 | 0.836 | 0.002 |
FAZ (mm2) | 0.263 ± 0.08 | 0.320 ± 0.08 | 0.011 | 0.265 ± 0.08 | 1 | 0.261 ± 0.07 | 1 | 0.002 |
RPC (%) | ||||||||
Whole Image | 53.17 ± 4.14 | 46.04 ± 4.70 | <0.001 | 51.46 ± 4.11 | 0.602 | 52.18 ± 4.64 | 0.958 | <0.001 |
Inside disc | 53.08 ± 5.04 | 49.15 ± 3.99 | 0.001 | 53.20 ± 4.25 | 1 | 53.28 ± 4.85 | 1 | <0.001 |
Peripapillary region | 54.74 ± 5.81 | 48.64 ± 4.09 | <0.001 | 52.57 ± 4.22 | 0.271 | 53.34 ± 4.17 | 0.947 | <0.001 |
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Cennamo, G.; Montorio, D.; Mazzella, G.; Ricchi, P.; Costantini, S.; Spasiano, A.; Filosa, A.; Storino, M.R.; Aquila, F.; Tranfa, F.; 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. https://doi.org/10.3390/biology10040276
Cennamo G, Montorio D, Mazzella G, Ricchi P, Costantini S, Spasiano A, Filosa A, Storino MR, Aquila F, Tranfa F, 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(4):276. https://doi.org/10.3390/biology10040276
Chicago/Turabian StyleCennamo, Gilda, Daniela Montorio, Giuliano Mazzella, Paolo Ricchi, Silvia Costantini, Anna Spasiano, Aldo Filosa, Maria Rosaria Storino, Francesca Aquila, Fausto Tranfa, and et al. 2021. "Retinal and Choriocapillaris Vascular Changes in Patients Affected by Different Clinical Phenotypes of β-Thalassemia: An Optical Coherence Tomography Angiography Study" Biology 10, no. 4: 276. https://doi.org/10.3390/biology10040276