A study of the foveal structure in prematurely born children by the use of optical coherence tomography
During the last decades there has been a rapid development in techniques for retinal imaging. The optical coherence tomography (OCT) examination is non-invasive, fast and patient-friendly which are good qualities when examining children. There is a steadily increasing survival rate of extremely premature infants due to improved neonatal care. These children are at higher risk of having visual impairment and OCT gives important information about the retinal structure in these children.
Purpose: The purpose of the first study was to evaluate different methods for examination and evaluation of the retinal structure. The purpose of study II, III and IV was to investigate and describe the foveal anatomy in 6.5 year old children born extremely preterm (EPT) by comparing the immature fovea and the normally developed fovea in age-matched control children.
Methods: The macular thickness was measured in healthy adult subjects and patients with macular oedema with the Heidelberg Retina Tomograph 3 (HRT3) and the Stratus OCT (study I). The study cohort in study II, III and IV were children born EPT and age-matched control children from Stockholm health care region (study II and IV) and from Stockholm and Uppsala health care region (study III). All participants were from the national population based Extremely Preterm Infants in Sweden Study (EXPRESS), which investigates the short- and long-term morbidity and mortality in infants born before 27 weeks of gestational age (GA). At the age of 6.5 years the children had their macular structure imaged with Cirrus SD-OCT. In study II and IV the foveal structure were evaluated by measuring foveal depth (FD), inner retinal layer (IRL), ganglion cell layer (GCL) and inner plexiform layer (IPL) (GCL+ when combined), outer nuclear layer (ONL) and outer segment (OS) thickness. In study III macular thickness was measured in 9 areas defined by the Early Treatment Diabetic Retinopathy Study as the ETDRS grid.
Results: In study I, no significant differences were found between the measurements at different sessions for any of the imaging techniques in either patients (n=9) or healthy subjects (n=30). The HRT3 showed lower repeatability and reproducibility compared to Stratus OCT. The results from study II, showed that children born EPT (n=30) had a shallower FD, thicker IRL and thicker ONL at the foveal center comped to children born at term (n=10). In study III, the 134 children born EPT had significantly thicker central macula compared to the 145 control children. Study IV showed that the 89 children born EPT has thicker central GCL+ thickness and reduced FD compared to the 92 children born at term. Low GA, retinopathy of prematurity (ROP), and male sex within the EPT group were associated with a thicker central macula in study III and reduced FD and increased central GCL+ thickness in study IV. In study IV, ROP treatment was also an associated factor.
Conclusion: The measurements with the HRT3 had lower repeatability and reproducibility compared with the Stratus OCT and OCT came out as a more promising technique for examination of children. Macular imaging using OCT has shown that a preterm birth can inhibit foveal maturation resulting in structural deviations. Typical signs are a shallow FD, thicker IRL and GCL+ at the foveal center, contributing to a thicker central macular thickness. Low GA, ROP, ROP treatment and male sex are factors associated to these structural deviations.
List of scientific papers
I. Rosén, R., Nilsson, M., Tallstedt, L., Martin, L.(2012). Test-retest variation in macular thickness measurements with the Heidelberg Retina Tomograph. Clin Exp Opto. 95(5), 515-521.
https://doi.org/10.1111/j.1444-0938.2012.00721.x
II. Rosén, R., Sjöstrand, J., Nilsson, M., Hellgren, K. (2015). A methodological approach for evaluation of foveal immaturity after extremely preterm birth. Ophthalmic Physiol Opt. 35(4), 433-441.
https://doi.org/10.1111/opo.12221
III. Molnar, A. E., Rosén, R. M., Nilsson, M., Larsson, E. K., Holmström, G. E., Hellgren, K. M. (2017). Central macular thickness in 6.5-year-old children born extremely preterm is strongly associated with gestational age even when adjusted for risk factors. Retina. 37(12), 2281-2288.
https://doi.org/10.1097/IAE.0000000000001469
IV. Rosén, R., Hellgren, K., Venkataraman, A., Dominguez Vicent, A., Nilsson, M. Increased foveal ganglion cell- and inner plexiform layer thickness in children aged 6.5 years born extremely preterm. [Submitted]
History
Defence date
2018-09-21Department
- Department of Clinical Neuroscience
Publisher/Institution
Karolinska InstitutetMain supervisor
Nilsson, MariaCo-supervisors
Martin, Lene; Hellgren, KerstinPublication year
2018Thesis type
- Doctoral thesis
ISBN
978-91-7676-924-9Number of supporting papers
4Language
- eng