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Associations between systemic health and retinal nerve fibre layer thickness in preterm infants at 36 weeks postmenstrual age
  1. Liangbo L Shen1,
  2. Shwetha Mangalesh2,
  3. Suzanne M Michalak2,
  4. Brendan McGeehan3,
  5. Neeru Sarin2,
  6. Joanne Finkle4,
  7. Katrina P Winter2,
  8. Du Tran-Viet2,
  9. Eric J Benner4,
  10. Lejla Vajzovic2,
  11. Sharon F Freedman2,4,
  12. Noelle Younge4,
  13. C Michael Cotten4,
  14. Mays El-Dairi2,
  15. Gui-Shuang Ying3,
  16. Cynthia Toth2,5
  1. 1Department of Ophthalmology, University of California San Francisco, San Francisco, California, USA
  2. 2Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA
  3. 3Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  4. 4Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA
  5. 5Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
  1. Correspondence to Dr Cynthia Toth, Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA; Cynthia.toth{at}


Background/aims Neonatal insults from systemic diseases have been implicated in the pathway of impaired neurodevelopment in preterm infants. We aimed to investigate the associations between systemic health factors and retinal nerve fibre layer (RNFL) thickness in preterm infants.

Methods We prospectively enrolled infants and imaged both eyes at 36±1 weeks postmenstrual age (PMA) using a hand-held optical coherence tomography system at the bedside in the Duke intensive care nurseries. We evaluated associations between RNFL thickness and 29 systemic health factors using univariable and multivariable regression models.

Results 83 infants with RNFL thickness measures were included in this study. Based on the multivariable model, RNFL thickness was positively associated with infant weight at imaging and was negatively associated with sepsis/necrotising enterocolitis (NEC). RNFL thickness was 10.4 µm (95% CI −15.9 to −4.9) lower in infants with than without sepsis/NEC in the univariable analysis (p<0.001). This difference remained statistically significant after adjustment for confounding variables in various combinations (birth weight, birthweight percentile, gestational age, infant weight at imaging and growth velocity). A 250 g increase in infant weight at imaging was associated with a 3.1 µm (95% CI 2.1 to 4.2) increase in RNFL thickness in the univariable analysis (p<0.001).

Conclusions Low infant weight and sepsis/NEC were independently associated with thinner RNFL in preterm infants at 36 weeks PMA. To our knowledge, this study is the first to suggest that sepsis/NEC may affect retinal neurodevelopment. Future longitudinal studies are needed to investigate this relationship further.

  • child health (paediatrics)
  • imaging
  • inflammation
  • optic nerve
  • retina

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • Contributors Conception and design: LLS, SM, SMM, BM, LV, ME-D, G-SY and CT. Data collection: SM, BM, NS, JF, KPW and DT-V. Data Analysis: LLS and BM. Data interpretation: LLS, SM, BM, SFF, ME-D, G-SY and CT. Obtained funding: G-SY and CT. Manuscript writing: LLS, SM, SMM, BM, NS, JF, KPW, DT-V, EJB, LV, SFF, NY, CMC, ME-D, GY and CT.

  • Funding The study was supported by grants RO1 EY025009 and P30 EY005722 from the National Eye Institute (NEI) (Toth).

  • Disclaimer The sponsor or funding organisation had no role in the design or conduct of this research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the institution or funder. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NEI, or NIH.

  • Competing interests LV: Heidelberg Engineering: Investigator, Research grant. CT: Alcon Laboratories: Patents/Royalty; EMMES: Consultant/Advisor; National Eye Institute and Research to Prevent Blindness: Grant Support; Theia Imaging: Equity Owner.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.