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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-09-2020 | Magnetic Resonance Imaging | Pediatrics

Subclinical Retinal versus Brain Findings in Infants with Hypoxic Ischemic Encephalopathy

Authors: Shwetha Mangalesh, Du Tran-Viet, Carolyn Pizoli, Vincent Tai, Mays Antoine El-Dairi, Xi Chen, Christian Viehland, Laura Edwards, Joanne Finkle, Sharon F. Freedman, Cynthia Ann Toth

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 9/2020

Abstract

Purpose

To detect retinal features and abnormalities on optical coherence tomography (OCT) without pupil dilation and relate these to brain injury in infants with a clinical diagnosis of hypoxic ischemic encephalopathy (HIE).

Methods

Under an institutional review board-approved protocol, we imaged eight infants without pharmacologic mydriasis, using handheld, non-contact spectral-domain (Leica Microsystems, IL) or investigational swept-source OCT at the bedside in an intensive care nursery, after birth (depending on primary clinical care team permission based on health status) and weekly until discharge. The newborn infant with HIE is neurologically unstable; therefore, pharmacologic mydriasis and stimulation with visible light for retinal examination are usually avoided. We analyzed images for retinal pathologies, central foveal thickness, and retinal nerve fiber layer (RNFL) thickness at the papillomacular bundle and compared them to historical controls and published normative data, HIE clinical assessment, and abnormalities on brain magnetic resonance imaging (MRI).

Results

On OCT, three of eight infants had bilateral multiple small macular and perimacular cystoid spaces; two of these three infants also had pronounced retinal ganglion cell layer thinning and severe brain injury on MRI and the third had bilateral paracentral acute middle maculopathy and mild brain injury on MRI. Other findings in HIE infant eyes included abnormally thin fovea and thin RNFL and markers of retinal immaturity such as the absence of sub-foveal photoreceptor development and sub-foveal fluid.

Conclusions

Bedside handheld OCT imaging within the first 2 weeks of life revealed retinal injury in infants with HIE-related brain injury. Future studies may determine the relationship between acute/subacute retinal abnormalities and brain injury severity and neurodevelopmental outcomes in HIE.

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Douglas-Escobar M, Weiss MD (2015) Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr 169(4):397–403. https://doi.org/10.1001/jamapediatrics.2014.3269CrossRefPubMed

Shankaran S, Pappas A, McDonald SA, Vohr BR, Hintz SR, Yolton K, Gustafson KE, Leach TM, Green C, Bara R, Petrie Huitema CM, Ehrenkranz RA, Tyson JE, Das A, Hammond J, Peralta-Carcelen M, Evans PW, Heyne RJ, Wilson-Costello DE, Vaucher YE, Bauer CR, Dusick AM, Adams-Chapman I, Goldstein RF, Guillet R, Papile LA, Higgins RD, Eunice Kennedy Shriver NNRN (2012) Childhood outcomes after hypothermia for neonatal encephalopathy. N Engl J Med 366(22):2085–2092. https://doi.org/10.1056/NEJMoa1112066CrossRefPubMedPubMedCentral

de Vries LS, Jongmans MJ (2010) Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 95(3):F220–F224. https://doi.org/10.1136/adc.2008.148205CrossRefPubMed

Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D (2010) Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ 340:c363. https://doi.org/10.1136/bmj.c363CrossRefPubMedPubMedCentral

Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P, Group TS (2009) Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 361(14):1349–1358. https://doi.org/10.1056/NEJMoa0900854CrossRefPubMed

Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D (2010) Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Lancet Neurol 9(1):39–45. https://doi.org/10.1016/S1474-4422(09)70295-9CrossRefPubMedPubMedCentral

Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, SA MD, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH, National Institute of Child H, Human Development Neonatal Research N (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353(15):1574–1584. https://doi.org/10.1056/NEJMcps050929CrossRefPubMed

Shankaran S, Barnes PD, Hintz SR, Laptook AR, Zaterka-Baxter KM, McDonald SA, Ehrenkranz RA, Walsh MC, Tyson JE, Donovan EF, Goldberg RN, Bara R, Das A, Finer NN, Sanchez PJ, Poindexter BB, Van Meurs KP, Carlo WA, Stoll BJ, Duara S, Guillet R, Higgins RD, Eunice Kennedy Shriver National Institute of Child H, Human Development Neonatal Research N (2012) Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 97(6):F398–F404. https://doi.org/10.1136/archdischild-2011-301524CrossRefPubMedPubMedCentral

Tong AY, El-Dairi M, Maldonado RS, Rothman AL, Yuan EL, Stinnett SS, Kupper L, Cotten CM, Gustafson KE, Goldstein RF, Freedman SF, Toth CA (2014) Evaluation of optic nerve development in preterm and term infants using handheld spectral-domain optical coherence tomography. Ophthalmology 121(9):1818–1826. https://doi.org/10.1016/j.ophtha.2014.03.020CrossRefPubMedPubMedCentral

10.

Rothman AL, Tran-Viet D, Gustafson KE, Goldstein RF, Maguire MG, Tai V, Sarin N, Tong AY, Huang J, Kupper L, Cotten CM, Freedman SF, Toth CA (2015) Poorer neurodevelopmental outcomes associated with cystoid macular edema identified in preterm infants in the intensive care nursery. Ophthalmology 122(3):610–619. https://doi.org/10.1016/j.ophtha.2014.09.022CrossRefPubMed

11.

Chan KC, Kancherla S, Fan SJ, Wu EX (2014) Long-term effects of neonatal hypoxia-ischemia on structural and physiological integrity of the eye and visual pathway by multimodal MRI. Invest Ophthalmol Vis Sci 56(1):1–9. https://doi.org/10.1167/iovs.14-14287CrossRefPubMed

12.

Maldonado RS, Izatt JA, Sarin N, Wallace DK, Freedman S, Cotten CM, Toth CA (2010) Optimizing hand-held spectral domain optical coherence tomography imaging for neonates, infants, and children. Invest Ophthalmol Vis Sci 51(5):2678–2685. https://doi.org/10.1167/iovs.09-4403CrossRefPubMedPubMedCentral

13.

Rothman AL, Sevilla MB, Mangalesh S, Gustafson KE, Edwards L, Cotten CM, Shimony JS, Pizoli CE, El-Dairi MA, Freedman SF, Toth CA (2015) Thinner retinal nerve fiber layer in very preterm versus term infants and relationship to brain anatomy and neurodevelopment. Am J Ophthalmol 160(6):1296–1308. https://doi.org/10.1016/j.ajo.2015.09.015CrossRefPubMedPubMedCentral

14.

Tran-Viet D, Wong BM, Mangalesh S, Maldonado RS, Cotten CM, Toth CA (2017) Handheld spectral domain optical coherence tomography imaging through the undilated pupil in infants born preterm or with hypoxic injury or hydrocephalus. (Accepted). Retina

15.

Sarnat HB, Sarnat MS (1976) Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 33(10):696–705. https://doi.org/10.1001/archneur.1976.00500100030012CrossRefPubMed

16.

Maldonado RS, O'Connell R, Ascher SB, Sarin N, Freedman SF, Wallace DK, Chiu SJ, Farsiu S, Cotten M, Toth CA (2012) Spectral-domain optical coherence tomographic assessment of severity of cystoid macular edema in retinopathy of prematurity. Arch Ophthalmol (Chicago Ill: 1960) 130(5):569–578. https://doi.org/10.1001/archopthalmol.2011.1846CrossRef

17.

Zawadzki RJ, Rowe TS, Fuller AR, Hamann B, Werner JS (2010) Toward building an anatomically correct solid eye model with volumetric representation of retinal morphology, pp 75502F-75502F-75507

18.

Folgar FA, Yuan EL, Farsiu S, Toth CA (2014) Lateral and axial measurement differences between spectral-domain optical coherence tomography systems. J Biomed Opt 19(1):16014. https://doi.org/10.1117/1.JBO.19.1.016014CrossRefPubMed

19.

Lee H, Purohit R, Patel A, Papageorgiou E, Sheth V, Maconachie G, Pilat A, McLean RJ, Proudlock FA, Gottlob I (2015) In vivo foveal development using optical coherence tomography. Invest Ophthalmol Vis Sci 56(8):4537–4545. https://doi.org/10.1167/iovs.15-16542CrossRefPubMed

20.

Rothman AL, Sevilla MB, Freedman SF, Tong AY, Tai V, Tran-Viet D, Farsiu S, Toth CA, El-Dairi MA (2015) Assessment of retinal nerve fiber layer thickness in healthy, full-term neonates. Am J Ophthalmol 159(4):803–811. https://doi.org/10.1016/j.ajo.2015.01.017CrossRefPubMedPubMedCentral

21.

Bednarek N, Mathur A, Inder T, Wilkinson J, Neil J, Shimony J (2012) Impact of therapeutic hypothermia on MRI diffusion changes in neonatal encephalopathy. Neurology 78(18):1420–1427. https://doi.org/10.1212/WNL.0b013e318253d589CrossRefPubMedPubMedCentral

22.

Vinekar A, Avadhani K, Sivakumar M, Mahendradas P, Kurian M, Braganza S, Shetty R, Shetty BK (2011) Understanding clinically undetected macular changes in early retinopathy of prematurity on spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 52(8):5183–5188. https://doi.org/10.1167/iovs.10-7155CrossRefPubMed

23.

Grewal DS, Polascik BA, Kelly MP, Fekrat S (2017) Widefield en face optical coherence tomography to quantify the extent of paracentral acute middle maculopathy. Can J Ophthalmol 52(3):e85–e88. https://doi.org/10.1016/j.jcjo.2016.11.028CrossRefPubMed

24.

Trese MG, Thanos A, Yonekawa Y, Randhawa S (2017) Optical coherence tomography angiography of paracentral acute middle maculopathy associated with primary antiphospholipid syndrome. Ophthal Surg Lasers Imaging Retina 48(2):175–178. https://doi.org/10.3928/23258160-20170130-13CrossRef

25.

Cabrera MT, Maldonado RS, Toth CA, O’Connell RV, Chen BB, Chiu SJ, Farsiu S, Wallace DK, Stinnett SS, Panayotti GM, Swamy GK, Freedman SF (2012) Subfoveal fluid in healthy full-term newborns observed by handheld spectral-domain optical coherence tomography. Am J Ophthalmol 153(1):167–175 e163. https://doi.org/10.1016/j.ajo.2011.06.017CrossRefPubMed

26.

Lee AC, Maldonado RS, Sarin N, O’Connell RV, Wallace DK, Freedman SF, Cotten M, Toth CA (2011) Macular features from spectral-domain optical coherence tomography as an adjunct to indirect ophthalmoscopy in retinopathy of prematurity. Retina 31(8):1470–1482. https://doi.org/10.1097/IAE.0b013e31821dfa6dCrossRefPubMedPubMedCentral

27.

Vajzovic L, Rothman AL, Tran-Viet D, Cabrera MT, Freedman SF, Toth CA (2015) Delay in retinal photoreceptor development in very preterm compared to term infants. Invest Ophthalmol Vis Sci 56(2):908–913. https://doi.org/10.1167/iovs.14-16021CrossRefPubMedPubMedCentral

28.

Wolff B, Basdekidou C, Vasseur V, Mauget-Faysse M, Sahel JA, Vignal C (2013) Retinal inner nuclear layer microcystic changes in optic nerve atrophy: a novel spectral-domain OCT finding. Retina 33(10):2133–2138. https://doi.org/10.1097/IAE.0b013e31828e68d0CrossRefPubMed

29.

Jiramongkolchai K, Bhatti MT, Proia A, Freedman SF, El-Dairi MA (2016) Formation of macular inner nuclear layer cysts in optic atrophy. Invest Ophthalmol Vis Sci 57(3):989–991. https://doi.org/10.1167/iovs.15-18814CrossRefPubMed

30.

Browning DJ, Punjabi OS, Lee C (2017) Assessment of ischemia in acute central retinal vein occlusion from inner retinal reflectivity on spectral domain optical coherence tomography. Clin Ophthalmol 11:71–79. https://doi.org/10.2147/OPTH.S122683CrossRefPubMed

31.

Goldberg MR, Zakka FR, Carroll JJ, Costakos DM (2016) Attenuation of the ganglion cell layer in a premature infant revealed with handheld spectral domain optical coherence tomography. Retin Cases Brief Rep 10(3):229–231. https://doi.org/10.1097/ICB.0000000000000235CrossRefPubMedPubMedCentral

32.

Huang HM, Huang CC, Hung PL, Chang YC (2012) Hypoxic-ischemic retinal injury in rat pups. Pediatr Res 72(3):224–231. https://doi.org/10.1038/pr.2012.74CrossRefPubMed

33.

Jacobson L, Hellstrom A, Flodmark O (1997) Large cups in normal-sized optic discs: a variant of optic nerve hypoplasia in children with periventricular leukomalacia. Arch Ophthalmol (Chicago Ill : 1960) 115(10):1263–1269. https://doi.org/10.1001/archopht.1997.01100160433007CrossRef

34.

Grazioli E, Zivadinov R, Weinstock-Guttman B, Lincoff N, Baier M, Wong JR, Hussein S, Cox JL, Hojnacki D, Ramanathan M (2008) Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis. J Neurol Sci 268(1-2):12–17. https://doi.org/10.1016/j.jns.2007.10.020CrossRefPubMed

35.

Frohman EM, Dwyer MG, Frohman T, Cox JL, Salter A, Greenberg BM, Hussein S, Conger A, Calabresi P, Balcer LJ, Zivadinov R (2009) Relationship of optic nerve and brain conventional and non-conventional MRI measures and retinal nerve fiber layer thickness, as assessed by OCT and GDx: a pilot study. J Neurol Sci 282(1-2):96–105. https://doi.org/10.1016/j.jns.2009.04.010CrossRefPubMed

36.

Laghmari M, Skiker H, Handor H, Mansouri B, Ouazzani Chahdi K, Lachkar R, Salhi Y, Cherkaoui O, Ouazzani Tnacheri B, Ibrahimy W, Alami H, Bezad R, Ahid S, Abouqal R, Daoudi R (2014) Birth-related retinal hemorrhages in the newborn: incidence and relationship with maternal, obstetric and neonatal factors. Prospective study of 2,031 cases. J Fr Ophtalmol 37(4):313–319. https://doi.org/10.1016/j.jfo.2013.06.005CrossRefPubMed

37.

Moral-Pumarega MT, Caserio-Carbonero S, De-La-Cruz-Bertolo J, Tejada-Palacios P, Lora-Pablos D, Pallas-Alonso CR (2012) Pain and stress assessment after retinopathy of prematurity screening examination: indirect ophthalmoscopy versus digital retinal imaging. BMC Pediatr 12:132. https://doi.org/10.1186/1471-2431-12-132CrossRefPubMedPubMedCentral

38.

Wu YW, Mathur AM, Chang T, McKinstry RC, Mulkey SB, Mayock DE, Van Meurs KP, Rogers EE, Gonzalez FF, Comstock BA, Juul SE, Msall ME, Bonifacio SL, Glass HC, Massaro AN, Dong L, Tan KW, Heagerty PJ, Ballard RA (2016) High-dose erythropoietin and hypothermia for hypoxic-ischemic encephalopathy: a phase II trial. Pediatrics 137(6). https://doi.org/10.1542/peds.2016-0191

Title: Subclinical Retinal versus Brain Findings in Infants with Hypoxic Ischemic Encephalopathy
Authors: Shwetha Mangalesh
Du Tran-Viet
Carolyn Pizoli
Vincent Tai
Mays Antoine El-Dairi
Xi Chen
Christian Viehland
Laura Edwards
Joanne Finkle
Sharon F. Freedman
Cynthia Ann Toth
Publication date: 01-09-2020
Publisher: Springer Berlin Heidelberg
Keywords: Magnetic Resonance Imaging
Magnetic Resonance Imaging
Encephalopathy
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 9/2020
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-020-04738-0

At a glance: The STEP trials

Springer Medicine

Subclinical Retinal versus Brain Findings in Infants with Hypoxic Ischemic Encephalopathy

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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