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Structure and Function of the Retina in Children Born Extremely Preterm and in Children Born At Term
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology. (Oftalmiatrik/Ophthalmology)
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Optical coherence tomography (OCT), multifocal electroretinography (mfERG) and full-field electroretinography (ffERG) give important information about retinal structure and function.

Purpose: To collect normative data of macular Cirrus Spectral domain (SD)-OCT assessments and of mfERG measurements of healthy children (papers I and II). To assess the macular thickness with Cirrus SD-OCT and the retinal function with ffERG in 6.5-year-old children born extremely preterm and in children born at term (papers III and IV).

Methods: Study participants aged 5-15 years and living in Uppsala County were randomly chosen from the Swedish Birth Register (papers I and II). In papers III and IV, the study participants consisted of children born extremely preterm and children born at term – all were aged 6.5 years. In paper III, the children were living in Stockholm and Uppsala health care regions and, in paper IV, in Uppsala health care region only. Macular thickness was assessed with Cirrus SD-OCT and macular function with mfERG, using the Espion Multifocal system and DTL-electrodes. The retinal function was assessed with ffERG and DTL-electrodes, using the Espion Ganzfield system.

Results: Altogether, 58 children participated in paper I and 49 children in paper II. In paper I, the repeatability and reproducibility of the OCT assessments were good. In paper II, the results of the mfERG measurements were in accordance with retinal cone density and there were no significant differences between the right and left eyes. In paper III, 134 preterm children and 145 children born at term constituted the study population. The central macular thickness was significantly thicker in the preterm group than in the control group. Within the preterm group, gestational age (GA), former retinopathy of prematurity (ROP) and male gender were all important risk factors for an increased macular thickness. In paper IV, 52 preterm children and 45 control children constituted the study population. Significantly lower amplitudes and prolonged implicit times of the combined rod and cone responses, as well as of the isolated cone responses, were found in the preterm group when compared with the control group. In paper IV, there was no association between GA, ROP or male gender and the ffERG assessments.

Conclusion: Normative data of Cirrus SD-OCT and mfERG assessments were reported. The results of the assessments were reliable. Children aged 6.5 years, born extremely preterm, had a significantly thicker central macula and both rod and cone function were significantly reduced in comparison to children born at term. ROP had an influence on retinal structure but not retinal function in the present cohorts. Our results suggest that retinal development is abnormal in children born extremely preterm. Long-term follow-up studies are necessary in order to evaluate the functional ophthalmological outcome in this vulnerable population of children growing up today.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. , p. 79
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1318
Keywords [en]
optical coherence tomography, multifocal electroretinogram, full-field electroretinography, extremely preterm children, retinopathy of prematurity, gestational age, gender
National Category
Ophthalmology
Research subject
Ophtalmology
Identifiers
URN: urn:nbn:se:uu:diva-317550ISBN: 978-91-554-9862-7 (print)OAI: oai:DiVA.org:uu-317550DiVA, id: diva2:1082877
Public defence
2017-05-13, Gunnesalen, Psykiatrins hus, Ingång 10, Akademiska sjukhuset, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2017-04-21 Created: 2017-03-19 Last updated: 2017-05-05
List of papers
1. Macular thickness assessed with spectral domain OCT in a population-based study of children: normative data, repeatability and reproducibility and comparison with time domain OCT
Open this publication in new window or tab >>Macular thickness assessed with spectral domain OCT in a population-based study of children: normative data, repeatability and reproducibility and comparison with time domain OCT
2015 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 93, no 5, p. 470-475Article in journal (Refereed) Published
Abstract [en]

PurposeTo collect data on macular thickness assessed with Cirrus OCT in healthy children in a population-based study, to examine the repeatability and reproducibility, and to compare the values with Stratus OCT. MethodsFifty-eight 6- to 15-year-old children, born at term, were examined. Best-corrected visual acuity and refraction were assessed. One examiner performed three OCT assessments, and the repeatability was calculated. Thereafter, a second examiner repeated the examinations to calculate the reproducibility. One eye was randomized to be included in the normal material. Finally, the second examiner assessed the macular thickness with the Stratus OCT. ResultsThe mean value (SD) of central macular thickness was 255 +/- 17m, and the total macular volume was 10.3 +/- 0.5mm(3). No correlations were found between macular thickness and age, gender or refraction. The coefficients of variance (CoVs) for both repeatability and reproducibility were <1.21%, and the intraclass correlations (ICCs) were over 0.86. The Cirrus OCT showed a 29% thicker central macular thickness than the Stratus OCT. ConclusionNormal values for macular thickness assessed with Cirrus OCT in healthy full-term children in a population-based study were reported. The assessments showed high repeatability and reproducibility. The values of Cirrus and Stratus OCT differed and the techniques were not interchangeable.

Keywords
children, normal values, optical coherence tomography, repeatability, reproducibility
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-260806 (URN)10.1111/aos.12695 (DOI)000358440700034 ()25726865 (PubMedID)
Funder
Swedish Society of Medicine
Available from: 2015-08-31 Created: 2015-08-25 Last updated: 2017-12-04Bibliographically approved
2. Macular function measured by binocular mfERG and compared with macular structure in healthy children
Open this publication in new window or tab >>Macular function measured by binocular mfERG and compared with macular structure in healthy children
Show others...
2015 (English)In: Documenta Ophthalmologica, ISSN 0012-4486, E-ISSN 1573-2622, Vol. 131, no 3, p. 169-176Article in journal (Refereed) Published
Abstract [en]

To create normative data in children from binocular multifocal ERG (mfERG) recordings and compare results with the macular thickness. Forty-nine 5- to 15-year-old healthy, full-term children were examined with Espion Multifocal System, using DTL electrodes. The stimulus matrix consisted of 37 hexagonal elements. Amplitudes, implicit times and response densities (presented in three rings) of the first-order component P1 were analyzed. Measurements of macular thickness were performed with spectral-domain Cirrus OCT. There were no significant differences between right and left eyes regarding mfERG recordings. Median P1 implicit times of Rings 1-3 of the 46 right eyes were 30.0, 30.0 and 30.8 ms and response densities 20.5, 10.9 and 7.6 nV/deg(2), respectively. Implicit time was longer in boys than in girls (p = 0.009, 0.039, 0.005 in Rings 1-3) and was correlated with age (r (s) = 0.417, 0.316, 0.274 in Rings 1-3). Implicit time in Ring 1 correlated significantly with the inner circle of the OCT measurements (p = 0.014). Binocular mfERG with DTL electrodes is a reliable test of the central macular function in children and correlates with macular structure. As previously not shown, there was a significant difference in implicit time between boys and girls.

Keywords
Binocular, Multifocal electroretinogram, DTL electrodes, Healthy children, Optic coherence tomography
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-270938 (URN)10.1007/s10633-015-9513-y (DOI)000365757200002 ()
Available from: 2016-01-05 Created: 2016-01-05 Last updated: 2017-12-01Bibliographically approved
3. Central macular thickness in 6.5-year-old children born extremely preterm is strongly associated with gestational age even when adjusted for risk factors
Open this publication in new window or tab >>Central macular thickness in 6.5-year-old children born extremely preterm is strongly associated with gestational age even when adjusted for risk factors
Show others...
2017 (English)In: Retina, ISSN 0275-004X, E-ISSN 1539-2864, Vol. 37, no 12, p. 2281-2288Article in journal (Refereed) Published
Abstract [en]

Purpose:To assess the macular thickness in 6.5-year-old children born extremelypreterm (EPT) in comparison with children born at term and to investigate risk factorsassociated with the macular thickness in the preterm group.

Methods:A population-based study of 6.5-year-old children born before the gestationalage of 27 weeks and age-matched control subjects. Macular assessments with opticalcoherence tomography were performed, and the results were compared with neonatal riskfactors and sex.

Results:Adequate optical coherence tomography measurements were obtained from134 children born EPT (mean gestational age of 25 weeks [range 23–26]) and 145 controlsubjects. The mean (range) of central macula thickness was significantly increased (P,0.001)in the EPT group (right eyes: 282mm [238–356], left eyes: 283mm[229–351]), compared withthe control group (right eyes: 249mm [208–293], left eyes: 248mm[207–290]). A multiple linearmixed model analysis of the EPT group revealed gestational age, retinopathy of prematurity,and male gender as important risk factors for an increased macular thickness. The macularthickness decreased by 3.9mm per gestational week, when adjusted for retinopathy of pre-maturity and sex.

Conclusion:Extremely preterm birth constitutes a substantial risk factor for a thickcentral macula, even when adjusted for retinopathy of prematurity and male gender.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2017
National Category
Ophthalmology
Research subject
Ophtalmology
Identifiers
urn:nbn:se:uu:diva-317548 (URN)10.1097/IAE.0000000000001469 (DOI)000425214400009 ()28098724 (PubMedID)
Funder
Swedish Society of MedicineSven Jerring FoundationStockholm County Council
Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2018-04-10Bibliographically approved
4. Both rod and cone function are reduced in 6.5-year-old children born extremely preterm
Open this publication in new window or tab >>Both rod and cone function are reduced in 6.5-year-old children born extremely preterm
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Ophthalmology
Research subject
Ophtalmology
Identifiers
urn:nbn:se:uu:diva-317559 (URN)
Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2017-03-21

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