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Morphometry of the Optic Nerve Head as a Diagnostic Tool for Glaucoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.ORCID iD: 0000-0001-6649-3088
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

Glaucoma is a chronic optic nerve head (ONH) disease. Gradual retinal ganglion cell and nerve fiber loss lead to morphological ONH change and visual field defects. Initial loss is often focal. Rate of progression and life expectancy guide treatment. Currently, confocal scanning laser tomoghraphy (HRT) and optic coherence tomography (OCT) are available for ONH imaging. However, there is no consensus for which morphometric measurement of ONH nerve fiber content to use for glaucoma follow-up.

Purpose: To measure ONH nerve fiber content as neuroretinal rim area (NRA) with HRT, estimate NRA measurement variation and its impact on designing a follow-up strategy. To develop a custom algorithm, Pigment epithelium central limit-Inner limit of the retina Minimal Distance (PIMD), for measuring ONH nerve fiber content in OCT data cubes. To measure PIMD in glaucomatous eyes, estimate the variance sources for PIMD and their impact on designing strategies for glaucoma follow-up.

Methods: NRA was measured with HRT in non-glaucomatous and glaucomatous eyes. Sources of variance for NRA were estimated. An OCT data cube of a non-glaucomatous eye was used in developing the PIMD algorithm. PIMD was measured in 500 radii along the ONH circumference. PIMD averaged over the circumference is PIMD-2π. Sources of variance for PIMD-2π were estimated for glaucomatous eyes. Strategies for following PIMD-2π and segments of PIMD-2π within subject over time were proposed.

Results: Variation among subjects was substantial for NRA and PIMD-2π. Contrarily, within subject variation was small for NRA and PIMD-2π. When within subject variation, a previously reported loss rate for progressing glaucoma, and measuring NRA 3 times every 4 months were applied, a significant loss was detected after 54 months. When within subject variation and a PIMD-2π loss rate resulting in blindness after 20 years were applied, a significant PIMD-2π loss was detected in 16 months with visits every 4 months. Within subject segmental PIMD-2π loss can be detected from the 3rd visit. Loss rate of each PIMD can be estimated with linear regression from the 4th visit. Change in segmental PIMD-2π loss rate can be detected at a later visit.

Conclusions: Small within subject variation allows for within subject NRA and PIMD follow-up over time. Segmental PIMD-2π has potential to detect focal glaucomatous defects and worsening of existing defects. There is potential to detect a change in segmental PIMD-2π loss rate. Segmental PIMD-2π has potential as a tool for within subject follow-up of glaucoma.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 67
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1610
Keywords [en]
optic nerve head, ONH, nerve fibers, glaucoma, optical coherence tomography, OCT, Pigment epithelium central limit-inner limit of the retina minimal distance, PIMD, PIMD-2π, Segmental PIMD-2π, confocal scanning laser tomography, HRT, NRA, variation, variability, variance, loss rate, follow-up.
National Category
Ophthalmology
Identifiers
URN: urn:nbn:se:uu:diva-393989ISBN: 978-91-513-0798-5 (print)OAI: oai:DiVA.org:uu-393989DiVA, id: diva2:1356291
Public defence
2019-12-20, Rudbeckssalen, Rudbecklaboratoriet, entréplan, C11, Dag Hammarskjöldsväg 20, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2019-11-27 Created: 2019-10-01 Last updated: 2019-11-27
List of papers
1. Variance components in confocal scanning laser tomography measurements of neuro-retinal rim area and the effect of repeated measurements on the power to detect loss over time
Open this publication in new window or tab >>Variance components in confocal scanning laser tomography measurements of neuro-retinal rim area and the effect of repeated measurements on the power to detect loss over time
Show others...
2016 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 94, no 7, p. 705-711Article in journal (Refereed) Published
Abstract [en]

PurposeTo estimate the variation in measurements of neuro-retinal rim area (NRA) determined by confocal scanning laser tomography and consequences for clinical follow-up. MethodsAltogether, 24 healthy subjects were randomized on -320m, Moorfields and Standard NRA plane strategies. Additionally, NRA was measured in 32 glaucoma subjects. Variance components for subjects, visits and measurements were estimated with analysis of variance. Sample sizes required to detect a 6.0x10(-2)mm(2) NRA change were estimated assuming a significance level of 0.05 and a power of 0.8. Consequences for independent group, and paired comparison design, respectively, were analysed. Further, precision in estimates within subjects over time was investigated. ResultsThe variation of NRA among subjects was considerably larger than the variation among visits and measurements. For glaucoma subjects, the variation among visits and measurements were of the same order but larger than in healthy subjects. It was found that independent group comparisons require inconveniently large sample sizes. Within-subject paired comparisons over time require sample sizes of below 15 subjects. The estimated variations for glaucoma subjects imply that 54months of follow-up is required for detection of change from baseline. ConclusionsThe variance for subjects is substantial in relation to those for visits and measurements. Cross-sectional independent group comparisons of levels of NRA are unsuitable, due to considerable subject variation. Levels of NRA differences within subjects between visits can be estimated with acceptable precision. Neuro-retinal rim area (NRA) measurement can be used for long-term follow-up of glaucoma progression.

Keywords
confocal scanning laser tomography; glaucoma; neuro-retinal rim area; variation
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-295356 (URN)10.1111/aos.13079 (DOI)000386631400044 ()27233465 (PubMedID)
Available from: 2016-06-05 Created: 2016-06-05 Last updated: 2019-10-01Bibliographically approved
2. A strategy for OCT estimation of the optic nerve head pigment epithelium central limit-inner limit of the retina minimal distance, PIMD-2π
Open this publication in new window or tab >>A strategy for OCT estimation of the optic nerve head pigment epithelium central limit-inner limit of the retina minimal distance, PIMD-2π
2019 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 97, no 2, p. 208-213Article in journal (Refereed) Published
Abstract [en]

Purpose To develop a semi-automatic algorithm for estimation of pigment epithelium central limit-inner limit of the retina minimal distance averaged over 2 pi radians (PIMD-2 pi) and to estimate the precision of the algorithm. Further, the variances in estimates of PIMD-2 pi were to be estimated in a pilot sample of glaucomatous eyes. Methods Three-dimensional cubes of the optic nerve head (ONH) were captured with a commercial SD-OCT device. Raw cube data were exported for semi-automatic segmentation. The inner limit of the retina was automatically detected. Custom software aided the delineation of the ONH pigment epithelium central limit resolved in 500 evenly distributed radii. Sources of variation in PIMD estimates were analysed with an analysis of variance. Results The estimated variance for segmentations and angles was 130 mu m(2) and 1280 mu m(2), respectively. Considering averaging eight segmentations, a 95 % confidence interval for mean PIMD-2 pi was estimated to 212 +/- 10 mu m (df = 7). The coefficient of variation for segmentation was estimated at 0.05. In the glaucomatous eyes, the within-subject variance for captured volumes and for segmentations within volumes was 10 mu m(2) and 50 mu m(2), respectively. Conclusion The developed semi-automatic algorithm enables estimation of PIMD-2 pi in glaucomatous eyes with relevant precision using few segmentations of each captured volume.

National Category
Ophthalmology Medical Image Processing
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-362723 (URN)10.1111/aos.13908 (DOI)000459637900020 ()30198106 (PubMedID)
Funder
Gun och Bertil Stohnes Stiftelse
Available from: 2018-09-10 Created: 2018-10-09 Last updated: 2019-10-01
3. Variance components for PIMD-2π estimation of the optic nerve head and consequences in clinical measurements of glaucoma
Open this publication in new window or tab >>Variance components for PIMD-2π estimation of the optic nerve head and consequences in clinical measurements of glaucoma
2019 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768Article in journal (Refereed) Epub ahead of print
Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
glaucoma, oct, optic nerve head, PIMD, follow-up
National Category
Ophthalmology
Research subject
Ophtalmology
Identifiers
urn:nbn:se:uu:diva-389416 (URN)10.1111/aos. 14197 (DOI)
Available from: 2019-07-11 Created: 2019-07-11 Last updated: 2019-10-01
4. Detection and clinical follow-up of segmental glaucomatous optic nerve head damage using OCT.
Open this publication in new window or tab >>Detection and clinical follow-up of segmental glaucomatous optic nerve head damage using OCT.
(English)Manuscript (preprint) (Other academic)
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-393969 (URN)
Available from: 2019-09-30 Created: 2019-09-30 Last updated: 2019-10-01

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