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  • 1.
    Eriksson, Urban
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Optical coherence tomography in the diagnosis of juvenile X-linked retinoschisis.2004In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 82, no 2, p. 218-223Article in journal (Refereed)
  • 2.
    Holmström, Gerd
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Hellström, Ann
    Section for Ophthalmology, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg.
    Gränse, Lotta
    Department of Clinical Sciences, Ophthalmology, Skåne University Hospital, Lund University, Lund.
    Sarec, Mari
    Department of Clinical Sciences, Ophthalmology, Umeå University, Umeå.
    Wallin, Agneta
    St Erik Eye Hospital, Stockholm.
    Sunnqvist, Birgitta
    Department of Ophthalmology, Länssjukhuset Ryhov, Jönköping.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    New modifications of Swedish ROP guidelines based on 10-year data from the SWEDROP register2019In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS:

    During the last decade, improved neonatal care has resulted in increased survival of the most immature infants and improved health of more mature infants. We hypothesise that this has affected incidence and treatment of retinopathy of prematurity (ROP), enabling guidelines for screening to be modified.

    METHODS: 

    In Sweden, all infants with gestational age (GA) at birth ≤30 weeks are screened for ROP. Results are registered in a web-based register, Swedish National ROP Register, with a coverage rate of 97%. Incidence of ROP and frequency of treatment, aspects on natural course of ROP and number of examinations, are calculated in relation to GA at birth in infants born during 2008-2017.

    RESULTS: 

    Of 7249 infants, 31.9% (2310) had ROP and 6.1% (440) were treated. No infant with GA 30 weeks was treated. Incidence of ROP remained similar, but frequency of treatment increased (p=0.023). Over time, GA and birth weight were reduced in infants with ROP and with treated ROP. In the most immature infants, postmenstrual age was lower and postnatal age was higher when any ROP and stage 3 ROP were first detected (p<0.001). At treatment, postmenstrual but not postnatal age of the infant was associated with GA (p<0.001). During the 10-year period, 46 038 examinations were performed.

    CONCLUSION: 

    Modification of Swedish guidelines is proposed, including only infants with a GA of <30 weeks and postponing the first examination with 1 week in infants with GA 26-29 weeks. This would spare many infants from stressful examinations and reduce eye examinations with at least 20%.

  • 3.
    Killer, Hanspeter E.
    et al.
    Kantonsspital Aarau, Dept Ophthalmol, Aarau, Switzerland;Univ Hosp Basel, Dept Ophthalmol, Basel, Switzerland.
    Pircher, Achmed
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics. Kantonsspital Aarau, Dept Ophthalmol, Aarau, Switzerland.
    Response to: 'Comment on: Pressure and velocity in intraocular and subarachnoid space fluid chambers: an inseparable couple'2019In: Eye (London. 1987), ISSN 0950-222X, E-ISSN 1476-5454, Vol. 33, no 9, p. 1515-1516Article in journal (Other academic)
  • 4.
    Klevebro, S.
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden;South Gen Hosp, Sachs Children & Youth Hosp, Stockholm, Sweden.
    Hammar, U.
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Bottai, M.
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Hellstrom, A.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Ophthalmol, Gothenburg, Sweden.
    Hallberg, B.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden;Karolinska Univ Hosp, Dept Neonatal Med, Stockholm, Sweden.
    Adherence to oxygen saturation targets increased in preterm infants when a higher target range and tighter alarm limits were introduced2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 9, p. 1584-1589Article in journal (Refereed)
    Abstract [en]

    Aim

    European consensus guidelines published in May 2013 recommended a target peripheral capillary oxygen saturation (SpO2) range of 90–95% for preterm infants. These were incorporated into guidelines at the Karolinska University Hospital, Sweden, in November 2013. This study compared clinical practice before and after those local guidelines.

    Methods

    We included infants who were born between 23 + 0 and 30 + 6 weeks from January 1, 2013 to December, 31 2015 and received intensive care in two Karolinska units. The lower saturation target of 88–92% and alarm limits of 85–95% used before November 2013 were compared to the new higher saturation target of 90–95% and alarm limits of 89–96%.

    Results

    Data from 399 infants were analysed. The mean SpO2 was 92.4% with the higher target (n = 301) and 91.1% with the lower target (n = 98). Using the higher instead of lower target meant that the SpO2 was within the prescribed target range more frequently (51% versus 30%) and the proportion of time with SpO2 >95% was increased by 9% (95% confidence interval 7–11%, p < 0.001).

    Conclusion

    The higher saturation target and tighter alarm limits led to higher mean oxygen saturation, increased adherence to the target and increased time with hyperoxaemia.

  • 5.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Screening for retinopathy of prematurity: evaluation and modification of guidelines.2002In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, no 12, p. 1399-1402Article in journal (Refereed)
  • 6.
    Larsson, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Carle-Petrelius, Berit
    Cernerud, Gunilla
    Ots, Lena
    Wallin, Agneta
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Incidence of ROP in two consecutive Swedish population based studies.2002In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079, Vol. 86, no 10, p. 1122-1126Article in journal (Refereed)
  • 7.
    Martin, Lene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Martin, Lene
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Peripheral and central visual fields in 11-year-old children who had been born prematurely and at term.2004In: Journal of pediatric ophthalmology and strabismus, ISSN 0191-3913, E-ISSN 1938-2405, no 1, p. 39-45Article in journal (Refereed)
  • 8.
    Norman, Mikael
    et al.
    Karolinska Inst, Div Pediat, Dept Clin Sci Intervent & Technol, Stockholm, Sweden;Karolinska Univ Hosp, Dept Neonatal Med, Stockholm, Sweden;Vasterbotten Cty Council, Swedish Neonatal Qual Register SNQ, Umea, Sweden.
    Källén, Karin
    Vasterbotten Cty Council, Swedish Neonatal Qual Register SNQ, Umea, Sweden;Lund Univ, Ctr Reprod Epidemiol, Lund, Sweden.
    Wahlström, Erik
    Natl Board Hlth & Welf, Stockholm, Sweden.
    Håkansson, Stellan
    Vasterbotten Cty Council, Swedish Neonatal Qual Register SNQ, Umea, Sweden;Umea Univ, Dept Clin Sci, Div Pediat, Umea, Sweden.
    Skiöld, Beatrice
    Swedish Neonatal Soc, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Navér, Lars
    Karolinska Inst, Stockholm, Sweden.
    Domellöf, Magnus
    Umea Univ, Umea, Sweden.
    Abrahamsson, Thomas
    Linkoping Univ, Linkoping, Sweden.
    Stigson, Lennart
    Gothenburg Univ, Gothenburg, Sweden.
    Thernström Blomqvist, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Perinatal, Neonatal and Pediatric Cardiology Research.
    Nyholm, Annika
    Umea Univ, Umea, Sweden.
    Ingemansson, Fredrik
    Jonkoping Acad, Jonkoping, Sweden.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Björklund, Lars
    Lund Univ, Lund, Sweden.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Wallin-Gyökeres, Annica
    Parent Representat, Stockholm, Sweden.
    The Swedish Neonatal Quality Register - contents, completeness and validity2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 8, p. 1411-1418Article in journal (Refereed)
    Abstract [en]

    Aim: To describe the Swedish Neonatal Quality Register (SNQ) and to determine its completeness and agreement with other registers.

    Methods: SNQ collects data for infants admitted to neonatal units during the first four postnatal weeks. Completeness and registers' agreement were determined cross-linking SNQ data with Swedish population registers (the Inpatient, Medical Birth and Cause of Death Registers) for a study period of five years.

    Results: In total, 84 712 infants were hospitalised. A total of 52 806 infants occurred in both SNQ and the population registers; 28 692 were only found in the population registers, and 3214 infants were only found in SNQ. Between gestational weeks 24-34, completeness of SNQ was 98-99%. Below and above these gestational ages, completeness was lower. Infants missing in SNQ were term or near-term in 99% of the cases, and their diagnoses indicated conditions managed in maternity units, or re-admissions for acute infections, managed in paediatric units. For most diagnoses, the agreement between SNQ and population registers was high, but some (bronchopulmonary dysplasia and grade of hypoxic-ischaemic encephalopathy) were often missing in the population registers.

    Conclusion: SNQ completeness and agreement against other registers, especially for preterm infants, is excellent. SNQ is a valid tool for benchmarking, quality improvement and research.

  • 9.
    Petursdottir, Dyrleif
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Larsson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Visual function is reduced in young adults foremely born prematurely: a population-based study2019In: British Journal of Ophthalmology, ISSN 0007-1161, E-ISSN 1468-2079Article in journal (Refereed)
    Abstract [en]

    AIMS:

    To assess visual function in young adults born preterm and compare with full-term individuals of the same age.

    METHODS: 

    Young adults, born preterm (birth weight ≤1500 g) in 1988-1990, previously included in a population-based study on the incidence of retinopathy of prematurity (ROP) in Stockholm County, Sweden were included. A control group of participants born at term, in the same area during the same time period, was used for comparison. Best-corrected visual acuities were assessed at distance and near with logMAR charts. Distance visual acuity was also measured with single symbols to calculate crowding. Visual fields were measured with Humphrey 24-2 and the mean deviation was noted. Contrast sensitivity was assessed with Vistech contrast sensitivity test and the area under the curve was calculated.

    RESULTS: 

    Fifty-nine preterm (females 37) and 44 full-term (females 18) individuals were included. All individuals were between 25 and 29 years of age. Preterm individuals had significantly lower distance visual acuity (mean -0.08 (SD 0.11) vs -0.14 (SD 0.07) logMAR, p=0.009), near visual acuity (mean -0.08 (SD 0.11) vs -0.13 (SD 0.06) logMAR, p=0.049), mean deviation (mean -1.09 (SD 1.13) vs -0.80 (SD 1.03) dB, p=0.05) and contrast sensitivity (mean 2.02 (SD 0.19) vs 2.16 (SD 0.14), p<0.001) in the better eye compared with full-term individuals. The differences in distance visual acuity and contrast sensitivity were also evident after excluding persons with previous ROP and neurological complications. In multivariable analyses, treated ROP was a risk factor for reduced near visual acuity and visual fields.

    CONCLUSION: 

    Visual function seems to be reduced in prematurely born individuals even in adulthood. The reason may be prematurity per se since individuals without previous ROP or neurological complications are also affected.

    SYNOPSIS: 

    Visual function, assessed as visual acuity, visual fields and contrast sensitivity, was reduced in young adults born preterm and previously included in a population-based study on the incidence of retinopathy of prematurity, as compared with controls.

  • 10.
    Pivodic, Aldina
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Ophthalmol, S-41685 Gothenburg, Sweden;Stat Konsultgrp, Gothenburg, Sweden.
    Hård, Anna-Lena
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Ophthalmol, S-41685 Gothenburg, Sweden.
    Löfqvist, Chatarina
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Ophthalmol, S-41685 Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Hlth Care Sci, Gothenburg, Sweden.
    Smith, Lois E. H.
    Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
    Wu, Carolyn
    Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA.
    Bründer, Marie-Christine
    Univ Med Ctr Greifswald, Dept Ophthalmol, Greifswald, Germany.
    Lagreze, Wolf A.
    Univ Freiburg, Eye Ctr, Med Ctr, Fac Med, Freiburg, Germany.
    Stahl, Andreas
    Univ Med Ctr Greifswald, Dept Ophthalmol, Greifswald, Germany.
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Albertsson-Wikland, Kerstin
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol,Unit Endocrinol, Gothenburg, Sweden.
    Johansson, Helena
    Australian Catholic Univ, McKillop Hlth Inst, Melbourne, Vic, Australia;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Publ Hlth & Community Med, Gothenburg, Sweden.
    Nilsson, Staffan
    Chalmers Univ Technol, Math Sci, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Gothenburg, Sweden.
    Hellström, Ann
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Ophthalmol, S-41685 Gothenburg, Sweden.
    Individual Risk Prediction for Sight-Threatening Retinopathy of Prematurity Using Birth Characteristics2020In: JAMA ophthalmology, ISSN 2168-6165, E-ISSN 2168-6173, Vol. 138, no 1, p. 21-29Article in journal (Refereed)
    Abstract [en]

    Question: Can a prediction model be constructed for retinopathy of prematurity needing treatment by using only birth characteristics data and applying advanced statistical methods?

    Findings: In this cohort study of 6947 infants born at gestational age 24 to 30 weeks, the prediction model incorporating only postnatal age, gestational age, sex, and birth weight provided a predictive ability for retinopathy of prematurity needing treatment that was comparable to current models requiring postnatal data (not always available). The risk for retinopathy of prematurity needing treatment increased up to 12 weeks' postnatal age irrespective of the infants' gestational age.

    Meaning: This prediction model identifying infants with a high risk for developing sight-threatening disease at an early time may improve the conditions for optimal screening. This cohort study creates and validates an easy-to-use prediction model using only birth characteristics and describes a continuous hazard function for retinopathy of prematurity treatment.

    Importance: To prevent blindness, repeated infant eye examinations are performed to detect severe retinopathy of prematurity (ROP), yet only a small fraction of those screened need treatment. Early individual risk stratification would improve screening timing and efficiency and potentially reduce the risk of blindness.

    Objectives: To create and validate an easy-to-use prediction model using only birth characteristics and to describe a continuous hazard function for ROP treatment.

    Design, Setting, and Participants: In this retrospective cohort study, Swedish National Patient Registry data from infants screened for ROP (born between January 1, 2007, and August 7, 2018) were analyzed with Poisson regression for time-varying data (postnatal age, gestational age [GA], sex, birth weight, and important interactions) to develop an individualized predictive model for ROP treatment (called DIGIROP-Birth [Digital ROP]). The model was validated internally and externally (in US and European cohorts) and compared with 4 published prediction models.

    Main Outcomes and Measures: The study outcome was ROP treatment. The measures were estimated momentary and cumulative risks, hazard ratios with 95% CIs, area under the receiver operating characteristic curve (hereinafter referred to as AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

    Results: Among 7609 infants (54.6% boys; mean [SD] GA, 28.1 [2.1] weeks; mean [SD] birth weight, 1119 [353] g), 442 (5.8%) were treated for ROP, including 142 (40.1%) treated of 354 born at less than 24 gestational weeks. Irrespective of GA, the risk for receiving ROP treatment increased during postnatal weeks 8 through 12 and decreased thereafter. Validations of DIGIROP-Birth for 24 to 30 weeks' GA showed high predictive ability for the model overall (AUC, 0.90 [95% CI, 0.89-0.92] for internal validation, 0.94 [95% CI, 0.90-0.98] for temporal validation, 0.87 [95% CI, 0.84-0.89] for US external validation, and 0.90 [95% CI, 0.85-0.95] for European external validation) by calendar periods and by race/ethnicity. The sensitivity, specificity, PPV, and NPV were numerically at least as high as those obtained from CHOP-ROP (Children's Hospital of Philadelphia-ROP), OMA-ROP (Omaha-ROP), WINROP (weight, insulinlike growth factor 1, neonatal, ROP), and CO-ROP (Colorado-ROP), models requiring more complex postnatal data.

    Conclusions and Relevance: This study validated an individualized prediction model for infants born at 24 to 30 weeks' GA, enabling early risk prediction of ROP treatment based on birth characteristics data. Postnatal age rather than postmenstrual age was a better predictive variable for the temporal risk of ROP treatment. The model is an accessible online application that appears to be generalizable and to have at least as good test statistics as other models requiring longitudinal neonatal data not always readily available to ophthalmologists.

  • 11.
    Sandberg Melin, Camilla
    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.
    Morphometry of the Optic Nerve Head as a Diagnostic Tool for Glaucoma2019Doctoral thesis, comprehensive summary (Other academic)
    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.

    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: 2020-02-20Bibliographically approved
    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: 2020-02-20Bibliographically approved
    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
  • 12.
    Sandberg Melin, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics. centrum för forskning och utveckling Uppsala universitet/Gävleborg.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Söderberg, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Detection and clinical follow-up of segmental glaucomatous optic nerve head damage using OCT.Manuscript (preprint) (Other academic)
  • 13.
    Söderberg, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Yu, Zhaohua
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Söderberg: Ophthalmic Biophysics.
    Sandberg Melin, Camilla
    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.
    Optic nerve head morphometry for glaucoma diagnosis, optimization of clinical measurement strategy2019In: Proceedings of SPIE, ISSN 0277-786X, Vol. 10858, p. 45:1-45:8, article id 108581CArticle in journal (Refereed)
    Abstract [en]

    The present study aimed to develop a strategy for evaluation of instant PIMD-2 pi measurements as a basis for clinical monitoring of glaucoma. PIMD-2 pi is a morphometric measure of the waist of the nerve fiber layer at the optic nerve head (ONH). Clinical measurements of PIMD-2 pi in patients with early to moderate stage glaucoma demonstrated a high variability among subjects. The high variability among subjects renders comparison of instant PIMD-2 pi measurements to tolerance limits for normality derived from a normative database inefficient. It is suggested to instead compare sequential measurements of PIMD-2 pi within a patient. Initially, the difference between an instant measurement and the average of previous measurements can be compared to tolerance limits for difference between measurements within subject. Once, a potential loss of PIMD-2 pi is detected, a sufficient number of measurements within a sufficiently wide time interval can be used to estimate the PIMD-2 pi loss rate with regression and the deviation of the estimated loss rate can be evaluated as a 95 % confidence interval for the loss rate. If the upper confidence limit excludes 0, a significant loss rate has been detected. The currently proposed strategy has the potential to detect glaucoma earlier than the current gold standard, computer perimetry, with less inconvenience for the patient.

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