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Retinal ganglion cell examination with Optical Coherence Tomography reflects physiological and pathological changes in the eye and the brain.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Sensory Organs and Communication. Linköping University, Faculty of Medicine and Health Sciences.
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The retinal ganglion cell is situated in the inner retina and its axons, composing the retinal nerve fiber layer (RNFL), leave the eye to form the optic nerve. These cells develop embryologically from the forebrain and later during development re-establish connections with different parts of the brain serving different purposes. This unique position and connections make it possible to be investigated with different methods. Optical Coherence Tomography (OCT) is an accessible and easily operated clinical device that can provide a detailed image of this layer at a few micrometers level of precision in measurements. In this thesis we aimed to see whether examining these cells with OCT could reflect physiological and pathological changes in the eye and brain.

In cases of optic neuritis (Paper I), the OCT examination showed early thickening of the peripapillary (pRNFL) followed by thinning which takes 6-9 months to reduce to below normal thickness without the ability to distinguish between the real from pseudo thinning. The ganglion cell -inner plexiform layer (GCL-IPL) layer, however, showed a thickness reduction within a few weeks to 3 months without pseudo thinning.         

In cases of Idiopathic Intracranial Hypertension (IIH) (Paper II), the GCL-IPL remained unchanged and there was no difference in pRNFL thickness compared to healthy controls, whereas  the optic disc parameters of rim thickness, rim area, cup volume and cup/disc ratio differed significantly (P<0.05).

In cases of benign multiple sclerosis (Paper IV), the OCT could detect that eyes which are not affected by optic neuritis had an annual thinning rate of the RNFL and GCL-IPL similar to a healthy population (P>0.05) which may indicate the benign course of the disease.       

In cases of physiological factors affecting the GCL in healthy population (Paper III) the OCT examination showed that there was a significant thinning rate of the layer with age (P<0.05), but the thinning was not significant when sex and axial length of the eye were taken into consideration. Males had a thicker GCL volume than females and with age a significant reduction in GCL volume was noted in females but not in males. A Longer axial length of the eye found to be associated with thinner GCL volume.     

In conclusion retinal ganglion cell changes detected with OCT can reflect physiological and pathological changes in the eye and brain.   

Abstract [sv]

Den retinala ganglioncellen är belägen i den inre näthinnan och dess axoner, näthinnans nervfiberskikt (RNFL) eller nervfibrer, lämnar ögat för att bilda synnerven. Dessa ganglionceller utvecklas under fosterstadiet från framhjärnan och återskapar senare under utvecklingen förbindelser med olika delar av hjärnan som tjänar olika syften bland annat synen. Denna unika position och kopplingar gör det möjligt att undersöka dem med olika metoder. Optical Coherence Tomography (OCT) är en tillgänglig apparat på de flesta ögonkliniker och används vid olika ögonsjukdomar som grönstarr och sjukdomar i gula fläcken. Apparaten är lättmanövrerad, kostnadseffektiv och undersökningen kan göras i samband med kliniska besök. Undersökningen kan ge en detaljerad bild av näthinnas olika lager med en mikrometers precisionsnivå vid mätningar. I detta projekt har vi syftat till att se om undersökning av gangliecellerna med OCT kunde återspegla fysiologiska och patologiska förändringar i ögat och hjärnan.            

I fall av synnervsinflammation (Arbete I), visar OCT-undersökningen tidig förtjockning av nervfibrerna följt av uttunning, det tog 6–9 månader för att minska till under den normala tjockleken utan att kunna skilja mellan verklig och falsk förtunning. Gangliecell-skiktet däremot visade en tjockleksminskning redan inom några veckor till 3 månader. Detta faktum ger ett snabbare och mer pålitligt resultat.

I fall av tryck på synnerven på grund av ökat tryck i hjärnan, (idiopatisk Intrakraniell hypertoni) (Arbete II), förblir gangliecellslagret oförändrat och det finns ingen skillnad i nervfibrernas tjocklek jämfört med friska kontroller medan synnervshuvudets parameter som rim tjocklek och area, exkavationsvolymen och exkavation/synnervhuvudets-förhållande skiljer sig signifikant. Det bevisar att vid denna sjukdom, synnervshuvudet är först att bli påverkat medan gangliecell lagret visade ingen direkt eller bestående skada på nerven.   Vid Multipel skleros drabbas patienterna av sjukdomen ofta successivt och man behöver sätta in behandling för att förhindra funktionshinder. En grupp av dessa patienter slipper uppenbara funktionshinder även efter flera år av sjukdomen trots uteblivet behandlingsbehov. Den typen kallas för godartad eller benign (BMS).          

I fall av godartad multipel skleros (Arbete IV) kan OCT undersökningen upptäcka och visa att ögonen som inte är drabbade av inflammation på synnerven har en årlig förtunning som liknar den hos en frisk population vilket är mindre uttalad än hos dem med MS med svårare sjukdomsförlopp. Med hjälp av undersökningen kan man bevisa ett mer godartat sjukdomsförlopp hos MS patienter och möjligen inget behov till behandling.

I fall av fysiologiska faktorer som påverkar GCL i frisk population (Arbete III) visar OCT-undersökningen att det finns en signifikant förtunning av lagret med åldern men förtunningen är inte statistiskt signifikant när kön och axiell längd tas i beaktande. Män har en större gangliecell-volym än kvinnor och med åldern är det en signifikant minskning av volymen hos kvinnor, medan hos männen uteblir en signifikant förändring. Samma mönster ses i hjärnstorlek både med åldern och hos båda könen. En ökad axiell längd är associerad med tunnare ganglioncellskiktsvolym.        

Sammanfattningsvis, en undersökning av retinala ganglieceller med OCT kan återspegla fysiologiska och patologiska förändringar i ögat och hjärnan och borde användas oftare för undersökning av patienter med olika sjukdomar. 

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2023. , p. 81
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1886
Keywords [en]
Retinal ganglion cell, Retinal nerve fiber layer, Optical Coherence Tomography
National Category
Ophthalmology
Identifiers
URN: urn:nbn:se:liu:diva-199194DOI: 10.3384/9789180754194ISBN: 9789180754187 (print)ISBN: 9789180754194 (electronic)OAI: oai:DiVA.org:liu-199194DiVA, id: diva2:1812489
Public defence
2023-12-19, Hugo Theorell, Building 448, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2023-11-16 Created: 2023-11-16 Last updated: 2023-11-16Bibliographically approved
List of papers
1. Acute optic neuritis: retinal ganglion cell loss precedes retinal nerve fiber thinning.
Open this publication in new window or tab >>Acute optic neuritis: retinal ganglion cell loss precedes retinal nerve fiber thinning.
2015 (English)In: Neurological Sciences, ISSN 1590-1874, E-ISSN 1590-3478, Vol. 36, no 4, p. 617-620Article in journal (Refereed) Published
Abstract [en]

Optic neuritis (ON) causes axonal loss as reflected by thinning of retinal nerve fiber layer (RNFL) and can be tracked by optical coherence tomography (OCT) about 6 months after ON onset, when swelling of optic nerve head (ONH) has vanished. Changes of macular ganglion cell layer (GCL) thickness provide another window to track the disease process in ON. GCL thinning over time in relation to RNFL change after ON remains elusive. Using OCT, we followed 4 patients with acute unilateral isolated ON for more than 9 months. A diagnosis of multiple sclerosis (MS) was established in all 4 patients. First follow-up was 2-3 weeks after ON onset, and thereafter every 2-3 months. RNFL swelling peaked during first month after acute ON, followed by rapidly reduced swelling (pseudoatrophy) during following 2 months, and thereafter successively vanished 6 months after ON onset. GCL thinning was observed 1-3 months after ON onset, i.e. already during optic disk swelling and before real RNFL thinning. The results imply that quantifying GCL thickness provides opportunities to monitor early axonal loss and ON-to-MS progression, and facilitates distinguishing real atrophy from pseudoatrophy of RNFL after acute ON.

National Category
Ophthalmology
Identifiers
urn:nbn:se:liu:diva-117096 (URN)10.1007/s10072-014-1982-3 (DOI)000351612200017 ()25311917 (PubMedID)
Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2023-11-16
2. OCT measurements of optic nerve head changes in idiopathic intracranial hypertension
Open this publication in new window or tab >>OCT measurements of optic nerve head changes in idiopathic intracranial hypertension
2015 (English)In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 130, p. 122-127Article in journal (Refereed) Published
Abstract [en]

Objective: Severity of papilledema and vision loss constitute a basis for therapeutic intervention in idiopathic intracranial hypertension (IIH), but both are often subjective and insensitive in guiding clinical management. The aim of this study was to identify reliable and sensitive measurements of optic nerve head (ONH) and macula, to provide objective guidance for prognostic evaluation and treatment in IIH. We analyzed potential of spectral domain optical coherence tomography (SD-OCT), to measure neuro-retinal rim thickness and area, optic cup-to-disc ratio (C/D) and cup volume of ONH which have not previously been reported in IIH. In parallel, thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer (GCL) together with inner plexiform layer (IPL) (GCL-IPL) were examined. Results: All 7 enrolled IIH patients had increased neuro-retinal rim thickness (p less than 0.01 for both eyes) and rim area (p less than 0.05), decreased C/D (p less than 0.01) and optic cup volume (p less than 0.01) when compared to findings in 18 sex- and age-matched healthy controls (HC). In a longitudinal study, two IIH patients were followed repetitively by SD-OCT before and after measurement of intracranial pressure (ICP) and removal of cerebrospinal fluid (CSF) by lumbar puncture. Rim thickness and area, C/D and optic cup volume remained altered. RNFL thickness may change with very high ICP, but not immediately after CSF removal. GCL-IPL thickness was unchanged irrespective of ICP change or CSF removal. Conclusion: SD-OCT allows detection of ONH changes even in subtle IIH without papilledema and has potential for routine use in IIH.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Cerebrospinal fluid; Idiopathic intracranial hypertension; Optic nerve head; Optical coherence tomography; Papilledema
National Category
Ophthalmology
Identifiers
urn:nbn:se:liu:diva-116821 (URN)10.1016/j.clineuro.2014.12.021 (DOI)000350186200024 ()25614195 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland, Sweden [LIO-121641, LiO-207242, LIO-276241]; Linkoping University

Available from: 2015-04-07 Created: 2015-04-07 Last updated: 2023-11-16
3. Retinal ganglion cell layer thickness and volume measured by OCT changes with age, sex, and axial length in a healthy population
Open this publication in new window or tab >>Retinal ganglion cell layer thickness and volume measured by OCT changes with age, sex, and axial length in a healthy population
2022 (English)In: BMC Ophthalmology, ISSN 1471-2415, E-ISSN 1471-2415, Vol. 22, no 1, article id 278Article in journal (Refereed) Published
Abstract [en]

Background The ganglion cell layer (GCL) measurements with Optical Coherence Tomography (OCT) are important for both ophthalmologists and neurologists because of their association with many ophthalmic and neurological diseases. Different factors can affect these measurements, such as brain pathologies, ocular axial length (AL) as well as age and sex. Studies conducted to measure the GCL have overlooked many of these factors. The purpose of this study is to examine the effect of age, sex, and AL on normal retinal GCL thickness and volume in a healthy population without any neurological diseases. Methods A prospective cross-sectional study was designed to measure GCL thickness and total volume with OCT with automated segmentation and manual correction where needed. Visual acuity, AL, and autorefraction were also measured. A mixed linear model was used to determine the association of the effect of the various parameters on the GCL thickness and volume. Results One hundred and sixteen eyes of 60 subjects (12-76 years of age, 55% female) were examined of which 77% had 0 +/- 2 D of spherical equivalent, and mean axial length was 23.86 mm. About 25% of the OCT-automated GCL measurements required manual correction. GCL thickness did not differ in similar anatomic regions in right and left eyes (P &gt; 0.05). GCL volume was greater in males relative to females after adjustment for age and axial length (1.13 +/- 0.07 mm(3) for males vs 1.09 +/- 0.09 mm(3) for females; P = 0.031). GCL thickness differed between males and females in the inner retinal ring (P = 0.025) but not in the outer ring (P = 0.66). GCL volume declined with age (P = 0.031) but not after adjustment for sex and axial length (P = 0.138). GCL volume declined with longer axial length after adjustment for age and sex (P = 0.048). Conclusion Age, sex and axial length should be taken into consideration when measuring the GCL thickness and volume with OCT. Automated OCT segmentation should be reviewed for manual adjustments.

Place, publisher, year, edition, pages
BMC, 2022
Keywords
Ganglion cell layer (GCL); Retinal ganglion cell layer (RGCL); Ganglion cell layer thickness (GCLT); Optical coherence tomography (OCT); Ganglion cell volume (GCV)
National Category
Ophthalmology
Identifiers
urn:nbn:se:liu:diva-186815 (URN)10.1186/s12886-022-02488-7 (DOI)000815497900004 ()35751115 (PubMedID)
Note

Funding Agencies|Linkoping University

Available from: 2022-07-04 Created: 2022-07-04 Last updated: 2023-11-16
4. Longitudinal Optical Coherence Tomography Measurement of Retinal Ganglion Cell and Nerve Fiber Layer to Assess Benign Course in Multiple Sclerosis
Open this publication in new window or tab >>Longitudinal Optical Coherence Tomography Measurement of Retinal Ganglion Cell and Nerve Fiber Layer to Assess Benign Course in Multiple Sclerosis
2023 (English)In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 12, no 6, article id 2240Article in journal (Refereed) Published
Abstract [en]

A benign form of multiple sclerosis (BMS) is not easily diagnosed, but changes of the retinal ganglion cell layer-inner plexiform layer (GCL-IPL) and retinal nerve fiber layer (RNFL) may be sensitive to the disease. The aim of this study was to use optical coherence tomography (OCT) to investigate longitudinal changes of GCL-IPL and RNFL in BMS. Eighteen patients with BMS and 22 healthy control (HC) subjects were included, with a mean follow-up period of 32.1 months in BMS and 34.3 months in HC. Mean disease duration in BMS was 23.3 years, with 14 patients left untreated. Unilateral optic neuritis (ON) was found in eight patients. Non-ON eyes showed thinner GCL-IPL layer in the BMS group relative to HC (p &lt; 0.001). The thinning rate of GCL-IPL in non-ON BMS, however, was -0.19 +/- 0.15 mu m/year vs. 0 +/- 0.11 mu m/year for HC (p = 0.573, age-adjusted). Thinning rate of RNFL in non-ON BMS was -0.2 +/- 0.27 mu m/year vs. -0.05 +/- 0.3 mu m/year for HC (p = 0.454, age adjusted). Conclusions: Thinning rate of the GCL-IPL and RNFL in BMS is similar to the healthy population but differs from the thinning rate in relapsing-remitting MS, presenting a non-invasive OCT-based criterion for assessing a benign course in multiple sclerosis.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
retinal ganglion cell; retinal nerve fiber layer; ganglion cell complex; multiple sclerosis; benign multiple sclerosis; optical coherence tomography; biomarker; neural biomarker
National Category
Ophthalmology
Identifiers
urn:nbn:se:liu:diva-193025 (URN)10.3390/jcm12062240 (DOI)000955333800001 ()36983241 (PubMedID)
Available from: 2023-04-14 Created: 2023-04-14 Last updated: 2023-11-16

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