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Identifier 000419330
Title Αξιολόγηση επαναληψιμότητας και κλινικές εφαρμογές της συνεστιακής μικροσκοπίας στην απεικόνιση του αμφιβληστροειδούς και των φωτοϋποδοχέων
Alternative Title Evaluation of repeatability and clinical applications of confocal microscopy in retinal and photoreceptor imaging
Author Παλλήκαρης, Αριστοφάνης
Thesis advisor Τσιλιμπάρης, Μ.
Select a value Θερμού, Κ.
Πλαϊτάκης, Α.
Καραγωγέως, Δ.
Χλουβεράκης, Γ.
Κυμιωνής, Γ.
Τοπούζης, Φ.
Abstract Introduction: Besides the conventional application of confocal microscopy, or more appropriately refered to us ophthalmoscopy, of the retina in the qualitative evaluation of of retina, the specific imaging modality has been combined with additional technics such as Doppler and angiography with fluorescein or indiocyanine for the quantitative evaluation of the retinal and choroidal arteries’ blood flow, axial tomography for the quantitative evaluation of the pachymetric and topographic data of the retina, and perimetry (microperimetry) for the detailed examination of light sensitivity of the retina and fixation stability of the eye. With the respect to the first two aforementioned techniques, confocal ophthalmoscopy has been studied extensively. On the contrary, studies of axial tomography and microperimetry in conjunction with confocal ophthalmoscopy has been mainly confined to the investigation of the eye’s optic nerve and the light sensitivity of the retina as a whole whereas fairly limited investigations have focused on the macula. The general scope of the current dissertation is the extensive investigation and additional development of the quantitative data of axial tomography and microperimetry with confocal ophthalmoscopy towards evaluation of the macula. With respect to axial tomography with confocal ophthalmoscopy, calculation of the repeatability of the existed axial tomography parameters of the macula and their correlation with the gold standard of fluorescein angiography of the retina in normal and pathological eyes, and the development and investigation of additional topographic indices of the macula in normal eyes represent specific aims of the this dissertation. With respect to microperimetry with confocal ophthalmoscopy, the determination of light sensitivity and fixation stability in a large cohort of normal eyes as well as two groups with early and intermediate age related macular degeneration, the investigation of the differences between an advanced and limited plexus of light stimuli, and the investigation of the differences among normal and pathological eyes represent specific aims of this dissertation. Methodology: The evaluation of repeatability of edema index and the additional parameters of the axial intesity profile of the axial tomography with confocal ophthalmoscopy was carried out in three groups of eyes: normal eyes, eyes with choroidal neovascularisation, and eyes with diabetic macula edema. Besides the basic clinical evaluation, all eyes were imaged with a clinical version of a confocal ophthalmoscope which was used throughout the entire experimental protocols of the first part of this dissertation. Three successive acquisition of the macula were performed within a single day whereas in the group with normal eyes, the examination was performed a second time within a different day of the same week. Measurement of the depth of the retinal surface, the width of the axial intensity profile, and the edema index was performed for three circles of interest with radia of 0.25 mm, 0.5 mm, and 0.75 mm. In terms of the correlation of the edema index with fluorescein angiography, data from pathological eyes that underwent photodynamic therapy of neovascularisations secondary to age related macula degeneration were used. Besides the basic clinical evaluation, fluorescein angiography images were quantitatively analysed using custom written software that provided the integrated contrast amplitude (ICA) of the neovascularisation areas as compared to the surrounding retina. Measurements were performed prior to the therapy as well as 1 and 3 months post therapy. In addition, all eyes underwent examination of the pathological area with the acquisition of confocal ophthalmoscopy images 1 hour prior to the therapy as well as 1 hours, 1 month, and 3 months post therapy. For the development and investigation of additional indices of the macula topographym two groups of eyes were formed. The initial 20 eyes were used for the development and evaluation of repeatability of the custom written software, whereas the both eyes of 30 subjects were used in the second stage in which the custom written software was applied. To describe macula topography, a supergaussian function was used as the mathematical mode that was fitted to the topography data. The entire analysis was performed in 12 semi-meridians whereas 3 images per eye were used during the development and evaluation of the algorithm. In terms of the investigation of light sensitivity of the macula and fixation stability of the eye, 3 groups were formed: normal eyes, eyes with early age related macula degeneration, and eyes with intermediate age related macula degeneration. Besides the basic clinical evaluation, categorisation of eyes was performed based on commonly accepted standards from prior publications. In addition, all eyes were examined with a prototype microperimeter with confocal ophthalmoscopy, whereas both eyes of normal subjects were included in the experiments. The analysis of light sensitivity was performed for a circular plexus of 63 light stimuli as well as a limited plexus, whereas the analysis of the average values was conducted based on both their eccentricity from the center of the plexus as well as along 12 semi-meridians. Results: The repeatability of all parameters of axial tomography with confocal ophthalmoscopy exhibit satisfactory results. The valus of the coefficient of variability ranged from 5.7 to 10.1% for all the parameters besides the depth of the retinal surface which exhibit values from 15.1 to 29.9%. For this specific parameter, the highest values of the coefficient of variability were observed in the group of eyes with choroidal neovascularisation. The 95% confidence interval between measurements in different days in normal eyes was considerably improved with the acquisition of three succesive measurements and its reported values were ±61.5 μm, ±46.7 μm, και ±0.06 for the three parameters, accordingly. The edema index of the confocal ophthalmoscope as well as its changes over time post therapy exhibited statistically significant correlation with the ICA of neovascularisations. Nonetheless, the edema index values did not exhibit statistical significant changes between the various time points of examination. Finally, the fitting of the mathematical model to the macula topography data exhibited an error comparable to similar prior approaches, providing five additional indices for the description of macula topography. During the investigation of these indices on the second group of eyes, great variability of the macula topography was observed both within the subjects as well within the semi-meridians of each examined eye. Statistically significant correlations were observed in numerous occasions when comparing eyes of the same subjects. In any case and on average, the macula topography data as these were calculated based on these five parameters seem to deviation from the most common view that the macula is a circular area of the retina with a Gaussian contour dip in its central location. With respect to microperimetry with confocal ophthalmoscopy of the retina, 140 normals eyes (70 subjects), 33 eyes with early age related macula degeneration, and 41 eyes with intermediate macula degeneration were included in the study. Statistically significant correlations of light sensitivity between the left and right eyes of the same subjects were observed, whereas statistically significant changes of light sensitivity were observed when comparing either the various semi-meridians or the different rings. With respect to the comparison of the various semi-meridians and/or rings, similar results were observed for all groups with slightly smaller differences reported in the eyes with intermediate age related macula degeneration. Statistically significant, yet small, differences were observed when comparing the two different plexuses. In any case, the average light sensitivity exhibited statistically significant correlation with age. Finally, differences in light sensitivity between the groups featured various results with the most important observation being the statistically significant difference between the normal eyes and the eyes with intermediate age related macula degeneration. Accordingly, similar results were observed in the analysis of fixation stability of the eye Conclusions: From the total results of confocal ophthalmoscopy in conjunction with both axial tomography analysis and microperimetry analysis of light sensitivity, it seems that the specific technology may contribute to numerous additional examinations besides the most commonly used examination of the optic nerve head or the general evaluation of retinal light sensitivity through the provision of reliable measurements. Both the analysis of reliability of measurements and the development of additional indices of this dissertation provide notable information that may be used both at the level of basic reasearch and the everyday clinical practice towards development of standardised clinical examination by means of the this specific technology. In any event, additional investigations both on the comparison between the basic functional characteristics of the macula and the existed indices and the analysis of the existed indices on additional pathologies are required to give even further promises to the abilities of the technology.
Language Greek
Subject Age related macula degeneration
Axial tomography
Diabetic retinopathy
Fluorescein angiography
Αξονική τομογραφία
Διαβητική αμφιβληστροειδοπάθεια
Ηλικιακή εκφύλιση ωχράς κηλίδας
Ωχρά κηλίδα
Issue date 2018-12-5
Collection   Faculty/Department--School of Medicine--Department of Medicine--Doctoral theses
  Type of Work--Doctoral theses
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