| 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.
|
Search
